Publications by authors named "Malizia A"

120 Publications

Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines.

J Psychopharmacol 2015 May 12;29(5):459-525. Epub 2015 May 12.

Associate Professor, Canada Research Chair in Early Interventions, Dalhousie University, Department of Psychiatry, Halifax, NS, Canada.

A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations are made. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse and stopping treatment. Significant changes since the last guidelines were published in 2008 include the availability of new antidepressant treatment options, improved evidence supporting certain augmentation strategies (drug and non-drug), management of potential long-term side effects, updated guidance for prescribing in elderly and adolescent populations and updated guidance for optimal prescribing. Suggestions for future research priorities are also made.
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http://dx.doi.org/10.1177/0269881115581093DOI Listing
May 2015

Ebola virus disease 2013-2014 outbreak in west Africa: an analysis of the epidemic spread and response.

Int J Microbiol 2015 17;2015:769121. Epub 2015 Mar 17.

Department of Industrial Engineering, University of Rome Tor Vergata, Via del Politecnico 1, 00173 Rome, Italy ; International Master Courses in Protection against CBRNe Events, Department of Industrial Engineering and School of Medicine and Surgery, University of Rome Tor Vergata, Via del Politecnico 1, 00173 Rome, Italy.

The Ebola virus epidemic burst in West Africa in late 2013, started in Guinea, reached in a few months an alarming diffusion, actually involving several countries (Liberia, Sierra Leone, Nigeria, Senegal, and Mali). Guinea and Liberia, the first nations affected by the outbreak, have put in place measures to contain the spread, supported by international organizations; then they were followed by the other nations affected. In the present EVD outbreak, the geographical spread of the virus has followed a new route: the achievement of large urban areas at an early stage of the epidemic has led to an unprecedented diffusion, featuring the largest outbreak of EVD of all time. This has caused significant concerns all over the world: the potential reaching of far countries from endemic areas, mainly through fast transports, induced several countries to issue information documents and health supervision for individuals going to or coming from the areas at risk. In this paper the geographical spread of the epidemic was analyzed, assessing the sequential appearance of cases by geographic area, considering the increase in cases and mortality according to affected nations. The measures implemented by each government and international organizations to contain the outbreak, and their effectiveness, were also evaluated.
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http://dx.doi.org/10.1155/2015/769121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380098PMC
April 2015

UMEL: a new regression tool to identify measurement peaks in LIDAR/DIAL systems for environmental physics applications.

Rev Sci Instrum 2014 Jun;85(6):063112

Asociación EURATOM/CIEMAT para Fusión. Avda. Complutense, 40. 28040 Madrid, Spain.

Recently, surveying large areas in an automatic way, for early detection of both harmful chemical agents and forest fires, has become a strategic objective of defence and public health organisations. The Lidar and Dial techniques are widely recognized as a cost-effective alternative to monitor large portions of the atmosphere. To maximize the effectiveness of the measurements and to guarantee reliable monitoring of large areas, new data analysis techniques are required. In this paper, an original tool, the Universal Multi Event Locator, is applied to the problem of automatically identifying the time location of peaks in Lidar and Dial measurements for environmental physics applications. This analysis technique improves various aspects of the measurements, ranging from the resilience to drift in the laser sources to the increase of the system sensitivity. The method is also fully general, purely software, and can therefore be applied to a large variety of problems without any additional cost. The potential of the proposed technique is exemplified with the help of data of various instruments acquired during several experimental campaigns in the field.
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http://dx.doi.org/10.1063/1.4883184DOI Listing
June 2014

Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology.

J Psychopharmacol 2014 May 8;28(5):403-39. Epub 2014 Apr 8.

1Faculty of Medicine, University of Southampton, Southampton, UK.

This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions. A consensus meeting involving international experts in anxiety disorders reviewed the main subject areas and considered the strength of supporting evidence and its clinical implications. The guidelines are based on available evidence, were constructed after extensive feedback from participants, and are presented as recommendations to aid clinical decision-making in primary, secondary and tertiary medical care. They may also serve as a source of information for patients, their carers, and medicines management and formulary committees.
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http://dx.doi.org/10.1177/0269881114525674DOI Listing
May 2014

Parasitism underground: lice (Insecta: Phthiraptera) from Ctenomys talarum (Rodentia: Ctenomyidae) along its coastal distribution in Argentina.

Acta Parasitol 2014 Mar;60(1):154-7

Species of South American subterranean rodents belonging to the genus Ctenomys (commonly called tuco-tucos) are widely distributed across the southern Neotropical region. Despite their relatively well-studied biology and reproductive physiology, current knowledge of their ectoparasite fauna is limited to a few ambiguous studies, based on scattered samples from a small number of host individuals. Ctenomys talarum is the most widely distributed species in the genus. Lice (Phthiraptera) were collected from these tuco-tucos throughout their entire coastal range. Two species, one chewing louse (Gyropus parvus), and one sucking louse (Eulinognathus americanus) were collected. The distribution ranges for both louse species were extended with new locality records. No lice were found in two host populations. Furthermore, co-occurrence of both ectoparasites was not detected.
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http://dx.doi.org/10.1515/ap-2015-0021DOI Listing
March 2014

Drugs for addiction: a therapeutic area in need of a 'shot in the arm'.

Br J Clin Pharmacol 2014 Feb;77(2):225-7

Clinical Psychopharmacology and Neurostimulation, Department of Neurosurgery, Frenchay hospital, North Bristol NHS Trust, Bristol, BS16 1LE, UK.

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http://dx.doi.org/10.1111/bcp.12316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014028PMC
February 2014

Rate of tree carbon accumulation increases continuously with tree size.

Nature 2014 Mar 15;507(7490):90-3. Epub 2014 Jan 15.

Faculty of Forestry, Kasetsart University, ChatuChak Bangkok 10900, Thailand.

Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.
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http://dx.doi.org/10.1038/nature12914DOI Listing
March 2014

Rapid structural and compositional change in an old-growth subtropical forest: using plant traits to identify probable drivers.

PLoS One 2013 17;8(9):e73546. Epub 2013 Sep 17.

CONICET-Instituto de Ecología Regional (IER), Universidad Nacional de Tucumán, Tucumán, Argentina.

Recent studies have shown directional changes in old-growth tropical forests, but changes are complex and diverse, and their drivers unclear. Here, we report rapid net structural and compositional changes in an old-growth subtropical forest and we assess the functional nature of these changes to test hypothetical drivers including recovery from past disturbances, reduction in ungulate browsing, CO2 fertilization, and increases in rainfall and temperature. The study relies on 15 years of demographic monitoring within 8 ha of subtropical montane forest in Argentina. Between 1992 and 2007, stem density markedly increased by 50% (12 stems ha(-1) y(-1)) and basal area by 6% (0.13 m(2) ha(-1) y(-1)). Increased stem density resulted from enhanced recruitment of understory treelets (Piper tucumanum, Eugenia uniflora, Allophylus edulis) into small size classes. Among 27 common tree species, net population growth was negatively correlated with maximum tree size and longevity, and positively correlated with leaf size and leaf nutrient content, especially so when initial population size was controlled for. Changes were inconsistent with predictions derived from past disturbances (no increase in shade-tolerant or long-lived late-succesional species), rainfall or temperature increase (no increase in evergreen or deciduous species, respectively). However, the increase in nutrient-rich soft-leaved species was consistent with exclusion of large herbivores two decades before monitoring started; and CO2 fertilization could help explain the disproportionate increase in small stems. Reductions in populations of large vertebrates have been observed in many otherwise undisturbed tropical forests, and our results suggest they can have important structural and functional repercussions in these forests.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073546PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775741PMC
April 2014

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.

Proc Natl Acad Sci U S A 2012 Feb 23;109(6):2138-43. Epub 2012 Jan 23.

Neuropsychopharmacology Unit, University of Bristol, Bristol BS8 2BN, United Kingdom.

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.
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http://dx.doi.org/10.1073/pnas.1119598109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277566PMC
February 2012

MicroRNAs in cardiomyocyte development.

Wiley Interdiscip Rev Syst Biol Med 2011 Mar-Apr;3(2):183-90

Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.

MicroRNAs (miRNAs) negatively regulate gene expression at the post-transcriptional level, primarily by base-pairing with the 3'-untranslated region (3'-UTR) of their target mRNAs. Many miRNAs are expressed in a tissue/organ-specific manner and are associated with an increasing number of cell proliferation, differentiation, and tissue development events. Cardiac muscle expresses distinct genes encoding structural proteins and a subset of signal molecules that control tissue specification and differentiation. The transcriptional regulation of cardiomyocyte development has been well established, yet only until recently has it been uncovered that miRNAs participate in the regulatory networks. A subset of miRNAs are either specifically or highly expressed in cardiac muscle, providing an opportunity to understand how gene expression is controlled by miRNAs at the post-transcriptional level in this muscle type. miR-1, miR-133, miR-206, and miR-208 have been found to be muscle-specific, and thus have been called myomiRs. The discovery of myomiRs as a previously unrecognized component in the regulation of gene expression adds an entirely new layer of complexity to our understanding of cardiac muscle development. Investigating myomiRs will not only reveal novel molecular mechanisms of the miRNA-mediated regulatory network in cardiomyocyte development, but also raise new opportunities for therapeutic intervention for cardiovascular disease.
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http://dx.doi.org/10.1002/wsbm.111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058499PMC
June 2011

Deep brain stimulation relieves refractory hypertension.

Neurology 2011 Jan;76(4):405-7

Department of Neurosurgery, Institute of Neurosciences, Frenchay Hospital, Bristol, UK.

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http://dx.doi.org/10.1212/WNL.0b013e3182088108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034421PMC
January 2011

Parasitism underground: determinants of helminth infections in two species of subterranean rodents (Octodontidae).

Parasitology 2010 Sep 26;137(10):1569-75. Epub 2010 May 26.

Laboratorio de Parasitología, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Funes 3350, (7600) Mar del Plata, Argentina.

Patterns of infection among hosts in a population are often driven by intrinsic host features such as age or sex, as well as by positive or negative interactions between parasite species. We investigated helminth parasitism in 2 South American rodent species, Ctenomys australis and C. talarum (Octodontidae), to determine whether the unusual solitary and subterranean nature of these hosts would impact their patterns of infection. We applied generalized linear models to infection data on a total of 7 helminth species (1 in C. australis and 6 in C. talarum). Host age and season of capture influenced infection levels in some of the helminth species, but none were influenced by host body condition. In C. talarum, 4 pairs of helminth species showed significant associations, either asymmetrical or symmetrical, and with 3 of the 4 being positive; strong inter-specific facilitation appears likely in 1 case. Also, we found that female hosts, especially non-pregnant ones, harboured heavier infections of 2 nematode species than male hosts. This is in sharp contrast to the general male-bias reported for most studies of nematodes in wild mammals, and we develop explanations for these results based on the unusual ecology of these subterranean rodents.
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http://dx.doi.org/10.1017/S0031182010000351DOI Listing
September 2010

Modulation of ion channels in clinical psychopharmacology: adults and younger people.

Expert Rev Clin Pharmacol 2010 May;3(3):397-416

Psychopharmacology Unit, Department of Community Based Medicine, University of Bristol, Bristol, UK.

This review focuses on the use of Na(+), Ca(2+) and Cl(-) channel modulators in psychiatric disease. Drugs that modulate ion channels have been used in psychiatry for more than a century, and in this review we critically evaluate clinical research that reports the therapeutic effects of drugs acting on GABA(A), voltage-gated Na(+) and voltage-gated Ca(2+) channels in pediatric and adult patients. As in other fields, the evidence underpinning the use of medicines in younger people is far less robust than for adults. In addition, we discuss some current developments and highlight clinical disorders in which current molecules could be further tested. Notable success stories, such as benzodiazepines (in sleep and anxiety disorders) and antiepileptics (in bipolar disorder), have been the result of serendipitous discoveries or refinements of serendipitous discoveries, as in all other major treatments in psychiatry. Genomic, high-throughput screening and molecular pharmacology discoveries may, however, guide further developments in the future. This could include increased research in promising targets that have been perceived as commercially risky, such as selective α-subunit GABA(A) receptors.
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http://dx.doi.org/10.1586/ecp.10.21DOI Listing
May 2010

CUX1/Wnt signaling regulates epithelial mesenchymal transition in EBV infected epithelial cells.

Exp Cell Res 2009 Jul 8;315(11):1819-31. Epub 2009 Apr 8.

Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland.

Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGFbeta1-mediated lytic phase. EBV lytic reactivation by TGFbeta1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM_181552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.
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http://dx.doi.org/10.1016/j.yexcr.2009.04.001DOI Listing
July 2009

IL-4 increases CD21-dependent infection of pulmonary alveolar epithelial type II cells by EBV.

Mol Immunol 2009 May 4;46(8-9):1905-10. Epub 2009 Feb 4.

Advanced Lung Disease and Lung Transplant Program, Mater Misericordiae University Hospital. 44, Eccles Street, Dublin, 7, Ireland.

EBV infection has been implicated in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Viral infection may occur from the early or late stage in IPF development. Whether alveolar epithelial cells, AECs, normally express EBV main receptor, CD21, remains uncertain. Such situations prompted us to exploit an efficient direct infection system to investigate EBV receptor repertoire in primary human AECs. Using human primary type 2 AECs, which have been grown in basal medium supplemented with 10 ng/ml Keratinocyte Growth Factor, and type 1 AECs, supplemented with Epithelial Growth Factor, both AEC lines express CD21 mRNA and protein with a significant increase in type 2 cells. Type 2 AECs have been exposed to TGFbeta1 and IL-4, whose expression is associated with IPF development. CD21 is highly expressed in type 2 AECs following IL-4 exposure. EBV bound to type 2 AECs membrane increases significantly following pre-treatment with IL-4 (p<0.001) and decreasing antagonizing CD21 receptor (p<0.01). 200 microg/ml G418-mediated selection of EBV-Neomycin resistant infected cells selected IL-4 pre-exposed type 2 AECs. Our study of a viral cell line model provides evidence to suggest that CD21-dependent viral entry plays a crucial role in type 2 AECs, indicative of an IL-4 response EBV infection in IPF.
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http://dx.doi.org/10.1016/j.molimm.2009.01.002DOI Listing
May 2009

Cobalt ions induce chemokine secretion in primary human osteoblasts.

J Orthop Res 2009 Jul;27(7):855-64

UCD Clinical Research Centre, UCD School of Medicine & Medical Sciences, Mater University Hospital, Dublin, Ireland.

Chemokines are major regulators of the inflammatory response and have been shown to play an important role in periprosthetic osteolysis. Titanium particles have previously been shown to induce IL-8 and MCP-1 secretion in osteoblasts. These chemokines result in the chemotaxis and activation of neutrophils and macrophages, respectively. Despite a resurgence in the use of cobalt-chromium-molybdenum alloys in metal-on-metal arthroplasty, cobalt and chromium ion toxicity in the periprosthetic area has been insufficiently studied. In this study we investigate the in vitro effect of cobalt ions on primary human osteoblast activity. We demonstrate that cobalt ions rapidly induce the protein secretion of IL-8 and MCP-1 in primary human osteoblasts. This elevated chemokine secretion is preceded by an increase in the transcription of the corresponding chemokine gene. Using a Transwell migration chemotaxis assay we also demonstrate that the chemokines secreted are capable of inducing neutrophil and macrophage migration. Furthermore, cobalt ions significantly inhibit osteoblast function as demonstrated by reduced alkaline phosphatase activity and calcium deposition. In aggregate these data demonstrate that cobalt ions can activate transcription of the chemokine genes IL-8 and MCP-1 in primary human osteoblasts. Cobalt ions are not benign and may play an important role in the pathogenesis of osteolysis by suppressing osteoblast function and stimulating the production and secretion of chemokines that attract inflammatory and osteoclastic cells to the periprosthetic area.
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http://dx.doi.org/10.1002/jor.20837DOI Listing
July 2009

Lung tissue storage: optimizing conditions for future use in molecular research.

Exp Lung Res 2008 Oct;34(8):455-66

General Clinical Research Unit, School of Medicine and Medical Sciences, University College Dublin, Mater Misericordiae University Hospital, and Dublin Molecular Medicine Centre, Dublin, Ireland.

The quality of tissue studied impacts greatly on oligonucleotide microarray results, emphasizing the importance of harvesting techniques. The analyzed RNA extracted from human lung samples preserved via 4 different storage conditions (RNAlater, phosphate-buffered saline, TRIzol, liquid nitrogen). RNA was assessed by denaturing gel electrophoresis, Agilent bioanalysis, real-time polymerase chain reaction (PCR), and Test3 Affymetrix chip hybridization. Results revealed better quality RNA from RNAlater samples on gel electrophoresis and bioanalysis. RNAlater samples also showed greater yield (r18s via PCR P < .05) and resulted in better Test3 chips hybridization (p < .05), suggesting RNAlater was superior at preserving lung tissue nucleic acid.
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http://dx.doi.org/10.1080/01902140802093162DOI Listing
October 2008

Mourning and melancholia revisited: correspondences between principles of Freudian metapsychology and empirical findings in neuropsychiatry.

Ann Gen Psychiatry 2008 Jul 24;7. Epub 2008 Jul 24.

Psychopharmacology Unit, University of Bristol, Bristol, UK.

Freud began his career as a neurologist studying the anatomy and physiology of the nervous system, but it was his later work in psychology that would secure his place in history. This paper draws attention to consistencies between physiological processes identified by modern clinical research and psychological processes described by Freud, with a special emphasis on his famous paper on depression entitled 'Mourning and melancholia'. Inspired by neuroimaging findings in depression and deep brain stimulation for treatment resistant depression, some preliminary physiological correlates are proposed for a number of key psychoanalytic processes. Specifically, activation of the subgenual cingulate is discussed in relation to repression and the default mode network is discussed in relation to the ego. If these correlates are found to be reliable, this may have implications for the manner in which psychoanalysis is viewed by the wider psychological and psychiatric communities.
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http://dx.doi.org/10.1186/1744-859X-7-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515304PMC
July 2008

Alveolar epithelial cell injury with Epstein-Barr virus upregulates TGFbeta1 expression.

Am J Physiol Lung Cell Mol Physiol 2008 Sep 11;295(3):L451-60. Epub 2008 Jul 11.

Advanced Lung Disease and Lung Transplant Program, Mater Misericordiae Univ. Hospital, Dublin, Ireland.

Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation, and ECM protein deposition. Epstein-Barr virus (EBV) has previously been localized to alveolar epithelial cells of IPF patients and is associated with a poor prognosis. In this study, we utilized a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV-associated lung fibrosis. Two cell lines, primary human alveolar epithelial cells type 2 and A549 cells, were infected with EBV. EBV lytic phase induction increased active and total transforming growth factor-beta1 (TGFbeta1) transcript expression in association with reduced cell proliferation and increased caspase 3/7 activity. Exposing EBV-infected cells to ganciclovir resulted in TGFbeta1 deregulation and reduced expression of EBV early response genes, BRLF1 and BZLF1. We targeted the BRLF1 and BZLF1 gene products, Rta and Zta, by silencing RNA, and this resulted in the normalization of TGFbeta1 transcript and cell proliferation levels. Our study using a viral cell line model complements existing human and animal model data and further provides evidence to suggest that viral epithelial cell injury may play a role in IPF.
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http://dx.doi.org/10.1152/ajplung.00376.2007DOI Listing
September 2008

Why does the world have such a 'down' on antidepressants?

J Psychopharmacol 2008 May;22(3):223-6

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http://dx.doi.org/10.1177/0269881108091877DOI Listing
May 2008

HIV proteins regulate bone marker secretion and transcription factor activity in cultured human osteoblasts with consequent potential implications for osteoblast function and development.

AIDS Res Hum Retroviruses 2007 Dec;23(12):1521-30

General Clinical Research Unit, School of Medicine and Medical Sciences, University College Dublin, Ireland.

A high incidence of decreased bone mineral density (BMD) has increasingly been associated with HIV infection. In this study mesenchymal stem cell (MSC) and human osteoblast (hOB) cell lines were treated with HIV tat, HIV rev, HIV p55-gag, HIV gp120 and HTLV env (100 ng/ml, 24 h). Cells were then analyzed for calcium deposition, alkaline phosphatase (ALP) activity, and lipid levels using established methods. Real-time PCR with gene-specific primers was used to quantify the mRNA levels of the transcription factors RUNX-2 and PPARgamma, transcription factors known to be pro-osteogenic and pro-adipogenic, respectively. The levels of secreted bone markers and transcription factor activity were determined using commercial assays. In OBs, HIV p55-gag and gp120 were seen to reduce calcium deposition, ALP activity, levels of secreted BMP-2, -7, and RANK-L, and the expression and activity of RUNX-2. The levels of osteocalcin were also significantly reduced by p55-gag treatment, while gp120 also increased PPARgamma activity. Lipid levels were also increased by gp120 treatment. The ability of MSCs to develop into functioning OBs was also affected by the presence of HIV proteins, with p55-gag inducing a decrease in osteogenesis, while rev induced an increase. HIV proteins can potentially modulate OB development and function in vitro via modulation of bone maker secretion and RUNX-2 and PPARgamma transcription factor activity.
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http://dx.doi.org/10.1089/aid.2007.0112DOI Listing
December 2007

A propos time and autoimmunity.

Clin Rev Allergy Immunol 2008 Jun;34(3):380-4

Facultad de Ingenieria, Universidad Nacional de Mar del Plata, Mar del Plata, Argentina.

The integrated defense system has been shaped over eons showing noteworthy robustness by surviving a million-year prehistory, a comparatively short evolving history and current transformation. Self-identification being part of it, so are deviations manifold expressed in autoimmunity. Epidemiological incidence and intensity, both being subject of change, are focused in the light of the time factor. Furthermore, it is stressed that there is no bi-univocal mutual relationship between immunity and defense and the origins of autoimmunity still remain mysterious. We question whether the present transforming events have occurred within too short a time to be attributed to genetic predisposition exclusively.
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http://dx.doi.org/10.1007/s12016-007-8054-xDOI Listing
June 2008

Host predisposition by endogenous Transforming Growth Factor-beta1 overexpression promotes pulmonary fibrosis following bleomycin injury.

J Inflamm (Lond) 2007 Sep 20;4:18. Epub 2007 Sep 20.

National Heart and Lung Transplant Program, Mater Misericordiae University Hospital, University College Dublin, Dublin.

Background: Idiopathic Pulmonary Fibrosis (IPF) is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGFbeta1 as a key effector cytokine in the development of lung fibrosis.

Methods: In this study we have used a transgenic mouse based strategy to identify the effect of overexpression of this key effector mediator on the development of pulmonary fibrosis in response to exogenous injury. We bred two lines (line 25 and 18) of transgenic mice (Tr+) that overexpressed active TGFbeta1. Three-month old transgenic and wild type mice were subsequently wounded with intraperitoneal bleomycin. Mice were sacrificed at 6 weeks post-bleomycin and their lungs analysed histologically and biochemically.

Results: The severity of lung fibrosis was significantly greater in the Tr+ mice compared to the wild type mice. Using an oligonucleotide microarray based strategy we identified discrete patterns of gene expression contributing to TGFbeta1 associated pulmonary fibrosis.

Conclusion: This data emphasises the importance of a host predisposition in the form of endogenous TGFbeta1, in the development of pulmonary fibrosis in response to an exogenous injury.
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http://dx.doi.org/10.1186/1476-9255-4-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169220PMC
September 2007

A prospective, double-blind, multicenter, randomized trial comparing ertapenem 3 vs >or=5 days in community-acquired intraabdominal infection.

J Gastrointest Surg 2008 Mar 11;12(3):592-600. Epub 2007 Sep 11.

Department Paride Stefanini, University La Sapienza, Policlinico Umberto I Viale del Policlinico, 00161, Rome, Italy.

Severe secondary peritonitis is diagnosed in only 20-30% of all patients, but studies to date have persisted in using a standard fixed duration of antibiotic therapy. This prospective, double-blind, multicenter, randomized clinical study compared the clinical and bacteriological efficacy and tolerability of ertapenem (1 g/day) 3 days (group I) vs >or=5 days (group II) in 111 patients with localized peritonitis (appendicitis vs non-appendicitis) of mild to moderate severity, requiring surgical intervention. In evaluable patients, the clinical response as primary efficacy outcome were assessed at the test-of-cure 2 and 4 weeks after discontinuation of antibacterial therapy. Ninety patients were evaluable. In groups I and II, 92.9 and 89.6% of patients were cured, respectively; 95.3% in group I and 93.7% in group II showed eradication. These differences were not statistically significant. The most frequent bacteria recovered were Escherichia coli and Bacteroides fragilis. A wound infection developed in seven patients (7.7%) and an intraabdominal infection in one patient (1.1%). There was a low frequency of drug-related clinical or laboratory adverse effects in both groups. Our study demonstrated that, in patients with localized community-acquired intraabdominal infection, a 3-day course of ertapenem had the same clinical and bacteriological efficacy as a standard duration.
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http://dx.doi.org/10.1007/s11605-007-0277-xDOI Listing
March 2008

HIV protease inhibitors selectively induce gene expression alterations associated with reduced calcium deposition in primary human osteoblasts.

AIDS Res Hum Retroviruses 2007 Feb;23(2):243-50

General Clinical Research Unit, Mater Misericordiae University Hospital, School of Medicine and Medical Sciences, University College Dublin, 44 Eccles Street, Dublin 7, Ireland.

HIV-infected patients are at increased risk of decreased bone mineral density. Some studies have implicated antiretroviral therapy as a contributor to the decreased bone mineral density seen in treated HIV-1 patients. In this study we explore the interactions between protease inhibitors (PI) and primary human osteoblast gene expression, highlighting a group of dysregulated genes that potentially are key factors in reducing bone formation. Runx-2 mRNA expression, calcium deposition, and alkaline phosphatase (ALP) activity decreased significantly in human osteoblast cultures after exposure to the PIs nelfinavir (NFV) and indinavir (IDV). Saquinavir (SQV), ritonavir (RTV), indinavir (IDV), or nelfinavir (NFV) exposure induced significant changes in genotypic expression as assessed by gene-chip microarray analysis. The altered genes from each group were compared to each other and a list of 8 upregulated and 13 downregulated genes only after NFV and IDV exposure was identified. This set includes TIMP-3, which has previously been demonstrated to be involved in osteoblast differentiation and extracellular matrix development processes. Silencing TIMP-3 mRNA expression using siRNA duplexes enhanced calcium deposition and ALP activity significantly, even after exposure to NFV and IDV. Our data suggest a link between reduced osteoblastic phenotype and a group of 21 altered genes following NFV and IDV treatment, and also suggest TIMP-3 may be involved in the PI-induced inhibition of osteoblast function.
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http://dx.doi.org/10.1089/aid.2006.0084DOI Listing
February 2007

HIV1 protease inhibitors selectively induce inflammatory chemokine expression in primary human osteoblasts.

Antiviral Res 2007 Apr 9;74(1):72-6. Epub 2007 Jan 9.

General Clinical Research Unit, School of Medicine and Medical Sciences, University College Dublin, Ireland.

HIV-infected patients are at increased risk of decreased bone mineral density. Several studies have implicated antiretroviral therapy as a contributor to the decreased bone mineral density seen in treated HIV-1 patients. Whilst the exact molecular mechanisms underlying decreased bone density remain to be elucidated, inflammation has been postulated to be an important pathogenomic mechanism. In this study, we have explored primary human osteoblast gene expression in response to protease inhibitors (PIs), by oligonucleotide microarray analysis. A list of dysregulated genes, correlated with the inflammatory response, increased significantly after NFV and RTV exposure. Analysis of gene and protein expression determined a selectively increase of the pro-inflammatory cytokines monocyte chemoattractant protein (MCP)-1 and interleukin-8 (IL-8) following exposure to a pharmacological concentration of NFV and RTV. These data suggested that generation of local inflammatory cascades may contribute to the development of decreased bone mineral density in highly active antiretroviral therapy (HAART)-treated HIV patients.
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http://dx.doi.org/10.1016/j.antiviral.2006.12.003DOI Listing
April 2007

Anxiety and OCD - the chicken or the egg?

J Psychopharmacol 2006 Nov;20(6):729-31

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http://dx.doi.org/10.1177/0269881106068424DOI Listing
November 2006

The role of emission tomography in pharmacokinetic and pharmacodynamic studies in clinical psychopharmacology.

Authors:
Andrea L Malizia

J Psychopharmacol 2006 Jul;20(4 Suppl):100-7

Psychopharmacology Unit, University of Bristol, Bristol, UK.

Position Emission Tomography (PET) and Single Photon Emission Tomography (SPECT) can be used for both pharmacokinetic and pharmacodynamic measures in vivo in man. As such they have a wide range of applications including description of neurochemical changes in disease, occupancy, brain effects of medicines and discovery and validation of biomarkers. The power of these tools is in their chemical specificity and sensitivity, and in the ability to describe processes in vivo, thus documenting the effects of genetic and environmental interactions. The future of these technologies is dependent on an investment in bringing out and validating new radiotracers.
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http://dx.doi.org/10.1177/1359786806066555DOI Listing
July 2006

New Pudicinae (Trichostrongylina, Heligmosomoidea), Pudica ctenomydis n. sp. parasite of Ctenomys talarum (Rodentia: Octodontidae) from Argentina.

Parasitol Int 2006 Mar 27;55(1):83-7. Epub 2005 Dec 27.

Laboratorio de Ecofisiología, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Casilla de Correo 1245, 7600-Mar del Plata, Argentina.

A total of 138 nematodes were found in the small intestine of Ctenomys talarum (Octodontidae) from Mar de Cobo, Argentina. A new nematode species, Pudica ctenomydis n. sp., is described. The new species more closely resembles P. pujoli Durette-Desset, 1990, parasite of Microcavia niata Thomas, from Bolivia. It can be distinguished from P. pujoli by the number of ridges and characteristics of the synlophe, the spicular morphology, differences in length between rays 9 and 10, and by the presence of a symmetrical caudal bursa and a cuticular expansion surrounding the body between vulva and anus in females.
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http://dx.doi.org/10.1016/j.parint.2005.10.004DOI Listing
March 2006
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