Decreased peak bone mass is associated with a 3-bp deletion/insertion of the CYP19 intron 4 polymorphism: preliminary data from the GOOS study.

Finding that estrogen plays an important role in bone homeostasis in men prompted research on relationship of polymorphism at the CYP19 gene and the bone mass. Therefore, influence of 3-bp deletion/insertion polymorphism of CYP19 (TTTA)7 allele on the peak bone mass attainment in males was studied. Fifty-eight unrelated male participants, aged 21-35, were selected depending on the presence of (TTTA)7 (no.=19) or (TTTA)7-3 (no.=39) alleles from the initial cohort of 92 young males. Heterozygotes (TTTA)7/(TTTA)7-3 (no.=13) were not included in the analysis. Serum levels of estradiol, free testosterone, 25-hydroxyvitamin D, bone alkaline phosphatase, osteocalcin, and beta-crosslaps were measured. Bone mass was measured by DXA at the hip and at the spine. (TTTA)7-3 allele was associated with significantly lower femoral neck bone mineral density (BMD) (p=0.02). Logistic regression model indicated strong association of (TTTA)7-3 allele with low BMD in the range of osteopenia/osteoporosis (p=0.014, odds ratio 12.36, confidence intervals 1.65-92.46). In the present study association of 3-bp deletion polymorphism of the (TTTA)7 allele with decreased peak bone mass in males is reported for the first time. However, further studies are necessary to elucidate the functional relevance of this polymorphism.

Age-related changes in functions of peripheral blood phagocytes.

Ingestion, digestion and antibody-dependent cell-mediated cytotoxicity (ADCC) of opsonized sheep red blood cells (SRBC), as effector functions of peripheral blood phagocytes, were studied in newborns, children, mature and aged adults. All tested functions changed non-synchronously during the lifetime. The ingestion was maximal in newborns, digestion in children and ADCC in mature adults. The ingestion was minimal in aged, but digestion was minimal both in newborns and aged. Such changes of phagocytes' functions could possibly contribute to differences in immune reactions of the age-groups studied. The study indicates the need for establishing age-adjusted normal values for major granulocyte and monocyte effector functions.

Phenotypic analysis of receptor-ligand pairs on B-cells in B-chronic lymphocytic leukemia.

Whole-blood three-color immunofluorescence analysis was used to investigate the role of CD5/CD72 and CD21/CD23 receptor-ligand pair formation on B-chronic lymphocytic leukemia (B-CLL) cells as well as sCD23 and bcl-2 oncoprotein expression in disease progression and activity and total tumor mass in B-cell chronic leukemia (B-CLL) patients. Thirty-four patients with B-CLL and 19 controls were included in the study. The majority of B-cells in B-CLL patients coexpressed CD5 and CD72 as well as the CD23 antigen. Unlike B-cells in B-CLL patients, B-cells in all healthy controls tested had high expression of CD21 antigen. We identified two groups of B-CLL patients according to high (n = 20) or low levels (n = 14) of CD21 expression on CD19+CD23+ B-cells. Only in the patients with high CD21 expression, were sCD23 levels positively correlated with factors known to have prognostic significance in B-CLL (Rai stage and TTM) and could, therefore, be used as a prognostic parameter for these B-CLL patients. Bcl-2 oncoprotein expression did not differ between these patient groups. We presumed that in patients with a lower expression of CD21 antigen, the contribution of the CD21 molecule to homotypic adhesion was lacking. Further studies are necessary to determine the possible association of higher expression of the CD21 antigen with disease progression and the aggressive character of the B-CLL.

Calcaneus ultrasound in males: normative data in the Croatian population (ECUM study).

Limited number of dual X-ray absorptiometry (DXA) devices in Croatia makes this diagnostic technique unavailable to the majority of the population. Quantitative ultrasound (QUS) of the calcaneus could be an alternative tool for assessing fracture risk. However, age-specific normative data should be obtained before using the QUS in everyday clinical practice. The aim of our Epidemiology of Calcaneus Ultrasound in Males (ECUM) study is to establish the normative QUS data in a healthy sample of Croatian males. A total of 1002 male participants, aged 20-99, recruited in different Croatian counties, were included in the study. In each subject broadband ultrasound attenuation (BUA), speed of sound (SOS) and quantitative ultrasound index (QUI) of the left calcaneus were measured using the Sahara ultrasound device (Hologic). The coefficients of variation were 2.85 for BUA, 0.37 for SOS and 2.49 for QUI. Significant declining with age was found for all three parameters, BUA (p<0.001), SOS (p<0.001) and QUI (p<0.001), with respective r values 0.14, 0.27 and 0.23. The peak SOS (1,562.8+/-28.5 m/sec) and QUI (103.6+/-16.5) values were observed in the third decade, whereas the peak BUA value (86.2+/-19.2 db/MHz) was observed in the fourth decade. A subgroup of 103 participants, aged 20-29, was used to estimate young adult mean and SD for QUI and calculate the T-scores. Using the World Health Organization diagnostic criteria the rates of osteoporosis (T-score<-2.5) in the males aged 50 and older was 5.8%. However, when we used the cut-off value of the T-score<-1.8, as previously suggested, prevalence of osteoporosis in Croatian males >50 yr was 16.2%. Although further studies might improve our understanding of the QUS role in the fracture prediction, we hope that the results presented here will improve the clinical management of osteoporosis in males.

Naloxone interferes with granulocytopoiesis in long-term cultures of mouse bone marrow; buffering by the stromal layer.

Long-term cultures of mouse bone marrow cells were treated with naloxone, starting at the time of culture initiation or in the 2nd or 4th week of culture. Cell proliferation was suppressed and the ratio of immature and mature granulocytes to macrophages diminished by naloxone treatment. The effect depended on the timing of naloxone addition to the cultures and on its concentration, with a bell-shaped dose-response curve. High and low concentrations of naloxone (10(-4), 10(-6), 10(-14) M) interfered with hematopoiesis more strongly than the intermediate concentrations (10(-8) to 10(-12) M). Early cultures lacking the stromal layer were more sensitive to naloxone than the cultures with established stroma. The bell-shaped dose-response curve has been attributed to an interplay of specific (opioid-receptor-mediated) and nonspecific mechanisms. Opioidergic mechanisms apparently participate in the regulation of hematopoiesis.