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 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.

Avaliação toxicológica dos benzodiazepínicos diazepam e maleato de midazolam sobre o desenvolvimento pré-natal de ratos wistar.

Benzodiazepínicos são amplamente utilizados em animais e humanos, inclusive durante a gestação. Benzodiazepínicos são utilizados como ansiolíticos, anticonvulsivantes, relaxantes musculares e sedativos. Este trabalho investiga o potencial teratogênico dos benzodiazepínicos diazepam e maleato de midazolam em ratos Wistar. Os animais foram divididos em três grupos “experimentais”, um grupo controle que recebeu água destilada, um grupo que recebeu diazepam na dose de 10 mg/kg/dia, e um grupo que recebeu 5 mg/kg/dia de midazolam. Os animais receberam os tratamentos por administração via oral. As fêmeas gestantes foram tratadas durante o período de organogênese, que no rato é do 6° ao 15° dia da gestação. Durante a gestação as fêmeas foram monitoradas quanto ao desenvolvimento corporal, ingesta de água e ração. No 21° dia de gestação as progenitoras foram sacrificadas e avaliadas quanto à toxicidade materna sistêmica. Os fetos foram avaliados quanto a embriotoxicidade e alterações esqueléticas. Os resultados demonstraram que as fêmeas dos três grupos tiveram ganho de peso, consumo de água e consumo de ração semelhante, assim como peso dos órgãos internos, sugerindo não haver toxicidade materna. Nos grupos diazepam e maleto de midazolam houve uma diminuição do número de fetos por ninhada (9,2 ± 3,17 e 9,29 ± 3,29) comparado ao grupo controle (10,76 ± 2,62), também houve diminuição no peso dos fetos nos grupos diazepam e midazolam (4,73 ± 0,59 e 4,79 ± 0,64) em comparação ao grupo controle (5,02 ± 0,36). Houve um aumento no número de abortos precoces nos grupos diazepam e midazolam As perdas pós-implantação foram de 1,47% no grupo controle, 10,76% no grupo diazepam e 13,30% no grupo midazolam. A taxa de viabilidade fetal foi semelhante nos três grupos. As avaliações das anormalidades esqueléticas demonstraram um retardo de desenvolvimento assim como houve evidências de malformações nos grupos diazepam e midazolam, sendo que o grupo tratado com maleato de midazolam demonstrou um maior percentual de anormalidades esqueléticas que os fetos do grupo tratado com diazepam. Este estudo sugere efeitos teratogênicos dos medicamentos diazepam e midazolam quando utilizados nas doses testadas.

Global slowing of network oscillations in mouse neocortex by diazepam

SCHEFFZUK, C. , KUKUSHKA, V. , VYSSOTSKI, A. L. , DRAGUHN, A. , TORT, A. B. L. , BRANKACK, J. . Global slowing of network oscillations in mouse neocortex by diazepam. Neuropharmacology , v. 65, p. 123-133, 2013.

The effects of anesthesia with a combination of intramuscular xylazine-diazepam-ketamine on heart rate, respiratory rate and cloacal temperature in roosters

Objective To examine the anesthetic effects of a xylazine-diazepam-ketamine (XDK) combination in roosters.Study design Prospective experimental trial.Animals Six healthy white Leghorn roosters weighing 2.03 +/- 0.08 kg.Methods Each rooster was pre-medicated with xylazine (3 mg kg(-1), IM) and after 15 minutes anesthesia was induced with a diazepam (4 mg kg(-1)) and ketamine (25 mg kg(-1)) combination injected into the pectoral muscles. Heart and respiratory rates were recorded before anesthesia and every 15 minutes after induction for 165 minutes. Cloacal temperature was measured before and 15 minutes after pre-medication and every 75 minutes thereafter during anesthesia. Quality of induction and recovery were scored subjectively; duration of loss of righting reflex, abolition of response to a painful stimulus and palpebral reflex were also recorded.Results Intramuscular injection of xylazine smoothly induced loss of the righting reflex within 3-4 minutes. Loss of response to a painful stimulus occurred at 13.1 +/- 2.9 minutes (mean +/- SD) after the administration of the D-K combination, and lasted for 63.0 +/- 5.3 minutes. Roosters anesthetized with this combination had a significant decrease in heart and respiratory rates and cloacal temperature. The recovery period lasted for up to 4 hours (227.5 +/- 15.4 minutes). Quality of recovery was satisfactory for four roosters but excitation was noted in two birds.Conclusions and clinical relevance The XDK combination was a useful anesthetic technique for typhlectomy in roosters. Nevertheless this drug combination should be used with caution and cardiopulmonary parameters monitored carefully. Under the conditions of this experiment it was associated with a decreased cloacal temperature and prolonged recoveries.

Influence of chlorine added to drinking water during the preslaughter feed withdrawal on microbiology and morphology of the broiler gastrointestinal tract

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)