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.     

Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma

The treatment of patients with relapsed and refractory Hodgkin lymphoma (HL), especially those who relapse after autologous stem cell transplantation, remains challenging. Patients with HL whose disease relapses after stem cell transplantation are rarely cured with current treatment modalities, and have a median survival of less than 3 years. Since no new drugs have been approved by the FDA for HL in more than three decades, there is a clear unmet medical need for drug development for this patient population. New treatment strategies that are based on targeting oncogenic signaling pathways are currently explored. This review will focus on emerging new treatment modalities that are currently under investigation for patients with relapsed classical HL.     

Velocity–pressure loops for continuous assessment of ventricular afterload: influence of pressure measurement site

VPloop, the graphical representation of pressure versus velocity, and its characteristic angles, GALA and β, can be used to monitor cardiac afterload during anesthesia. Ideally VPloop should be measured from pressure and velocity obtained at the same arterial location but standard of care usually provide either radial or femoral pressure waveforms. The purpose of this study was to look at the influence of arterial sites and the use of a transfer function (TF) on VPloop and its related angles. Invasive pressure signals were recorded in 25 patients undergoing neuroradiology intervention under general anesthesia with transesophageal flow velocity monitoring. Pressures were recorded in the descending thoracic aorta, abdominal aorta, femoral and radial arteries. We compared GALA and β from VPloops generated from each location and in high and low risk patients. GALA was similar in the central locations (55°[49–63], 52°[47–61] and 54°[45–62] from descending thoracic to femoral artery, median[interquartile], p?=?0.10), while there was a difference in β angle (16°[4–27] to 8°[3–15], p?<?0.0001). GALA and β obtained from radial waveforms were different (39°[31–47] compared to 46°[36–54] and 6°[2–14] compared to 16°[4–27] for GALA and β angles respectively, p?<?0.001) which was corrected by the use of a TF (45°[32–55] and 17°[5–28], p?=?ns). GALA and β are underestimated when measured with a radial catheter. Using pressure waveforms from femoral locations alters VPloops, GALA and β in a smaller extend. The use of a TF on radial pressure allows to correctly plot VPloops and their characteristic angles for routine clinical use.     

Two circulating neutrophil populations in acute inflammation in mice

Objective and design

Recent studies indicate that neutrophils are heterogeneous and may have an immunosuppressive role in addition to their well-known phagocytic and bactericidal function. This study examined neutrophil subpopulations in the circulation, peritoneum, spleen and bone marrow from mice at various time points after induction of acute inflammation.

Material, treatment and methods

Female C57BL/6 mice were injected intraperitoneally with lipopolysaccharide (LPS). Blood, peritoneal, spleen and bone marrow cells were collected and counted and expression of surface molecules and chemokine receptors analyzed with flow cytometry. Chemokine and cytokine concentrations in serum and peritoneal fluid were determined by ELISA.

Results

Neutrophil numbers in the circulation decreased following administration of LPS but reached similar numbers to those prior to inflammation at 8?h. At that time point, two distinct neutrophil populations were present in the circulation. These two neutrophil populations differed in size, granularity and expression of CD11b and Ly6G. Few neutrophils were recruited into the peritoneum until 24?h after administration of LPS at a time when the neutrophils in the circulation had increased their expression of the chemokine receptor CXCR2.

Conclusions

Induction of acute inflammation leads to the appearance of two circulating neutrophil subpopulations, which may differ in their activation state and function.