Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men.

Androgens are important regulators of bone and prostate health in elderly men. The role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in men is unclear. We show that specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. INTRODUCTION: Androgens are important regulators of bone and prostate health in elderly men. Local synthesis and degradation of androgens are likely to be important parameters of biological action of androgens in androgen-responsive tissues. The aim of this study was to determine the role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in elderly men. MATERIALS AND METHODS: A subsample of the population-based Swedish part of the MrOS study (n = 631, average age = 75.9 years) was investigated. Bone parameters were measured using DXA. Serum levels of total testosterone (T) and dihydrotestosterone (DHT) were measured by gas chromatography/mass spectroscopy (GC-MS); androstane-3alpha,17beta-diol-3glucuronide (3G) and androstane-3alpha,17beta-diol-17glucuronide (17G) were measured by liquid chromatography/mass spectroscopy. Prostate volume (n = 159) was measured by transrectal ultrasound. RESULTS: The general pattern is that two of the glucuronidated androgen metabolites, namely 17G and 3G, are stronger positive predictors of BMD than the bioactive androgens (T and DHT). In addition, 17G is a clear positive predictor of prostate volume, explaining 4.5% of the variance in prostate volume, whereas the bioactive androgens do not display any association with prostate volume. CONCLUSIONS: Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. Future studies should determine if the glucuronidated androgen metabolites also reflect other biological correlates of androgenic activity, including prostate cancer, and if low levels might be a marker of general androgen deficiency in men.     

Mechanisms of neutrophil damage to human alveolar extracellular matrix: the role of serine and metalloproteases.

Many syndromes of lung injury are associated with accumulation of neutrophils within the pulmonary parenchyma. These neutrophils have the capacity to produce lung injury by products including proteases and reactive oxygen species (ROS). We examined the ability of activated neutrophils to solubilize human alveolar extracellular matrix (ECM), and by use of scavengers and inhibitors, evaluated the role of ROS and proteases in this process. Supernatants of phorbol myristate acetate-activated neutrophils routinely solubilized 10.2% +/- 0.8% (n = 30) of collagen in human alveolar ECM, as measured by hydroxyproline release. Scavengers of ROS had no significant effect on ECM solubilization. Inhibitors of metalloproteases partially inhibited ECM solubilization (38.5% +/- 4.6% inhibition by ethylenediaminetetraacetic acid [n = 6], and 37.0% +/- 14.7% by 1,10-phenanthroline [n = 6]; p less than 0.05). Inhibitors of the neutrophil serine proteases, elastase and cathepsin G, markedly inhibited ECM solubilization (100.9% +/- 3.7% by alpha 1-protease inhibitor [alpha 1-PI] [n = 6] and 81.9% +/- 0.1% by soybean trypsin inhibitor [n = 6]; p less than 0.01). Since alpha 1-PI completely inhibited solubilization, metalloprotease activity appeared to be related to serine protease activity. This finding was confirmed by the observation that addition of a metalloenzyme activator, p-aminophenylmercuric acetate, in the presence of alpha 1-PI, restored solubilization to the same level as that inhibited by metal chelators. We conclude that human neutrophil metalloproteases and serine proteases directly solubilize human alveolar ECM. Furthermore, neutrophil serine proteases activate latent metalloproteases. However, ROS were not demonstrated to play a major role in ECM solubilization in our system.     

Variability in nutrient and food intakes among older middle-aged men. Implications for design of epidemiologic and validation studies using food recording

The authors conducted a dietary methodology study in 1984 in Finnish men aged 55-69 years in order to validate two dietary assessment instruments being used in the US-Finland Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Trial. Twelve 2-day food records collected from 162 men over a 6-month period, including every day of the week, served as the reference measure. This report focuses on three important questions for investigating diet and disease relations: 1) How many days are necessary to classify "usual" intake? 2) Is there loss as a result of using consecutive days? 3) Which days are necessary for assessment and classification of "usual" diet? A repeated-measures regression model was used to estimate the variance components and the effects of consecutive days, weekday (weekday vs. weekend), and season. Correlations between the averages of different numbers of days of food records and "true" usual intake were examined along with the resulting attenuations in relative risk. Results suggest that 7-14 days are required to adequately classify most individuals into categories of intake for most nutrients and some foods. There appears to be some loss of information from using consecutive days rather than days further apart. Weekday/weekend differences in mean intakes are slight, and the rank ordering of individuals appears to be preserved. A moderate seasonal effect is shown for classification of fruits, but only a slight one is seen for micronutrients and berries. Implications for the design of epidemiologic and validation studies are discussed.     

Clinical effects and plasma levels of Δ9-Tetrahydrocannabinol (Δ9-THC) in heavy and light users of cannabis

⁹-Tetrahydrocannabinol (⁹-THC) was administered in a crossover design by smoking and IV injection to groups of heavy and light users of marihuana. Plasma concentrations of ⁹-THC were similar for the groups after IV injection of 5.0 mg ⁹-THC, but the AUC_{0–240 min} showed a trend towards lower values for the heavy user group. To achieve a maximum desired high, both groups smoked similar amounts (about 13 mg) of ⁹-THC. Heavy users tended to have higher plasma levels than light users. The systemic availability of smoked ⁹-THC was significantly higher for the heavy users (heavy users 23±16% vs 10±7% for light users). These results also indicate that heavy cannabis users smoke more efficiently than casual smokers.Both light and heavy users showed more clinical effect following IV administration than after smoking. The response of the heavy users, both with respect to effect on heart and high, was quite comparable to that of light users.The present study does not suggest that tolerance readily develops in heavy users.     

Nurse-led heart failure clinics improve survival and self-care behaviour in patients with heart failure: results from a prospective, randomised trial.

AIM: The aim of this trial was to prospectively evaluate the effect of follow-up at a nurse-led heart failure clinic on mortality, morbidity and self-care behaviour for patients hospitalised due to heart failure for 12 months after discharge. METHODS: A total of 106 patients were randomly assigned to either follow-up at a nurse-led heart failure clinic or to usual care. The nurse-led heart failure clinic was staffed by specially educated and experienced cardiac nurses, delegated the responsibility for making protocol-led changes in medications. The first follow-up visit was 2-3 weeks after discharge. During the visit the nurse evaluated the heart failure status and the treatment, gave education about heart failure and social support to the patient and his family. RESULTS: There were fewer patients with events (death or admission) after 12 months in the intervention group compared to the control group (29 vs 40, p=0.03) and fewer deaths after 12 months (7 vs 20, p=0.005). The intervention group had fewer admissions (33 vs 56, p=0.047) and days in hospital (350 vs 592, p=0.045) during the first 3 months. After 12 months the intervention was associated with a 55% decrease in admissions/patient/month (0.18 vs 0.40, p=0.06) and fewer days in hospital/patient/month (1.4 vs 3.9, p=0.02). The intervention group had significantly higher self-care scores at 3 and 12 months compared to the control group (p=0.02 and p=0.01). CONCLUSIONS: Follow up after hospitalisation at a nurse-led heart failure clinic can improve survival and self-care behaviour in patients with heart failure as well as reduce the number of events, readmissions and days in hospital.