Comparative analysis of inflammatory response in the BALB/c and C57BL/6 mouse strains in an endotoxin-induced uveitis model.

Uveitis is an inflammatory disease associated with diverse systemic and autoimmune diseases, defined as the inflammation of any given segment of the uveal tract, uveitis contributes with 5-20% cases of blindness in the USA/Europe and >25% of cases in third-world countries. To understand its pathogenic mechanisms, BALB/c and C57BL/6 mice were induced to develop the condition by a single intraperitoneal injection of E. coli lipopolysaccharide, the aim of the present work is to determine leukocyte infiltration in an endotoxin-induced uveitis (EIU) in two non-related mouse strains. Histopathological findings and clinical analysis were conducted 24 and 48 h postinjection. Both strains presented conventional clinical signs of uveitis 24 h post LPS injection and the highest inflammatory leukocyte infiltration in the uveal tract was found in the BALB/c mouse strain. This article will give an insight on the difference of the inflammatory response in the EIU model in two different mouse strains and the relationship between the pathologic response.

Multifocal electroretinography changes at the 1-year follow-up in a cohort of diabetic macular edema patients treated with ranibizumab.

PURPOSE: To determine the changes in the multifocal electroretinogram (mfERG) at 1 year in a clinical series of diabetic macular edema (DME) patients treated with ranibizumab (RNBZ) using a pro re nata protocol. METHODS: We analyzed a clinical series of 35 eyes of 35 patients with DME at baseline and after treating them with RNBZ over 1 year, in order to determine the change in the macular function, which was assessed by means of the response density and the implicit time of the first-order kernel (FOK) P1 wave of the mfERG at the foveola (R1), fovea (R2) and parafovea (R3). These electrophysiological parameters were studied taking into account different independent variables, such as DME type, degree of diabetic retinopathy (DR), level of preservation of both the ellipsoid zone (IS/OS) and the external limiting membrane (ELM) and changes in central retinal thickness (CRT) and total macular volume (TMV). We also studied the relationship between the response density and the best-corrected visual acuity (BCVA). RESULTS: Eyes with cystic and spongiform DME showed better response density with respect to the serous type (p < 0.001) at baseline. Similarly, eyes with high IS/OS and ELM preservation rates showed higher initial response density compared to the others (p < 0.001). Eyes with moderate DR had better response density compared to those with severe and proliferative DR (p = 0.001). At the beginning of the study, those eyes with proliferative and severe DR showed longer implicit times with respect to those with moderate DR (p = 0.04). The response density significantly increased in eyes that anatomically restored the IS/OS and the ELM after being treated with RNBZ (both p < 0.001). Similarly, eyes with spongiform DME further improved the response density with respect to those with cystic and serous DME (p < 0.001). On the contrary, eyes with hard exudates showed less improvement in their response density at the end of the study (p < 0.001). We observed a significant relationship between BCVA and the response density achieved at the end of the study (p = 0.012). Eyes with severe and proliferative DR significantly shortened implicit time compared to those with moderate DR (p = 0.04). CONCLUSIONS: The multifocal electroretinogram allowed us to differentiate groups of eyes with DME according to their electrophysiological profile, both initially and after being treated with RNBZ. Ranibizumab increased the response density in all DME types included in the study, with a maximum response in those eyes with spongiform type. Once treated with RNBZ, the macular electrophysiological activity improved in eyes that had a well-preserved ellipsoid zone and ELM. The presence of hard exudates was a limitation to the response density achieved at the foveola.

Tissue and cellular characterisation of nucleolin in a murine model of corneal angiogenesis.

PURPOSE: Corneal neovascularisation (CNV), with consequent loss of transparency, is due to an imbalance of proangiogenic factors. Cell-surface nucleolin (NCL) has been associated with neo-angiogenesis. There are studies identifying NCL translocation from nucleus to the cell surface, which is essential for endothelial cell proliferation. To find the possible role of NCL in the generation of corneal neovessels, the aim of this study is to characterise the NCL presence and cell-localisation in non-injured corneas, as well as to describe the changes in NCL cell and tissue localisation in CNV, and to analyse the effect of bevacizumab on NCL cellular and tissular distribution. METHODS: Suture-induced CNV was performed in mice. The corneal tissues were obtained and the histological and co-immunofluorescence assays were performed using different proteins, such as CD31, cadherin and isolectin B4. To determine the possible role of VEGF in NCL presence and localisation in our CNV model, bevacizumab was concomitantly used. RESULTS: Nucleolin was principally observed in the nucleus of the basal epithelial cells of normal corneas. Interestingly, angiogenesis-induced changes were observed in the localisation of NCL, not only in tissue but also at the cellular level where NCL was extranuclear in epithelial cells, stromal cells and neovessels. In contrast, these changes were reverted when bevacizumab was used. Besides, NCL was able to stain only aberrant corneal neovessels in comparison with retinal vessels. CONCLUSIONS: NCL mobilisation outside the nucleus during angiogenesis could have a possible role as a proangiogenic molecule in the corneal tissue.

Decreased orthostatic adrenergic reactivity in non-dipping postural tachycardia syndrome.

Whether non-dipping - the loss of the physiologic nocturnal drop in blood pressure - among patients with postural tachycardia syndrome (POTS) is secondary to autonomic neuropathy, a hyperadrenergic state, or other factors remains to be determined. In 51 patients with POTS (44 females), we retrospectively analyzed 24-hour ambulatory blood pressure recordings, laboratory indices of autonomic function, orthostatic norepinephrine response, 24-hour natriuresis and peak exercise oxygen consumption. Non-dipping (<10% day-night drop in systolic blood pressure) was found in 55% (n=28). Dippers and non-dippers did not differ in: 1) baseline characteristics including demographic and clinical profile, sleep duration, daytime blood pressure, 24-hour natriuresis, and peak exercise oxygen consumption; 2) severity of laboratory autonomic deficits (sudomotor, cardiovagal and adrenergic); 3) frequency of autonomic neuropathy (7/23 vs. 8/28, P=0.885); 4) supine resting heart rate (75.3±14.0bpm vs. 74.0±13.8bpm, P=0.532); or 5) supine plasma norepinephrine level (250.0±94.9pg/ml vs. 207.0±86.8pg/ml, P=0.08). However, dippers differed significantly from non-dippers in that they had significantly greater orthostatic heart rate increment (43±16bpm vs. 35±10bpm, P=0.007) and significantly greater orthostatic plasma norepinephrine increase (293±136.6pg/ml vs. 209±91.1pg/ml, P=0.028). Our data indicate that in patients with POTS, a non-dipping blood pressure profile is associated with a reduced orthostatic sympathetic reactivity not accounted for by autonomic neuropathy.

Presentación sistémica de Aspergillus spp con semiología neurológica en un Pastor Alemán: informe de un caso clínico / Systemic presentation of Aspergillus spp with neurological involvement in a German Shepherd: clinical case report

Infections of the central nervous system are uncommon in dogs. Pathogenic fungi such as Aspergillus, Cryptococcus spp, Blastomyces dermatitidis and Coccidioides immitis have been reported. An Aspergillus infection is mainly a respiratory event and very seldom it may become disseminated, the German shepherd seems to be the more prone to this type of aspergillosis specially if an immunological deficiency is present. A 1.5 year old female German Shepherd from Cancun, Quintana Roo, State, in the southeast of Mexico was presented to the small animal hospital, she showed tetraparesis, hiporeflex and deep retarded sensitivity in all four members, loss of sensitivity in the left side of the face, absence of pupil reflex and menace reflex as well as absence of muscular tone of the vulva and anal sphincter. The third day after presentation, she died. At necropsy polyencephalomalace, mielitis and diffuse leucomielitis piogranomalotosus were found. In the cytology of lymph node and other tissues aspergilli like hiphae were observed, this was confirmed by using the highly specific double diffusion test. Then, a PCR test was carried out with tissue fixed in 10% formaldehyde, but it failed probably due to destruction of the DNA.

La infección del sistema nervioso en el perro es poco común; posibles causas son Aspergillus spp, Cryptococcus neoformans, Blastomyces dermatidis y Coccidioides immitis. La infección por Aspergillus spp afecta al aparato respiratorio y en pocas ocasiones se presenta de manera diseminada. Sin embargo, en el Pastor Alemán hay mayor incidencia de éste, pues dicha infección se asocia con una deficiencia inmunológica. Se describe el caso de una perra de raza Pastor Alemán, de 1.5 años de edad, referida de Cancún, Quintana Roo, México, con tetraparesis, hiporreflexia y sensibilidad profunda retardada en los cuatro miembros, disminución de sensibilidad en el lado derecho de la cara y ausencia de reflejo pupilar y de amenaza en ojo derecho; además de ausencia de tono vulvar y de esfínter anal. A los tres días después del ingreso la perra falleció. A la necropsia se encontró polioencefalomalacia, mielitis y leucomielitis piogranulomatosa difusa. En la citología de linfonodo y en la histopatología de diferentes tejidos se identificaron hifas compatibles con Aspergillus spp. Con el fin de dar certeza al diagnóstico, se realizó prueba de doble inmunodifusión, que es altamente específica, la cual confirmó el diagnóstico de Aspergillus spp. Posteriormente se corrió PCR a partir de una muestra de tejido en formalina al 10%, para identificar la especie, en donde no se lograron resultados, probablemente debido a la destrucción del ADN por el formaldehído.

Macular and extramacular optical coherence tomography findings in X-linked retinoschisis.

Two brothers with X-linked retinoschisis were evaluated using optical coherence tomography. Macular cleavage was observed at the inner nuclear layer. Retinal nerve fiber layer loss or detachment was observed outside the macular area, even in areas of clinically normal retina. Macular thickening and cavitation with multiple septa was characteristic, decreasing rapidly from the center toward the macular periphery and being more pronounced in the younger patient. No abnormal vitreomacular relationship or traction over the macular and extramacular schisis areas was observed. Optical coherence tomography showed a characteristic pattern of macular schisis in X-linked retinoschisis and confirmed a widespread retinal splitting despite mild clinical findings. Middle and outer neurosensory retina was principally compromised in the macular area and the retinal nerve fiber layer in extramacular areas. No vitreous traction was apparently involved in the foveal and extramacular splitting and elevation.

Parálisis unilateral de la elevación / Unilateral elevation palsy

Objetivos: analizar la incidencia y características clínicas de pacientes con parálisis unilateral de la elevación (PUE) en nuestra consulta privada. Pacientes y métodos: evaluamos las historias clínicas de 822 pacientes estrábicos estudiados consecutivamente. Estudiamos la presencia de estrabismo horizontal asociado, de inversión anómala, del fenómeno de Bell, tortícolis y ptosis o pseudoptosis. Estudiamos clínicamente los movimientos sacádicos en el plano vertical. Cuatro pacientes con doble parálisis de los elevadores (DPE) fueron operados mediante la técnica de Knapp modificada. Resultados: 7 pacientes presentaron una PUE. Seis casos correspondían a una DPE presentando hipotropia en el ojo afectado, pseudoptosis y ptosis y fénomeno de Bell negativo ipsilateral. El caso restante correspondía a una parálisis unilateral de la elevación de origen supranuclear presentando ortotropia en PPM y fenómeno de Bell positivo en el ojo afectado. Entre los casos de DPE dos estaban asociados al fenómeno de Marcus Gunn (FMG). Clínicamente no pudimos establecer diferencias en la velocidad sucádica entre ambos ejes en los 7 pacientes estudiados. Los cuatro pacientes con DPE operados mostraron ducciones pasivas normales y obtuvieron un buen alineamiento ocular en PPM. Conclusión: Las PUE son cuadros clínicos infrecuentes. La asociación de PUE y FMG confirmaría el diagnóstico de DPE.

Purpose: to analyze the incidence and clinical characteristics of patients with unilateral elevation palsy (UEP) in our private practice. Patients and methods: 822 clinical recordd of strabismus patients seen consecutively were evaluated. We studied the existence of horizontal strabismus, anomalous innervations, Bell's phenomenon, torticollis and ptosis or pseudoptosis. We studied vertical saccadic movements. Four patients with double elevator palsy (DEP) were operated with a Knapp modified procedure. Results: 7 patients had UEP. Six had double elevator paresis (DEP) presenting hypotropia of the involved eye, pseudoptosis, ptosis and ipsilateral negative Bell's phenomenon. The other case was a supranuclear elevation palsy with ortotropia in primary position and, positive Bell's phenomenon in the affected eye. Two DEP patients were associated with Marcus Gunn phenomenon (MGF). Clinically we couldn't find differences in saccadic velocity between both eyes of 7 patients. The four patients with DEP that were operated had normal passive ductions and attained good results. Conclusions: clinical causes of UEP are infrequent. The association of UEP and MGF would support DEP diagnosis.