Two pathways of placental lactogen secretion by cultured human trophoblast

To assess the relative importance of regulated and of constitutive secretion of placental lactogen, a cell culture model of term human trophoblast was utilized. Time courses of secretion revealed a constant secretion rate over 9 days of culture, with relatively small constant intracellular hormone concentration. Potassium, 21 mM, produced a slight but significant increase in hormone secretion into the medium. Growth hormone-releasing hormone (5 X 10(-10)-5 X 10(-9)) stimulated a 27-48% increase in placental lactogen secretion. The data suggest a major process of constitutive secretion and a minor role for regulated secretion from a storage pool.     

The Distribution of Hydrobiids and the Effects of Sediment Characteristics on the Population Dynamics of Hydrobia ventrosa in a Coastal Region of the Southern Baltic

The composition of the hydrobiid fauna in a coastal water of the southern Baltic was studied in 1990/91 at three stations with different sediment characteristics (grain size, organic content). Four species were found (Hydrobia ventrosa, H. ulvae, H. neglecta and Potamopyrgus jenkinsi). H. ventrosa was dominant at all stations. The mean hydrobiid abundances were 4,000 (stn. C), 18,000 (stn. B) and 40,000 (stn. A) ind./m² respectively. Abundance was found to correlate with the organic content of the sediment. The reproduction and growth of H. ventrosa was studied. Two reproduction phases were observed, one in summer and the other in late autumn. The autumn reproduction peaks were staggered owing to the different growth rates at the various stations. Possible correlations between the differences in shell size of H. ventrosa at the various stations and both sediment characteristics and abundance are discussed.     

The dual effect of calcium on aromatization by cultured human trophoblast

To study the effect of calcium ion on aromatization of an androgenic precursor to estradiol by the placenta, cultured term trophoblasts were used as a model system. Secretion of estradiol into the culture medium was regarded as indicating aromatization, since cells cultured with no androgenic precursors produced only insignificant amounts of estradiol. EGTA, verapamil and ionophore A23187 inhibited aromatization, while trifluoperazine, an inhibitor of the calcium-calmodulin complex, interfered with the stimulatory effect of cyclic AMP on aromatization. We conclude that calcium ion has an essential role in the aromatization of 4-androstene-3,17-dione to estradiol. The calcium-calmodulin complex is required for activation of aromatase by cyclic AMP. However, when flooded with calcium by ionophore A23187, the trophoblast is unable to effectively buffer calcium, and aromatization is inhibited.     

Reversal of myocyte hypertrophy by ventricular unloading: cardiac improvement without adrenergic receptor up-regulation and relocalization

In previous studies, we found that the improved contractile ability of cardiac myocytes from patients who have had left ventricular assist device (LVAD) support was due to a number of beneficial changes, most notably in calcium handling (increased sarcoplasmic reticulum calcium binding and uptake), improved integrity of cell membranes due to phospholipid reconstruction (reduced lysophospholipid content), and an upregulation of adrenoreceptors (increased adrenoreceptor numbers). However, in the case presented here, there was no increase in adrenoreceptor number, which is something that we usually find in core tissue at the time of LVAD removal or organ transplantation; also, there was no homogeneous postassist device receptor distribution. However, the patient was well maintained for 10 months following LVAD implantation, until a donor organ was available, regardless of the lack of adrenoreceptor improvement. We conclude from these studies that cardiac recovery is the result of the initiation of multiple repair mechanisms, and that the lack of expected changes, in this case increased adrenoreceptors, is not always an accurate indicator of anticipated outcome. We suggest that interventions and strategies have to consider multiple, beneficial changes due to unloading and target a number of biochemical and structural areas to produce improvement, even if not all of these improvements occur.     

Ginseng: Cardiotonic in adult rat cardiomyocytes, cardiotoxic in neonatal rat cardiomyocytes

Ginsengs are widely used to improve cardiac health and circulation. Loosely termed as ginsengs, Asian (Panax), Siberian and Ashwagandha (Indian Ginseng) Indian ginsengs are prepared from different plants. We tested the popular belief of cardiotonic effects of ginsengs using both neonatal and adult rat cardiomyocytes, comparing extracts from the three ginsengs. Addition of 10% v/v of extract (100 microl of extract/ml of culture medium) of each of the ginsengs resulted in a rapid (<10 s) cessation of beating in neonatal cardiomyocytes due to calcium overload, while sequential dilutions revealed that treatment with a low dose (0.01% v/v, 0.1 microl/ml of the medium) resulted in constant, regular beats (transients), and a slight elevation of diastolic calcium without overload. Addition of extracts to sparking, calcium-tolerant adult cardiomyocytes resulted in initiation of calcium transients, and adult cells were able to tolerate exposure to high concentrations of extract. Cardiotonic effects in adult cells (cardiotoxicity in neonatal cells) were most profound with Asian ginseng (2.6 times that of Siberian ginseng, 1.6 times that of Indian ginseng) probably due to the active ingredients (ginsenosides in Asian, eleutherosides in Siberian and withanolides in Indian) being structurally different. We conclude that fully developed cardiomyocytes are able to accommodate higher doses of ginseng than neonatal cells, and that the effects of ginseng on newly formed, developing myocytes, could be extremely deleterious to the fetus. However, for adults, ginseng might well be a 'tonic' in its ability to increase beating and intramyocytic calcium levels.     

Determination of 5′-bromodeoxyuridine in DNA by buoyant density

Cesium chloride buoyant density analysis shows the density difference between the double-stranded alternating copolymers of dT and dA, poly(dAT·dAT) and of dA and BrdU, (dABU·dABU), to be 0.1730 g/cm³. A mammalian DNA fully substituted with 5′-bromodeoxyuridine (BrdU) increases in density over control, unsubstituted, DNA by a value within 1% of that predicted from analysis of the copolymers. A simple relationship is presented for the accurate determination of the extent of BrdU substitution in a DNA of heterogeneous base composition.     

A quantitative method for distinguishing BrdUTP and dTTP in soluble pools

5-Bromodeoxyuridine (BrdU) has the well-known property of inhibiting differentiated cell functions in a variety of biological systems, and considerable attention has been focused on elucidating its mechanism of action [see Ref. (1) for review]. While most studies are consistent with a DNA-mediated mode of action, it is becoming clear that most experiments to date are insufficient to exclude other levels of action. Therefore, it is becoming increasingly relevant to examine aspects of BrdU metabolism in addition to its incorporation into DNA, including its uptake and equilibration into nucleotide pools.     

Average beta burst duration profiles provide a signature of dynamical changes between the ON and OFF medication states in Parkinson’s disease

Parkinson’s disease motor symptoms are associated with an increase in subthalamic nucleus beta band oscillatory power. However, these oscillations are phasic, and there is a growing body of evidence suggesting that beta burst duration may be of critical importance to motor symptoms. This makes insights into the dynamics of beta bursting generation valuable, in particular to refine closed-loop deep brain stimulation in Parkinson’s disease. In this study, we ask the question “Can average burst duration reveal how dynamics change between the ON and OFF medication states?”. Our analysis of local field potentials from the subthalamic nucleus demonstrates using linear surrogates that the system generating beta oscillations is more likely to act in a non-linear regime OFF medication and that the change in a non-linearity measure is correlated with motor impairment. In addition, we pinpoint the simplest dynamical changes that could be responsible for changes in the temporal patterning of beta oscillations between medication states by fitting to data biologically inspired models, and simpler beta envelope models. Finally, we show that the non-linearity can be directly extracted from average burst duration profiles under the assumption of constant noise in envelope models. This reveals that average burst duration profiles provide a window into burst dynamics, which may underlie the success of burst duration as a biomarker. In summary, we demonstrate a relationship between average burst duration profiles, dynamics of the system generating beta oscillations, and motor impairment, which puts us in a better position to understand the pathology and improve therapies such as deep brain stimulation.