Primary cutaneous anaplasic large-cell lymphoma involving medial canthus of the eyelid. / Linfoma anaplásico de células grandes primario cutáneo del canto medio palpebral.

Cutaneous anaplastic large-cell lymphoma (cALCL) is a condition within CD30 lymphoid proliferations spectrum. Involving the eyelid is unusual and all cases found in the literature are located in the upper eyelid. In this case we report an cALCL atypical presentation. A 39 year-old woman with no significant medical history, presents a fast-growing mass in the medial canthus, with inflamatory-infectious appearance. After a week with antibiotics with no response, an excisional biopsy was practiced. The hystopathology analysis with a negative systemic work up confirmed the diagnosis of a cALCL. After two-year follow up, patient is asymptomatic. cALCL involving the eyelid are rare but potentially life-threatening disorders, so more information about diagnosis, treatment and follow up is needed.

Taste and smell in aquatic and terrestrial environments.

Covering: up to 2017The review summarizes results up to 2017 on chemosensory cues occurring in both aquatic and terrestrial environments. The chemicals are grouped by their physicochemical properties to compare their potential mobility in the different media. In contrast to what is widely asserted in the literature, the report emphasizes that living organisms encounter and sense molecules of various degrees of solubility and volatility both on land and in aquatic environments. The picture that emerges from the review suggests a substantial revision of the traditional definitions of the chemical senses based on their spatial range, which is currently orienting the literature on chemosensory signaling, in favor of a new vision based on the natural products that are the actual mediators of the chemosensory perceptions. According to this perspective, natural product chemistry is a powerful tool with which to explore the evolutionary history of the chemical senses.

Eyelid metastasis as first presentation of renal cell carcinoma. / Metástasis palpebral como primera manifestación de un tumor renal.

CASE REPORT: An 87-year-old male presented with a slow-growing, painless and well defined nodule in the upper eyelid. The tumour measured 1cm, and was pigmented and adhered to deep planes. The histopathology analysis was compatible with renal cell carcinoma. The extension study showed a tumour mass in each kidney, as well as multiple pulmonary metastases. DISCUSSION: The ophthalmologist can play an important role in the diagnosis of metastatic cancer when eye disease is present. Therefore, the importance of a biopsy should be noted in those suspicious and/or recurrent lesions of the eyelid.

Could molecular effects of Caulerpa racemosa metabolites modulate the impact on fish populations of Diplodus sargus?

The green alga Caulerpa racemosa is a non-native, invasive species in the Mediterranean, and an important stressor for several native organisms. The algal capacity to produce secondary metabolites has been suggested to modulate success of the C. racemosa invasion, although many of potentially involved biological pathways still remain unexplored. In this respect, the aim of the present study was to investigate some molecular and cellular effects in the white seabream Diplodus sargus, an ecologically key species, which included the alien C. racemosa in its diet. Organisms were sampled in 2 seasonal periods from 3 locations of Southern Italy, each characterized by different levels of algal abundance. The level of caulerpin, one of the main secondary algal metabolites, in fish tissues has been used as an indicator of the trophic exposure to the seaweed and related with molecular and cellular responses. Chemical analyses indicated that fish from invaded sites can accumulate caulerpin, with liver concentrations ranging from a few up to hundreds of µg/g. Biomarkers analyses revealed only limited alterations of the main antioxidant defences, such as glutathione reductase and levels of glutathione; on the other hand, increased enzymatic activities of cytochrome P450, glutathione S-transferases and acyl CoA oxidase, as well as enhanced gene transcription for peroxisome proliferator-activated receptor alpha, cytochrome P4501A and vitellogenin 1 were observed in fish more exposed to C. racemosa as indicated by liver concentrations of caulerpin higher than 50 µg/g. Despite a direct molecular relationship with this algal metabolite could not be established, our results suggest that a C. racemosa enriched diet can modulate biotransformation and fatty acids metabolism of D. sargus. Assessing whether similar effects represent short- or long-term effects will be of crucial importance to understand consequences on the general health status and reproductive performance of exposed key fish species in the Mediterranean region.

[Vascular morphological and microdensity changes of corneal neovascularization induced by topical bevacizumab and sunitinib in an animal model]. / Cambios en la morfología y la microdensidad neovascular corneal inducidos tras la administración tópica de bevacizumab y sunitinib en un modelo animal.

OBJECTIVE: To evaluate the effects of topical bevacizumab and topical sunitinib on vascular microdensity and morphology of corneal neovascularization (NV). METHODS: A total of 33 rabbits were distributed into 3 groups: group 1 (control; n=11): saline; group 2 (n=11): bevacizumab 5mg/ml; and group 3 (n=11): sunitinib 0.5mg/ml. A corneal NV model was used, based on sutures in the right eye of each rabbit. Each treatment was administered topically 3 times daily for 14 days. Corneas were then processed for the study of vascular microdensity (6 eyes) and vascular morphology analysis (5 eyes) using enzymatic staining histological techniques RESULTS: The vascular response in group 3 was limited to small-sized tree formations with various vascular axes compared with the extensive, lush and directional corneal NV of group 1 and 2. In the histological sections near the limb, there were no differences in vascular microdensity studies between the three groups. However, the mean sectional area of vessels (MSAV) in group 3 was 41.88% lower than in group 1 and 19.19% lower than in group 2. In distal sections, there were no differences between groups 1 and 2. However, group 3 was characterized by absence of vessels. CONCLUSIONS: Bevacizumab produced no changes in the morphology of the vessels or the vascular microdensity. Sunitinib reduced the size of the new vessels and induced changes in the vascular tree.

The current situation and needs of rare disease registries in Europe.

BACKGROUND: Registries are considered key instruments for developing rare disease (RD) clinical research, enhancing patient care and health planning, and improving social, economic and quality-of-life outcomes. Indeed, it is usually the case that no single institution, and in many cases no single country, has sufficient data to provide results that can be applied broadly to clinical and translational research. However, the fragmentation and heterogeneity of the registries, which are often the result of spontaneous initiatives, limit the general applicability of their observations. METHODS: An inquiry has been carried out by the EPIRARE, a European Union (EU)-funded project ('Building Consensus and Synergies for the EU Registration of Rare Disease Patients') aiming at paving the way to the creation of a European Platform for RD Registries, by means of an on-line questionnaire among European RD registries on their main activities and needs, the way they deal with methodological, technical and regulatory issues and the way they find resources to carry on their activities. RESULTS: In spite of the heterogeneity of the European registries, some elements of relevance for an action to improve the situation of patient registries in the EU are apparent. The needs more frequently indicated by registry holders were financial support, motivation of data providers, data quality assessment, improvement of communication and visibility, and extension of collaborations. Moreover, the registry holders were in favor of a common EU platform providing services for RD registries. CONCLUSION: It appears that the current situation of the European registries provides the transition towards a more uniform, higher quality and better coordinated approach.

A model for the European platform for rare disease registries.

BACKGROUND: The current situation of rare disease (RD) registries is rather heterogeneous, and new ways to support the registration of RD patients are being sought in the European Union (EU) and the US. The project 'Building Consensus and Synergies for the EU Registration of RD Patients', funded by the EU, aimed to define a model platform for EU RD registries. METHODS: A number of surveys and extensive consultations among registry stakeholders have been carried out to study how the platform can best fulfill their needs. RESULTS: This web-based, multidisease and multipurpose platform is intended to provide a number of functions: a metadata and data repository function supporting the planning of research studies and the production of predefined outputs for the funding organizations and the public, provision of tools and resources of use to registries, promotion of registration and networking among patients and professionals. CONCLUSION: Its main impact is expected to be on data and procedures standardization, on the establishment of new registries, on the sustainability of the smaller ones, and on the registration of those RDs for which a dedicated registry is not sustainable, e.g. ultra-rare diseases or diseases for which there is no special research, clinical or economic interest. It will also impact on the production of sounder information on RD and RD-dedicated health systems, by promoting registry data comparability and quality.

[Vitreous haemorrhage associated with persistent hyaloid artery]. / Hemorragia vítrea asociada a arteria hialoidea persistente.

INTRODUCTION: Haemorrhage from an entire persistent hyaloid artery (PHA) is an uncommon anomaly. CASE REPORT: A 52 year old female presented with blurred vision in her amblyopic eye. Biomicroscopy revealed a blood filled PHA which was inserted in the posterior crystalloid. Ophthalmoscopy showed a mild vitreous haemorrhage. A tubular structure showing a hypo-reflexivity inside the PHA was able to be analysed using optical coherence tomography (OCT). However, Doppler ultrasound did not detect the presence of active blood flow within it. CONCLUSIONS: The performance of non-invasive imaging tests such as the OCT and Doppler ultrasound may be useful in the study of vitreous haemorrhage associated with PHA.

Functional analysis of CYP1B1 mutations and association of heterozygous hypomorphic alleles with primary open-angle glaucoma.

Glaucoma is an inherited complex and heterogeneous disease, and one of the most prevalent causes of definitive blindness in the world. Recent reports have indicated that heterozygous mutations of the CYTOCHOROME P4501B1 (CYP1B1) gene are present in 4-10% of patients with primary open-angle glaucoma (POAG). To further evaluate the role of CYP1B1 mutations in POAG we extended our previous association study and carried out a functional analysis of the mutations identified by polymerase chain reaction (PCR) DNA sequencing of the three exons of the gene in a total of 245 unrelated Spanish patients and 326 control subjects. Eight of nine different mutations identified in these patients were cloned and functionally assessed by measuring ethoxyresorufin O-deethylation activity and CYP1B1 stability in transiently transfected HEK-293T cells. All these mutants showed reduced catalytic activity, ranging from 20% to 60% of wild-type and/or decreased protein stability and, therefore, they were classified as hypomorphic alleles. No null alleles were identified in these patients. We found heterozygous hypomorphic CYP1B1 mutations in 17 (6.7%) patients and in seven controls (2.1%) showing that these mutations are associated with an increased risk of POAG (p = 0.005; odds ratio = 3.2; 95% confidence interval = 1.30-9.19). Our data suggest that hypomorphic CYP1B1 mutations are, to date, the main known genetic risk factor in POAG.

Primary congenital glaucoma caused by the homozygous F261L CYP1B1 mutation and paternal isodisomy of chromosome 2.

Primary congenital glaucoma (PCG), a rare, severe and blinding disease, usually results from mutations in the CYP1B1 gene located in chromosome 2p22.2. Uniparental isodisomy (UPID) is also a rare condition in which a diploid offspring carries two identical copies of a single parental chromosome. By DNA sequence analysis, we found that a proband (female newborn) affected by PCG was homozygous for the null-allele F261L of the CYP1B1 gene. Her father was a heterozygous carrier for this mutation, and unexpectedly her mother carried only the G168D mutation in the heterozygous state. Segregation analysis of eight microsatellite markers which spanned the two arms of chromosome 2 was consistent with paternal isodisomy for this chromosome in the proband. To the best of our knowledge, this is the first reported case of UPID resulting in PCG and the fifth reported case of paternal UPID for chromosome 2. In addition, the absence of a clinical phenotype other than PCG confirms previous observations of there being no paternally imprinted genes in chromosome 2 that have major phenotypic effects. These results, along with previous reports, also suggest that UPID may play a relevant role in recessive diseases linked to chromosome 2.

[Combined trabeculotomy-trabeculectomy as the initial surgical procedure of primary developmental glaucoma]. / Trabeculotomía-trabeculectomía combinada como tratamiento quirúrgico inicial del glaucoma congénito primario.

PURPOSE: To evaluate the long-term outcome of trabeculotomy-trabeculectomy as the primary surgical treatment for primary congenital glaucoma. METHODS: Twenty-two eyes of 14 consecutive patients with primary congenital glaucoma who underwent combined trabeculotomy-trabeculectomy as the initial procedure between 1981 and 2005 were selected for review. Records of ocular family history, age at onset of glaucoma, symptoms and signs, corneal integrity, intraocular pressure (IOP), gonioscopy, surgery, postoperative complications, visual acuity, refractive error, endothelial microscopy, axial length, visual fields and final status of the optic nerve head were entered into a computer database. The outcome, in terms of IOP obtained, was evaluated using Kaplan-Meier survival analysis. RESULTS: Cumulative probabilities of success, after performing combined trabeculotomy-trabeculectomy as the initial operative procedure, were 95.5% after 12 months and 78.2% after 24 months, with this rate being maintained during 15 years of follow-up. Four eyes (18.1%) required more than one operative procedure because of persistent raised IOP. Postoperative complications were rare. At the time of the last follow-up, of 12 eyes from 8 co-operative patients, the final best spectacle-corrected visual acuity was 0.5 (20/40) or better, in 75% (9 eyes). CONCLUSION: Combined trabeculotomy-trabeculectomy as the primary surgical procedure offers long-term high efficacy in the control of IOP without medical treatment, is rarely associated with surgical complications, and a low need for re-operations

[Orbital penetrating wound by a bull horn]. / Herida penetrante orbitaria por asta de toro.

INTRODUCTION: Bull horn injuries are severe lesions with a high risk of bacterial contamination, and are common in countries where people are fond of bullfighting and related spectacles. CASE REPORT: A 19-year-old man was referred with a penetrating wound in the superior left eyelid produced by a bull horn and resulting in a fracture of the orbital roof and a fat hernia. Prophylactic antibiotics and tetanus toxoid were administered and surgical reconstruction of the wound performed. Orbital cellulitis did develop, but this responded to systemic antibiotic therapy within a few days. DISCUSSION: Successful treatment of this type of lesion requires early diagnosis, meticulous surgical exploration and appropriate use of prophylactic antibiotics and tetanus toxoid.

Actinomyces neuii subspecies anitratus chronic endophthalmitis after cataract surgery.

PURPOSE: To report a case of unusual chronic endophthalmitis by Actinomyces neuii subspecies anitratus. METHODS: A 75-year-old man underwent uneventful phacoemulsification with implantation of a foldable posterior chamber intraocular lens in his right eye. Four weeks after surgery, a chronic post-operative endophthalmitis characterized by anterior chamber and vitreous cellular debris developed in this eye. Cultures were positive, and A neuii subspecies anitratus was identified by polymerase chain reaction and subsequent rRNA sequence analysis. Immediate treatment included intravitreal and intensive topical antibiotics along with oral ciprofloxacin. RESULTS: The condition improved rapidly, and 6 months after surgery the patient was asymptomatic, the best spectacle-corrected visual acuity was 20/22, and the anterior chamber was quiet. CONCLUSIONS: A neuii subspecies anitratus should be considered in the differential diagnosis of chronic endophthalmitis after cataract surgery. Polymerase chain reaction and subsequent RNA typing were useful in detecting the causative organism, and intravitreal antibiotics were successful.

Chemical diversity in opisthobranch molluscs from scarcely investigated Indo-Pacific areas.

Opisthobranch molluscs with both a rich variety of secondary metabolites and great biomedical potential represent the most intensively studied group of molluscs in natural product chemistry. We review here the chemical investigations into secondary metabolites of "sea slugs" from less-studied Indian, Chinese and Egyptian coasts, giving an overview of their most relevant biological activities. In addition to the biomedical interest of the metabolites, in which both structures and organisms often lose their own importance, this chapter emphasizes the phyletic and geographic distribution of the compounds in order to provide a further informational base for chemotaxonomical generalizations.

3-Oxo-axisonitrile-3, a new sesquiterpene isocyanide from the Chinese marine sponge Acanthella sp.

A new sesquiterpene isocyanide, 3-oxo-axisonitrile-3 (1), with a spiro [5,6] decane skeleton (spiroaxane) together with a known related sesquiterpene isonitrile (2), sesquiterpene isothiocyanates (3-8) and two diterpene isonitriles (9, 10) have been isolated from the Chinese marine sponge Acanthella sp. The structure of 1 has been determined on the basis of spectroscopic analysis.

A new spiro-sesquiterpene from the sponge Dysidea fragilis.

A new spiro-sesquiterpene, spirofragilin (1), along with a known related sesquiterpene, dehydroherbadysidolide (2), have been isolated from the marine sponge Dysidea fragilis collected in the South China Sea. The structure of 1 was elucidated on the basis of detailed spectroscopic analysis.

[An orbital metastasis as the presentation of lung adenocarcinoma]. / Metástasis orbitaria como primera manifestación de adenocarcinoma pulmonar.

INTRODUCTION: Metastasis of primary tumours can involve the orbit via the blood stream. In 19% of cases this type of metastasis is the first oncologic symptom. CASE REPORT: A 42-year-old woman with a hard, well-defined nodule situated anteriorly in the right orbit and with mild associated inflammation. MR showed an oval image with homogeneous gadolinium uptake. On excision-biopsy a ductal cancer was found and determined on CAT scan to be of pulmonary origin. Chemotherapy was given and no recurrence occurred in the orbit. CONCLUSION: Ophthalmologic examination was the first step in the diagnosis of a metastasis of adenocarcinoma of the lung.

New acetogenin peroxides from the Indian sponge Acarnus bicladotylota.

Two new cyclic peroxides (1 and 2) and the known metabolite 3 have been found in the organic extract of the Indian sponge Acarnus bicladotylota. The structure of the new products has been assured by chemical and spectroscopic methods. The absolute stereochemistry of 1-3 has been determined by Mosher's method on the semisynthetic derivative 4.

Scalarane and homoscalarane compounds from the nudibranchs Glossodoris sedna and Glossodoris dalli: chemical and biological properties.

A series of homoscalarane and scalarane compounds (2-7) have been isolated from two distinct species of Pacific Glossodoris nudibranchs. The structure and elucidation of the relative stereochemistry of the new metabolites 2 and 3 were obtained by spectroscopic methods. Compound 2 was ichthyotoxic at 0.1 ppm against Gambusia affinis and showed moderate activity (IC(50) 18 microM) to inhibit mammalian phospholipase A(2).

Three new butenolide lipids from the caribbean gorgonian pterogorgia anceps

Three novel fatty acid derivatives (1-3), containing one or two butenolide moieties, were isolated from the Caribbean gorgonian Pterogorgia anceps and chemically characterized by spectroscopic methods and comparison with known compounds. The new molecules were structurally related to ancepsenolide (4), a typical metabolite from Pterogorgia species, which was not detected in this collection of P. anceps.