abstract: Type 2 diabetes affects approximately 7.3% of Americans, leading to debilitating and life-threatening comorbidities. Estrogen and testosterone levels have been linked to inflammatory and oxidative stress markers, as well as glucose and insulin concentrations. The present study was designed to determine the link between sex differences, glucose control, and inflammation and oxidative stress related to daily almond ingestion among subjects with type 2 diabetes. Subjects were randomized to an intervention group, which received 1.5 oz. almonds daily for 12 weeks, or to the matched control group, which maintained their current diet. No significant differences were found in changes in glucose control in response to ingestion of almonds. However, CRP was significantly reduced by an average of 36.2% in those that received almonds daily (p = 0.017). Although not significant, women randomized to the intervention group appeared to have improvements in insulin resistance compared to women with no dietary change. Results suggest that the addition of almonds to the diet may be an effective intervention for managing inflammation associated with type 2 diabetes. The addition of almonds to the diet is a low cost intervention that is easily implemented into daily lifestyle. Due to the small sample size, additional studies are needed to determine the impact and mechanisms of almond ingestion in subjects with type 2 diabetes. / Dissertation/Thesis / M.S. Nutrition 2014

Syfte: I ett flertal tidigare studier har positiva samband mellan hållbarhetsprestationer (CRP) och finansiella resultat (CFP) hittats och försökt förklaras. Dock har endast ett fåtal antagit synsättet att immateriella resurser fungerar som medlare för dessa samband. Vi menar att de immateriella resurserna har en betydande roll, för sambandet. Med hjälp av de immateriella resurserna formas en positiv spiral som ökar hållbarhetsprestationer och finansiellt resultat i båda kausala riktningarna. Vi vill belysa huruvida detta positiva, medlande samband existerar samt om tillväxt stärker sambandet mellan CRP och CFP, genom de immateriella resurserna. Metod: Studien har antagit en positivistisk forskningsfilosofi med en hypotetisk-deduktiv ansats. En kvantitativ metod har använts genom att sekundärdata samlats in från databasen Thomson Reuters Eikon. I en longitudinell design har fem års observationer använts för ett urval av 113 publika industriföretag där inhämtat data har analyserats statistiskt. Resultat & slutsats: Denna studie fann övervägande negativa samband och kan inte visa att de immateriella resurserna medlar kopplingen mellan CRP och CFP i en positiv spiral. Studiens resultat visar dock att immateriella resurser har betydelse för uppbyggnaden av CRP och CFP men de fungerar inte som verktyg som påverkar prestationsmåtten i båda kausala riktningarna. De har en egen effekt på CRP och CFP direkt vars verkan skiljer sig mellan de olika immateriella resurserna. Endast i tillväxt har studiens resultat visat på en positiv påverkan av CRP på CFP och tvärt om. Examensarbetets bidrag: Ur ett teoretiskt perspektiv bidrar studien till insikter om att immateriella resurser och satsningar på CRP är vägar att öka finansiella prestationer hos industriföretag i tillväxt. Praktiskt kan detta vara användbar kunskap för företagsledare i beslut om satsningar på immateriella resurser. Förslag till fortsatt forskning: Denna studie bygger på mätdata från en femårsperiod som sträcker sig över en tidsperiod då det råder lågkonjunktur. Studien bygger också på ett relativt litet urval som försvårar möjligheten att dra slutsatser med precision. Studien undersöker också endast fyra immateriella resurser. En studie med ett större urval under en längre tidsperiod där fler immateriella resurser tas med i beräkningsmodellen kan kasta ljus över hur de immateriella resurserna bidrar till förändringar i CRP och CFP. Nyckelord: CRP, CFP, immateriella resurser, tillväxt, positiv spiral

Abstract Chlamydiae are obligatory intracellular gram-negative bacteria with a unique growth cycle. They are very successful pathogens and responsible for a wide variety infections in humans and different animal species. In addition, they have a tendency to cause recurrent, persistent or chronic infections with potentially severe sequelae years or decades later. The general purpose of this work was to study the possible serological associations between chronic chlamydial infection, systemic inflammation and reproductive health in a general population. The chlamydial heat shock proteins 60 and 10 (Hs10 and Hsp60) have been suggested to contribute to the pathogenesis of chronic chlamydial infections. Thus, the antibodies to chlamydial Hsp10 and Hsp60 were also investigated in complications of pregnancy. The present study was a longitudinal population-based birth cohort study, and all of the original papers of this dissertation are based on a nested case - control design. Our results confirmed the serological association between C. trachomatis infections and subfertility and the rather high incidence of undiagnosed C. trachomatis infections in the male partners of subfertile couples. We further demonstrated a serological association between previous C. trachomatis infections, immunity to chlamydial Hsps and female subfertility. We also showed that serological markers of chronic chlamydial infection present as early as the first trimester are associated with preterm delivery among nulliparous women. When elevated levels of C. trachomatis IgG and hsCRP were present, the estimated risk for preterm delivery was over 4-fold. According to our study, nulliparous women who subsequently developed preeclampsia leading to preterm delivery, which was used as a marker of more serious illness, had significantly more often serum IgG antibodies to C. pneumoniae during the first trimester of pregnancy compared to the preeclamptic women who delivered at term. In conclusion, chronic C. trachomatis infection was found to associate with subfertility both in men and in women. In addition, a subclinical chronic inflammatory process associated at least partly with chronic C. trachomatis infection and present in the first trimester already may be important in the development of preterm delivery. Chronic C. pneumoniae infection and systemic low-grade inflammation were found to associate with pregnancies that lead to preeclampsia and preterm delivery.

Phthalates are industrial chemicals added to plastics found in products such as children’s toys, cosmetics, and household items, and some laboratory studies suggest phthalates may increase levels of inflammation. Chronic inflammation is associated with many chronic health conditions, such as diabetes and rheumatoid arthritis. Although research is limited, recent studies suggest a strong positive relationship between mono-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), and monocarboxynonyl phthalate (MCNP) and c-reactive protein (CRP), as well as monoethyl phthalate (MEP) and mono-3-carboxypropyl phthalate (MCPP) and interleukin-6 (IL-6). Additionally, this relationship has not been examined among postmenopausal women, a population that is at higher risk of developing chronic health conditions. Our aim was to examine the association between urinary phthalate biomarkers and inflammation biomarkers among postmenopausal women using baseline data from a subset of participants of the Women’s Health Initiative (WHI) (n=443). Phthalate exposure was assessed using phthalate biomarkers (i.e. phthalate metabolites or their molar sum) from urine samples collected at WHI clinical centers from 1993-1998. We measured 13 phthalate metabolites: MEP, MBP, mono-hydroxybutyl phthalate (MHBP), MiBP, mono-hydroxyisobutyl phthalate (MHiBP), monobenzyl phthalate (MBzP), MCPP, mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-carboxyoctyl phthalate (MCOP), and MCNP. Serum and plasma inflammatory biomarker levels (i.e. CRP, IL-6) were measured in separate WHI ancillary studies, using blood samples collected at baseline. We used multivariable linear regression to analyze associations between each phthalate biomarker and inflammation biomarker, adjusting for important covariates. Phthalate biomarkers MCNP (Model 1: b = 0.523; Model 2: b = 0.362) and MCOP (Model 1: b = 0.384; Model 2: b = 0.240) were positively associated with CRP. Additionally, MCNP (Model 1: b = 0.369; Model 2: b = 0.181) was positively associated with IL-6. Statistically significant associations were not observed among the remaining phthalate biomarkers. Our findings suggest that certain phthalates may be related to increasing levels of inflammation.

Canine Parvovirus remains a leading cause of enteritis in dogs in South Africa and many other countries despite the wide availability of effective vaccines. The virus does not affect all dogs equally and the course of the disease depends on the age, immune status and breed of the puppies as well as the viral dose, route of exposure and the virulence of the strain. Although aggressive supportive treatment can be successful, the treatment and convalescent periods may be prolonged and consequently expensive and the mortality rate relatively high, causing many clients to forego treatment and elect for euthanasia of their pet. Acute phase proteins (APP) are proteins that change in concentration by at least 25% in animals subjected to external or internal inflammatory challenges, such as infection, inflammation or surgical trauma. Increased concentrations are associated with poor outcome in certain diseases. C-reactive protein (CRP) is the most sensitive APP in dogs. Its normal physiological concentration is low but increases rapidly with inflammation or tissue destruction. Due to the fact that CRP has a relatively short half life in serum (6-8 hours) and a high response in diseased animals, it can be used as a valid measure of a systemic response to an initiating stimulus at the time of blood sampling. By taking serial measurements, objective information about the extent of the ongoing lesions in the patient can be obtained and therefore may be used as a prognostic indicator. The objective of this prospective observational study was to evaluate the association of serum CRP concentrations in puppies suffering from canine parvoviral enteritis with morbidity and mortality, and to determine the usefulness of CRP to predict duration of hospitalisation time. Seventy-nine client owned puppies naturally infected with canine parvovirus were included. Parvovirus infection was diagnosed on electron microscopic examination of faeces from the puppies. CRP was measured using an automated human C-Reactive Protein Turbidimetric Immunoassay (TIA), which has been validated for use in dogs. Serum CRP measurements were performed at admission, twice daily for the first 48 hours, then once daily until death or discharge. There was a positive association between odds of mortality and CRP concentration on admission, as well as 12 and 24 hours after admission (P=0.04,P=0.005 and P=0.003, respectively). Survival time was negatively associated with CRP concentration at 12 and 24 hours after admission (P=0.002and P=0.001, respectively). Among the survivors, length of hospitalisation was positively associated with CRP concentration at 12, 24 and 36 hours after admission (P=0.012, P=0.001 and P=0.002, respectively). Utility for CRP concentration to correctly differentiate between survivors and non-survivors at 24 hours after admission had a sensitivity and specificity of 78.7% and 86.7% respectively. Although serum CRP concentration is associated with outcome in puppies infected with canine parvovirus, when used alone it did not prove to be a good predictor of survival. / Dissertation (MMedVet)--University of Pretoria, 2012. / Companion Animal Clinical Studies / unrestricted

Acute phase proteins (APP) are ideal biomarkers for inflammation due to their stability, relative ease of assay and apparent relation between their concentration and the extent of the insult to tissue. C-reactive protein (CRP) is a positive major APP in dogs and can be used as a predictive marker for risk of disease and to monitor the response to treatment. Increased concentrations in certain diseases are associated with poor outcome. This cross-sectional, observational study of 75 dogs naturally infected with Babesia rossi, a cause of virulent canine babesiosis, was designed to examine the association of CRP concentration at admission and the magnitude of CRP change 24 hours after admission with outcome. Dogs were excluded if there was evidence of concurrent inflammatory diseases at the time of admission, infection with subtypes other than B. rossi, concurrent Ehrlichia canis infections or euthanasia for reasons other than poor prognosis. Diagnosis was confirmed by polymerase chain reaction and reverse line blot. CRP concentrations were determined by an automated human CRP Turbidometric Immunoassay (TIA), previously validated for use in dogs (Bayer CRP TIA, Newbury, UK), on serum samples collected by jugular venipuncture on admission, prior to any therapy, and thereafter daily until discharge or death. There was no significant difference in admission CRP concentration between survivors (n = 57; median = 97.4 mg/l; mean ± SD = 107.5 ± 49.5), and non-survivors (n = 11; median = 101.4 mg/l; mean ± SD = 122.1 ± 64.6) (p = 0.39). After elimination of non-significant predictors, a multiple exact logistic regression model for predicting mortality contained glucose and CRP. Mortality was associated with decreased glucose levels (p = 0.0002) and increased CRP levels (p = 0.045) on admission. Multiple regression analysis failed to show a significant relationship between admission CRP concentration and number of days of hospitalization in the survivors, adjusting for age and sex (p = 0.65). No significance was found in the relationship between the magnitude of change in CRP concentration 24 hours after admission, and the number of days of hospitalization in survivors, (p = 0.34). Using an admission CRP concentration cut-off of 60 mg/l, survival proportions between the two groups were no different (p = 0.34) and when applied to the group of dogs that survived, it was not associated with length of hospitalization (p = 0.25). In corroboration with previous reports glucose was identified as a major prognostic marker for mortality, but additionally the pro-inflammatory marker CRP was identified as a significant co-prognosticator. Copyright / Dissertation (MMedVet)--University of Pretoria, 2009. / Companion Animal Clinical Studies / unrestricted

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第19639号 / 社医博第72号 / 新制||社医||9(附属図書館) / 32675 / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 今中 雄一, 教授 佐藤 俊哉, 教授 木原 正博 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

No description available.

Background: Colorectal adenocarcinoma is the third commonest cancer in Sweden, with 6100 new cases every year. Several factors have been identified as contributors in the development of colorectal adenocarcinoma, amongst them is inflammation inducing angiogenesis, cell migration and mutations. C-reactive protein (CRP) is an acute phase protein that is produced by the liver in response to inflammation. Method: CRP was measured at diagnosis and six weeks after surgery in 271 patients with stage II and III colorectal adenocarcinoma. The concentration of CRP in plasma was compared to parameters and outcomes as registered in the Swedish Colorectal Cancer Registry. Results: Age over 70, co-morbidities, acute operation and mortality were significantly correlated with CRP concentrations over 5 mg/l. Using Cox-regressions univariate hazard ratios (HR) were calculated. CRP (HR 1.19-7.22, p<0.05), age (HR 6.02 p=0.0001), ASA-classification (HR 5.47, p=0.000), acute operation (HR 3.25, p=0.004), positive lymph nodes (HR 4.45-5.71, p=0.006), postoperative complications (HR 3.03, p=0.005) of which ICU-care (HR 13.86, p=0.000) and re- operation (HR 5.48, p=0.000) were the best predictors of mortality using the univariate model. In the multivariate model age over 70 (HR 4.792, p=0.006), postoperative complications (HR 3.645, p=0.012), N1- or N2-stage (HR 5.490 and 16.397, p=0.003 and 0.000 respectively) and preoperative CRP over 5 mg/l (HR 3.227, p=0.045) were significant predictors of mortality. Including only elective patients, N2-stage (HR 12.829, p= 0.000), age over 70 (HR 5.240, p= 0.017) and ASA-classification III and IV (HR 4.465, p= 0.012) were correlated to excess mortality.Discussion: The results confirm previous studies and adds to the evidence in support of CRP as a predictor of mortality in patients with colorectal adenocarcinoma. In the future these results might be valuable in predicting mortality and tailoring the care for patients with colorectal adenocarcinoma. / Bakgrund: Tjock- och ändtarmscancer är ett folkhälsoproblem som drabbar cirka 6 100 personer årligen, vilket gör sjukdomen till den tredje vanligaste cancerformen. Det finns flera teorier om tjock- och ändtarmscancers uppkomstmekanism. En faktor som identifierats som grundläggande för all cancer är inflammation. Kroppen reagerar vid inflammation genom att bland annat uttrycka mer av vissa äggviteämnen. Ett sådant äggviteämne är C-reaktivt protein (CRP). Denna studies syfte är att undersöka om det finns någon korrelation mellan CRP och hur allvarlig cancern är, ålder, samsjuklighet, överlevnad och prognos hos patienter med tjock- och ändtarmscancer. Metod: Journaler från 525 patienter som inkluderats i ett lokalt kvalitetsregister för tjock- och ändtarmscancer användes för att jämföra hur nivån av CRP i plasma före och efter operation påverkar cancerutfallet för patienterna. En grupp på 271 patienter valdes ut baserat på tumörstadie och analyserades med statistiska metoder. Resultat: Pre- och postoperativt CRP är korrelerar till hög ålder (över 70 år), samsjuklighet, akut operation och överlevnad hos patienterna. Patienter äldre än 70 år, de som hade CRP över 5 mg/l, lymfkörtelmetastaser eller som drabbats av en komplikation efter operationen var överrepresenterade bland de avlidna. Delades patienterna in i två grupper baserat på CRP- koncentrationen i blodet sågs en ökad dödlighet hos de med CRP över 5 mg/l före operationen. Diskussion: Tidigare studier som gjorts på området visar liknande resultat. Fortsatta studier bör göras på patientgruppen då uppföljningstiden och antalet patienter i registret ökar. I framtiden kan man använda resultaten för att hitta de patienter som löper större risk att avlida och anpassa deras behandling för att minska risken.

Envenenamentos por serpentes do gênero Bothrops provocam reações sistêmicas e locais como coagulopatias, hemorragias, reação inflamatória, dor e mionecrose. Proteínas secretadas ricas em cisteínas (CRISPs) estão presentes nas peçonhas de serpentes e estão amplamente distribuídas entre mamíferos, répteis e anfíbios. Estão envolvidas em algumas reações biológicas, porém muitas funções ainda são desconhecidas. O presente trabalho objetivou o isolamento, a caracterização bioquímica/estrutural, enzimática e funcional, a avaliação do potencial inflamatório e avaliação da atividade sobre o sistema complemento de uma CRISP isolada da peçonha de Bothrops jararaca. A CRISP denominada BJ-CRP, foi isolada da peçonha de Bothrops jararaca através da combinação de três etapas cromatográficas: exclusão molecular em Sephacryl S-200, cromatografia de troca aniônica em coluna Source 15Q e cromatografia de fase reversa em coluna C18. O grau de homogeneidade foi determinado e confirmado por eletroforese SDS-PAGE, que mostrou uma banda única de 25,19 kDa, e por MALDI-TOF/TOF que apresentou a massa molecular de 24,6 kDa. A sequência N-terminal e a análise dos peptídeos trípticos por MALDI TOF/TOF demonstrou a presença de 100 resíduos de aminoácidos, os quais apresentaram até 96% de similaridade com sequências de outras CRISPs já descritas, porém de outros gêneros e espécies de serpentes, pois ainda não há CRISPs isoladas do gênero Bothrops. A BJ-CRP não possui atividade proteolítica sobre a azocaseína, o fibrinogênio e a fibrina. Também não apresentou atividade coagulante e hemorrágica, e não demonstrou atividade quando testada na concentração de 1?M em 13 diferentes canais para potássio dependentes de voltagem. Por outro lado, esta toxina foi capaz de induzir um processo inflamatório agudo (tempos de 1 e 4 horas), observado pelo recrutamento de neutrófilos e aumento da citocina pró-inflamatória IL-6 na cavidade peritoneal de camundongos. Ensaios realizados com a BJ-CRP e a peçonha de Bothrops jararaca mostraram modulação na atividade hemolítica promovida pela via clássica do sistema complemento. A BJ-CRP também promoveu ação direta sobre alguns componentes isolados do sistema complemento, como C3 e C4, conforme avaliado por SDS-PAGE e Western blot. O presente trabalho descreve a purificação da BJ-CRP, a primeira CRISP isolada da peçonha da serpente do gênero Bothrops. Os resultados obtidos são promissores e abrem perspectivas para o melhor entendimento desta classe de proteínas, e para a compreensão do mecanismo de ação desta classe de toxinas na resposta inflamatória induzida pelo envenenamento botrópico. / Envenomation by snakes from Bothrops genus is characterized by systemic and local effects such as coagulopathies, bleeding disorders, inflammation, pain and myonecrosis.The cysteine rich secretory proteins (CRISPs) are present in snake venoms and are widely distributed mammals, reptiles and amphibians. They are involved in certain biological activities, however many of their functions are still unknown. The aim of the present study was to isolate a CRISP from Bothrops jararaca and to biochemically/functionally characterize it by evaluating its involvement on inflammatory responses and on the complement system. The CRISP named BJ-CRP was isolated from Bothrops jararaca crude venom through the combination of three chromatographic steps: molecular exclusion on Sephacryl S-200 column, anion exchange chromatography on Source 15Q and reverse phase chromatography using C18 column. A high purity degree was obtained as confirmed by SDSPAGE, showing a single band of 25.19 kDa, and by MALDI-TOF/MS showing a molecular mass of 24.6 kDa. The N-terminal sequence and analysis of tryptic peptides by MALDI TOF/ MS resulted in the determination of 100 amino acid residues, which had up to 96% similarity to sequences from other snake venom CRISPs that were previously described, but from other genus and snake species. The BJ-CRP did not have proteolytic activity on azocasein, fibrinogen or fibrin. It did not show coagulant or hemorrhagic activity, and also did not show activity on 13 different voltage dependent potassium channels when tested at a concentration of 1?M. Moreover, this toxin was able to induce an acute inflammatory response (1 and 4 hours after injection), observed by the recruitment of neutrophils and increase of interleukin-6 into the peritoneal cavity of mice. BJ-CRP and B. jararaca crude venom were capable of modulating the hemolytic activity promoted by the classical pathway of the complement system, and BJ-CRP also showed direct action on some complement system components, such as C3 and C4 as evaluated by SDS-PAGE and Western blot. The present work describes the purification of BJ-CRP, the first CRISP isolated from a Bothrops snake venom. The results obtained showed to be promising and open up prospects in order to better understand the involvement of this class of toxins in the inflammatory response induced by Bothrops envenomation.