Antitumoral Effects of D-Fraction from Grifola Frondosa (Maitake) Mushroom in Breast Cancer

D-Fraction is protein-bound β-1,6 and β-1,3 glucans (proteoglucan) extracted from the edible and medicinal mushroom Grifola frondosa (Maitake). The antitumoral effect of D-Fraction has long been exclusively attributed to their immunostimulatory capacity. However, in recent years increasing evidence showed that D-Fraction directly affects the viability of canine and human tumor cells, independent of the immune system. Previously, we have reported that D-Fraction modulates the expression of genes associated with cell proliferation, cell death, migration, invasion, and metastasis in MCF7 human breast cancer cells. Therefore, the purpose of the current study is to investigate if this modulation of gene expression by Maitake D-Fraction really modulates tumor progression. In the present work, we demonstrate for the first time that Maitake D-Fraction is able to act directly on mammary tumor cells, modulating different cellular processes involved in the development and progression of cancer. We demonstrate that D-Fraction decreases cell viability, increases cell adhesion, and reduces the migration and invasion of mammary tumor cells, generating a less aggressive cell behavior. In concordance with these results, we also demonstrate that D-Fraction decreases tumor burden and the number of lung metastases in a murine model of breast cancer.     

Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway

Nonalcoholic fatty liver disease (NAFLD) is a serious health problem. Although NAFLD represents a form of lipotoxicity, its pathogenesis remains poorly understood. The aim of this study was to examine the cellular mechanisms involved in free fatty acid (FFA)-mediated hepatic lipotoxicity. FFA treatment of liver cells resulted in Bax translocation to lysosomes and lysosomal destabilization with release of cathepsin B (ctsb), a lysosomal cysteine protease, into the cytosol. This process was also partially dependent on ctsb. Lysosomal destabilization resulted in nuclear factor kappa B-dependent tumor necrosis factor alpha expression. Release of ctsb into the cytoplasm was also observed in humans with NAFLD and correlated with disease severity. In a dietary murine model of NAFLD, either genetic or pharmacological inactivation of ctsb protected against development of hepatic steatosis, liver injury, and insulin resistance with its associated "dysmetabolic syndrome." In conclusion, these data support a lipotoxic model of FFA-mediated lysosomal destabilization.     

Gender images and sexual and reproductive conduct

OBJECTIVE: To analyze some of the factors associated with material living conditions of adolescents and their means for earning a living, such as idea construction and gender representations, related to sexual and reproductive conduct. MATERIAL AND METHODS: The investigation was conducted in Asuncion, Paraguay, in 2000. Qualitative data collection techniques (in-depth interviews) and interpretive analysis were used. A total of 40 interviews were conducted of young people between the ages of 15 and 20, grouped as "schooled" and "not schooled." RESULTS: Gender constructions exist, denominated in this study as "modern" and "traditional," that classify perceptions about gender roles for women and their position in relation to males, as well as for partner relationships and the exercise of power in such contexts. Ideas and representations about maternity are also defined. CONCLUSIONS: The distinct gender image "types" associated with the adolescents means for earning a living simultaneously condition certain perceptions about gender roles and reproductive conduct.     

Stereotactic Magnetic Resonance Guidance for Anatomically Targeted Ablations of the Fossa Ovalis and the Left Atrium

INTRODUCTION: Targets for radiofrequency ablation (RFA) of atrial fibrillation are increasingly being selected based on anatomic considerations. Because fluoroscopy provides only limited information about the relationship between catheter positions and cardiac structures, we evaluated whether stereotactic catheter guidance might facilitate anatomical catheter navigation and RFA to the great vessels, the fossa ovalis and the left atrium (LA). METHODS AND RESULTS: An electromagnetic catheter's position system was superimposed on three-dimensional (3D) MR images using fiducial markers. This allowed the dynamic display of the catheter position on the true anatomy of previously acquired MRI in real-time. To assess the reproducibility of RFA, repeat ablations were created at the identical anatomic site in the inferior vena cava (IVC) in 5 swine. Average distance of the repeated ablations was 4.4 +/- 2.4 mm.In five swine the catheter was anatomically guided with the MRI to the fossa ovalis and a single RFA was performed. On the pathological specimen all ablation sites were located within the fossa ovalis with an average distance of 3.9 +/- 2.1 mm from its center. In two of the experiments the ablation catheter was passed into the left atrium and anatomically targeted ablation performed in the lateral wall of the left atrial appendage. Catheter location and ablation site were confirmed by autopsy and histology. CONCLUSION: Real-time display of the catheter position on 3D-MRI allows anatomically targeted catheter navigation and RFA in the IVC, the fossa ovalis, and the left atrium. This may facilitate anatomically based interventions like septal puncture or pulmonary vein ablation and decrease fluoroscopy times.     

Decreased pituitary-gonadal secretion in men with obstructive sleep apnea

Decreased libido is frequently reported in male patients with obstructive sleep apnea (OSA). The decline in morning serum testosterone levels previously reported in these patients was within the normal adult male range and does not explain the frequent association of OSA and sexual dysfunction. We determined serum LH and testosterone levels every 20 min between 2200-0700 h with simultaneous sleep recordings in 10 men with sleep apnea and in 5 normal men free of any breathing disorder in sleep. The mean levels and area under the curve of LH and testosterone were significantly lower in OSA patients compared with controls [LH, 24.9 +/- 10.2 IU/liter.h vs. 43.4 +/- 9.5 (P < 0.005); testosterone, 67.2 +/- 11.5 nmol/liter.h vs. 113.3 +/- 26.8 (P < 0.003)]. Four of 10 patients had hypogonadal morning (0700 h) serum testosterone levels. Analysis of covariance (ANCOVA) revealed that the 2 groups differed significantly in the amount of LH and testosterone secreted at night independent of age or degree of obesity. After partialing out body mass index, there was a significant negative correlation between the amounts of LH and testosterone secreted at night and the respiratory distress index, but not with degree of hypoxia. Our findings suggest that OSA in men is associated with dysfunction of the pituitary-gonadal axis. The relation between LH-testosterone profiles and the severity of OSA suggests that sleep fragmentation and, to a lesser extent, hypoxia in addition to the degree of obesity and aging may be responsible for the central suppression of testosterone in these patients.     

Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant

CONTEXT: In clinical practice, patients with acromegaly may be switched from therapy with long-acting somatostatin analogs to pegvisomant. The effect of changing therapies on glucose homeostasis and safety has not been reported. OBJECTIVES: The objectives of this study were to monitor changes in IGF-I levels, glycemic control, and safety, particularly liver function and tumor size. DESIGN: This was a multicenter, open-label, 32-wk trial study. SETTING: The study was performed at outpatient clinics. PATIENTS: Fifty-three patients with acromegaly previously treated with octreotide long-acting release (LAR) participated in this study. Intervention: Pegvisomant (10 mg/d) was initiated 4 wk after the last dose of octreotide LAR and was adjusted based on serum IGF-I concentrations at wk 12, 20, and 28. MAIN OUTCOME MEASURES: The main outcome measures were changes in IGF-I, glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose, and safety during the first 12 wk after conversion. RESULTS: At the end of pegvisomant treatment, IGF-I was normalized in 78% of patients. At wk 32, median fasting glucose concentration and HbA1c were reduced (-1.4 mmol/liter and -0.4%, respectively; both P < or = 0.0001) in the study population. Improvements in glycemic control occurred in patients with normal IGF-I concentrations at wk 4 [n = 15; fasting glucose, -1.7 mmol/liter (P < or = 0.0001); HbA1c -0.2% (P = 0.03)]. Decreases in fasting glucose and HbA1c levels were observed in patients with and without diabetes. HbA1c was reduced by more than 1.0% in patients with diabetes. Median pituitary tumor volume did not change, although tumor volume increased in two patients with macroadenomas. CONCLUSIONS: Conversion from octreotide LAR to pegvisomant was safe and well tolerated. Improved glycemic control indicates that pegvisomant should be considered in patients with acromegaly and diabetes.