CSF biochemical correlates of mixed affective states

To evaluate the question of whether “mixed” bipolar disorder is a distinct entity, we compared selected cerebrospinal fluid (CSF) biochemical parameters from patients with bipolar disorder, mixed, to those with mania and major depression. Fourteen patients in each category (DSM-III) were studied with regard to CSF HVA, 5HIAA, sodium, potassium, calcium, and magnesium levels under carefully controlled conditions. CSF HVA, 5HIAA, and sodium were found to be significantly higher in manics than in major depressives. Discriminant analysis of the biochemical variables of the mixed affective group identified two biochemically distinct and clinically different subgroups of seven patients each, one resembling the manic group and the other the major depressive group. These findings suggest that mixed affective states do not exist as a separate entity, but are compsed of two subgroups obtained from the manic and major depressive categories.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66203/1/j.1600-0447.1988.tb06339.x.pd

Impaired Brain Dopamine and Serotonin Release and Uptake in Wistar Rats Following Treatment with Carbotplatin

Chemotherapy-induced cognitive impairment, known also as “chemobrain”, is a medical complication of cancer treatment that is characterized by a general decline in cognition affecting visual and verbal memory, attention, complex problem solving skills, and motor function. It is estimated that one-third of patients who undergo chemotherapy treatment will experience cognitive impairment. Alterations in the release and uptake of dopamine and serotonin, central nervous system neurotransmitters that play important roles in cognition, could potentially contribute to impaired intellectual performance in those impacted by chemobrain. To investigate how chemotherapy treatment affects these systems, fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes was used to measure dopamine and serotonin release and uptake in coronal brain slices containing the striatum and dorsal raphe nucleus, respectively. Measurements were taken from rats treated weekly with selected doses of carboplatin and from control rats treated with saline. Modeling the stimulated dopamine release plots revealed an impairment of dopamine release per stimulus pulse (80% of saline control at 5 mg/kg and 58% at 20 mg/kg) after 4 weeks of carboplatin treatment. Moreover, Vmax, the maximum uptake rate of dopamine, was also decreased (55% of saline control at 5 mg/kg and 57% at 20 mg/kg). Nevertheless, overall dopamine content, measured in striatal brain lysates by high performance liquid chromatography, and reserve pool dopamine, measured by FSCV after pharmacological manipulation, did not significantly change, suggesting that chemotherapy treatment selectively impairs the dopamine release and uptake processes. Similarly, serotonin release upon electrical stimulation was impaired (45% of saline control at 20 mg/kg). Measurements of spatial learning discrimination were taken throughout the treatment period and carboplatin was found to alter cognition. These studies support the need for additional neurochemical and behavioral analyses to identify the underlying mechanisms of chemotherapy-induced cognitive disorders

Cardiac regeneration: different cells same goal

Cardiovascular diseases are the leading cause of mortality, morbidity, hospitalization and impaired quality of life. In most, if not all, pathologic cardiac ischemia ensues triggering a succession of events leading to massive death of cardiomyocytes, fibroblast and extracellular matrix accumulation, cardiomyocyte hypertrophy which culminates in heart failure and eventually death. Though current pharmacological treatment is able to delay the succession of events and as a consequence the development of heart failure, the only currently available and effective treatment of end-stage heart failure is heart transplantation. However, donor heart availability and immunorejection upon transplantation seriously limit the applicability. Cardiac regeneration could provide a solution, making real a dream of both scientist and clinician in the previous century and ending an ongoing challenge for this century. In this review, we present a basic overview of the various cell types that have been used in both the clinical and research setting with respect to myocardial differentiation

The Renin-Angiotensin-Aldosterone system in patients with depression compared to controls – a sleep endocrine study

BACKGROUND: Hypercortisolism as a sign of hypothamamus-pituitary-adrenocortical (HPA) axis overactivity and sleep EEG changes are frequently observed in depression. Closely related to the HPA axis is the renin-angiotensin-aldosterone system (RAAS) as 1. adrenocorticotropic hormone (ACTH) is a common stimulus for cortisol and aldosterone, 2. cortisol release is suppressed by mineralocorticoid receptor (MR) agonists 3. angiotensin II (ATII) releases CRH and vasopressin from the hypothalamus. Furthermore renin and aldosterone secretion are synchronized to the rapid eyed movement (REM)-nonREM cycle. METHODS: Here we focus on the difference of sleep related activity of the RAAS between depressed patients and healthy controls. We studied the nocturnal plasma concentration of ACTH, cortisol, renin and aldosterone, and sleep EEG in 7 medication free patients with depression (1 male, 6 females, age: (mean +/-SD) 53.3 ± 14.4 yr.) and 7 age matched controls (2 males, 5 females, age: 54.7 ± 19.5 yr.). After one night of accommodation a polysomnography was performed between 23.00 h and 7.00 h. During examination nights blood samples were taken every 20 min between 23.00 h and 7.00 h. Area under the curve (AUC) for the hormones separated for the halves of the night (23.00 h to 3.00 h and 3.00 h to 7.00 h) were used for statistical analysis, with analysis of co variance being performed with age as a covariate. RESULTS: No differences in ACTH and renin concentrations were found. For cortisol, a trend to an increase was found in the first half of the night in patients compared to controls (p < 0.06). Aldosterone was largely increased in the first (p < 0.05) and second (p < 0.01) half of the night. Cross correlations between hormone concentrations revealed that in contrast to earlier findings, which included only male subjects, in our primarily female sample, renin and aldosterone secretion were not coupled and no difference between patients and controls could be found, suggesting a gender difference in RAAS regulation. No difference in conventional sleep EEG parameters were found in our sample. CONCLUSION: Hyperaldosteronism could be a sensitive marker for depression. Further our findings point to an altered renal mineralocorticoid sensitivity in patients with depression

Adult Raphe-Specific Deletion of Lmx1b Leads to Central Serotonin Deficiency

The transcription factor Lmx1b is essential for the differentiation and survival of central serotonergic (5-HTergic) neurons during embryonic development. However, the role of Lmx1b in adult 5-HTergic neurons is unknown. We used an inducible Cre-LoxP system to selectively inactivate Lmx1b expression in the raphe nuclei of adult mice. Pet1-CreERT2 mice were generated and crossed with Lmx1bflox/flox mice to obtain Pet1-CreERT2; Lmx1bflox/flox mice (which termed as Lmx1b iCKO). After administration of tamoxifen, the level of 5-HT in the brain of Lmx1b iCKO mice was reduced to 60% of that in control mice, and the expression of tryptophan hydroxylase 2 (Tph2), serotonin transporter (Sert) and vesicular monoamine transporter 2 (Vmat2) was greatly down-regulated. On the other hand, the expression of dopamine and norepinephrine as well as aromatic L-amino acid decarboxylase (Aadc) and Pet1 was unchanged. Our results reveal that Lmx1b is required for the biosynthesis of 5-HT in adult mouse brain, and it may be involved in maintaining normal functions of central 5-HTergic neurons by regulating the expression of Tph2, Sert and Vmat2

Crop Updates 2006 - Weeds

This session covers thirty seven papers from different authors: 1. ACKNOWLEDGEMENTS, Alexandra Douglas, CONVENOR – WEEDS DEPARTMENT OF AGRICULTURE SPRAY TECHNOLOGY 2. Meeting the variable application goals with new application technology, Thomas M. Wolf, Agriculture and Agri-Food Canada, Saskatoon Research Centre 3. Spray nozzles for grass weed control, Harm van Rees, BCG (Birchip Cropping Group) 4. Boom sprayer setups – achieving coarse droplets with different operating parameters, Bill Gordon, Bill Gordon Consulting 5. Complying with product label requirements, Bill Gordon, Bill Gordon Consulting 6. IWM a proven performer over 5 years in 33 focus paddocks, Peter Newman and Glenn Adam, Department of Agriculture 7. Crop topping of wild radish in lupins and barley, how long is a piece of string? Peter Newman and Glenn Adam, Department of Agriculture 8. Determining the right timing to maximise seed set control of wild radish, Aik Cheam and Siew Lee, Department of Agriculture 9. Why weed wiping varies in success rates in broadacre crops? Aik Cheam1, Katherine Hollaway2, Siew Lee1, Brad Rayner1 and John Peirce1,1Department of Agriculture, 2Department of Primary Industries, Victoria 10. Are WA growers successfully managing herbicide resistant annual ryegrass? Rick Llewellynabc, Frank D’Emdena, Mechelle Owenb and Stephen Powlesb aCRC Australian Weed Management, School of Agricultural and Resource Economics, University of Western Australia; bWA Herbicide Resistance Initiative, University of Western Australia. cCurrent address: CSIRO Sustainable Ecosystems 11. Do herbicide resistant wild radish populations look different? Michael Walsh, Western Australian Herbicide Resistance Initiative, University of Western Australia 12. Can glyphosate and paraquat annual ryegrass reduce crop topping efficacy? Emma Glasfurd, Michael Walsh and Kathryn Steadman, Western Australian Herbicide Resistance Initiative, University of Western Australia 13. Tetraploid ryegrass for WA. Productive pasture phase AND defeating herbicide resistant ryegrass, Stephen Powlesa, David Ferrisab and Bevan Addisonc, aWA Herbicide Resistance Initiative, University of Western Australia; bDepartment of Agriculture, and cElders Limited 14. Long-term management impact on seedbank of wild radish with multiple resistance to diflufenican and triazines, Aik Cheam, Siew Lee, Dave Nicholson and Ruben Vargas, Department of Agriculture 15. East-west crop row orientation improves wheat and barley yields, Dr Shahab Pathan, Dr Abul Hashem, Nerys Wilkins and Catherine Borger3, Department of Agriculture, 3WAHRI, The University ofWestern Australia 16. Competitiveness of different lupin cultivars with wild radish, Dr Shahab Pathan, Dr Bob French and Dr Abul Hashem, Department of Agriculture 17. Managing herbicide resistant weeds through farming systems, Kari-Lee Falconer, Martin Harries and Chris Matthews, Department of Agriculture 18. Lupins tolerate in-row herbicides well, Peter Newman and Martin Harries, Department of Agriculture 19. Summer weeds can reduce wheat grain yield and protein, Dr Abul Hashem1, Dr Shahab Pathan1 and Vikki Osten3, 1Department Agriculture, 3Senior Agronomist, CRC for Australian Weed Management, Queensland Department of Primary Industries and Fisheries 20. Diuron post-emergent in lupins, the full story, Peter Newman and Glenn Adam, Department of Agriculture 21. Double incorporation of trifluralin, Peter Newman and Glenn Adam, Department of Agriculture 22. Herbicide tolerance of narrow leafed and yellow lupins, Harmohinder Dhammu, David Nicholson, Department of Agriculture 23. MIG narrow leaf lupin herbicide tolerance trial, Richard Quinlan, Planfarm Pty Ltd, Trials Coordinator MIG; Debbie Allen, Research Agronomist – MIG 24. Herbicide tolerance of new albus lupins, Harmohinder Dhammu, David Nicholson, Department of Agriculture 25. Field pea x herbicide tolerance, Mark Seymour and Harmohinder Dhammu, Research Officers, and Pam Burgess, Department of Agriculture 26. Faba bean variety x herbicide tolerance, Mark Seymour and Harmohinder Dhammu, Research Officers, and Pam Burgess, Department of Agriculture 27. Herbicide tolerance of new Kabili chickpeas, Harmohinder Dhammu, Owen Coppen and Chris Roberts, Department of Agriculture 28. Timing of phenoxys application in EAG Eagle Rock, Harmohinder Dhammu, David Nicholson, Department of Agriculture 29. Herbicide tolerance of new wheat varieties, Harmohinder Dhammu, David Nicholson, Department of Agriculture 30. Lathyrus sativus x herbicide tolerance, Mark Seymour, Department of Agriculture 31. Tolerance of annual pasture species to herbicides and mixtures containing diuron, Christiaan Valentine and David Ferris, Department of Agriculture 32. The impact of herbicides on pasture legume species – a summary of scientific trial results across 8 years, Christiaan Valentine and David Ferris, Department of Agriculture 33. The impact of spraytopping on pasture legume seed set, Christiaan Valentine and David Ferris, Department of Agriculture 34. Ascochyta interaction with Broadstrike in chickpeas, H.S. Dhammu1, A.K. Basandrai2,3, W.J. MacLeod1, 3 and C. Roberts1, 1Department of Agriculture, 2CSKHPAU, Dhaulakuan, Sirmour (HP), India and 3CLIMA 35. Best management practices for atrazine in broadacre crops, John Moore, Department of Agriculture, Neil Rothnie, Chemistry Centre of WA, Russell Speed, Department of Agriculture, John Simons, Department of Agriculture, and Ted Spadek, Chemistry Centre of WA 36. Biology and management of red dodder (Cuscuta planiflolia) – a new threat to the grains industry, Abul Hashem, Daya Patabendige and Chris Roberts, Department Agriculture 37. Help the wizard stop the green invaders! Michael Renton, Sally Peltzer and Art Diggle, Department of Agricultur

Aripiprazole in the Maintenance Treatment of Bipolar Disorder: A Critical Review of the Evidence and Its Dissemination into the Scientific Literature

A systematic search of the literature reveals limited evidence to support use of aripiprazole, a second-generation antipsychotic medication, in maintenance therapy of bipolar disorder, despite widespread use

Nicotinic receptors

Regulation of normal or abnormal behaviour is critically controlled by the central serotonergic systems. Recent evidence has suggested that serotonin (5-HT) neurotransmission dysfunction contributes to a variety of pathological conditions, including depression, anxiety, schizophrenia and Parkinson’s disorders. There is also a great amount of evidence indicating that 5-HT signalling may affect the reinforcing properties of drugs of abuse by the interaction and modulation of dopamine (DA) function. This chapter is focused on one of the more addictive drugs, nicotine. It is widely recognised that the effects of nicotine are strongly associated with the stimulatory action it exhibits on mesolimbic DAergic function. We outline the role of 5-HT and its plethora of receptors, focusing on 5-HT2 subtypes with relation to their involvement in the neurobiology of nicotine addiction. We also explore the novel pharmacological approaches using 5-HT agents for the treatment of nicotine dependence. Compelling evidence shows that 5-HT2C receptor agonists may be possible therapeutic targets for smoking cessation, although further investigation is required.peer-reviewe

Extracellular High Mobility Group Box 1 Plays a Role in the Effect of Bone Marrow Mononuclear Cell Transplantation for Heart Failure

Transplantation of unfractionated bone marrow mononuclear cells (BMCs) repairs and/or regenerates the damaged myocardium allegedly due to secretion from surviving BMCs (paracrine effect). However, donor cell survival after transplantation is known to be markedly poor. This discrepancy led us to hypothesize that dead donor BMCs might also contribute to the therapeutic benefits from BMC transplantation. High mobility group box 1 (HMGB1) is a nuclear protein that stabilizes nucleosomes, and also acts as a multi-functional cytokine when released from damaged cells. We thus studied the role of extracellular HMGB1 in the effect of BMC transplantation for heart failure. Four weeks after coronary artery ligation in female rats, syngeneic male BMCs (or PBS only as control) were intramyocardially injected with/without anti-HMGB1 antibody or control IgG. One hour after injection, ELISA showed that circulating extracellular HMGB1 levels were elevated after BMC transplantation compared to the PBS injection. Quantitative donor cell survival assessed by PCR for male-specific sry gene at days 3 and 28 was similarly poor. Echocardiography and catheterization showed enhanced cardiac function after BMC transplantation compared to PBS injection at day 28, while this effect was abolished by antibody-neutralization of HMGB1. BMC transplantation reduced post-infarction fibrosis, improved neovascularization, and increased proliferation, while all these effects in repairing the failing myocardium were eliminated by HMGB1-inhibition. Furthermore, BMC transplantation drove the macrophage polarization towards alternatively-activated, anti-inflammatory M2 macrophages in the heart at day 3, while this was abolished by HMGB1-inhibition. Quantitative RT-PCR showed that BMC transplantation upregulated expression of an anti-inflammatory cytokine IL-10 in the heart at day 3 compared to PBS injection. In contrast, neutralizing HMGB1 by antibody-treatment suppressed this anti-inflammatory expression. These data suggest that extracellular HMGB1 contributes to the effect of BMC transplantation to recover the damaged myocardium by favorably modulating innate immunity in heart failure