An in situ tensile test apparatus for polymers in high pressure hydrogen.

Degradation of material properties by high-pressure hydrogen is an important factor in determining the safety and reliability of materials used in high-pressure hydrogen storage and delivery. Hydrogen damage mechanisms have a time dependence that is linked to hydrogen outgassing after exposure to the hydrogen atmosphere that makes ex situ measurements of mechanical properties problematic. Designing in situ measurement instruments for high-pressure hydrogen is challenging due to known hydrogen incompatibility with many metals and standard high-power motor materials such as Nd. Here we detail the design and operation of a solenoid based in situ tensile tester under high-pressure hydrogen environments up to 42 MPa (6000 psi). Modulus data from high-density polyethylene samples tested under high-pressure hydrogen at 35 MPa (5000 psi) are also reported as compared to baseline measurements taken in air.

Cytotoxic sesquiterpenoids from Ratibida columnifera.

Bioassay-directed fractionation of the flowers and leaves of Ratibida columnifera using a hormone-dependent human prostate (LNCaP) cancer cell line led to the isolation of 10 cytotoxic substances, composed of five novel xanthanolide derivatives (2-4, 7, and 8), a novel nerolidol derivative (9), and three known sesquiterpene lactones, 9alpha-hydroxy-seco-ratiferolide-5alpha-O-angelate+ ++ (1), 9alpha-hydroxy-seco-ratiferolide-5alpha-O-(2-methylbut yrate) (5), 9-oxo-seco-ratiferolide-5alpha-O-(2-methylbutyrate) (6), as well as a known flavonoid, hispidulin (10). On the basis of its cytotoxicity profile, compound 5 was selected for further biological evaluation, and was found to induce G1 arrest and slow S traverse time in parental wild type p53 A2780S cells, but only G2/M arrest in p53 mutant A2780R cells, with strong apoptosis shown for both cell lines. The activity of 5 was not mediated by the multidrug resistance (MDR) pump, and it was not active against several anticancer molecular targets (i.e., tubulin polymerization/depolymerization, topoisomerases, and DNA intercalation). While these results indicate that compound 5 acts as a cytotoxic agent via a novel mechanism, this substance was inactive in in vivo evaluations using the murine lung carcinoma (M109) and human colon carcinoma (HCT116) models.

Triterpenes from the combined leaf and stem of Lithospermum caroliniense.

An investigation of the combined leaf and stem of Lithospermum caroliniense afforded two new pentacyclic triterpenoids based on the olean-12-ene and taraxast-12-ene skeletal types. The structures of these compounds were elucidated on the basis of spectral analysis as 1 alpha,3 beta,23-trihydroxyolean-12-ene-28-oic acid and 3 alpha,19 beta,21 alpha,23-tetrahydroxytaraxast-12-ene-28-oic acid.

Two isoflavones from the bark of Petalostemon purpureus.

Two new isoflavones, 6,7,8,3',4',5'-hexamethoxyisoflavone and 7,8,3',4',5'-pentamethoxyisoflavone, have been isolated and characterized from the combined root bark and stem bark of Petalostemon purpureus.

A new prenylated flavonol from the root of Petalostemon purpureus.

A new prenylated flavonol, petalopurpurenol (1), and a known dihydroflavonol, petalostemumol (2), have been isolated by DNA scission-guided fractionation of the organic portion of a 20% MeOH/CHCl3/H2O partition of a 50% MeOH/CHCl3 extract of the roots of Petalostemon purpureus. Compound 2 displayed moderate activity in DNA-scission assay. Both compounds 1 and 2 were evaluated for cytotoxicity in a panel of human cancer cell lines. The structures of petalopurpurenol (1) and petalostemumol (2) were determined by spectroscopic analysis.

Two isoflavones from the bark of Petalostemon purpureus.

Two new isoflavones, 6,7,8,3',4',5'-hexamethoxyisoflavone and 7,8,3',4',5'-pentamethoxyisoflavone, have been isolated and characterized from the combined root bark and stem bark of Petalostemon purpureus.

A rapid technique for visualizing cerebral arteries in rat.

Intracardiac perfusion with cresyl violet acetate dissolved in 0.9% isotonic saline and dimethyl sulfoxide (DMSO) allows one to visualize the arterial blood supply to the central hemispheres. This technique is especially useful in demonstrating the ramifications of and areas supplied by the middle cerebral artery. Many individual differences in the course traversed by the artery and the distal areas supplied were observed. This technique could prove to be a useful adjunct to neurohistological techniques in studies investigating rodent models of stroke.

A behavioral study of bilateral middle cerebral artery hemorrhagic ischemia in rats.

The middle cerebral artery was severed bilaterally (bMCA) in adult rats, and controls experienced sham operations. Tactile sensorimotor and gross locomotor functions, measured by the tape test and a rod walking test, were initially impaired in the injured animals. However, these deficits had resolved within 9 and 30 days respectively. The animals were trained in a multiple T water maze task to find the location of a hidden escape platform at the rate of one trial per day for 30 days. Analyses of the number of errors committed and latency to find the escape platform revealed that the bMCA injured rats suffered deficient reference memory, but no decline in working memory. These data support further the use of the bMCA preparation as a model of stroke.

The behavioral effects of bilateral middle cerebral artery hemorrhagic ischemia in rat.

After learning position discrimination in a T-maze water escape task, rats had either a 2 mm section of the middle cerebral artery removed bilaterally (bMCA) or they received a sham operation. Beginning on the day of surgery either total brain gangliosides (50 mg kg-1) or saline were administered daily for five days. Of the several measures of neurological function that were tested, only a temporary deficit in grasping with the front paws was observed in bMCA damaged rats. Ganglioside treatment normalized this practical function. Memory of the preoperative habit was not influenced by bMCA damage, but acquisition of a reversal of this habit was compromised. Ganglioside treatment did not influence this deficit. Acquisition of a spatial alternation strategy was influenced by neither the bMCA lesion nor the ganglioside treatment. The preservation that accompanies bMCA interruption might serve as a useful model of the functional declines that accompany stroke and frontal lobe damage.

Behavioral consequences of antidepressant treatment in rodents.

This review discusses the effects of antidepressant drugs on behaviors that are changed during the clinical treatment of depression. We first consider whether there is a similar subjective state produced by antidepressant drugs that might be akin to the mood changes caused clinically by these drugs. We thus review the evidence that antidepressant drugs can produce a distinctive enough subjective state to serve as a discriminative stimulus, and then discuss the nature of the cue produced. Secondly, we discuss whether there is any evidence that antidepressants enhance the rewarding aspects of stimuli since this aspect of behavior is reported to change during the successful treatment of depression. In this section we review the effects on electrical brain stimulation, water and food intake, exploratory and social behaviors. Finally, because of the proposed role of stress in the aetiology of depression, we review the effects of antidepressants on the responses to acute and chronic stress.

The effects of tricyclic and 'atypical' antidepressants on spontaneous locomotor activity in rodents.

With the exception of amineptin, buproprion and nomifensine all tricyclic and 'atypical' antidepressants have been reported to reduce spontaneous motor activity in rodents, after both acute and chronic administration. However, with the diversity of chemical actions of these drugs it is unlikely that a single neurochemical mechanism is underlying this one behavioral effect. These widespread sedative effects have implications for interpreting behavioral changes in other test situations, since sedation generally occurs at doses that fall within the dose-range effective in other tests. We also review the effects on spontaneous motor activity of withdrawal from chronic antidepressant treatment.

Benzodiazepines and the developing rat: a critical review.

This paper reviews: the development of benzodiazepine binding-sites and the GABA system; the evidence that prenatal exposure to benzodiazepines can cause malformations; other persisting effects of developmental exposure to benzodiazepines; and the behavioral effects of benzodiazepines (and other relevant drugs) in immature animals. The review concentrates on the rat, since fundamental work in other species is scarce. The data on neurochemical development are found to be generally consistent; however, reports that the enhancement of benzodiazepine binding by GABA varies with age are controversial. The physical development of the rat is disturbed only by extremely high doses of benzodiazepines. The evidence for persisting effects after early exposure to benzodiazepines is impressive at first sight, but in most studies, confounding variables have not been eliminated. Startle and some learning tasks are affected by prenatal diazepam; submissiveness is affected by neonatal lorazepam; social behaviour and convulsions are affected by neonatal CGS 8216. Benzodiazepines inhibit chemically-induced seizures in neonatal rats, but the developmental profile of sensitivity to the convulsants is disputed. Benzodiazepines stimulate motor behavior in the neonatal rat.

Intrinsic behavioural actions of n-propyl beta-carboline-3-carboxylate.

The behavioural effects of n-propyl beta-carboline-3-carboxylate (beta-CCP) were assessed in the social interaction test of anxiety and in the holeboard test of exploratory behaviour. n-Propyl beta-carboline-3-carboxylate (2 mg/kg) significantly reduced the time spent in social interaction without affecting locomotor activity, indicating an anxiogenic action. This reduction was not significantly reversed by chlordiazepoxide (3 mg/kg). In the holeboard, beta-CCP (4 mg/kg) reduced exploratory head-dipping and rearing; neither of these effects was significantly reversed by chlordiazepoxide (5 mg/kg). The actions of beta-CCP in these two tests are similar to those of the structurally-related compound ethyl beta-carboline-3-carboxylate.

Chronic neonatal treatment with CGS 8216: effects on the behaviour of adolescent rats.

The behaviour of male adolescent rats was studied after neonatal administration of CGS 8216 (2.5 or 10 mg/kg/day). The pups were cross-fostered, and drug treatment (in a split-litter design) lasted from postnatal day 7 to day 28; behavioural tests began on day 31. In the social interaction test, neonatally-treated adolescents displayed an unusual profile of behaviour that was the opposite to the profile caused by acute CGS 8216 in adults. Their response to challenge doses of CGS 8216 was not significantly different from that of neonatal controls. In the holeboard test of exploratory behaviour, there was little sign of effects of the neonatal treatment, and the response to challenge doses of Ro 15-1788 or chlordiazepoxide was not differentially affected. However, neonatally-treated animals were less sensitive to the convulsant effects of pentylenetetrazole and picrotoxin. Lasting effects of neonatal CGS 8216 have been detected in adults; the effects seen in adolescents appear not to be identical, since a proconvulsant effect occurs in adults.

Lasting behavioral effects after treating rats with CGS 8216 on postnatal days 9 to 21.

The lasting effects of chronic exposure to CGS 8216 in early postnatal life were studied in the social interaction test of anxiety, the holeboard test of exploratory behavior, a startle test and on convulsions induced by pentylenetetrazole. Male rat pups were treated with CGS 8216 (10 or 20 mg/kg/day) from postnatal day 9 until weaning (day 21), and tested in adulthood. In the social interaction test, the pups that had been exposed to CGS 8216 during development showed increased social interaction in both unfamiliar and familiar test conditions, (particularly the latter), in contrast to the decrease in social interaction that results when CGS 8216 is given acutely to adult animals. Conversely, the developmentally-treated rats were more sensitive to the convulsant effects of pentylenetetrazole, and this effect is in the same direction as that seen in adults after acute administration. No effects of the early treatment were detected in adult animals in the holeboard or startle tests.

Prenatal treatment with clomipramine: effects on the behaviour of male and female adolescent rats.

The tricyclic anti-depressant clomipramine (7.5 or 15 mg/kg/day) was administered to pregnant rats between days 8 and 21 of gestation. Between postnatal days 31 and 47, both male and female offspring received three behavioural test. Prenatal clomipramine (15 mg/kg/day) increased baseline acoustic startle in females, but not in males; both sexes showed greater between-day response decrements if they had received clomipramine. In the social interaction test of anxiety, males prenatally exposed to clomipramine (both dosages), and females prenatally exposed to 7.5 mg/kg/day, revealed a similar profile to that seen after chronic administration of benzodiazepines in the adult. The likelihood that differences in within-session habituation could underlie the changes in social interaction that have been found in this and other studies is assessed.

Prenatal treatment with clomipramine has an anxiolytic profile in the adolescent rat.

The tricyclic anti-depressant clomipramine (3, 10 or 30 mg/kg/day) was administered to pregnant rats between days 8 and 21 of gestation. Male pups were cross-fostered at birth and raised in litters of eight. After weaning (postnatal day 21) the offspring were raised in an enriched environment and were then subjected to a variety of behavioral tests, lasting through adolescence (days 35 to 42), and repeated in adulthood (day 70 onwards). As has been found when imipramine was administered prenatally, the offspring showed decreased rearing and less exploration; however, the latter was entirely due to more rapid habituation to the test environment. The treatment produced an anxiolytic profile when the adolescents were tested in the Social Interaction test of anxiety. Effects did not persist into adulthood, although it may be that this was the result of repeated testing.

Lorazepam treatment in the neonatal rat alters submissive behavior in adulthood.

Male hooded Lister rats were cross-fostered at birth (day 0) and reared in litters of eight. Within each litter, one pup was treated with each dose of lorazepam (0.25 or 1.25 mg/kg) and one was treated with the placebo vehicle. The pups received daily subcutaneous injections between postnatal days 7 and 21 inclusive. Starting on day 70 the animals were subjected to four tests of exploratory and social behavior: Open Field, Holeboard, Social Interaction and Home-Cage Aggression. The drug-treated animals showed an increase in submissive behavior, particularly when intruding into another animal's territory, but only minimal changes in their performance in the other three tests.

Neonatal clomipramine treatment in the rat does not affect social, sexual and exploratory behaviors in adulthood.

The potential ability of the tricyclic anti-depressant clomipramine to cause an increase in anxiety in adult animals following neonatal treatment with the drug has been investigated; no such anxiogenic actions were found in the social interaction test. Furthermore, the behavior of animals that had received the drug as pups did not differ from that of the controls in open field or holeboard tests, nor in tests of sexual behavior, aggressive and dominance behaviors or passive avoidance learning.