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Daniele Maggioni,1 Annamaria Cimicata,1 Antonella Praticò,1 Roberta Villa,1 Ferdinando Marco Bianchi,1,2 Silvia Busoli Badiale,1 Claudio Angelinetta1 1Bio Basic Europe Srl, Milan, Italy; 2Dermo-Cosmetic and Medical R&D Center of Bio Basic Europe Srl, Milan, ItalyCorrespondence: Annamaria Cimicata Tel +39 02 4155729Fax +39 0242174243Email annamariacimicata@libero.itIntroduction: Rosacea is a chronic multifactorial skin disorder mainly affecting facial skin with an estimated prevalence of about 5% worldwide. Its main symptoms, occurring early during pathology development, are skin dehydration, redness, erythema, and telangiectasia. Given the lack of a resolutive cure, therapeutic approaches able to relieve the main symptoms are needed.Purpose: The aim of this research article is to evaluate the beneficial effect of a topical product (Serum BK46) on rosacea symptoms.Patients and Methods: A monocentric single-arm, non-blinded study was performed to assess the clinical effectofSerum BK46 in relieving the main symptoms of rosacea: skin dryness, increased trans epidermal water loss (TEWL), redness, and abnormal vascularization. Twenty patients with mild to moderate rosacea were enrolled in the study and asked to apply the product twice per day for 56 days. Skin moisturization, TEWL, and erythema index were instrumentally assessed at baseline and following 24 h and 14, 28 and 56 days of treatment. Clinical parameters, including redness and telangiectasia imperfection visibility, were evaluated on a 5-point scale by a specialized dermatologist at baseline and after 14, 28, and 56 days of treatment. Finally, the visibility of vessel diameter was evaluated at baseline and after 28 and 56 days of treatment.Results: Serum BK46 application restored skin hydration and prevented the loss of water by the skin. Long-term treatment with Serum BK46 significantly reduced skin redness, erythema index, and the visibility of telangiectasia imperfections and superficial vessels. The investigated product’s clinical effect was demonstrated by both instrumental and clinical evaluation. Furthermore, Serum BK46 was completely tolerated and no adverse effects were recorded.Conclusion: The moisturizing and skin barrier restoring action of Serum BK46 has been clearly proven in patients displaying mild to moderate rosacea; thus, this product is a good candidate for rosacea treatment.Keywords: rosacea, topical product, transepidermal water loss, skin redness, telangiectasia

Data table showing cytokine serum concentrations (pg/ml) of samples determined from 3-PLEX (MSD) in CIA mice. Arthritis was induced in mice by intradermal injection of bovine type II collagen. Upon onset, animals were recruited and randomised into experimental groups. Oral treatments with drugs were administered daily and lasted 10 days. At the end of the study, sera were isolated for determination of indicated cytokines by multiplex analysis on the MSD platform (Artialis, Liège, Belgium). Data represent mean ¹ SEM of the number of animals per group: N = 8 (sham, vehicle, 30 mg/kg CR6086), 6 (60 mg/kg CR6086) and 7 (60 mg/kg naproxen). (DOCX 40 kb)

Chemical structure of CR6086. (DOCX 41 kb)

Data table showing the effect of repeated administration of CR6086, MTX and their combination in arthritic mice (CIA model). Arthritic CIA mice, recruited upon arthritis onset, were treated with test drugs for 16 days. CR6086 was administered orally once daily, whereas MTX was administered intraperitoneally every third day. Clinical score (a) and paw swelling in millimetres (b) were reported as median (IQR) and mean (SD), respectively. (DOCX 45 kb)

Data tables showing the cross-reactivity data for CR6086: 10 eicosanoid receptors, 2 cyclooxygenase isoforms and 76 receptors/transporters/channels. (DOCX 58 kb)

Epidemiological data consistently demonstrate a reduced cancer risk associated with a polyphenols rich diet. Hibiscus sabdarifa (HS), a polyphenols rich plant widely consumed worldwide as beverage and used in folk medicine, has recently gained interest thanks to its antioxidant, anti-inflammatory and chemopreventive properties. In the present study we investigated the antitumoral potential of HS extract in two different human tumor cell lines: Multiple Myeloma cells (RPMI 8226) and Oral Squamous Cell Carcinoma cells (SCC-25). MTT assays showed that HS extract induced a dose-dependent viability reduction in both the cells lines. For the subsequent experiments we used HS at the concentration of 5 mg/ml that was the most effective in inducing cell viability reduction after 48h of treatment. Viable cell count using trypan blue staining demonstrated that the HS extract induced decrease in cell growth of both the cell lines and this was due to a reversible cytostatic rather than a cytotoxic effect. Wound-healing and cell invasion assays, respectively performed by a scratch of cell monolayer and Boyden Chamber transwell test, demonstrated that HS extract was able to reduce motility and invasiveness in both RPMI 8226 and SCC-25 cells. The chemical inhibition of ERK1/ERK2 and PI3K, with U0126 and wortmannin respectively, reduces proliferation and migration of both SSC-25 and RPMI cells and HB extract treatment played an additive action with the inhibitors. In conclusion, our results suggest that HS extract have antitumoral properties, since it proved to inhibit tumoral cell growth and cell migration and invasiveness. It is interesting to note that HS extract is effective against two very different tumor cell lines. In fact, RPMI 8226 cells are of hematopoietic origin and grow in suspension, whereas SCC-25 cells derive from epithelium and are characterized by adherent cell growth. Therefore, although further studies are needed to clarify the molecular mechanisms involved in its action, we proposed HS as a potential chemopreventive agent., Italian Journal of Anatomy and Embryology, Vol 118, No 2 (Supplement) 2013

Cholangiocarcinoma (CCA) is the second most frequent primary liver neoplasia. It mainly arises from the malignant transformation of biliary epithelial cells, although it might originate from either hepatic progenitor cells at the Hering canals or transformed hepatocytes. CCA is a highly aggressive tumor with extremely poor prognosis and limited therapeutic approaches. Baicalin (BA) is one of the main bioactive flavonoids identified in the Scutellaria Baicalensis Georgi root dried extract which is extensively used in the Chinese traditional medicine. Together with the anti-inflammatory effect, the anti-neoplastic action is the most relevant BA property demonstrated on cancer cells of different origin. Being aware of the need of new therapeutic weapons for CCA treatment, we investigated whether Baicalin could exert anti-proliferative and anti-migratory effect on EGI-1 cells, a highly metastatic CCA cell line derived from bile duct carcinoma. We first tested different BA concentrations (from 5 to 200μM) in limiting EGI-1 viability using MTT assay. After 24h and 48h treatment, 5 and 10μM BA had no effect while rising from 25μM to 200μM (i.e. 25, 50, 100 and 200μM) BA exerted a significant cell viability reduction already at 24h and increased after 48h BA exposure. This reduction well correlated with the adherent absolute cell number decrease and it cannot be due to BA induced cell cycle impairment after neither 24 nor 48h treatment. We also evaluated the anti-migratory BA potential by a wound healing assay adding different BA concentrations (5, 25, 50,100 and 200μM) to the culture medium immediately after performing a wound on confluent cell cultures. All BA concentrations but 5μM induced a significant reduction in the EGI-1 migration rate after 24h treatment. Moreover 25, 50 and 10μM BA showed similar migration inhibition extent at 24 and 48h whilst 200μM BA exerted a stronger inhibitory effect already after 24h exposure which increased with time in a significant way. Taken together our preliminary results demonstrate that BA impairs CCA cell viability and migration suggesting a promising adjuvant therapeutic use for BA as antitumoral agent., Italian Journal of Anatomy and Embryology, Vol 119, No 1 (Supplement) 2014

Neurotoxicity is a common dose-limiting side-effect of several drugs (Cavaletti et al., 2008). So far a validated test method to screen drugs neurotoxicity does not exist, therefore in this interdepartment study we have analyzed the effectiveness of a morphometric neurotoxicty assessment model. Drug neurotoxicity evaluation is based on embryonic rat dorsal root ganglia (DRG) organotypic culture. DRG primary sensory neurons are the principal target of drugs neurotoxic action. In fact, primary sensory neurons lie outside the blood-nerve barrier and are supplied by capillaries with fenestrated walls. Moreover, the axons of these cells are among the longest of the entire nervous system and, therefore, are more susceptible to any agent that interferes with the energy metabolism or the structural basis of axonal transport. In particular, in this interdepartment study, the interference of the under study neurotoxic compound with NGF-induced neurite elongation is analysed. The effectiveness and reproducibility of this model, even if commonly used to test drugs, has not yet been demonstrated. In order to assess the validity of this in vitro model, antineoplastic drugs known to be in clinical use and in animal models neurotoxic (paclitaxel and oxaliplatin) or not dangerous (cyclophosphamide and 5-Fluorouracil) have been tested. DRGs explanted from E15 rat embryos have been treated for 24h with drugs concentrations comparable to those achievable in vivo. The length of the longest neurite of each DRG has been measured by ImageJ program. Experiments have been performed by three different blinded researchers in two different laboratories. Mean and standard deviation of each experiment were obtained, subsequently the mean value and standard deviation of the three independent experiments for each researcher were calculated. Data obtained by the three researchers in two different laboratories resulted statistically comparable and no significant differences were detected (One Way Anova analysis of variance and Tukey post test; p, Italian Journal of Anatomy and Embryology, Vol 117, No 2 (Supplement) 2012

Oral Cancer (OC) is one of the most frequent cancer in Head and Neck district and Oral Squamous Cell Carcinoma (OSCC) constitutes the large majority of the neoplasia arising in oral cavity. OSCC remains a hampering matters for clinics, since the overall disease free survival has not significantly increased during the last decades and invasion to surrounding tissue and to regional lymph nodes is often reported. Therefore new strategies to prevent and inhibit OSCC growth and invasion are highly desirable and new therapeutic approaches are currently tempted also with the use of natural compounds. Myricetin (MYR) and Naringenin (NAR), two naturally occurring flavonoids, widely diffused in plants, fruits and vegetable, have recently gained consideration thanks to their anti oxidant, anti inflammatory and anti tumoral properties. In this study their potential anticancer effect has been evaluated on an OSCC cell line, SCC-25 and on spontaneously immortalized non tumoral keratinocytes, HaCaT cells. MYR and NAR induce a significant cell growth inhibition in SCC-25 cells, in addition NAR selectively affected cancer cells, since it does not impair HaCaT cell growth. Furthermore an additive effect of MYR and NAR has been highlighted. The cell proliferation inhibition is not related to apoptosis induction, as demonstrated by evaluation of phosphatidyl serine membrane translocation and dapi staining. On the contrary MYR and NAR effect depends on the cell cycle progression impairment. Wound-healing and cell invasion assays, respectively performed by cell monolayer scratch and Boyden Chamber transwell test, demonstrate that the two flavonoids are able to reduce motility and invasiveness on both SCC-25 and HaCaT cells. In conclusion the results of the present study show the anticancer potential of NAR and MYR on OSCC, since both flavonoids prevent cancer cell proliferation through a cytostatic effect, by the impairment of cell cycle progression. Moreover both the flavonoids inhibit cell migration, thus highlighting their potential effect as anti metastatic agents., Italian Journal of Anatomy and Embryology, Vol 118, No 2 (Supplement) 2013

Oxygen and glucose deprivation (OGD) due to ischemic events or trauma in the brain result in neuronal loss. The therapeutic approaches available for the treatment of these conditions are not and often the outcome is unfavorable for the patient or at least unpredictable. Stem cells could be useful for the treatment of OGD injured-neurons. Mesenchymal Stem Cells (MSCs), isolated from bone marrow as well as from various tissues, have poor immunogenicity and neuroprotective properties being able to alleviate ischemic brain injuries in animal models. The Endothelial Progenitor Cells (EPCs) are present at low frequencies both in the bone marrow and in the peripheral blood and can be mobilized by the administration of drugs such as statins. They are thought to play a role in the recovery of cerebrovasculature integrity after stroke. In the present study we evaluated the potential neuroprotective effect of human MSC and human EPCs on rat embryonic cortical neurons injured by OGD. OGD was induced by incubating the cortical neurons in a hypoxia chamber in a 95% N2 + 5% CO2 atmosphere at 37°C without glucose for periods ranging from 30 minutes and 6 hours. When the neurons were returned in normoxic atmosphere they were 1) co-cultured with either MSCs or EPCs seeded on a cell culture avoiding neurons and MSCs or EPCs direct contact while sharing the same medium, or 2) cultured in a medium previously conditioned by either MSCs or EPCs. Neuronal survival was evaluated by MTT assay and viable cellular counting. Also neuronal morphology was taken into account to evaluate the potential MSCs and EPCs neuroprotective effect. Both MSCs and EPCs increased neuronal survival after ODG. This effect was observed in absence of a direct contact between MSCs or EPCs and the injured neurons, suggesting that the release of soluble factors may be the main mechanism of action. In conclusion both MSCs and EPCs could represent a potential therapeutic approach for the treatment of brain ischemic injury. Further studies are needed to identify the specific molecules involved in the neuroprotective effect of MSCs and EPCs.

Mesenchymal Stem Cells (MSCs) are frequently proposed as potentially suitable for the regenerative therapeutic approach for several neurological diseases both of the central nervous system, such as Multiple Sclerosis, and at the same way also of the peripheral nervous system, thanks to their ability to increase neuronal survival and to release neurotrophic factors. Since there are great differences between neurons of the central and of the peripheral nervous system, in this study we have verified the existence of a different susceptibility of cortical and sensory neurons to the effect of MSCs after different toxic stimuli, in order to mimic the damages observed in some neurological diseases. For this aim we set up direct and indirect co-cultures of MSCs and cortical or sensory neurons previousl exposed to toxic doses of glutamate, as a paradigm of Multiple Sclerosis, or treated with two widely used chemotherapeutic drugs, cisplatin and paclitaxel, which induce peripheral neuropathies. On the same cells we evaluated also the effect of conditioned medium of MSCs, by using morphological and molecular analysis. Neuronal viability was assessed by MTT test and by count of viable cells. Our results demonstrated the protective action of MSC direct and indirect co-cultures only on sensory neurons previously exposed to the toxic agents, while conditioned medium was ineffective to rescue it. On the contrary MSCs failed at all to protect cortical neurons from the drugs used, and their conditioned medium further reduces neuronal viability. We are now investigating the putative interference of MSCs with apoptotic molecules in sensory neurons, while in cortical neurons we are evaluating the possible causes of MSC-medium toxicity by analyzing the factors released. The different effect of MSCs on cortical and sensory neurons protection observed in vitro may be not the same in vivo, where the environments differ, anyway, it suggests to address the use of MSCs against the diseases affecting the peripheral nervous system rather than the central one. This makes mandatory to further investigate the causes of the different response of neuronal populations to MSC treatment, in order to widen their potential use.

The induction of a peripheral neuropathy is a very common side effect of many chemotherapeutic agents, including platinum compounds, and it often represents the dose limiting factor for drug clinical use. Several strategies have been suggested to reduce drug neurotoxicity without affecting the antineoplastic potential, but up to now results were not encouraging. Recently, it has been demonstrated that Mesenchymal Stem Cells (MSCs) are able to promote the survival and the maturation of untreated sensory neurons of dorsal root ganglia (DRG), which represent also the target of drug neurotoxicity. Aim of this work is to verify the neuroprotective potential of MSCs on rat DRG exposed to cisplatin (CDDP), a chemotherapeutic and neurotoxic agent. DRG post-mitotic explants from E15 rat embryos were exposed for 24 hours to different cisplatin concentrations. After 24 hours, medium was changed and DRG were directly co-cultured with human MSCs (hMSCs) or with hMSCs conditioned medium (hMSC-CM). DRG explants were photographed every day up to 1 month, and the longest neurite of each DRG was measured to evaluate neurotoxicity. DRG survival was estimated by measuring the death area percentage. The survival of CDDP-treated DRG was increased after the co-cultures with hMSCs, and both hMSCs and hMSC-CM were able to improve the neurite outgrowth of untreated and CDDP-treated DRG after 48 hours. This MSC-dependent increase of neurite length was however no longer evident at later times (1 month). This effect on neurite elongation was probably mediated by CSPG, MAG and Nogo, some proteins involved in the modulation of neurite elongation, which resulted expressed and released in the culture medium of hMSCS. Our results demonstrated a neuroprotective effect of hMSCs on CDDP toxicity and evidenced the ability of these cells to modulate neurite elongation. In this way MSCs could represent a possible mean to limit the neurotoxicity on DRG which arises after cisplatin therapy.

Multiple sclerosis (MS) is a chronic immuno-mediated inflammatory and demyelinating disease characterised by the presence of both demyelinating lesions and axonal degeneration, which lead to the reduction of nerve conduction velocity and the development of concomitant neurological deficits. Recently, Mesenchymal Stem Cells (MSCs) have been proposed in in vivo studies as promising therapeutic treatment for MS mainly for their capacity to modulate the immune response, moreover, during our previous experiments we found that rat undifferentiated MSC promote Dorsal Root Ganglia neurons survival and maturation. The aim of this study is to verify the potential protective effect of MSCs on an in vitro model of MS represented by rat primary cultures of cortical neurons. Since glutamate excitotoxicity is an important mechanism in neurodegenerative diseases, and it induces neuronal alterations similar to those observed in advanced MS, cortical neurons cultures were treated with different concentrations of glutamate (25, 50, 100, 200 and 500 µM) for 24 hours. After the treatment cortical neurons show a suffering appearance, with damaged axons and cellular degeneration. Neuronal viability, assessed by DAPI staining and by count of viable cells, was glutamate dose-dependent. In order to evaluate the possible positive effect of MSCs on neuronal survival, both direct and indirect co-cultures of MSCs and cortical neurons were set up, and the survival after glutamate treatment analyzed. Cortical neurons treated with glutamate were still suffering after the direct co-cultures with MSCs, while in indirect co-cultures with MSCs neurons were alive, without important signs of axonal degeneration. These preliminary findings suggest that MSCs are able to reduce the cellular death induced by glutamate exposure in cortical neurons and encouraged the further study and characterization of their positive effect

Neurotoxicity is a common dose-limiting side-effect of several drugs. So far a validated test method to screen drugs neurotoxicity does not exist, therefore in this interdepartment study we have analyzed the effectiveness of a neurotoxicty assessment model. Drug neurotoxicity evaluation in this model is based on the ability of NGF exposed embryonic rat dorsal root ganglia (DRG) organotypic culture to grow neurite; in particular the interference of the under study neurotoxic compound with neurite elongation is analysed. The effectiveness and reproducibility of this model , even if commonly used to test drugs , has not yet been demonstrated. In order to assess the validity of this in vitro model, antineoplastic drugs known to be in clinical use and in animal models neurotoxic (paclitaxel and oxaliplatin) or not dangerous (cyclophosphamide and 5-Fluorouracil) have been tested. DRGs explanted from E15 rat embryos have been treated for 24h with drugs concentrations comparable to those achievable in vivo. The length of the longest neurite of each DRG has been measured by ImageJ program. Experiments have been performed by three different blinded researchers in two different laboratories. Mean and standard deviation of each experiment were obtained, subsequently the mean value and standard deviation of the three independent experiments for each researcher were calculated. Data obtained by the three researchers in two different laboratories resulted statistically comparable and no significant differences were detected (One Way Anova analysis of variance and Tukey post test; p

Multiple sclerosis (MS) is a chronic immuno-mediated inflammatory and demyelinating disease characterised by both demyelinating lesions and axonal degeneration, leading to the reduction of nerve conduction velocity and the development of neurological deficits. Recently, some in vivo studies have proposed Mesenchymal Stem Cells (MSCs) as promising therapeutic treatment for MS mainly for their capacity to modulate the immune response, although it is not yet known if other mechanisms, different from immune modulation, are involved in MSCs positive. We investigate the therapeutic potential and the clinical effects of MSCs by using an animal model of multiple sclerosis, represented by Lewis rats affected by acute experimental autoimmune encephalomyelitis (EAE). MSCs were intravenously administered immediately after EAE induction (T0) or one week later (T7), in both the cases before disease onset. The clinical course of acute EAE was ameliorated only in EAE animals in which MSCs were injected one week after disease induction, while EAE rats and EAE rats with MSCs injected at T0 showed similar clinical scores. Moreover, the EAE rats which received MSCs at T7 displayed a cytokines pattern expression comparable to untreated control rats, while both EAE group and EAE+MSCs (T0) group showed an increased expression of pro-inflammatory cytokines. These results evidenced that the intravenous administration of MSCs one week after EAE induction (and before disease onset) induces the amelioration of the clinical scores of EAE-rats, thus supporting the potential role for MSCs in cell therapy in multiple sclerosis. We are now investigating the molecular mechanisms of this positive effect, focusing our attention on the Metalloproteinases pathway, involved in multiple sclerosis and modulated by MSCs.

Italian Journal of Anatomy and Embryology, Vol 115, No 1/2 (Supplement) 2010

Twenty-one crossbreeding heifers (½ Nelore vs ½ Aberdeen Angus) with about 307.90 kg of live weight and eighteen months of age were used in a complete randomized design with three treatments and seven repetitions. The treatments were: control heifers, ovariectomized animals and with fifty gunshot spheres in uterine corn. The heifers were fed with 50% of corn silage and 50% concentrated. The feed intake was about 2,5% weight live in dry matter. The heifers gunshot treatments showed was bigger weight gain than the heifers ovariectomized treatments and this more weight gains what control heifers treatments. There was not difference in carcass yield and fat covering amongst treatments. The hematocrito increased in three heifers groups in the first collection (before) for the second collection (after treatments). However, the increase was superior (P < 0,05) in the control heifers group. Foram utilizadas vinte e uma novilhas mestiças ½ Nelore vs ½ Aberdeen Angus, com idade aproximada de dezoito meses e peso médio de 307,90 kg. Os animais foram distribuídos em delineamento inteiramente casualizado, com três tratamentos e sete repetições. Os tratamentos foram compostos por: novilhas vazias, novilhas ovariectomizadas e novilhas com implante de cinqüenta esferas de chumbo esterilizadas no interior do corno uterino. As novilhas foram alimentadas com ração composta de 50% silagem de milho (MS) e 50% concentrado (MS), fornecida na base de 2,5% (MS) do peso vivo dos animais. As novilhas com implante de chumbo apresentaram ganho médio diário superior (P < 0,05) aos das novilhas ovariectomizadas e das vazias. Ainda, as novilhas ovariectomizadas apresentam ganho superior (P < 0,05) aos das novilhas vazias. Todavia, não houve diferença no que se refere ao rendimento de carcaça e cobertura de gordura. O valor do hematócrito aumentou nos três grupos de animais da primeira coleta (antes) para a segunda coleta (depois dos tratamentos). Todavia, este aumento foi maior (P < 0,05) nas novilhas vazias.

Chemotherapy induced Peripheral Neuropathy (CIPN) is a a well known complication limiting Cisplatin (CDDP) and Docetaxel (DOCE) chemotherapy in patients with cancer. Erythropoietin (EPO) is an heamatopoietic growth factor that has been reported to display neurothrophic properties, in particular it has proved to be neuroprotective in several rodent models of nervous system damage, including CDDP induced peripheral neuropathy. In this study we evaluated the neuroprotective ability of EPO against CDDP and DOCE induced neurotoxicity in primary cultures of sensitive neurons dissociated from Dorsal Root Ganglia (DRG) obtained from 15-day-old rat embryos, aiming to investigate the mechanism underlying EPO neuroprotective action. Briefly, primary cultures of sensitive neurons have been exposed to CDDP (25M), DOCE (100nM) or to the same doses of the chemotherapics but in the presence of EPO (10nM). In this in vitro model EPO turned out to be protective against both CDDP and DOCE induced neurotoxicity, in fact an increased neuronal survival was evident in cultures exposed to the combination treatment with CDDP plus EPO and DOCE plus EPO. Several evidences suggest that AKT pathway may play an important role in EPO neuroprotective action. Therefore we analyzed by western blot the levels of expression and activation (phosphorylation) of AKT in neurons exposed to the CDDP, DOCE or to the cotreatment with EPO. Results obtained indicated that modulation of the levels of phosphorylated AKT (pAKT) occurs following 14 hours treatment with CDDP, when a sharp decrease in the levels of activated AKT was highlighted, on the contrary DOCE induced only a sligth increase in the level of pAKT. Cotreatment with EPO was able to partially prevent CDDP induced decrease in the level of pAKT. Using a specific inhibitor of AKT activation (Wortmannin) we therefore investigate the role of AKT in EPO neuroprotection. The presence of Wortmannin (100nM) did prevent EPO neuroprotective action against CDDP induced neurotoxicity, but did not have any effect on EPO action against DOCE induced neurotoxicity. In conclusion in this study EPO has proved to be an effective neuroprotectant against neurotoxicity induced by both Cisplatin and Docetaxel, in addition results obtained suggest that AKT is an essential element in EPO neuroprotection. However, considering that AKT activation appears essential for EPO neuroprotection against CDDP induced neurotoxity, but not against DOCE, we assume that EPO neuroprotective action may act on two distinct cellular signalling pathways following CDDP or DOCE induced neurotoxicity.

Orientador: Prof. Dr. Ivanor Nunes do Prado Tese (doutorado em Zootecnia)--Universidade Estadual de Maringá, 2009 Resumo: O trabalho foi desenvolvido para avaliar o desempenho, as características de carcaça, a qualidade da carne maturada (pH, força de cisalhamento, capacidade de retenção de água, cor, tipo e frequência de fibras musculares), composição química e de ácidos graxos do músculo Longissimus de bovinos de três grupos genéticos, alimentados com silagem de sorgo ou cana-de-açúcar e abatidos com dois graus de acabamento. Foram avaliados 36 tourinhos com idade média de 21 meses e peso médio inicial de 330 ± 44 kg, terminados em confinamento e alimentados com duas dietas: 1) silagem de sorgo + 1,0% do peso vivo de concentrado (SIL) ou 2) cana-de-açúcar + 1,2% do peso vivo de concentrado (CAN). Os bovinos pertenciam a três grupos genéticos distintos: Zebu (ZEB); Limousin vs Zebu (LIZ) e Red Angus vs Zebu (ANZ) e foram abatidos com dois graus de acabamento de carcaça (3,4 ou 4,8 mm de espessura de gordura de cobertura). No primeiro trabalho observou-se que os animais alimentados com a dieta SIL apresentaram maior (P0,05) para o rendimento de carcaça quente (RC) entre as duas dietas. Ainda, o tipo de volumoso (SIL ou CAN) não alterou (P>0,05) as características de carcaça e composição da carne. Em relação aos grupos genéticos, os animais dos grupos LIZ e ANZ apresentaram maior (P0,05) para as IMS, IMS/PV, FDN e IFDN/PV, PCQ e RC entre os grupos genéticos. Animais do grupo genético LIZ apresentaram menor (P0,05) entre grupos genéticos sobre as demais características de carcaça. O abate de animais com dois graus de acabamento (3,4 ou 4,8 mm) não afetou (P>0,05) o PVF, PCQ e RC. Todavia, o GMD foi maior (P0,05) nos teores de umidade, cinzas, proteína, lipídios totais e colesterol total entre os grupos genéticos e as dietas. O músculo Longissimus de bovinos abatidos com 3,4 mm de gordura de cobertura apresentou maiores (P0,05) a composição dos ácidos graxos, com exceção para a razão ômega 6/ômega 3, que foi melhor para os bovinos abatidos com 3,4 mm de gordura de cobertura Abstract: This work was carried out to evaluate the performance, carcass characteristics, quality of the ageing meat (pH, shear force, ability to retain water, color, type and frequency of muscle fibers), chemical composition and fatty acids of the Longissimus muscle from cattle of three genetic groups, fed with sorghum silage or sugar cane and slaughtered at two levels of fat thickness. It was used 36 young bulls aging 21 months and weighing 330 ± 44 kg, feedlot with one of two diets: 1) sorghum silage + 1.0% live weight of concentrate (SIL) or 2) sugar cane + 1.2% live weight of concentrate (CAN). The cattle were from three distinct genetic groups: Zebu (ZEB), Limousin vs Zebu (LIZ) and Red Angus vs Zebu (ANZ) and were slaughtered at one of two levels of cover fat thickness (3.4 or 4.8 mm). In the first work it was observed that animals fed with SIL had higher (P0.05) for hot carcass yield (HCY) between the two diets. Also, the type of forage (SIL or CAN) did not significantly change (P>0.05) the carcass characteristics and the composition of the meat. As for the genetic groups, the LIZ and ANZ animals had higher (P0.05) for DMI, DMI/BW, INDF and INDF/BW, HCW and HCY between the genetic groups. LIZ had lower (P0.05) among genetic groups on the other carcass characteristics. The slaughter of animals with two levels of fat thickness (3.4 or 4.8 mm) did not affect (P>0.05) FLW, HCW and HCY. However, the ADG was higher (P0.05) in moisture content, ash, protein, total lipids and total cholesterol between the genetic groups and diets. The Longissimus muscle of animals slaughtered at 3.4 mm fat thickness had higher moisture and ash when compared to those slaughtered at 4.8 mm, while protein content, total lipids and total cholesterol were similar between the two fat thicknesses. LIZ bovines showed higher concentrations (P0.05) on fatty acid composition, except for the ratio omega 6/omega 3, that was better for the animals slaughtered with 3.4 mm of fat thickness