Da fração hexânica do extrato metanólico das folhas de Guarea guidonia (Meliaceae), foram isolados os diterpenos: [11S-(1α,2E,6E,10α)]-3,7,11-trimetil-11-(4-metil-pent-3-en-1-i1)biciclo[8.1.0]undeca-2,6-dieno e [1S(1aβ,4aα,7aβ,7bβ)]-decaidro-1,7-dimetil-1-(4-metil-pent-3-en-1-il)-4-metilen-1H-cicloprop[e]azulen-7-ol, já descritos na literatura, além de dois novos isômeros de [1S-(1aβ,4aα,7aβ, 7aβ)]-decaidro-1,7-dimetil-1-(2-hidroxi-4-metil-pent-3-en-1-il)-4metilen-1H-cicloprop[e]azulen-7-ol. No óleo essencial obtido das folhas do mesmo espécimen foram identificados, através da análise dos dados espectroscópicos (RMN 13C, RMN 1H e EM), os sesquiterpenos: eudesma-5,7-dieno, 5α,6α-epoxi-eudesm-7-eno, eudesma-5,7-dien-2α-ol, 5α,6α-epoxi-eudesm-7-en-9-ol e guaia-6-en-10-ol, ainda não descritos na literatura, além de eudesma-4(15), 11(13)-dieno, eudesm-6-em-4α-ol, eudesma-4,11-dieno e 5α,6α,7α,8α-diepoxieudesmano. Diversos extratos vegetais assim como substâncias puras e misturas de composições conhecidas foram testadas com a finalidade de se detectarem substâncias com atividade anticancerígena. Para tal, empregou-se o bioensaio com linhagens mutantes do fungo Saccharomyces cerevisiae, utilizados pelo grupo do Prof. Dr. David Kingston, do Virgínia Tech Institute. Também foi realizado um estudo químico biomonitorado por aquele bioensaio. / From the hexanic extract of the dry leaves of Guarea guidonia (Meliaceae) two new isomers of decahydro-1,7-dimethyl-1-(2-hydroxy-4-methyl-pent-3-en-1-yl)4- methylen-1H-cycloprop[e]azulen-7-ol were isolated together with the known diterpenes [11S-(1α,2E,6E,10α)]-3,7,11-trimethyl-11-(4-methyl-pent-3-en-1yl) bicyclo[8.1.0]undeca-2,6-dien and [1S-(1aβ,4aα,7aβ,7bJ3)]-decahydro-1,7dimethyl- 1-(4-methyl-pent-3-en-1-yl)-4-methylen-1H-cycloprop[e]azulen-7-ol. The essential oil from the leaves of the same plant afforded the sesquiterpenes eudesma-5,7-diene, 5α,6α-epoxy-eudesm-7-ene, eudesma-5,7-dien-2α-ol, 5α,6α-epoxy-eudesm-7-en-9-ol and guaia-6-en-10-ol not previouly described, besides eudesma-4(15),11 (13)-diene, eudesm-6-en-4α-ol, eudesma-4,11-diene and 5α,6α,7α,8α-bisiepoxy-eudesmane. All of these compounds were identified through 13C and 1H NMR spectroscopy as well as MS. Several plant extracts and pure compounds were tested in the search for potential anticancer agents, through the mechanism-based yeast bioassay, utilizing mutants of the yeast Saccharomyces cerevisiae. The screening of those plant materials and a bioassay-guided fractionation of an active extract were both carryed out in the laboratories of Professor David G.I. Kingston at Virginia Tech Institute.

Da fração hexânica do extrato metanólico das folhas de Guarea guidonia (Meliaceae), foram isolados os diterpenos: [11S-(1α,2E,6E,10α)]-3,7,11-trimetil-11-(4-metil-pent-3-en-1-i1)biciclo[8.1.0]undeca-2,6-dieno e [1S(1aβ,4aα,7aβ,7bβ)]-decaidro-1,7-dimetil-1-(4-metil-pent-3-en-1-il)-4-metilen-1H-cicloprop[e]azulen-7-ol, já descritos na literatura, além de dois novos isômeros de [1S-(1aβ,4aα,7aβ, 7aβ)]-decaidro-1,7-dimetil-1-(2-hidroxi-4-metil-pent-3-en-1-il)-4metilen-1H-cicloprop[e]azulen-7-ol. No óleo essencial obtido das folhas do mesmo espécimen foram identificados, através da análise dos dados espectroscópicos (RMN 13C, RMN 1H e EM), os sesquiterpenos: eudesma-5,7-dieno, 5α,6α-epoxi-eudesm-7-eno, eudesma-5,7-dien-2α-ol, 5α,6α-epoxi-eudesm-7-en-9-ol e guaia-6-en-10-ol, ainda não descritos na literatura, além de eudesma-4(15), 11(13)-dieno, eudesm-6-em-4α-ol, eudesma-4,11-dieno e 5α,6α,7α,8α-diepoxieudesmano. Diversos extratos vegetais assim como substâncias puras e misturas de composições conhecidas foram testadas com a finalidade de se detectarem substâncias com atividade anticancerígena. Para tal, empregou-se o bioensaio com linhagens mutantes do fungo Saccharomyces cerevisiae, utilizados pelo grupo do Prof. Dr. David Kingston, do Virgínia Tech Institute. Também foi realizado um estudo químico biomonitorado por aquele bioensaio. / From the hexanic extract of the dry leaves of Guarea guidonia (Meliaceae) two new isomers of decahydro-1,7-dimethyl-1-(2-hydroxy-4-methyl-pent-3-en-1-yl)4- methylen-1H-cycloprop[e]azulen-7-ol were isolated together with the known diterpenes [11S-(1α,2E,6E,10α)]-3,7,11-trimethyl-11-(4-methyl-pent-3-en-1yl) bicyclo[8.1.0]undeca-2,6-dien and [1S-(1aβ,4aα,7aβ,7bJ3)]-decahydro-1,7dimethyl- 1-(4-methyl-pent-3-en-1-yl)-4-methylen-1H-cycloprop[e]azulen-7-ol. The essential oil from the leaves of the same plant afforded the sesquiterpenes eudesma-5,7-diene, 5α,6α-epoxy-eudesm-7-ene, eudesma-5,7-dien-2α-ol, 5α,6α-epoxy-eudesm-7-en-9-ol and guaia-6-en-10-ol not previouly described, besides eudesma-4(15),11 (13)-diene, eudesm-6-en-4α-ol, eudesma-4,11-diene and 5α,6α,7α,8α-bisiepoxy-eudesmane. All of these compounds were identified through 13C and 1H NMR spectroscopy as well as MS. Several plant extracts and pure compounds were tested in the search for potential anticancer agents, through the mechanism-based yeast bioassay, utilizing mutants of the yeast Saccharomyces cerevisiae. The screening of those plant materials and a bioassay-guided fractionation of an active extract were both carryed out in the laboratories of Professor David G.I. Kingston at Virginia Tech Institute.

The longevity of high productivity sows in the herd has become a challenge in pig production. Several factors may contribute to increased mortality rates observed over the past few years as well as lower retention rates of young sows. Chronic inflammation and metabolic disorders are conditions that sows had evolved over the years together with the greater productivity. This dissertation underlines the immunomodulatory effects of using yeast fermentation product fed to lactating sows. In the interest of determining patterns of local and systemic immune response, a new methodology to access cytokine profiles in puerperium sows was developed. In Chapter 2, one hundred-forty sows were used to evaluate the effects of two different <i>Saccharomyces cerevisiae</i> fermentation product (SCFP), a liquid source (LIQ) and a dry source (XPC®; Diamond V), on sow and litter performance. Sows were fed a common gestation diet until d 112 of pregnancy and then allotted to one of four treatments: 1) Control diet (CON), 2) CON + 15 mL/d of LIQ from d 112 to weaning (LIQ), 3) CON + 0.20% of XPC from d 112 to weaning (DRY), and 4) DRY + 15 mL/d of LIQ from d 112 to d 7 post-farrowing (D+L). Colostrum immunoglobulin concentrations were estimated using Brix refractometer. Plasma of piglets (2/sow) was collected 24 h after birth for immunocrit ratio analysis and for determination of plasma IgA and IgG concentrations. Lactation water and feed intake (ADFI) were recorded daily. Post-weaning follicle growth was evaluated by transrectal ultrasonography. Sows had the same initial BW (P > 0.13) but those fed any SCFP were heavier at weaning (P = 0.03) while not affecting sow backfat and loin depth (P>0.05). Overall, sows fed SCFP had greater ADFI than CON fed pigs (P < 0.01) while water intake, reproductive performance (total born, stillborn, weaned) did not differ among treatments (P > 0.05). Sows fed LIQ had the greatest ADFI on weeks 1, 2, 3, and overall compared to CON (P < 0.05). Litter ADG from SCFP treatments tended to be greater than CON (P = 0.10) and litter weight variability was lower (P = 0.10). No treatment effects were observed in colostrum Brix values (P > 0.77), in the piglet plasma IgG and IgA, and serum immunocrit ratio (P > 0.21). The average daily post-weaning follicle growth was greater for SCFP treatments than CON (P = 0.05). The wean to estrus interval was shorter for sows fed LIQ than CON and DRY (P < 0.01).<br><div><br></div><div>In Chapter 3 a non-invasive methodology to assess cytokine profiles from post-partum uterine lavage is described. The uteri of fourteen second and third parity sows were flushed with sterile saline solution (0.9%) on days 2, 4, and 14 post-parturition. Uterine fluid collected was immediately centrifuged and the supernatant stored at -20°C. Samples were freeze-dried, re-suspended in sterile saline (2 mL), and stored at -80°C. Cytokine profiles of the uterine fluid were evaluated using a multiplex ELISA panel including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Cytokine concentrations were calculated relative to protein content (pg/mg of protein). IFN-γ and TNF-α were lower than the limit of detection in most samples (5/38 and 1/38, respectively). IL-4 and IL-10 concentrations did not differ among days of collection (P>0.14). IL-8 was greater on day 4 than on days 2 or 14 (P<0.05). IL-1β and IL-6 were greater on days 2 and 4 than on day 14 (P<0.05).<br></div><div><br></div><div>The study presented in Chapter 4 refers to a subsample of sows (n=40) from the entire group of sows used in the study presented in Chapter 2. In this case, the methodology presented in Chapter 3 was used to evaluate SCFP effects on blood and uterine cytokine profiles in sows. A similar set of cytokines from Chapter 3 were evaluated on d 112 of gestation, d 2 and 6 post-farrowing in the plasma, and from uterine fluid collected on d 2, 4, and 6 post-farrowing. Serum C-Reactive protein (CRP) and haptoglobin concentrations were evaluated. No interactions between treatments and day of collection were observed (P>0.13). LIQ and D+L sows had the greatest serum IL-10 concentration (P<0.001) and sows fed CON tended to have lower serum concentration of IL-8 (P<0.06) vs. other treatments. Serum CRP concentrations were greatest on d 2 (P<0.001), serum IL-10 (P<0.04) and IL-4 (P<0.07) linearly decreased while serum haptoglobin (P<0.02) and IFN-γ (P<0.001) linearly increased post-farrowing. In the uterine fluid, LIQ and D+L sows had greater IFN-γ (P=0.04) concentrations and CON tended to have the least concentration of TNF-α (P=0.08). Uterine fluid IL-1 tended to linearly increase (P<0.07) and IL-6 linearly decrease (P<0.01) post-farrowing. LIQ sows had the greatest daily feed intake and CON the least during the first week of lactation (P=0.04).<br></div><div><br></div><div>In conclusion, feeding SCFP to lactating sows improved feed intake and litter growth while not affecting milk yield and colostrum quality. Besides improvements on litter ADG, the uniformity was better for all sources of SCFP. The liquid sources had slightly better results over the other sources and CON, including the greatest feed intake, less body weight mobilization, and a reduction in WEI. The method proposed to evaluate cytokine profiles in the uterine fluids of sows after farrowing, accomplished the objective of being a non-invasive procedure to be applied in puerperium sows. This new procedure was applied to analyze the immunomodulatory effects of SCFP. The correlations observed between the uterine and serum cytokines lead to a refined description of immune response in puerperium sows. Feeding SCFP to lactating sows stimulates the immune system allowing sows to build a desirable immune responses. Thus, the quicker resolution of acute phase reaction as demonstrated by greater daily feed intake in the first week post-farrowing can be attributed to SCFP immunomodulatory effects, ensuring better lactation performance.<br></div>