The kinetics of the PuO2 to Pu2O3 conversion.

In an oxidizing environment, the oxide formed on plutonium (Pu) metal is composed of a plutonium dioxide (PuO2) top layer and a thin cubic plutonium sesquioxide (Pu2O3) middle layer. In a reducing environment, the PuO2 layer auto-reduces to cubic Pu2O3. The speed and extent of this conversion depend on the combination of temperature and time. While PuO2 provides a strong diffusion barrier against unwanted Pu corrosion by gaseous species (like hydrogen), Pu2O3 does not, since its crystal structure has chains of oxygen vacancies. The kinetics of the PuO2 reduction are, therefore, of fundamental interest and enable researchers to better protect Pu from corrosion. In this report, the oxygen-diffusion-limited kinetics of the dioxide to sesquioxide conversion were obtained by dynamically heating a PuO2-covered Pu sample from 294 to 418 K in a high-vacuum vessel equipped with an in situ spectroscopic ellipsometer. The physical/chemical constraints in the conversion process were combined with the ellipsometry method of multi-sample analysis to track the percentage of PuO2 and to compute the extent of Pu2O3 formation. The resulting diffusion coefficients were compared against and then combined with complementary literature data to produce a comprehensive set of kinetic parameters for reliably modeling oxide conversion over a larger temperature range than spanned by prior studies. The extracted thermal activation energy barrier (43.7 kJ/mol) and pre-exponential factor (5.0 × 10-10 cm2/s) for the oxygen-diffusion-limited process can be used to accurately model the PuO2 to Pu2O3 transformation in vacuum and/or inert gas applications.

Optical properties and stability of small hollow gold nanoparticles.

In the current work, small hollow Au nanoparticles (d ≈ 16 nm) with excellent thermal stability and high photo-thermal conversion efficiency, which have great potential for use in photo-thermal cancer therapy, were prepared through galvanic replacement reaction between Ag nano-templates and gold salt. The position of surface plasmon resonance (SPR) bands for these nanoparticles could be tuned by varying the amount of gold salt. The hydrophobic hollow nanostructures were made water-dispersible by being encapsulated with poly(maleic anhydride-alt-1-octadecene) - PMAO. The obtained nanostructures were stable in an aqueous solution of NaCl with concentration up to 280 mM. The hollow gold nanoparticles (HGNPs) were then heated using an 808 nm laser at different power densities, the obtained data showed that they are highly photo-thermal stable under a high power density laser up to 1.6 W cm-2 after three circles of irradiation at 20 min per circle (20 min continuous irradiation for each circle). The facile synthesis of small size HGNPs with a plasmon peak in the near infrared range, colloidal and photo-thermal stability, and high capacity of conversion of photon energy into heat makes them a promising material for photo-thermal and imaging applications.

Practitioner Education and Feedback to Decrease Ciprofloxacin Prescriptions in Patients with Acute Uncomplicated Cystitis.

CONTEXT: Current guidelines recommend a nonfluoroquinolone agent as first-line treatment of acute uncomplicated cystitis (AUC) because of concerns of antimicrobial resistance and adverse effects. OBJECTIVE: To test whether a multifaceted intervention involving education and feedback reduced primary care practitioners' ciprofloxacin prescriptions for AUC therapy. DESIGN: Primary care practitioners at 3 medical offices participated: 65 in the intervention group and 51 in the control group. Intervention group participants received an educational lecture and emailed summary of antimicrobial guidelines, their AUC prescriptions were audited, and feedback was provided on inappropriate antibiotic choices. Prescriptions at AUC encounters were tracked during baseline, intervention, and postintervention periods. MAIN OUTCOME MEASURES: Proportion of AUC encounters at which ciprofloxacin was prescribed vs recommended first-line antibiotics. RESULTS: Intervention group participants had 5262 eligible AUC encounters, and control group participants had 5473. At baseline, ciprofloxacin was prescribed at 29.7% and 33.7% of eligible AUC encounters in the intervention and control groups, respectively (p = 0.003). After intervention, ciprofloxacin was prescribed at 10.8% of eligible AUC encounters in the intervention group and 34.3% in the control (p < 0.001). Adjusted odds ratios of ciprofloxacin prescription for AUC therapy were significantly lower in the intervention group during postintervention and intervention periods vs baseline (0.29, 95% confidence interval = 0.20-0.44, p < 0.001 and 0.80, 95% confidence interval = 0.66-0.97, p = 0.03). Adjusted odds ratios did not change over time in the controls. CONCLUSION: Educating primary care practitioners and conducting audit and feedback reduced their prescriptions of ciprofloxacin for AUC therapy.

Growth scaling for the early dynamics of HIV/AIDS epidemics in Brazil and the influence of socio-demographic factors.

The early dynamics of an infectious disease outbreak can be affected by various factors including the transmission mode of the disease and host-specific factors. While recent works have highlighted the presence of sub-exponential growth patterns during the early phase of epidemics, empirical studies examining the contribution of different factors to early epidemic growth dynamics are lacking. Here we aim to characterize and explain the early incidence growth patterns of local HIV/AIDS epidemics in Brazil as a function of socio-demographic factors. For this purpose, we accessed annual AIDS incidence series and state-level socio-demographic variables from publicly available databases. To characterize the early growth dynamics of the HIV/AIDS epidemic, we employed the generalized-growth model to estimate with quantified uncertainty the scaling of growth parameter (p) which captures growth patterns ranging from constant incidence (p=0) to sub-exponential (0 < p < 1) and exponential growth dynamics (p=1) at three spatial scales: national, regional, and state levels. We evaluated the relationship between socio-demographic variables and epidemic growth patterns across 27 Brazilian states using mixed-effect regression analyses. We found wide variation in the early dynamics of the AIDS epidemic in Brazil, displaying sub-exponential growth patterns with the p parameter estimated substantially below 1.0. The mean p was estimated to be 0.81 at the national level, with a range of 0.72-0.85 at the regional level, and a range of 0.28-0.96 at the state level. Our findings support the notion that socio-demographic factors contribute to shaping the early growth dynamics of the epidemic at the local level. Gini index and socio-demographic index were negatively associated with the parameter p, whereas urbanicity was positively associated with p. The results could have theoretical significance in understanding differences in growth scaling across different sexually transmitted disease systems, and have public health implications to guide control.

Temperature-Dependent Kinetic Prediction for Reactions Described by Isothermal Mathematics.

Most kinetic models are expressed in isothermal mathematics. This may lead unaware scientists either to the misconception that classical isothermal kinetic models cannot be used for any chemical process in an environment with a time-dependent temperature profile or, even worse, to a misuse of them. In reality, classical isothermal models can be employed to make kinetic predictions for reactions in environments with time-dependent temperature profiles, provided that there is a continuity/conservation in the reaction extent at every temperature-time step. In this article, fundamental analyses, illustrations, guiding tables, and examples are given to help the interested readers using either conventional isothermal reacted fraction curves or rate equations to make proper kinetic predictions for chemical reactions in environments with temperature profiles that vary, even arbitrarily, with time simply by the requirement of continuity/conservation of reaction extent whenever there is an external temperature change.

A randomised controlled trial of cemented and cementless femoral components for metal-on-metal hip resurfacing: a bone mineral density study.

The primary purpose of this study of metal-on-metal (MoM) hip resurfacing was to compare the effect of using a cementless or cemented femoral component on the subsequent bone mineral density (BMD) of the femoral neck. This was a single-centre, prospective, double-blinded control trial which randomised 120 patients (105 men and 15 women) with a mean age of 49.4 years (21 to 68) to receive either a cemented or cementless femoral component. Follow-up was to two years. Outcome measures included total and six-point region-of-interest BMD of the femoral neck, radiological measurements of acetabular inclination, neck-shaft and stem-shaft angles, and functional outcome scores including the Harris hip score, the Western Ontario and McMaster Universities Osteoarthritis Index and the University of California at Los Angeles activity scale. In total, 17 patients were lost to follow-up leaving 103 patients at two years. There were no revisions in the cementless group and three revisions (5%) in the cemented group (two because of hip pain and one for pseudotumour). The total BMD was significantly higher in the cementless group at six months (p < 0.001) and one year (p = 0.01) than in the cemented group, although there was a loss of statistical significance in the difference at two years (p = 0.155). All patient outcomes improved significantly: there were no significant differences between the two groups. The results show better preservation of femoral neck BMD with a cementless femoral component after two years of follow-up. Further investigation is needed to establish whether this translates into improved survivorship.

Mechanism and kinetic modeling of hydrogenation in the organic getter/palladium catalyst/activated carbon systems.

Experiments to measure the hydrogen uptake kinetics of DEB getter/Pd catalyst/activated carbon pellets have been performed under isothermal isobaric conditions. The extracted kinetics were then used to predict the performance of the getter pellets under different temperatures and pressures, including nonisobaric situations. For isothermal isobaric uptake at higher H2 pressure (666.6-2666.5 Pa), H2 solubility in the getter matrix is responsible for the uptake observed up to a 40-60% reacted fraction. Once the hydrogenated product becomes thicker, the diffusions of the reactants (atomic hydrogen and getter molecules) toward the reaction front become the rate limiting step. However, in a dynamic but very low H2 pressure, encountered in many vacuum electronic applications, the hydrogen spillover effect, over micrometer scale, becomes the dominant reaction mechanism. Despite such a complex dependence of the rate limiting mechanisms on the experimental environment, there is good agreement between kinetic prediction models and experiments. The investigation also reveals that the ultimate uptake capacity in the getter pellets scales inversely with the free volume of the vacuum vessel in which the DEB getter pellets are used, and that DEB getter pellets' performance greatly deteriorates during the final 10-15% capacity (as evidenced by the sharp bend in the slopes of the reacted fraction vs time curves at 85-90% reacted fraction).

Peri-acetabular bone mineral densityin total hip replacement.

OBJECTIVES: To quantify and compare peri-acetabular bone mineral density (BMD) between a monoblock acetabular component using a metal-on-metal (MoM) bearing and a modular titanium shell with a polyethylene (PE) insert. The secondary outcome was to measure patient-reported clinical function. METHODS: A total of 50 patients (25 per group) were randomised to MoM or metal-on-polyethlene (MoP). There were 27 women (11 MoM) and 23 men (14 MoM) with a mean age of 61.6 years (47.7 to 73.2). Measurements of peri-prosthetic acetabular and contralateral hip (covariate) BMD were performed at baseline and at one and two years' follow-up. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC), University of California, Los Angeles (UCLA) activity score, Harris hip score, and RAND-36 were also completed at these intervals. RESULTS: At two years, only zone 1 showed a loss in BMD (-2.5%) in MoM group compared with a gain in the MoP group (+2.2%). Zone 2 showed loss in both groups (-2.2% for MoM; -3.9% for MoP) and zones 3 and 4 a gain in both groups (+0.1% for MoM; +3.3% for MoP). No other between-group differences were detected. When adjusting for BMD of the contralateral hip, no differences in BMD were observed. The only significant differences in functional scores at two years were higher UCLA activity (7.3 (sd 1.2) vs 6.1 (sd 1.5); p = 0.01) and RAND-36 physical function (82.1 (sd 13.0) vs 64.5 (sd 26.4); p = 0.02) for MoM bearings versus MoP. One revision was performed in the MoM group, for aseptic acetabular loosening at 11 months. CONCLUSIONS: When controlling for systemic BMD, there were no significant differences between MoM and MoP groups in peri-acetabular BMD. However, increasing reports of adverse tissue reactions with large head MoM THR have restricted the use of the monoblock acetabular component to resurfacing only.

Controlled manipulation of elastomers with radiation: Insights from multiquantum nuclear-magnetic-resonance data and mechanical measurements.

Filled and cross-linked elastomeric rubbers are versatile network materials with a multitude of applications ranging from artificial organs and biomedical devices to cushions, coatings, adhesives, interconnects, and seismic-isolation, thermal, and electrical barriers. External factors such as mechanical stress, temperature fluctuations, or radiation are known to create chemical changes in such materials that can directly affect the molecular weight distribution (MWD) of the polymer between cross-links and alter the structural and mechanical properties. From a materials science point of view it is highly desirable to understand, affect, and manipulate such property changes in a controlled manner. Unfortunately, that has not yet been possible due to the lack of experimental characterization of such networks under controlled environments. In this work we expose a known rubber material to controlled dosages of γ radiation and utilize a newly developed multiquantum nuclear-magnetic-resonance technique to characterize the MWD as a function of radiation. We show that such data along with mechanical stress-strain measurements are amenable to accurate analysis by simple network models and yield important insights into radiation-induced molecular-level processes.

Chinese medicinal herb Scutellaria barbata modulates apoptosis and cell survival in murine and human prostate cancer cells and tumor development in TRAMP mice.

Scutellaria barbata (SB) has been used in Chinese medicine to treat various cancers. This study investigated the effects of SB on prostate cancer prevention. Male TRansgenic Adenocarcinoma Mouse Prostate (TRAMP) mice at 9 weeks were randomly divided into four groups and given daily oral feedings of 8, 16, or 32 mg SB or sterilized water. In the control group, palpable tumors initially appeared at 19 weeks of age and were present in all mice by 32 weeks. In the respective treatment groups, palpable tumor development was delayed by 2, 4, and 7 weeks and 22, 30, and 38% of the mice were free of palpable tumors. Palpable tumor development in 50% of the mice occurred at 25 weeks in the placebo group, 29 weeks in the low-dose and mid-dose treatment groups, and 33 weeks in the high-dose group (log rank, P = 0.0211). Histological assessment further showed that the SB treatment (32 mg) delayed prostate tumor progression in the TRAMP mice. Caspase 3 activation was observed in SB-treated prostate tissue. Positive TUNEL assay results were detected in TRAMP-C1 and LNCaP cells treated with SB (1 mg/ml), which indicated significant apoptosis induction. Western blotting of SB-treated LNCaP cells also showed elevated expression of Bax, p53, Akt, and JNK. In-vivo data showed that the SB delayed tumor development in TRAMP mice. Complementary in-vitro data indicated that SB might exert this function by upregulating the apoptotic pathway and downregulating the survival pathway in prostate cancer cells, thus suggesting that SB possesses chemopreventive properties and has potential for cancer treatment.

Environmental enrichment selectively increases glutamatergic responses in layer II/III of the auditory cortex of the rat.

Prolonged exposure to environmental enrichment (EE) induces behavioral adaptation accompanied by detectable morphological and physiological changes. Auditory EE is associated with an increased auditory evoked potential (AEP) and increased auditory gating in the primary auditory cortex. We sought physiological correlates to such changes by comparing synaptic currents in control vs. EE-raised rats, in a primary auditory cortex (AI) slice preparation. Pharmacologically isolated glutamatergic or GABA(A)-receptor-mediated currents were measured using perforated patch whole-cell recordings. Glutamatergic AMPA receptor (AMPAR)-mediated excitatory postsynaptic currents (EPSCs) displayed a large amplitude increase (64+/-11% in EE vs. control) accompanied by a rise-time decrease (-29+/-6% in EE vs. control) and decrease in pair pulse ratio in layer II/III but not in layer V. Changes in glutamatergic signaling were not associated with changes in the ratio between N-methyl-D aspartate-receptor (NMDAR)-mediated vs. AMPAR-mediated components, in amplitude or pair pulse ratio of GABAergic transmission, or in passive neuronal properties. A realistic computational model was used for integrating in vivo and in vitro results, and for determining how EE synapses correct for phase error of the inputs. We found that EE not only increases the mean firing frequency of the responses, but also improves the robustness of auditory processing by decreasing the dependence of the output firing on the phase difference of the input signals. We conclude that behavioral and electrophysiological differences detected in vivo in rats exposed to an auditory EE are accompanied and possibly caused by selective changes in cortical excitatory transmission. Our data suggest that auditory EE selectively enhances excitatory glutamatergic synaptic transmission in layer II/III without greatly altering inhibitory GABAergic transmission.

H2O outgassing from silica-filled polysiloxane TR55.

Temperature-programmed desorption/decomposition (TPD) was employed to obtain the moisture content and outgassing kinetics of TR55, a silica-filled cross-linked polysiloxane. The total moisture content of TR55 in the as-received state and after 20-30 min of vacuum pumping in the load-lock prior to TPD was measured to be on the order of 0.35 wt%. Physisorbed H(2)O and chemisorbed H(2)O account for about 13.2 and 86.8%, respectively, of the 0.35 wt% measured moisture content. H(2)O outgassing models based on the kinetics measured from TPD experiments suggest that loosely bound chemisorbed water outgasses in a dry environment slowly but continuously over many decades at or a little above room temperature. However, physisorbed water can be easily pumped out in a matter of hours at around 400 K.

Interaction of various Piper methysticum cultivars with CNS receptors in vitro.

Methanolic leaf and root extracts of the Hawaiian kava (Piper methysticum Forst.) cultivars, Mahakea, Nene, Purple Moi and PNG, were tested on binding affinities to CNS receptors including GABAA (GABA and benzodiazepine binding site), dopamine D2, opioid (mu and delta), serotonin (5-HT6 and 5-HT7) and histamine (H1 and H2). HPLC analysis was carried out in order to determine the amount of the main kavalactones kavain, 7,8-dihydrokavain, methysticin, 7,8-dihydromethysticin, yangonin and 5,6-demethoxyyangonin. The most potent binding inhibition was observed for leaf extracts to GABAA receptors (GABA binding site) with IC50 values of approximately 3 micrograms/ml, whereas root extracts were less active with IC50 values ranging from 5 micrograms/ml (Nene) to 87 micrograms/ml (Mahakea). Since the leaf extracts generally contained lower amounts of the kavalactones than the root extracts, there might exist additional substances responsible for these activities. Leaf extracts also inhibited binding to dopamine D2, opioid (mu and delta) and histamine (H1 and H2) receptors more potently than the corresponding root extracts with IC50 values ranging from 1 to 100 micrograms/ml vs. > or = 100 micrograms/l, respectively. Significant differences in the potential of binding inhibition were also observed between cultivars. Binding to serotonin (5-HT6 and 5-HT7) and benzodiazepine receptors was only weakly inhibited by both root and leaf extracts of all four cultivars. In conclusion, our investigation indicates that the GABAA, dopamine D2, opioid (mu and delta) and histamine (H1 and H2) receptors might be involved in the pharmacological action of kava extracts. Since the cultivars contained similar amounts of kavalactones, while their pharmacological activities differed markedly, other constituents may play a role in the observed activities. Additionally, leaves generally exhibited more potent binding inhibition than roots, therefore leaf of P. methysticum might be an interesting subject for further pharmacological studies.

Do saw palmetto extracts block human alpha1-adrenoceptor subtypes in vivo?

BACKGROUND: To test whether saw palmetto extracts, which act as alpha1-adrenoceptor antagonists in vitro, also do so in vivo in man. METHODS: In a placebo-controlled, double-blind, four-way cross-over study 12 healthy young men were treated with three different saw palmetto extract preparations (320 mg o.d.) for 8 days each. On the last day, before and 2, 4 and 6 hr after drug intake blood pressure and heart rate were determined and blood samples obtained, which were used in an ex vivo radioreceptor assay with cloned human alpha1-adrenoceptor subtypes. RESULTS: Saw palmetto extract treatment did not result in alpha1-adrenoceptor subtype occupancy in the radioreceptor assay. Although the saw palmetto extracts caused minor reductions of supine blood pressure, they did not affect blood pressure during orthostatic stress testing and did not alter heart rate under either condition. Moreover, plasma catecholamines remained largely unaltered. CONCLUSIONS: Despite their alpha1-adrenoceptor antagonist effects in vitro, therapeutically used doses of saw palmetto extracts do not cause alpha1-adrenoceptor antagonism in man in vivo.

Accounting for radioactivity before and after nebulization of tobramycin to insure accuracy of quantification of lung deposition.

The ability to predict drug deposition of inhaled drugs used in cystic fibrosis (CF) is important if there is a need to target specific doses of drug to the lungs of individual patients. The gold standard of measuring pulmonary deposition is the quantification of an aerosolized radiolabel either mixed with the drug solution or tagged directly to the compound of interest. Accuracy of the quantification could be assured if there is agreement between the amount of radioactivity before and after administration. Before administration, the radiolabel is concentrated in the well of the nebulizer, whereas after administration, it is distributed throughout the nebulizer, the expiratory filter and connectors, and the upper airway, stomach, trachea, and lung. Not only is the geometry of the distribution that is presented to the gamma camera different, but there are different attenuation factors for the various body tissues. The primary aim of this study was to evaluate the accuracy of the quantification of deposition. Secondary goals were to compare in vitro nebulizer performance with that measured in vivo during the deposition study. Eighty milligrams of tobramycin and technetium bound to human serum albumin was administered to 10 normal adults using a Pari LC Jet Plus (Pari Respiratory Equipment, Inc., Richmond, VA) breath-enhanced nebulizer. Techniques were developed that allowed for the accounting of 99 +/- 2% of the initial radioactivity. The fraction of the rate of lung deposition to total body deposition was the in vivo respirable fraction (0.62 +/- 0.07), which closely agreed with in vitro measurements of respirable fraction (0.62 +/- 0.04). Drug output measured from the change in weight and concentration in the nebulizer systematically overestimated drug output measured by the deposition study. The results indicate that 11.8 of the initial 80 mg would be deposited in the lungs. This technique could be adapted to accurately quantify the amount of deposition on any inhaled therapeutic agent, but caution must be used when extrapolating performance of a nebulizer on the bench to expected deposition in patients.

Vitamin E deficiency has different effects on brain and liver phospholipid hydroperoxide glutathione peroxidase activities in the rat.

The effect of vitamin E deficiency on glutathione peroxidase activity (GPX) and on the activity of a selenoenzyme (phospholipid hydroperoxide glutathione peroxidase (PHGPX) was measured in rat brain and liver. In brain, the activity of both enzymes was in the same range in homogenate and in microsomes. In contrast, in liver homogenate, PHGPX activity was approximately 20 times lower than that of GPX. Very interestingly, PHGPX activity was significantly decreased in brain microsomes by vitamin E deficiency, but slightly significantly increased in liver microsomes. In contrast, GPX activity was not affected in brain by vitamin E deficiency, but was significantly lower in liver homogenate and microsomes. Thus, PHGPX activity is partially controlled by vitamin E in membranes, and PHGPX is probably an enzyme different from GPX.

Restricted unilateral Sydenham's chorea: reversible contralateral striatal hypermetabolism demonstrated on single photon emission computed tomographic scanning.

Sydenham's chorea results from group A streptococcus infection and subsequent generation of antineuronal antibodies directed at the caudate nucleus and putamen. Predominantly bilateral, in up to 30% of cases the chorea can be unilaterally restricted. Imaging studies, both structural (magnetic resonance imaging) and functional (positron emission tomography), in patients with bilateral Sydenham's chorea have suggested reversible striatal abnormalities. Two patients with unilateral Sydenham's chorea are presented. Computed tomographic and magnetic resonance imaging were normal in both. However, hexamethylpropylenamine oxime single photon emission tomographic (HMPAO SPECT) studies demonstrated hypermetabolism in the contralateral basal ganglia. Resolution of symptoms in one of the patients coincided with normalization of the SPECT scan. Thus, unilateral striatal hypermetabolism appears to underlie the contralateral chorea observed. A SPECT scan probably should be included in the work-up of new-onset chorea.

Supranormal renographic differential renal function in congenital hydronephrosis: fact, not artifact.

PURPOSE: Children with unilateral hydronephrosis, who had been prospectively examined with diethylenetriaminepentaacetic acid (DTPA) and dimercapto-succinic acid (DMSA) renography, were evaluated to determine whether supranormal renographic differential renal function exists. MATERIALS AND METHODS: A total of 54 children with congenital single system hydronephrosis underwent abdominal ultrasound, voiding cystourethrogram, and DTPA and DMSA renal scans. None had abnormalities of the bladder or contralateral kidney. Differential renal function greater than 55% was defined as supranormal. RESULTS: Of the 54 patients 15 (28%) with a median age of 4 months (range 0.5 to 66) were identified with supranormal renographic renal function on either DTPA or DMSA. Supranormal renographic renal function was detected by DMSA in 9 cases (mean 57+/-2%), DTPA in 8 (mean 58+/-2%) and both in 2 (mean 57+/-2%). Average function demonstrated in the 15 patients was 55+/-3% (range 51 to 62) with DMSA which was not different from that found with DTPA (mean 55+/-4%, range 46 to 61%). The kidneys with supranormal renographic renal function were significantly larger than hydronephrotic controls according to longitudinal parenchymal area on DMSA. Mean followup was 20 months for 13 patients, with 8 of 13 (62%) undergoing pyeloplasty. Followup DTPA renal scans available in 9 children revealed persistent supranormal function in 6, despite pyeloplasty in 3. CONCLUSIONS: Supranormal renographic differential renal function does exist in congenital hydronephrosis and when found the kidneys are consistently enlarged. The position of supranormal renographic renal function in the management algorithm of hydronephrosis remains to be elucidated as it does not appear to be a benign prognostic factor.

NT-3-mediated TrkC receptor activation promotes proliferation and cell survival of rodent progenitor oligodendrocyte cells in vitro and in vivo.

We have previously described the expression of a functional full-length trkC transcript for neurotrophin-3 (NT-3) receptor in oligodendroglia (OL) cells (Kumar and de Vellis, 1996). To date, the role of NT-3 and its signal transduction cascade in OL remains poorly defined. We report that the NT-3 responsive population of cells in the OL lineage are the progenitor cells and that the addition of NT-3 results in the autophosphorylation of p145TrkC. Furthermore, NT-3-mediated activation of p21ras and mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinase2 (ERK2), were also observed in the progenitor OL cells. These protein tyrosine kinase (PTK)-induced responses were sensitive to the presence of K252a, an inhibitor for tyrosine kinase. We have determined that NT-3 promotes progenitor OL cell commitment to enter into S-phase of cell cycle to initiate DNA synthesis, in a manner similar to platelet-derived growth factor-AA (PDGF-AA). NT-3 thus plays a role in cell proliferation when present alone, while augmenting the proliferation capacity of PDGF-AA as indicated by the nuclear binding activity of the transcription factor, E2F-1. Both the initiation and progression of mitotic events were confirmed by the expression of c-myc and cdc2 in the presence of NT-3, PDGF-AA or NT-3 plus PDGF-AA. A cell survival assay examining interleukin 1-beta-converting enzyme (ICE)-like protease-mediated cleavage of poly (ADP-ribose) polymerase (PARP) revealed an increase in OL progenitor cell death in the absence of NT-3 or PDGF-AA. In corroboration with our in vitro studies, in vivo results show an increased expression of the progenitor OL cell marker, glycerol phosphate dehydrogenase (GPDH) within 48 hr following an intracranial injection of NT-3, PDGF-AA, or NT-3 plus PDGF-AA in PN4-5 rats. These novel findings suggest that PDGF-AA potentiates the OL progenitor cell's ability to enter into the S-phase of the cell cycle and that NT-3 can augment this activity. Furthermore, PDGF-AA and NT-3 can block ICE-like protease-mediated PARP fragmentation in progenitor OL cells. These results provide important information which further delineates the signal transduction cascades and the role of NT-3 and PDGF-AA on OL progenitor cells.