Search

Homocysteine has been associated to the stroke, which enhances the interest for the investigation about the role of vitamins involved on its metabolism. Stroke Prone rats were treated by pyridoxine and folic acid at doses correspondent to five, ten and twenty times their nutritional needs. The systolic blood pressure and general parameters were analyzed and compared to control group. The doses correspondents to 10 and 20 times RDA promoted a hypotensive effect, but doses correspondents to 5 times, did not. The treated animals at 190 days of age presented a significant reduction of systolic blood pressure: 204 ± 3mmHg when compared to control group: 230 ± 5mmHg. At seven months of age the animals under treatment did not present signs of stroke naturally detected in that linkage. Our results suggest that vitamins B6 and B9 could be beneficial for preventive therapy of stroke. [ABSTRACT FROM AUTHOR]

Background: Considering the potential of p16 as a marker for diagnosis, prognosis and therapeutic response, the aim of this study was to assess its presence, via immunocytochemistry, in metastatic carcinoma of different primary sites and histological types obtained from effusions and peritoneal washings. A total of 118 samples including 85 of metastatic carcinoma and 33 samples of benign effusion/peritoneal washing were prepared by the plasma/thromboplastin method. Immunocytochemistry reactions were performed on cell block sections using antibodies against p16, claudin-4, MOC-31, calretinin, HBME and CD68., Results: P16 overexpression was observed in 88.23% of all carcinoma samples. All cervix adenocarcinoma samples showed p16 overexpression. Overexpression in adenocarcinomas of ovary, lung and breast was observed in 93.75, 93.10 and 75% of the samples, respectively. Overexpression was observed in all different histological types analyzed: small cell carcinoma (lung), squamous cell carcinoma (cervical) and urothelial carcinoma (bladder). The specificity of p16 for carcinoma detection was of 96.96%., Conclusion: Overexpression of p16 was observed in most metastatic carcinoma, from different primary sites and histological types, obtained from effusions and peritoneal washings. Due to its high frequency of overexpression in metastatic carcinoma, p16 may play a possible role in tumor progression and it may be considered as a complementary diagnostic marker depending on histological type and primary site of carcinoma.

Epithelial cell adhesion molecule (EpCAM) has been used as diagnostic/prognostic marker and therapeutic target. The aim of the present study was to compare immunoreactivity of antibodies against distinct epitopes in the ectodomain of EpCAM for detection of carcinoma from different primary sites and of different histological types in effusions and peritoneal wash. Two antibodies against epitopes in the EGF-like domain I (clones Moc-31 and Ber-EP4) and one antibody against the epitope in the cysteine-poor region (158210) of EpCAM were used (all commercially available). Independently of the clone used, EpCAM overexpression was observed in almost all samples when all the adenocarcinoma samples were analyzed together. By using Moc-31, EpCAM overexpression was observed in all samples of adenocarcinoma. Absence of EpCAM overexpression was observed in a few adenocarcinoma samples at some sites of tumor origin, including ovary, breast and stomach, when Ber-EP4 and 158210 were used. Regarding carcinomas aside from adenocarcinomas, histological types, such as squamous cell, urothelial and small cell carcinoma showed different degrees of EpCAM expression according to the antibody used. In squamous cell carcinoma, overexpression was observed only with the clone 158210. It was concluded that, overall, most samples of metastatic carcinoma from effusions showed overexpression of EpCAM. However, there are significant variations in its detection according to the primary site, histological type of the carcinoma and depending on the antibody used. Thus, the use of more than one type of anti-EpCAM antibody would increase the chance of its detection in metastatic carcinoma effusion.

Background: Anti-Tumor Necrosis Factor-alpha therapy has become clinically important for treating inflammatory bowel disease. However, the use of conventional immunotherapy requires a systemic exposure of patients and collateral side effects. Lactic acid bacteria have been shown to be effective as mucosal delivering system for cytokine and single domain antibodies, and it is amenable to clinical purposes. Therefore, lactic acid bacteria may function as vehicles for delivery of therapeutic antibodies molecules to the gastrointestinal tract restricting the pharmacological effect towards the gut. Here, we use the mucosal delivery of Lactococcus lactis carrying an anti-TNFα scFv expression plasmid on a DSS-induced colitis model in mice., Results: Experimental colitis was induced with DSS administered in drinking water. L. lactis carrying the scFv expression vector was introduced by gavage. After four days of treatment, animals showed a significant improvement in histological score and disease activity index compared to those of untreated animals. Moreover, treated mice display IL-6, IL17A, IL1β, IL10 and FOXP3 mRNA levels similar to health control mice. Therefore, morphological and molecular markers suggest amelioration of the experimentally induced colitis., Conclusion: These results provide evidence for the use of this alternative system for delivering therapeutic biopharmaceuticals in loco for treating inflammatory bowel disease, paving the way for a novel low-cost and site-specific biotechnological route for the treatment of inflammatory disorders.

Objective: To describe a clinical case of successful conservative management of Localized Juvenile Spongiotic Gingivitis Hyperplasia (LJSGH) using photodynamic therapy (PDT) and reviews the current literature on this pathology. Background data: LJSGH is a recently described rare disease with controversial treatment results. As of today, 13 publications report surgical treatment approaches. The use of CO 2 laser and cryotherapy was reported only in one study. The use of PDT was not previously reported. Patients and methods: A 9-year-old male patient was referred to our institution with the chief complaint of asymptomatic "inflamed gingiva" starting 1 year before. Clinical examination revealed an erythematous line accompanying the gingival contour, with a certain degree of hyperplasia. The diagnosis of LJSGH was performed based on clinical features and later confirmed histopathologically. A novel approach using PDT was then proposed. The photosensitizer was methylene blue, and a semiconductor laser diode was used. Results: One week after starting PDT, gingival hyperplasia was partially reduced. Immediately after the end of treatment, a significant reduction of gingival hyperplasia was observed. PDT proved to be safe, quick and painless, with no esthetic harm. Conclusions: This case illustrates the benefit of a more conservative approach as opposed to surgical procedure, with good clinical response and decreased morbidity over a 2-year follow-up period.

Objective: To describe a clinical case of successful conservative management of Localized Juvenile Spongiotic Gingivitis Hyperplasia (LJSGH) using photodynamic therapy (PDT) and reviews the current literature on this pathology., Background Data: LJSGH is a recently described rare disease with controversial treatment results. As of today, 13 publications report surgical treatment approaches. The use of CO 2 laser and cryotherapy was reported only in one study. The use of PDT was not previously reported., Patients and Methods: A 9-year-old male patient was referred to our institution with the chief complaint of asymptomatic "inflamed gingiva" starting 1 year before. Clinical examination revealed an erythematous line accompanying the gingival contour, with a certain degree of hyperplasia. The diagnosis of LJSGH was performed based on clinical features and later confirmed histopathologically. A novel approach using PDT was then proposed. The photosensitizer was methylene blue, and a semiconductor laser diode was used., Results: One week after starting PDT, gingival hyperplasia was partially reduced. Immediately after the end of treatment, a significant reduction of gingival hyperplasia was observed. PDT proved to be safe, quick and painless, with no esthetic harm., Conclusions: This case illustrates the benefit of a more conservative approach as opposed to surgical procedure, with good clinical response and decreased morbidity over a 2-year follow-up period.

Purpose: MicroRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. We reported that levels of microRNA (miR)-29 family are decreased in corneas of patients with Fuchs endothelial corneal dystrophy (FECD). The miR-29 family regulates the production of extracellular matrix (ECM) proteins. Accumulation of ECM proteins in Descemet membrane is an important pathologic change in FECD. In this study, we transfected miR-29b into human corneal endothelial cells and tissues and evaluated ECM protein expression levels., Methods: An immortalized Fuchs human corneal endothelial cell line (iFECD) was established by infection of corneal endothelial cells from patients with FECD with hTERT lentivirus. MiR-29b was transfected into iFECD, and the expression levels of ECMs collagen type 1 alpha 1 (COL1A1), collagen type 4 alpha 1 (COL4A1), and laminin gamma 1 (LAMC1) were evaluated with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot. Expression level of LAMC1 protein in miR-29b-transfected donor corneal endothelium was also evaluated by Western blot., Results: Compared with control, miR-29b expression level after transfection of iFECD was increased to 335.6% (±91.0%), and ECM expression levels were significantly decreased. Compared with control, qRT-PCR demonstrated reduction of ECM to the following levels: COL1A1: 1.9% (±0.4%); COL4A1: 7.1% (±1.7%); and LAMC1: 21.5% (±2.7%). Western blot showed reduced protein expression: COL1A1: 4.8% (±3.2%); COL4A1: 42.5% (±25.0%); and LAMC1: 44.8% (±3.1%). In miR-29b-transfected corneal tissue, LAMC1 protein expression level was decreased to 14.4% (±20.5%)., Conclusions: Overexpression of miR-29b decreased ECM protein production in human corneal endothelial cells. Thus, miR-29 replacement therapy might be a new treatment strategy for FECD aimed at reducing pathologic production of ECM proteins in Descemet membrane., Competing Interests: No authors have conflicts of interest or proprietary interests in the contents of this manuscript.

It is proposed a method for the determination of (226)Ra in offshore platform liquid effluent samples (produced water). The method is based on a two-phase liquid scintillation counting system and allows for the direct and simple determination of (226)Ra content. Samples with high barium content may also have high (226)Ra concentration. Therefore, the sample volume is based on the barium concentration and ranges from 10 mL to 100 mL. Our new method was tested using multiple real samples and was compared with the BaSO4 precipitation method. The results based on the LSC were 30% higher than the precipitation method, which is attributed to the self-absorption of alpha particles in the BaSO4 precipitate. The determination of both (226)Ra and (228)Ra in the liquid effluent of offshore oil platforms is mandatory in Brazil. Thus, a second method of accurately assessing (228)Ra content remains necessary., (Copyright © 2016. Published by Elsevier Ltd.)

Purpose: To compare cryopreserved human corneal endothelial cells (HCECs) grown in human serum-supplemented media (HS-SM) with cryopreserved HCECs grown in fetal bovine serum-supplemented media (FBS-SM)., Methods: Three pairs of human corneas from donors aged 8, 28, and 31 years were obtained from the eye bank. From each pair, one cornea was used to start a HCEC culture using HS-SM; the other cornea was grown in FBS-SM. On reaching confluence, the six cell populations were frozen using 10% dimethyl sulfoxidecontaining medium. Thawed cells grown in HS-SM were compared with those grown in FBS-SM with respect to morphology, growth curves, immunohistochemistry, real time-reverse transcriptase polymerase chain reaction (RT-PCR) for endothelial cell markers, and detachment time., Results: No difference in morphology was observed for cells grown in the two media before or after cryopreservation. By growth curves, cell counts after thawing were similar in both media, with a slight trend toward higher cell counts in FBS-SM. Cells grown in both the media demonstrated a similar expression of endothelial cell markers when assessed by immunohistochemistry, although HCEC marker gene expression was higher in cells grown in HS-SM than in those grown in FBS-SM as assessed by RT-PCR. With FBS-SM, there was a tendency of longer detachment time and lower cell passages., Conclusions: HS-SM was similar to FBS-SM for cryopreservation of cultured HCECs as assessed by analysis of cell morphology, proliferation, and protein expression, although marker gene expression was higher in cells grown in HS-SM than in those grown in FBS-SM. Detachment time was longer with FBS-SM and in lower passages.

Purpose: Corneal collagen cross-linking (CXL) alone cannot substantially improve refractive errors. We designed a novel corneal-shaping device, showing that a prototype applied during CXL can alter corneal curvature to a greater extent than CXL alone in a porcine eye model., Methods: The device prototype was made with flat, UV-transmissible material. Enucleated porcine eyes were deepithelialized and perfused. Preexperimental and postexperimental corneal curvature (K) measurements and Anterior Segment Optical Coherence Tomography imaging were performed. A conventional CXL protocol was followed. Six experiments of 6 treatment groups in duplicate were performed (n = 12/group): (A) no CXL + no device, (B) no CXL + 30 minutes device, (C) 10 minutes, CXL + no device, (D) 10 minutes, CXL + device, (E) 30 minutes, CXL + no device, and (F) 30 minutes, CXL + device., Results: There was a significant decrease (P < 0.001) in corneal curvature after 30 minutes. CXL between group F (-1.54 ± 0.90 D) and groups E (+0.34 ± 0.53 D), B (+0.69 ± 1.02 D), or A (+0.22 ± 1.24 D). The demarcation line depth was greater in group F (34% ± 4%) than group D (30% ± 4%, P < 0.05). Groups D (-2.3% ± 21%) and F (0.24% ± 15%) had less change in corneal thickness than in control groups A (15% ± 12%, P < 0.05) and E (12% ± 11%, P < 0.05)., Conclusions: Application of our corneal-shaping device during CXL significantly decreased corneal curvature compared with controls. Anterior Segment Optical Coherence Tomography imaging showed comparable extent of cross-linking in eyes treated ± device. This demonstrates that our novel device used during CXL may further promote corneal strengthening and refractive correction in patients.

Strokes are preceded by oxidative stress and inflammation, two processes linked to atherosclerosis and hypertension. Statins have been widely employed to control atherosclerosis; however, there could be neurological implications to its use—including cognitive impairment. Thus,we aimed to determine whether alpha-tocopherol is capable of reversing the neurological side effects of statins and enhancing its anti-inflammatory properties. To assess these effects, 15-week-old stroke-prone spontaneously hypertensive rats (SHRSPs) were divided into four groups (n = 6, each): alpha-tocopherol (AT), lovastatin (LoV), alpha-tocopherol + lovastatin (AT + LoV), and control (C).We administered 120 IU of alpha-tocopherol diluted in 0.1 ml of coconut oil,whereas the dose of lovastatin was administered at a ratio of 1 mg/kg of rat body weight. The control group received 0.1 ml coconut oil. All animals received the treatments via orogastric gavage.We assessed body weight, diuresis, food and water intake, oxidative stress (malondialdehyde levels), the total cellular injury marker (lactate dehydrogenase), short and long-term memory, cognition, and histopathological changes in the hippocampus. The results demonstrated that lovastatin treatment did not negatively affect the memory of our animal model. In fact, the animals treated with AT and LoV showed improvement in memory and cognition. Additionally, both treatments decrease lactate dehydrogenase and oxidative stress levels. Furthermore, our study also demonstrated hippocampal tissue preservation in the treated groups.

Purpose: To investigate the relationship between quantitative iris parameters and the presence of keratoconus., Methods: Cross-sectional observational study that included 15 affected eyes of 15 patients with keratoconus and 26 eyes of 26 normal age- and sex-matched controls. Iris parameters (area, thickness, and pupil diameter) of affected and unaffected eyes were measured under standardized light and dark conditions using anterior segment optical coherence tomography (AS-OCT). To identify optimal iris thickness cutoff points to maximize the sensitivity and specificity when discriminating keratoconus eyes from normal eyes, the analysis included the use of receiver operating characteristic (ROC) curves., Results: Iris thickness and area were lower in keratoconus eyes than in normal eyes. The mean thickness at the pupillary margin under both light and dark conditions was found to be the best parameter for discriminating normal patients from keratoconus patients. Diagnostic performance was assessed by the area under the ROC curve (AROC), which had a value of 0.8256 with 80.0% sensitivity and 84.6% specificity, using a cutoff of 0.4125 mm. The sensitivity increased to 86.7% when a cutoff of 0.4700 mm was used., Conclusions: In our sample, iris thickness was lower in keratoconus eyes than in normal eyes. These results suggest that tomographic parameters may provide novel adjunct approaches for keratoconus screening.

Purpose: To assess the results of a single eye bank preparing a high volume of Descemet membrane endothelial keratoplasty (DMEK) tissues using multiple technicians to provide an overview of the experience and to identify possible risk factors for DMEK preparation failure., Design: Cross-sectional study., Methods: setting: Lions VisionGift and Wilmer Eye Institute at Johns Hopkins Hospital., Study Population: All 563 corneal tissues processed by technicians at Lions VisionGift for DMEK between October 2011 and May 2014 inclusive., Observation Procedures: Tissues were divided into 2 groups: DMEK preparation success and DMEK preparation failure., Main Outcome Measures: We compared donor characteristics, including past medical history., Results: The overall tissue preparation failure rate was 5.2%. Univariate analysis showed diabetes mellitus (P = .000028) and its duration (P = .023), hypertension (P = .021), and hyperlipidemia or obesity (P = .0004) were more common in the failure group. Multivariate analysis showed diabetes mellitus (P = .0001) and hyperlipidemia or obesity (P = .0142) were more common in the failure group. Elimination of tissues from donors either with diabetes or with hyperlipidemia or obesity reduced the failure rate from 5.2% to 2.2%. Trends toward lower failure rates occurring with increased technician experience also were found., Conclusions: Our work showed that tissues from donors with diabetes mellitus (especially with longer disease duration) and hyperlipidemia or obesity were associated with higher failure rates in DMEK preparation. Elimination of tissues from donors either with diabetes mellitus or with hyperlipidemia or obesity reduced the failure rate. In addition, our data may provide useful initial guidelines and benchmark values for eye banks seeking to establish and maintain DMEK programs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to determine intertest variability of measurements taken by the Pentacam tomographer in eyes with keratoconus., Methods: Three Pentacam measurements with 1-minute intervals were taken from 101 eyes (81 keratoconus and 20 controls) from 57 patients (47 keratoconus and 10 controls) by the same examiner and under the same conditions. Keratoconus eyes were divided into 3 subgroups based on topographic astigmatism (TA). Variability in astigmatism, mean keratometry, central corneal thickness, and fixation values were compared within the patient subgroups versus normal controls., Results: Variability of all studied parameters (astigmatism, mean keratometry, central corneal thickness, and fixation values) increased with increasing TA in patients with keratoconus., Conclusions: Pentacam measurements show increased variability in patients with keratoconus. The degree of variability correlates with TA.

Background/aims: To study human corneal endothelial cells (HCECs) cultured in vitro with human serum (HS) supplemented media (HS-SM) compared with HCEC cultured in fetal bovine serum (FBS) supplemented media (FBS-SM)., Methods: One cornea from a donor aged 21 years and a pair of corneas from a 16 year-old donor were obtained from the eye bank and used to create two different cell populations. At the first passage, the cell populations were equally divided and seeded in two different wells containing FBS-SM or HS-SM. In subsequent passages, HS-SM was compared with FBS-SM by morphology, growth curves, immunohistochemistry and real-time reverse-transcriptase PCR for endothelial cell markers., Results: No difference in morphology could be seen in P2, P5 or in any other passages for cells grown in the two media. By growth curves, cell counts were similar in FBS-SM and HS-SM from days 1 to 5, with a trend towards higher cell counts in HS-SM at day 7. Cells grown in FBS-SM and HS-SM media showed similar expression of endothelial cell markers when assessed by immunohistochemistry and real-time reverse-transcriptase PCR., Conclusions: HS-SM was similar to FBS-SM for HCEC culture when assessed by cell morphology, proliferation and protein/gene expression., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The aim of this study was to evaluate the expression of IMP3, an independent poor prognostic factor for many cancers, and its association with clinicopathological features and HER2 status., Methods: Gastrectomy specimens from 106 patients were evaluated by immunohistochemistry and fluorescence in situ hybridization., Results: HER2 overexpression was found in 4.71 % of the samples. A negative association was observed between HER2 overexpression and grade of differentiation. No association was observed between HER2 overexpression and status of surgical margins, vascular invasion, perineural invasion, nodal metastasis and depth of invasion. Among all specimens of gastric cancer, 67.92 % were positive for IMP3. Expression of IMP3 was significantly higher in specimens with vascular invasion, perineural invasion, nodal metastasis and higher depth of invasion. HER2 overexpression was detected in only 5.55 % of IMP3 positive specimens., Conclusions: IMP3 expression was frequently observed in gastric cancer and was associated with poor prognostic clinicopathological features. A survival benefit with HER2 therapy should be expected for the minority of patients with IMP3 positive specimens. Studies should be conducted to evaluate the response to HER2 therapy of gastric cancer expressing IMP3.

Objective: To investigate the effect of administration of supraphysiological β carotene on biological, laboratory and histological parameters of spontaneously hypertensive rats prone to stroke (SHR-sp)., Methods: we used 36 male rats divided into three groups, each containing 12 rats of the types Wistar SHR and SHR-sp, subdivided into six control animals and six animals treated with supraphysiological doses of β carotene for two ten-week periods, interspersed by a one-week interruption. We carried out daily physical examination and blood pressure assessment. We collected blood for measurement of serum malondialdehyde; the liver and carotid arteries were subsequently harvested for histological examination., Results: there was a temporary change in the color of hair, a significant decrease (p <0.0001) in blood pressure (20 mg β carotene supplementation) and serum levels of malondialdehyde (p<0.05) and increased amount of elastic fibers in the carotid wall of SHR and SHR-sp., Conclusion: β carotene supraphysiological supplementation caused no toxic effects, showed positive response in the modulation of blood pressure and lower serum malondialdehyde. No significant morphological changes were observed in the groups studied, except for an increase in the number of elastic fibers in the carotid muscular layer, suggesting elastosis in SHR and SHR-sp.

Purpose: The aim of this study was to relate a case of deep anterior lamellar keratoplasty (DALK) converted to penetrating keratoplasty in which the host central Descemet membrane (DM) with a large perforation was left attached to the host cornea., Methods: This is a case report of a 34-year-old man who underwent an attempted DALK for keratoconus in his left eye, which became complicated with a large rupture in DM during dissection. The host DM was left in place, the donor cornea with DM intact was sutured onto the host bed, and air was injected into the anterior chamber. The patient was monitored by biomicroscopy, pachymetry, topography, anterior segment optical coherence tomography, and specular microscopy., Results: The postoperative course resulted in improved uncorrected visual acuity, best spectacle-corrected visual acuity, and topography. Corneal edema was observed in the host cornea peripheral to the graft. Three months after the surgery, the endothelial cell density was reduced by 63% compared with the preoperative donor cell density., Conclusions: Leaving the host DM during conversion of DALK to penetrating keratoplasty was uneventful in this case, although corneal edema was observed in the area overlying the host cornea. It is possible that the retained DM could provide additional autologous endothelial cells to prolong graft survival.

Purpose: To evaluate the efficacy and safety of a novel lutein-based dye for the anterior capsulorhexis during phacoemulsification in cataract surgery in humans., Methods: Twenty-five eyes from 25 patients were operated by 25 different surgeons who performed continuous circular capsulorhexis (CCC) guided by a lutein-based dye (Phacodyne™) during cataract surgery by phacoemulsification. A questionnaire assessed the surgeon’s opinion regarding the efficacy of the dye. Follow-up examinations were performed at 1, 7, and 30 days post-surgery. Eyes were evaluated by full ophthalmic examination, corneal topography/pachymetry, and corneal endothelial cell count., Results: As revealed by the answers to the questionnaire, the dye facilitated the CCC procedure in all eyes. Baseline nuclear cataract classification (according to the Lens Opacities Classification System III; LOCS III) was 3.24 (± 1.12). Preoperative BCVA (logMAR) was 0.89 ± 0.59 and improved to 0.23 ± 0.22 on day 30 after surgery. The intraocular pressure (IOP) remained stable and the inflammatory reaction subsided in all cases within the first 7 days after surgery. The pre-operative values of corneal pachymetry and IOP were similar to those found on follow-up day 30. Loss in endothelial cell number was similar to earlier reports., Conclusion: Phacodyne™ was efficient when used for anterior capsulorhexis during cataract surgery by phacoemulsification and

Oxidative stress has an important role in neuronal damage during cerebral ischemia and can lead to cognitive and behavioral impairment. Alpha-tocopherol, a powerful antioxidant, may be able to preserve neuronal tissue and circumvent neurological deficits. Thus, this study aimed to investigate the influence of alpha-tocopherol in the preservation of brain tissue and the maintenance of memory formation in stroke-prone spontaneously hypertensive rats (SHRSP). To achieve this aim, twenty-four 15-week-old male SHRSP rats were separated into the following four groups (n = 6 each) that received different treatments over a 4-week period: the alpha-tocopherol group, the control group, the L-NAME group, and the L-NAME + alpha-tocopherol group. We evaluated the physiological parameters (body weight, diuresis, and food and water intake), an oxidative stress marker (malondialdehyde levels), and neurological responses (the Morris Water Maze and Novel Objects Recognition tests). Afterwards, the brains were removed for histopathological analysis and quantification of the number of cells in the hippocampus. Statistically, the alpha-tocopherol group demonstrated better results when compared to all groups. The data indicated a reduction in oxidative stress and the preservation of neurological responses in groups treated with alpha-tocopherol. In contrast, the L-NAME group exhibited increased malondialdehyde levels, impairment of neurological responses, and several hippocampus tissue injuries. The others groups exhibited nerve tissue changes that were restricted to the glial nodes. No significant alterations were observed in the physiologic parameters. Based on these findings, we suggest that alpha-tocopherol can prevent stroke, preserve the structure of the hippocampus, and maintain both memory and cognition functions.

Carcinogenesis concerns several changes that eventually result in the inactivation of tumor suppressor genes and activation of protooncogenes, leading to loss of cell cycle control. Inactivation of p16 seems to be an early event in this process and occurs in approximately 80% of squamous cell carcinoma cases. The aims of this study were to evaluate the immunohistochemical expression of p16 protein in oral and oropharyngeal squamous cell carcinoma cases, with both the tumoral area itself and its surgical margin being analyzed (dysplastic areas and histologically normal epithelium adjacent to carcinoma), and to verify the presence of human papillomavirus (HPV) and its relation to p16 expression. Paraffin-embedded biopsy tissues from 26 patients, 13 with oral squamous cell carcinoma and 13 with oropharyngeal squamous cell carcinoma, comprised the analyzed samples. To detect HPV, a nested polymerase chain reaction test using PGMY 09/11 and GP5*/GP6* primers and visualization of the product on a 2% agarose gel was performed. Demographic data were obtained from medical records. The results showed low expression of p16 in the tumor area (38.46%), compared with surgical margins in the histologically normal epithelium (84.6%) and dysplastic areas (57.7%). These findings indicate the inactivation of p16 in the process of malignant transformation. The association described in the literature between expression of p16 and presence of HPV could not be verified in this study, because none of the cases was HPV positive.

Purpose: To relate the outcomes of 7 eyes of 7 patients in which a dexamethasone 0.7 mg implant (Ozurdex(®)) was placed inside the capsule bag after phacoemulsification and intraocular lens (IOL) implantation and compare with the fellow eyes, that were operated by the same technique and received dexamethasone eyedrops in the post-operatory., Methods: Report review of 7 eyes of 7 patients who received dexamethasone 0.7 mg implant after phacoemulsification and IOL, comparing them to the fellow eyes. All the patients underwent bilateral cataract surgery, with one month interval, by the same technique and by experienced surgeons, without complications. Post operatory medication consisted of moxifloxacin eye drops for all the 14 eyes and topic dexamethasone for the 7 eyes that did not received the implant., Results: Nuclear cataract classification (according to LOCS III) was 3.28 ± 0.69 in the implant eye group and 3.14 ± 0.83 in the fellow eye group. Postoperative best spectacle correct visual acuity (BSCVA) was 0.85 ± 0.12 and 0.87 ± 0.13, respectively in the implant and fellow eye groups. The intraocular pressure remained stable and similar to the pre-operative measurements. Anterior chamber reaction and cornea edema were similar in both groups in the follow-up. Two of the four no sutured pellet migrated to the anterior chamber during the first post-operative week and had to be repositioned. Another no sutured pellet dislocated and remained partially inside the capsule bag. The 3 patients with IOL haptic-sutured pellet had no complications., Conclusions: In the present study, dexamethasone 0.7 mg implant were effective in controlling the inflammation after phacoemulsification and IOL implantation, with no significant side effects.

Paracoccidioidomycosis (PCM) is a common deep mycosis in South America caused by Paracoccidioides brasiliensis, a dimorphic fungus. Biopsy is the most frequent diagnostic method. The aim of this article is reporting four cases of PCM, in which intraoral involvement simulated squamous-cell carcinoma and was diagnosed by exfoliative cytology. We highlight this diagnostic tool as a simple, low cost, painless, noninvasive, and fast diagnostic method for PCM., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma., Methods: Mice were evaluated with regard to the treatments' toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry., Results: Regarding the treatments' toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining., Conclusions: In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications.

Objectives: To characterise and confirm the presence of Mansonella ozzardi microfilariae in the cornea by biomicroscopy and corneal confocal microscopy., Design: Cross-sectional study., Settings: Clinical practice study in patients from rural communities in Coari city on the Solimões river, Amazonas state, Brazil., Participants: The eyes of 212 consecutive volunteer patients were examined using a flash light and their blood checked for the presence of microfilariae by an expert microscopist. Patients with suspicious corneal lesions (characterised as nummular keratitis) were submitted to biomicroscopy, fundoscopy and corneal confocal microscopy evaluation (CCME). In two patients, a biopsy of the limbal conjunctiva adjacent to the nummular keratitis was carried out and blood collected from the surgical wound for microfilariae investigation by thick blood film examination., Primary and Secondary Outcome Measures: Positive correlation between corneal biomicroscopic and confocal lesions and M ozzardi microfilaremia., Results: Of the 212 patients, 56 (26.4%) were positive for microfilaremia. 22 patients with nummular keratitis identified under flash light examination underwent biomicroscopy and CCME. Corneal lesions were positively correlated to microfilaremia (p=0.0001). At biomicroscopy, lesions were classified as quiescent or active. At CCME, lesions were categorised as circular or filiform. The associations between corneal lesions, CCME findings and microfilaremia are shown., Conclusions: We describe M ozzardi microfilariae in the cornea and the associated eye pathology. Further studies using ocular tissue PCR and other imaging techniques would be helpful.

This in vitro study aimed to investigate the anti-erosive effect of antacid suspensions applied to enamel after exposure to hydrochloric acid (HCl). Ninety bovine enamel slabs were embedded, flattened, and polished. Reference areas were created and specimens were divided into six groups. They were exposed to 0.01 M HCl (pH 2) for 2 min, followed by immersion for 1 min in one of the following test suspensions: magnesium hydroxide, aluminum hydroxide, magnesium hydroxide/aluminum hydroxide, sodium alginate/sodium bicarbonate/calcium carbonate, or hydrated magnesium aluminate. Artificial saliva was used as a negative control. Specimens were subjected to a total of five cycles of erosion/antacid treatment. Enamel surface loss was measured (in micrometers) by optical profilometry. In addition, baseline and final surface microhardness (SMH) values of enamel were obtained. It was found that antacid suspensions significantly reduced enamel loss, and that similar protection was afforded by all formulations. No differences were observed between the final enamel SMH values among groups. Antacid suspensions counteracted HCl-induced enamel loss, although they were not effective in reducing enamel softening. Mouth rinsing with antacid suspensions after vomiting can potentially represent a promising strategy to counteract enamel loss caused by erosion., (© 2012 Eur J Oral Sci.)

Folliculosebaceous cystic hamartoma (FSCH) is a cutaneous hamartoma of pilosebaceous origin that usually occurs on the face. We present what we believe is only the second reported case of FSCH of the external auditory canal, and the first in an adult. The patient was a 59-year-old woman who presented with a 4-year history of a firm nodule on the left external auditory canal that had caused hearing loss, pruritus, and pain. The lesion was excised, and histopathologic examination identified infundibular cysts, hyperplasia of the sebaceous lobules, and a large amount of mucin, features that are consistent with FSCH. One year postoperatively, the patient was asymptomatic, and no evidence of recurrence was noted.

Sebaceous carcinoma of the eyelid is a very rare slow-growing tumor and is considered an aggressive eyelid neoplasm. It can reach mortality rate of about 6%. Diagnosis is often delayed because of its ability to masquerade as other periocular lesions, both clinically and histologically. We present three cases of sebaceous carcinoma, with different surgical outcomes, showing the importance of early diagnosis.

Cerebrovascular disease studies have shown similarity between humans and spontaneously hypertensive rats stroke-prone rats in the development of spontaneous stroke and transitory ischemic attacks (TIA). In addition, nitric oxide (NO) suppression by L-arginine methyl ester (L-NAME) can precipitate several vascular diseases including TIA and strokes. On the other hand, alpha-tocopherol (AT) has been associated with beneficial effects on vascular disorders. Four groups were tested to evaluate AT effects on NO inhibition: AT, control (C), AT + L-NAME, and L-NAME. During 4 weeks, all groups had their physiologic parameters evaluated and were submitted to neurological tests. After the sacrifice of the animals, total L-lactate dehydrogenase, fibrinogen levels, and platelet counts were measured. Our results demonstrated improvement in memory function and sensory-motor function of the rats treated with AT. The AT treatment also demonstrated a significant difference on the injury identifier, fibrinogen levels, and platelet count between the treated groups and the L-NAME group. In conclusion, AT reversed damaging L-NAME neurological effects and could be considered as a possible protective agent in neurological diseases., (Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.)

The spontaneously hypertensive stroke-prone rat (SHRSP) is a recognized animal model for the study of severe hypertension and stroke, being characterized by presenting an elevated tissue levels of free radicals. Therefore, this study has the main goal to identify the effect of B vitamins, closely associated to the control of oxidative stress, on SHRSP rats. After 10 days (baseline period), the animals, 18 SHRSP rats at 18 weeks of age, were divided into three groups with six rats treated with riboflavin (B2), six treated with pyridoxine (B6) plus folic acid (B9), and control. Body weight, water and food intake, diuresis, sensory-motor responses, and systolic blood pressure of all the rats were determined daily. Physical aspects of whole body (i.e., distribution and coloring of hair, skin and mucosa, and an eventual presence of bleeding, stains, cracks, or opacification) and behavior were equally monitored. The data were evaluated by ANOVA two-way and p < .05 was considered significant. The supraphysiologic doses did not cause toxic effects. There was a significant decrease of systolic blood pressure, homocysteine, and malondialdehyde (MDA) blood levels in animals under B vitamin supplementation. The treatment also inhibited the neurological signs of an ischemic attack (unbalance, ataxia, and convulsions). The findings reported here suggest that B vitamin therapy was effective for the control of systolic blood pressure and oxidative stress. Hence, it could be thought as one of the alternative therapies to prevent the occurrence of stroke.

We report a case of lobomycosis in the left leg of a patient that had traveled to the endemic Brazilian Amazon region. After surgical resection of the lesion, there was relapse with local dissemination of the disease and the treatment was successfully performed by oral itraconazole and cryosurgery.

Decylubiquinone treatment in vitro has demonstrated a potent inhibitor effect on reactive oxidative species production. However, the effectin vivo has not been demonstrated yet. Thus, rats SHRSP male were divided in two groups: treated and controls (n=6, each). The treated group received 10 mg/Kg(-)/body weight of decylubiquinone diluted in coconut oil by oral gavage during four weeks. Control rats just received the vehicle. Body weight, diuresis, food and water intake, systolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, blood glucose levels and malondialdehyde were determined. There were a significant (p<0.05) reduction on systolic blood pressure, plasma malondialdehyde, total cholesterol and LDL-cholesterol in the treated group. Additionally, HDL-cholesterol also increased significantly. However, body weight, diuresis, food and water intake, blood glucose levels and triglycerides did not alter after treatment. Thus, decylubiquinone can be a new antihypertensive, hypolipidemic and antioxidant agent on the prevention and treatment of diseases linked to oxidative stress.

Background: Vitamin D might have an influence on glucose concentrations, due to the presence of VDR receptors on the pancreas. We established an experimental model of type 2 diabetes in spontaneously hypertensive rats (SHR) and Wistar rats in order to investigate the glycemic response., Methods: SHR males (n=6) and Wistar rats (n=6) weighing approximately 89+/-5.5 g and 123.5+/-6.5 g, respectively, after 7 days of basal period, had the chow pattern substituted (350 kcal/100 g) for a hypercaloric/hyperlipidic (HC/HL) diet (490 kcal/100g) and then injected with 40 mg/kg (SHR) and 20 mg/kg (Wistar) streptozotocin I.P. After the creation of diabetes, the rats suffered daily gavage of cholecalciferol (12.5 microg/kg(-) (1)) for 14 days. The blood glucose was assessed twice a week with a glucometer. The data were analyzed by ANOVA., Results: SHR and Wistar rats fed on a HC/HL diet gained 60 g and 32 g in once week, vs. the basal period, where they only gained 23 g and 13 g, respectively. The cholecalciferol supplementation did not change the glucose concentration in all of the SHR animals. About 40% of the group responded by treatment with reduction of about 60% in glucose concentrations. We did find a 40% of the blood glucose levels in all Wistar rats., Conclusions: Cholecalciferol is able to reduce blood glucose in this experimental diabetes model.

The authors describe a case of entomophthoromycosis in a previously healthy patient, who presented with an abscess in the right buttock. After surgical drainage it evolved into a retroperitoneal tumor. The patient improved clinically after resection of the mass and ketoconazole treatment. The histopathological analysis showed the Splendore-Hoeppli phenomenon, suggesting Basidiobolus ranarum infection, a zygomycosis generally restricted to the subcutaneous tissue, with rare gastrointestinal involvement.

Spontaneously hypertensive rats (SHR) were separated into two groups (n = 6 per group) and, since 5 months old, received alpha-tocopherol (alpha-tocopherol acetate120 IU) or vehicle by daily gavage for 2 weeks. Blood viscosity, blood pressure (BP) and myocardial remodeling were analyzed. The SHRs treated with alpha-tocopherol showed a significant reduction of BP and a major reduction of blood viscosity in comparison with the control SHRs. The cardiac hypertrophy indices showed some differences when the two SHR groups were compared, the LV mass index was not different between the groups; however, the cardiomyocyte size was more than 20% smaller in SHRs treated with alpha-tocopherol than in control SHRs (P < .05). The intramyocardial vessels distribution was more than 45% greater in alpha-tocopherol-treated SHRs than in control rats, significantly improving the vessels-to-myocytes ratio in treated SHRs than in control SHRs (P < .05). In conclusion, present findings strongly suggest a beneficial effect of alpha-tocopherol supplementation to genetically hypertensive rats. This was observed by a reduction of both blood viscosity and BP, and a consequent cardiomyocyte hypertrophy in treated SHRs; an improvement of vessels-to-myocytes ratio in these rats was also observed.

Introduction: Antioxidants has been utilized to prevent oxidative damage in diabetes and hypertensive diseases. The current study evaluated the effect of alpha-tocopherol supplementation on blood pressure and the lipid profile in streptozotocin-induced diabetes mellitus in spontaneously hypertensive rats (SHR)., Methods: The systolic blood pressure and total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were measured in SHR-diabetes induced., Results: Treatment with alpha-tocopherol (vitamin E) led to a decrease on systolic blood pressure and showed an increase of HDL-cholesterol and a decrease of LDL-cholesterol, but the concentrations of triglycerides and total cholesterol were not changed., Conclusions: The vitamin E was able to modulate the blood pressure and the lipidic profile as well, and therefore can be considered as an alternative treatment of lipid disorder found on diabetes and hypertension diseases.

The vasodilation and hyperpolarization induced by bradykinin (BK) in the mesenteric vascular bed and mesenteric arteries from spontaneously hypertensive rats (SHR) and from normotensive Wistar rats (NWR), as well as Wistar Kyoto rats (WKY), was investigated before and after prolonged oral treatment with cholecalciferol (125 mg kg(-1) body weight per day) for 3 weeks. The cholecalciferol treatment caused a decrease in the SHR blood pressure, as well as a normalization in the resting potential of the smooth muscle cell membrane of mesenteric arteries and restored their hyperpolarizing response to BK. The concentration-response curves for the vasodilator effect of BK on the mesenteric vascular bed were significantly decreased in SHR and in WKY when compared with NWR. Cholecalciferol treatment improved the maximum responses of the SHR preparation, bringing them to levels similar to those of the NWR preparations, which themselves were unaffected by the treatment. In the presence of apamin, a Ca(2+)-dependent K(+) channel inhibitor, the maximum responses to BK in preparations from NWR or cholecalciferol-treated SHR decreased to values similar to those observed in untreated SHR. Our results indicate that the low responsivity of the SHR resistance vessels to the relaxant effect of BK is due to impaired Ca(2+)-dependent K(+) channels and that reversion of this impairment contributes to the blood pressure reduction caused by the cholecalciferol treatment. However, the mechanism of the low responsivity in WKY remains to be investigated.

During an outbreak of yellow fever (rural form of the infection) occurred recently in the State of Goiás, Brazil, a patient, with clinical manifestations suggestive of the infection, died in the University Hospital of Brasilia, DF, on the fifth day from admission. Postmortem examination revealed, microscopically, the characteristic alterations of the infection, and discovered in the lungs and hilar lymph nodes round microrganisms identified as adiaconidia of Emmonsia parva var. crescens.

We studied the effect of oral cholecalciferol treatment on the endothelium-dependent vascular relaxation and hyperpolarization induced by acetylcholine (ACh), which is impaired in spontaneously hypertensive rats (SHR). Adult female SHR and normotensive Wistar-Kyoto rat (WKY) controls received 125 microg of cholecalciferol per kilogram body weight per day for 6 weeks. The responses to ACh of the isolated mesenteric vascular bed and mesenteric artery rings were measured, as well as the smooth muscle cell membrane potential. After cholecalciferol treatment, the systolic blood pressure and basal perfusion pressure of the mesenteric vascular bed of the SHR fell to control levels. The relaxant and hyperpolarizing effects of ACh, which are reduced in SHR, were also brought to control levels after cholecalciferol treatment. These effects of ACh were inhibited by N(omega)-nitro-L-arginine in SHR and by apamin in WKY. After cholecalciferol treatment, SHR hyperpolarizing responses showed the same inhibition pattern as those of WKY. This indicates that, after cholecalciferol treatment, SHR vascular mesenteric preparation responses to ACh are mediated by endothelium-derived hyperpolarizing factor, which induces activation of Ca(2+)-dependent K(+) channels, as in WKY. In untreated SHR, the ACh-mediated response is entirely due to ACh acting via the release of nitric oxide.

1. The mechanism responsible for blood pressure reduction in spontaneously hypertensive rats (SHR) after prolonged cholecalciferol treatment was studied. Two-week treatment of SHR with 0.125 mg cholecalciferol kg-1 body weight per day orally caused significant reductions of systolic blood pressure and of the resting perfusion pressure of the mesenteric vascular bed at constant flow. 2. In addition, the treated animals presented a normalization of the maximum vasoconstriction response to noradrenaline and a reduction of the maximum effect of the adrenaline concentration-response curves. This latter effect probably was due to recovery of the impaired Ca(2+)-dependent K+ channels coupled to alpha 2-adrenoceptors since it was prevented by apamin. 3. The treatment with cholecalciferol also normalized the smooth muscle cell membrane potential of de-endothelialized mesenteric arteries of SHR and their hyperpolarizing responses to alpha 2-adrenergic agonists, which were depressed in untreated SHR. 4. In mesenteric rings with endothelium, alpha 2-adrenergic agonists caused similar hyperpolarizing responses in the SHR and in normotensive Wistar (NWR) and Wistar Kyoto (WKY). In non cholecalciferol-treated SHR the hyperpolarizing mediator involved in this effect was NO, while in NWR it was the endothelium-derived hyperpolarizing factor (EDHF). After cholecalciferol treatment, the hyperpolarization induced by alpha 2-adrenergic agonists in SHR smooth muscle cells was mediated by EDHF, as in NWR. 5. Our results indicate that the hypotensive effect of cholecalciferol in the SHR is probably due to the normalization of vascular reactivity, by restoring the functioning of apamin- and ATP-sensitive K+ channels located in the vascular smooth muscle cell membrane, which are impaired in the SHR.

1. The diet of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NWR) was supplemented with 12.5 micrograms cholecalciferol per 100 g body weight daily, by gavage, for 4 weeks. 2. The amplitude of the contractile responses of aortic rings from SHR to potassium and adrenaline, which was smaller than in NWR aortae, was increased after treatment with cholecalciferol. No further changes were observed in the responses of NWR and SHR aortae in the presence of 100 nM apamin. 3. The membrane potentials of aortae from SHR, which were higher than those of aortae from NWR, decreased after treatment with cholecalciferol. Further depolarization was observed in aortic rings from NWR, but not in aortic rings from SHR, after their preincubation with 100 nM apamin. 4. It is concluded that cholecalciferol normalizes the membrane potential and contractility of aortae from SHR, probably through an effect on lipid composition and structure of the plasma membrane.

The effect of clonidine on the mesenteric vascular bed and the isolated mesenteric artery was examined in preparations in which tonus was induced by norepinephrine or endothelin. In preparations precontracted by norepinephrine, clonidine caused a relaxation which was not inhibited by the alpha-2 antagonists yohimbine and idazoxan or by the K+ channel blockers apamine, tetraethylammonium and glibenclamide. In preparations precontracted with endothelin, clonidine increased the depolarization and induced a contraction. Both these effects were inhibited by prazosin. In isolated mesenteric arteries, norepinephrine cause a significant depolarization that was inhibited by clonidine or prazosin. On the other hand, clonidine caused a hyperpolarization which was inhibited by idazoxan or yohimbine, but not by prazosin. This hyperpolarization was also abolished by apamine, tetraethylammonium and glibenclamide. It is concluded that clonidine acts on alpha-1 adrenoceptors as a partial agonist, causing relaxation of the mesenteric artery precontracted with norepinephrine or contraction of preparations precontracted with endothelin. Moreover, clonidine can open K+ channels and hyperpolarize the plasma membrane of mesenteric artery by acting on alpha-2 adrenoceptors.

1. The diet of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar (NWR) rats was supplemented with either 2% calcium lactate in the drinking water or 12.5 micrograms vitamin D3 100 g-1 body weight daily by gavage, for 14 days. 2. The blood pressure of the SHR treated with either calcium or vitamin D decreased to the same levels as that of WKY and NWR. 3. The response to bradykinin of the SHR isolated duodenum, which is predominantly contractile, upon treatment with vitamin D (but not with calcium), became predominantly relaxant, approaching the normal behavior of the WKY and NWR duodenum. 4. The relaxant responses of the SHR and WKY duodenum to potassium were smaller than those of NWR, but treatment with vitamin D increased the response in all three rat strains. 5. It is concluded that, besides sharing the hypotensive effect of calcium, vitamin D treatment of SHR has an effect on the duodenum smooth muscle which might be due to calmodulin-dependent activation of calcium-dependent potassium channels.