Endothelial nitric oxide synthase gene transfer restores endothelium-dependent relaxations and attenuates lesion formation in carotid arteries in apolipoprotein E-deficient mice.

Nitric oxide (NO) and monocyte chemoattractant protein-1 (MCP-1) exert partly opposing effects in vascular biology. NO plays pleiotropic vasoprotective roles including vasodilation and inhibition of platelet aggregation, smooth muscle cell proliferation, and endothelial monocyte adhesion, the last effect being mediated by MCP-1 downregulation. Early stages of arteriosclerosis are associated with reduced NO bioactivity and enhanced MCP-1 expression. We have evaluated adenovirus-mediated gene transfer of human endothelial NO synthase (eNOS) and of a N-terminal deletion (8ND) mutant of the MCP-1 gene that acts as a MCP-1 inhibitor in arteriosclerosis-prone, apolipoprotein E-deficient (ApoE(-/-)) mice. Endothelium-dependent relaxations were impaired in carotid arteries instilled with a noncoding adenoviral vector but were restored by eNOS gene transfer (p < 0.01). A perivascular collar was placed around the common carotid artery to accelerate lesion formation. eNOS gene transfer reduced lesion surface areas, intima/media ratios, and macrophage contents in the media at 5-week follow-up (p < 0.05). In contrast, 8ND-MCP-1 gene transfer did not prevent lesion formation. In conclusion, eNOS gene transfer restores endothelium-dependent vasodilation and inhibits lesion formation in ApoE(-/-) mouse carotids. Further studies are needed to assess whether vasoprotection is maintained at later disease stages and to evaluate the long-term efficacy of eNOS gene therapy for primary arteriosclerosis.

Reversible congestive heart failure associated with primary carnitin deficiency: report of a case and review of the literature.

A 5-year-old previously healthy boy was admitted for abdominal pain and vomiting. Physical examination showed tachypnoe (32/min), hepatomegaly and painful palpation of the upper right abdominal quadrant. Laboratory tests were normal except for elevated ammonium (202mcmol/l). Chest X-ray was performed, showing cardiomegaly and interstitial edema. Transthoracic echocardiography revealed dilated left cavities and LV hypertrophy together with a diffuse hypokinesia and LVEF of 30-40%. Diuretics and ACE-inhibitors were introduced. At that time, the differential diagnosis for the DCM included myocarditis, congenital or genetic, metabolic or autoimmune disease. The next day, the boy underwent cardiac magnetic resonance (CMR) examination, showing a severe dilatation of the LV with an end-diastolic diameter of 50mm and a volume of 150ml. LVEF was 20% with diffuse LV hypokinesia (Fig. 1). No late enhancement was present after Gadolinium injection, ruling out myocarditis. Further laboratory metabolic analysis indicated severely decreased total and free carnitin levels and low renal carnitin reabsorption, corroborating the diagnosis of primary carnitin deficiency (PCD). Carnitin substitution was initiated. The clinical condition rapidly improved. No symptoms of heart failure were present anymore. A follow-up CMR performed 9 months later confirmed the recovery. LV end-diastolic volume decreased from 150ml to 66ml, LVEF increased from 20% to 55% (Fig. 2). Late enhancement was absent after Gadolinum injection (Fig. 3).Carnitin is required for the transport of fatty acids from the cytosol into mitochondria during lipid breakdown. 75% of carnitin is obtained from food, 25% is endogenously synthesized. PCD is an autosomal recessive disorder resulting from impairment of a transporter activity, caused by mutation of the SLC22A5 gene. Incidence is about 1 in 40'000 newborns. Diagnosis is usually made at age 1 to 7. Three forms of PCD are described. In the form associated with cardiomyopathy, the disease is progressive and patient die from heart failure if not treated. Substitution of L-Carnitin leads to a dramatic improvement of disease course.This case underlines the crucial role of etiologic diagnostics in this reversible form of DCM. Early diagnostics and therapy are critical for the prognosis of the patient. This is furthermore an example of a role played by CMR in the diagnostic work-up of heart failure and its follow-up under therapy.

Alcool et comorbidités psychiatriques pour le praticien [Alcohol and psychiatric comorbidities in primary care].

Patients presenting with alcohol-related problems frequently suffer from comorbid mental health problems. From a broader perspective, patients having a comorbid situation between an addiction and a psychiatric trouble are at risk of being underdiagnosed for one of the two diseases. This litterature review tries to outline the issues linked to rigorous psychiatric diagnoses in the alcoologic situation, to describe the epidemiology of alcohol dual diagnosis, and to sum up scientific knowledge about the most adapted medication options and treatment settings.

Ecology of mosquitoes (Diptera: Culicidae) in areas of Serra do Mar State Park, State of São Paulo, Brazil. I - Monthly frequency and climatic factors

The ecology of mosquitoes were studied (Diptera: Culicidae) in areas of Serra do Mar State Park, State of São Paulo, Brazil. Systematized monthly human bait collections were made three times a day, for periods of 2 or 3 h each, in sylvatic and rural areas for 24 consecutive months (January 1991 to December 1992). A total of 24,943 specimens of adult mosquitoes belonging to 57 species were collected during 622 collective periods. Coquillettidia chrysonotum was the most frequent collected mosquito (45.8%) followed by Aedes serratus (6.8%), Cq. venezuelensis (6.5%), Psorophora ferox (5.2) and Ps. albipes (3.1%). The monthly averages of temperature and relative humidity were inserted in the ten-year average limits of maximum and minimum of the previous ten-years. Rainfall accompanied the curve of the ten-year averages. Those climatic factors were influential in the incidence of some species; temperature: Anopheles cruzii, An. mediopunctatus, Ae. scapularis, Ae. fulvus, Cq. chrysonotum, Cq. venezuelensis, Runchomyia reversa, Wyeomyia dyari, Wy. confusa, Wy. shannoni, Wy. theobaldi and Limatus flavisetosus; relative humidity: Ae. serratus, Ae. scapularis, Cq. venezuelensis and Ru. reversa; rainfall: An. cruzii, Ae. scapularis, Ae. fulvus, Cq. venezuelensis Ru. reversa, Wy. theobaldi and Li. flavisetosus.

Ecology of mosquitoes (Diptera: Culicidae) in areas of Serra do Mar State Park, State of São Paulo, Brazil. II - Habitat distribution

The mosquito (Diptera: Culicidae) ecology was studied in areas of Serra do Mar State Park, State of São Paulo, Brazil. Systematized biweekly human bait collections were made three times a day, for periods of 2 or 3 h each, in sylvatic and rural areas for 24 consecutive months (January 1991 to December 1992). A total of 24,943 adult mosquitoes belonging to 57 species were collected during 622 collective periods. Aedes scapularis, Coquillettidia chrysonotum, Cq. venezuelensis, Wyeomyia dyari, Wy. longirostris, Wy. theobaldi and Wy. palmata were more frequently collected at swampy and at flooded areas. Anopheles mediopunctatus, Culex nigripalpus, Ae. serratus, Ae. fulvus, Psorophora ferox, Ps. albipes and the Sabethini in general, were captured almost exclusively in forested areas. An. cruzii, An. oswaldoi and An. fluminensis were captured more frequently in a residence area. However, Cx. quinquefasciatus was the only one truly eusynanthropic. An. cruzii and Ae. scapularis were captured feeding on blood inside and around the residence, indicating that both species, malaria and arbovirus vectors respectively, may be involved in the transmission of these such diseases in rural areas.

Submission to the Department of Environment, Heritage and Local Government: Sustainable Residential Development in Urban Areas

The Institute of Public Health in Ireland is an all-island body which aims to improve health in Ireland by working to combat health inequalities and influence public policies in favour of health. The Institute promotes co-operation in research, training, information and policy in order to contribute to policies which tackle inequalities in health.   Over the past ten years the Institute has worked closely with the Department of Health and Children and the Department of Health, Social Services and Public Safety in Northern Ireland to build capacity for public health across the island of Ireland.   The Institute takes the view that health is determined by policies, plans and programmes in many sectors outside the health sector as well as being dependent on access to and availability of first class health services. The importance of other sectors is encapsulated in a social determinants of health perspective which recognises that health is largely shaped and influenced by the physical, social, economic and cultural environments in which people live, work and play. Figure 1 illustrates these multi-dimensional impacts on health and also serves to highlight the clear and inextricable links between health and sustainable development. Factors that impact on long-term sustainability will thus also impact on health.

IPH Submission to the Department of Health and Children Statement of Strategy 2008-2010

The Department of Health and Children Statement of Strategy will map out in broad terms the Department’s key areas of strategic action in the coming three years and act as the backdrop against which the Business Plans of each division of the Department will be prepared. The Institute’s recent submission on the Department’s Strategy Statement proposes that tackling inequalities in health form a key area of strategic action across all divisions within the Department in the coming three years. The Institute called for the Department to make additional commitments to tackle health inequalities at their root causes, in addition to developing services to meet the needs of poor and vulnerable members of society. The submission states that the full implementation of the National Health Information Strategy is now a matter of urgency and also strongly recommends that the Department makes the achievement of the recommendations of the recent A Strategy for Cancer Control in Ireland a priority in the coming years within its enhanced policy evaluation and analysis role. A stronger leadership role to advance the vision set out in the Primary Care Strategy is encouraged. The submission also recommends the development of a new set of high-level long-term targets relating to the reduction of inequalities to provide an overarching policy context against which related policies and the HSE operations could be structured.

Lassa virus entry in antigen presenting cells and evaluation of a novel nanoparticle vaccine platform against arena viruses

Arenaviruses are a large and diverse family of viruses that merit significant attention as causative agents of severe hemorrhagic fevers in humans. Lassa virus (LASV) in Africa and the South American hemorrhagic fever viruses Junin (JUNV), Machupo (MACV), and Guanarito (GTOV) have emerged as important human pathogens and represent serious public health problems in their respective endemic areas. A hallmark of fatal arenaviruses hemorrhagic fevers is a marked immunosuppression of the infected patients. Antigen presenting cells (APCs) such as macrophages and in particular dendritic cells (DCs) are early and preferred targets of arenaviruses infection. Instead of being recognized and presented as foreign antigens by DCs, arenaviruses subvert the normal mechanisms of pathogen recognition, invade DCs and establish a productive infection. Viral replication perturbs the DCs' ability to present antigens and to activate T and B cells, contributing to the marked virus-induced immunosuppression observed in fatal disease. Considering their crucial role in the development of an anti-viral immune response, the mechanisms by which arenaviruses, and in particular LASV, invade DCs are of particular interest. The C-type lectin DC-specific Intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) was recently identified as a potential entry receptor for LASV. The first project of my thesis focused therefore on the investigation of the role of DC-SIGN in LASV entry into primary human DCs. My data revealed that DC-SIGN serves as an attachment factor for LASV on human DCs and can facilitate capture of free virus and subsequent cell entry. However, in contrast to other emerging viruses, of the phlebovirus family, I found that DC-SIGN does likely not function as an authentic entry receptor for LASV. Moreover, I was able to show that LASV enters DCs via an unusually slow pathway that depends on actin, but is independent of clathrin and dynamin. Considering the lack of effective treatments and the limited public health infrastructure in endemic regions, the development of protective vaccines against arenaviruses is an urgent need. To address this issue, the second project of my thesis aimed at the development of a novel recombinant arenavirus vaccine based on a nanoparticle (NPs) platform and its evaluation in a small animal model. During the first phase of the project I designed, produced, and characterized suitable vaccine antigens. In the second phase of the project, I generated antigen-conjugated NPs, developed vaccine formulations, and tested the NPs for their ability to elicit anti-viral T cell responses as well as anti-viral antibodies. I demonstrated that the NPs platform is able to activate both cellular and humoral branches of the adaptive anti-viral immunity, providing proof-of-principle. In sum, my first project will allow, in a long term perspective, a better understanding of the viral pathogenesis and contribute to the development of novel antiviral strategies. The second project will expectidly offer a new treatment option against arenaviruses.

Northern Ireland Primary and Secondary Care Opioid Substitute Treatment Guidelines 2013 (PDF 4.5MB)

Drugs misuse

Primary School Survey 2006 - Knowledge and use of Alcohol Cigarettes and Drugs (PDF 565 KB)

Primary School Survey 2006 - Knowledge and use of alcohol, cigarettes and drugs.

Craigavon & Banbridge Community HSS Trust - Primary Care Mental Health Services Triage Pilot Scheme (PDF 266 KB)

Craigavon & Banbridge Community HSS Trust's final report on Primary Care Mental Health Services Triage Pilot Scheme. Part of the Department's redesign of community nursing project.