8-Methoxy-naphtho[2,3-b]thiophen-4,9-quinone, a non-competitive inhibitor of trypanothione reductase

The enzyme trypanothione reductase is a recognised drug target in trypanosomatids and has been used in the search of new compounds with potential activity against diseases such as leishmaniasis, Chagas disease and African trypanosomiasis. 8-Methoxy-naphtho [2,3-b] thiophen-4,9-quinone was selected in a screening of natural and synthetic compounds using an in vitro assay with the recombinant enzyme from Trypanosoma cruzi. Its mode of inhibition fits a non-competitive model with respect to the substrate (trypanothione) and to the co-factor (NADPH), with Ki-values of 5 and 3.6 µM, respectively. When tested against human glutathione reductase, this compound did not display any significant inhibition at 100 µM, indicating a good selectivity against the parasite enzyme.

Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by captopril

Captopril, an inhibitor of angiotensin converting enzyme, was administered twice daily to 13 hypertensive patients for a mean period of 9 weeks. Continuous blood pressure control in the ambulatory patients was established with a portable blood pressure recorder. Notwithstanding, in eight patients with normal renal function, plasma converting enzyme was found to resume normal activity before administration of the morning dose of captopril. Only in 5 patients with impaired renal function did some blockade of plasma converting enzyme persist for more than 12 hours. Measured plasma converting enzyme activity seemed to reflect total conversion of angiotensin I, including conversion in the pulmonary vascular bed, since changes in its activity were closely paralled by changes in plasma aldosterone levels. Bradykinin accumulation seems unlikely when converting enzyme and thus, presumably, kininase II has resumed normal activity. Captopril administration does not seem to alter plasma epinephrine or norepinephrine levels. Blood pressure reduction in the face of normal angiotensin converting enzyme activity is probably due to hyporesponsiveness of the arterioles to pressor hormones, which may be due to specific renin-related and/or nonspecific effects of captopril.

Enterobiasis and strongyloidiasis and associated co-infections and morbidity markers in infants, preschool- and school-aged children from rural coastal Tanzania: a cross-sectional study.

Background. There is a paucity of data pertaining to the epidemiology and public health impact of Enterobius vermicularis and Strongyloides stercoralis infections. We aimed to determine the extent of enterobiasis, strongyloidiasis, and other helminth infections and their association with asymptomatic Plasmodium parasitaemia, anaemia, nutritional status, and blood cell counts in infants, preschool-aged (PSAC), and school-aged children (SAC) from rural coastal Tanzania.MethodsA total of 1,033 children were included in a cross-sectional study implemented in the Bagamoyo district in 2011/2012. Faecal samples were examined for intestinal helminth infections using a broad set of quality controlled methods. Finger-prick blood samples were subjected to filariasis and Plasmodium parasitaemia testing and full blood cell count examination. Weight, length/height, and/or mid-upper arm circumference were measured and the nutritional status determined in accordance with age.Results E. vermicularis infections were found in 4.2% of infants, 16.7%, of PSAC, and 26.3% of SAC. S. stercoralis infections were detected in 5.8%, 7.5%, and 7.1% of infants, PSAC, and SAC, respectively. Multivariable regression analyses revealed higher odds of enterobiasis in children of all age-groups with a reported anthelminthic treatment history over the past six months (odds ratio (OR): 2.15; 95% confidence interval (CI): 1.22 - 3.79) and in SAC with a higher temperature (OR: 2.21; CI: 1.13 - 4.33). Strongyloidiasis was associated with eosinophilia (OR: 2.04; CI: 1.20-3.48) and with Trichuris trichiura infections (OR: 4.13; CI: 1.04-16.52) in children of all age-groups, and with asymptomatic Plasmodium parasitaemia (OR: 13.03; CI: 1.34 - 127.23) in infants. None of the investigated helminthiases impacted significantly on the nutritional status and anaemia, but moderate asymptomatic Plasmodium parasitaemia was a strong predictor for anaemia in children aged older than two years (OR: 2.69; 95% CI: 1.23 ¿ 5.86).Conclusions E. vermicularis and S. stercoralis infections were moderately prevalent in children from rural coastal Tanzania. Our data can contribute to inform yet missing global burden of disease and prevalence estimates for strongyloidiasis and enterobiasis. The association between S stercoralis and asymptomatic Plasmodium parasitaemia found here warrants further comprehensive investigations.

Long-term transcutaneous monitoring of oxygen tension and carbon dioxide at 42 degrees C in critically ill neonates: improved performance of the tcpo2 monitor with topical metabolic inhibition.

Whereas during the last few years handling of the transcutaneous PO2 (tcPO2) and PCO2 (tcPCO2) sensor has been simplified, the high electrode temperature and the short application time remain major drawbacks. In order to determine whether the application of a topical metabolic inhibitor allows reliable measurement at a sensor temperature of 42 degrees C for a period of up to 12 h, we performed a prospective, open, nonrandomized study in a sequential sample of 20 critically ill neonates. A total of 120 comparisons (six repeated measurements per patient) between arterial and transcutaneous values were obtained. Transcutaneous values were measured with a control sensor at 44 degrees C (conventional contact medium, average application time 3 h) and a test sensor at 42 degrees C (Eugenol solution, average application time 8 h). Comparison of tcPO2 and PaO2 at 42 degrees C (Eugenol solution) showed a mean difference of +0.16 kPa (range +1.60 to -2.00 kPa), limits of agreement +1.88 and -1.56 kPa. Comparison of tcPO2 and PaO2 at 44 degrees C (control sensor) revealed a mean difference of +0.02 kPa (range +2.60 to -1.90 kPa), limits of agreement +2.12 and -2.08 kPa. Comparison of tcPCO2 and PaCO2 at 42 degrees C (Eugenol solution) showed a mean difference of +0.91 (range +2.30 to +0.10 kPa), limits of agreement +2.24 and -0.42 kPa. Comparison of tcPCO2 and PaCO2 at 44 degrees C (control sensor) revealed a mean difference of +0.63 kPa (range 1.50 to -0.30 kPa), limits of agreement +1.73 and -0.47 kPa. CONCLUSION: Our results show that the use of an Eugenol solution allows reliable measurement of tcPO2 at a heating temperature of 42 degrees C; the application time can be prolongued up to a maximum of 12 h without aggravating the skin lesions. The performance of the tcPCO2 monitor was slightly worse at 42 degrees C than at 44 degrees C suggesting that for the Eugenol solution the metabolic offset should be corrected.

Diagnosing poisoning: Carbon monoxide (CO)

Guidance for primarycareon how to deal withpatients presenting with possible symptoms of carbon monoxide (CO) poisoning. Produced by the Health Protection Agency and adapted by the Public Health Agency.

Therapeutic Drug Monitoring of the new targeted anticancer agents imatinib, nilotinib, dasatinib, sunitinib, sorafenib and lapatinib by LC tandem mass spectrometry.

The treatment of some cancer patients has shifted from traditional, non-specific cytotoxic chemotherapy to chronic treatment with molecular targeted therapies. Imatinib mesylate, a selective inhibitor of tyrosine kinases (TKIs) is the most prominent example of this new era and has opened the way to the development of several additional TKIs, including sunitinib, nilotinib, dasatinib, sorafenib and lapatinib, in the treatment of various hematological malignancies and solid tumors. All these agents are characterized by an important inter-individual pharmacokinetic variability, are at risk for drug interactions, and are not devoid of toxicity. Additionally, they are administered for prolonged periods, anticipating the careful monitoring of their plasma exposure via Therapeutic Drug Monitoring (TDM) to be an important component of patients' follow-up. We have developed a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) requiring 100 microL of plasma for the simultaneous determination of the six major TKIs currently in use. Plasma is purified by protein precipitation and the supernatant is diluted in ammonium formate 20 mM (pH 4.0) 1:2. Reverse-phase chromatographic separation of TKIs is obtained using a gradient elution of 20 mM ammonium formate pH 2.2 and acetonitrile containing 1% formic acid, followed by rinsing and re-equilibration to the initial solvent composition up to 20 min. Analyte quantification, using matrix-matched calibration samples, is performed by electro-spray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<9.6%), overall process efficiency (87.1-104.2%), as well as TKIs short- and long-term stability in plasma. The method is precise (inter-day CV%: 1.3-9.4%), accurate (-9.2 to +9.9%) and sensitive (lower limits of quantification comprised between 1 and 10 ng/mL). This is the first broad-range LC-MS/MS assay covering the major currently in-use TKIs. It is an improvement over previous methods in terms of convenience (a single extraction procedure for six major TKIs, reducing significantly the analytical time), sensitivity, selectivity and throughput. It may contribute to filling the current knowledge gaps in the pharmacokinetics/pharmacodynamics relationships of the latest TKIs developed after imatinib and better define their therapeutic ranges in different patient populations in order to evaluate whether a systematic TDM-guided dose adjustment of these anticancer drugs could contribute to minimize the risk of major adverse reactions and to increase the probability of efficient, long lasting, therapeutic response.

Pharmacological inhibition of interleukin-15 prevents colitis and associated bone loss in IL-10 knockout mice

Bone loss secondary to inflammatory bowel diseases (IBD) is largely explained by activated T cells producing cytokines that trigger osteoclastogenesis and accelerate bone resorptionwhile inhibiting bone formation. In IBD, elevated expression of interleukin (IL)-15, a T cell growth factor, plays a central role in T cell activation, pro-inflammatory cytokine production and the development of colitis. We previously reported that IL-15 enhances RANKL-induced osteoclastogenesis and that an IL-15 antagonist, CRB-15, prevents weight and bone loss in a mousemodel of dextran sulfate sodium-induced colitis.We hypothesized that inhibition of IL-15 signalingmight prevent bone loss in IL-10 deficient (IL10−/−) mice, that develop spontaneous bowel inflammation associatedwith osteopeniawhen they are no longer raised under germ-free conditions.Mice received anIL-15 antagonist (CRB-15, 5 μg/day, n=5) or IgG2a (5 μg/day, n=4) fromweek 10 to 14 of age. The severity of colitis was assessed by histology and bowel cytokine gene expression by real time PCR. Bone mass and architecturewere evaluated by ex vivo DXA on femur and micro-computed tomography on femur and vertebra. Bodyweight gainwas similar in the two groups. After 4 weeks, colonwas 29% shorter in CRB-15 treatedmice (p<0.006), a sign of reduced inflammation. Histological analysis indicated a transmural infiltration of inflammatory cells, lymphoepithelial lesions and increased size of villi (histological score=4/6) in IgG2a treated mice, whereas colon from CRB-15 treated mice exhibited mild infiltration of inflammatory cells of the lamina propria, no mucosal damages and a minimal increased size of villi (histological score=1.6/6). Levels of TNFα, IL-17 and IL-6 mRNA in the colon were significantly reduced in CRB-15 treated mice (p<0.04 vs IgG2), indicating a decrease in colon inflammation. CRB-15 improved femur BMD (+10.6% vs IgG2a, p<0.002), vertebral trabecular bone volume fraction (BV/TV, +19.7% vs IgG2a, p<0.05) and thickness (+11.6% vs IgG2a, p<0.02). A modest but not significant increase in trabecular BV/TV was observed at the distal femur. Cortical thicknesswas also higher at themidshaft femur in CRB-15 treatedmice (+8.3% vs IgG2a, p<0.02). In conclusion, we confirm and extend our results about the effects of CRB-15 in colitis. Antagonizing IL-15 may exert favorable effects on intestinal inflammation and prevent bone loss and microarchitecture alterations induced by colitis. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: B. Brounais-Le Royer Grant / Research Support from Novartis Consumer Health Foundation, S. Ferrari-Lacraz: none declared, D. Velin: none declared, X. Zheng: none declared, S. Ferrari: none declared, D. Pierroz: none declared.

How local excitation-inhibition ratio impacts the whole brain dynamics.

The spontaneous activity of the brain shows different features at different scales. On one hand, neuroimaging studies show that long-range correlations are highly structured in spatiotemporal patterns, known as resting-state networks, on the other hand, neurophysiological reports show that short-range correlations between neighboring neurons are low, despite a large amount of shared presynaptic inputs. Different dynamical mechanisms of local decorrelation have been proposed, among which is feedback inhibition. Here, we investigated the effect of locally regulating the feedback inhibition on the global dynamics of a large-scale brain model, in which the long-range connections are given by diffusion imaging data of human subjects. We used simulations and analytical methods to show that locally constraining the feedback inhibition to compensate for the excess of long-range excitatory connectivity, to preserve the asynchronous state, crucially changes the characteristics of the emergent resting and evoked activity. First, it significantly improves the model's prediction of the empirical human functional connectivity. Second, relaxing this constraint leads to an unrealistic network evoked activity, with systematic coactivation of cortical areas which are components of the default-mode network, whereas regulation of feedback inhibition prevents this. Finally, information theoretic analysis shows that regulation of the local feedback inhibition increases both the entropy and the Fisher information of the network evoked responses. Hence, it enhances the information capacity and the discrimination accuracy of the global network. In conclusion, the local excitation-inhibition ratio impacts the structure of the spontaneous activity and the information transmission at the large-scale brain level.

Regulation of the epithelial Na+ channel ENaC by Tsg101 in renal epithelial cells

Kidneys are the main regulator of salt homeostasis and blood pressure. In the distal region of the tubule active Na-transport is finely tuned. This transport is regulated by various hormonal pathways including aldosterone that regulates the reabsorption at the level of the ASDN, comprising the late DCT, the CNT and the CCD. In the ASDN, the amiloride-sensitive epithelial Na-channel (ENaC) plays a major role in Na-homeostasis, as evidenced by gain-of function mutations in the genes encoding ENaC, causing Liddle's syndrome, a severe form of salt-sensitive hypertension. In this disease, regulation of ENaC is compromised due to mutations that delete or mutate a PY-motif in ENaC. Such mutations interfere with Nedd4-2- dependent ubiquitylation of ENaC, leading to reduced endocytosis of the channel, and consequently to increased channel activity at the cell surface. After endocytosis ENaC is targeted to the lysosome and rapidly degraded. Similarly to other ubiquitylated and endocytosed plasma membrane proteins (such as the EGFR), it is likely that the multi-protein complex system ESCRT is involved. To investigate the involvement of this system we tested the role of one of the ESCRT proteins, Tsg101. Here we show that Tsg101 interacts endogenously and in transfected HEK-293 cells with all three ENaC sub-units. Furthermore, mutations of cytoplasmic lysines of ENaC subunits lead to the disruption of this interaction, indicating a potential involvement of ubiquitin in Tsg101 / ENaC interaction. Tsg101 knockdown in renal epithelial cells increases the total and cell surface pool of ENaC, thus implying TsglOl and consequently the ESCRT system in ENaC degradation by the endosomal/lysosomal system. - Les reins sont les principaux organes responsables de la régulation de la pression artérielle ainsi que de la balance saline du corps. Dans la région distale du tubule, le transport actif de sodium est finement régulé. Ce transport est contrôlé par plusieurs hormones comme l'aldostérone, qui régule la réabsorption au niveau de l'ASDN, segment comprenant la fin du DCT, le CNT et le CCD. Dans l'ASDN, le canal à sodium épithélial sensible à l'amiloride (ENaC) joue un rôle majeur dans l'homéostasie sodique, comme cela fut démontré par les mutations « gain de fonction » dans les gênes encodant ENaC, causant ainsi le syndrome de Liddle, une forme sévère d'hypertension sensible au sel. Dans cette maladie, la régulation d'ENaC est compromise du fait des mutations qui supprime ou mute le domaine PY présent sur les sous-unités d'ENaC. Ces mutations préviennent l'ubiquitylation d'ENaC par Nedd4-2, conduisant ainsi à une baisse de l'endocytose du canal et par conséquent une activité accrue d'ENaC à la surface membranaire. Après endocytose, ENaC est envoyé vers le lysosome et rapidement dégradé. Comme d'autres protéines membranaires ubiquitylées et endocytées (comme l'EGFR), il est probable que le complexe multi-protéique ESCRT est impliqué dans le transport d'ENaC au lysosome. Pour étudier l'implication du système d'ESCRT dans la régulation d'ENaC nous avons testé le rôle d'une protéine de ces complexes, TsglOl. Notre étude nous a permis de démontrer que TsglOl se lie aux trois sous-unités ENaC aussi bien en co-transfection dans des cellules HEK-293 que de manière endogène. De plus, nous avons pu démontrer l'importance de l'ubiquitine dans cette interaction par la mutation de toutes les lysines placées du côté cytoplasmique des sous-unités d'ENaC, empêchant ainsi l'ubiquitylation de ces sous-unités. Enfin, le « knockdown » de TsglOl dans des cellules épithéliales de rein induit une augmentation de l'expression d'ENaC aussi bien dans le «pool» total qu'à la surface membranaire, indiquant ainsi un rôle pour TsglOl et par conséquent du système d'ESCRT dans la dégradation d'ENaC par la voie endosome / lysosome. - Le corps humain est composé d'organes chacun spécialisé dans une fonction précise. Chaque organe est composé de cellules, qui assurent la fonction de l'organe en question. Ces cellules se caractérisent par : - une membrane qui leur permet d'isoler leur compartiment interne (milieu intracellulaire ou cytoplasme) du liquide externe (milieu extracellulaire), - un noyau, où l'ADN est situé, - des protéines, sortent d'unités fonctionnelles ayant une fonction bien définie dans la cellule. La séparation entre l'extérieure et l'intérieure de la cellule est essentielle pour le maintien des composants de ces milieux ainsi que pour la bonne fonction de l'organisme et des cellules. Parmi ces composants, le sodium joue un rôle essentiel car il conditionne le maintien de volume sanguin en participant au maintien du volume extracellulaire. Une augmentation du sodium dans l'organisme provoque donc une augmentation du volume sanguin et ainsi provoque une hypertension. De ce fait, le contrôle de la quantité de sodium présente dans l'organisme est essentiel pour le bon fonctionnement de l'organisme. Le sodium est apporté par l'alimentation, et c'est au niveau du rein que va s'effectuer le contrôle de la quantité de sodium qui va être retenue dans l'organisme pour le maintien d'une concentration normale de sodium dans le milieu extracellulaire. Le rein va se charger de réabsorber toutes sortes de solutés nécessaires pour l'organisme avant d'évacuer les déchets ou le surplus de ces solutés en produisant l'urine. Le rein va se charger de réabsorber le sodium grâce à différentes protéines, parmi elle, nous nous sommes intéressés à une protéine appelée ENaC. Cette protéine joue un rôle important dans la réabsorption du sodium, et lorsqu'elle fonctionne mal, comme il a pu être observé dans certaines maladies génétiques, il en résulte des problèmes d'hypo- ou d'hypertension. Les problèmes résultant du mauvais fonctionnement de cette protéine obligent donc la cellule à réguler efficacement ENaC par différents mécanismes, notamment en diminuant son expression et en dégradant le « surplus ». Dans cette travail de thèse, nous nous sommes intéressés au mécanisme impliqué dans la dégradation d'ENaC et plus précisément à un ensemble de protéines, appelé ESCRT, qui va se charger « d'escorter » une protéine vers un sous compartiment à l'intérieur de la cellule ou elle sera dégradée.

Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes

N-allyl (NAOx) and N-propyl (NPOx) oxamates were designed as inhibitors of alpha-hydroxyacid dehydrogenase (HADH) isozyme II from Trypanosoma cruzi. The kinetic studies showed that NAOx and NPOx were competitive inhibitors of HADH-isozyme II (Ki = 72 µM, IC50 = 0.33 mM and 70 µM, IC50 = 0.32 mM, respectively). The attachment of the allylic and propylic chains to nitrogen of the competitive inhibitor oxamate (Ki = 0.91 mM, IC50 = 4.25 mM), increased 12.6 and 13-folds respectively, the affinity for T. cruzi HADH-isozyme II. NAOx and NPOx were selective inhibitors of HADH-isozyme II, because other T. cruzi dehydrogenases were not inhibited by these substances. Since HADH-isozyme II participates in the energy metabolism of T. cruzi, a trypanocidal effect can be expected with these inhibitors. However, we were not able to detect any trypanocidal activity with these oxamates. When the corresponding ethyl esters of N-allyl (Et-NAOx) and N-propyl (Et-NPOx) oxamates were tested as a possible trypanocidal prodrugs, in comparison with nifurtimox and benznidazole, the expected trypanocidal effects were obtained.

Substance abuse treatment for persons with co-occurring disorders.

This TIP, Substance Abuse Treatment for Persons With Co-Occurring Disorders, revises TIP 9, Assessment and Treatment of Patients With Coexisting Mental Illness and Alcohol and Other Drug Abuse. The revised TIP provides information about new developments in the rapidly growing field of co-occurring substance use and mental disorders and captures the state-of-the-art in the treatment of people with co-occurring disorders. The TIP focuses on what the substance abuse treatment clinician needs to know and provides that information in an accessible manner. The TIP synthesizes knowledge and grounds it in the practical realities of clinical cases and real situations so the reader will come away with increased knowledge, encouragement, and resourcefulness in working with clients with co-occurring disorders. Contents: Executive Summary â?¢ 1 Introduction  2 Definitions, Terms, and Classification Systems for Co-Occurring Disorders  3 Keys to Successful Programming  4 Assessment  5 Strategies for Working With Clients With Co-Occurring Disorders  6 Traditional Settings and Models  7 Special Settings and Specific Populations  8 A Brief Overview of Specific Mental Disorders and Cross-Cutting Issues 9 Substance-Induced Disorders Appendix A: Bibliography Appendix B: Acronyms  Appendix C: Glossary of Terms Appendix D: Specific Mental Disorders: Additional Guidance for the Counselor  Appendix E: Emerging Models â?¢ Appendix F: Common Medications for Disorders  Appendix G: Screening and Assessment Instruments  Appendix H: Screening Instruments  Appendix I: Selected Sources of Training  Appendix J: Dual Recovery Mutual Self-Help Programs and Other Resources for Consumers and Providers  Appendix K: Confidentiality  Appendix L: Resource Panel  Appendix M: Cultural Competency and Diversity Network Participants Appendix N: Field ReviewersThis resource was contributed by The National Documentation Centre on Drug Use.

Clinical and immunological consequences of human T cell leukemia virus type-I and Schistosoma mansoni co-infection

Human T cell leukemia virus type-I (HTLV-I) infection is associated with spontaneous T cell activation and uncontrolled lymphocyte proliferation. An exacerbated type-1 immune response with production of pro-inflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha) is significantly higher in patients with myelopathy associated to HTLV-I than in HTLV-I asymptomatic carriers. In contrast with HTLV-I, a chronic Schistosoma mansoni infection is associated with a type-2 immune response with high levels of interleukin (IL-4, IL-5, and IL-10) and low levels of IFN-gamma. In this study, clinical and immunological consequences of the HTLV-I and S. mansoni infection were evaluated. The immune response in patients with schistosomiasis co-infected with HTLV-I showed low levels of IL-5 (p < 0.05) in peripheral blood mononuclear cells cultures stimulated with S. mansoni antigen (SWAP) and decreased SWAP-specific IgE levels when compared with patients with only schistosomiasis (p < 0.05). Liver fibrosis was mild in all HTLV-I co-infected patients. Immunological response was also compared in individuals who had only HTLV-I infection with those who were co-infected with HTLV-I and helminths (S. mansoni and Strongyloides stercoralis). In patients HTLV-I positive co-infected with helminths the IFN-gamma levels were lower than in individuals who had only HTLV-I. Moreover, there were fewer cells expressing IFN-gamma and more cells expressing IL-10 in individuals co-infected with HTLV-I and helminths. These dates indicate that HTLV-I infection decrease type 2-response and IgE synthesis and are inversely associated with the development of liver fibrosis. Moreover, helminths may protect HTLV-I infected patients to produce large quantities of pro-inflammatory cytokines such as IFN-gamma.

Immune response in cervical dysplasia induced by human papillomavirus: the influence of human immunodeficiency virus-1 co-infection - review

Human immunodeficiency virus (HIV-1) has become an important risk factor for human papillomavirus (HPV) infection and the development of HPV associated lesions in the female genital tract. HIV-1 may also increase the oncogenicity of high risk HPV types and the activation of low risk types. The Center for Disease Control and Prevention declared invasive cervical cancer an acquired immunodeficience virus (AIDS) defining illness in HIV positive women. Furthermore, cervical cancer happens to be the second most common female cancer worldwide. The host's local immune response plays a critical factor in controlling these conditions, as well as in changes in the number of professional antigen-presenting cells, cytokine, and MHC molecules expression. Also, the production of cytokines may determine which arm of the immune response will be stimulated and may influence the magnitude of immune protection. Although there are many studies describing the inflammatory response in HPV infection, few data are available to demonstrate the influence of the HIV infection and several questions regarding the cervical immune response are still unknown. In this review we present a brief account of the current understanding of HIV/HPV co-infection, emphasizing cervical immune response.

Ballina Eat Wise Project

The Mayo North East Ballina Eat Wise project will proactively engage with disadvantaged communities, including migrant and Traveller groups, in Ballina to encourage and support people to make informed decisions regarding their diet and that of their families. The project aims to empower people with the resources, skills and knowledge to improve their physical and mental wellbeing through affordable healthy eating. A steering group comprising local stakeholders will be established to co-ordinate and inform the CFI’s work and to ensure it is fully addressing the needs of the target group. The CFI will begin by developing a training module to equip a group of peer researchers to carry out a needs analysis. The information gathered will inform the practical aspects of the project ensuring participation and a sense of ownership from the local community. Young people will be targeted through local schools and youth organisations. Training will be provided for both adults and young people in vegetable/fruit growing, nutrition, cooking, preventing food wastage, smart shopping and budgeting. Practical cookery demonstrations coupled with advice on healthy eating will take place in the target areas. The project will also engage with local supermarkets and takeaways to encourage the provision of healthy affordable options. Other options to increase the availability of healthy food in the target areas will be explored. Part of theCFI Programme 2013-2015 Initiative Type Nutrition Education and Training Programmes Location Mayo Target Groups Children (13-18 years) Families Partner Agencies safefood