The association of dietary fat with ability to obtain breast fluid by nipple aspiration.

The ability to obtain breast fluid by nipple aspiration was examined in relation to self-reported dietary fat intake in 1347 white and 153 black women. Study participants were between 20 and 59 years of age, were not pregnant or breastfeeding, and had no history of breast cancer. The proportion of women from whom nipple aspirate fluid was obtained increased with increasing dietary fat consumption; the odds ratio for obtaining breast fluid was 1.4 (95% confidence interval, 1.0-1.8) in white women who consumed over 90 g of fat/day compared with those who consumed less than 50 g of fat/day, adjusting for age, smoking, and parity. Among black women, the association was much stronger; the odds ratio for obtaining nipple aspirate fluid in those who consumed over 90 g of fat/day was 3.6 (95% confidence interval, 1.3-10.1) compared with those who consumed less than 50 g of fat/day. In both blacks and whites, the associations were most pronounced in women aged 30-44 years. These findings suggest a relationship between dietary fat consumption and breast secretion.     

Tissue plasminogen activator in brain tissues infected with transmissible spongiform encephalopathies

Prion propagation involves conversion of host PrP(C) to a disease-related isoform, PrP(Sc), which accumulates during disease and is the principal component of the transmissible agent. Proteolysis seems to play an important role in PrP metabolism. Plasminogen, a serine protease precursor, has been shown to interact with PrP(Sc). Plasminogen can be proteolytically activated by tissue plasminogen activator (tPA). Recent reports imply a crosstalk between tPA-mediated plasmin activation and PrP. In our study, both tPA activity and tPA gene expression were found elevated in TSE-infected brains as compared to their normal counterparts. Furthermore, it was proved that PrP(Sc), in contrast to PrP(C), could not be degraded by plasmin. In addition, it was observed that TSE symptoms and subsequent death of plasminogen-deficient and tPA-deficient scrapie challenged mice preceded that of wild-type controls. Our data imply that enhanced tPA activity observed in prion infected brains may reflect a neuro-protective response.     

Prospective study of transcutaneous oxygen tension (TcPO2) measurement in the testing period of spinal cord stimulation in diabetic patients with critical lower limb ischaemia.

BACKGROUND: Spinal cord stimulation improves microcirculatory blood flow, relieves diabetic neuropathic and ischaemic pain and reduces the amputation rate in patients with severe peripheral arterial occlusive disease. Aim: To evaluate whether transcutaneous oxygen tension (TcPO2) measurements can be used as a specific prognostic parameter in the assessment of suitability for permanent device implantation in a prospective controlled study on diabetic patients with peripheral arterial occlusive disease. METHODS: Sixty patients (39 men, 21 women; mean age: 60 years; range: 46-75) were submitted to implantation of a spinal cord electrical generator for severe peripheral vascular disease, after failed conservative or surgical treatment. The clinical status was classified as Fontaine's stage III and IV and the main pathology was diabetic vascular disease. Pedal TcPO2 was assessed on the dorsum of the foot and ankle and toe pressure Doppler measurements were performed before, two weeks and four weeks after implantation. RESULTS: Pain relief of over 75% and limb salvage were achieved in 35 diabetic patients, while in 12 a partial success with pain relief over 50% and limb salvage for at least 6 months was obtained. In 13 patients the method failed and the affected limbs were amputated. Clinical improvement and spinal cord stimulation success were associated with increases of TcPO2, within the first two weeks after implantation (temporary period). Limb salvage was achieved with significant increase of TcPO2 within the first two weeks of the testing period (from 21.4 to 31.5 mmHg in rest pain patients, p=0.030, from 15.1 to 22.0 mmHg, p=0.030 in patients with trophic lesions under 3 cm2 in size and in those with trophic lesions over 3 cm2, from 12.1 to 17.9 mmHg, p=0.025) unrelated to the stage of the disease and the initial TcPO2 value. TcPO2 changes were related to the presence of adequate paraesthesias and warmth in the painful area during the trial period. The systolic ankle/brachial blood pressure index and toe pressure did not change under stimulation. CONCLUSIONS: A two-week testing period should be performed in all diabetic patients treated with spinal cord stimulation for peripheral arterial occlusive disease to identify the candidates for permanent implantation. Only diabetic patients with significant increases of TcPO2 and clinical improvement, during the test period, should be considered for permanent implantation and not merely all patients with pain relief. TcPO2 changes could be used as a predictive index of the therapy success and should be considered in terms of cost effectiveness before the final decision to permanent implantation.     

Breast fluid cholesterol and cholesterol epoxides: relationship to breast cancer risk factors and other characteristics

We measured levels of cholesterol and its oxidation products, 5,6 alpha- and beta-epoxides and their common hydrolysis product cholestane triol, in breast fluids of women without breast disease, compared these levels to serum cholesterol levels, and explored associations of these breast fluid measurements with known breast cancer risk factors and other characteristics. Subjects were 105 women with no history of breast disease from whom breast fluid could be obtained by nipple aspiration. The four breast fluid measurements were significantly correlated with each other (P less than 0.0001) but none was correlated with serum cholesterol. In subsequent analyses restricted to breast fluid cholesterol and cholesterol beta-epoxide, cholesterol levels (but not beta-epoxide levels) increased with age and were higher in white than nonwhite women. Both measurements were low in women who were lactating, who were parous, or who had breast-fed. The lower levels among parous women persisted for at least 2 years postpartum or postlactation. Because breast fluid levels of cholesterol beta-epoxide are reduced for some time following a birth or cessation of lactation, the alveolar-ductal systems of parous women presumably have less cumulative exposure to this potentially carcinogenic substance. This biochemical mechanism may, in part, explain the observed reduction of breast cancer risk associated with parity.     

Effects of chronic estrogen treatment on modulating age‐related bone loss in female mice

While female mice do not have the equivalent of a menopause, they do undergo reproductive senescence. Thus, to dissociate the effects of aging versus estrogen deficiency on age‐related bone loss, we sham‐operated, ovariectomized, or ovariectomized and estrogen‐replaced female C57/BL6 mice at 6 months of age and followed them to age 18 to 22 months. Lumbar spines and femurs were excised for analysis, and bone marrow hematopoietic lineage negative (lin–) cells (enriched for osteoprogenitor cells) were isolated for gene expression studies. Six‐month‐old intact control mice were euthanized to define baseline parameters. Compared with young mice, aged/sham‐operated mice had a 42% reduction in lumbar spine bone volume/total volume (BV/TV), and maintaining constant estrogen levels over life in ovariectomized/estrogen‐treated mice did not prevent age‐related trabecular bone loss at this site. By contrast, lifelong estrogen treatment of ovariectomized mice completely prevented the age‐related reduction in cortical volumetric bone mineral density (vBMD) and thickness at the tibial diaphysis present in the aged/sham‐operated mice. As compared with cells from young mice, lin– cells from aged/sham‐operated mice expressed significantly higher mRNA levels for osteoblast differentiation and proliferation marker genes. These data thus demonstrate that, in mice, age‐related loss of cortical bone in the appendicular skeleton, but not loss of trabecular bone in the spine, can be prevented by maintaining constant estrogen levels over life. The observed increase in osteoblastic differentiation and proliferation marker gene expression in progenitor bone marrow cells from aged versus young mice may represent a compensatory mechanism in response to ongoing bone loss. © 2010 American Society for Bone and Mineral Research.     

Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence

The wars in Iraq and Afghanistan are associated with high rates of post-traumatic stress disorder (PTSD) and comorbid alcohol use disorders. The pharmacotherapy of these comorbid conditions has received relatively little study. The current study compared the serotonin uptake inhibitor, paroxetine, to the norepinephrine uptake inhibitor, desipramine. It also evaluated the adjunctive efficacy of the Food and Drug Administration (FDA)-approved alcoholism pharmacotherapy, naltrexone, relative to placebo. Four groups of predominately male veterans (n=88) meeting current diagnostic criteria for both alcohol dependence (AD) and PTSD were randomly assigned under double-blind conditions to one of four groups: paroxetine+naltrexone; paroxetine+placebo; desipramine+naltrexone; desipramine+placebo. Main outcome measures included standardized scales that assessed symptoms of PTSD and alcohol consumption. Paroxetine did not show statistical superiority to desipramine for the treatment of PTSD symptoms. However, desipramine was superior to paroxetine with respect to study retention and alcohol use outcomes. Naltrexone reduced alcohol craving relative to placebo, but it conferred no advantage on drinking use outcomes. Although the serotonin uptake inhibitors are the only FDA-approved medications for the treatment of PTSD, the current study suggests that norepinephrine uptake inhibitors may present clinical advantages when treating male veterans with PTSD and AD. However, naltrexone did not show evidence of efficacy in this population. This study was registered with ClinicalTrials.gov, registration number NCT00338962 and URL: http://clinicaltrials.gov/ct2/show/NCT00338962?term=desipramine+AND+alcohol+dependence+AND+depression&recr= Closed&rank=1.     

Modulation of the cortical processing of novel and target stimuli by drugs affecting glutamate and GABA neurotransmission

In this double-blind, placebo-controlled study, we examined the effects of subanaesthetic doses of ketamine (an NMDA glutamate receptor antagonist) and thiopental (a GABA-A receptor agonist) on the event-related potential (ERP) correlates of deviant stimulus processing in 24 healthy adults. Participants completed three separate pharmacological challenge sessions (ketamine, thiopental, saline) in a counterbalanced order. EEG data were recorded both before and during each challenge while participants performed a visual 'oddball' task consisting of infrequent 'target' and 'novel' stimuli intermixed with frequent 'standard' stimuli. We examined drug effects on the amplitude and latency of the P300 (P3) component of the ERP elicited by target (P3b) and novel stimuli (P3a), as well as the N200 (N2) component elicited by both target and novel stimuli, and the N100 (N1) elicited by standard stimuli. Relative to placebo, both drugs reduced the amplitude of parietal P3b. While both drugs reduced parietal P3a and Novelty N2, ketamine also shortened P3a latency, reduced Novelty N2 amplitude more than thiopental, and increased frontal P3a amplitude relative to placebo. Overall, the data suggest that both the GABA-A and NMDA receptor systems modulate P3b and P3a. NMDA antagonism appears to lead to more varied effects on the neural correlates of novelty processing.