Correlation of functional and structural measurements in eyes suspected of having glaucoma.

PURPOSE: This study was conducted to determine the correlation between structural changes in the retinal nerve fiber layer (RNFL) and functional loss detected on short-wavelength automated perimetry (SWAP) in a population of patients with suspected glaucoma. METHODS: With a selection criteria of intraocular pressure (IOP) more than 21 mmHg and normal results of conventional automated perimetry, 49 eyes of 49 patients with ocular hypertension were enrolled in the study. The SWAP was performed with a modified Humphrey field analyzer, and visual field indexes (mean deviation [MD], corrected pattern standard deviation [CPSD]) were calculated. Semiquantitative RNFL scores were given separately to diffuse and localized defects of the RNFL. RESULTS: The MD increased significantly with higher diffuse and total RNFL scores, with good correlation coefficients. A weak correlation was found between CPSD and diffuse, total, and localized RNFL scores. CONCLUSION: Diffuse RNFL loss are associated with abnormalities in visual field indexes (MD), whereas focal structural damage showed no correlation with visual field loss.     

Tooth and periodontal clinical attachment loss are associated with hyperglycemia in patients with diabetes

Background: Periodontal disease has been associated with diabetes, but there is still controversy on the relationship between periodontal clinical parameters and glycemic control. The purpose of this study is to assess the relationship between blood glucose levels and clinical parameters of periodontal disease in individuals with diabetes. Methods: A total of 65 individuals with diabetes and 81 individuals without diabetes were included in the study. A full-mouth periodontal examination and preprandial fasting glycemia values were recorded for each individual. Glycosylated hemoglobin was only measured in patients with diabetes. A comparative analysis between groups (Mann-Whitney U test) and a correlation analysis between glycemia and periodontal parameters were performed (Spearman test). Results: Patients without diabetes presented more teeth than individuals with diabetes (P <0.05). Patients with diabetes with periodontitis displayed loss of periodontal clinical attachment compared to patients without diabetes, but the highest value was observed in patients with periodontitis that reported a smoking habit. Furthermore, patients with diabetes with periodontitis presented higher glycemia and glycated hemoglobin values in contrast to patients with gingivitis. Patients with diabetes with hyperglycemia had a higher risk to develop periodontitis (odds ratio = 2.24; 95% confidence interval = 1.02 to 4.93). A positive correlation was observed between glycemia and clinical attachment loss (AL), whereas a negative correlation between glycemia and the number of teeth present was found (P <0.05). Conclusions: Tooth and periodontal AL were increased by hyperglycemia in individuals with diabetes. This study contributes additional evidence that diabetes could aggravate periodontal disease and affect the systemic health of individuals.     

Oral pigmented lesions: Clinicopathologic features and review of the literature

Diagnosis of pigmented lesions of the oral cavity and perioral tissues is challenging. Even though epidemiology may be of some help in orientating the clinician and even though some lesions may confidently be diagnosed on clinical grounds alone, the definitive diagnosis usually requires histopathologic evaluation. Oral pigmentation can be physiological or pathological, and exogenous or endogenous. Color, location, distribution, and duration as well as drugs use, family history, and change in pattern are important for the differential diagnosis. Dark or black pigmented lesions can be focal, multifocal or diffuse macules, including entities such as racial pigmentation, melanotic macule, melanocytic nevus, blue nevus, smoker’s melanosis, oral melanoacanthoma, pigmentation by foreign bodies or induced by drugs, Peutz-Jeghers syndrome, Addison´s disease and oral melanoma. The aim of this review is to present the main oral black lesions contributing to better approach of the patients. Key words:Pigmentation, melanin, oral, diagnosis, management.     

Functional significance of Smad2 in regulating basal keratinocyte migration during wound healing

Members of the transforming growth factor-beta (TGF-beta) superfamily are critical regulators for wound healing. Transduction of TGF-beta signaling depends on activation of Smad2 and Smad3 by heteromeric complexes of ligand-specific receptors. Mice lacking Smad3 show accelerated wound healing, whereas the biological significance of Smad2-mediated TGF-beta signaling in wound healing remains unknown. To understand the function of Smad2 in regulating wound healing, we investigated the effect of Smad2 overexpression on epithelialization of incision wounds. Cutaneous wounds made in K14-Smad2 mice showed delayed healing. This delay in wound healing resulted from a defect in basal keratinocyte migration in K14-Smad2 mice. Instead of basal keratinocytes, the suprabasal layer of keratinocytes migrated into the wound region. Furthermore, overexpression of Smad2 activated the Smad2/Smad4 complex in keratinocytes and inhibited keratin 16 (K16) expression. As K16 functions as a critical mediator for reorganization of keratin filaments following skin injury, we propose that altered K16 expression affects the migration of basal keratinocytes in the K14-Smad2 mice. Taken together, these findings demonstrate a crucial role of TGF-beta signaling mediator Smad2 in regulating keratinocyte migration and re-epithelialization during wound healing. The K14-Smad2 transgenic mice can serve as an animal model for the investigation of TGF-beta signaling mechanism in regulating wound healing.     

Subacute cutaneous systemic lupus erythematosus. Presentation of two clinical cases

We present two cases of systemic lupus erythematosus (SLE) which began with subacute clinical manifestations. Both cutaneous and systemic lupus are the result of interactions between susceptibility genes and environmental factors such as ultraviolet radiation, giving rise to an anomalous response with hyperreactivity of T and B lymphocytes. Over 50 % of subacute cutaneous lupus cases have or will have SLE, while only 16 to 61 % of SLE cases have acute cutaneous lupus lesions.     

Assay of mucins in human tear fluid

Mucin genes, both secreted (MUC2, MUC5AC, MUC5B, MUC7) and membrane associated (MUC1, MUC4, MUC16), have been reported to be expressed by ocular surface epithelia. The purpose of this study was to comprehensively assay the mucin content of human tear fluid using multiple antibodies for each mucin and to develop a sensitive, semi-quantitative method for the assay of mucins in tears. Tear washes were obtained by instillation of saline onto the ocular surface, followed by collection from the inferior fornix. Tear proteins were separated in 1% agarose gels, transferred to nitrocellulose membrane by vacuum blotting and probed with multiple antibodies recognizing MUC1, MUC2, MUC4, MUC5AC, MUC5B, MUC7 and MUC16. Binding was detected using chemiluminescence, and quantity was determined by densitometry. Serial dilutions of pooled tears from normal individuals were assayed to determine the linear range of detectability. MUC1, MUC4, MUC16, MUC5AC and low levels of MUC2 were consistently detected in human tear fluid, while MUC5B and MUC7 were not. Use of several antibodies recognizing different epitopes on the same mucin confirmed these findings. The antibodies to mucins bound to serial dilutions of tears in a linear fashion (r2 > 0.9), indicating the feasibility of semi-quantitation. MUC5AC in tear fluid had an increased electrophoretic mobility compared to MUC5AC isolated from conjunctival tissue. This study provides clear evidence that the mucin component of tears is a mixture of secreted and shed membrane-associated mucins, and for the first time demonstrates MUC16 in tear fluid. Immunoblots of tears using agarose gel electrophoresis and chemiluminescence detection provide a semi-quantitative assay for mucin protein that will be useful for comparisons with tears from diseased eyes or after pharmacological intervention.     

Metabolic expression of intrinsic developmental programs for dentine and enamel biomineralization in serumless,chemically-defined,organotypic culture

Summary Biomineralization was investigated using embryonic mouse mandibular first molars (M₁) cultured in the presence or absence of fetal calf serum. Metabolic features including cell division and Ca²⁺ and phosphate incorporation into dentine and enamel extracellular matrices were analyzed. The relative timing and magnitude of DNA synthesis for serumless cultures was comparable toin vivo controls. Isotopic calcium and phosphate incorporation into the mineral phase of dentine and enamel matrices, in the absence of serum, fluctuated during development. Molar tooth morphogenesis, cytodifferentiation, and extracellular matrix formation approximated late crown-stage development in serumless cultures. Von Kossa histochemical staining indicated calcium phosphate salt formation in serumless cultures. Analysis of anhydrous fixation-prepared enamel and dentine representing serumless cultured explants indicated that crystal size and orientation were comparable toin vivo enamel and dentine. In contrast, serum-supplemented cultures showed atypical crystal size and orientation. Calcium/phosphorous (Ca/P) ratio values for serumless cultures after 21 days showed Ca/P enamel values of 2.03 (SD±0.04, p<0.025) and dentine values of 1.89 (SD±0.01, p<0.025). Electron diffraction patterns of enamel and dentine formed in serumless cultures were principally those of highly-ordered crystalline hydroxyapatite. Our results suggest that tissue-specific dentine and enamel biomineralization is regulated by endogenous factors intrinsic to the developmental program of embryonic tooth organs during serumless culture.     

Switch from ritonavir-boosted to unboosted atazanavir guided by therapeutic drug monitoring

Plasma concentration of atazanavir (ATV) may be reduced when coadministered with tenofovir (TDF) or proton pump inhibitors. Boosting ATV exposure with ritonavir (r) may make it possible to overcome these drug interactions. However, jaundice and loss of the metabolic advantages of ATV are more frequent using ATV/r than ATV alone. Herein, we assessed whether therapeutic drug monitoring (TDM) could make it possible to identify the subset of patients in whom removal of ritonavir could be attempted without risk of suboptimal plasma ATV exposure and subsequent virological failure. A total of 56 patients with undetectable plasma HIV-RNA under a stable triple regimen containing ATV 300/100 mg qd were switched to ATV 400 mg qd. Plasma ATV concentrations were measured using a reliable high-performance liquid chromatography method. Median plasma ATV C(min) fell from 880 to 283 ng/ml (p = 0.03) after removal of ritonavir. While all patients on ATV/r showed ATV plasma concentrations within therapeutic values (IC(min) above 150 ng/ml) before switching, four patients (7%) fell below this threshold after switching to ATV 400 mg qd. However, only one of this group experienced virological failure at week 24 of follow-up. TDF was part of the antiretroviral regimen in all four cases. From a total of 29 (52%) patients on ATV/r showing grade 3-4 hyperbilirubinemia, only 7 (12%) remained on it upon switching to ATV 400 mg qd (p < 0.001). Patients with complete viral suppression under ATV/r 300/100 mg qd may benefit from switching to ATV 400 mg qd guided by TDM, which may make it possible to minimize adverse events without compromising antiviral efficacy in most cases.     

Alcohol Modulation of Human Normal T-Cell Activation, Maturation, and Migration

We are interested in the characterization of the effects of alcohol on human T-cell activation, maturation, and migration, because this cell population is crucial in the initiation, regulation, and propagation of cellular immunity. We and others have described the effects of both acute and chronic exposure of human immune cells to ethanol (EtOH) in vitro. Herein, we briefly, review these reports and expand this body of literature with the inclusion of new data recently obtained in our laboratory. We confirm the blunting effects of EtOH on the production of interleukin-2 and mitogen proliferative response following T-cell mitogen stimulation, and on the expression of membrane markers of activation. We show that EtOH significantly alters the expression of the CD4 cell-associated marker of activation, CD26. We report the effect of EtOH on the expression of the homing receptor CD62L by CD4⁺ cells, and on their ability to adhere by a CD18-mediated process to a defined cellular substratum. Furthermore, we demonstrate the effects of EtOH and EtOH and 0-endor-phin pretreatment on the activation of CD4⁺ lymphocytes endowed with the homing receptor CD62L.