Tra i componenti naturali biologicamente attivi, e con cui è possibile arricchire il latte, notevole importanza rivestono gli acidi grassi Omega3 e i CLA. I ruoli benefici svolti da questi particolari lipidi si manifestano soprattutto nella regolazione dei processi infiammatori, nella prevenzione del diabete e delle malattie cardiovascolari; è inoltre dimostrato come i CLA abbiano attività anticancerogena e ipocolesterolemica, stimolino il sistema immunitario e prevengano l’insorgenza del diabete e delle malattie croniche non trasmissibili. Lo scopo di questo lavoro è stato quello di individuare, in condizioni sperimentali controllate e nelle comuni realtà di allevamento, le possibili strategie alimentari atte ad aumentare le concentrazioni di Omega-3 e CLA del latte vaccino, senza penalizzare i titoli di grasso del latte. I lavori sperimentali effettuati possono essere distinti in 3 fasi: una prima fase in cui l’oggetto principale delle ricerche svolte è stato l’incremento in acidi grassi Omega3 del latte, una seconda fase in cui l’obiettivo si è allargato anche all’incremento delle concentrazioni in CLA, e una terza fase che ha avuto come scopo quello di incrementare i livelli di Omega3 e CLA del latte senza penalizzare i titoli di grasso. Le strategie alimentari più efficaci si sono basate sulla modificazione degli apporti lipidici della razione attraverso la supplementazione con seme di soia o relativo olio, semi di lino o relativo olio, olii di pesce e acido stearico. Le ricerche svolte hanno evidenziato come, attraverso opportune ed accurate modulazioni degli apporti lipidici delle razioni, sia di fatto possibile innalzare i contenuti di acidi grassi della serie Omega3 e CLA nel latte vaccino, senza penalizzare i titoli del grasso del latte. / Omega3 and CLA are among the most important active biologic components usually used as milk-enricheners. The main beneficial roles accomplished by these particular lipids are: the regulation of inflammatory processes and the prevention of diabetes and cardiovascular diseases. Furthermore, it is proven the CLA anticancer and hypocholesterolemic effect. Aim of this study was to identify the feed strategies to increase the Omega-3 and CLA concentration in milk, without affecting the titles of milk fat. Tests were carried out under controlled experimental conditions and in accomplishment with the common farming reality. The research was divided in three phases. Main object of the first phase was to find the best strategies to increase Omega-3 fatty acids of milk. The second phase collected the tests in which the goal was extended to include the increase also in CLA concentrations. The third phase aimed to enrich the levels of Omega-3 and CLA in milk without affecting the fat titles of milk. The researches were mostly conducted at the didactic-experimental farm of Bologna University; other tests were directed also in commercial farms, in order to respect the common operating conditions. The most effective dietary strategies based on the modification of lipid dietary intake. Supplementation of the ration was mainly based on soybean and relative oil, linseed and relative oil, fish oils and stearic acid. Results from this research show that operating an appropriate and accurate modulation of lipid intake of rations allows to raise the content of fatty acids Omega-3 and CLA in cow's milk, without penalizing the titles of milk fat.

In this thesis two approaches were applied to achieve a double general objective. The first chapter was dedicated to the study of the distribution of the expression of genes of several bitter and fat receptor in several gastrointestinal tracts. A set of 7 genes for bitter taste and for 3 genes for fat taste was amplified with real-time PCR from mRNA extracted from 5 gastrointestinal segments of weaned pigs. The presence of gene expression for several chemosensing receptors for bitter and fat taste in different compartments of the stomach confirms that this organ should be considered a player for the early detection of bolus composition. In the second chapter we investigated in young pigs the distribution of butyrate-sensing olfactory receptor (OR51E1) receptor along the GIT, its relation with some endocrine markers, its variation with age, and after interventions affecting the gut environment and intestinal microbiota in piglets and in different tissues. Our results indicate that OR51E1 is strictly related to the normal GIT enteroendocrine activity. In the third chapter we investigated the differential gene expression between oxyntic and pyloric mucosa in seven starter pigs. The obtained data indicate that there is significant differential gene exression between oxintic of the young pig and pyloric mucosa and further functional studies are needed to confirm their physiological importance. In the last chapter, thymol, that has been proposed as an oral alternative to antibiotics in the feed of pigs and broilers, was introduced directly into the stomach of 8 weaned pigs and sampled for gastric oxyntic and pyloric mucosa. The analysis of the whole transcript expression shoes that the stimulation of gastric proliferative activity and the control of digestive activity by thymol can influence positively gastric maturation and function in the weaned pigs.

Il microbiota intestinale riveste un ruolo importantissimo nell’influenzare la salute dell’ospite. È stato dimostrato come la composizione della dieta possa condizionare lo stato di benessere dell’animale, inducendo importanti cambiamenti tra le popolazioni batteriche che coabitano l’intestino; l’uso di prebiotici rappresenta una delle strategie maggiormente impiegate per modulare positivamente la composizione ed il metabolismo dell’ecosistema gastroenterico. Il presente progetto di dottorato si è proposto di indagare gli effetti sul microbiota intestinale del cane e del gatto di diete a diverso tenore proteico e contenenti proteine di diversa digeribilità in presenza o meno di sostanze prebiotiche. Inoltre, sono stati valutati gli effetti della presenza di un estratto di Yucca schidigera e di tannini sulla microflora intestinale del gatto. In ultima istanza, sono state valutate le conseguenze di dosi crescenti di lattosio sul benessere intestinale del cane. I risultati del presente studio hanno rilevato come le sostanze prebiotiche influiscono sulla composizione e sul metabolismo della microflora del cane e del gatto, e come l’impiego di diete ricche di proteine possa avere conseguenze negative sull’ambiente intestinale. Tuttavia, la presenza di oligosaccaridi non sembra contrastare gli effetti negativi che diete ad alto tenore proteico potrebbero avere sull’ecosistema intestinale dell’animale. Nella successiva prova è stato evidenziato come l’inclusione nella dieta di estratti di Yucca e tannini possa contribuire a mitigare l’emanazione di sostanze maleodoranti dalle deiezioni degli animali da compagnia. Nel corso dell’ultima prova, nonostante non siano state osservate differenze tra le popolazioni microbiche intestinali, la somministrazione di dosi crescenti di lattosio ha indotto una certa riduzione delle fermentazioni proteolitiche microbiche. Ulteriori studi sono necessari per stabilire in che misura la dieta e gli alimenti “funzionali” possano influire sul microbiota intestinale del cane e del gatto e come queste informazioni possono essere utilizzate per migliorare miratamente l’alimentazione e lo stato di salute degli animali da compagnia. / The microbiota of the large intestine plays a fundamental role in maintaining the state of health of the gastrointestinal tract and the host. Considerable evidence suggests that dietary macronutrients and prebiotic substances may affect microbial composition and activity. Knowledge about the modulation of canine and feline intestinal microbiota in response to macronutrients and prebiotic supplementation is limited. However, such information is necessary to investigate further the complex interplay between host and intestinal microbiota in response to changes of diet. The research for this PhD thesis focused upon the changes of the intestinal microbiota and bacterial metabolites of dogs and cats, in response to feeding diets differing in their protein content and digestibility, and containing or not a source of prebiotics. Additionally, the effects of tannins and Yucca schidigera extract on feline intestinal microbiota were evaluated. Furthermore, aim of the last trial was to evaluate the effect of increasing level of lactose on composition and metabolism of dog intestinal microbiota. The results from the present thesis show that different prebiotics exert different effects on the composition and activity of canine and feline intestinal microbiota and that high dietary protein levels can have negative effects on the animal intestinal environment. However, administration of oligosaccharides doesn’t seem to counteract the negative effects that can be observed when companion animals are fed high-protein diets. In the other study, Yucca extract and tannins does not affect feline fecal microbiota. Despite this, a reduction of odour components was observed due to fermentation of substrates. Finally, results from the final study showed no difference between treatments on canine microbial population. However, proteolytic compounds were decreased by lactose. Future studies must determine how diet composition and prebiotic supplementation affect the gut microbiota and how this information may be used to improve diets and the host’s health.

Several cardiac diseases, including hypertrophy, cardiomyopathy, and myocardial infarction, result in the upregulation of cardiac angiotensin II type-1 receptors (AT1R). Imaging the AT1R in vivo via PET provides the potential to monitor disease progression and guide therapy accordingly. The aim of this research was to develop a novel F-18 labeled losartan analog as an AT1R PET tracer and begin evaluation in rats. Due to the longer half-life and shorter positron range of F-18, we presume that an F-18 labeled tracer will be more beneficial than current C-11 labeled tracers. Prior structure-activity relationship (SAR) studies suggested the addition of substituents to the hydroxyl group of losartan would minimally affect AT1R binding affinity. [18F]Fluoropyridine losartan ([18F]FPyrLos) was synthesized in an automated module through conjugation of [18F]fluoro-3-pent-4-yn-1-yloxypyridine ([18F]FPyKYNE) to azide-modified losartan via the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) ‘click’ reaction. [18F]FPyrLos was produced in approximately 10% yield (decay-corrected) with > 97.5% purity and specific activities up to 4,200 mCi/µmol. MicroPET (Siemens Inveon) images of normal Sprague Dawley rats displayed high uptake in the kidneys (ratio of 8.3 compared to surrounding tissue at 10 min). Metabolite analysis in the kidneys and plasma by column-switch HPLC revealed that roughly two-thirds of the tracer was unchanged 10 min post-injection and that one labeled hydrophilic metabolite exists, accounting for roughly 6% of the total activity. Both microPET and metabolism studies displayed a dose-dependent reduction in renal uptake upon co-injection with AT1R blocker candesartan indicating specific binding. Further work in rat disease models is required to evaluate the potential of this tracer for imaging cardiac AT1R.

Ulm, Univ., Diss., 2001.

Zugl.: Berlin, Freie Univ., Diss., 1982.

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AGUIAR, Marco Antônio Nasser. Expressão de fator nuclear kappa b (nf-kb) e de interleucina 18 (il-18) no carcinoma inflamatório e carcinoma localmente avançado não inflamatório da mama. 2015. 80 f. Dissertação (Mestrado em Cirurgia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015. / Submitted by denise santos (denise.santos@ufc.br) on 2015-10-21T16:44:29Z No. of bitstreams: 1 2015_dis_managuiar.pdf: 2988742 bytes, checksum: 04fd575dfb37c38097501ea20eec3e8b (MD5) / Approved for entry into archive by denise santos(denise.santos@ufc.br) on 2015-10-21T16:46:11Z (GMT) No. of bitstreams: 1 2015_dis_managuiar.pdf: 2988742 bytes, checksum: 04fd575dfb37c38097501ea20eec3e8b (MD5) / Made available in DSpace on 2015-10-21T16:46:11Z (GMT). No. of bitstreams: 1 2015_dis_managuiar.pdf: 2988742 bytes, checksum: 04fd575dfb37c38097501ea20eec3e8b (MD5) Previous issue date: 2015 / Inflammatory Breast Cancer (IBC) is the most aggressive form of locally advanced breast cancer. It is more common in young women and unfavorably, in most of the times, evolves quickly. Presents with typical signs of inflammation such as hyperemia and hyperthermia its pathogenesis and evolution has been associated with possible participation of inflammatory mediators such as cytokines (TNF-α e IL-1β), enzymes (cyclooxygenase-2 [COX-2] and nitric oxide synthase [iNOS]), as well as, transcription factors (Nuclear Factor kappa B [NF-kB]) able to inducing them. In this regard, the objective of this research was to determine the NF-kB and Interleukin-18 (IL-18) expression in tissue samples obtained from IBC and Noninflammatory Locally Advanced Breast Cancer (LABC). The Hypothesis is that IBC would presents an increased expression of these factors than LABC. Demographics data and tumor characteristics, including response to neoadjuvant chemotherapy and overall survival in both tumor populations were also used to assessment and comparison. Furthermore, in this study, we evaluated the expression of IL-18 and p50 nuclear fraction of NF-kB by immunohistochemistry in specimens from IBC and LABC (T4b). Data analysis showed that about a quarter of cases of CIM occur in women up to 40 years. The overall survival is less in the group of CIM compared to LABC (2.3 vs. 4.3 years, respectively). This difference was also evident in the subgroups RE+, C-erbB-, and triple negative (2.3 vs. 4.4 years to ER+; 2.1 vs. 4.4 years to C-erbB2-; 2.0 vs. 3.4 for triple negative, respectively). Furthermore, it was not possible to detect differences in expression of NF-kB or IL-18 in the CIM and LABC groups. In summary, a quarter of the IBC cases studied appear in younger women (up to 40 years). The IBC has worse prognosis associated with less survival compared to LABC, as evidenced also in subgroups RE+, C-erbB-, and triple negative. Furthermore, there was no correlation between the expression of NF-kB and IL-18 in the IBC and LABC groups. / O Carcinoma Inflamatório da Mama (CIM) é a mais agressiva forma de câncer de mama localmente avançado. É mais frequente em mulheres jovens e evolui desfavoravelmente de forma rápida em boa parte das vezes. Ao se apresentar com sinais típicos de processos infamatórios como hiperemia e hipertermia sua patogênese e evolução tem sido associado a possível participação de mediadores inflamatórios como citocinas (TNF-α e IL-1β) assim como fatores de transcrição (Fator Nuclear kappa B [NF-kB]) capazes de induzi-los bem como enzimas participes de sua gênese (ciclooxigenase-2 [COX-2] e a óxido nítrico sintase induzida [iNOS]). Neste sentido, objetivou-se na presente investigação avaliar a imunoexpressão do NF-kB e da Interleucina-18 (IL-18) em amostras teciduais obtidas de CIM e de Carcinoma da Mama Localmente Avançado não inflamatório (CMLA). Hipotetizou-se que nos CIM haveria uma expressão aumentada diferencial em relação CMLA. Dados demográficos e características tumorais incluindo a resposta a quimioterapia neoadjuvante e a sobrevida geral nas duas populações tumorais foram também motivo de avalição e de comparação. Além disso, no presente estudo, foi avaliada a expressão através de imunoistoquímica, da IL-18 e da fração nuclear p50 do NF-kB em espécimes de CIM e de CMLA (T4b). A análise dos dados mostrou que na população estudada aproximadamente um quarto dos casos de CIM ocorrem em mulheres com até 40 anos. A sobrevida média é mais desfavorável no grupo dos CIM quando comparado ao CMLA (2,3 vs. 4,3 anos, respectivamente). Esta diferença também foi evidenciada nos subgrupos RE+, C-erbB-, e triplo negativo (2,3 vs. 4,4 anos para RE+; 2,1 vs. 4,4 anos para C-erbB2-; 2,0 vs. 3,4 para triplo negativos, respectivamente). Além disso, não foi possível detectar diferenças na expressão de NF-kB ou IL-18 nos grupos CIM ou CMLA. Em suma, na população aqui estudada um quarto dos casos de CIM aparecem em mulheres mais jovens (até 40 anos). O grupo CIM tem pior prognóstico associado a menor sobrevida quando comparado ao CMLA, como evidenciado também nos subgrupos RE+, C-erbB-, e triplo negativo. Além disso, não foi observado correlação entre a expressão de NF-kB e IL-18 nos grupos CIM e CMLA.

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