Targeting Antiapoptotic Genes Upregulated by Androgen Withdrawal Using Antisense Oligodeoxynucleotides to Enhance Androgen-and Chemo-Sensitivity in Prostate Cancer

Androgen withdrawal is the only effective form of systemic therapy for men with advanced disease, producing symptomatic and/or objective response in 80% of patients. Unfortunately, androgen independent (AI) progression and death occurs within a few years in the majority of these cases (6). Prostate cancer is highly chemoresistant, with objective response rates of 10% and no demonstrated survival benefit (28). Hormone refractory prostate cancer (HRPC) is therefore the main obstacle to improving the survival and quality of life in patients with advanced disease, and novel therapeutic strategies that target the molecular basis of androgen and chemoresistance are required.

Reduced withdrawal and failure rates of accelerated nursing students enrolled in pharmacology is associated with a supportive intervention

Background To reduce nursing shortages, accelerated nursing programs are available for domestic and international students. However, the withdrawal and failure rates from these programs may be different than for the traditional programs. The main aim of our study was to improve the retention and experience of accelerated nursing students. Methods The academic background, age, withdrawal and failure rates of the accelerated and traditional students were determined. Data from 2009 and 2010 were collected prior to intervention. In an attempt to reduce the withdrawal of accelerated students, we set up an intervention, which was available to all students. The assessment of the intervention was a pre-post-test design with non-equivalent groups (the traditional and the accelerated students). The elements of the intervention were a) a formative website activity of some basic concepts in anatomy, physiology and pharmacology, b) a workshop addressing study skills and online resources, and c) resource lectures in anatomy/physiology and microbiology. The formative website and workshop was evaluated using questionnaires. Results The accelerated nursing students were five years older than the traditional students (p < 0.0001). The withdrawal rates from a pharmacology course are higher for accelerated nursing students, than for traditional students who have undertaken first year courses in anatomy and physiology (p = 0.04 in 2010). The withdrawing students were predominantly the domestic students with non-university qualifications or equivalent experience. The failure rates were also higher for this group, compared to the traditional students (p = 0.05 in 2009 and 0.03 in 2010). In contrast, the withdrawal rates for the international and domestic graduate accelerated students were very low. After the intervention, the withdrawal and failure rates in pharmacology for domestic accelerated students with non-university qualifications were not significantly different than those of traditional students. Conclusions The accelerated international and domestic graduate nursing students have low withdrawal rates and high success rates in a pharmacology course. However, domestic students with non-university qualifications have higher withdrawal and failure rates than other nursing students and may be underprepared for university study in pharmacology in nursing programs. The introduction of an intervention was associated with reduced withdrawal and failure rates for these students in the pharmacology course.

Survey of fish protective facilities at water withdrawal sites on the Snake and Columbia Rivers

Proliferation of water withdrawals and new pump intake and screen designs has occurred with the growth of irrigated agriculture along the Columbia and Snake Rivers. Concern for the protection of anadromous and resident fish populations resulted in formulation of a survey of the water withdrawal systems. The survey included distribution studies of juvenile fish near pump sites and field inspection of those sites to determine adequacy of screening for protection of fish. A total of 225 sites were inspected in 1979 and 1980, with a follow-up inspection of 95 sites in 1982. Results indicated a definite trend toward lack of concern for the condition of fish protective facilities. Only 4 out of 22 sites not meeting criteria in 1979 had been upgraded to acceptable conditions. Of more concern, 13 of the sites meeting criteria in 1979 were below criteria when reinspected in 1982. Some of the discrepancies included lack of protective screens, poorly maintained screens, and screens permitting excessive velocity that could result in impingement of larvae or small fish. A conclusion from these surveys is that if adequate protection for fish is to exist, screens for water withdrawals need to be properly installed, inspected, and maintained. (PDF file contains 40 pages.)

Effects of morphine and its withdrawal on Y-maze spatial recognition memory in mice

Effects of morphine on acquisition and retrieval of memory have been proven in the avoidance paradigms. In present study, we used a two-trial recognition Y-maze to test the effects of acute morphine and morphine withdrawal on spatial recognition memory. T

Dynamic changes in orbitofrontal neuronal activity in rats during opiate administration and withdrawal

The orbitofrontal cortex is involved in the reinforcing effects of drugs of abuse. However, how the dynamic activity in OFC changes during opiate administration and withdrawal period has not been investigated. We first tested the effects of opiates and dr

EEG activities in the orbitofrontal cortex and dorsolateral prefrontal cortex during the development of morphine dependence, tolerance and withdrawal in rhesus monkeys

Investigating the activities of the prefrontal cortex (PFC) in the process of addiction is valuable for understanding the neural mechanism underlying the impairments of the PFC after drug abuse. However, limited data are obtained from primate animals and few studies analyze Electroencephalogram (EEG) in the gamma band, which plays an important role in cognitive functions. In addition, it is yet unclear whether drug abuse affects the orbitofrontal cortex (OFC) and dorsolateral PFC (DLPFC) - the two most important subregions of the PFC - in similar ways or not. The aim of this study is to address these issues. We recorded EEG in the OFC and DLPFC in three rhesus monkeys. All animals received a course of saline (NaCl 0.9%, 2 ml) injection (5 days) followed by 10 days of morphine injection (every 12 h), and then a further series of saline injection (7 days). A main finding in the present study was that morphine decreased EEG power in all frequency bands in a short period after injection in both the OFC and DLPFC in monkeys. And gamma power decreased not just in short period after morphine injection but lasted to 12 h after injection. Moreover, we found that although the changes in EEG activities in the OFC and DLPFC at 30-35 min after injection were similar, the DLPFC was more sensitive to the effect of morphine than the OFC. (c) 2005 Elsevier B.V. All rights reserved.

The dynamics of hippocampal sensory gating during the development of morphine dependence and withdrawal in rats

The effects of morphine on hippocampal sensory gating (N40) during the development of morphine dependence and withdrawal were investigated in the double click auditory evoked potential (EP) suppression paradigm. Rats were made dependent upon morphine hydrochloride by a series of injections (every 12h) over 6 days, followed by withdrawal after stopping morphine administration. Hippocampal gating was examined during the development of dependence and withdrawal. Moreover, the DA antagonist haloperidol was used to assess the contribution of dopamine to hippocampal gating induced by morphine. Our results showed that the morphine-treated rats exhibited significantly disrupted hippocampal gating during the development of morphine dependence and this disrupted gating was partially reversed by haloperidol pretreatment. In contrast, there was significantly enhanced hippocampal gating at the fifth and sixth days of withdrawal. The dynamics of hippocampal gating during the development of morphine dependence and withdrawal suggests the interaction between the hippocampus and opioids. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Extremely low-frequency electromagnetic field exposure during chronic morphine treatment strengthens downregulation of dopamine D2 receptors in rat dorsal hippocampus after morphine withdrawal

The aim of this study was to investigate the effect of extremely low-frequency electromagnetic field (ELF-EMF) exposure during morphine treatment on dopamine D2 receptor (D2R) density in the rat dorsal hippocampus following withdrawal. Rats were exposed t

Stress evoked by opiate withdrawal facilitates hippocampal LTP in vivo

Stress impairs hippocampal long-term potentiation (LTP), but it is unknown whether the stress evoked by opiate withdrawal has the same effect. Here the authors report that opiate withdrawal for 4 days does not influence basal synaptic transmission, but re

Opiate withdrawal induces dynamic-expressions of AMPA receptors and its regulatory molecule CaMKII alpha in hippocampal synapses

Adaptive changes in brain areas following drug withdrawal are believed to contribute to drug seeking and relapse. Cocaine withdrawal alters the expression of GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) rec

Morphine withdrawal modifies antinociceptive effects of acute morphine in rats

Repeated opioid use is known to cause tolerance of antinociceptive effects. Whether opioid abstinence modifies antinociceptive effects is unknown. Here we reported that morphine withdrawal for 18 h and 4 days after repeated morphine treatment largely redu

Opiate withdrawal modifies synaptic plasticity in subicular-nucleus accumbens pathway in vivo

Subiculum receives output of hippocampal CAI neurons and projects glutamatergic synapses onto nucleus accumbens (NAc), the subicular-NAc pathway linking memory and reward system. It is unknown whether morphine withdrawal influences synaptic plasticity in

Morphine withdrawal affects both delayed-escape behaviour in Morris water maze and hippocampal NR2A/2B expression ratio

Repeated low-dose morphine treatment facilitates delayed-escape behaviour of hippocampus-dependent Morris water maze and morphine withdrawal influences hippocampal NMDA receptor-dependent synaptic plasticity. Here, we examined whether and how morphine wit

Opioid Withdrawal for 4 Days Prevents Synaptic Depression Induced by Low Dose of Morphine or Naloxone in Rat Hippocampal CA1 Area In Vivo

The formation of memory is believed to depend on experience- or activity-dependent synaptic plasticity, which is exquisitely sensitive to psychological stress since inescapable stress impairs long-term potentiation (LTP) but facilitates long-term depression (LTD). Our recent studies demonstrated that 4 days of opioid withdrawal enables maximal extents of both hippocampal LTP and drug-reinforced behavior; while elevated-platform stress enables these phenomena at 18 h of opioid withdrawal. Here, we examined the effects of low dose of morphine (0.5 mg kg(-1), i.p.) or the opioid receptor antagonist naloxone (1 mg kg(-1), i.p.) on synaptic efficacy in the hippocampal CA1 region of anesthetized rats. A form of synaptic depression was induced by low dose of morphine or naloxone in rats after 18 h but not 4 days of opioid withdrawal. This synaptic depression was dependent on both N-methyl-D-aspartate receptor and synaptic activity, similar to the hippocampal long-term depression induced by low frequency stimulation. Elevated-platform stress given 2 h before experiment prevented the synaptic depression at 18 h of opioid withdrawal; in contrast, the glucocorticoid receptor (GR) antagonist RU38486 treatment (20 mg kg(-1), s.c., twice per day for first 3 days of withdrawal), or a high dose of morphine reexposure (15 mg kg(-1), s.c., 12 h before experiment), enabled the synaptic depression on 4 days of opioid withdrawal. This temporal shift of synaptic depression by stress or GR blockade supplements our previous findings of potentially correlated temporal shifts of LTP induction and drug-reinforced behavior during opioid withdrawal. Our results therefore support the idea that stress experience during opioid withdrawal may modify hippocampal synaptic plasticity and play important roles in drug-associated memory. (C) 2009 Wiley-Liss, Inc.