Orientadores: Tatiana de Sousa da Cunha, Fernanda Klein Marcondes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-20T06:59:33Z (GMT). No. of bitstreams: 1 Sanches_Andrea_M.pdf: 1126813 bytes, checksum: 30cc93581a60db907dc7c938e7d40caf (MD5) Previous issue date: 2012 / Resumo: O estresse crônico é um fator de risco para o desenvolvimento de hipertensão, aterosclerose e diabetes. O protocolo de estresse crônico moderado e imprevisível (ECMI) é um modelo animal de estresse crônico. Em estudo prévio, foi observado que o ECMI induziu resistência à insulina, dislipidemia e disfunção endotelial, em ratos. Considerando que o aumento na atividade do sistema renina-angiotensina (SRA) tem sido associado à disfunção endotelial e à resistência à insulina, o objetivo deste estudo foi investigar a participação do SRA sobre os efeitos cardiovasculares e metabólicos induzidos pelo ECMI, em ratos. Foram utilizados 62 ratos machos Sprague-Dawley, com dois meses de idade. A duração do período experimental foi de 7 semanas. No Experimento 1, os animais foram divididos em 2 grupos: controle e estresse. O ECMI foi aplicado nas semanas 3, 4 e 5 e os animais foram eutanasiados 1 e 15 dias após a aplicação do protocolo de ECMI. O ECMI aumentou a atividade sistêmica da renina e da enzima conversora de angiotensina (ECA), da ECA na aorta torácica e as concentrações plasmáticas de angiotensina II e angiotensina (1-7). Com base nestes resultados, que mostraram aumento da atividade do SRA induzido pelo ECMI, o Experimento 2 foi delineado com o objetivo de avaliar a participação da angiotensina II e do seu receptor AT1 nos efeitos desencadeados pelo ECMI sobre a captação de glicose e sobre o sistema cardiovascular. Outros animais foram divididos em 4 grupos experimentais: controle, estresse, controle losartan (antagonista do receptor AT1 - 50 mg/Kg/dia, v.o.) e estresse losartan. O ECMI induziu aumento da área sob a curva, no teste de tolerância à glicose (TTG), diminuição da resposta vasodilatadora à acetilcolina na aorta torácica in vitro e aumento da pressão arterial in vivo, em comparação com o grupo controle, sem haver diferença entre os grupos controle, controle losartan e estresse losartan. Estes resultados mostram que os efeitos do ECMI levaram ao processo de disfunção endotelial em ratos, os quais foram associados positivamente à hiperatividade do SRA, bem como foram cancelados pelo tratamento com losartan. Assim, este estudo esclarece parte dos mecanismos fisiológicos envolvidos nas alterações metabólicas e cardiovasculares decorrentes do estresse crônico, demonstrando que estas alterações são mediadas pelo receptor AT1, provavelmente pela ligação da angiotensina II ao mesmo / Abstract: Chronic stress is a risk factor for the development of hypertension, atherosclerosis and diabetes. The protocol of chronic mild and unpredictable stress (CMUS) is an animal model of chronic stress. Previously, it has been shown that CMUS induced insulin resistance, dyslipidemia and endothelial dysfunction in rats. Considering that endothelial dysfunction and insulin resistance have been associated with high activity of renin-angiotensin system (RAS), the aim of this study was to investigate the involvement of RAS components on cardiovascular effects induced by CMUS in rats. Sixty two male Sprague-Dawley rats, (2 months old) were used. The experiment period was 7 weeks. In experiment 1, animals were divided into 2 groups: control and stress. The CMUS was applied on weeks 3, 4 and 5 and animals were euthanized 1 and 15 days after the CMUS. The CMUS increased systemic renin and angiotensin converting enzyme (ACE) activity, ACE activity in the thoracic aorta and plasma angiotensin II and angiotensin (1-7) concentrations. Based on these results, showing increased activity of the RAS induced by ECMI, the second experiment was designed to evaluate the involvement of angiotensin II and its AT1 receptor in the effects triggered by CMUS on glucose uptake and on cardiovascular system. Other animals were divided into 4 experimental groups: control, stress, losartan control (AT1 receptor antagonist, losartan - 50 mg /kg/day, orally) and losartan stress. The CMUS induced an increase in area under the curve in the glucose tolerance test (GTT), decreased the in vitro vasodilator response to acetylcholine in the thoracic aorta and increased blood pressure, compared to control group, without difference among control, losartan control and losartan stress group. These results show that the effects of CMUS led to endothelial dysfunction in rats, which was positively associated with hyperactivity of the RAS and was canceled by the treatment with losartan. Thus, this study explains part of the physiological mechanisms involved in cardiovascular and metabolic changes resulting from chronic stress, demonstrating that these changes are mediated by the AT1 receptor, probably by angiotensin II binding to it / Mestrado / Fisiologia Oral / Mestre em Odontologia

Unter dem Motto „Verarbeitung & Verpackung 4.0“ gab es 47 Vorträge zu folgenden Themenschwerpunkten: Bewegungstechnik und Robotik, Verteilte Prozessintelligenz, Prozesssicherheit, Adaptivität und Wandelbarkeit von Verarbeitungsprozessen, hygienegerechte Produktion in der Lebensmittel- und Pharmaproduktion sowie zu neuen Ansätzen aus dem Bereich der Simulation und der Prozessoptimierung. Das Anwenderforum – ein eher praxisorientierter Vortragsstrang - bot Vorträge und Disskussionsraum zu Themen wie Smart Tool und zu neuen Ansätzen der Prozessüberwachung und –kontrolle durch die gezielte Datenanalyse.

Class of 2014 Abstract / Specific Aims: To identify reasons that an angiotensin converting enzyme inhibitor (ACEi) would not be indicated in diabetic patients with repeated clinical alerts to add ACEi therapy for preservation of renal function and/or hypertension. In addition, to identify if these repeated clinical alerts to add ACEi therapy are appropriate. Methods: Eligible patient charts were reviewed by researchers using a data dictionary to complete a standardized spreadsheet with patient demographic information (age, gender, and location), type of diabetes mellitus, evidence indicative of comorbid hypertension, action taken by pharmacist in response to clinical alert (letter sent to patient and letter sent to prescriber), and rationale of that action. This data, along with SOAP notes of patient interactions, was used by researchers to classify the repeated clinical alert as appropriate or inappropriate. Main Results: There were a total of 200 charts reviewed (male n = 61 (30.5%), female n = 139 (69.5%), mean age = 70 ± 11 years). Reasons for not contacting patients again include previous failure or adverse drug reaction (n = 62, 31.0%), patient did not meet call script requirements (n = 55, 27.5%), patient did not have diabetes or hypertension (n = 20, 10.0%), potential drug-disease interaction (n = 17, 8.5%), overlapping or previously addressed alerts (1.9%), or documentation was provided for “other” reasons (n = 43, 21.5%). The previous failure or adverse drug reaction rationale was appropriate in 32 of 62 repeated clinical alerts (52%; χ2= 10.15). The patient did not have diabetes or hypertension rationale was appropriate in 11 of 20 repeated clinical alerts (55%, χ2= 2.72). The potential drug-disease interaction rationale was appropriate in 3 of 17 repeated clinical alerts (8%, χ2= 9.89). The patient did not meet call script requirements rationale was appropriate in 31 of 55 repeated clinical alerts (56%, χ2= 6.91). The overlapping or previous alerts rationale was appropriate in 2 of 3 repeated clinical alerts (67%, χ2= 0.18). The “other” rationale were appropriate in 22 of 43 repeated clinical alerts (51%, χ2= 7.21) Overall, retrigger alerts were considered appropriate 50.5% of the time compared to the predicted value of 90% (χ2= 347 > critical value = 3.84 for p = 0.05 Conclusion: There are multiple reasons pharmacists do not recommend initiating ACEi therapy in patients with diabetes. Although the Medication Management Center (MMC) has rationale of these reasons documented after individual patient interactions, there are still several reasons why a retrigger alert would be appropriate despite that rationale. In addition, retrigger alerts were not considered appropriate as frequently as expected.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Cardiovascular disease is a major health problem and remains the number one cause of death worldwide. For centuries, medicinal plants have been used in different cultures as medicines for the treatment and control of various diseases. Olea africana, also known as the wild olive, is amongst the herbal plants used by people to treat many ailments.Recently, scientific studies on the hypotensive, vasodilatory and antidysarrhythmic effects of O. africana have been reported. Triterpenoids isolated from the O. africana leaves, for example, have antioxidant properties. The aqueous extract from the leaves of O. africana also have angiotensin-converting enzyme (ACE) inhibitory effects. ACE inhibitors and antioxidants protect the heart against ischemic-reperfusion injury. The serine / threonine protein kinase B (PKB) also known as Akt is activated downstream of phosphoinositide 3- (PI-3) kinase (PI-3-Kinase) and is involved in cardioprotection against ischemia-reperfusion injury. Angiotensin II (AII) decreases the intrinsic PI-3-kinase activity. In this study, we hypothesized that ACE inhibitors increase PI-3-kinase activity and thus activates PKB. The aims of this study were: 1) to determine whether treatment with the crude aqueous extract of leaves of O. africana protect the heart against ischemic-reperfusion injury and 2) if so, to determine whether the protection is mediated via the PKB signaling mechanism. Hearts isolated from male Wistar rats were perfused with different concentrations of the plant extract. In one set of experiments, male Wistar rats were treated with the plant extract (1000 mg/kg/day) for 5 weeks for the evaluation of cardiac function before and after ischemia. At the end of the experiments, hearts were freeze-clamped and kept for PKB / Akt determination. In another set of experiments, we determined the effect of O. africana extract (1000 mg/kg/day) or captopril (50 mg/kg/day) on infarct size. Rats fed jelly served as controls for captopril. In a subset of experiments, hearts were frozen immediately after treatment with O. africana extract (1000 mg/kg/day) or captopril (50mg/kg/day) and PKB were determined.Perfusion with the plant extract significantly decreased coronary flow (p<0.05). The heart function was decreased as evidenced by observed decreases in the force of contraction and heart rate, although these were not measured. Chronic treatment with the crude aqueous plant extract had no effect on cardiac function before ischemia, functional recovery (% left ventricular developed pressure and % rate pressure product) and PKB /Akt phosphorylation (p>0.05). Both the aqueous extract of O. africana leaves and captopril had no effect on infarct size compared to the control group (p>0.05). Captopril,however, improved the recovery of the left ventricular developed pressure. Non-perfused hearts isolated from rats treated with O. africana extract and captopril did not show any response to both captopril and the O. africana extract treatment as measured by PKB /Akt phosphorylation. The results of the present study suggest that the crude aqueous extract of O. africana is not cardioprotective against ischemia-reperfusion injury in this system of the isolated perfused rat heart.

Orientador: Gilberto de Nucci / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T17:06:06Z (GMT). No. of bitstreams: 1 Okuyama_CristinaEunice_D.pdf: 791888 bytes, checksum: 44bf756719cf0cdc26ab70b220532e28 (MD5) Previous issue date: 2006 / Resumo: Compostos farmacológicos que liberam óxido nítrico (NO) têm sido utilizados para avaliar o amplo papel do NO na fisiopatologia e terapêutica de diversas doenças. Estudos demonstram que a deficiência de NO está envolvida com a gênese e evolução de diversos estágios de doenças como, por exemplo, a hipertensão. Deste modo, a adição de uma molécula de NO em drogas previamente estudadas vem sendo praticada por diversos pesquisadores na última década. Estes pesquisadores buscam associar as propriedades farmacológicas de cada droga com as atividades proporcionadas pelo NO exógeno. No presente trabalho, comparamos a farmacocinética e a farmacodinâmica do enalapril com as de um nitro-derivado do enalapril (NCX899), em Beagles machos não anestesiados. Os efeitos do enalapril e NCX899 na hipertensão arterial, bradicardia e vasoconstrição periférica induzida pela inibição aguda da síntese de NO em cães anestesiados também foram investigados. Na avaliação farmacocinética, os cães receberam NCX899 (4 µmol/Kg) ou Enalapril (4 µmol/Kg) pela via intravenosa. Em seguida, as concentrações plasmáticas dos analitos e metabólitos foram quantificadas pelo método de cromatografia líquida de alta eficiência, acoplada à espectrometria de massa (LCMS- MS). No grupo NCX899, a área sob a curva (ASC0-24h) foi 29,18 ± 4,72, 229,37 ± 51,32 e 5159,23 ± 514,88 µgh/l para os analitos nitro-enalapril, enalapril e enalaprilato, respectivamente. No grupo Enalapril, a ASC0-24h foi de 704,53 ± 158,86 e 4149,27 ± 847,30 µgh/l para os analitos enalapril e enalaprilato, respectivamente. As análises estatísticas entre os grupos demonstraram uma diferença significativa para o analito enalapril, mas não para o analito enalaprilato, o metabólito ativo. Entretanto, o NCX899 e o Enalapril foram efetivos de maneira semelhante na inibição da atividade da enzima conversora de angiotensina sérica. Em cães anestesiados, a administração intravenosa do inibidor da síntese de NO, o N?-nitro-L-arginina metil éster (L-NAME; 0,1-10 mg/kg), elevou significativamente a pressão arterial e causou bradicardia. O composto NCX899 atenuou significativamente a hipertensão arterial, bradicardia e vasoconstrição periférica, enquanto o Enalapril não apresentou efeito significativo. Além disso, nossos estudos também demonstraram que o NCX899 pode atuar não só como anti-hipertensivo, mas também auxiliar na inibição da agregação plaquetária. Assim, concluímos que o nitro-derivado do enalapril (NCX899) apresenta uma relação farmacocinética/farmacodinâmica similar ao composto enalapril. No entanto, ao contrário do Enalapril, o NCX899 apresenta um efeito protetor nas alterações cardiovasculares induzidas pela inibição aguda de NO / Abstract: Pharmacological compounds that release nitric oxide (NO) have been useful tools for evaluating the broad role of NO in physiopathology and therapeutics of several diseases. Studies show that lack of NO can cause several diseases such as hypertension. Thus, the addition of a NO molecule in drugs previously studied has been reported by some researchers in the last decade. They look for the combination of the pharmacologic properties of each drug, plus exogenous NO properties. This work has compared the pharmacokinetics and pharmacodynamics of enalapril and a NO-releasing enalapril molecule (NCX899) in conscious male Beagles. The effects of both enalapril and NCX899 in the arterial hypertension, bradycardia and peripheral vasoconstriction induced by acute NO inhibition in anesthetized dogs have also been investigated. In the pharmacokinetic evaluation, dogs received either NCX899 (4 µmol/Kg) or Enalapril (4 µmol/Kg) intravenously. Later, the plasma concentrations of the analytes and metabolites were quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). In the NCX899 group, the area under time-course curve (AUC0-24h) was 29.18 ± 4.72, 229.37 ± 51.32 and 5159.23 ± 514.88 µgh/l for the nitro-enalapril, enalapril and enalaprilat analytes, respectively. In the Enalapril group, the AUC0-24h was 704.53 ± 158.86 and 4149.27 ± 847.30 µgh/l for the enalapril and enalaprilat analytes, respectively. The statistical analysis between both groups showed a significant difference for the enalapril analyte, but not for enalaprilat, the active metabolite. Moreover, NCX899 and Enalapril were equally effective on inhibiting the activity of serum angiotensin-converting enzyme. In anesthetized dogs, intravenous administration of the NO synthase (NOS) inhibitor N?-nitro-L-arginine methyl ester (L-NAME; 0.1-10 mg/kg) significantly elevated arterial blood pressure with concomitant bradycardia. The compound NCX899 significantly attenuated arterial hypertension, bradycardia and peripheral vasoconstriction, whereas Enalapril had no significant effect. In addition, our work showed that NCX899 also has properties of inhibiting the activity of platelets aggregation. In conclusion, our results showed that the NO-releasing derivative of enalapril NCX899 presents a pharmacokinetic / pharmacodynamic relationship similar to the enalapril compound. Moreover, different from Enalapril, NCX899 presented protective effect in the cardiovascular alterations induced by acute NOS inhibition / Doutorado / Doutor em Farmacologia

Submitted by biblioteca unifenas (biblioteca@unifenas.br) on 2016-06-21T18:48:24Z No. of bitstreams: 1 Edison Clayton Pistelli dissertacao.pdf: 3899985 bytes, checksum: dc3575ed8916b86bd0e4913fafda260c (MD5) / Made available in DSpace on 2016-06-21T18:48:24Z (GMT). No. of bitstreams: 1 Edison Clayton Pistelli dissertacao.pdf: 3899985 bytes, checksum: dc3575ed8916b86bd0e4913fafda260c (MD5) Previous issue date: 2014-04-02 / Medicinal plants are cultivated for use in popular medicine, and in food, pharmaceutical and perfumes industry. New technology in mineral nutrition, irrigation, protected culture, as well as alterations in quality and intensity of exposure to light have been applied in the cultivation of medicinal plants. This present work aimed to assess the influence of the quality and intensity of lighting on different medicinal plants. Treatments consisted of citronella (Cymbopogon nardus L.), lemongrass (Cymbopogon citratus DC. Stapf) and vetiver (Vetiveria zizanioides L. Nash) under different photo-converting filter colours (black, red and blue) as well as under plain sunlight. Medicinal plant seedlings were transplanted in SLAB type substrate and kept under the different treatments. Drip fertirrigation was carried out throughout treatment cycle. Assessments on plant growth, leaf anatomy, chlorophyll content, photosynthesis, production and composition of the essential oil were performed on the 180th day. Plant height fared best results on cultivation under the red mesh. Plain sun favoured higher accumulation of dry biomass by the plants. Photo-converting promoted alterations on leaf anatomy in plants. Citronella and lemongrass plants, respectively, showed thinner leaf mesophylls when kept under the blue and red filters. The black filter mesh promoted greater leaf mesophylls on vetiver plants. Citronella leaves showed 1240 stomata/mm-2, vetiver 409 stomata/mm-2 and lemmongrass showed 806 stomata/mm-2. The highest contents of chlorophyll a and b were noticed on lemongrass plants cultivated under plain sunlight, while citronella plants fared higher chlorophyll rates when under black filter. Lower rates of chlorophyll were verified on vetiver under the black mesh. Medicinal plants cultivated under the red mesh as well as those cultivated under plain sunlight yielded the highest photo-synthetic rates. The highest essential oil yielding was obtained from plants growing under plain sunlight. The main compound found in citronella was citronellal with rates above 30%. Citral was the main constituent in the lemongrass essential oil, and muuroladieno, dehydro isolongifeno and muurolol were found in the vetiver plants. The photo-converting mesh pieces promoted morpho-physiological alterations on medicinal plants, as well as on the yielding and contents of their essential oil constituents. / As plantas medicinais são cultivadas por serem usadas na medicina popular, na indústria alimentícia, farmacêutica e de perfumes. Novas tecnologias em nutrição mineral, irrigação, cultivo protegido e alterações na qualidade e intensidade luminosa vêm sendo empregada no cultivo de plantas medicinais. O presente trabalho teve por objetivo verificar a influência da qualidade e intensidade luminosa em diferentes plantas medicinais. Os tratamentos foram compostos pelo cultivo de citronela (Cymbopogon nardus L.), capim-limão (Cymbopogon citratus DC. Stapf) e vetiver (Vetiveria zizanioides L. Nash) sob diferentes malhas fotoconversoras (preto, vermelho e azul) e no cultivo protegido. As mudas das plantas medicinais foram transplantadas em substrato tipo SLAB e assim mantidas nos diferentes tratamentos. Foi realizada fertirrigação (NPK) por gotejamento durante todo o ciclo do experimento. Aos 180 dias foram realizadas as avaliações das características de crescimento das plantas, anatomia foliar, teor de clorofila, fotossíntese, produção e composição do óleo essencial. A maior altura das plantas foi observada no cultivo sob a malha vermelha. O cultivo protegido favoreceu o maior acúmulo de biomassa seca das plantas medicinais. As malhas fotoconversoras promoveram alterações na anatomia foliar das plantas. Plantas de citronela e capim-limão apresentaram menor espessura do mesofilo foliar quando mantidas sob as malhas azul e vermelha, respectivamente. A malha preta promoveu em plantas de vetiver o maior mesofilo foliar. As folhas de citronela apresentaram (1240 estômatos mm-2), vetiver (409 estômatos mm-2) e capim-limão (806 estômatos mm-2). Maiores conteúdos de clorofilas a e b foram observados em plantas de capim-limão cultivadas a cultivo protegido e as plantas de citronela apresentaram maior teor de clorofila enquanto mantidas em malha preta. Menores teores de clorofila foram observados em plantas de vetiver mantidas sob a malha vermelha. Plantas medicinais cultivadas sob a malha vermelha e no cultivo protegido apresentaram as maiores taxas fotossintéticas. O maior rendimento em óleo essencial foi obtido em plantas crescendo a cultivo protegido. O principal composto encontrado em citronela foi o citronelal com teores acima de 30%. O citral foi o constituinte majoritário do óleo essencial de capim-limão e nas plantas de vetiver foram encontrados o muuroladieno, mehidro isolongifeno e o muurolol. As malhas fotoconversoras promoveram alterações morfofisiológicas, bem como no rendimento e teor dos constituintes dos óleos essenciais das plantas medicinais.

This work deals with the public data network covering of the locality of the noth-east part of Brno and neighbouring villages.

Die Firma Schubert baut TLM-Verpackungsmaschinen. TLM bedeutet Top Loading Maschine, d.h. die Aufgabe einer TLM-Maschine ist in der Regel das Aufrichten, Befüllen und Verschließen von Schachteln. TLM-Maschinen bestehen aus Teilmaschinen, die über Transmodulstrecken miteinander verbunden sind. Transmodule transportieren Produkte und Verpackungseinheiten, die Prozessvernetzung wird einfacher und es ergeben sich neue Möglichkeiten.

Wissenschaft trifft Praxis - das Motto der Tagung steht für einen Dialog, der in diesen Tagen besonders von folgenden Spannungsfeldern lebt: Komplexe Prozesse vs. einfache Maschinenbedienung, Adaptivität vs. Robistheit, Flexibilität vs. effizienz, technischer Vorsprung vs. technischer Aufwand. Zwischen diesen und anderen Themenfeldern gibt es Schnittmengen aber auch spannende Antagonismen. In 34 Vorträgen + 5 Plenarbeiträgen werden neue Gedanken und Lösungsansätze vorgestellt, die Wissen vermitteln und Anregungen bieten.

Getrieben durch einen rapid wachsenden Verbrauchermarkt für Lebensmittel und Getränke, insbesondere in Schwellenländern wie China, Brasilien und Indien, werden an den Verpackungssektor hohe Anforderungen hinsichtlich der Verpackungsqualität und -formen und nicht zuletzt der Stückzahl gestellt. Bei der Entwicklung von Verpackungssystemen stellt die Leistungssteigerung das vorrangige Ziel für die Verpackungsmaschinen- und Packstoffhersteller stellt dar. Die SIG Combibloc Systems GmbH, einer der weltweit führenden Systemanbieter von Packstoff und entsprechenden Füllmaschinen für Getränke und Lebensmittel, hat sich als Ziel gesetzt, die Leistung eines ihrer Verpackungssysteme um 50 % zu steigern.