Darbo tikslas – įvertinti Marijampolės apskrities šeimos gydytojų nuomonę apie imunoprofilaktiką bei jos organizavimą pirminėje sveikatos priežiūroje. Metodika. Tyrimo metu apklausėme visus Marijampolės apskrities šeimos gydytojus, dirbančius viešosiose ir privačiose pirminės sveikatos priežiūros įstaigose. Respondentams buvo išdalintos 109 anketos, iš kurių teisingai užpildytos ir grąžintos buvo 86 (atsako dažnis 79,0 proc.). Duomenų analizę atlikome naudojant statistinį programinį paketą SPSS (17.0 versija). Hipotezės apie požymių priklausomybę buvo tikrinamos naudojant chi kvadrato (χ2) ir z kriterijus bei Spearmano koreliacijos koeficientą (r). Rezultatai. Šeimos gydytojai, teikiantys paslaugas vaikams, gana aktyviai vykdo jų imunoprofilaktiką pagal Lietuvos Respublikos vaikų profilaktinių skiepijimų kalendorių. Didžioji dalis respondentų (87,2 proc.) tėvus (globėjus) apie vaiko skiepijimą informuoja žodžiu, šiems atvykus į sveikatos priežiūros įstaigą, ir (ar) lankydami savo pacientus namuose (70,9 proc.). Skiepijimo mokamomis vakcinomis srityje apklaustieji dalyvauja gana pasyviai: kiek daugiau nei pusė tirtųjų (53,5 proc.) teigė visada informuojantys pacientus apie galimybę pasiskiepyti šiomis vakcinomis, mažiau nei trečdalis tyrimo dalyvių (31,4 proc.) nurodė tai darantys kartais, o likusioji dalis (15,1 proc.) – retai. Informaciją apie mokamas vakcinas savo pacientams teikiantys telefonu ir (ar) lankstinukuose, stenduose, esančiuose sveikatos priežiūros įstaigoje... [toliau žr. visą tekstą] / Aim of the study - to evaluate the attitude of the family physicians working in Marijampolė County towards the immunoprophylaxis and its organization in the primary health care settings. Methods. All the family physicians working in the public and private primary health care institutions of Marijampolė County took part in the survey. 109 questionnaires were delivered to the respondents. 86 of them were filled-in and returned (the response 79.0%). The data analysis was performed by the application of statistical program package SPSS (version 17.0). The hypotheses about the dependence of the variables were checked using the Chi square (χ2), z criteria and Spearman correlation coefficient (r). Results. The family physicians providing services to the children were actively performing the immunoprophylaxis activities according to the Calendar of the Preventive Vaccination of the Children of the Republic of Lithuania. The major part of the respondents (87.2%) were informing the parents (guardians) about the need to vaccinate their children upon their arrival to the health care institutions and (or) while visiting the patients at home (70.9%). The respondents were passively participating in the vaccination with chargeable vaccines activities. Little more than a half of the respondents (53.5%) told that they were always informing their patients about the possibilities to vaccinate their children with the chargeable vaccines, less than one third (31.4%) indicated that they were... [to full text]

An estimated 500 million cases of malaria occur each year. The increasing prevalence of drug resistant strains of Plasmodium in most malaria endemic areas has significantly reduced the efficacy of current antimalarial drugs for prophylaxis and treatment of this disease. Therefore, discovery of new, inexpensive, and effective drugs are urgently needed to combat this disease. Marine biodiversity is an enormous source of novel chemical entities and has been barely investigated for antimalarial drug discovery. In an effort to discover novel therapeutics for malaria, we studied the antimalarial activities of a unique marine-derived peak fraction library provided by Harbor Branch Oceanographic Institute (HBOI). Within this unique library, we have screened 2,830 marine natural product (MNP) peak fractions through a medium throughput screening effort utilizing the SYBR Green-I fluorescence based assay, and have identified 253 fractions that exhibit antimalarial activity. From those inhibiting fractions we have identified twenty species of marine organisms that inhibit Plasmodium falciparum growth, from which thirty-five fractions were selected for further study. Among those thirty-five, eighty-three percent were also found to inhibit the chloroquine resistant strain of P. falciparum, Dd2. The most potent inhibitors were then screened for their cytotoxic properties using the MTT cell viability assay. Among the samples that exhibited potent inhibition of P. falciparum growth were fractions derived from a sponge of the genus Spongosorites sp.. This genus of sponge has been reported to contain the nortopsentin and topsentin class of bis-indole imidazole alkaloids. Nortopsentin A inhibited the parasite growth at the trophozoite stage with an IC50 value of 1.6 µM. This is the first report of antimalarial activity for this class of compound.

Fluvastatin, the HMG-CoA reductase inhibitor known for its role in the treatment of hypercholesterolemia and cardiovascular disease, has more recently been shown to play a role in the immune response. Given the critical role that mast cells play in allergy and inflammatory diseases such as asthma, which effects one third of America’s population, we assessed the effect of fluvastatin on mast cell and basophils function. We demonstrate that fluvastatin downregulated IgE-mediated cytokine production. Additionally, in vivo studies showed that fluvastatin suppressed IgE-mediated anaphylaxis. Interestingly, the effects of fluvastatin showed dependence on genetic background, as C57BL/6 mast cells were sensitive, while 129/Sv mast cells were resistant to fluvastatin. Characterizing the role of fluvastatin on mast cells may prove to be therapeutically important.

Estima-se que aproximadamente 400 milhões de indivíduos sejam portadores crônicos do vírus da hepatite B no mundo. Quando incide em adultos, a doença apresenta elevada proporção de evolução para a cura, ao passo que na ocorrência de transmissão vertical, o risco de cronificação chega a 90%, aumentando muito a possibilidade de graves conseqüências para a criança, entre as quais cirrose e hepatocarcinoma primário. A possibilidade de triagem para a identificação das gestantes portadoras do vírus da hepatite B e a conseqüente adoção de medidas profiláticas – imunização ativa e passiva – permite a prevenção segura da transmissão vertical. Em 1999, o Programa do Pré-Natal da Secretaria Municipal da Saúde de Ribeirão Preto introduziu em sua rotina o screening para o HBsAg, com a finalidade de identificar as gestantes portadoras do vírus. Este trabalho objetiva estudar alguns aspectos referentes à hepatite B entre as gestantes atendidas pela Rede Municipal de Saúde, bem como realizar uma avaliação sistematizada do Programa do Pré-Natal. Para este trabalho foram criados dois grupos de gestantes. O primeiro formado pelas pacientes com primeira avaliação sorológica do Pré-Natal para aquela gestação, realizada no período de 01 de novembro de 2001 a 31 de outubro de 2002, com a finalidade de estimar a prevalência do HBsAg e também verificar a proporção de recém-nascidos, filhos de mães portadoras deste marcador, que receberam os cuidados preconizados para tal situação. Já o segundo grupo foi formado pelas pacientes, na mesma condição, avaliadas no período de 01 de julho de 2002 a 30 de junho de 2003, com a finalidade de também estimar a prevalência do HBsAg, bem como a proporção de portadoras do HbeAg e anti-Hbe. Os valores de prevalência do HBsAg encontrados foram os seguintes: para o primeiro grupo 0,5 (IC 95% : 0,3 – 0,7) e, 0,4 (IC 95%: 0,2 – 0,6) para o segundo. Verificou-se que em 25,0% dos 24 partos realizados no município não foram realizados os procedimentos de profilaxia preconizados como ideais, no que diz respeito à rapidez da solicitação de vacina e imunoglobulina. Isso foi devido, parcialmente, a deficiências na qualidade de registro das informações em diferentes instâncias. As proporções de portadoras do HBeAg e anti-HBe foram respectivamente 5,9% (IC 95%: 0 – 17,1) e 90,5% (IC 95%: 77,9 – 100). Este trabalho procura apresentar informações que sirvam de base para reflexões a respeito do fluxo de procedimentos do Programa do Pré-Natal, visando elevar sua efetividade e superar os obstáculos encontrados. / It is estimated that about 400 million persons are chronic carriers of the hepatitis B virus worldwide. When it occurs in adults, the disease shows high proportions of benign evolution, meanwhile in vertical transmission the risk of becoming a chronic carrier approaches 90%, elevating the possibilities of serious consequences to the child, including cirrhosis and primary hepatocellular carcinoma. The possibility of performing screening tests for the identification of pregnant women carriers of the hepatitis B virus and the consequent adoption of prophylactic measures – active and passive immunization – allow safe prevention of the vertical transmission. In 1999, the Pre-Natal Program of the Municipal Secretary of Health of Ribeirão Preto, SP, Brasil, included in its routine services the screening for the HBsAg, towards the identification of pregnant carriers of the virus. This study aims to look into some aspects referring to hepatitis B among the pregnants being attended by the Municipal Health Network, as well as perform a careful systematic evaluation of the Pre-Natal Program. In order to perform this study, two groups of pregnants were selected. The first one formed by those patients having had their first pre-natal serological evaluation done for that pregnancy during the period of November 1, 2001 until October 31, 2002, with the purpose of estimating the HBsAg prevalence and also to verify the proportion of the new-borns of HBsAg carriers that received the recommended care for that situation. The second group was formed by those patients on the same condition, evaluated during the period of July 1, 2002 until June 30, 2003, with the purpose of also estimating the HBsAg prevalence, as well as estimating the proportion of HBeAg and anti-HBe carriers. The HBsAg prevalences were the following: for the first group of pregnants 0,5 (CI 95% : 0,3 – 0,7) and 0,4 (CI 95%: 0,2 – 0,6) for the second one. It was verified that in 25,0% of the 24 births that happened in the city, the recommended care were not taken, when it comes to the prompt request of the specific vaccine and immunoglobulin. This fact was, partially, due to deficiency in the data files quality of the different institutions. The proportions of HBeAg and anti-HBe carriers found were, respectively, 5,9% (CI 95%: 0 – 17,1) and 90,5% (CI 95%: 77,9 – 100). This study intends to present data that can be the starting point towards reflections on the established procedures of the Pre-Natal Program, in order to increase its effectiveness and surpass the found obstacles.

Estima-se que aproximadamente 400 milhões de indivíduos sejam portadores crônicos do vírus da hepatite B no mundo. Quando incide em adultos, a doença apresenta elevada proporção de evolução para a cura, ao passo que na ocorrência de transmissão vertical, o risco de cronificação chega a 90%, aumentando muito a possibilidade de graves conseqüências para a criança, entre as quais cirrose e hepatocarcinoma primário. A possibilidade de triagem para a identificação das gestantes portadoras do vírus da hepatite B e a conseqüente adoção de medidas profiláticas – imunização ativa e passiva – permite a prevenção segura da transmissão vertical. Em 1999, o Programa do Pré-Natal da Secretaria Municipal da Saúde de Ribeirão Preto introduziu em sua rotina o screening para o HBsAg, com a finalidade de identificar as gestantes portadoras do vírus. Este trabalho objetiva estudar alguns aspectos referentes à hepatite B entre as gestantes atendidas pela Rede Municipal de Saúde, bem como realizar uma avaliação sistematizada do Programa do Pré-Natal. Para este trabalho foram criados dois grupos de gestantes. O primeiro formado pelas pacientes com primeira avaliação sorológica do Pré-Natal para aquela gestação, realizada no período de 01 de novembro de 2001 a 31 de outubro de 2002, com a finalidade de estimar a prevalência do HBsAg e também verificar a proporção de recém-nascidos, filhos de mães portadoras deste marcador, que receberam os cuidados preconizados para tal situação. Já o segundo grupo foi formado pelas pacientes, na mesma condição, avaliadas no período de 01 de julho de 2002 a 30 de junho de 2003, com a finalidade de também estimar a prevalência do HBsAg, bem como a proporção de portadoras do HbeAg e anti-Hbe. Os valores de prevalência do HBsAg encontrados foram os seguintes: para o primeiro grupo 0,5 (IC 95% : 0,3 – 0,7) e, 0,4 (IC 95%: 0,2 – 0,6) para o segundo. Verificou-se que em 25,0% dos 24 partos realizados no município não foram realizados os procedimentos de profilaxia preconizados como ideais, no que diz respeito à rapidez da solicitação de vacina e imunoglobulina. Isso foi devido, parcialmente, a deficiências na qualidade de registro das informações em diferentes instâncias. As proporções de portadoras do HBeAg e anti-HBe foram respectivamente 5,9% (IC 95%: 0 – 17,1) e 90,5% (IC 95%: 77,9 – 100). Este trabalho procura apresentar informações que sirvam de base para reflexões a respeito do fluxo de procedimentos do Programa do Pré-Natal, visando elevar sua efetividade e superar os obstáculos encontrados. / It is estimated that about 400 million persons are chronic carriers of the hepatitis B virus worldwide. When it occurs in adults, the disease shows high proportions of benign evolution, meanwhile in vertical transmission the risk of becoming a chronic carrier approaches 90%, elevating the possibilities of serious consequences to the child, including cirrhosis and primary hepatocellular carcinoma. The possibility of performing screening tests for the identification of pregnant women carriers of the hepatitis B virus and the consequent adoption of prophylactic measures – active and passive immunization – allow safe prevention of the vertical transmission. In 1999, the Pre-Natal Program of the Municipal Secretary of Health of Ribeirão Preto, SP, Brasil, included in its routine services the screening for the HBsAg, towards the identification of pregnant carriers of the virus. This study aims to look into some aspects referring to hepatitis B among the pregnants being attended by the Municipal Health Network, as well as perform a careful systematic evaluation of the Pre-Natal Program. In order to perform this study, two groups of pregnants were selected. The first one formed by those patients having had their first pre-natal serological evaluation done for that pregnancy during the period of November 1, 2001 until October 31, 2002, with the purpose of estimating the HBsAg prevalence and also to verify the proportion of the new-borns of HBsAg carriers that received the recommended care for that situation. The second group was formed by those patients on the same condition, evaluated during the period of July 1, 2002 until June 30, 2003, with the purpose of also estimating the HBsAg prevalence, as well as estimating the proportion of HBeAg and anti-HBe carriers. The HBsAg prevalences were the following: for the first group of pregnants 0,5 (CI 95% : 0,3 – 0,7) and 0,4 (CI 95%: 0,2 – 0,6) for the second one. It was verified that in 25,0% of the 24 births that happened in the city, the recommended care were not taken, when it comes to the prompt request of the specific vaccine and immunoglobulin. This fact was, partially, due to deficiency in the data files quality of the different institutions. The proportions of HBeAg and anti-HBe carriers found were, respectively, 5,9% (CI 95%: 0 – 17,1) and 90,5% (CI 95%: 77,9 – 100). This study intends to present data that can be the starting point towards reflections on the established procedures of the Pre-Natal Program, in order to increase its effectiveness and surpass the found obstacles.

Rabies is one of the oldest and most dangerous human and animal diseases. This is a disease that is transmitted directly from animal to animal and from an animal to a human being. People usually contract this disease from stray domestic animals therefore a realistic threat is posed to everyone to become infected with the rabies virus (RV). The only and the most effective way of protecting oneself from rabies after an infected or unknown animal has bitten one, is immunoprophylaxis. Between 2003 and 2011, the epidemiological situation of rabies in Lithuania was assessed. The methods that were used to diagnose rabies are noted for specificity and sensitivity. It has been proved that applying simultaneously the direct fluorescent antibody test (FAT) and rabies tissue culture infections test (RTCIT) methods it was possible to ensure a fast and effective determination of RV in the samples of wild and domestic animals under investigation thereby ensuring confirmation of the diagnosis of being infected with RV. During the wild fauna oral rabies vaccination (ORV) period between 2007 and 2011, the philogenetic analysis of RV isolates of domestic and wild animals in the sphere of N gene by means of the reverse transcription-polymerase chain reaction (RT-PCR) was carried out for the first time. In 2006-2011, the assessment of the efficacy of ORV in raccoon dogs and red foxes by means of the quantitative the Enzyme-linked immunoassay test (ELISA) research method... [to full text] / Pasiutligė – viena iš seniausių ir pavojingiausių žmonių ir gyvūnų ligų. Šia liga užsikrečiama kai pasiutlige sergantis gyvūnas įkanda žmogui ar kitam gyvūnui, ar apseilėja sužalotą odą. Žmonės dažniausiai užsikrečia nuo valkataujančių naminių gyvūnų, todėl išlieka visiems reali užsikrėtimo pasiutligės virusu grėsmė. Vienintelis ir efektyviausias apsisaugojimo būdas nuo pasiutligės yra imunoprofilaktika. Šiame darbe ištirtas pasiutligės viruso paplitimas 2003-2011 metų laikotarpiu ir nustatyta laukinių ir naminių gyvūnų pasiutligės epidemiologinė situacija Lietuvoje. Atliekant 2007–2011 metų pasiutligės geografinio paplitimo analizę buvo nustatyta, kad nagrinėjamu laikotarpiu didžiausias tiek laukinių, tiek naminių gyvūnų infekuotumas buvo nustatytas Lietuvos Rytinėje ir Pietrytinėje dalyje. Naudoti pasiutligės diagnostikos metodai pasižymi speciškumu ir jautrumu. Įrodyta, kad kartu taikant tiesioginį fluorescuojančių antikūnų ir audinių kultūrų infekavimo pasiutligės virusu metodus, galima užtikrinti greitą ir efektyvų pasiutligės viruso nustatymą laukinių ir naminių gyvūnų tiriamuosiuose galvos smegenų mėginiuose, tuo užtikrinant diagnozės patvirtinimą dėl užsikrėtimo pasiutligės virusu. Laukinių gyvūnų oralinės vakcinacijos nuo pasiutligės (ORV) periodu 2007-2011 metais atlikta naminių ir laukinių gyvūnų pasiutligės viruso izoliatų filogenetinė analizė N geno srityje atvirkštinės transkripcijos polimerazės grandininės reakcijos (AT-PGR) metodu. Pirmą... [toliau žr. visą tekstą]

Introduction: Infants with Bronchopulmonary Dysplasia (BPD) are at higher risk of developing severe RSV Bronchiolitis requiring hospitalisation. Palivizumab Immunoprophylaxis (PIP) was shown to reduce the severity of illness and hence the need for hospitalisation. Currently PIP is recommended for all infants with BPD, but there is little evidence on which infants with BPD would most benefit from PIP. Aim: This study aims to identify the clinical benefit of administering PIP to infants with BPD of different severities and to determine which infants would benefit most from PIP. In order to achieve this, the study also identifies the incidence of BPD, categorised into mild, moderate and severe in infants, in the Greater Manchester Region (GMR).Methods: This is a multi-centre, prospective, observational cohort study, involving 11 hospitals across GMR. Patients were recruited over 2 years, from 1st April 2009 to 31st March 2011. The infants with BPD were recruited and further categorised in various severities, based on Jobe’s BPD classification [Jobe et al 2001]. Patients were followed up for a minimum of one year. Results: The incidence of BPD in the GMR was 5.9 infants per 1000 live births. On categorisation by level of severity, the study found 31% of these to have mild BPD, 39% moderate and 30% severe BPD. Around 60% of infants received PIP in our cohort: one third of mild group, two thirds of moderate and three quarters of severe BPD. The overall proportion of hospitalisation for all the respiratory illnesses in infants with BPD was 44%. The overall incidence of hospitalization secondary to RSV infection was 7.6% of the cohort, and 14.8% due to other respiratory viruses. PIP was most beneficial in infants with moderate BPD (p = 0.016). Infants hospitalised with RSV infection required more admissions to HDU, required a longer duration of supplemental oxygen as well as a longer hospital stay compared to infants hospitalised due to other respiratory viruses and all other respiratory illnesses. Conclusion: This is the first study identifying the incidence of BPD in the GMR, which was lower than expected based on estimates from the JCVI. Both, the distribution of BPD into the various severity categories, as well as the requirement of hospital admission secondary to respiratory illness, were in keeping with published evidence from the USA and UK. PIP practices across North West of England were varied and not compliant with JCVI guidelines. Infants with moderate BPD showed the largest benefit from receiving PIP. This is a novel finding that highlights the need for further research, to determine whether a subgroup of infants might benefit from PIP.

TCR signal strength is critical for CD8+ T cell clonal expansion after antigen stimulation. Levels of the transcription factor IRF4 control the magnitude of this process through induction of genes involved in proliferation and glycolytic metabolism. The signaling mechanism connecting graded TCR signaling to the generation of varying amounts of IRF4 is not well understood. Here, using multiple methods to vary TCR signal strength and measure changes in transcriptional activation in single CD8+ T cells, we connect antigen potency to the kinetics of NFAT activation and Irf4 mRNA expression. T cells that transduce weaker TCR signals exhibit a marked delay in Irf4 mRNA induction resulting in decreased overall IRF4 expression in individual cells and increased heterogeneity within the clonal population. The activity of the tyrosine kinase ITK acts as a signaling catalyst that accelerates the rate of the cellular response to TCR stimulation, controlling the time to onset of Irf4 gene transcription. These findings provide insight into the signal transduction pathway accounting for the reduced clonal expansion of low affinity CD8+ T cells following infection. We also describe another context for ITK activity, autoreactive T cell migration. Here, we connect TCR signaling strength to modulation of selectin binding and autoreactive T cell-mediated pathology in an adoptive transfer model system of autoimmune disease. Understanding the signaling mechanisms linking changes in TCR signaling to CD8 T cell function is important in furthering the understanding of vaccine development and T cell adoptive immunotherapy.

Pre-exposure prophylaxis (PrEP) is an effective tool for preventing human immunodeficiency virus (HIV) acquisition in sexually active at-risk individuals such as men who have sex with men (MSM). The purpose of this study is to examine factors associated with intent to engage in risky sexual behavior among HIV-negative college aged (18-24) MSM who are currently adherent to PrEP or who have expressed interest in the future adoption of PrEP. A multiracial/ethnic sample of 31 men expressing interest in the adoption of PrEP and 6 men currently taking PrEP completed a quantitative survey identifying key themes regarding attitudes towards PrEP and potential behaviors associated with adherence. Themes associated with current adherence to PrEP included protection from HIV infection, the opportunity to engage in sexual activities with a non-condom HIV prevention method, and perceived protection from sexually transmitted infections. Themes associated with potential adoption of PrEP included protection from HIV infection, opportunity to engage in sexual activity with known HIV-positive partners, opportunity to engage in sexual activities with a non-condom HIV prevention method, and perceived protection from sexually transmitted infections. Review found that decreased condom use and increased sexual partners are key themes related to initiation of PrEP, and a decrease in frequency of condom use was indicated among the adherent sample. Other key themes identified include barriers to PrEP implementation and misinformation regarding sexually transmitted infections among the population.

<p><strong>INTRODUCTION: </strong>Pre-clinical and clinical data strongly support the feasibility of employing immunotherapy as a strategy to treat cancer.</p> <p><strong>METHODS: </strong>Using the B16F10 murine melanoma model, we have been investigating mechanisms of T cell-mediated antitumor immunity following immunization with dopachrome tautomerase (DCT), a melanoma-associated antigen.</p> <p><strong>RESULTS: </strong>In <strong>Chapter 2</strong>, we uncovered an interesting dichotomy whereby DCT-specific CD4⁺ T cell-mediated tumor protection and autoimmunity are dependent on IL-4/STAT-6 and IFN-g/STAT-4, respectively. Our data also revealed that this phenomenon is extrinsic of CD4⁺ T cell polarization.</p> <p>To gain further insight into the targets recognized by CD4⁺ T cells, we conducted in <strong>Chapter 3</strong> extensive CD4⁺ T cell epitope mapping experiments using overlapping peptide libraries. Interestingly, while we were able to identify “helper” epitopes within DCT that were required for maximal CD8⁺ T cell expansion, we were unable to identify “effector” epitopes responsible for tumor rejection. Further examination of the requirements for the generation of CD4⁺ T cell effector epitopes showed that post-translational modifications of the protein were involved.</p> <p>In <strong>Chapter 4</strong>, we investigated the modest efficacy afforded by DCT immunization in the context of established B16F10 melanomas. Using intratumoral transcriptional analysis, we demonstrated that the vaccine rapidly promoted an IFN-g-dependent immunosuppressive state inside the tumor. Concurrent treatment with the immunomodulatory antibodies anti-4-1BB and anti-PD-1 effectively counteracted this tumor immunosuppression, resulting in complete regression of tumors and long-term survival in 70% of the mice.</p> <p><strong>CONCLUSIONS: </strong>The research described in this thesis sheds new light into the mechanisms by which vaccine-mediated CD4⁺ T cell responses participate to tumor rejection and autoimmunity. Moreover, our findings indicate that cancer vaccine-induced tumor immunosuppression significantly limits tumor regression, emphasizing the requirement of combinatorial approaches for successful cancer immunotherapy. Overall, our research offers new insight for future vaccine development.</p> / Doctor of Philosophy (Medical Science)