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Newly synthesized membrane proteins pass through the secretory pathway, starting at the endoplasmic reticulum and packaged into COPII vesicles, to continue to the Golgi apparatus before reaching their membrane of residence. It is known that cargo receptor proteins form part of the COPII complex and play a role in the recruitment of cargo proteins for their subsequent transport through the secretory pathway. The role of cornichon proteins is conserved from yeast to vertebrates, but it is poorly characterized in plants. Here, we studied the role of the two cornichon homologs in the secretory pathway of the moss Physcomitrium patens. Mutant analyses revealed that cornichon genes regulate different growth processes during the moss life cycle by controlling auxin transport, with CNIH2 functioning as a specific cargo receptor for the auxin efflux carrier PINA, with the C terminus of the receptor regulating the interaction, trafficking and membrane localization of PINA.
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Vesículas Cubiertas por Proteínas de Revestimiento , Proteínas de Transporte de Membrana , Animales , Transporte de Proteínas , Vesículas Cubiertas por Proteínas de Revestimiento/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Transporte Biológico/fisiología , Proteínas de la Membrana/metabolismo , Proteínas Portadoras/metabolismo , Aparato de Golgi/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMEN
Neurological disorders (NDs) are diseases of the central and peripheral nervous systems that affect more than one billion people worldwide. The risk of developing an ND increases with age due to the vulnerability of the different organs and systems to genetic, environmental, and social changes that consequently cause motor and cognitive deficits that disable the person from their daily activities and individual and social productivity. Intrinsic factors (genetic factors, age, gender) and extrinsic factors (addictions, infections, or lifestyle) favor the persistence of systemic inflammatory processes that contribute to the evolution of NDs. Neuroinflammation is recognized as a common etiopathogenic factor of ND. The study of new pharmacological options for the treatment of ND should focus on improving the characteristic symptoms and attacking specific molecular targets that allow the delay of damage processes such as neuroinflammation, oxidative stress, cellular metabolic dysfunction, and deregulation of transcriptional processes. In this review, we describe the possible role of sodium phenylbutyrate (NaPB) in the pathogenesis of Alzheimer's disease, hepatic encephalopathy, aging, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis; in addition, we describe the mechanism of action of NaPB and its beneficial effects that have been shown in various in vivo and in vitro studies to delay the evolution of any ND.
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Enfermedades del Sistema Nervioso , Fenilbutiratos , Humanos , Fenilbutiratos/uso terapéutico , Fenilbutiratos/farmacología , Animales , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/metabolismoRESUMEN
BACKGROUND: Social media sites are becoming an increasingly important source of information about mental health disorders. Among them, eating disorders are complex psychological problems that involve unhealthy eating habits. In particular, there is evidence showing that signs and symptoms of anorexia nervosa can be traced in social media platforms. Knowing that input data biases tend to be amplified by artificial intelligence algorithms and, in particular, machine learning, these methods should be revised to mitigate biased discrimination in such important domains. OBJECTIVE: The main goal of this study was to detect and analyze the performance disparities across genders in algorithms trained for the detection of anorexia nervosa on social media posts. We used a collection of automated predictors trained on a data set in Spanish containing cases of 177 users that showed signs of anorexia (471,262 tweets) and 326 control cases (910,967 tweets). METHODS: We first inspected the predictive performance differences between the algorithms for male and female users. Once biases were detected, we applied a feature-level bias characterization to evaluate the source of such biases and performed a comparative analysis of such features and those that are relevant for clinicians. Finally, we showcased different bias mitigation strategies to develop fairer automated classifiers, particularly for risk assessment in sensitive domains. RESULTS: Our results revealed concerning predictive performance differences, with substantially higher false negative rates (FNRs) for female samples (FNR=0.082) compared with male samples (FNR=0.005). The findings show that biological processes and suicide risk factors were relevant for classifying positive male cases, whereas age, emotions, and personal concerns were more relevant for female cases. We also proposed techniques for bias mitigation, and we could see that, even though disparities can be mitigated, they cannot be eliminated. CONCLUSIONS: We concluded that more attention should be paid to the assessment of biases in automated methods dedicated to the detection of mental health issues. This is particularly relevant before the deployment of systems that are thought to assist clinicians, especially considering that the outputs of such systems can have an impact on the diagnosis of people at risk.
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Anorexia Nerviosa , Trastornos de Alimentación y de la Ingestión de Alimentos , Medios de Comunicación Sociales , Femenino , Humanos , Masculino , Anorexia Nerviosa/diagnóstico , Inteligencia Artificial , SexismoRESUMEN
BACKGROUND: Eating disorders are psychological conditions characterized by unhealthy eating habits. Anorexia nervosa (AN) is defined as the belief of being overweight despite being dangerously underweight. The psychological signs involve emotional and behavioral issues. There is evidence that signs and symptoms can manifest on social media, wherein both harmful and beneficial content is shared daily. OBJECTIVE: This study aims to characterize Spanish-speaking users showing anorexia signs on Twitter through the extraction and inference of behavioral, demographical, relational, and multimodal data. By using the transtheoretical model of health behavior change, we focus on characterizing and comparing users at the different stages of the model for overcoming AN, including treatment and full recovery periods. METHODS: We analyzed the writings, posting patterns, social relationships, and images shared by Twitter users who underwent different stages of anorexia nervosa and compared the differences among users going through each stage of the illness and users in the control group (ie, users without AN). We also analyzed the topics of interest of their followees (ie, users followed by study participants). We used a clustering approach to distinguish users at an early phase of the illness (precontemplation) from those that recognize that their behavior is problematic (contemplation) and generated models for the detection of tweets and images related to AN. We considered two types of control users-focused control users, which are those that use terms related to anorexia, and random control users. RESULTS: We found significant differences between users at each stage of the recovery process (P<.001) and control groups. Users with AN tweeted more frequently at night, with a median sleep time tweets ratio (STTR) of 0.05, than random control users (STTR=0.04) and focused control users (STTR=0.03). Pictures were relevant for the characterization of users. Focused and random control users were characterized by the use of text in their profile pictures. We also found a strong polarization between focused control users and users in the first stages of the disorder. There was a strong correlation among the shared interests between users with AN and their followees (ρ=0.96). In addition, the interests of recovered users and users in treatment were more highly correlated to those corresponding to the focused control group (ρ=0.87 for both) than those of AN users (ρ=0.67), suggesting a shift in users' interest during the recovery process. CONCLUSIONS: We mapped the signs of AN to social media context. These results support the findings of previous studies that focused on other languages and involved a deep analysis of the topics of interest of users at each phase of the disorder. The features and patterns identified provide a basis for the development of detection tools and recommender systems.
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Anorexia Nerviosa , Trastornos de Alimentación y de la Ingestión de Alimentos , Medios de Comunicación Sociales , Anorexia Nerviosa/diagnóstico , Conductas Relacionadas con la Salud , Humanos , LenguajeRESUMEN
[This corrects the article DOI: 10.2196/25925.].
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BACKGROUND: Suicide risk assessment usually involves an interaction between doctors and patients. However, a significant number of people with mental disorders receive no treatment for their condition due to the limited access to mental health care facilities; the reduced availability of clinicians; the lack of awareness; and stigma, neglect, and discrimination surrounding mental disorders. In contrast, internet access and social media usage have increased significantly, providing experts and patients with a means of communication that may contribute to the development of methods to detect mental health issues among social media users. OBJECTIVE: This paper aimed to describe an approach for the suicide risk assessment of Spanish-speaking users on social media. We aimed to explore behavioral, relational, and multimodal data extracted from multiple social platforms and develop machine learning models to detect users at risk. METHODS: We characterized users based on their writings, posting patterns, relations with other users, and images posted. We also evaluated statistical and deep learning approaches to handle multimodal data for the detection of users with signs of suicidal ideation (suicidal ideation risk group). Our methods were evaluated over a dataset of 252 users annotated by clinicians. To evaluate the performance of our models, we distinguished 2 control groups: users who make use of suicide-related vocabulary (focused control group) and generic random users (generic control group). RESULTS: We identified significant statistical differences between the textual and behavioral attributes of each of the control groups compared with the suicidal ideation risk group. At a 95% CI, when comparing the suicidal ideation risk group and the focused control group, the number of friends (P=.04) and median tweet length (P=.04) were significantly different. The median number of friends for a focused control user (median 578.5) was higher than that for a user at risk (median 372.0). Similarly, the median tweet length was higher for focused control users, with 16 words against 13 words of suicidal ideation risk users. Our findings also show that the combination of textual, visual, relational, and behavioral data outperforms the accuracy of using each modality separately. We defined text-based baseline models based on bag of words and word embeddings, which were outperformed by our models, obtaining an increase in accuracy of up to 8% when distinguishing users at risk from both types of control users. CONCLUSIONS: The types of attributes analyzed are significant for detecting users at risk, and their combination outperforms the results provided by generic, exclusively text-based baseline models. After evaluating the contribution of image-based predictive models, we believe that our results can be improved by enhancing the models based on textual and relational features. These methods can be extended and applied to different use cases related to other mental disorders.
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Conductas Relacionadas con la Salud/ética , Medios de Comunicación Sociales/normas , Ideación Suicida , Femenino , Humanos , Masculino , Medición de RiesgoRESUMEN
The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-ß (Aß) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0.001), collateral recruitment (- 24%, P < 0.001), capillary density (- 22%; P < 0.01) and arteriole density (- 28%; P < 0.05) in hind limbs of AD mice compared to control WT littermates. The reactivity of large arteries was not affected in AD mice, as confirmed by unaltered size, and vasoactive responses to pharmacological stimuli of the femoral artery. We identified blood as the only source of Aß in the hind limb; thus, circulating Aß is likely responsible for the impairment of peripheral vasculature repair mechanisms. The levels of the majority of pro-angiogenic mediators were not significantly modified in AD mice compared to WT mice, except for TGF-ß1 and PlGF-2, both of which are involved in vessel stabilization and decreased in AD mice (P = 0.025 and 0.019, respectively). Importantly, endothelin-1 levels were significantly increased, while those of nitric oxide were decreased in the hind limb of AD mice (P < 0.05). Our results suggest that vascular dysfunction is a systemic disorder in AD mice. Assessment of peripheral vascular function may therefore provide additional tools for early diagnosis and management of AD.
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Enfermedad de Alzheimer/fisiopatología , Miembro Posterior/fisiopatología , Isquemia/fisiopatología , Enfermedades Vasculares Periféricas/fisiopatología , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Arteriolas/metabolismo , Arteriolas/fisiopatología , Capilares/metabolismo , Capilares/fisiopatología , Modelos Animales de Enfermedad , Endotelina-1/sangre , Arteria Femoral/metabolismo , Arteria Femoral/fisiopatología , Miembro Posterior/irrigación sanguínea , Humanos , Isquemia/genética , Ratones , Ratones Transgénicos , Microcirculación/genética , Óxido Nítrico/sangre , Enfermedades Vasculares Periféricas/sangre , Enfermedades Vasculares Periféricas/genética , Factor de Crecimiento Placentario/sangre , Factor de Crecimiento Transformador beta1/sangreRESUMEN
BACKGROUND: Detection of an incipient Peritoneal Carcinomatosis (PC) is still challenging, and there is a crucial need for technological improvements in order to diagnose and to treat early this condition. The aim of this study was to create a murine model of incipient PC and to explore the PC with Fujinon Intelligent Chromo Endoscopy (FICE) in order to determine the wavelengths of the white light (WL) spectre that offer the highest contrast between PC nodules and surrounding peritoneum. METHODS: Eighteen BALB/c mice had intraperitoneal injection of murine colonic cancer CT26 cells. Peritoneal exploration with FICE was performed at different times. For each PC nodule, 1 WL and 10 FICE images were recorded. Each image was then divided into its elementary red, green and blue band images. Depending on the FICE channel, each elementary image corresponds to a specific wavelength of the WL spectre. Through numerical analysis of these images, the value of the nodule and the background peritoneum were obtained, and the contrast value was calculated. Contrast values obtained with the different wavelengths were then compared. RESULTS: PC grew in all the mice. The number as well as the size of PC nodules was increasingly high depending on the day of exploration. Mean PCI was 1.6 ± 1.2 at day 5, 7.7 ± 2.6 at day 8 and 15.0 ± 7.3 at day 10. A total number of 1805 elementary images of PC nodules were analysed. The wavelength that offered the best contrast between PC nodules and background peritoneum was 460 nm with a mean contrast value of 0.240 ± 0.151 (p < 0.0001). CONCLUSION: This murine model of incipient PC is effective, reliable and reproducible. A monochromatic light with a wavelength at 460 nm offers the highest contrast between PC nodules and background peritoneum, allowing a better detection of PC.
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Endoscopía/métodos , Aumento de la Imagen/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias Peritoneales/diagnóstico , Peritoneo/patología , Animales , Técnicas de Cultivo de Célula , Color , Modelos Animales de Enfermedad , Femenino , Humanos , Luz , Ratones , Ratones Endogámicos BALB C , Neoplasias Peritoneales/patologíaRESUMEN
To infect the human host, Entamoeba histolytica carries out processes requiring cytoskeleton remodeling, which involves reorganizing the actin fibers. However, little is known about the external influence factors, e.g., the pH, on the parasite's cytoskeleton remodeling or cell morphology. Such influence becomes relevant given the pH gradient that the amoeba cope with when going through the human colonic mucus during infection. Therefore, we analyzed the proliferation, the reorganization of the actin fibers, and other actin structures and cell shape during adhesion to fibronectin and erythrophagocytosis in trophozoites at different external pH conditions (6.0, 6.5, 6.8, 7.5, 8.0). We found that the best condition of external pH to perform such functions was 6.8. At acid pH, the trophozoites presented better-defined actin fibers that formed a more compact network, while at alkaline pH, the fibers reorganized, forming a looser and less defined network. Similarly, the number of actin dots also changed from acid to alkaline pH. In conclusion, the external pH alters the proliferation of the amoebas and promotes the dynamic restructuration of their cytoskeleton, allowing them to carry out their functions.
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Entamoeba histolytica , Actinas/metabolismo , Animales , Proliferación Celular , Citoesqueleto/metabolismo , Entamoeba histolytica/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Trofozoítos/metabolismoRESUMEN
The Entamoeba histolytica parasite is the causative agent of amebiasis, infecting approximately 1% of the world population and causing 100,000 deaths per year. It binds to Fibronectin (FN), activating signaling pathways regulated by kinases and phosphatases. EhLMW-PTPs genes from E. histolytica encode for Low Molecular Weight Tyrosine Phosphatases expressed in trophozoites and amoebic cysts. The role of these phosphatases in the virulence of the parasite has not yet been well characterized. Our results showed a differential expression of the EhLMW-PTPs, at the mRNA and protein levels, in an asynchronous trophozoites culture. Furthermore, we observed that trophozoites transfected that overexpressed EhLMW-PTP2 phagocytized fewer erythrocytes, possibly due to decreased phagocytic cups, and showed deficiencies in adherence to FN and less cytopathic effect. These analyzes suggest that the parasite's EhLMW-PTPs have an essential role in the mechanisms of proliferation, adhesion, and phagocytosis, regulating its pathogenicity.
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Entamoeba histolytica/patogenicidad , Proteínas Tirosina Fosfatasas/genética , Proteínas Protozoarias/genética , Trofozoítos/patogenicidad , Factores de Virulencia/genética , Animales , Células CACO-2 , Adhesión Celular , Proliferación Celular , Clonación Molecular , Técnicas de Cocultivo , Entamoeba histolytica/enzimología , Entamoeba histolytica/genética , Eritrocitos/citología , Escherichia coli/genética , Escherichia coli/metabolismo , Femenino , Fibronectinas/química , Fibronectinas/metabolismo , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Humanos , Ratones , Ratones Endogámicos BALB C , Peso Molecular , Fagocitosis/fisiología , Proteínas Tirosina Fosfatasas/metabolismo , Proteínas Tirosina Fosfatasas/farmacología , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/farmacología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Trofozoítos/enzimología , Trofozoítos/genética , Virulencia , Factores de Virulencia/metabolismo , Factores de Virulencia/farmacologíaRESUMEN
BACKGROUND: To date, the function of many hypothetical membrane proteins of Mycobacterium tuberculosis is still unknown and their involvement in pathogen-host interactions has not been yet clearly defined. In this study, the biological activity of peptides derived from the hypothetical membrane protein Rv0679c of M. tuberculosis and their involvement in pathogen-host interactions was assessed. Transcription of the Rv0679c gene was studied in 26 Mycobacterium spp. Strains. Antibodies raised against putative B-cell epitopes of Rv0679c were used in Western blot and immunoelectron microscopy assays. Synthetic peptides spanning the entire length of the protein were tested for their ability to bind to A549 and U937 cells. High-activity binding peptides (HABPs) identified in Rv0679c were tested for their ability to inhibit mycobacterial invasion into cells. RESULTS: The gene encoding Rv0679c was detected in all strains of the M. tuberculosis complex (MTC), but was only transcribed in M. tuberculosis H37Rv, M. tuberculosis H37Ra and M. africanum. Anti-Rv0679c antibodies specifically recognized the protein in M. tuberculosis H37Rv sonicate and showed its localization on mycobacterial surface. Four HABPs inhibited invasion of M. tuberculosis to target cells by up to 75%. CONCLUSIONS: The results indicate that Rv0679c HABPs and in particular HABP 30979 could be playing an important role during M. tuberculosis invasion of host cells, and therefore could be interesting research targets for studies aimed at developing strategies to control tuberculosis.
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Antígenos Bacterianos/fisiología , Proteínas Bacterianas/fisiología , Interacciones Huésped-Patógeno , Mycobacterium tuberculosis/patogenicidad , Factores de Virulencia/fisiología , Anticuerpos Antibacterianos/aislamiento & purificación , Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Western Blotting , Línea Celular , Células Epiteliales/microbiología , Epítopos de Linfocito B/inmunología , Perfilación de la Expresión Génica , Humanos , Microscopía Inmunoelectrónica , Monocitos/microbiología , Unión Proteica , Vacunas contra la Tuberculosis/inmunología , Factores de Virulencia/inmunologíaRESUMEN
OBJECTIVES: To determine the frequency, radiodensity characteristics, topographic location and number per patient of incidental findings observed in radiographs taken before orthodontic treatment and to evaluate the relationship of the findings with age and sex. METHODS: This was a cross-sectional study that investigated 1,887 panoramic and lateral cephalogram radiographs from 783 patients (23.31 ± 13.11 years of age; 453 women and 330 men) who were randomly selected from the orthodontics department of a private university. The images were systematically evaluated by an oral pathologist. A chi-square test was applied to evaluate the association between sex and the presence of pathology, radiodensity characteristics and topographic location. The Mann-Whitney U and Kruskal-Wallis tests were used to establish the association between age or number of findings per patient with other variables in the study. RESULTS: The prevalence of incidental findings was 88.12%. The most frequent finding was maxillary sinus pneumatisation (25.80%). No significant association was detected between frequency or number of findings per patient and either sex or diagnostic hypothesis. A significant association was found between age and the presence of pathology and number of incidental findings per patient (P < 0.001), as well as between the type of radiographic image and incidental finding (P < 0.001). CONCLUSION: The prevalence of incidental findings in the sample studied was high, and the structures most commonly involved were the maxillary sinuses. The results suggest that both the presence and the number of findings per patient increase with age but there is no association with sex.
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Hallazgos Incidentales , Ortodoncia , Radiografía Dental , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Radiografía Panorámica , Adulto JovenRESUMEN
PURPOSE: To evaluate motor alignment, motility, and sensorial outcomes of simultaneous three-muscle surgery for large-angle horizontal strabismus, with special attention to lateral incomitance and long-term success. METHODS: The medical records of consecutive patients with large-angle deviations (≥30Δ) who underwent simultaneous surgery on three horizontal muscles to correct esotropia or exotropia were reviewed retrospectively. Successful motor alignment was defined as residual deviation of ≤10Δ and consecutive deviation in primary position of ≤4Δ, with no induced lateral incomitance >5Δ between lateral gazes. Sensory success was defined as an improvement in stereopsis of ≥2 octaves. Surgical procedures included a combination of recessions and resections/plications depending on surgeon preference. The majority of cases were two-muscle recessions combined with one-muscle resection or plication. RESULTS: A total of 19 patients with exotropia and 9 patients with esotropia were included. In the esotropic group, the mean age at surgery was 48 ± 15 years and the mean preoperative deviation improved from 45.6Δ ± 11.9Δ to 1.5Δ ± 1.6Δ (P < 0.001); there was no undercorrection, recurrence or overcorrection. In the exotropic group, the mean age at surgery was 44 ± 25 years, and the mean preoperative deviation improved from 44.1Δ ± 8.7Δ to 5.8Δ ± 9.6Δ (P < 0.001), recurrence occurred in 2 (22%). Overall motor success at distance was 85%, with 1 (3.8%) unsuccessful patient due to induced incomitance. Sensory success was 44% for esotropia and 31% for exotropia. No patient lost stereopsis. CONCLUSIONS: Patients undergoing three-muscle surgery for horizontal strabismus had good motor outcomes with low incidence of induced lateral incomitance. Motor and sensorial outcomes for esotropia were very stable.
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Esotropía/cirugía , Exotropía/cirugía , Músculos Oculomotores/cirugía , Procedimientos Quirúrgicos Oftalmológicos/métodos , Estrabismo/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Percepción de Profundidad/fisiología , Esotropía/fisiopatología , Exotropía/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Músculos Oculomotores/fisiología , Estudios Retrospectivos , Estrabismo/fisiopatología , Visión Binocular/fisiología , Adulto JovenRESUMEN
Syf1 is a tetratricopeptide repeat (TPR) protein implicated in transcription elongation, spliceosome conformation, mRNA nuclear-cytoplasmic export and transcription-coupled DNA repair. Recently, we identified the spliceosomal components of the human parasite Entamoeba histolytica, among them is EhSyf. Molecular predictions confirmed that EhSyf contains 15 type 1 TPR tandem α-antiparallel array motifs. Amoeba transformants carrying plasmids overexpressing HA-tagged or EhSyf silencing plasmids were established to monitor the impact of EhSyf on the splicing of several test Entamoeba transcripts. EhSyf Entamoeba transformants efficiently silenced or overexpressed the proteins in the nucleus. The overexpression or absence of EhSyf notably enhanced or blocked splicing of transcripts irrespective of the strength of their 3' splice site. Finally, the absence of EhSyf negatively affected the transcription of an intron-less transcript. Altogether our data suggest that EhSyf is a bona fide Syf1 ortholog involved in transcription and splicing.
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Entamoeba histolytica/enzimología , Entamoeba histolytica/metabolismo , Proteínas Protozoarias/metabolismo , Empalme del ARN , ARN Mensajero/metabolismo , Secuencias de Aminoácidos , Entamoeba histolytica/genética , Regulación de la Expresión Génica , Conformación Proteica , Proteínas Protozoarias/genética , Secuencias Repetitivas de AminoácidoRESUMEN
The epidemiological link between hypertension and Alzheimer disease is established. We previously reported that hypertension aggravates the Alzheimer-like pathology in APPPS1 mice (amyloid precursor protein/presenilin-1, mouse model of Alzheimer disease) with angiotensin II-induced hypertension, in relation with hypertension and nitric oxide deficiency. To provide further insights into the role of nitric oxide in the hypertension-Alzheimer disease cross-talk, we studied the effects of nitric oxide blockade in APPPS1 mice using N(ω)-nitro-l-arginine methyl ester (l-NAME) alone or in combination with hydralazine, to normalize blood pressure. Compared with normotensive APPPS1 mice, those with l-NAME-induced hypertension had greater amyloid burden ( P<0.05), increased cortical amyloid angiopathy ( P<0.01), decreased regional microvascular density ( P<0.05), and deficient long-term spatial reference memory ( P<0.001). Blood pressure normalization with hydralazine did not protect APPPS1 mice from l-NAME-induced deterioration except for cortical amyloid angiopathy, linked to hypertension-induced arterial wall remodeling. By testing the cerebrovascular response to hypercapnic breathing, we evidenced early functional impairment of cerebral vasomotor activity in APPPS1 mice. Whereas in control wild-type normotensive mice, carbon dioxide breathing resulted in 15±1.3% increase in the mean blood flow velocity ( P<0.001), paradoxical mild decrease (1.5±0.4%) was recorded in normotensive APPPS1 mice ( P<0.001). Carbon dioxide-induced decrease in mean blood flow velocity was not significantly modified in l-NAME-treated hypertensive APPPS1 mice (2.5±1.2%) and partly reversed to mild vasodilation by hydralazine (3.2±1.5%, P<0.01). These results suggest that impaired nitric oxide bioavailability exacerbates the pathophysiology of Alzheimer disease, essentially impacting amyloid load and cognitive impairment, independently of l-NAME-induced hypertension. Only cerebral amyloid angiopathy seems to be dependent on hypertension.
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Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Hipertensión/fisiopatología , Óxido Nítrico/biosíntesis , Placa Amiloide/patología , Presenilina-1/metabolismo , Enfermedad de Alzheimer/patología , Animales , Disponibilidad Biológica , Modelos Animales de Enfermedad , Masculino , Ratones , Óxido Nítrico/deficienciaAsunto(s)
Enfermedad de Chagas , Reduviidae , Triatominae , Humanos , Animales , Citocromos b/genéticaRESUMEN
Introducción: La catarata es una causa de ceguera reversible, produce cambios refractivos de predominio miópicos. Objetivo: Describir y analizar los cambios refractivos inducidos por la catarata, según el compromiso de las capas del cristalino. Diseño del estudio: Estudio retrospectivo observacional, analítico. Método: Se recolectaron datos de 184 ojos pseudofacos operados por facoemulsifi cación. Se clasifi caron los ojos en tres grupos según el compromiso del cristalino: catarata nuclear + subcapsular posterior (N+SCP), catarata nuclear (N) y catarata subcapsular posterior (SCP). El grupo N+SCP se clasifi có en 3 subgrupos (N=SCP, N>SCP, SCP>N). Para el cálculo del estado refractivo del ojo sin catarata se planteó una fórmula con equivalentes esféricos basada en la Cómo citar este artículo: Araque RL, Cifuentes D, Rodriguez MF. Cambios refractivos inducidos por catarata según su morfología en una población adulta. Revista Sociedad Colombiana de Oft almología. Vol.53(2):65-71 Rev. Soc. Colomb. Oft almol. - Julio - Diciembre de 2020 66 queratometría, longitud axial y refracción del ojo pseudofaco. Para el cálculo del cambio refractivo debido a la catarata, a la refracción subjetiva con catarata se le resta el resultado de la fórmula. Resultados: El tipo más frecuente fue la catarata combinada nuclear y subcapsular posterior. En todos los grupos se observó una tendencia a la miopización, en promedio -2.24 D. La que más miopizó fue la nuclear y la combinada en donde predomina la nuclear sobre la SCP. Se observó tendencia a la hipermetropización cuando predomina la SCP. Conclusión: El oft almólogo y quien realiza la biometría deben tener en cuenta los cambios refractivos inducidos por cataratas. Este estudio propone una fórmula para correlacionar la queratometria y la longitud axial de la biometría con la refracción sin catarata. La refracción subjetiva con catarata no debe correlacionarse con los datos de la biometría por los cambios refractivos inducidos
Background: Cataract is a cause of reversible blindness, which can induce refractive changes, predominantly myopic shift . Objective: To describe and to analyze induced refractive changes due to cataract according to location of opacity in the diff erent lens layers. Study design: Observational retrospective, analytic study. Method: Included in the analysis were 184 pseudophakic eyes, which underwent cataract surgery with phacoemulsifi cation. Eyes were classifi ed in three groups according to the lens compromise: Nuclear + posterior subcapsular cataract (N + SCP), nuclear cataract (N) y posterior subcapsular cataract (SCP). Th e group (N+SCP) was classifi ed in three subgroups (N=SCP, N>SCP, SCP>N). To calculate refractive error of the eye without cataract we create a formula with spherical equivalent based on keratometry, axial length and pseudophakic eye refraction. To calculate the refractive change, the formula result is substracted from subjective refraction with cataract. Results: Th e most frequent cataract type was mixed cataract, nuclear and posterior subcapsular. In all cataract groups the most commonly observed shift was myopic. Th e mean myopic shift was -2.24. Nuclear cataract and mixed cataract with predominance of nuclear over posterior subcapsular opacity were responsible for the highest myopic changes. Hyperopic shift was observed in cataracts with predominance of posterior subcapsular opacity. Conclusions: Ophthalmologist and who performs biometry, must know about refractive changes associated with cataract. Th is study proposes a formula to correlate keratometry and axial length results of biometry with refraction without cataract. Subjective refraction with cataract should not be correlated with biometry data due to the shift s that this induces.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , AncianoRESUMEN
Cerebrovascular impairment is frequent in patients with Alzheimer disease and is believed to influence clinical manifestation and severity of the disease. Cardiovascular risk factors, especially hypertension, have been associated with higher risk of developing Alzheimer disease. To investigate the mechanisms underlying the hypertension, Alzheimer disease cross talk, we established a mouse model of dual pathology by infusing hypertensive doses of angiotensin II into transgenic APPPS1 mice overexpressing mutated human amyloid precursor and presenilin 1 proteins. At 4.5 months, at the early stage of disease progression, only hypertensive APPPS1 mice presented impairment of temporal order memory performance in the episodic-like memory task. This cognitive deficit was associated with an increased number of cortical amyloid deposits (223±5 versus 207±5 plaques/mm(2); P<0.05) and a 2-fold increase in soluble amyloid levels in the brain and in plasma. Hypertensive APPPS1 mice presented several cerebrovascular alterations, including a 25% reduction in cerebral microvessel density and a 30% to 40% increase in cerebral vascular amyloid deposits, as well as a decrease in vascular endothelial growth factor A expression in the brain, compared with normotensive APPPS1 mice. Moreover, the brain levels of nitric oxide synthase 1 and 3 and the nitrite/nitrate levels were reduced in hypertensive APPPS1 mice (by 49%, 34%, and 33%, respectively, compared with wild-type mice; P<0.05). Our results indicate that hypertension accelerates the development of Alzheimer disease-related structural and functional alterations, partially through cerebral vasculature impairment and reduced nitric oxide production.
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Enfermedad de Alzheimer/complicaciones , Regulación de la Expresión Génica , Hipertensión/complicaciones , ARN/genética , Factor A de Crecimiento Endotelial Vascular/genética , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Hipertensión/genética , Hipertensión/metabolismo , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Reacción en Cadena de la Polimerasa , Factor A de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
Objetivo: Describir resultados visuales y complicaciones de una serie de casos de pacientes pediátricos a los que se les realizó queratoplastia penetrante en el Hospital de San José, en Bogotá, Colombia. Diseño: Estudio observacional descriptivo, retrospectivo, serie de casos. Método: Se evaluaron 14 ojos de 12 pacientes menores de 16 años a quienes se les realizó queratoplastia penetrante entre los años 1999-2014. Se hizo una revisión de la literatura sobre etiología, manejo quirúrgico, seguimiento y sobrevida de injerto. Resultados: De los 14 ojos estudiados 8 ojos (57,1%) tenían patología congénita con injerto claro en 6 ojos (75%) entre los 3 y 9 meses, 3 ojos (21,4%) tenían etiología traumática, de estos, todos los injertos permanecieron claros en un rango de 3 meses a 11 años y 3 ojos (21,4%) tenían leucomas, queratitis o inminencia de perforación, de estos el injerto permaneció claro entre los 3 y 18 meses. Se encontró una mejoría de visión en 8 de los ojos evaluados (57,1%). Las complicaciones encontradas en estos pacientes fueron: glaucoma en 5 ojos (35.7%), falla de injerto en 6 ojos (42.8%), rechazo endotelial en 7 ojos (50%) y desprendimiento de retina en 1 ojo (7.14%). Conclusión: En el estudio, la mejoría visual fue ligeramente menor a la reportada en la literatura. Las complicaciones presentadas fueron principalmente rechazo endotelial y falla de injerto, lo que difiere de la literatura donde la catarata es la principal complicación.
Purpose: To describe visual results and complications in a case series of paediatric patients who underwent penetrating keratoplasty at Hospital de San José in Bogotá, Colombia. Design: Observational, descriptive and retrospective study, series of cases. Method: 14 eyes of 12 patients under 16 years (2 months - 16 years) who underwent penetrating keratoplasty in Hospital de San Jose from 1999 to 2014 were evaluated. A literature review of etiology, surgical management, monitoring and graft survival of pediatric patients was done. Results: Of the 14 eyes studied, 8 eyes (57.1%) had congenital pathology with clear graft in six eyes between 3 and 9 months, 3 eyes (21.4%) had traumatic aetiology, of these, all graft s remained clear in a range of 3 months to 11 years and 3 eyes (21.4%) had leucoma, keratitis or impending perforation, of these, the graft remained clear between 3 and 18 months. An improvement in vision was found in eight of the evaluated eyes (57.1%). The complications found in these patients were: glaucoma in 5 eyes (35.7%), graft failure in 6 eyes (42.8%), endothelial rejection in 7 eyes (50%) and retinal detachment in 1 eye (7.14%). Conclusion: In our study, the visual improvement was slightly lower than that reported in the literature. The complications presented were mainly endothelial rejection and graft failure, which differs from the literature where cataract is the main complication.