Effects of single or repeated amphetamine treatment and withdrawal on lung allergic inflammation in rats

The effects of single or repeated amphetamine (AMPH) treatment and those of AMPH withdrawals on immune-mediated lung inflammatory response were studied in rats. Two experiments were done. In the first, rats egg-albumin (OVA) sensitized were singularly or repeatedly (21 days, once daily) treated with AMPH (1.0 mg/kg) or with a similar number and volume of 0.9% NaCl. The OVA aerosol challenge was performed 12 h after the single or last repeated AMPH treatment and also 72 and 120 h after AMPH withdrawal. In the second experiment, the effects of reserpine (1.0 mg/kg/day for 5 consecutive days) on single AMPH actions on lung allergic response of rats were analyzed. Single and repeated AMPH treatment induced opposite actions on Bronchoalveolar lavage fluid (BAL) cellularity of allergic rats: single treatment decreased and repeated treatment increased the total number of cells as well as those of macrophages, neutrophils and eosinophils. Our data also showed that single but not repeated AMPH treatment decreased the number of neutrophils, monocytes and lymphocytes in the peripheral blood, and increased the total number of bone marrow cells in rats sensitized and challenged with OVA. Furthermore, it was shown that reserpine treatment precluded the effects of single AMPH treatment on cellular migration to the lung of OVA-sensitized and challenged rats. It was concluded that AMPH effects on lung inflammatory response and cell recruitment to the lung in allergic rats rely at least partially on corticosterone serum levels. The possible involvement of vesicular monoamine transporter type 2 (VMAT2) with these observed effects was discussed. (c) 2008 Elsevier B.V. All rights reserved.

A randomized controlled trial of buprenorphine in the management of short-term ambulatory heroin withdrawal

Aim: To determine whether buprenorphine is more effective than clondine and other symptomatic medications in managing ambulatory heroin withdrawal.
Design: Open label. prospective randomized controlled trial examining
withdrawal and 4-week postwithdrawal outcomes on intention-to-treat.
Setting: Two specialist, out-patient drug treatment centres in inner city
Melbourne and Sydney, Australia.
Participants: One hundred and fourteen dependent heroin users were recruited. Participants were 18 yea rs or over. and with no significant other drug dependence, medical or psychiatric conditions or recent methadone treatment. One hundred and one (89%) participants completed a day 8 research interview examining withdrawal outcomes, and 92 (81%) completed day 35 research interview examining postwithdrawal outcomes.
Interventions: Participants randomized to control (n = 56) (up to 8 days or
clonidine and other symptomatic medications) or experimental (n = 58) (up to 5 days of buprenorphine) withdrawal groups. Following the 8-day withdrawal episode, participants could self-select from range of postwithdrawal options (naltrexone, substitution maintenance or counselling).
Measurements: Retention in withdrawal: heroin use during withdrawl: and
retention in drug treatment 4 weeks after withdrawal.
Secondary outcomes: Withdrawal severity: adverse events, and heroin use in the postwithdrawal period.
Findings: The experimental group had better treatment retention at day 8 (86% versus 57%, P = 0.001, 95% CI for numbers needed to treat (NNT) = 3-8) and day 35 (62% versus 39%, P = 0.02, 95% CI for NNT = 4-18): used heroin on fewer days during the withdralwal programlme (2.6 ± 2.5 versus 4.5 ± 2. 3.
P < 0.001. 95% CI = 1- 2.5 days) and in the postwithdrawal period (9.0±8.2
versus 14.6± 10. P<O.Ol. 95% CI = I .8- 9.4): and reported less withdrawal
severity. No severe adverse events reported.
Conclusions: Buprenorphine is effective for short-term ambulatory heroin
withdrawaI, with greater retention, less heroin use and less withdrawal discomfort during withdrawal: and increased postwithdrawal treatment retention than symptomatic medications.

The skeletal benefits of calcium- and vitamin D3-fortified milk are sustained in older men after withdrawal of supplementation: an 18 mo follow-up study

Background: In a previous 2-y randomized controlled trial, we showed that calcium- and vitamin D₃–fortified milk stopped or slowed bone loss at several clinically relevant skeletal sites in older men.

Objective: The present study aimed to determine whether the skeletal benefits of the fortified milk were sustained after withdrawal of the supplementation.

Design: One hundred nine men >50 y old who had completed a 2-y fortified milk trial were followed for an additional 18 mo, during which no fortified milk was provided. Bone mineral density (BMD) of the total hip, femoral neck, lumbar spine, and forearm was measured by using dual-energy X-ray absorptiometry.

Results: Comparison of the mean changes from baseline between the groups (adjusted for baseline age, BMD, total calcium intake, and change in weight) showed that the net beneficial effects of fortified milk on femoral neck and ultradistal radius BMD at the end of the intervention (1.8% and 1.5%, respectively; P < 0.01 for both) were sustained at 18-mo follow-up (P < 0.05 for both). The nonsignificant between-group differences at the total hip (0.8%; P = 0.17) also persisted at follow-up (0.7%; P = 0.10), but there were no lasting benefits at the lumbar spine. The average total dietary calcium intake in the milk supplementation group at follow-up approximated recommended amounts for Australian men >50 y old (1000 mg/d) but did not differ significantly from that in the control subjects (1021 versus 890 mg/d).

Conclusion: Supplementation with calcium- and vitamin D₃–fortified milk for 2 y may provide some sustained benefits for BMD in older men after withdrawal of supplementation.

Effect of naloxone-precipitated morphine withdrawal on c-fos expression in rat corticotropin-releasing hormone neurons in the paraventricular hypothalamus and extended amygdala

Morphine withdrawal is characterized by physical symptoms and a negative affective state. The 41 amino acid polypeptide corticotropin-releasing hormone (CRH) is hypothesized to mediate, in part, both the negative affective state and the physical withdrawal syndrome. Here, by means of dual-immunohistochemical methodology, we examined the co-expression of the c-Fos protein and CRH following naloxone-precipitated morphine withdrawal. Rats were treated with slow-release morphine 50 mg/kg (subcutaneous, s.c.) or vehicle every 48 h for 5 days, then withdrawn with naloxone 5 mg/kg (s.c.) or saline 48 h after the final morphine injection. Two hours after withdrawal rats were perfused transcardially and their brains were removed and processed for immunohistochemistry. We found that naloxone-precipitated withdrawal of morphine-dependent rats increased c-Fos immunoreactivity (IR) in CRH positive neurons in the paraventricular hypothalamus. Withdrawal of morphine-dependent rats also increased c-Fos-IR in the central amygdala and bed nucleus of the stria terminalis, however these were in CRH negative neurons.

Peripheral withdrawal recruits distinct central nuclei in morphine-dependent rats

This study examined if brain pathways in morphine-dependent rats are activated by opioid withdrawal precipitated outside the central nervous system. Withdrawal precipitated with a peripherally acting quaternary opioid antagonist (naloxone methiodide) increased Fos expression but caused a more restricted pattern of neuronal activation than systemic withdrawal (precipitated with naloxone which enters the brain). There was no effect on locus coeruleus and significantly smaller increases in Fos neurons were produced in most other areas. However in the ventrolateral medulla (A1/C1 catecholamine neurons), nucleus of the solitary tract (A2/C2 catecholamine neurons), lateral parabrachial nucleus, supramamillary nucleus, bed nucleus of the stria terminalis, accumbens core and medial prefrontal cortex no differences in the withdrawal treatments were detected. We have shown that peripheral opioid withdrawal can affect central nervous system pathways.

The effect of lumbosacral manipulation on corticospinal and spinal reflex excitability on asymptomatic participants

Objective The aim of the study was to examine the effects of a high-velocity, low-amplitude (HVLA) manipulation to the lumbosacral joint on corticospinal excitability, as measured by motor evoked potentials (MEPs) using transcranial magnetic stimulation, and spinal reflex excitability, as measured by the Hoffman reflex (H-reflex).

Methods In a randomized, controlled, crossover design, 14 asymptomatic volunteers (mean age, 23 ± 5.4 years; 10 men; 4 women) were measured for MEPs and H-reflexes immediately before and after a randomly allocated intervention. The interventions consisted of HVLA applied bilaterally to the lumbosacral joint and a control intervention. Participants returned a week later, and the same procedures were performed using the other intervention. Data for H-reflex and MEP amplitudes were normalized to the M-wave maximum amplitude and analyzed using 2-way analysis of variance with repeated measures.

Results A significant interaction of treatment by time was found for MEP (F1,13 = 4.87, P = .04), and post hoc analyses showed that the MEP/M-wave maximum ratio decreased significantly in the HVLA treatment (P = .02; effect size, 0.68). For H-reflex, there was a significant effect of time (F1,13 = 8.186, P = .01) and treatment and time interaction (F1,13 = 9.05, P = .01), with post hoc analyses showing that H-reflexes were significantly reduced after the HVLA manipulation (P = .004; effect size, 0.94). There were no significant changes in MEP latency or silent period duration.

Conclusion An HVLA manipulation applied to the lumbosacral joint produced a significant decrease in corticospinal and spinal reflex excitability, and no significant change occurred after the control intervention. The changes in H-reflexes were larger than those in MEPs, suggesting a greater degree of inhibition at the level of the spinal cord.

The streak retinoscopy pupil reflex in the presence of astigmatism

Computer simulation is being increasingly used as a teaching tool. Having developed a computer-generated virtual focimeter, we are now in the process of developing a computer-generated virtual streak retinoscope to teach the principles of retinoscopy and the effect of residual refractive error and mirror movement on the pupil reflex. One of the important requirements was to provide as accurate a simulation as possible for the completely general case of an astigmatic patient and a streak in any orientation being moved also in any orientation. This required a thorough understanding of the optical theory of the retinoscope and equations that describe the behaviour of the pupil reflex. We have taken this opportunity to review the optics of the streak retinoscope and derive equations for the behaviour of the pupil streak reflex.

The politics of Australia's withdrawal from Iraq

This article examines the complex matrix of public, political and policy debates that were brought to bear on Australia's decision to withdraw from Iraq. In analysing the ‘politics of withdrawal’ in Australia, this article identifies four dominant frames that served to polarise the issue along party-political lines and reduce the complexities of Australia's withdrawal to a set of simple polarities (such as ‘stay the course’ versus ‘responsible withdrawal’). Specifically, these frames obfuscated an assessment of the myriad challenges facing post-Saddam Iraq and the prospects for peace, security and development beyond Australia's withdrawal. Understanding the ways in which Australia framed its decision to disengage from Iraq is critical to further analysis of Australia's approach to current (or future) military draw-downs (such as in Afghanistan), as well as those conducted by other liberal democracies, such as the US and the UK.

Introduction : The Iraq legacies: intervention, occupation, withdrawal and beyond

This chapter examines the various and complex legacies of the Iraq War of 2003. In follows the trajectory of these legacies back to the earliest days of the US intervention and examines the extent to which key decisions and errors of judgement on the part ofthe Coalition and the Iraqi political elite have had unexpected and devastating consequences for Iraq today. The chapter documents how the war dramatically altered the lives of ordinary Iraqis and led to many of the most deep-seated and intractable problems facing Iraq, the region and the world today. In discussing these legacies, this chapter also points to the root causes of the rapid turn of events that transpired after the dramatic advance of ISIS in mid-2014. The argument here being that the Iraq War of 2003 has left behind a sequence of deeply felt but rarely examined legacies and that together these legacies have served as the catalyst of Iraq’s current chaos. Therefore, this chapter is not only timely, but it also addresses a significant lacuna in academic and policy debates by addressing a series of urgent questions concerning the legacies of Iraq.

Triceps surae fascicle stretch is poorly correlated with short latency stretch reflex size

INTRODUCTION: The short latency stretch reflex (SLR) is well described, but the stimulus that evokes the SLR remains elusive. One hypothesis states that reflex size is proportional to muscle fiber stretch, so in this study we examined the relationship between these 2 parameters in human triceps surae muscles. METHODS: Achilles tendon taps and dorsiflexion stretches with different amplitudes and preactivation torques were applied to 6 participants while electromyography and muscle fascicle length changes were recorded in soleus and medial gastrocnemius (MG). RESULTS: In response to tendon taps, neither fascicle length nor velocity changes were correlated with SLR size in either muscle, but accelerometer peaks were observed immediately after hammer-tendon contact. Similar results were obtained after dorsiflexion stretches. CONCLUSION: Muscle fascicle stretch is poorly correlated with SLR size, regardless of perturbation parameters. We attribute the SLR trigger to the transmission of vibration through the lower limb, rather than muscle fiber stretch. Muscle Nerve, 2015.

Modeling upper eyelid kinematics during spontaneous and reflex blinks

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)