Spontaneous melanotic lesions in axillary seabream, Pagellus acarne (Risso)

In this paper, we describe spontaneous melanotic lesions in the skin of axillary seabream, Pagellus acarne (Risso) from a defined area of the Portuguese Coast, located in Cabo da Roca and Foz do Arelho. The lesions corresponded to black pigmentation spots on the skin of the head, fins, lips and conjunctiva and, additionally, black nodules on the skin of the head and lips. In some specimens, the nodular formations in the head changed their anatomical conformation. Histologically, there were melanophores scattered along the basement membrane or forming aggregates in the dermis, infiltrating the subcutaneous tissue but not invading the adjacent muscle tissue. The aim of this study was to characterize the macroscopic and microscopic features of the pigmented lesions. These fish show sessile hyperpigmented lesions (spots) that correspond to proliferative lesions of melanophores in the dermis and nodular lesions that correspond to neoplastic lesions, melanophoromas. The melanophores in such lesions showed high concentration of melanin in the cytoplasm, moderate pleomorphism and compact distribution throughout all of the dermis

Structural validation of oral mucosal tissue using optical coherence tomography

Background: Optical coherence tomography (OCT) is a non-invasive optical technology using near-infrared light to produce cross-sectional tissue images with lateral resolution. Objectives: The overall aims of this study was to generate a bank of normative and pathological OCT data of the oral tissues to allow identification of cellular structures of normal and pathological processes with the aim to create a diagnostic algorithm which can be used in the early detection of oral disorders. Material and methods: Seventy-three patients with 78 suspicious oral lesions were referred for further management to the UCLH Head and Neck Centre, London. The entire cohort had their lesions surgically biopsied (incisional or excisional). The immediate ex vivo phase involved scanning the specimens using optical coherence tomography. The specimens were then processed by a histopathologist. Five tissue structures were evaluated as part of this study, including: keratin cell layer, epithelial layer, basement membrane, lamina propria and other microanatomical structures. Two independent assessors (clinician and pathologist trained to use OCT) assessed the OCT images and were asked to comment on the cellular structures and changes involving the five tissue structures in non-blind fashion. Results: Correct identification of the keratin cell layer and its structural changes was achieved in 87% of the cohort; for the epithelial layer it reached 93.5%, and 94% for the basement membrane. Microanatomical structures identification was 64% for blood vessels, 58% for salivary gland ducts and 89% for rete pegs. The agreement was “good” between the clinician and the pathologist. OCT was able to differential normal from pathological tissue and pathological tissue of different entities in this immediate ex vivo study. Unfortunately, OCT provided inadequate cellular and subcellular information to enable the grading of oral premalignant disorders. Conclusion: This study enabled the creation of OCT bank of normal and pathological oral tissues. The pathological changes identified using OCT enabled differentiation between normal and pathological tissues, and identification of different tissue pathologies. Further studies are required to assess the accuracy of OCT in identification of various pathological processes involving the oral tissues

In Vivo Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques.

Nonhuman primates are the only mammals to possess a true macula similar to humans, and spontaneously develop drusenoid lesions which are hallmarks of age-related macular degeneration (AMD). Prior studies demonstrated similarities between human and nonhuman primate drusen based on clinical appearance and histopathology. Here, we employed fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR) to characterize drusenoid lesions in aged rhesus macaques. Of 65 animals evaluated, we identified lesions in 20 animals (30.7%). Using the Age-Related Eye Disease Study 2 (AREDS2) grading system and multimodal imaging, we identified two distinct drusen phenotypes - 1) soft drusen that are larger and appear as hyperreflective deposits between the retinal pigment epithelium (RPE) and Bruchs membrane on SD-OCT, and 2) hard, punctate lesions that are smaller and undetectable on SD-OCT. Both exhibit variable FAF intensities and are poorly visualized on IR. Eyes with drusen exhibited a slightly thicker RPE compared with control eyes (+3.4 μm, P=0.012). Genetic polymorphisms associated with drusenoid lesions in rhesus monkeys in ARMS2 and HTRA1 were similar in frequency between the two phenotypes. These results refine our understanding of drusen development, and provide insight into the absence of advanced AMD in nonhuman primates

A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice.

Dystrophin-deficient muscles experience large reductions in expression of nitric oxide synthase (NOS), which suggests that NO deficiency may influence the dystrophic pathology. Because NO can function as an antiinflammatory and cytoprotective molecule, we propose that the loss of NOS from dystrophic muscle exacerbates muscle inflammation and fiber damage by inflammatory cells. Analysis of transgenic mdx mice that were null mutants for dystrophin, but expressed normal levels of NO in muscle, showed that the normalization of NO production caused large reductions in macrophage concentrations in the mdx muscle. Expression of the NOS transgene in mdx muscle also prevented the majority of muscle membrane injury that is detectable in vivo, and resulted in large decreases in serum creatine kinase concentrations. Furthermore, our data show that mdx muscle macrophages are cytolytic at concentrations that occur in dystrophic, NOS-deficient muscle, but are not cytolytic at concentrations that occur in dystrophic mice that express the NOS transgene in muscle. Finally, our data show that antibody depletions of macrophages from mdx mice cause significant reductions in muscle membrane injury. Together, these findings indicate that macrophages promote injury of dystrophin-deficient muscle, and the loss of normal levels of NO production by dystrophic muscle exacerbates inflammation and membrane injury in muscular dystrophy

Degree of Cajal-Retzius cell mislocalisation correlates with the severity of structural brain defects in mouse models of dystroglycanopathy

The secondary dystroglycanopathies are characterized by the hypoglycosylation of alpha dystroglycan, and are associated with mutations in at least 18 genes that act on the glycosylation of this cell surface receptor rather than the Dag1 gene itself. At the severe end of the disease spectrum, there are substantial structural brain defects, the most striking of which is often cobblestone lissencephaly. The aim of this study was to determine the gene‐specific aspects of the dystroglycanopathy brain phenotype through a detailed investigation of the structural brain defects present at birth in three mouse models of dystroglycanopathy—the FKRPKD, which has an 80% reduction in Fkrp transcript levels; the Pomgnt1null, which carries a deletion of exons 7–16 of the Pomgnt1 gene; and the Largemyd mouse, which carries a deletion of exons 5–7 of the Large gene. We show a rostrocaudal and mediolateral gradient in the severity of brain lesions in FKRPKD, and to a lesser extent Pomgnt1null mice. Furthermore, the mislocalization of Cajal–Retzius cells is correlated with the gradient of these lesions and the severity of the brain phenotype in these models. Overall these observations implicate gene‐specific differences in the pathogenesis of brain lesions in this group of disorders

Detection rates of recurrent prostate cancer : 68Gallium (Ga)-labelled prostate-specific membrane antigen versus choline PET/CT scans. A systematic review

Background: The aim of this work was to assess the use of prostate-specific membrane antigen (PSMA)-labelled radiotracers in detecting the recurrence of prostate cancer. PSMA is thought to have higher detection rates when utilized in positron emission tomography (PET)/computed tomography (CT) scans, particularly at lower prostate-specific antigen (PSA) levels, compared with choline-based scans. Methods: A systematic review was conducted comparing choline and PSMA PET/CT scans in patients with recurrent prostate cancer following an initial curative attempt. The primary outcomes were overall detection rates, detection rates at low PSA thresholds, difference in detection rates and exclusive detection rates on a per-person analysis. Secondary outcome measures were total number of lesions, exclusive detection by each scan on a per-lesion basis and adverse side effects. Results: Overall detection rates were 79.8% for PSMA and 66.7% for choline. There was a statistically significant difference in detection rates favouring PSMA [OR (M–H, random, 95% confidence interval (CI)) 2.27 (1.06, 4.85), p = 0.04]. Direct comparison was limited to PSA < 2 ng/ml in two studies, with no statistically significant difference in detection rates between the scans [OR (M–H, random, 95% CI) 2.37 (0.61, 9.17) p = 0.21]. The difference in detection on the per-patient analysis was significantly higher in the PSMA scans (p < 0.00001). All three studies reported higher lymph node, bone metastasis and locoregional recurrence rates in PSMA. Conclusions: PSMA PET/CT has a better performance compared with choline PET/CT in detecting recurrent disease both on per-patient and per-lesion analysis and should be the imaging modality of choice while deciding on salvage and nonsystematic metastasis-directed therapy strategies.Peer reviewedFinal Published versio

In vivo testing of novel vaccine prototypes against Actinobacillus pleuropneumoniae

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is a Gram-negative bacterium that represents the main cause of porcine pleuropneumonia in pigs, causing significant economic losses to the livestock industry worldwide. A. pleuropneumoniae, as the majority of Gram-negative bacteria, excrete vesicles from its outer membrane (OM), accordingly defined as outer membrane vesicles (OMVs). Thanks to their antigenic similarity to the OM, OMVs have emerged as a promising tool in vaccinology. In this study we describe the in vivo testing of several vaccine prototypes for the prevention of infection by all known A. pleuropneumoniae serotypes. Previously identified vaccine candidates, the recombinant proteins ApfA and VacJ, administered individually or in various combinations with the OMVs, were employed as vaccination strategies. Our data show that the addition of the OMVs in the vaccine formulations significantly increased the specific IgG titer against both ApfA and VacJ in the immunized animals, confirming the previously postulated potential of the OMVs as adjuvant. Unfortunately, the antibody response raised did not translate into an effective protection against A. pleuropneumoniae infection, as none of the immunized groups following challenge showed a significantly lower degree of lesions than the controls. Interestingly, quite the opposite was true, as the animals with the highest IgG titers were also the ones bearing the most extensive lesions in their lungs. These results shed new light on A. pleuropneumoniae pathogenicity, suggesting that antibody-mediated cytotoxicity from the host immune response may play a central role in the development of the lesions typically associated with A. pleuropneumoniae infections

Evaluation qualitative macroscopique et microscopique du grasset chez un modèle expérimental d'arthrose canine 90 jours après section du ligament croisé crânial

La transection du ligament croisé crânial (CCLT) est une méthode couramment admise d'induction expérimentale d'arthrose (OA) au niveau du grasset chez le chien. Le but principal de cette étude était d'évaluer qualitativement les lésions d'arthrose induites par la CCLT par macroscopie et histologie 90 jours après chez 21 jeunes femelles de race beagle. Les lèvres de la trochlée fémorale présentaient le plus haut score ostéophytique tandis que la patelle présentait le plus bas et celui du condyle fémoral médial était supérieur à celui du condyle latéral. Les lésions méniscales ont été observées uniquement sur le ménisque médial de 5 genoux opérés. Les lésions macroscopiques du cartilage (stade de fibrillation) ont été notées dans un ordre de fréquence décroissant sur les condyles tibiaux médial et latéral, le condyle fémoral latéral, la trochlée fémorale, le condyle fémoral médial et enfin la patelle. L'examen histologique a révélé que la couche superficielle du cartilage était fibrillée et discontinue. La plupart des cellules étaient rondes et disposées tangentiellement à la surface. Dans les zones transitionnelle et profonde, quelques chondrocytes étaient modérément hypertrophiques et des amas de chondrocytes ont été uniquement observés dans la couche profonde. Concernant la membrane synoviale, un épaississement du mésothélium et une importante densité de collagène ont été notés et le rapport des épaisseurs mésothélium/fibres était entre 1/0.15 et 1/0.10 sur les genoux opérés et 1/0.05 sur les genoux témoins. Les images fournies ici pourront servir de références pour des travaux ultérieurs portant notamment sur les thérapies contre l'arthrose