A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice.

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1ß immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.

A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.

Clinical and epidemiological profile of women with breast cancer managed in a public referral hospital in northeastern Brazil.

AIM: To evaluate the clinical and epidemiological profile of women with breast cancer, managed in the Breast Service at Hospital Get6lio Vargas (HGV). MATERIALS AND METHODS: A descriptive, observational cross-sectional study, involving 174 breast cancer patients, managed at the Breast Service at HGV in Teresina, in the northeast of Brazil, from May 2011 to June 2014. Epidemiological variables included age group, age at menarche, age at first childbirth, and menopause. The tumor characteristics studied were histological type, TNM classification, and staging. The results were organized in distribution tables. RESULTS: Breast carcinoma was more common in patients aged 60 and over, in multiparous women, and in women who were menopausal before age 55. The most common histological type was ductal invasive carcinoma T2N1MO (Stage IIB) in 83 (48%) women. CONCLUSION: The current study shows that the majority of carcinomas were Stage II or advanced tumors, with clinically positive axillary lymph node status and weak correlation with reproductive risk factors.

Prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil.

Chemokines are low-molecular weight proteins that play a key role in inflammatory processes. Genomic variations in chemokine receptors are associated with the susceptibility to various diseases. Polymorphisms in chemokine receptor type 5 (CCR5)-Δ32 and CCR2-V64I are related to human immunodeficiency virus infection resistance, which has led to genetic association studies for several other diseases. Given the heterogeneous distribution of these polymorphisms in different global populations and within Brazilian populations, we analyzed the prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil. The study included 223 individuals from the general population of the city of Parnaíba, Piauí, who had a mean age of 73 years. Of these individuals, 37.2% were men and 62.8% were women. Polymorphisms were analyzed using DNA extracted from peripheral blood leukocytes by using polymerase chain reaction alone (CCR5-Δ32) or accompanied by restriction endonuclease digestion (CCR2-V64I). In both cases, the genotypes were determined using 8% polyacrylamide gel electrophoresis and silver nitrate staining. The population conformed to Hardy-Weinberg equilibrium for both the loci studied. No individuals were homozygous for allele-Δ32, which was present in 1.8% of the population, whereas allele-64I was present in 13.9% of the participants studied; 74.9% were homozygous for the wild-type allele, while 22.4 and 2.7% were heterozygous and homozygous for the mutant allele, respectively. Additional studies are needed to investigate the relationship between these polymorphisms and disease etiopathogenesis in reference populations.

Ki-67 antigen expression in the mammary epithelium of female rats in persistent estrus treated with raloxifene.

OBJECTIVE: To evaluate Ki-67 antigen expression in the mammary epithelium of female rats in persistent estrus treated with raloxifene. MATERIALS AND METHODS: Forty-one Wistar-Hannover rats in persistent estrus induced by 1.25 mg of testosterone propionate were randomly divided into two groups: Group A (control, n = 21) in which the animals received only the vehicle (propylene glycol) and Group B (experimental, n = 20) in which the rats received 750 µg/day of raloxifene by gavage. After 21 days of treatment, all the animals were sacrificed and the first pair of abdominal-inguinal mammary glands was extirpated and fixed in 10% buffered formalin to investigate Ki-67 expression by immunohistochemistry. The data were analysed using Student's t-test (p < 0.05). RESULTS: The percentage of Ki-67-stained nuclei per 500 cells in the mammary epithelium was 42.33 ± 6.18 and 15.51 ± 3.71 [mean ± standard error of the mean (SEM)] in the control and experimental groups, respectively (p < 0.001). CONCLUSION: Raloxifene treatment significantly reduced Ki-67 expression in the mammary epithelium of rats in persistent estrus.

Effects of tamoxifen and raloxifene on body and uterine weights of rats in persistent estrus.

PURPOSE: To evaluate the change in body and uterine weights of rats in persistent estrus, a model developed to mimic polycystic ovary syndrome treated with selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene. METHODS: Sixty Wistar-Hannover rats induced by a single subcutaneous dose of 1.25 mg testosterone propionate were divided into three groups of 20 animals: Group I (placebo); Group II (tamoxifen, 250 microg/day) and Group III (raloxifene, 750 microg/day). At 90 days of life, the treatment began for 30 consecutive days, in which the animals were weighed weekly. On the 31st day, the animals were sacrificed and the uterus removed. Data were analyzed statistically by analysis of variance and by the Tukey-Kramer multiple comparisons test (p<0.05). RESULTS: Means of body and uterine weights (g) after treatment were: 227.3+/-2.20 and 0.40+/-0.01; 185.3+/-2.45 and 0.25+/-0.01; 186.4+/-2.20 and 0.27+/-0.01 in Groups I, II and III, respectively (p<0.001). There was no statistical difference between groups II and III for body and uterine weight (p=0.727 and p=0.646, respectively). CONCLUSION: The present results indicate that, at the doses and during the time of treatment used, both tamoxifen and raloxifene reduce in a similar way the body and uterine weights of rats in persistent estrus showing a possible antiestrogenic effect of SERMs under high levels of estrogens.

Evaluation of Ki-67 and Bcl-2 antigen expression in breast carcinomas of women treated with raloxifene.

OBJECTIVES: To evaluate the effect of raloxifene on Ki-67 and Bcl-2 antigen expression in operable, stage II, oestrogen-receptor-positive invasive ductal breast carcinomas. MATERIALS AND METHODS: Twenty post-menopausal women who had taken 60 mg of raloxifene daily for 28 days prior to definitive surgery were enrolled in the investigation. Two tumour samples were obtained by incisional biopsy during the study, one at the time of confirmation of diagnosis of invasive ductal carcinoma and evaluation of oestrogen receptor status, and the other 29 days later, at the time of definitive surgery. Immunohistochemistry was performed on tumour samples, prior to and after raloxifene treatment, to evaluate Ki-67 and Bcl-2 expression. Friedman and McNemar tests were used for statistical analysis of the data, significance being established at 5%. RESULTS: Mean percentage of Ki-67-stained nuclei was 24.86 +/- 2.95 prior to raloxifene treatment and 13.33 +/- 1.52 after treatment (P < 0.001). Prior to raloxifene treatment, only 9/20 cases (45%) were classified as Bcl-2-positive, whereas after treatment, 17/20 (85%) were classified as Bcl-2-positive (P < 0.013). CONCLUSIONS: Raloxifene treatment significantly reduced Ki-67 antigen expression and increased Bcl-2 expression in breast carcinomas of post-menopausal women.

E-cadherin expression in estrogen receptor-positive and negative breast carcinomas of postmenopausal women.

BACKGROUND: Preservation of E-cadherin expression is usually related to non-invasive and well differentiated breast carcinomas. PURPOSE: The aim of this study was to evaluate E-cadherin immunohistochemical expression in estrogen receptor (ER) positive and negative infiltrating ductal breast carcinomas. METHODS: Twenty-three postmenopausal patients with Stage II, operable, infiltrating ductal breast carcinomas were divided into groups A (ER+; n = 13) and B (ER-; n = 10). E-cadherin immunohistochemical expression was assessed semiquantitatively according to membrane staining intensity and classified as negative (< 10% of cells with stained membranes), positive + (10-50% of cells stained) or positive ++ (> 50% of cells stained). Fisher's exact test was used to compare the distribution of staining intensity in the two groups (p < 0.05). RESULTS: In group A (ER+), E-cadherin staining was positive in all cases: + (n = 3; 23%) and ++ (n = 10; 77%) compared to three cases (30%) in group B (ER-), + (n = 2; 20%) and ++ (n = 1; 10%). This difference was statistically significant (p < 0.0005). CONCLUSIONS: The present results indicate that E-cadherin expression loss is significantly associated with ER-negative tumors and therefore with a more aggressive phenotype of invasive ductal breast carcinoma.

Comparison of three vascular endothelial markers in the evaluation of microvessel density in breast cancer.

PURPOSE: To evaluate the microvessel density by comparing the performance of anti-factor VIII-related antigen, anti-CD31 and anti-CD34 monoclonal antibodies in breast cancer. METHODS: Twenty-three postmenopausal women diagnosed with Stage II breast cancer submitted to definitive surgical treatment were evaluated. The monoclonal antibodies used were anti-factor VIII, anti-CD31 and anti-CD34. Microvessels were counted in the areas of highest microvessel density in ten random fields (200 x). The data were analyzed using the Kruskal-Wallis nonparametric test (p < 0.05). RESULTS: Mean microvessel densities with anti-factor VIII, anti-CD31 and anti-CD34 were 4.16 +/- 0.38, 4.09 +/- 0.23 and 6.59 +/- 0.42, respectively. Microvessel density as assessed by anti-CD34 was significantly greater than that detected by anti-CD31 or anti-factor VIII (p < 0.0001). There was no statistically significant difference between anti-CD31 and anti-factor VIII (p = 0.4889). CONCLUSION: The density of stained microvessels was greater and staining was more intense with anti-CD34 compared to anti-CD31 and anti-factor VIII-related antigen.

Effect of raloxifene on vascular endothelial growth factor expression in breast carcinomas of postmenopausal women.

OBJECTIVE: This study aimed to evaluate the effect of raloxifene on vascular endothelial growth factor (VEGF) expression in breast carcinomas of postmenopausal women. MATERIALS AND METHODS: Sixteen postmenopausal patients with operable stage II, oestrogen receptor-positive, infiltrating ductal breast carcinoma were treated with raloxifene at a dose of 60 mg/day, for a period of 28 days prior to definitive surgery. Tumour size varied from 3 to 5 cm (mean 3.7 cm) and mean age of patients was 61.8 years (range 49-72 years). Tumour samples were obtained by incisional biopsy at the time of diagnosis and again at the time of surgery. Immunohistochemical evaluation of VEGF expression was assessed semiquantitatively based on fraction of stained tumour cells and on intensity of staining. McNemar's test of symmetry was used to evaluate agreement between positive or negative classification of VEGF expression prior to and following raloxifene treatment (P < 0.05). RESULTS: Fourteen of the 16 patients (88%) were classified as positive for VEGF expression prior to raloxifene treatment, while only 5 (31%) were classified as positive following treatment (P < 0.007). CONCLUSION: Raloxifene significantly reduced VEGF expression in these oestrogen receptor-positive breast carcinomas of postmenopausal women.

Ovarian dermoid cyst with malignant transformation and rupture of the capsule associated with chemical peritonitis: a case report and literature review.

Malignant transformation of ovarian dermoid cysts is rare and spontaneous rupture provoking chemical peritonitis is even rarer. Laparotomy in a 75-year-old Brazilian woman with abdominal pain and signs of peritoneal irritation revealed a voluminous right ovarian cyst with rupture of the capsule, an abundant quantity of fatty material in the abdominal cavity, and signs of peritonitis. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with partial omentectomy were performed. Histopathology confirmed a dermoid cyst with a well-differentiated area of epidermoid carcinoma. The patient refused additional treatment and is currently in the seventh year of follow-up with no signs of recurrence. Rupture of a dermoid cyst of the ovary resulting in chemical peritonitis is very rare and may be associated with malignant transformation.

Tuberculosis of the breast: analysis of 20 cases and a literature review.

Tuberculosis (TB) of the breast is a very rare pathology. The clinical presentations of this disease are manifold, often mimicking carcinoma of the breast. We conducted a retrospective analysis of 20 women with TB of the breast receiving care at the mastology clinic at Getúlio Vargas Hospital, PI, Brazil, between 1994 and 2007. The clinical presentation of the disease, the diagnosis and the response to specific treatment were analyzed. Most of the patients were of reproductive age, with the disease affecting the right breast in eleven patients (55%) and the left breast in nine patients (45%). Palpable nodules were present in five patients (25%) and fistulae in 15 (75%). The mean time between onset of symptoms and diagnosis was 7.7 months (range 3-12 months). Skin testing with purified protein derivative of tuberculin was strongly reactive in all patients, six (30%) of whom were breastfeeding. Diagnosis was confirmed by histopathology and all patients were satisfactorily treated with a combination of rifampicin, isoniazid and pyrazinamide. In the present study, TB of the breast presented predominantly as breast abscesses and fistulae and responded satisfactorily to treatment with anti-TB drugs.

Bcl-2 oncogene expression in estrogen receptor-positive and negative breast carcinoma.

PURPOSE: The aim of this study was to evaluate Bcl-2 oncogene expression in estrogen receptor (ER)-positive and negative breast carcinomas. METHODS: A study involving 72 cases of infiltrating ductal carcinoma of the breast in postmenopausal women divided into two groups: Group A (ER positive, n=37) and Group B (ER negative, n=35). Immunohistochemical analysis of bcl-2 expression was carried out semiquantitatively based on the percentage of stained tumoral cells and the intensity of staining. The chi-square test was used in the statistical analysis of the data and significance was established at p < 0.05. RESULTS: Bcl-2 oncogene expression was statistically greater in tumors of Group A (59.5%) compared to those of Group B (8.6%), (p < 0.001). CONCLUSION: Bcl-2 had a significantly greater expression in the ER-positive breast tumors compared to ER-negative tumors.

Effects of raloxifene on the urethra of adult castrated female rats.

OBJECTIVE: The objective of this study was to evaluate the effects of raloxifene on the weight and epithelial thickness of the urethra of castrated female rats. METHODS: Forty castrated female rats were randomly separated into two groups: group I (control, n = 20) received only the vehicle, and group II (raloxifene, n = 20) received 750 microg/day of raloxifene for 30 days. On the 31st day, the animals were sacrificed and the urethras were removed for the study. A model for categorical data using the weighted minimum mean square error method and Student's t test were used for the data analysis (p < 0.05). RESULTS: The mean weights of the urethras in groups I and II were 22 +/- 1.6 mg and 24 +/- 1.7 mg, respectively (p = 0.371). There was an increase in the mean epithelial thickness of the distal segments in group II compared to group I (50.7 +/- 1.9 microm vs. 45.3 +/- 1.6 microm, respectively) (p < 0.04). No statistically significant difference was found in the mean epithelial thickness of the proximal urethra between the two groups (p = 0.187). CONCLUSION: Raloxifene administered to castrated female rats for 30 days increased the distal urethral epithelial thickness and did not alter the weight of the urethra.

Myiasis in the uterine cavity of an elderly woman with a complete uterine prolapse.

Myiasis is the infestation of the tissues of vertebrate animals by the larvae of flies (maggots). As the condition generally occurs in exposed areas of the body, genital myiasis is a rare condition, and myiasis of the uterine cavity is even rarer, only one case having been previously described in the literature. The case reported here describes myiasis of the uterine cavity and ulcerated vaginal mucosa of an 89-year-old woman with a severe (third-degree) genital prolapse. This case describes an extremely rare situation, and emphasizes the need for good hygiene and surgical correction in patients with a genital prolapse.

Ectopic breast cancer in the anterior chest wall: a case report and literature review.

Ectopic breast cancer is rare and when situated in the chest wall, it is even rarer. This report describes the case of an 86-year old Brazilian woman with a palpable carcinoma, located in the right inframammary fold, and right axillary adenopathy. The patient was submitted to excision of the accessory breast and to right axillary lymphadenectomy. All 28 resected lymph nodes contained metastatic cells. Diagnosis and treatment of ectopic breast cancer should be carried out early in view of its aggressivity.