Gut membrane proteins as candidate antigens for immunization of mice against the tick Amblyomma sculptum.

Amblyomma sculptum is widely distributed in Brazil and is the main vector of Rickettsia rickettsii, the causative agent of the Brazilian spotted fever (BSF). Tick gut proteins play an essential role in blood feeding, digestion, and protection of gut epithelium. Therefore, many of these were investigated as potential vaccine targets for tick-control strategies. The present study aimed to select transcripts corresponding to putative immunogenic proteins in the A. sculptum gut epithelial membrane, produce recombinant proteins and evaluate them as antigens against A. sculptum infestations. Three gut proteins - AsMucin, AsAPP, and AsLAMP - and a chimeric protein (rAsChimera) based on 22 peptides containing putative B cell epitopes from seven different gut proteins were evaluated as anti-A. sculptum antigens. Mice immunizations revealed that all recombinant targets elicited humoral response with significantly increased IgG levels compared to controls. For rAsChimera, IgG levels remained significantly higher than controls up to 75 days after the end of the immunization. Challenge trials revealed that vaccination with the chimeric protein was the most effective against A. sculptum, inducing 100 % nymph mortality and reaching 80.8 % efficacy against females. The other three proteins did not induce relevant protection, as AsAPP had only 26.6 % efficacy, whereas AsMucin and AsLAMP induced no protection. These data indicate that targeting gut protein immunogenic regions may be an effective strategy for a vaccine formulation againstA. sculptum.

Prevalence and Magnitude of Olfactory Dysfunction in Allergic Rhinitis.

BACKGROUND: Although allergic rhinitis (AR) can negatively impact the ability to smell, the degree to which this occurs is not clear and prevalence estimates vary among studies. This study had 4 main objectives: (1) To estimate the prevalence and the degree of olfactory dysfunction in AR patients; (2) To compare olfactory perception between AR patients with different persistence and severity of symptoms and determine if olfactory testing may aid in differentiating among Allergic Rhinitis and its Impact on Asthma (ARIA) groups; (3) To determine whether allergic reactions to different allergens differentially impact olfactory function, and (4) Verify possible changes in the olfactory epithelium (OE) caused by AR. METHODS: One hundred thirty-three patients with AR and one hundred controls were tested. The main outcome was the score in University of Pennsylvania Smell Identification Test (UPSIT®). The OE was examined using immunofluorescence markers for neuronal activity, apoptosis, oxidative stress, signal transduction, eosinophils, and epithelial thickness. RESULTS: Prevalence of olfactory dysfunction in the AR patients was higher (AR: 42.9% vs controls: 9%, P < .001). No difference was found either between intermittent and persistent disease cases (P = .58) or between cases with mild and those with moderate/severe symptomatology (P = .33). Lower olfactory capacity was not associated with the reaction to more (P = .48) or diverse types of allergens (Ps > .05). Although not significant, patients with AR had a greater amount of eosinophilia and a lower amount of cAMP (cyclic adenosine monophosphate) in the OE. CONCLUSION: The study highlights a higher prevalence of olfactory dysfunction in AR patients compared to controls, but olfactory testing may not effectively differentiate AR severity or allergen sensitivities. Although trends suggest potential pathophysiological changes in the OE of AR patients, further research is needed to validate these findings.

The Variation of the Fetal Esophageal Mucosa at the End of Gestation may be a Possible Etiopathogenic Factor for Barrett's Esophagus / La Variación de la Mucosa Esofágica Identificada al Final de la Gestación Puede ser un Posible Factor Etiopatogénico para el Esófago de Barrett

SUMMARY: Barrett's esophagus is a condition where the distal third of the esophagus changes its epithelial lining from non- keratinized stratified squamous to simple columnar. This cross-sectional descriptive study was conducted to characterize the esophageal mucosa in the third trimester of pregnancy and determine possible variants in its development and was carried out in the Morphology Laboratory of the Health Faculty of the Industrial University of Santander, Colombia, with 45 human fetuses in the third trimester of gestation (weeks 25-40). A section of the distal esophagus and the first portion of the cardial region of the stomach were obtained, and the histological sections were subjected to a fixation process with 5 % formaldehyde solution. The sections were stained with hematoxylin and eosin and were evaluated for the presence of epithelial change or glands in the esophageal lamina propria. The change from non- keratinized stratified squamous epithelium to simple columnar epithelium was observed in the esophageal mucosa in five fetuses (11.1 %). In 15 cases (33.3 %), the presence of mucous glands underlying the epithelium was determined. In two fetuses, simple columnar epithelium was observed in the esophageal mucosa and underlying submucosal glands (4.4 %). The lack of replacement of the columnar epithelium by squamous epithelium in the distal third of the esophagus and the presence of mucous glands in the last third of gestation may suggest the presentation of Barret's esophagus in adulthood and thus, a predisposition to develop esophageal adenocarcinoma.

El esófago de Barrett es una afección en la que el tercio distal del esófago cambia su revestimiento epitelial de escamoso estratificado no queratinizado a columnar simple. Este estudio descriptivo de corte transversal tiene como objetivo caracterizar la mucosa esofágica en el tercer trimestre del embarazo y determinar posibles variantes en su desarrollo y se realizó en el laboratorio de Morfología de la Facultad de Salud de la Universidad Industrial de Santander-Colombia, con 45 fetos humanos en el tercer trimestre de gestación (semanas 25-40). Se obtuvo una sección del esófago distal y la primera porción de la región cardial del estómago y las secciones histológicas se sometieron a un proceso de fijación con solución de formaldehído al 5 %. Los cortes se tiñeron con hematoxilina y eosina y se evaluaron determinando la presencia de cambio epitelial y glándulas en la lámina propia del esófago. El cambio de epitelio escamoso estratificado no queratinizado a epitelio cilíndrico simple se observó en la mucosa esofágica en cinco fetos (11,1 %). En 15 casos (33,3 %) se determinó la presencia de glándulas mucosas subyacentes al epitelio. En dos fetos se observó epitelio cilíndrico simple en la mucosa esofágica y glándulas submucosas subyacentes (4,4 %). La falta de reemplazo del epitelio cilíndrico por epitelio escamoso en el tercio distal del esófago y la presencia de glándulas mucosas en el último tercio de la gestación pueden sugerir la presentación de esófago de Barrett en la edad adulta y una predisposición a desarrollar adenocarcinoma de esófago.

Human olfactory neural progenitor cells reveal differences in IL-6, IL-8, thrombospondin-1, and MCP-1 in major depression disorder and borderline personality disorder.

Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC). Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression. Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD. Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders.

Mitochondrial quality control in non-exudative age-related macular degeneration: From molecular mechanisms to structural and functional recovery.

Non-exudative age-related macular degeneration (NE-AMD) is the leading blindness cause in the elderly. Clinical and experimental evidence supports that early alterations in macular retinal pigment epithelium (RPE) mitochondria play a key role in NE-AMD-induced damage. Mitochondrial dynamics (biogenesis, fusion, fission, and mitophagy), which is under the central control of AMP-activated kinase (AMPK), in turn, determines mitochondrial quality. We have developed a NE-AMD model in C57BL/6J mice induced by unilateral superior cervical ganglionectomy (SCGx), which progressively reproduces the disease hallmarks circumscribed to the temporal region of the RPE/outer retina that exhibits several characteristics of the human macula. In this work we have studied RPE mitochondrial structure, dynamics, function, and AMPK role on these parameters' regulation at the nasal and temporal RPE from control eyes and at an early stage of experimental NE-AMD (i.e., 4 weeks post-SCGx). Although RPE mitochondrial mass was preserved, their function, which was higher at the temporal than at the nasal RPE in control eyes, was significantly decreased at 4 weeks post-SCGx at the same region. Mitochondria were bigger, more elongated, and with denser cristae at the temporal RPE from control eyes. Exclusively at the temporal RPE, SCGx severely affected mitochondrial morphology and dynamics, together with the levels of phosphorylated AMPK (p-AMPK). AMPK activation with metformin restored RPE p-AMPK levels, and mitochondrial dynamics, structure, and function at 4 weeks post-SCGx, as well as visual function and RPE/outer retina structure at 10 weeks post-SCGx. These results demonstrate a key role of the temporal RPE mitochondrial homeostasis as an early target for NE-AMD-induced damage, and that pharmacological AMPK activation could preserve mitochondrial morphology, dynamics, and function, and, consequently, avoid the functional and structural damage induced by NE-AMD.

Tumor odontogénico adenomatoide. Reporte de un caso clínico / Adenomatoid odontogenic tumor. Clinical case report

El Tumor Odontogénico Adenomatoide (TOA) es una neoplasia benigna poco común, caracterizada por un crecimiento lento y progresivo, en la mayoría de los casos asintomático. Es una patología intraósea, que puede ser folicular o extrafolicular, siendo el tipo folicular el más común. Se presenta en hombres y mujeres, con predilección por el sexo femenino. Histológicamente está compuesto por epitelio odontogénico organizado en distintos patrones histoarquitectónicos, incrustado en un estroma de tejido fibroconectivo maduro. Se describe el caso clínico de una paciente femenina de 25 años, con aumento de volumen en la región maxilar anterior izquierda, que se extiende a la base de la nariz, produce desvío de la línea media a la derecha y tiene un año de evolución.

The Adenomatoid Odontogenic Tumor (AOT) is an uncommon benign neoplasm, characterized by slow and progressive growth, in most cases asymptomatic. It is an intraosseous pathology, which can be follicular or extrafollicular, with the follicular type being the most common. It occurs in both men and women, with a predilection for the female sex. Histologically, it is composed of odontogenic epithelium organized in different histoarchitectonic patterns, embedded in a stroma of mature fibroconnective tissue. We describe the clinical case of a 25-year-old female patient with increased volume in the left anterior maxillary region, extending to the base of the nose, causing deviation of the midline to the right and having one year of evolution.

Platelet-Activating Factor Receptor (PAFR) Regulates Retinal Progenitor/Stem Cells Profile in Ciliary Epithelium Cells.

The retina is a central nervous tissue essential to visual perception and highly susceptible to environmental damage. Lower vertebrate retinas activate intrinsic regeneration mechanisms in response to retinal injury regulated by a specialized population of progenitor cells. The mammalian retina does not have populations of progenitor/stem cells available to activate regeneration, but contains a subpopulation of differentiated cells that can be reprogrammed into retinal stem cells, the ciliary epithelium (CE) cells. Despite the regenerative potential, stem cells derived from CE exhibit limited reprogramming capacity probably associated with the expression of intrinsic regulatory mechanisms. Platelet-activating factor (PAF) is a lipid mediator widely expressed in many cells and plays an important role in stem cell proliferation and differentiation. During mammalian development, PAF receptor signaling showed important effects on retinal progenitors' cell cycle regulation and neuronal differentiation that need to be further investigated. In this study, our findings suggested a dynamic role for PAF receptor signaling in CE cells, impacting stem cell characteristics and neurosphere formation. We showed that PAF receptors and PAF-related enzymes are downregulated in retinal progenitor/stem cells derived from PE cells. Blocking PAFR activity using antagonists increased the expression of specific progenitor markers, revealing potential implications for retinal tissue development and maintenance.

Induced acute hyperglycemia modifies the barrier function of the intestinal epithelium by tissue inflammation and tight junction disruption resulting in hydroelectrolytic secretion in an animal model

Abstract Diabetic-metabolic syndrome (MetS-D) has a high prevalence worldwide, in which an association with the rupture of the intestinal epithelium barrier function (IEBF) has been pointed out, but the functional and morphological properties are still not well understood. This study aimed to evaluate the impact of acute hyperglycemia diabetes on intestinal tight junction proteins, metabolic failure, intestinal ion and water transports, and IEBF parameters. Diabetes was induced in male Rattus norvegicus (200-310 g) with 0.5 mL of streptozotocin (70 mg/kg). Glycemic and clinical parameters were evaluated every 7 days, and intestinal parameters were evaluated on the 14th day. The MetS-D animals showed a clinical pattern of hyperglycemia, with increases in the area of villi and crypts, lactulose:mannitol ratio, myeloperoxidase (MPO) activity, and intestinal tissue concentrations of malondialdehyde (MDA), but showed a reduction in reduced glutathione (GSH) when these parameters were compared to the control. The MetS-D group had increased secretion of Na+, K+, Cl-, and water compared to the control group in ileal tissue. Furthermore, we observed a reduction in mRNA transcript of claudin-2, claudin-15, and NHE3 and increases of SGLT-1 and ZO-1 in the MetS-D group. These results showed that MetS-D triggered intestinal tissue inflammation, oxidative stress, complex alterations in gene regulatory protein transcriptions of intestinal transporters and tight junctions, damaging the IEBF and causing hydroelectrolyte secretion.

Effect of carbohydrates on the adhesion of Bordetella bronchiseptica to the respiratory epithelium in rabbits.

This study proposes an ecological approach for preventing respiratory tract infections caused by Bordetella bronchiseptica in mammals using a mixture of carbohydrates. In an in vivo study, 51-day-old New Zealand rabbits were treated with a solution containing 1 × 107 CFUs of B. bronchiseptica and 250 µg of one of the following carbohydrates: N acetylglucosamine (GlcNAc), N acetylgalactosamine (GalNAc), alpha methyl mannose (AmeMan), alpha methyl glucose (AmeGlc) and sialic acid (Neu5AC). Positive (B. bronchiseptica) and negative (Physiological Saline Solution (PSS)) controls were included. Animals treated with GlcNAc or AmeGlc showed no clinical signs of infection and exhibited a significant reduction (p < 0.05) in the severity of microscopic lesions evaluated in the nasal cavity and lung compared with the positive controls. Additionally, the presence of bacteria was not detected through microbiological isolation or PCR in the lungs of animals treated with these sugars. Use of a mixture of GlcNAc and AmeGlc resulted in greater inhibition of microscopic lesions, with a significant reduction (p < 0.05) in the severity of these lesions compared to the results obtained using individual sugars. Furthermore, the bacterium was not detected through microbiological isolation, Polymerase Chain Reaction (PCR) or indirect immunoperoxidase (IIP) in this group.

Normal vision and development in mice with low functional expression of Kir7.1 in heterozygosis for a blindness-producing mutation inactivating the channel.

K+ channel Kir7.1 expressed at the apical membrane of the retinal pigment epithelium (RPE) plays an essential role in retinal function. An isoleucine-to-threonine mutation at position 120 of the protein is responsible for blindness-causing vitreo-retinal dystrophy. We have studied the molecular mechanism of action of Kir7.1-I120T in vitro by heterologous expression and in vivo in CRISPR-generated knockin mice. Full-size Kir7.1-I120T reaches the plasma membrane but lacks any activity. Analysis of Kir7.1 and the I120T mutant in mixed transfection experiments, and that of tandem tetrameric constructs made by combining wild type (WT) and mutant protomers, leads us to conclude that they do not form heterotetramers in vitro. Homozygous I120T/I120T mice show cleft palate and tracheomalacia and do not survive beyond P0, whereas heterozygous WT/I120T develop normally. Membrane conductance of RPE cells isolated from WT/WT and heterozygous WT/I120T mice is dominated by Kir7.1 current. Using Rb+ as a charge carrier, we demonstrate that the Kir7.1 current of WT/I120T RPE cells corresponds to approximately 50% of that in cells from WT/WT animals, in direct proportion to WT gene dosage. This suggests a lack of compensatory effects or interference from the mutated allele product, an interpretation consistent with results obtained using WT/- hemizygous mouse. Electroretinography and behavioral tests also show normal vision in WT/I120T animals. The hypomorphic ion channel phenotype of heterozygous Kir7.1-I120T mutants is therefore compatible with normal development and retinal function. The lack of detrimental effect of this degree of functional deficit might explain the recessive nature of Kir7.1 mutations causing human eye disease.NEW & NOTEWORTHY Human retinal pigment epithelium K+ channel Kir7.1 is affected by generally recessive mutations leading to blindness. We investigate one such mutation, isoleucine-to-threonine at position 120, both in vitro and in vivo in knockin mice. The mutated channel is inactive and in heterozygosis gives a hypomorphic phenotype with normal retinal function. Mutant channels do not interfere with wild-type Kir7.1 channels which are expressed concomitantly without hindrance, providing an explanation for the recessive nature of the disease.

Serous maculopathy with absence of retinal pigment epithelium (SMARPE) associated with large drusen.

PURPOSE: To describe the association of serous maculopathy with absence of retinal pigment epithelium (SMARPE) and large drusen in patients with non-neovascular age-related macular degeneration (AMD). METHODS: A retrospective study of ophthalmic examination and multimodal imaging data of individuals with SMARPE and large drusen observed over a period of 12-month was accomplished. SMARPE was defined as subretinal accumulation of fluid within the macular area due to retinal pigment epithelium (RPE) aperture. Large drusen were identified by the presence of sub-RPE deposits using multimodal imaging analysis (color fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography). RESULTS: Twelve eyes of 7 white patients with a mean age of 77 years were observed to have SMARPE associated with large drusen. The median visual acuity was 20/100. Bilateral SMARPE lesions were observed in 71% of study patients. All SMARPE lesions were hypoautofluorescent, located in the subretinal space between the RPE and the ellipsoid zone, and presented as complete or incomplete RPE apertures associated with subretinal fluid. The SMARPE in this study had coincident multimodal imaging features as the SMARPE described in other reports in the literature. CONCLUSIONS: Bilateral SMARPE can occur in association with typical AMD large drusen. Anomalisms resulting in drusen biogenesis or mechanisms that act alongside to these may be related to SMARPE development.

Cultivable Microbiome Approach Applied to Cervical Cancer Exploration.

Traditional microbiological methodology is valuable and essential for microbiota composition description and microbe role assignations at different anatomical sites, including cervical and vaginal tissues; that, combined with molecular biology strategies and modern identification approaches, could give a better perspective of the microbiome under different circumstances. This pilot work aimed to describe the differences in microbiota composition in non-cancer women and women with cervical cancer through a culturomics approach combining culture techniques with Vitek mass spectrometry and 16S rDNA sequencing. To determine the possible differences, diverse statistical, diversity, and multivariate analyses were applied; the results indicated a different microbiota composition between non-cancer women and cervical cancer patients. The Firmicutes phylum dominated the non-cancer (NC) group, whereas the cervical cancer (CC) group was characterized by the predominance of Firmicutes and Proteobacteria phyla; there was a depletion of lactic acid bacteria, an increase in the diversity of anaerobes, and opportunistic and non-typical human microbiota isolates were present. In this context, we hypothesize and propose a model in which microbial composition and dynamics may be essential for maintaining the balance in the cervical microenvironment or can be pro-oncogenesis microenvironmental mediators in a process called Ying-Yang or have a protagonist/antagonist microbiota role.

The association of pre-photorefractive keratectomy Schirmer-1 test value with postoperative corneal epithelial thickness, ocular surface discomfort, and visual acuity

ABSTRACT Purpose: To investigate the association of pre--photorefractive keratectomy Schirmer-1 test value with post--photorefractive keratectomy central corneal epithelial thickness, ocular surface disease index score, and uncorrected distance visual acuity. Methods: Patients were categorized according to preoperative Schirmer-1 value: the normal Schirmer Group (n=54; Schirmer-1 test value, >10 mm) and the low Schirmer Group (n=52; Schirmer-1 test value, between 6 and 10 mm). We analyzed ablation depth, visual acuity, result of Schirmer-1 test (with anesthesia), tear film break-up time, ocular surface disease index score, central corneal epithelial thickness, and spherical equivalent refraction. Results: We found significant differences between the groups in Schirmer-1 test value, tear film break-up time, and ocular surface disease index score, both preoperatively and postoperatively (p<0.001). The preoperative central corneal epithelial thicknesses of the two groups were similar (p>0.05). After photorefractive keratectomy, the Schirmer-1 test value and spherical equivalent refraction decreased in both groups (p<0.05), and ocular surface disease index scores and central corneal epithelial thickness values increased in the low Schirmer Group (p<0.001) but not in the normal Schirmer Group (p>0.05). The postoperative central corneal epithelial thicknesses of the low Schirmer Group were significantly higher than those of the normal Schirmer Group (p<0.001). Postoperative uncorrected distance visual acuity did not differ significantly between the two groups (p>0.05). Conclusions: In patients with low Schirmer-1 test values before photorefractive keratectomy, the corneal epithelium thickened and ocular surface complaints increased during the postoperative period. However, changes in the corneal epithelium did not affect the postoperative uncorrected distance visual acuity. To reduce postoperative problems on the ocular surface in these patients, we recommend that dry eye be treated before photorefractive keratectomy.

Bilateral acute depigmentation of the iris (BADI) and bilateral acute iris transillumination (BAIT): A case series from a center in Brazil

ABSTRACT Bilateral acute depigmentation of the iris and bilateral acute iris transillumination (BAIT) are similar clinical entities. The former causes acute-onset depigmentation of the iris stroma without transillumination, whereas the latter causes depigmentation of the iris pigment epithelium with transillumination. The etiopathogenesis of these conditions is not yet fully understood, but the proposed causes include the use of systemic antibiotics (especially moxifloxacin) and viral triggers. We present a case series of five female patients with a mean age of 41 (32-45) years, all of whom suffered acute onset of bilateral pain and redness of the eyes after moxifloxacin use (oral or topical). It is important for ophthalmologists to be aware of the two forms of iris depigmentation since this case series suggests that SARS-CoV-2 or its empirical treatment with moxifloxacin may trigger iris depigmentation. If this is the case, clinicians will likely see increased incidences of bilateral acute depigmentation of the iris and bilateral acute iris transillumination during and after the COVID-19 pandemic.

Sjögren: unique surname, two men, four syndromes and one disease / Sjögren: sobrenome único, dois homens, quatro síndromes e uma doença

Abstract Henrik and Torsten Sjögren (/'ogrƏn/ or SHOH-grƏn) were two Swedish physicians living in the same period, but completely unrelated, except for their notable contributions to Medicine. The first one described keratoconjunctivitis sicca, afterward called Sjögren's syndrome, and a fishing net aspect retinal pigmentation affecting visual acuity, nowadays known as Sjögren reticular dystrophy. The last one contributed to the understanding of Spielmeyer-Sjögren disease, Marinesco-Sjögren, and Sjögren-Larsson syndromes, all related to genetic disorders and neurological symptoms. In this paper, we aim to describe each disorder, in order to avoid any misunderstanding in diagnosis and for historical record.

Resumo Henrik e Torsten Sjögren (/'ogrƏn/ or SHOH-grƏn) foram dois médicos suecos que viveram na mesma época, mas não tinham nenhuma relação entre si, exceto por suas notáveis contribuições à medicina. O primeiro descreveu a ceratoconjuntivite sicca, posteriormente chamada de síndrome de Sjögren, e uma pigmentação da retina com aspecto de rede de pesca que afeta a acuidade visual, hoje conhecida como distrofia reticular de Sjögren. O último contribuiu para a compreensão da doença de Spielmeyer-Sjögren, das síndromes de Marinesco-Sjögren e Sjögren-Larsson, todas relacionadas a distúrbios genéticos e sintomas neurológicos. Neste artigo, pretendemos descrever cada desordem, a fim de evitar qualquer mal-entendido no diagnóstico e para registro histórico.

Pigment deposits in the retrolental space of Berger: a rare feature of pigment dispersion syndrome? / Depósitos de pigmento no espaço de Berger: uma característica rara de síndrome de dispersão pigmentar?

ABSTRACT Pigment dispersion syndrome is associated with clinical features such as Krukenberg's spindles, trabecular pigmentation, Scheie's stripe and Zentmayer's ring. Another less common feature of this syndrome is retrolental pigment deposits due to anterior hyaloid detachment or a defect in the Wieger's ligament. We present two cases of pigment deposits on the posterior lens capsule. In both cases, there is bilateral dispersion of pigment throughout the anterior segment. The retrolental deposits are unilateral in the first case and bilateral in the second. Both patients report a history of ocular trauma. This is a possible important clinical sign of pigment dispersion syndrome, rarely described.

RESUMO A síndrome de dispersão pigmentar associa-se a sinais clínicos característicos como fuso de Krukenberg, hiperpigmentação da malha trabecular, linha de Scheie e anel de Zentmeyer. Um sinal menos comum dessa síndrome é o depósito de pigmento posterior ao cristalino, que ocorre por um descolamento da hialoide anterior ou um defeito no ligamento de Wieger. Apresentamos dois casos de depósitos de pigmento posterior à cápsula posterior do cristalino. Em ambos os casos, existia dispersão bilateral de pigmento por todo o segmento anterior. No primeiro caso, os depósitos eram unilaterais e, no segundo, estavam presentes em ambos os olhos. Este pode corresponder a um sinal potencialmente importante da síndrome de dispersão pigmentar, raramente descrito.

Potential of olfactory neuroepithelial cells as a model to study schizophrenia: A focus on GPCRs (Review).

Schizophrenia (SZ) is a multifactorial disorder characterized by volume reduction in gray and white matter, oxidative stress, neuroinflammation, altered neurotransmission, as well as molecular deficiencies such as punctual mutation in Disrupted­in­Schizophrenia 1 protein. In this regard, it is essential to understand the underlying molecular disturbances to determine the pathophysiological mechanisms of the disease. The signaling pathways activated by G protein­coupled receptors (GPCRs) are key molecular signaling pathways altered in SZ. Convenient models need to be designed and validated to study these processes and mechanisms at the cellular level. Cultured olfactory stem cells are used to investigate neural molecular and cellular alterations related to the pathophysiology of SZ. Multipotent human olfactory stem cells are undifferentiated and express GPCRs involved in numerous physiological functions such as proliferation, differentiation and bioenergetics. The use of olfactory stem cells obtained from patients with SZ may identify alterations in GPCR signaling that underlie dysfunctional processes in both undifferentiated and specialized neurons or derived neuroglia. The present review aimed to analyze the role of GPCRs and their signaling in the pathophysiology of SZ. Culture of olfactory epithelial cells constitutes a suitable model to study SZ and other psychiatric disorders at the cellular level.

Gut dysbiosis induced by florfenicol increases susceptibility to Aeromonas hydrophila infection in Zebrafish Danio rerio after the recommended withdrawal period.

OBJECTIVE: Florfenicol (FFC) is a broad-spectrum antibiotic approved by the U.S. Food and Drug Administration to treat both systemic and external bacterial infections in food fish. The objective of this study was to evaluate the effect of FFC-medicated feed on the gut microbiota of Zebrafish Danio danio to determine (1) if the therapeutic dose of FFC-medicated feed induces dysbiosis and (2) if fish with altered gut microbiota were more susceptible to subsequent infection by the common opportunistic fish pathogen Aeromonas hydrophila. METHODS: Zebrafish that were treated with regular and FFC-medicated feeds were artificially challenged with A. hydrophila at the end of the recommended 15-day antibiotic withdrawal period. The gut microbiota of the Zebrafish at different stages was analyzed using 16S ribosomal RNA gene sequencing. RESULT: Our results found that FFC-medicated feed induced disruption of the gut microbiota. Dysbiosis was observed in all treated groups, with a significant increase in bacterial diversity, and was characterized by a remarkable bloom of Proteobacteria and a drastic decline of Mycoplasma and Cetobacterium in treated animals but without noticeable clinical signs or mortalities. In addition, the increase of Proteobacteria was not significantly reduced after the recommended 15-day withdrawal period, and the Zebrafish treated with FFC-medicated feed exhibited a significantly higher mortality rate when they were subsequently challenged with A. hydrophila compared to the control (regular feed) groups. Interestingly, the most dramatic changes in the gut microbiome composition occurred at the transition time between the late stage of the medicated treatment and the beginning of the withdrawal period instead of the time during the Aeromonas infection. CONCLUSION: The administration of FFC-medicated feed at the recommended dose induced gut dysbiosis in Zebrafish, and fish did not recover to the baseline after the recommended withdrawal period. Our findings suggest that the use of antibiotics in fish elicits a response similar to those previously described in mammals and possibly makes the host more susceptible to subsequent infections of opportunistic pathogens. This study using a controlled model system suggests that antibiotics in aquaculture may have long-term effects on the general well-being of the fish.

Role of Stress on Driving the Intestinal Paracellular Permeability.

The gut epithelium is a polarized monolayer that exhibits apical and basolateral membrane surfaces. Monolayer cell components are joined side by side via protein complexes known as tight junction proteins (TJPs), expressed at the most apical extreme of the basolateral membrane. The gut epithelium is a physical barrier that determinates intestinal permeability, referred to as the measurement of the transit of molecules from the intestinal lumen to the bloodstream or, conversely, from the blood to the gut lumen. TJPs play a role in the control of intestinal permeability that can be disrupted by stress through signal pathways triggered by the ligation of receptors with stress hormones like glucocorticoids. Preclinical studies conducted under in vitro and/or in vivo conditions have addressed underlying mechanisms that account for the impact of stress on gut permeability. These mechanisms may provide insights for novel therapeutic interventions in diseases in which stress is a risk factor, like irritable bowel syndrome. The focus of this study was to review, in an integrative context, the neuroendocrine effects of stress, with special emphasis on TJPs along with intestinal permeability.

Enteric Nervous System: Identification of a Novel Neuronal Sensory Network in the Duodenal Epithelium.

The communication between the intestinal epithelium and the enteric nervous system has been considered indirect. Mechanical or chemical stimuli activate enteroendocrine cells inducing hormone secretion, which act on sub-epithelial nerve ends, activating the enteric nervous system. However, we identified an epithelial cell that expresses NKAIN4, a neuronal protein associated with the ß-subunit of Na+/K+-ATPase. This cell overexpresses Na+/K+-ATPase and ouabain-insensitive Na+-ATPase, enzymes involved in active sodium transport. NKAIN4-positive cells also express neuronal markers as NeuN, acetylcholine-esterase, acetylcholine-transferase, α3- and α7-subunits of ACh receptors, glutamic-decarboxylase, and serotonin-receptor-7, suggesting they are neurons. NKAIN4-positive cells show a polarized shape with an oval body, an apical process finished in a knob-like terminal in contact with the lumen, a basal cilia body at the base of the apical extension, and basal axon-like soma projections connecting sub-epithelial nerve terminals, lymphoid nodules, glial cells, and enterochromaffin cells, forming a network that reaches the epithelial surface. We also showed, using retrograde labeling and immunofluorescence, that these cells receive afferent signals from the enteric nervous system. Finally, we demonstrated that acetylcholine activates NKAIN4-positive cells inducing Ca2+ mobilization and probably serotonin secretion in enterochromaffin cells. NKAIN4-positive cells are neurons that would form a part of a duodenal sensory network for physiological or noxious luminal stimuli.