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Biochemical Rationale (biochemical + rationale)
Selected AbstractsThe role of purine analogue combinations in the management of acute leukemiasHEMATOLOGICAL ONCOLOGY, Issue 4 2001R. J. Frewin Abstract Cytosine arabinoside plays a pivotal role in the therapy of acute myeloid leukemias with the concentration of its active metabolite, ara-CTP, being positively correlated with improved clinical outcome. Both in vitro studies and ex vivo studies have confirmed the ability of the purine analogues to enhance ara-CTP accumulation within leukemic cells via the stimulation of deoxycytidine kinase. Clinical studies have confirmed the efficacy of these combination regimes in the treatment of acute leukemias. The basis of the biochemical rationale for the development of combination chemotherapy regimes with purine analogues for acute leukemias is reviewed along with clinical studies of their effectiveness and toxicity. Copyright © 2001 John Wiley & Sons, Ltd. [source] HEALTH BENEFITS OF APPLE PHENOLICS FROM POSTHARVEST STAGES FOR POTENTIAL TYPE 2 DIABETES MANAGEMENT USING IN VITRO MODELSJOURNAL OF FOOD BIOCHEMISTRY, Issue 1 2010I. ADYANTHAYA ABSTRACT An increasing number of studies indicate that regular intake of fruits and vegetables have clear links to reduced risk of chronic diseases like diabetes and cardiovascular disease. The beneficial effects in many cases have been attributed to the phenolic and antioxidant content of the fruits and vegetables. Apples are a major source of fiber and contain good dietary phenolics with antioxidant function. Previous epidemiological studies have indicated that intake of apples reduces the risk of developing type 2 diabetes. Our studies indicate that this reduced risk is potentially because of the modulation of postprandial glucose increase by phenolics present in apples via inhibition of, -glucosidase. Phenolic content was evaluated during 3 months of postharvest storage of four varieties of apples and results indicated positive linkage to enhanced postharvest preservation and, -glucosidase inhibition. These in vitro results along with existing epidemiological studies provide strong biochemical rationale for further animal or human clinical studies. PRACTICAL APPLICATIONS The understanding of phenolic-linked antioxidant enzyme responses during postharvest storage of apples has implications for using the same phenolic functional ingredients toward health benefits such as ,-glucosidase inhibition linked to glycemic index control associated with type 2 diabetes. Therefore strategies to understand phenolic-linked postharvest preservation and natural treatments to extend this preservation in selected varieties, such as McIntosh and Cortland in this study, can be basis for food ingredient design for health benefits. These strategies can then be extended to prolong postharvest preservation and enhance phenolic linked human health benefits of a wide variety of fruits and vegetables. [source] INHIBITORY POTENTIAL OF WINE AND TEA AGAINST ,-AMYLASE AND ,-GLUCOSIDASE FOR MANAGEMENT OF HYPERGLYCEMIA LINKED TO TYPE 2 DIABETESJOURNAL OF FOOD BIOCHEMISTRY, Issue 1 2008YOUNG-IN KWON ABSTRACT Natural ,-amylase and ,-glucosidase inhibitors from food-grade plants offer an attractive strategy to manage postprandial hyperglycemia for type 2 diabetes management via control of starch breakdown and intestinal glucose absorption. In this study, four random sources of red and white wines as well as four types of teas were investigated for ,-amylase and ,-glucosidase inhibitory potential. Water extracts of black tea had the highest ,-glucosidase inhibitory activity, followed by white tea and oolong tea. All the randomly selected red wines had significant ,-glucosidase inhibitory activity compared to white wine. The ,-glucosidase inhibitory activity of the tea and wines correlated to the phenolic content, antioxidant activity and phenolic profile of the extracts. Further, these extracts had less or no ,-amylase inhibitory activity, indicating potential to overcome the side effects of undigested starch. This research has relevance for managing hyperglycemia and related oxidation-linked dysfunction and concurrently reducing problems of undigested starch. PRACTICAL APPLICATIONS In this study anti-diabetic-relevant potential of wines and teas were confirmed in four types of red and white wines as well as four types of commonly available teas using in vitro enzyme assays for alpha-glucosidase and alpha-amylase inhibitory activities. In vitro inhibitory activities of these enzymes provide a strong biochemical rationale for further in vivo studies and dietary management strategy for type 2 diabetes through the control of glucose absorption. Further this phenolic antioxidant-enriched dietary strategy using specific beverage combinations can generate a whole food profile that has the potential to reduce hyperglycemia-induced pathogenesis and also associated complications linked to cellular oxidation stress. [source] The relative kinetics of clotting and lysis provide a biochemical rationale for the correlation between elevated fibrinogen and cardiovascular diseaseJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2007P. Y. KIM Summary.,Background:,Elevated plasma fibrinogen is a well known risk factor for cardiovascular disease. The mechanistic rationale for this is not known.Objectives:,These studies were carried out to determine the fibrinogen concentration dependencies of clotting and lysis times and thereby determine whether these times rationalize the correlation between an increased risk of cardiovascular disease and elevated plasma fibrinogen.Methods:,The time courses of clot formation and lysis were measured by turbidity in systems comprising a) fibrinogen, thrombin and plasmin, or b) fibrinogen, thrombin, plasminogen and t-PA, or c) plasma, thrombin and t-PA. From the lysis times, kcat and Km values for plasmin action on fibrin were determined.Results:,The time to clot increased linearly from 2.9 to 5.6 minutes as the fibrinogen concentration increased from 1 to 9 ,M and did not increase further as the fibrinogen concentration was raised to 20 ,M. In contrast, the clot lysis time increased linearly over the input fibrinogen concentration range of 2 to 20 ,M. A similar linear trend was found in the two systems with t-PA and plasminogen. Apparent Km and kcat values for plasmin were 1.1 ± 0.6 ,M and 28 ± 2 min,1, respectively. Km values for plasmin in experiments initiated with t-PA and plasminogen were 1.6 ± 0.2 ,M in the purified system and 2.1 ± 0.9 ,M in plasma.Conclusion:,As the concentration of fibrinogen increases, especially above physiologic level, the balance between fibrinolysis and clotting shifts toward the latter, providing a rationale for the increased risk of cardiovascular disease associated with elevated fibrinogen. [source] Synthetic Strategy of Nonreducing Iterative Polyketide Synthases and the Origin of the Classical "Starter-Unit Effect"CHEMBIOCHEM, Issue 7 2008Jason M. Crawford Dr. Getting started: The starter-unit effect in fungal polyketides stems from starter unit:acyl-carrier protein transacylase (SAT) domains found in nonreducing polyketide synthases (PKSs). Dissection of the PKSs involved in the production of naphthopyrone YWA1, tetrahydroxynaphthalene, cercosporin, and bikaverin revealed that their SAT domains had high selectivity for acetyl-CoA (see figure); this provides a biochemical rationale for this classically observed effect. [source] | |||||||||||||