Enzyme convertedstarch in pigment coating

Tämän diplomityön tavoitteena oli selvittää entsyymikonvertoinnin mahdollisuudet vaikuttaa sideainetärkkelyksen toiminnallisiin ominaisuuksiin. Tärkein tehtävä oli etsiä vastaukset kysymykseen, kuinka paljon entsyymikonvertointia optimoimalla voidaan maksimoida tärkkelyksen positiivisia vaikutuksia. Tavoitteena oli myös tutkia, voiko lisäaineita käyttämällä ja tärkkelystä plastisoimalla säilyttää tärkkelyksen vaikutus paperin jäykkyyteen ja saada tärkkelysfilmille joustavuutta. Kirjallisuusosassa tarkasteltiin tärkkelyksen entsyymikonvertointiin vaikuttavia tekijöitä, eri tärkkelysraaka-aineiden eroja, sekä konvertoinnissa käytettävien entsyymien ominaisuuksia. Kirjallisuusosassa tarkasteltiin myöstärkkelyksen käyttöä sideaineena pigmenttipäällystyksessä. Kokeellisessa osassakeskityttiin selvittämään entsyymikonvertoinnin olosuhteiden, käytettävän raakatärkkelyksen ja entsyymin vaikutusta konvertoidun tärkkelyksen ominaisuuksiin. Konvertoiduista tärkkelyksistä valmistettiin päällystyspastat, ja tutkittiin niinpastan kuin päällystetyn paperin ominaisuuksia. Myös erilaisten pehmentimien vaikutusta niin päällystyspastaan, kuin paperin pinnalle tutkittiin. Havaittiin, että konvertoimalla tärkkelysketjua entsymaattisesti, voidaan tärkkelysketjun pituutta säädellä. Tarkoituksena oli konvertoida tärkkelystä niin, että tärkkelyksen molekyyliketjujakaumat sisältävät lyhyitä, keskipitkiä sekäpitkiä molekyylejä. Päällystämisen havaittiin olevan vaikeaa Helicoaterilla varsinkin pitkäketjuista tärkkelystä suuren määrän sisältävillä pastoilla. Myös tärkkelys/lateksi-suhde vaihteli eri pastoilla. Päällystyspastojen reologisia ominaisuuksia testattaessa huomattiin, että tärkkelysketjun pituuden kasvaessa pastanviskositeetti lisääntyy ja vesiretentio vähenee. Havaittiin vain muutamia teknisiä paperiominaisuuksia, jotka korreloivat hyvin tärkkelysketjun pituuden kanssa. Näitä olivat kiilto, Gurley-Hill huokoisuus, taivutusvastus, taivutuspituus sekä IGT pintalujuus. Pehmentimien ei havaittu vaikuttavan moneenkaan paperin eri tekniseen ominaisuuteen. Suurimmat erot huomattiin paperin taivutuspituudessa ja taivutusvastuksessa.

Angiotensin converting enzyme inhibitory peptides in Finnish cereals : a database survey

Selostus: Angiotensiini I -muuntavaa entsyymiä estävien peptidien aminohapposekvenssien esiintyminen viljan varastoproteiinien rakenteessa

Effects of Cytochrome P450 Enzyme Inhibitors on the Pharmacokinetics of Nonsteroidal Anti-inflammatory Drugs and Venlafaxine

Cytochrome P450 (CYP) enzymes play a pivotal role in the metabolism of many drugs. Inhibition of CYP enzymes usually increases the plasma concentrations of their substrate drugs and can thus alter the safety and efficacy of these drugs. The metabolism of many widely used nonsteroidal antiinflammatory drugs (NSAIDs) as well as the metabolism of the antidepressant venlafaxine is nown to be catalyzed by CYP enzymes. In the present studies, the effect of CYP inhibition on the armacokinetics and pharmacodynamics of NSAIDs and venlafaxine was studied in clinical trials with healthy volunteers and with a crossover design, by using different antifungal agents as CYP inhibitors. The results of these studies demonstrate that the inhibition of CYP enzymes leads to increased concentrations of NSAIDs. In most cases, the exposure to ibuprofen, diclofenac, etoricoxib, and meloxicam was increased 1.5to 2 fold when they were used concomitantly with antifungal agents. CYP2D6 inhibitor, terbinafine, substantially increased the concentration of parent venlafaxine, whereas the concentration of active moiety of venlafaxine (parent drug plus active metabolite) was only slightly increased. Voriconazole, an inhibitor of the minor metabolic pathway of venlafaxine, produced only minor changes in the pharmacokinetics of venlafaxine. These studies show that an evident increase in the concentrations of NSAIDs may be expected, if they are used concomitantly with CYP inhibitors. However, as NSAIDs are generally well tolerated, use of single doses of NSAIDs concomitantly with CYP inhibitors is not likely to adversely affect patient safety, whereas clinical relevance of longterm concomitant use of NSAIDs with CYP inhibitors needs further investigation. CYP2D6 inhibitors considerably affect the pharmacokinetics of venlafaxine, but the clinical significance of this interaction remains unclear.

Cyanobacteria from the Baltic Sea and Finnish lakes as an energy source and modulators of bioenergetic pathways

Cyanobacteria are a diverse group of oxygenic photosynthetic bacteria that inhabit in a wide range of environments. They are versatile and multifaceted organisms with great possibilities for different biotechnological applications. For example, cyanobacteria produce molecular hydrogen (H2), which is one of the most important alternatives for clean and sustainable energy. Apart from being beneficial, cyanobacteria also possess harmful characteristics and may become a source of threat to human health and other living organisms, as they are able to form surface blooms that are producing a variety of toxic or bioactive compounds. The University of Helsinki Culture Collection (UHCC) maintains around 1,000 cyanobacterial strains representing a large number of genera and species isolated from the Baltic Sea and Finnish lakes. The culture collection covers different life forms such as unicellular and filamentous, N2-fixing and non-N2-fixing strains, and planktonic and benthic cyanobacteria. In this thesis, the UHCC has been screened to identify potential strains for sustainable biohydrogen production and also for strains that produce compounds modifying the bioenergetic pathways of other cyanobacteria or terrestrial plants. Among the 400 cyanobacterial strains screened so far, ten were identified as high H2-producing strains. The enzyme systems involved in H2 metabolism of cyanobacteria were analyzed using the Southern hybridization approach. This revealed the presence of the enzyme nitrogenase in all strains tested, while none of them are likely to have contained alternative nitrogenases. All the strains tested, except for two Calothrix strains, XSPORK 36C and XSPORK 11A, were suggested to contain both uptake and bidirectional hydrogenases. Moreover, 55 methanol extracts of various cyanobacterial strains were screened to identify potent bioactive compounds affecting the photosynthetic apparatus of the model cyanobacterium, Synechocystis PCC 6803. The extract from Nostoc XPORK 14A was the only one that modified the photosynthetic machinery and dark respiration. The compound responsible for this effect was identified, purified, and named M22. M22 demonstrated a dual-action mechanism: production of reactive oxygen species (ROS) under illumination and an unknown mechanism that also prevailed in the dark. During summer, the Baltic Sea is occupied by toxic blooms of Nodularia spumigena (hereafter referred to as N. spumigena), which produces a hepatotoxin called nodularin. Long-term exposure of the terrestrial plant spinach to nodularin was studied. Such treatment resulted in inhibition of growth and chlorosis of the leaves. Moreover, the activity and amount of mitochondrial electron transfer complexes increased in the leaves exposed to nodularin-containing extract, indicating upregulation of respiratory reactions, whereas no marked changes were detected in the structure or function of the photosynthetic machinery. Nodularin-exposed plants suffered from oxidative stress, evidenced by oxidative modifications of various proteins. Plants initiated strategies to combat the stress by increasing the levels of alpha-tocopherol, mitochondrial alternative oxidase (AOX), and mitochondrial ascorbate peroxidase (mAPX).

Effects of cytochrome P450 enzyme inhibitors and inducers on the metabolism of S-ketamine

The human body eliminates foreign compounds primarily by metabolizing them to hydrophilic forms to facilitate effective excretion through the kidneys. Cytochrome P450 (CYP) enzymes in the liver and intestine contribute to the metabolism of many drugs. Pharmacokinetic drugdrug interactions occur if the activity of CYPs are inhibited or induced by another drug. Prescribing multiple drugs to the improve effectiveness of therapy or to treat coexisting diseases is a common practice in clinical medicine. Polypharmacy predisposes patients to adverse effects because of the profound unpredictability in CYP enzymatic-mediated drug metabolism. S-ketamine is a phencyclidine derivative which functions as an antagonist of the N-methyl-Daspartate (NMDA) receptor in the central nervous system. It is a unique anaesthetic producing “dissociative anaesthesia” in high doses and analgesia in low doses. Studies with human liver microsomes suggest that ketamine is metabolized primarily via CYP3A4 and CYP2B6 enzymes. In this thesis, in healthy volunteers, randomized and controlled cross-over studies were conducted to investigate the effects of different CYP inducers and inhibitors on the pharmacokinetics and pharmacodynamics of oral and intravenous S-ketamine. The plasma concentrations of ketamine and its metabolite, norketamine, were determined at different timepoints over a 24 hour period. Other pharmacodynamic variables were examined for 12 hours. Results of these studies showed that the inhibition of the CYP3A4 pathway by clarithromycin or grapefruit juice increased the exposure to oral S-ketamine by 2.6- and 3.0-fold. Unexpectedly, CYP3A4 inhibition by itraconazole caused no significant alterations in the plasma concentrations of oral S-ketamine. CYP3A4 induction by St. John´s wort or rifampicin decreased profoundly the concentrations of oral S-ketamine. However, after rifampicin, there were no significant differences in the plasma concentrations of S-ketamine when it was administered intravenously. This demonstrated that rifampicin inhibited the metabolism of Sketamine at the intestinal level. When CYP2B6 was inhibited by ticlopidine, there was a 2.4- fold increase in the exposure of S-ketamine. These studies demonstrated that low dose oral Sketamine is metabolized both via CYP3A4 and CYP2B6 pathways. The concomitant use of drugs that affect CYP3A4 or CYP2B6, during oral S-ketamine treatment, may cause clinically significant drug-drug interactions.