Subducting plate structure and megathrust morphology from deep seismic imaging linked to earthquake rupture segmentation at Cascadia.

The origin of rupture segmentation along subduction zone megathrusts and linkages to the structural evolution of the subduction zone are poorly understood. Here, regional-scale seismic imaging of the Cascadia margin is used to characterize the megathrust spanning ~900 km from Vancouver Island to the California border, across the seismogenic zone to a few tens of kilometers from the coast. Discrete domains in lower plate geometry and sediment underthrusting are identified, not evident in prior regional plate models, which align with changes in lithology and structure of the upper plate and interpreted paleo-rupture patches. Strike-slip faults in the lower plate associated with oblique subduction mark boundaries between regions of distinct lower plate geometry. Their formation may be linked to changes in upper plate structure across long-lived upper plate faults. The Juan de Fuca plate is fragmenting within the seismogenic zone at Cascadia as the young plate bends beneath the heterogeneous upper plate resulting in structural domains that coincide with paleo-rupture segmentation.

Autosomal recessive hypotrichosis with loose anagen hairs associated with TKFC mutations.

BACKGROUND: Loose anagen hair is a rare form of impaired hair anchorage in which anagen hairs that lack inner and outer root sheaths can be gently and painlessly plucked from the scalp. This condition usually occurs in children and is often self-limiting. A genetic basis for the disorder has been suggested but not proven. A better understanding the aetiology of loose anagen hair may improve prevention and treatment strategies. OBJECTIVES: To identify a possible genetic basis of loose anagen hair using next-generation DNA sequencing and functional analysis of variants identified. METHODS: In this case study, whole-exome sequencing analysis of a pedigree with one affected individual with features of loose anagen hair was performed. RESULTS: The patient was found to be compound heterozygous for two single-nucleotide substitutions in TKFC resulting in the following missense mutations: c.574G> C (p.Gly192Arg) and c.682C> T (p.Arg228Trp). Structural analysis of human TKFC showed that both mutations are located near the active site cavity. Kinetic assays of recombinant proteins bearing either of these amino acid substitutions showed almost no dihydroxyacetone kinase or D-glyceraldehyde kinase activity, and FMN cyclase activity reduced to just 10% of wildtype catalytic activity. CONCLUSIONS: TKFC missense mutations may predispose to the development of loose anagen hairs. Identification of this new biochemical pathobiology expands the metabolic and genetic basis of hypotrichosis.

Possible mechanisms involved in the effect of the subchronic administration of rosuvastatin on endothelial function in rats with metabolic syndrome.

Metabolic syndrome is a multifaceted condition associated with a greater risk of various disorders (e.g., diabetes and heart disease). In a rat model of metabolic syndrome, an acute in vitro application of rosuvastatin causes relaxation of aortic rings. Since the outcome of a subchronic rosuvastatin treatment is unknown, the present study explored its effect on acetylcholine-induced vasorelaxation of aortic rings from rats with metabolic syndrome. Animals were submitted to a 16-week treatment, including a standard diet, a cafeteria-style diet (CAF-diet), or a CAF-diet with daily rosuvastatin treatment (10 mg/kg). After confirming the development of metabolic syndrome in rats, aortic segments were extracted from these animals (those treated with rosuvastatin and untreated) and the acetylcholine-induced relaxant effect on the corresponding rings was evaluated. Concentration-response curves were constructed for this effect in the presence/absence of L-NAME, ODQ, KT 5823, 4-aminopyridine (4-AP), tetraethylammonium (TEA), apamin plus charybdotoxin, glibenclamide, indomethacin, clotrimazole, and cycloheximide pretreatment. Compared to rings from control rats, acetylcholine-induced vasorelaxation decreased in rings from animals with metabolic syndrome, and was maintained at a normal level in animals with metabolic syndrome plus rosuvastatin treatment. The effect of rosuvastatin was inhibited by L-NAME, ODQ, KT 5823, TEA, apamin plus charybdotoxin, but unaffected by 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. In conclusion, the subchronic administration of rosuvastatin to rats with metabolic syndrome improved the acetylcholine-induced relaxant response, involving stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

Treatment of symptomatic epiblepharon with Botulinum toxin type A in patients under 2years of age. / Experiencia del uso de la toxina botulínica tipo A para el tratamiento sintomático del epiblefaron en pacientes menores de 2 años.

INTRODUCTION: Epiblepharon is a congenital eyelid malposition due to a horizontal skin fold and a redundant orbicular muscle, resulting in the inward positioning of the eyelashes. OBJECTIVE: Personal experience is presented of the non-surgical correction of symptomatic epiblepharon using a pretarsal injection of 5 IU of botulinum toxin type A (BoNT-A) into the orbicular muscle. MATERIAL AND METHODS: Patients with epiblepharon younger than 2 year were included in the study. A review was made of their clinical charts and the symptoms and signs of epiblepharon were evaluated before and after treatment with BoNT-A. RESULTS: A total of 40 patients were included (28 girls [70%]). The mean age at treatment was 11 months (range, 4-24 months). A total of 76 eyelids were treated with BoNT-A. A statistically significant improvement in symptoms, lash-corneal touch, and punctate corneal epitheliopathy were reported after the treatment with 5IU BoNT-A. The mean final follow-up was 25.5 weeks (range, 4-92 months). CONCLUSIONS: The present study provides evidence that a pretarsal BoNT-A injection is an effective and safe treatment for the correction of symptomatic epiblepharon in patients younger than 2 years of age.

Possible mechanisms involved in the effect of the subchronic administration of rosuvastatin on endothelial function in rats with metabolic syndrome

Metabolic syndrome is a multifaceted condition associated with a greater risk of various disorders (e.g., diabetes and heart disease). In a rat model of metabolic syndrome, an acute in vitro application of rosuvastatin causes relaxation of aortic rings. Since the outcome of a subchronic rosuvastatin treatment is unknown, the present study explored its effect on acetylcholine-induced vasorelaxation of aortic rings from rats with metabolic syndrome. Animals were submitted to a 16-week treatment, including a standard diet, a cafeteria-style diet (CAF-diet), or a CAF-diet with daily rosuvastatin treatment (10 mg/kg). After confirming the development of metabolic syndrome in rats, aortic segments were extracted from these animals (those treated with rosuvastatin and untreated) and the acetylcholine-induced relaxant effect on the corresponding rings was evaluated. Concentration-response curves were constructed for this effect in the presence/absence of L-NAME, ODQ, KT 5823, 4-aminopyridine (4-AP), tetraethylammonium (TEA), apamin plus charybdotoxin, glibenclamide, indomethacin, clotrimazole, and cycloheximide pretreatment. Compared to rings from control rats, acetylcholine-induced vasorelaxation decreased in rings from animals with metabolic syndrome, and was maintained at a normal level in animals with metabolic syndrome plus rosuvastatin treatment. The effect of rosuvastatin was inhibited by L-NAME, ODQ, KT 5823, TEA, apamin plus charybdotoxin, but unaffected by 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. In conclusion, the subchronic administration of rosuvastatin to rats with metabolic syndrome improved the acetylcholine-induced relaxant response, involving stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

The effect of soft contact lens thickness in visual function after intracorneal ring segments surgery.

OBJECTIVE: To study the influence of soft contact lens (SCL) central thickness and material in keratoconus on visual function after intracorneal ring segment (ICRS) surgery. METHODS: A pilot, experimental, prospective, cross-sectional and double-blind study was performed. Fourteen keratoconus patients with age range of 34.75±9.22years (7 males and 7 females) with ICRS implanted were involved in the study. Two different SCL materials [Hioxifilcon A (G-5X/p-GMA/HEMA) and Lucifilcon A (silicone-hydrogel)] with four different central thicknesses (0.1, 0.2, 0.3 and 0.4mm) were fitted in one eye per patient, selected randomly. High and low corrected distance visual acuity (CDVA) and contrast sensitivity (CS), corneal topography and corneal and total aberrometry were measured. RESULTS: Corneal spherical like, coma like and root mean square (RMS) decreased significantly for 0.3 and 0.4mm in both SCL materials (p<0.05). Total RMS decreased significantly for 0.4mm with both SCL materials (p<0.05). High and low CDVA improved for 0.4mm of thickness for both materials (p<0.05). Statistically increasing were found in all thicknesses studied for CS in both materials (p<0.05). CONCLUSION: A central thickness of the SCL equal or superior to 0.4mm seems to decrease the ocular high order aberration (HOA) and to improve the visual function in keratoconus patients implanted with ICRS. However, the modulus of rigidity of the SCL would not influence the HOA correction.

¿Son efectivos los probióticos en prevenir infecciones del tracto urinario? / Are probiotics effective in preventing urinary tract infection?

INTRODUCCIÓN: La infección del tracto urinario es la infección bacteriana más común y su recurrencia es frecuente. Entre las variadas medidas que potencialmente disminuirían este riesgo se ha planteado el uso de probióticos. Sin embargo, no está claro si realmente son efectivos. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud a nivel mundial, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos seis revisiones sistemáticas que en conjunto incluyeron nueve estudios, entre ellos siete ensayos aleatorizados. Concluimos que no está claro si los probióticos disminuyen el riesgo de infección urinaria sintomática, porque la certeza de la evidencia es muy baja.

INTRODUCTION: Urinary tract infection is the most common bacterial infection and recurrences are common. Probiotics have been proposed as an alternative to decrease this risk. However, it is not clear if they are really effective. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified six systematic reviews including nine studies overall, of which seven were randomized trials. We concluded it is not clear whether probiotics decrease the risk of symptomatic urinary tract infection, because the certainty of the evidence is very low.

Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats.

Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05) by 10-5 M L-NAME (a direct inhibitor of nitric oxide synthase), 10-7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase), 10-6 M KT 5823 (an inhibitor of protein kinase G), 10-2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker) and 10-7 M apamin plus 10-7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively), and was blocked by 8×10-2 M potassium (a high concentration) and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

[Management of upper eyelid retraction associated with dysthyroid orbitopathy during the acute inflammatory phase with botulinum toxin type A]. / Traitement de la rétraction palpébrale supérieure associée à l'ophtalmopathie dysthyroïdienne en phase active inflammatoire avec l'injection de toxine botulique A.

PURPOSE: To evaluate the efficacy of transconjunctival botulinum toxin type A (BTX-A) in the treatment of upper eyelid retraction in the active inflammatory phase of dysthyroid orbitopathy, establish the ideal dose, and evaluate side effects. METHODS: This is a comparative, prospective study in patients with thyroid orbitopathy, conducted at the Conde Ophthalmology Institute in Valenciana, Mexico. The patients included had dysthyroid orbitopathy in the inflammatory phase, and they were treated with subconjunctival injection of botulinum toxin type A (BTX-A) in the upper eyelid. Five units (group 1) and ten units (group 2) of BTX-A, in a single subconjunctival dose were applied to the non-dominant eye. We evaluated visual acuity, margin-to-reflex distance (RPM1), crease height, ocular motility, diplopia and keratitis, before and after administration of the toxin. The patients were followed at one, 4 and 16 weeks, with the Student t-test as a statistical analysis. RESULTS: At week 4, 15 patients (100%) showed a reduced margin to reflex distance. The mean result for group 1 was -1.75mm (range -1 to -2.5mm) and group 2 was -2mm (range -1 to -4mm). Statistically significant differences were seen between pre-treatment and week 4 in both groups, but no differences between doses. Complete improvement of keratitis and lagophthalmos was observed in 5 and 2 patients, respectively. Visual acuity, ocular motility and crease height did not change in 93% of the patients. One patient (group 1) exhibited complete ptosis and vertical diplopia, which resolved spontaneously at week 6. CONCLUSION: Transconjunctival BTX-A application is safe and effective for the treatment of eyelid retraction in dysthyroid orbitopathy. No difference was found between doses. No severe side effects were reported.

Mutation profiles in early-stage lung squamous cell carcinoma with clinical follow-up and correlation with markers of immune function.

Background: Lung squamous cell carcinoma (LUSC) accounts for 20­30% of non-small cell lung cancers (NSCLCs). There are limited treatment strategies for LUSC in part due to our inadequate understanding of the molecular underpinnings of the disease. We performed whole-exome sequencing (WES) and comprehensive immune profiling of a unique set of clinically annotated early-stage LUSCs to increase our understanding of the pathobiology of this malignancy. Methods: Matched pairs of surgically resected stage I-III LUSCs and normal lung tissues (n = 108) were analyzed by WES. Immunohistochemistry and image analysis-based profiling of 10 immune markers were done on a subset of LUSCs (n = 91). Associations among mutations, immune markers and clinicopathological variables were statistically examined using analysis of variance and Fisher's exact test. Cox proportional hazards regression models were used for statistical analysis of clinical outcome. Results: This early-stage LUSC cohort displayed an average of 209 exonic mutations per tumor. Fourteen genes exhibited significant enrichment for somatic mutation: TP53, MLL2, PIK3CA, NFE2L2, CDH8, KEAP1, PTEN, ADCY8, PTPRT, CALCR, GRM8, FBXW7, RB1 and CDKN2A. Among mutated genes associated with poor recurrence-free survival, MLL2 mutations predicted poor prognosis in both TP53 mutant and wild-type LUSCs. We also found that in treated patients, FBXW7 and KEAP1 mutations were associated with poor response to adjuvant therapy, particularly in TP53-mutant tumors. Analysis of mutations with immune markers revealed that ADCY8 and PIK3CA mutations were associated with markedly decreased tumoral PD-L1 expression, LUSCs with PIK3CA mutations exhibited elevated CD45ro levels and CDKN2A-mutant tumors displayed an up-regulated immune response. Conclusion(s): Our findings pinpoint mutated genes that may impact clinical outcome as well as personalized strategies for targeted immunotherapies in early-stage LUSC.

Granulomatosis with polyangiitis confined to lacrimal gland, a case report. / Granulomatosis con poliangeítis localizado en la glándula lagrimal, a propósito de un caso.

CLINICAL CASE: A 43 year-old woman consulted due to 2 months of swelling on the superolateral side of the left orbit, with pain and erythema. An excisional biopsy was performed that revealed vasculitis with polyangiitis of the lacrimal gland. A systemic study showed that no other system was compromised. DISCUSSION: Orbital involvement occurs in up to 60% of patients with granulomatosis with polyangiitis. The involvement of the lacrimal gland is rare and often unilateral. Serological tests are generally negative, both in initial stages, as in localized forms of the disease.

ZEB1 induces LOXL2-mediated collagen stabilization and deposition in the extracellular matrix to drive lung cancer invasion and metastasis.

Lung cancer is the leading cause of cancer-related deaths, primarily due to distant metastatic disease. Metastatic lung cancer cells can undergo an epithelial-to-mesenchymal transition (EMT) regulated by various transcription factors, including a double-negative feedback loop between the microRNA-200 (miR-200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT promotes malignancy remain largely undefined. Although the cell-intrinsic effects of EMT are important for tumor progression, the reciprocal dynamic crosstalk between mesenchymal cancer cells and the extracellular matrix (ECM) is equally critical in regulating invasion and metastasis. Investigating the collaborative effect of EMT and ECM in the metastatic process reveals increased collagen deposition in metastatic tumor tissues as a direct consequence of amplified collagen gene expression in ZEB1-activated mesenchymal lung cancer cells. In addition, collagen fibers in metastatic lung tumors exhibit greater linearity and organization as a result of collagen crosslinking by the lysyl oxidase (LOX) family of enzymes. Expression of the LOX and LOXL2 isoforms is directly regulated by miR-200 and ZEB1, respectively, and their upregulation in metastatic tumors and mesenchymal cell lines is coordinated to that of collagen. Functionally, LOXL2, as opposed to LOX, is the principal isoform that crosslinks and stabilizes insoluble collagen deposition in tumor tissues. In turn, focal adhesion formation and FAK/SRC signaling is activated in mesenchymal tumor cells by crosslinked collagen in the ECM. Our study is the first to validate direct regulation of LOX and LOXL2 by the miR-200/ZEB1 axis, defines a novel mechanism driving tumor metastasis, delineates collagen as a prognostic marker, and identifies LOXL2 as a potential therapeutic target against tumor progression.

Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up.

Background: Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable to lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses of a unique set of clinically annotated early-stage LUADs to better understand the pathogenesis of this disease and identify clinically relevant molecular markers. Methods: We performed WES of 108 paired stage I-III LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B) were profiled by imaging-based immunohistochemistry (IHC) in a subset of LUADs (n = 92). Associations among mutations, immune markers and clinicopathological variables were analyzed using ANOVA and Fisher's exact test. Cox proportional hazards regression models were used for multivariate analysis of clinical outcome. Results: LUADs in this cohort exhibited an average of 243 coding mutations. We identified 28 genes with significant enrichment for mutation. SETD2-mutated LUADs exhibited relatively poor recurrence- free survival (RFS) and mutations in STK11 and ATM were associated with poor RFS among KRAS-mutant tumors. EGFR, KEAP1 and PIK3CA mutations were predictive of poor response to adjuvant therapy. Immune marker analysis revealed that LUADs in smokers and with relatively high mutation burdens exhibited increased levels of immune markers. Analysis of immunophenotypes revealed that LUADs with STK11 mutations exhibited relatively low levels of infiltrating CD4+/CD8+ T-cells indicative of a muted immune response. Tumoral PD-L1 was significantly elevated in TP53 mutant LUADs whereas PIK3CA mutant LUADs exhibited markedly down-regulated PD-L1 expression. LUADs with TP53 or KEAP1 mutations displayed relatively increased CD57 and Granzyme B levels indicative of augmented natural killer (NK) cell infiltration. Conclusion(s): Our study highlights molecular and immune phenotypes that warrant further analysis for their roles in clinical outcomes and personalized immune-based therapy of LUAD.

Evisceration surgery in a highly specialized center in Mexico: A retrospective study of 7 years of experience. / Cirugía de evisceración ocular en un centro de alta especialidad en México: estudio retrospectivo de 7 años de experiencia.

INTRODUCTION: Evisceration is currently becoming the technique of choice in the treatment of certain eye diseases, including, among others, painful blind eye and endophthalmitis. The most widely used implants are currently the hydroxyapatite and porous polyethylene for the rehabilitation of the anophthalmic socket. OBJECTIVE: To describe the indications, type of implant material used, and complications in evisceration surgery. METHODS: A retrospective, observational, descriptive study based on clinical records of patients that underwent evisceration between 2008 and 2015 in the Instituto Fundación Conde de Valenciana, Mexico. RESULTS: A total of 186 evisceration surgeries were performed, of which 52.7% of the patients were men. The mean age was 54 years. The right eye was eviscerated in 53% of cases, and 79.2% had a vision of no light perception. Most patients had preoperative pain. The most common diagnosis for which evisceration was performed was endophthalmitis. Phthisis bulbi was reported in 20 eyes. A primary implant was inserted in 86.81% of the cases, with 34.81% of the implants being made of porous polyethylene. Four cases showed extrusion of the implant, with 2 cases of porous polyethylene. The ocular prosthesis was tolerated in 91% of cases. There were no cases of sympathetic ophthalmia. CONCLUSION: Evisceration is shown to be a good alternative to enucleation in cases where the sclera can be preserved, showing a low incidence of sympathetic ophthalmia.

Role of adenylyl cyclase in reduced ß-adrenoceptor-mediated vasorelaxation during maturation.

Beta-adrenergic receptor (ßAR)-dependent blood vessel relaxation is impaired in older animals and G protein activation has been suggested as the causative mechanism. Here, we investigated the role of ßAR subtypes (ß1AR, ß2AR, and ß3AR) and cAMP in maturation-dependent vasorelaxation impairment. Aortic rings from 15 Sprague-Dawley male rats (3 or 9 weeks old) were harvested and left intact or denuded of the endothelium. Vascular relaxation in aortic rings from younger and older groups was compared in the presence of ßAR subtype agonists and antagonists along with cAMP and cGMP antagonists. Isolated aortic rings were used to evaluate relaxation responses, protein expression was evaluated by western blot or real time PCR, and metabolites were measured by ELISA. Expression of ßAR subtypes and adenylyl cyclase was assessed, and cAMP activity was measured in vascular tissue from both groups. Isoproterenol- and BRL744-dependent relaxation in aortic rings with and without endothelium from 9-week-old rats was impaired compared with younger rats. The ß1AR antagonist CGP20712A (10-7 M) did not affect isoproterenol or BRL744-dependent relaxation in arteries from either group. The ß2AR antagonist ICI-118,551 (10-7 M) inhibited isoproterenol-dependent aortic relaxation in both groups. The ß3AR antagonist SR59230A (10-7 M) inhibited isoproterenol- and BRL744-dependent aortic ring relaxation in younger but not in older rats. All ßAR subtypes were expressed in both groups, although ß3AR expression was lower in the older group. Adenylyl cyclase (SQ 22536) or protein kinase A (H89) inhibitors prevented isoproterenol-induced relaxation in younger but not in older rats. Production of cAMP was reduced in the older group. Adenylyl cyclase III and RyR3 protein expression was higher in the younger group. In conclusion, altered expression of ß3AR and adenylyl cyclase III may be responsible for reduced cAMP production in the older group.

Pharmacological study of the mechanisms involved in the vasodilator effect produced by the acute application of triiodothyronine to rat aortic rings.

A relationship between thyroid hormones and the cardiovascular system has been well established in the literature. The present in vitro study aimed to investigate the mechanisms involved in the vasodilator effect produced by the acute application of 10-8-10-4 M triiodothyronine (T3) to isolated rat aortic rings. Thoracic aortic rings from 80 adult male Wistar rats were isolated and mounted in tissue chambers filled with Krebs-Henseleit bicarbonate buffer in order to analyze the influence of endothelial tissue, inhibitors and blockers on the vascular effect produced by T3. T3 induced a vasorelaxant response in phenylephrine-precontracted rat aortic rings at higher concentrations (10-4.5-10-4.0 M). This outcome was unaffected by 3.1×10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin, or 10-5 M cycloheximide. Contrarily, vasorelaxant responses to T3 were significantly (P<0.05) attenuated by endothelium removal or the application of 10-6 M atropine, 10-5 M L-NG-nitroarginine methyl ester (L-NAME), 10-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10-6 M (9S,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i](1,6)benzodiazocine-10-carboxylic acid, methyl ester KT 5823, 10-2 M tetraethylammonium (TEA), or 10-7 M apamin plus 10-7 M charybdotoxin. The results suggest the involvement of endothelial mechanisms in the vasodilator effect produced by the acute in vitro application of T3 to rat aortic rings. Possible mechanisms include the stimulation of muscarinic receptors, activation of the NO-cGMP-PKG pathway, and opening of Ca2+-activated K+ channels.

Orbital ossifying fibroma: A case report. / Fibroma osificante orbitario, a propósito de un caso.

CLINICAL CASE: The case concerns a 34 year-old man, who presented with pain in the medial canthus in his left eye, with proptosis and diplopia. The examination showed exophthalmus and a palpable mass at the inner canthus. The computed tomography revealed a lesion, which was confirmed by biopsy to be a ossifying fibroma. DISCUSSION: Ossifying fibroma is a benign fibro-osseous lesion that mostly affects the jaw. Clinical presentation and complications vary according to its location. Clinical examination, imaging, and histopathology are essential for definitive diagnosis. Surgical treatment is multidisciplinary and long-term follow up is needed.