Immunohistochemical Expression of Cyclooxygenases in Hypertrophic Scars and Keloids.

BACKGROUND: There are studies demonstrating an increased expression of cyclooxygenase (COX) in keloids and hypertrophic scars, suggesting that anti-inflammatory drugs could be used in their treatment. However, a precise relationship between COX and pathological scarring has not been established in the literature yet. This study aims to evaluate the immunohistochemical expression of COXs in these scars. METHODS: Prospective study, including 54 patients (aged 18-60 years) undergoing scar excision: 18 normal scars (group 1), 18 hypertrophic scar (group 2), and 18 keloids (group 3). The group classification was performed by clinical criteria. Scars samples were collected and anatomopathological examination (through hematoxylin-eosin method) was performed to confirm the scar type. Immunohistochemistry was performed to assess the expression of COX1 and COX2 in epidermis and dermis. Results were compared among all groups and between group I versus II and III together (abnormal scars). RESULTS: For COX1, in the epidermis, there was no significant difference in the immunohistochemical expression when comparing the 3 groups. In the dermis, groups 2 and 3 had greater expression than group 1, with a significant difference being found when comparing all groups (P = 0.014), and in the comparison between normal versus abnormal scars (P = 0.004). For COX2, there was no significant difference between the groups in both the epidermis and dermis. CONCLUSIONS: The immunohistochemical expression of COX1 was greater in the dermis of abnormal scars when compared with normal scars. Future studies can be performed involving COX blockade as a perspective of these scars treatment.

Oxidative Stress in Aortas of Patients with Advanced Occlusive and Aneurysmal Diseases.

BACKGROUND: Aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA) are very important cardiovascular diseases that present different aspects of pathophysiology; however, oxidative stress and inflammatory response seem be relevant in both of them. Our objective was to evaluate oxidative damage and degree of inflammatory infiltrate in aortas of patients surgically treated for AOD and AAA. MATERIALS AND METHODS: Levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and myeloperoxidase (MPO) expression as well as nitrite levels and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in aortas of patients with AOD (n = 16) or AAA (n = 14), while the control group was formed by cadaveric organ donors (n = 10). We also analyzed the degree of inflammatory infiltrate in these aortas. RESULTS: There was an increase in ROS levels and NADPH oxidase activity in patients with AOD and AAA when compared with the control group, and the AOD group demonstrated higher ROS production and NADPH oxidase activity and also nitrite levels when compared with the AAA group (P < 0.001). On the other hand, an increase of SOD activity in the AOD group and CAT activity in the AAA group was observed. Inflammatory infiltrate and MPO expression were higher in the AOD group when compared with the control group (P < 0.05). CONCLUSIONS: Oxidative stress is relevant in both AOD and AAA, though AOD presented higher ROS levels and NADPH activity. Increased activities of antioxidant enzymes may be a compensatory phenomenon which occurs in aortas of patients with AOD and AAA. Perhaps, a relationship between oxidative stress and degree of inflammatory infiltrate may exist in the pathophysiology of AOD and AAA.

How to identify patients with increased risk of breast cancer relapse?

A cohort of 362 breast cancer patients had subtype classification accomplished using 4 immunohistochemical markers: luminal A (ER or PR positive, HER2 negative, Ki-67<14%), luminal B (ER or PR positive, HER2 negative, Ki-67≥14%), luminal HER2 (ER or PR positive, HER2 positive), HER2 enriched (ER or PR negative, HER2 positive) or triple negative (ER, PR, and HER2 negative). Multivariable Cox analysis was used to determine the risk of local (LR) or distant (DR) relapse associated with the intrinsic subtypes, adjusting for standard clinicopathologic factors. There have been a total of 124 recurrences. Triple-negative patients were associated with increased risk of LR. Luminal B subtype showed statistical tendency (P=0.053) to LR. For patients undergoing breast conservation surgery, luminal B and HER2-enriched subtypes demonstrated an increased risk to LR, and this was statistically significant on multivariable analysis. After mastectomy, there was no statistical difference between subtypes of LR or DR on multivariable analysis. Luminal A tumors are associated with a low risk of LR or DR. Despite the existence of gene expression profiling, in the current study we demonstrate that analysis of 4 immunohistochemical markers is equally effective and less expensive alternative to identify higher recurrence risk patients.

Effects of the chronic use of finasteride and doxazosin mesylate on the histomorphometric characteristics of the prostate: experimental study in rats.

OBJECTIVE: The objective of the present study is to evaluate the histomorphometric characteristics of the prostate of rats submitted to chronic (long-time) treatment with doxazosin mesylate, finasteride and both substances combined. MATERIALS AND METHODS: Four groups of eight rats each were selected for this study and treated with saline solution (control), doxazosin mesylate, finasteride and combination of the drugs, during 10 months. After this time, the prostate was removed, weighed and sent for histological analysis. Prostate sections were stained with Masson trichrome. With an image analyzer, the percentage of smooth muscle, collagen, epithelium, acinar lumen and interstitial space was measured. Also, the minimum, medium and maximum epithelial thickness, number of acini per field, mean acinar area and the presence of papillary projections were evaluated. RESULTS: The mean prostate weight of rats treated with finasteride and combined treatment was lower when compared to the control group (P < 0.05). Prostate from rats treated with finasteride alone had a lower percentage of the epithelial component and a smaller minimum epithelial thickness than the control group (P < 0.05). The number of acini per field in the combined groups was higher than that observed in all other groups (P < 0.05). Also, rats of the finasteride and combined groups presented a reduced number of papillary projections when compared to the other groups (P < 0.05). CONCLUSION: Our study clearly showed the effects of finasteride on prostate tissue, and from a histomorphometric perspective, it was not able to detect any advantage of the combined treatment over the use of finasteride alone.

Cistoadenoma mucinoso de pâncreas durante a gravidez / Mucinous cystadenoma of the pancreas developing during pregnancy

Cistoadenoma mucinoso de pâncreas durante a gravidez é extremamente raro e relatado somente cinco vezes na literatura. Nós descrevemos caso de uma mulher de 26 anos, na sua segunda gestação, com um acentuado aumento de volume intra-abdominal por massa cística, cuja gestação foi interrompida durante a trigésima primeira semana por severa pré-eclâmpsia. A cirurgia de retirada do cisto ocorreu 26 dias após o parto, com enucleação total da lesão. O exame anatomopatológico evidenciou o cisto como cistoadenoma mucinoso, que mediu 23x20x15 cm e pesou 9070 g. Até onde é do nosso conhecimento, é um dos maiores cistoadenomas mucinosos pancreáticos relatados durante a gestação

Mucinous cystadenoma of the pancreas during pregnancy is an extremely rare condition and was reported only five times in the literature. We report the case of a 26-year-old female who, in her second pregnancy, had a sharp intra-abdominal volume increase due to cystic mass, whose pregnancy was interrupted at the thirty-first week of gestation because of severe pre-eclampsia. The surgery to remove the cyst was performed 26 days after delivery, with total enucleation of the lesion. The anatomico-pathological examination showed a mucinous cystadenoma that measured 23x20x15 cm and weighed 9,070 g. To the best of our knowledge this is one of the largest pancreatic mucinous cystadenomas reported during pregnancy

Tamoxifen use and endometrial lesions: hysteroscopic, histological, and immunohistochemical findings in postmenopausal women with breast cancer.

OBJECTIVE: To evaluate immunohistochemical, hysteroscopic, and histological findings in postmenopausal women taking tamoxifen for breast cancer. METHODS: Forty postmenopausal women taking 20 mg/day tamoxifen for breast cancer underwent hysteroscopy and endometrial biopsy from January 2000 to December 2003. Medical records and paraffin blocks were analyzed retrospectively, and Ki-67, estrogen receptors (ERs), and progesterone receptors were measured using an immunohistochemical technique. RESULTS: The mean +/- SD age of the women was 59 +/- 14 years at hysteroscopy (95% CI, 54.2-63.7) and 45.1 +/- 7 years at menopause (95% CI, 42.6-47.6). Mean +/- SD duration of tamoxifen therapy was 27.3 +/- 16.5 months (95% CI, 22.0-32.5). Hysteroscopies were performed because of abnormal sonographic findings in 60% of the women and postmenopausal bleeding in 40%. The most common hysteroscopic and histological findings were endometrial polyps (32.5%) and atrophic endometria (22.5%). Immunohistochemistry showed that 85% of the women were progesterone receptor positive, 75% were ER positive, and 50% were Ki-67 positive. Endometrial polyps and polyps associated with atrophic endometrium were ER positive (P = 0.019). Results that were ER negative were more frequent in atrophic endometria (P = 0.01). The longer the time since menopause, the lower the Ki-67 expression in the endometrium was (P = 0.03). Ki-67 expression was greater in the endometrium of younger postmenopausal women (P = 0.01). CONCLUSIONS: The expression of steroid receptors in the endometrium was high in our series. All cases of endometrial polyps were ER positive. Estrogen receptors may play a major role in the development of endometrial polyps in postmenopausal women taking tamoxifen. Although most histological findings were benign, 22.5% were atrophic.

Halothane induces oxidative stress and NF-kappaB activation in rat liver: protective effect of propofol.

We investigated the effects of propofol on markers of oxidative stress, nuclear factor kappa B (NF-kappaB) activation and inducible nitric oxide synthase (iNOS) expression in liver of rats treated with halothane under hypoxic conditions. Male Wistar rats received halothane 1%/oxygen 14%, oxygen 14%/propofol 60 mg kg(-1) i.p., or halothane 1%/oxygen 14%/propofol 60 mg kg(-1) i.p. Morphological examination showed complete loss of architecture with massive necrosis of parenchyma in the halothane group, while only minor histological abnormalities were observed in rats receiving halothane plus propofol. The cytosolic concentration of TBARS and the hydroperoxide-initiated chemiluminescence increased significantly in the liver of animals from the halothane group (+62% and +40% versus controls, respectively), and this increase was abolished by propofol administration. Halothane induced a marked activation of NF-kappaB (+180%), and resulted in a significant decrease of the nonphosphorylated form of the inhibitor IkappaBalpha (-53%), while phosphorylated IkappaBalpha protein level was markedly increased (+146%). Propofol administration lowered these effects to +30% (NF-kappaB), -26% (nonphosphorylated IkappaBalpha), and +56% (phosphorylated IkappaBalpha). The increase of iNOS protein level (+59%) induced by halothane was significantly reduced to +22% by additional administration of propofol. Results obtained show that administration of propofol inhibits oxidative stress, NF-kappaB nuclear traslocation and iNOS overexpression in liver of rats receiving halothane. Propofol treatment, by inhibiting the NF-kappaB signal transduction pathway, might block the production of noxious mediators involved in the development of halothane-induced injury.

Evidence for an association of human papillomavirus and breast carcinomas.

Human papillomavirus (HPV) DNA has been detected in breast carcinoma by different laboratorial techniques, suggesting the virus could play a role in the pathogenesis of this tumor. The aim of the present study is to investigate the presence of HPV in patients with breast carcinoma and the correlation of the viral infection with prognostic factors for the disease outcome. Between June 2001 and July 2002, 101 paraffin embedded breast carcinoma specimens were analyzed through polymerase chain reaction (PCR) and sequencing of HPV-E6 gene. Twenty specimens of reduction mammoplasty and 21 specimens of fibroadenomas were also studied as a non-malignant control group. Two different specific primer sets targeting E6 region of the HPVs 16 and 18 were used for the analysis. The HPV DNA was detected in 25 breast carcinomas (24.75%), but in none of the benign breast specimens ( p < 0.001). Out of the 25 positive cases, 14 were HPV-16 positive (56%) and 10 were HPV-18 positive (40%). An original finding was the detection of both HPV-16 and -18 in a single tumor (4%). The amplified viral sequences confirmed the presence of HPV-16 and -18. No correlation between the presence of HPV DNA and specific prognostic predictors for the disease outcome was observed. Our results suggest that the presence in the breast of either HPV-16 or -18 might be related to development of the malignant phenotype. Further studies are warranted.

DNA damage in brain cells of mice treated with an oxidized form of apomorphine.

We investigated whether systemic injection of apomorphine and its oxidation derivative 8-oxo-apomorphine-semiquinone (8-OASQ) could induce DNA damage in mice brain, using the single-cell gel assay. 8-OASQ induced DNA damage in the brains at 1 and 3 h, but not at 24 h after treatment whereas apomorphine induced a slight increase in brain DNA damage frequency at 3 h after treatment, suggesting that both drugs display genotoxic activity in brain tissue.

Tumor de células granulares da mama: revisäo e relato de caso / Granular cell tumour of the breast: case report and review

Os autores apresentam um caso raro de neoplasia com localizaçäo mamária, e revisam a literatura. Estes tumores säo lesöes incomuns e têm etiologia desconhecida. Embora com histogênese näo completamente elucidada, os avanços na patologia deste tumor sugerem que é preferível chamá-lo de tumor de células granulares. Os achados clínicos e patológicos säo revisados por causa do diagnóstico diferencial com o câncer da mama