[Choroidal metastasis from a breast carcinoma. Diagnosis and follow-up with optical coherence tomography and fluorescein angiography and autofluorescence with HRA-II (Heidelberg Retina Angiograph)]. / Metástasis coroideas de carcinoma de mama. Diagnóstico y seguimiento mediante tomografía de coherencia óptica y angiofluoresceingrafía y autofluorescencia con HRA-II (Heidelberg Retina Angiograph).

CLINICAL CASE: A 69-year-old woman developed choroidal metastasis from a breast carcinoma 2 years after the initial diagnosis, surgery and chemotherapy. After treatment with palliative chemotherapy and external radiotherapy, we used fluorescein angiography (FA) and optical coherence tomography (OCT) to evaluate the resolution of the serous retinal detachment, as well as a later relapse in the optic nerve. DISCUSSION: OCT is useful in the follow-up of choroidal metastasis after treatment. However, OCT imaging is limited by the initial choroidal location of metastasis. The autofluorescence can detect exudative tumoral activity even without obvious changes in OCT or FA.

Vimentin isoform expression in the human retina characterized with the monoclonal antibody 3CB2.

The antigen recognized by the monoclonal antibody 3CB2 (3CB2-Ag and 3CB2 mAb) is expressed by radial glia and astrocytes in the developing and adult vertebrate central nervous system (CNS) of vertebrates as well as in neural stem cells. Here we identified the 3CB2-Ag as vimentin by proteomic analysis of human glial cell line U-87 extracts (derived from a malignant astrocytoma). Indeed, the 3CB2 mAb recognized three vimentin isoforms in glial cell lines. In the human retina, 3CB2-Ag was expressed in Müller cells, astrocytes, some blood vessels, and cells in the horizontal cell layer, as determined by immunoprecipitation and immunofluorescence. Three populations of astrocytes were distinguishable by double-labeling immunohistochemistry: vimentin+/GFAP+, vimentin-/GFAP+, and vimentin+/GFAP-. Hence, we conclude that 1) the 3CB2-Ag is vimentin; 2) vimentin isoforms are differentially expressed in normal and transformed astrocytes; 3) human retinal astrocytes display molecular heterogeneity; and 4) the 3CB2 mAb is a valuable tool to study vimentin expression and its function in the human retina.

[Combined hamartoma of the retina and retinal pigment epithelium diagnosed by retinal angiography and optical coherence tomography]. / Hamartoma combinado de retina y epitelio pigmentario retiniano. Diagnóstico mediante tomografía de coherencia óptica y angiofluoresceingrafía.

CLINICAL CASE: This report is based on the case of a 35-year-old woman who developed a combined hamartoma of the retina and retinal pigment epithelium in her right eye. The diagnosis was determined based on the fundus examination: hyperplasia of the retinal pigment epithelium cells, tortuosity of the vessels and epiretinal membrane. DISCUSSION: Optical coherence tomography and retinal angiography are important to rule out malignant melanoma of the choroid and retinoblastoma. Regular follow-up is essential because reduction in visual acuity can be related to an epiretinal membrane, neovascular membrane or vitreous hemorrhage.

[Short- and medium-term intraocular pressure lowering effects of combined phacoemulsification and non-penetrating deep sclerectomy without scleral implant or antifibrotics]. / Control tensional a corto y medio plazo de facoesclerectomía profunda no perforante sin implante escleral ni antimetabolito.

PURPOSE: To examine the short- and medium-term intraocular pressure (IOP) lowering effects of combined phacoemulsification and non-penetrating deep sclerectomy without the use of scleral implant or antifibrotics in open-angle glaucoma (primary and pseudoexfoliative) and coexisting cataract in eyes with no known risk factors for bleb failure. METHODS: Retrospective study of 15 eyes of 12 patients with medically uncontrolled open-angle glaucoma or open-angle glaucoma treated with two or more drugs and coexisting cataract with no known risk factors for glaucoma surgery failure. All patients received combined phacoemulsification and non-penetrating deep sclerectomy without scleral implant or antifibrotics performed by the same surgeon. Nd-YAG perforation of the trabeculodescemetic membrane and/or needling with mitomycin-C was performed postoperatively for IOP control. Main outcome measures were postoperative IOP, percentage of eyes with IOP < 17 mmHg, complications and final visual acuity (VA). Median follow-up was 12.0 months (SD: 0.6) and ranged from 1 to 30 months. RESULTS: Mean preoperative IOP with medical treatment was 21.80 mmHg (SD: 5.14) and decreased to 14.42 mmHg (SD: 2.15) at 12-month visit. Mean antiglaucoma medication preoperative was 1.93 (SD: 0.70) and was reduced to 0.13 (DE: 0.35) postoperative. At 12-month visit, 80% had an IOP lower than 17 mmHg with a mean VA gain of 2.50 Snellen lines. Conjuntival wound leakage was the most frequent complication (20%; 3/15). CONCLUSIONS: Primary combined phacoemulsification and non-penetrating deep sclerectomy without collagen implant or antifibrotics in primary open-angle glaucoma with coexisting cataract, significantly lowers IOP in the short- and medium term in low-risk cases for glaucoma surgery failure, allowing for rapid visual improvement with a low complication rate.

Historical dimensions of population structure in a continuously distributed marine species: The case of the endemic Chilean dolphin.

The complementarity of historical and contemporary processes contributes to understanding the genetic structure of continuously distributed marine species with high dispersal capabilities. Cephalorhynchus eutropia, has a continuous coastal distribution with strong genetic differentiation identified by nuclear DNA markers. We explored the historical dimension of this genetic differentiation between northern and southern populations to evaluate phylogeographic structure. Additionally, we conducted mtDNA and microsatellite analyses to detect past and recent demographic changes. The southern population was characterized by lower genetic diversity with a signal of population expansion, likely associated with ice retreat and habitat extension after the Last Glacial Maximum (LGM). In contrast, structure within the northern population was more consistent with stable historical population size. Approximate Bayesian Computation analyses suggested that during the LGM, C. eutropia persisted in the northern area; while the south was colonized by dispersal ~11,000 years ago followed by population expansion. This study shows that Chilean dolphin population structure is consistent with predictions from the Expansion-Contraction biogeographic model, with a poleward post-glacial shift revealed in current genetic structure. The results also confirm the validity of the population units previously identified, demonstrating their historical origin and highlighting the utility of integrating genetic markers with different temporal scale resolutions.

[Panuveitis as a possible ophthalmic complication of Kikuchi-Fujimoto disease]. / Panuveítis como posible manifestación oftalmológica de la enfermedad de Kikuchi-Fujimoto.

CLINICAL CASE: A 37 year old female with histologically proven Kikuchi-Fujimoto disease is presented. She developed panuveitis, vasculitis and subretinal macular infiltrate, probably as a recurrence of the disease. Immunosuppressive treatment (methotrexate) was initiated in the absence of response to systemic steroid therapy and threat to vision owing to macular involvement. DISCUSSION: Ophthalmic complications of Kikuchi-Fujimoto disease are unusual. We discuss differential diagnosis and emphasize the aggresiveness of our case.

Endoglin overexpression modulates cellular morphology, migration, and adhesion of mouse fibroblasts.

Endoglin is the gene mutated in hereditary hemorrhagic telangiectasia type 1 (HHT1), a dominantly inherited vascular disorder. Endoglin glycoprotein is a component of the transforming growth factor type beta (TGF-beta) receptor system which is highly expressed by endothelial cells, and at lower levels on fibroblasts and smooth muscle cells, suggesting the involvement of these lineages in the HHT1 vascular dysplasia. Overexpression of endoglin in mouse NCTC929 fibroblasts led to decreased migration in chemotactic and wound healing assays, as well as changes in the cellular morphology. When plated on uncoated surfaces, endoglin transfectants formed intercellular clusters, endoglin being not specifically localized to the cell-cell junctions, but homogenously distributed on the cellular surface. Although the expression of alpha5beta1 integrin and of an activation epitope of beta1 integrin were unchanged, a polyclonal antibody to alpha5beta1 integrin was able to inhibit cluster formation, suggesting the involvement of integrin ligand/s. In fact, coating with fibronectin, laminin, or an RGD-containing 80 kDa fragment of fibronectin were able to prevent the cellular clustering. Furthermore, synthesis of plasminogen activator inhibitor 1 (PAI-1), and to a weak extent that of fibronectin, were inhibited in endoglin transfectants. Thus, the presence of endoglin in mouse NCTC929 fibroblasts is associated with reduced production of certain extracellular matrix (ECM) components, which might explain their altered morphology, migration and intercellular cluster formation.

Induction of apoptosis by the bis-Pt(III) complex [Pt(2)(2-mercaptopyrimidine)(4)Cl(2)].

We analyzed both the cytotoxicity and the type of cell death produced by the novel binuclear Pt(III) compound Pt-Spym ([Pt(2)(2-mercaptopyrimidine)(4)Cl(2)]) in kidney human fibroblasts and in human tumor cell lines (HeLa, CH1, CH1cisR and HL-60). The data showed that Pt-Spym displayed higher cytotoxicity against these tumor cells than cisplatin. In contrast, Pt-Spym had low toxicity against normal human fibroblasts. Interestingly, Pt-Spym circumvented cisplatin resistance in CH1cisR cells. We also observed that Pt-Spym induced the characteristic changes attributed to apoptosis in cells with normal levels of p53 protein (CH1 and CH1cisR) and with low levels of p53 protein (HeLa), but not in cells lacking p53 (HL-60). Interestingly, Western blot data indicated that apoptosis induction by Pt-Spym in HeLa, CH1, and CH1cisR cells was not associated with drastic changes in p53 levels. However, cis-DDP strongly decreased p53 levels in CH1 and CH1cisR cells and abolish p53 protein in HeLa cells. Altogether, these results suggest that induction of apoptosis by Pt-Spym requires the presence of p53 protein.

Endothelin-1 increases isoprenaline-enhanced cyclic AMP levels in cerebral cortex.

We examined the effect of ET-1 on cyclic AMP levels in rat cerebral cortex. The peptide caused a concentration-dependent increase of [(3)H]cyclic AMP accumulation after 10 min of treatment. This effect was due to adenosine accumulation since it was inhibited by the treatment with adenosine deaminase. ET-1, apart from being able to increase cyclic AMP, also potentiated the cyclic AMP generated by isoprenaline in the presence of adenosine deaminase. Experiments performed in the presence of BQ-123 or BQ-788, specific ET(A) or ET(B) receptor antagonists respectively indicated that ET(B) was the receptor involved. This effect was dependent on extracellular and intracellular calcium concentration. These findings suggest that ET-1 plays a modulatory role in cyclic AMP generation systems in cerebral cortex.

Platelet-activating factor stimulation of p125(FAK) and p130(Cas) tyrosine phosphorylation in brain.

The effect of platelet-activating factor (PAF) on protein tyrosine phosphorylation was studied in rat brain slices. PAF induced a time- and concentration-dependent increase in tyrosine phosphorylation of a doublet of approximately 125 kDa. These proteins were identified by immunoprecipitation as p125(FAK) and p130(Cas), using monoclonal antibodies. This effect was mediated by PAF receptors, as shown by its inhibition by the action of a PAF antagonist. The tyrosine phosphorylation evoked by PAF was dependent, at least in part, on external calcium. The involvement of protein kinase C was demonstrated by the synergistic effect of TPA on PAF-stimulated tyrosine phosphorylation. The finding that PAF stimulates tyrosine phosphorylation of both focal adhesion protein p125(FAK) and p130(Cas) suggests that PAF might modulate the integrin mediated signal transduction in the brain.

Modulation of protein kinase C isoforms by PAF in cerebral cortex.

The effect of platelet activating factor (PAF) on subcellular distribution of protein kinase C isoforms in rat cerebral cortex was investigated. PAF induced an increase in levels of protein kinase C epsilon and gamma in membrane fraction. Results also indicate that PAF induced an increase in protein kinase C delta levels in both cytosolic and membrane fraction. This effect is possibly due to an increase in enzyme synthesis, as indicated by the results obtained from the experiments performed in the presence of cycloheximide and actinomycin. All the effects induced by PAF were time- and dose-dependent, and were mediated through the activation of PAF receptor. These findings indicate that the three isoforms may be involved in signal transduction of PAF in the brain.

Histochemical and ultrastructural changes induced by zidovudine in mitochondria of rat cardiac muscle.

Zidovudine (azidothymidine, AZT), a drug used in acquired immune deficiency syndrome (AIDS), blocks reverse transcriptase and therefore inhibits human immunodeficiency virus (HIV) replication. We carried out an ultrastructural and histoenzymatic study in rat cardiac muscle. Groups of animals (3 rats per group) were given drinking water with or without AZT (1 or 2 mg AZT/ml). After 30, 60 and 120 days, the hearts were studied by light and electron microscopy. Histochemical analysis of isocitrate, succinic, malic, NADH and NADPH dehydrogenase activities revealed no changes in AZT-treated rats compared with control rats. The ultrastructural study showed a disruption of cristae and an increased size of mitochondria in rats treated with AZT for 30- and 60-days. No alterations were observed in rats that received the 120-day treatment. A statistical analysis based on electron micrographs demonstrated a time-dependent ratio between intact and disrupted mitochondria. Rats that received AZT for 30 days showed a higher number of abnormal mitochondria than rats that received the 60 day treatment. No differences with respect to rat controls were observed in the rats that received AZT for 120 days. We conclude that AZT-induced ultrastructural alterations in cardiac muscle did not modify the histochemical activity of several mitochondrial enzymes.

[No X-chromosome linked juvenile foveal retinoschisis]. / Retinosquisis foveal juvenil no ligada al cromosoma X.

PURPOSE: To describe the clinical characteristics of two cases of juvenile foveal retinoschisis in women with an atypical hereditary pattern, no X-chromosome linked. An autosomal recessive inheritance is proposed. METHODS: Two generations of a family (5 members) in which only two sisters were evaluated. The complete examination of these two cases includes retinography, fluorescein angiography, automated perimetry, color vision testing, electroretinogram, electrooculogram and visually evoked potentials. RESULTS: Comparing our cases with the classic form of X-linked juvenile retinoschisis, they are less severely affected. The best visual acuity and the less disturbed or even normal electroretinogram confirm this fact. We emphasise the existence of isolated plaques of retinal pigment epithelium atrophy with perivascular pigment clumps without foveal schisis in one patient, which could represent an evolved form of this entity. CONCLUSIONS: The hereditary foveal juvenile retinoschisis in women suggests an autosomal inheritance (autosomal recessive in our cases) and presents less severe involvement (Arch Soc Esp Oftalmol 2002; 77: 443-448).

[Benign concentric annular macular dystrophy: two cases]. / Distrofia macular anular benigna concéntrica: dos casos.

CLINICAL CASE: We present two cases of two sisters with the presumed diagnosis of benign concentric annular macular dystrophy. Age was 16 and 22 years old respectively. They presented with decrease in visual acuity and annular atrophy of the macular retinal pigment epithelium. The fluorescein angiography showed <> pattern and the electrophysiologic tests were normal. DISCUSSION: The prognosis of this dystrophy is fairly good, therefore it is important to make an accurate diagnosis to be able to distinguish it from others entities, mainly those presenting <> pattern in fluorescein angiography. We emphasize the usefulness of fluorescein angiography and electrophysiologic test (electroretinogram and electrooculogram).

[Tuberculous meningitis. One case: ophthalmic complications]. / Meningitis tuberculosa. Un caso: complicaciones oftalmológicas.

CASE REPORT: An 18 year old female suffering from tuberculous meningitis with bilateral amaurosis, ophthalmoplegia, other cranial nerve palsies and loss of consciousness, is presented. DISCUSSION: Tuberculous meningitis is a rare cause of basal arachnoiditis with a bad prognosis. Possible causes of visual acuity loss and ophthalmoplegia are discussed and a favourable outcome without sequelae is noteworthy in our case.

[Cavernous sinus aneurysms. Treatment and evolution]. / Aneurismas intracavernosos. Tratamiento y evolución.

CASE REPORT: Two clinical cases of painful ophthalmoplegia from a cavernous sinus syndrome induced by carotid intracavernous aneurysm are presented. Two women presenting similar clinical patterns: total restriction of ocular movements, pthosis, alterations in the pupil and intense cephalalgia of sudden onset. Carotid aneurysms were found to be responsible for these clinical patterns. A carotid embolization was performed in one of the cases while a <> attitude was adopted for the other. DISCUSSION: Both cases showed similar favorable evolution, after a follow up period of one year. We concluded that in these cases a close collaboration with other specialties is required in order to adopt the most adequate therapeutic option.

[Tuberculous peripheral multifocal choroiditis]. / Coroiditis multifocal periférica tuberculosa.

CASE REPORT: A healthy 57 year-old woman with past untreated pulmonary tuberculosis, disclosed a bilateral uveitic syndrome characte rized by iritis, vitreitis, multiple peripheral retinal punched-out lesions, and cystoid macular edema. Systemic evaluation was unremarkable except for a 30 mm tuberculin skin test. Relapses occurred after oral and periocular corticosteroids were interrupted, but the inflammation completely disappeared after a 6 month course of isoniazid, rifampicin and pyrazinamide. DISCUSSION: Intraocular tuberculosis should be considered as a treatable cause of peripheral multifocal choroiditis, after ruling out other etiologies.

Isolation of chick retina cones and study of their diversity based on oil droplet colour and nucleus position.

The chick retina has four morphological cone types that differ not only in shape, but also in the visual pigment in the outer segment, in the colour of the oil droplet in the inner segment and in synaptic connectivity. Neither the type of droplet nor the visual pigment has been definitively established for the four cone types. The main aim of the present work has been the isolation of entire live photoreceptors in order to study the oil droplet colour in each cone type and to quantify each type. We have improved an earlier retinal cell isolation method and obtained large numbers of entire cones. Principal cones (27% of the cones) possess a yellow or colourless droplet. Accessory cones (27% of the cones) all contain a small pale green droplet. Straight cones (44% of the cones) have a red, orange, yellow, or colourless droplet. Oblique cones (1.66% of the cones) all have a colourless droplet. We have found that straight cones with a red, orange, or yellow droplet differ in terms of the position of the nucleus and their percentage and conclude that they are distributed in three rows in the outer nuclear layer (ONL) of the central retina. Our study of 4,6-diamidino-2-phenylindole-stained retinal sections has revealed three rows of nuclei instead of the two currently thought to form the ONL. Together, our results show a larger cone diversity than previously known, suggest a larger functional diversity and provide an efficient method for isolating entire chick photoreceptors.

Characterisation of a monoclonal antibody recognising specifically the HSP70 from Leishmania.

Heat-shock protein 70 (HSP70) is ubiquitously distributed along the evolutionary scale and has such an amino acid sequence conservation that it is considered the most evolutionarily conserved protein. In order to obtain immunological tools specific against Leishmania infantum HSP70, hybridomas were established that secreted monoclonal antibodies (mAbs) against recombinant L. infantum HSP70. One of them, named mAb 2B8D2, specifically reacted with the Leishmania protein and did not recognise HSP70 from the related kinetoplastid Trypanosoma cruzi. The use of synthetic peptides allowed us to determine the B-cell epitope recognised by this mAb, an epitope located in the divergent C-terminal domain of the protein. Remarkably, the mAb possesses the capacity to immunoprecipate HSP70 from promastigote extracts of L. infantum. The fact that human HSP70 is not recognised by this mAb assures the usefulness of this antibody for diagnostic purposes and studies involving Leishmania infection of macrophages.