Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.      

Volume and surface area estimates of astrocytes in the sensorimotor cortex of the cat

Electron micrographs of random sections through 133 astrocytes taken from the anterior and posterior sigmoid gyri of adult cats were used to estimate average astrocyte cell volume. Average soma volume was derived by two methods: (1) assuming that each approximated the shape of a prolate spheroid, a value of 2.2 ± 0.1 × 10^?13l. was calculated by substituting measurements of major (mean 10.4 ± 0.2 μm) and minor (mean 6.2 ± 0.1 μm) cell axes into the formula for volume; (2) applying Weibel's point-counting method of morphometry, a value of 1.9 ± 0.09 × 10^?13l. was obtained based on ratios of volume density and nuclear volume, calculated from measurements of nuclear axes. Because of the use of random sections through the cells sampled, the axial measurements on which both methods depend represent possible underestimations by as much as 21%; the resulting average value for soma volume might be as much as 3.2 × 10^?13l. Astrocyte somata from the deepest layer of the cortex had a significantly larger average volume than those from more superficial layers (P < 0.05). Average total cell volume (soma plus processes), estimated by calculating the volume of the tissue sample that was occupied by astrocytes and dividing that value by the number of astrocytes in the sample, amounted to 5.7 × 10^?13l. Point-counting morphometry revealed that 15.5% of the cortex consists of astrocytic cytoplasm. Average total cell surface area, estimated from intercepts of grid lines with cell membrane profiles of astrocytes within the sample, was 1.9 × 10^?5 cm²; average surface area of astrocyte somata, based on axial measurements, amounted to 2.5 × 10^?6 cm² or 13% of the surface area of the whole cell.Only 18 gap junctions were identified in the random sections through 133 astrocytes; these and other considerations bearing on the possible relationship of the data presented to electrical measurements in living astrocytes are discussed.     

A locus for autosomal dominant anterior polar cataract on chromosome 17p

Inherited cataract is a clinically and genetically heterogeneous disease. Here we report the identification of a new locus for an autosomal dominant anterior polar cataract on the short arm of chromosome 17. To map this new locus we performed genetic linkage analysis with microsatellite markers in a four-generation pedigree. After exclusion of seven candidate loci for cataract, we obtained significant positive LOD scores for markers D17S849 (Z = 4.01 / theta = 0.05) and D17S796 (Z = 4.17 / theta = 0.05). Multipoint analysis gave a maximum LOD score of 5.2 (theta max = 0.06) between these two markers. From haplotype analysis, the cataract locus lies in the 13 cM interval between markers D17S849 and D17S796. This study provides the first genetic mapping of an autosomal dominant anterior polar cataract.      

Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons

Complement activation products are major components of the inflammatory response induced by cardiac surgery and cardiopulmonary bypass which contribute to postoperative organ dysfunction, fluid accumulation, and morbidity. Activation of the complement system occurs during extracorporeal circulation, during reperfusion of ischemic tissue, and after the formation of heparin-protamine complexes. In this study we examine the efficacy of Compstatin, a recently discovered peptide inhibitor of complement, in preventing heparin/protamine-induced complement activation in baboons. The study was performed in baboons because Compstatin binds to baboon C3 and is resistant to proteolytic cleavage in baboon blood (similar to humans); Compstatin inhibits only the activation of primates' complement system. After testing various doses and administration regimens, Compstatin produced complete inhibition at a total dose of 21 mg/kg when given as a combination of bolus injection and infusion. Compstatin completely inhibited in vivo heparin/protamine-induced complement activation without adverse effects on heart rate or systemic arterial, central venous, and pulmonary arterial pressures. This study indicates that Compstatin is a safe and effective complement inhibitor that has the potential to prevent complement activation during and after clinical cardiac surgery. Furthermore, Compstatin can serve as the prototype for designing an orally administrated drug.     

Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis

Lack of expression of the fragile X mental retardation protein (FMRP) results in mental retardation and macroorchidism, seen as the major pathological symptoms in fragile X patients. FMRP is a cytoplasmic RNA- binding protein which cosediments with the 60S ribosomal subunit. Recently, two proteins homologous to FMRP were discovered: FXR1 and FXR2. These novel proteins interact with FMRP and with each other and they are also associated with the 60S ribosomal subunit. Here, we studied the expression pattern of the three proteins in brain and testis by immunohistochemistry. In adult brain, FMR1, FXR1 and FXR2 proteins are coexpressed in the cytoplasm of specific differentiated neurons only. However, we observed a different expression pattern in fetal brain as well as in adult and fetal testis, suggesting independent functions for the three proteins in those tissues during embryonic development and adult life.      

Relationship between total mechanical energy and oxygen consumption in the stunned myocardium

We studied the relationship between left ventricular oxygen consumption (LVVO2) and total ventricular mechanical energy production as determined by calculation of the systolic pressure-volume area (P-VA) before and after 25 minutes of warm ischemia in 7 sheep. We compared the relationship between LVVO2 and P-VA with the relationships between LVVO2 and stroke work and between LVVO2 and the systolic stress integral. Using the methods presented, P-VA can be measured in vivo (n = 123) in both preischemic and postischemic hearts. Ischemia increases the slopes of the relationship between LVVO2 and P-VA and between stroke work and the systolic stress integral, and reduces the oxygen utilization efficiency of stroke work to less than 2%. Coefficients of determination for the relationship between LVVO2 and P-VA are, in general, higher than those between LVVO2 and either stroke work or the systolic stress integral. We conclude that systolic P-VA can be measured in vivo using recently developed methods and that it is applicable to postischemic "stunned" hearts. Because P-VA and LVVO2 can be converted into identical energy units, calculation of P-VA permits calculation of myocardial oxygen utilization efficiency.     

Undercover 'shopping' to evaluate lab services

Wonder what goes on at your outpatient labs when you're not there? This clever adaptation from the retail world can help you ferret out foul play and affirm first-rate employees.     

Reporter gene assay for fish-killing activity produced by Pfiesteria piscicida.

Collaborative studies were performed to develop a functional assay for fish-killing activity produced by Pfiesteria piscicida. Eight cell lines were used to screen organic fractions and residual water fraction by using a 3-[4, 5-dimethylthiazol-(2-4)]-diphenyltetrazolium bromide cytotoxicity assay. Diethyl ether and a residual water fraction were cytotoxic to several cell lines including rat pituitary (GH(4)C(1)) cells. Residual water as well as preextracted culture water containing P. piscicida cells induced c-fos-luciferase expressed in GH(4)C(1) cells with a rapid time course of induction and sensitive detection. The reporter gene assay detected activity in toxic isolates of P. piscicida from several North Carolina estuaries in 1997 and 1998 and may also be suitable for detecting toxic activity in human and animal serum.