Elucidating the mechanism of action of alpha-1-antitrypsin using retinal pigment epithelium cells exposed to high glucose. Potential use in diabetic retinopathy.

BACKGROUND: Alpha-1-antitrypsin is a protein involved in avoidance of different processes that are seen in diabetic retinopathy pathogenesis. These processes include apoptosis, extracellular matrix remodeling and damage of vessel walls and capillaries. Furthermore, because of its anti-inflammatory effects, alpha-1-antitrypsin has been proposed as a possible therapeutic approach for diabetic retinopathy. Our group tested alpha-1-antitrypsin in a type 1 diabetes mouse model and observed a reduction of inflammation and retinal neurodegeneration. Thus, shedding light on the mechanism of action of alpha-1-antitrypsin at molecular level may explain how it works in the diabetic retinopathy context and show its potential for use in other retinal diseases. METHODS: In this work, we evaluated alpha-1-antitrypsin in an ARPE-19 human cell line exposed to high glucose. We explored the expression of different mediators on signaling pathways related to pro-inflammatory cytokines production, glucose metabolism, epithelial-mesenchymal transition and other proteins involved in the normal function of retinal pigment epithelium by RT-qPCR and Western Blot. RESULTS: We obtained different expression patterns for evaluated mediators altered with high glucose exposure and corrected with the use of alpha-1-antitrypsin. CONCLUSIONS: The expression profile obtained in vitro for the evaluated proteins and mRNA allowed us to explain our previous results obtained on mouse models and to hypothesize how alpha-1-antitrypsin hinder diabetic retinopathy progression on a complex network between different signaling pathways. GENERAL SIGNIFICANCE: This network helps to understand the way alpha-1-antitrypsin works in diabetic retinopathy and its scope of action.

Corneal Neovascularization: A Combined Approach of Bevacizumab and Suramin Showed Increased Antiangiogenic Effect Through Downregulation of BFGF and P2X2.

PURPOSE: The objective is to analyze the antiangiogenic mechanism of suramab, a pharmaceutical compound of bevacizumab and suramin, in a rabbit model of corneal angiogenesis. MATERIAL AND METHODS: Corneal neovascularization was induced in four groups of six New Zealand White rabbits by applying a filter paper disk soaked in 1 M Na (OH) on the central cornea. Group one was treated after injury with intravenous suramab at a dose equivalent to 3 mg/kg of bevacizumab and 10 mg/kg of suramin. Group two was treated with intravenous bevacizumab (5 mg/kg). Group three was treated with 10 mg/kg of suramin while the control group received no treatment. Digital photographs were taken at days 9, 15, 21, and 35. Neovessel formation was quantified giving a 0-4 score to each quadrant according to the centripetal growth of the longest vessel (neovessel index, NVI). Animals were sacrificed at day 35. Corneas were processed for histology, immunohistochemistry, and Western-blot using primary antibodies against P2X2, basic fibroblast growth factor (bFGF), LYVE-1, PECAM-1, and vascular endothelial growth factor-A (VEGF-A). RESULTS: Suramab significantly reduced neovessel growth (mean NVI: 4.2) compared to bevacizumab (8.4), suramin (7.22), and control animals (12.2) at 35 days post-injury (p < 0.01). A lower protein expression of P2X2, bFGF, LYVE-1, PECAM-1, and VEGF-A was found in the cornea of suramab animals than in the other groups of animals. CONCLUSIONS: Joint downregulation of bFGF, P2X2, bFGF, and LYVE-1 constitutes a mechanism that induces greater and longer inhibition of corneal angiogenesis. Results might be relevant to ophthalmic care. Ocular administration of suramab is currently being investigated.

[May Thurner syndrome with ischemic cerebrovascular accident and permeable oval foramen]. / Síndrome de May Thurner con accidente cerebrovascular isquémico y foramen oval permeable.

The association of cerebral ischemic attack with patent foramen ovale has not been extensively studied, and frequently the site of origin of embolism is not detected despite routine studies. We present the case of a young patient with ischemic stroke and permeable oval foramen in the context of May Thurner syndrome. The May Thurner syndrome is an entity scarcely studied in the medical literature and it has also been infrequently related to ischemic vascular cerebral accident, but in patients with permeable oval foramen without evidence of the emboligen source, it is interesting to rule it out as a cause of paradoxical embolism.

Racial and ethnic disparities in stroke subtypes: a multiethnic sample of patients with stroke.

Stroke subtypes have been reported to differ by race and ethnic subgroups and have not been adequately explained. We aim to evaluate if the prevalence of vascular risk factors accounts for differences observed in stroke subtypes by race/ethnicity. Patients with acute stroke were prospectively enrolled in the Miami Stroke Registry. Patients' demographic, clinical and radiological characteristics were systematically collected. Stroke subtypes were ascertained using TOAST criteria. The sample was divided into Non-Hispanic Whites (NHW), Hispanics, African Americans (AA), and Non-Hispanic Black Caribbean (NHBC). Univariable and multivariable logistic regression analyses were performed to assess differences among groups. Among 473 stroke patients (mean age 64 ± 14 years; 63.7% were men) of which 52.9% were Hispanic, 22.6% were AA, 13.5% NHBC and 11.0% were NHW. Large artery atherosclerosis was more prevalent in NHBC (OR 1.74, 95% CI 1.02-2.97) than in the other groups. Adjusting for covariates rendered the association not significant (OR 1.71, 95% CI 0.93-3.16). Cardioembolism was more frequent in Hispanics (OR 1.94, 95% CI 1.28-2.96) and NHW (OR 2.66, 95% CI 1.42-4.96) as compared to NHBC and AA combined. Adjusting for covariates, the association was no longer significant for Hispanics but was further strengthened for NHW (OR 3.02, 95% CI 1.42-6.42). Our results suggest that the vascular risk factors prevalence among different racial and ethnic groups partially explains disparities found in the prevalence of some stroke subtypes. Addressing health disparities remains an important public health aspect of stroke prevention.

Clasificación internacional del funcionamiento, la discapacidad y certificación de discapacidad en Colombia / International classification of functioning, disability and disability certification in Colombia

Lograr la certificación de la discapacidad en Colombia ha sido un reto que las personas con discapacidad se han impuesto y que el país ha asumido, en el marco de la legislación vigente y de los acuerdos internacionales a los que ha adherido Colombia. Para el efecto, se ha adoptado el modelo de clasificación internacional del funcionamiento, la discapacidad y la salud (CIF), en razón a que este instrumento, validado internacionalmente en diversos estudios, permite incorporar un estándar internacional de evaluación del estado funcional de los individuos. En este ensayo, inicialmente se define el concepto "discapacidad" y se ubica en el contexto histórico que lo precede, hasta llegar a la actual estructura de dominios y categorías de la CIF, instrumento que proporciona un marco común y generalizado, de forma tal que se permita proporcionar una adecuada asignación de servicios y beneficios generales, específicos, y a la vez se evalúa el diferencial existente entre el funcionamiento real y el potencial de las personas con discapacidad.

Certifying disability in Colombia has been demanded by disabled people; the country has assumed such challenge within the frame work of current legislation and international agreements signed by Colombia. A model of international classification of functioning (ICF), disability and healthwas thus adopted as it has been validated internationally in several studies; it incorporates international standards thereby allowing reliable evaluation of individuals' functional status. This essayinitially defines the concept of disabilityand locates it within a historical context leading to current ICF domain structure and categories. Such instrument provides a common, wide-ranging framework for providing suitable allocation of services and general and specific benefits, while assessing the differential between disabled people's current performance and their potential.

[International classification of functioning, disability and disability certification in Colombia]. / Clasificación internacional del funcionamiento, la discapacidad y certificación de discapacidad en Colombia.

Certifying disability in Colombia has been demanded by disabled people; the country has assumed such challenge within the frame work of current legislation and international agreements signed by Colombia. A model of international classification of functioning (ICF), disability and healthwas thus adopted as it has been validated internationally in several studies; it incorporates international standards thereby allowing reliable evaluation of individuals' functional status. This essayinitially defines the concept of disabilityand locates it within a historical context leading to current ICF domain structure and categories. Such instrument provides a common, wide-ranging framework for providing suitable allocation of services and general and specific benefits, while assessing the differential between disabled people's current performance and their potential.

Propylthiouracil-induced lupus, antiphospholipid syndrome, and stroke in a patient with Graves hyperthyroidism.

OBJECTIVE: To describe a case of propylthiouracil-induced lupus, complicated with antiphospholipid syndrome and acute ischemic stroke. DESIGN: Case report. SETTING: Academic medical center. PATIENT: A 27-year-old man with a diagnosis of Graves disease developed multiple ischemic strokes 2 weeks after starting treatment with propylthiouracil. Thyrotoxicosis and abnormal hypercoagulable and rheumatological profiles were remarkable, with prolonged partial thromboplastin time, elevated anticardiolipin antibody level, and positive antinuclear antibody, lupus anticoagulant, Sjögren antibody, and anti-double-stranded DNA antibody test results, which were more than 8-fold greater than normal values. No clinical manifestations of systemic lupus erythematosus were present. INTERVENTION: Discontinuation of propylthiouracil and treatment with radioactive iodine. RESULTS: Hyperthyroidism resolved and anti-double-stranded DNA antibodies returned to normal levels. Eventually, antiphospholipid syndrome was diagnosed. He was treated with oral anticoagulation and remained asymptomatic for 1 year of follow-up. CONCLUSION: In this young man with Graves hyperthyroidism, treatment with propylthiouracil was associated with transient autoimmune reactions suggestive of drug-induced lupus, antiphospholipid syndrome, and acute ischemic stroke.

Successful intravenous thrombolysis for acute stroke in a child.

We report an 8-year-old white girl with no previous medical history who developed sudden onset right hemiplegia, left gaze preference, and global aphasia. An acute left middle cerebral artery stroke syndrome was diagnosed. She was treated with intravenous recombinant tissue plasminogen activator, 2 hours after the onset of symptoms. A magnetic resonance image demonstrated an acute left middle cerebral artery stroke, and a magnetic resonance angiography showed a patent left middle cerebral artery. At discharge, she was able to speak normally and walk without support. She was also able to raise the right arm up to the level of the shoulder and showed increased motility of the hand and fingers. No treatment-related complications happened. To the best of our knowledge, this is, so far, the youngest child successfully treated with intravenous recombinant tissue plasminogen activator for acute ischemic stroke.

[Genetics of epilepsy]. / Genética de las epilepsias.

In the last few years, the presence of specific genetic abnormalities leading to some of the classical epileptic syndromes has been clearly elucidated. This means that for the first time, it has become possible to create a strong relationship between the presence of specific genomic and/or proteomic abnormalities and epileptic syndromes previously considered to be "idiopathic". The majority of such genetic defects have been found in genes coding for either ion channels and/or membrane receptors, a fact that somehow seems to confirm the previously postulated importance of the latter structures in the electrochemical activity of neurons. This review will focus on the genetic and clinical aspects of such conditions. Some of the most relevant data suggesting the existence of additional genetic defects in many other epileptic syndromes will also be briefly reviewed, even though a definitive relationship to many of them has not yet been established in the form of specific gene defects. In addition, the worrisome fact that despite the importance of such advances, their application in routine clinical practice remains very limited will be emphasized, in particular in the pharmacological management of most patients. Finally, a brief discussion about the intriguing possibilities of such findings, including the development of neuro-pharmacogenomics plus several ethical issues, will also be attempted.

Maxillary cyst associated with an invaginated tooth: a case report and literature review.

Dental invagination or dens in dente is a rare malformation with a widely varied morphology. Radiographically, the affected tooth shows an infolding of the enamel and dentin that can extend to within the pulp cavity and the root and sometimes to the root apex. It can occur in both primary and permanent teeth, and its prevalence is reported to be 1.7% to 10%. The dental anomalies observed in association with dental invagination include taurodontia, microdontia, supernumerary teeth, gemination, and dentinogenesis imperfecta. This article presents a clinical case in which a radiographic finding could be compatible with the presence of a nasopalatine or globulomaxillary cyst and a dens in dente. It was decided to extract the invaginated tooth, and by 15 days postextraction, the radiolucid area had completely disappeared. The complex surgery that would have been required to remove the patient's supposed cyst was thus avoided. Clinical and radiographic examination is suggested before making further decisions that could complicate treatment when a lesion is associated with other dental anomalies.