Atypical posterior scleritis mimicking an amelanotic choroidal melanoma. A case report.

Purpose: To describe a clinical case of atypical posterior scleritis mimicking an amelanotic choroidal melanoma. Method: Observational case report of a 54-year-old woman who presented to the emergency department with photophobia and blurred vision in her left eye for three days. The development of a raised hypopigmented lesion superior to the papilla with choroidal folds and without vitritis simulated an amelanotic choroidal melanoma. Differential diagnosis took into consideration other compatible entities, including choroidal masses or orbital pseudotumor. Results: The patient was subject to full clinical examination, laboratory test, optical coherence tomography, orbital echography, and magnetic resonance imaging. Treatment with oral prednisone showed a significant improvement in all clinical and anatomical parameters. Discussions: Posterior scleritis is characterized by great clinical variability and sometimes can simulate an amelanotic choroidal melanoma. Performing an appropriate differential diagnosis of a large amelanotic lesion is the most important point during a routine ocular examination due to the implications for the patient. Conclusions: Posterior scleritis is a rare and incompletely understood inflammatory disease that affects the posterior part of the sclera. It can be associated with a range of conditions and very often is underdiagnosed. In about one third of the cases, it is related to some systemic disease, especially to autoimmune entity, so it may require a multidisciplinary approach. This case highlighted the importance of a solid differential diagnosis and an early treatment in order to help prevent the appearance of complications that can limit not only the visual outcome of the patient but even his survival in the most extreme cases. Abbreviations: LE = left eye; RE = right eye; BCVA = best corrected visual acuity; BO = both eyes; IOP = intraocular pressure; OCT = optical coherence tomography; MRI = Magnetic Resonance Imaging.

Polyphasic Characterisation of Non-Starter Lactic Acid Bacteria from Algerian Raw Camel's Milk and Their Technological Aptitudes.

RESEARCH BACKGROUND: Consumption of spontaneously fermented camel´s milk is common in Algeria, making it a feasible source of diverse lactic acid bacteria (LAB) with the potential to be used as adjunct cultures to improve quality and safety of fermented dairy products. EXPERIMENTAL APPROACH: Twelve raw camel´s milk samples were used as a source of indigenous LAB, which were further characterised by examining39 phenotypic traits with technological relevance. RESULTS AND CONCLUSIONS: Thirty-five non-starter LAB (NSLAB) were isolated from 12 Algerian raw camel's milk samples and they were microbiologically, biochemically and genetically characterised. Some isolates showed proteolytic activity, acidifying capacity, the ability to use citrate, and to produce dextran and acetoin. Ethanol, acetaldehyde, methyl acetate, acetoin and acetic acid were the major volatile compounds detected. Cluster analysis performed using the unweighted group with arithmetic average (UPGMA) method, and based on the thirty-nine phenotypic characteristics investigated, reflected the microbial diversity that can be found in raw camel´s milk. NOVELTY AND SCIENTIFIC CONTRIBUTION: The isolated strains, from a non-typical source, showed interesting technological traits to be considered as potential adjunct cultures. Cluster analysis based on the examined phenotypic characteristics proved to be a useful tool for the typification of isolates when no genetic information is available. These findings may be of use towards an industrialised production of camel's milk dairy products.

Muscle Tension Dysphonia: Which Laryngoscopic Features Can We Rely on for Diagnosis?

OBJECTIVES: Muscle tension dysphonia (MTD) is generally diagnosed through clinical history and physical examination. Several diagnostic or classification systems exist, such as those of Van Lawrence, Morrison-Rammage, and Koufman, that delineate MTD and distinguish subtypes on the basis of laryngoscopic features. The aim of this study is to determine which of the clinical features included in these classifications are most related to the aerodynamic profile of MTD. STUDY DESIGN: This is an analytic retrospective study. MATERIAL AND METHODS: This study evaluates a series of 30 consecutive patients, all over 18 years old, who attended the voice clinic consult of our department and were diagnosed with MTD. All subjects underwent fiberoptic nasal endoscopy, acoustic voice assessment, and aerodynamic voice assessment. The study only includes patients with a pathological aerodynamic profile. Presence or absence of each laryngoscopic feature in the full range of features in the Van Lawrence, Morrison-Rammage, and Koufman classification systems was evaluated independently by three experts. Cohen's kappa coefficient was calculated to indicate the degree of concordance between the experts. The chi-squared test was used to determine the degree of association between clinical features and mean value of the subglottic pressure peak (mmH2O). RESULTS: Clinical parameters that were found to have a statistically significant association (P < 0.05) with an alteration in mean subglottic pressure peak were those related to anteroposterior and lateral compression of the larynx in Van Lawrence, Morrison-Rammage, and Koufman classification systems. CONCLUSIONS: While several studies have sought to clarify the laryngoscopic features of MTD, the current study is the first to evaluate these features in subjects who have been objectively diagnosed by means of aerodynamic voice assessment. The laryngoscopic features most strongly related to an aerodynamic profile of MTD were anteroposterior compression of the larynx, lateral compression of the larynx, and vestibular fold contribution to phonation.

An altered gene expression profile in tyramine-exposed intestinal cell cultures supports the genotoxicity of this biogenic amine at dietary concentrations.

Tyramine, histamine and putrescine are the most commonly detected and most abundant biogenic amines (BA) in food. The consumption of food with high concentrations of these BA is discouraged by the main food safety agencies, but legal limits have only been set for histamine. The present work reports a transcriptomic investigation of the oncogenic potential of the above-mentioned BA, as assessed in the HT29 human intestinal epithelial cell line. Tyramine had a greater effect on the expression of genes involved in tumorigenesis than did histamine or putrescine. Since some of the genes that showed altered expression in tyramine-exposed cells are involved in DNA damage and repair, the effect of this BA on the expression of other genes involved in the DNA damage response was investigated. The results suggest that tyramine might be genotoxic for intestinal cells at concentrations easily found in BA-rich food. Moreover, a role in promoting intestinal cancer cannot be excluded.

The dietary biogenic amines tyramine and histamine show synergistic toxicity towards intestinal cells in culture.

Tyramine and histamine are the biogenic amines (BA) most commonly found at high concentrations in food; they may even appear together at toxic concentrations. The present work examines, via real-time cell analysis, whether histamine and tyramine show synergistic toxicity towards intestinal cell cultures. Employing a constant equipotency ratio, their interaction was examined via the combination index (CI) method of Chou & Talalay. Co-treatment with tyramine and histamine was associated with a stronger cytotoxic effect than was treatment with either BA or on its own. Indeed, a synergistic interaction (CI<1) was observed in the range of concentrations found in foods. The results also show that histamine, at concentrations below the legal limit, increases the cytotoxicity of tyramine at concentrations frequently reached in some foods. The synergistic cytotoxicity of tyramine and histamine should be taken into account when establishing legal limits designed to ensure consumer safety.

Histamine-producing Lactobacillus parabuchneri strains isolated from grated cheese can form biofilms on stainless steel.

The consumption of food containing large amounts of histamine can lead to histamine poisoning. Cheese is one of the most frequently involved foods. Histamine, one of the biogenic amines (BAs) exhibiting the highest safety risk, accumulates in food contaminated by microorganisms with histidine decarboxylase activity. The origin of these microorganisms may be very diverse with contamination likely occurring during post-ripening processing, but the microorganisms involved during this manufacturing step have never been identified. The present work reports the isolation of 21 histamine-producing Lactobacillus parabuchneri strains from a histamine-containing grated cheese. PCR revealed that every isolate carried the histidine decarboxylase gene (hdcA). Eight lineages were identified based on the results of genome PFGE restriction analysis plus endonuclease restriction profile analysis of the carried plasmids. Members of all lineages were able to form biofilms on polystyrene and stainless steel surfaces. L. parabuchneri is therefore an undesirable species in the dairy industry; the biofilms it can produce on food processing equipment represent a reservoir of histamine-producing bacteria and thus a source of contamination of post-ripening-processed cheeses.

Platform technology to deliver prophylactic molecules orally: an example using the Class A select agent Yersinia pestis.

Consumed for centuries, lactic acid bacteria are excellent candidates for the development of safe mucosal delivery vehicles for prophylactic and therapeutic molecules. We have recently reported that the immune response to an effective OspA-expressing L. plantarum vaccine for Lyme disease is modulated by the lipid modification of the antigen. In this study, we investigated if this technology can be applied to developing vaccines for other diseases by focusing on the Class A select agent, Yersinia pestis. We used a number of biochemistry and immunology techniques to determine the localization of the immunogen in our delivery vehicle and to evaluate the mucosal as well as the systemic immune response to the immunogen. We found that only LcrV cloned downstream of the signal sequence of B. burgdorferi OspA ((ss)LcrV), but not wildtype LcrV (LcrV), is localized to the desired peptidoglycan layer of the delivery vehicle. In addition, only mice that received L. plantarum expressing (ss)LcrV produced significant titers of IgG antibody as well as IgA in distant mucosal sites such as lungs and vagina. Furthermore, only L. plantarum expressing (ss)LcrV induced significant amounts of pro-inflammatory cytokines TNFα, IL-12, IFNγ and IL-6 as well as anti-inflammatory IL-10 in human peripheral blood mononuclear cells derived dendritic cells, suggesting that the mechanism by which LcrV-expressing L. plantarum stimulates the immune response involves polarization to Th1 mediated immunity with some involvement of Th2. The study reported here proves that this system is a platform technology to develop oral vaccines for multiple diseases.

Melatonin, an endogenous-specific inhibitor of estrogen receptor alpha via calmodulin.

Melatonin is an indole hormone produced mainly by the pineal gland. We have previously demonstrated that melatonin interferes with estrogen (E(2)) signaling in MCF7 cells by impairing estrogen receptor (ER) pathways. Here we present the characterization of its mechanism of action showing that melatonin is a specific inhibitor of E(2)-induced ERalpha-mediated transcription in both estrogen response element- and AP1-containing promoters, whereas ERbeta-mediated transactivation is not inhibited or even activated at certain promoters. We show that the sensitivity of MCF-7 cells to melatonin depends on the ERalpha/ERbeta ratio, and ectopic expression of ERbeta results in MCF-7 cells becoming insensitive to this hormone. Melatonin acts as a calmodulin antagonist inducing conformational changes in the ERalpha-calmodulin (CaM) complex, thus impairing the binding of E(2).ERalpha.CaM complex to DNA and, therefore, preventing ERalpha-dependent transcription. Moreover the mutant ERalpha (K302G,K303G), unable to bind calmodulin, becomes insensitive to melatonin. The effect of melatonin is specific since other related indoles neither interact with CaM nor inhibit ERalpha-mediated transactivation. Interestingly, melatonin does not affect the binding of coactivators to ERalpha, indicating that melatonin action is different from that of current therapeutic anti-estrogens used in breast cancer therapy. Thus, they target ERalpha at different levels, representing two independent ways to control ERalpha activity. It is, therefore, conceivably a synergistic pharmacological effect of melatonin and current anti-estrogen drugs.

Calmodulin is a selective modulator of estrogen receptors.

In the search for differences between ERalpha and ERbeta, we analyzed the interaction of both receptors with calmodulin (CaM) and demonstrated that ERalpha but not ERbeta directly interacts with CaM. Using transiently transfected HeLa cells, we examined the effect of the CaM antagonist N-(6-aminohexyl)-5-chloro-naphthalene sulfonilamide hydrochloride (W7) on the transactivation properties of ERalpha and ERbeta in promoters containing either estrogen response elements or activator protein 1 elements. Transactivation by ERalpha was dose-dependently inhibited by W7, whereas that of ERbeta was not inhibited or even activated at low W7 concentrations. In agreement with these results, transactivation of an estrogen response element containing promoter in MCF-7 cells (which express a high ERalpha/ERbeta ratio) was also inhibited by W7. In contrast, transactivation in T47D cells (which express a low ERalpha/ERbeta ratio) was not affected by this CaM antagonist. The sensitivity of MCF-7 cells to W7 was abolished when cells were transfected with increasing amounts of ERbeta, indicating that the sensitivity to CaM antagonists of estrogen-responsive tissues correlates with a high ERalpha/ERbeta ratio. Finally, substitution of lysine residues 302 and 303 of ERalpha for glycine rendered a mutant ERalpha unable to interact with CaM whose transactivation activity became insensitive to W7. Our results indicate that CaM antagonists are selective modulators of ER able to inhibit ERalpha-mediated activity, whereas ERbeta actions were not affected or even potentiated by W7.