Multienzyme-mediated stable and transient multidrug resistance and collateral sensitivity induced by xenobiotics

Several high affinity sigma (sigma) ligands, such as DTG, JO-1784, (+)-pentazocine, BD-737 and L-687,384, administered at low doses act as agonists by potentiating N-methyl-D-aspartate (NMDA)-induced activation of pyramidal neurons in the CA3 region of the rat dorsal hippocampus. This potentiation is dose-dependent at doses between 1 and 1000 micrograms/kg, IV but bell-shaped dose-response curves are obtained. Other sigma ligands like haloperidol, BMY-14802, (+)3-PPP and NE-100 administered at low doses act as sigma antagonists, since they do not modify the NMDA response but suppress the potentiation of the NMDA response induced by sigma agonists. Because high doses of the sigma agonists do not potentiate the NMDA response, the present experiments were undertaken to assess if, at high doses, these sigma ligands could also act as sigma antagonists and suppress the potentiation induced by low doses of sigma agonists. High doses of DTG, JO-1784, BD-737, and L-687,384, administered acutely, had an effect similar to that of low doses of haloperidol, by suppressing and preventing the potentiation induced by low doses of DTG, JO-1784, BD-737, L-687,384 and (+)-pentazocine. High doses of (+)-pentazocine suppressed the effect of a low dose of (+)-pentazocine but did not affect the potentiation induced by a low dose of the other sigma agonists. The potentiation induced by a low dose of a sigma 1 agonist was not further increased by the subsequent administration of another low dose of a sigma 1 agonist. All together, these results strongly suggest that more than two subtypes of sigma receptors exist in the CNS.     

A clinical trial to reduce restraints in nursing homes

Plasma concentrations of isepamicin, a new aminoglycoside antibiotic, were determined by radioimmunoassay (RIA), microbiological assay (MA), and high-performance liquid chromatography (HPLC) in healthy volunteers after administration of 7.5 mg/kg intramuscular dosages once daily for 10 days. Plasma samples were collected on days 1, 7, and 10. The limit of quantitation (LOQ) was 0.1 microg/ml for HPLC and RIA and 0.5 microg/ml for MA. The HPLC and RIA yielded superimposable plasma concentration-time curves, whereas the plasma concentrations obtained with MA appeared to be 20% to 30% lower. Regression analysis indicated good correlations among the three assays, with coefficients of correlation measuring 0.935 to 0.960 for RIA compared with HPLC, 0.925 to 0.945 for MA compared with HPLC, and 0.920 to 0.945 for RIA compared with MA.     

Role of estrogen receptor gene demethylation and DNA methyltransferase.DNA adduct formation in 5-aza-2'deoxycytidine-induced cytotoxicity in human breast cancer cells

The cytosine analog 5-aza-2'-deoxycytidine is a potent inhibitor of DNA methyltransferase. Its cytotoxicity has been attributed to several possible mechanisms including reexpression of growth suppressor genes and formation of covalent adducts between DNA methyltransferase and 5-aza-2'-deoxycytidine-substituted DNA which may lead to steric inhibition of DNA function. In this study, we use a panel of human breast cancer cell lines as a model system to examine the relative contribution of two mechanisms, gene reactivation and adduct formation. Estrogen receptor-negative cells, which have a hypermethylated estrogen receptor gene promoter, are more sensitive than estrogen receptor-positive cells and underwent apoptosis in response to 5-aza-2'-deoxycytidine. For the first time, we show that reactivation of a gene silenced by methylation, estrogen receptor, plays a major role in this toxicity in one estrogen receptor-negative cell line as treatment of the cells with anti-estrogen-blocked cell death. However, drug sensitivity of other tumor cell lines correlated best with increased levels of DNA methyltransferase activity and formation DNA.DNA methyltransferase adducts as analyzed in situ. Therefore, both reexpression of genes like estrogen receptor and formation of covalent enzyme. DNA adducts can play a role in 5-aza-2'-deoxycytidine toxicity in cancer cells.     

Relationships among alcohol availability, drinking location, alcohol consumption, and drinking problems in adolescents

We examined relationships among perceived alcohol availability, drinking location, alcohol consumption, and drinking problems. Subjects were 3,372 adolescent drinkers, ages 16-18, who participated in the Communities Mobilizing for Change on Alcohol Project baseline survey. Mixed-model regression was employed to identify predictors of alcohol consumption and drinking consequences. Perceived alcohol availability was significantly associated with higher levels of alcohol consumption for males. Drinking in a public location with higher levels of alcohol consumption for females. Results underscore the importance of youth alcohol assessibility.     

Neural substrates of crossmodal association memory in monkeys: The amygdala versus the anterior rhinal cortex.

Nine rhesus monkeys were trained on visual, tactual, and crossmodal (tactual–visual) versions of delayed nonmatching-to-sample (DNMS). They then received bilateral aspiration lesions of the anterior rhinal cortex or bilateral excitotoxic lesions of the amygdala or were retained as unoperated controls. Monkeys with anterior rhinal cortex lesions displayed a persistent deficit on crossmodal DNMS as well as a deficit on tactual DNMS. In contrast, monkeys with amygdala lesions exhibited only a transient impairment on crossmodal DNMS, and their difficulty appeared to be related to inadvertent damage to the anterior rhinal cortex. The present findings support the idea that the rhinal cortex is important for the formation and retrieval of stimulus–stimulus associations across sensory modalities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Driving and the elderly

Apoptotic cell changes occurring under certain developmental, physiological, and pathological conditions have been of increasing interest during recent years. Due to occasional difficulties in detecting apoptosis in routinely stained sections, various methods have been developed to facilitate tissue examination. Fragmentation of DNA during the process of apoptosis is a prerequisite for detection in the in situ end-labeling (ISEL) procedure. It is yet unclear whether other mechanisms of cell change that induce DNA fragmentation such as necrosis and postmortem autolysis also show positive staining with the ISEL technique. To investigate whether the ISEL assay visualizes autolytic DNA changes along with apoptotic DNA fragmentation, we tested the technique on brain tissue of mice after different time intervals (0, 6, 12, 24, 48, 72 h) of postmortem delay (PMD) and at 2 different temperatures of postmortem storage (4 degrees C and room temperature (RT)). Our semiquantitative results show that up to 24 h of PMD no prominent difference in labeling is observable at both temperatures. After 48 and 72 h of PMD at RT clusters of labeled cells begin to appear. Clusters of stained cells should therefore not be considered as apoptosis when using the ISEL assay.     

Athletics and osteoarthritis

Athletes, and an increasing number of middle aged and older people who want to participate in athletics, may question whether regular vigorous physical activity increases their risk of developing osteoarthritis. To answer this, the clinical syndrome of osteoarthritis must be distinguished from periarticular soft tissue pain associated with activity and from the development of osteophytes. Sports that subject joints to repetitive high levels of impact and torsional loading increase the risk of articular cartilage degeneration and the resulting clinical syndrome of osteoarthritis. However, moderate habitual exercise does not increase the risk of osteoarthritis; selected sports improve strength and mobility in older people and people with mild and moderate osteoarthritis. People with abnormal joint anatomy or alignment, previous significant joint injury or surgery, joint instability, above-average body weight, disturbances of joint or muscle innervation or inadequate muscle strength probably have increased risk of osteoarthritis. These people and those with early osteoarthritis can benefit from regular physical activity, but they should have a careful evaluation of their joint structure and function before participation. They should consider measures that decrease the intensity and frequency of impact and torsional loading of joints, including use of sports equipment that decreases joint impact loading, maintaining or improving muscle strength, tone, and general conditioning so that muscle contractions help protect joints from injury and high impact, and decreasing body weight.     

Parenting in mothers with and without attention-deficit/ hyperactivity disorder.

The authors examined the impact of maternal attention-deficit/hyperactivity disorder (ADHD) on parenting behaviors. Sixty mothers between the ages of 31 and 50 with (n = 30) and without (n = 30) ADHD and their 8- to 14-year-old children with ADHD completed self-report and laboratory measures of monitoring of child behavior, consistency in parenting, and parenting problem-solving abilities. These parenting behaviors were selected because of their established links to the development of child behavior problems. As predicted, mothers with ADHD were found to be poorer at monitoring child behavior and less consistent disciplinarians compared with mothers without ADHD. There was some evidence to support the prediction that mothers with ADHD were less effective at problem solving about childrearing issues than control mothers. The differences between the 2 groups of mothers persisted after child oppositional and conduct-disordered behavior were controlled. These results indicate that parenting is an area of functioning that requires more attention in adult ADHD research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regional scale impacts of Tamarix leaf beetles (Diorhabda carinulata) on the water availability of western U.S. rivers as determined by multi-scale remote sensing methods

Tamarix leaf beetles (Diorhabda carinulata) have been widely released on western U.S. rivers to control introduced shrubs in the genus Tamarix. Part of the motivation to control Tamarix is to salvage water for human use. Information is needed on the impact of beetles on Tamarix seasonal leaf production and subsequent water use over wide areas and multiple cycles of annual defoliation. Here we combine ground data with high resolution phenocam imagery and moderate resolution (Landsat) and coarser resolution (MODIS) satellite imagery to test the effects of beetles on Tamarix evapotranspiration (ET) and leaf phenology at sites on six western rivers. Satellite imagery covered the period 2000 to 2010 which encompassed years before and after beetle release at each study site. Phenocam images showed that beetles reduced green leaf cover of individual canopies by about 30% during a 6–8 week period in summer, but plants produced new leaves after beetles became dormant in August, and over three years no net reduction in peak summer leaf production was noted. ET was estimated by vegetation index methods, and both Landsat and MODIS analyses showed that beetles reduced ET markedly in the first year of defoliation, but ET recovered in subsequent years. Over all six sites, ET decreased by 14% to 15% by Landsat and MODIS estimates, respectively. However, results were variable among sites, ranging from no apparent effect on ET to substantial reduction in ET. Baseline ET rates before defoliation were low, 394 mm yr^? 1 by Landsat and 314 mm yr^? 1 by MODIS estimates (20–25% of potential ET), further constraining the amount of water that could be salvaged. Beetle–Tamarix interactions are in their early stage of development on this continent and it is too soon to predict the eventual extent to which Tamarix populations will be reduced. The utility of remote sensing methods for monitoring defoliation was constrained by the small area covered by each phenocam image, the low temporal resolution of Landsat, and the low spatial resolution of MODIS imagery. Even combined image sets did not adequately reveal the details of the defoliation process, and remote sensing data should be combined with ground observations to develop operational monitoring protocols.