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Female Wistar rats (n = 34 animals) (Charles River Laboratories, Sulzfeld, Germany) with an average weight of 282 ± 19 g were housed under laboratory conditions (temperature: mean 21°C ± 2°C standard deviation, humidity: mean 55% ± 10% standard deviation, 12:12-hour light-dark-cycle) for ten days. Food (10 mm pellets, Provimi Kliba AG, Kaiseraugst, Switzerland) and tap water were available ad libitum. Pre-operatively, a maximum of four animals were kept per cage (1354G Eurostandard type IV cages, Tecniplast Deutschland GmbH, Hohenpeissenberg, Germany) in no particular order. Cages were lined with 5 x 5 x 1 mm wood chips (Abedd Lab & Vet Service GmbH, Vienna, Austria). After each surgical procedure the animals were housed in separate cages (1291H Eurostandard type III H cages, Tecniplast Deutschland GmbH, Hohenpeissenberg, Germany), each lined with unbleached chemical pulp (Paul Hartmann AG, Heidenheim, Germany). After post-operative day 2, four animals were kept per cage (1354G Eurostandard type IV cages, Tecniplast Deutschland GmbH, Hohenpeissenberg, Germany). These cages were lined with 5 x 5 x 1 mm wood chips (Abedd - lab & vet Service GmbH, Vienna, Austria).. be the root cause of neurodegeneration gained attention with the report. Substantial data suggest that flavonoid-rich food could help prevent cardiovascular disease and cancer. Cocoa is the richest source of flavonoids, but current processing reduces the content substantially. The Kuna living in the San Blas drink a flavanol-rich cocoa as their main beverage, contributing more than 900 mg/day and thus probably have the most flavonoid-rich diet of any population. We used diagnosis on death certificates to compare cause-specific death rates from year 2000 to 2004 in mainland and the San Blas islands where only Kuna live. Our hypothesis was that if the high flavanoid intake and consequent nitric oxide system activation were important the result would be a reduction in the frequency of ischemic heart disease, stroke, diabetes mellitus, and cancer – all nitric oxide sensitive processes. There were 77,375 deaths in mainland Panama and 558 deaths in the San Blas. In mainland Panama, as anticipated, cardiovascular disease was the leading cause of death (83.4 ± 0.70 age adjusted deaths/100,000) and cancer was second (68.4 ± 1.6). In contrast, the rate of CVD and cancer among island-dwelling Kuna was much lower (9.2 ± 3.1) and (4.4 ± 4.4) respectively. Similarly deaths due to diabetes mellitus were much more common in the mainland (24.1 ± 0.74) than in the San Blas (6.6 ± 1.94). This comparatively lower risk among Kuna in the San Blas from the most common causes of morbidity and mortality in much of the world, possibly reflects a very high flavanol intake and sustained nitric oxide synthesis activation. However, there are many risk factors and an observational study cannot provide definitive evidence.

Substantial data suggest that flavonoid-rich food could help prevent cardiovascular disease and cancer. Cocoa is the richest source of flavonoids, but current processing reduces the content substantially. The Kuna living in the San Blas drink a flavanol-rich cocoa as their main beverage, contributing more than 900 mg/day and thus probably have the most flavonoid-rich diet of any population. We used diagnosis on death certificates to compare cause-specific death rates from year 2000 to 2004 in mainland and the San Blas islands where only Kuna live. Our hypothesis was that if the high flavanoid intake and consequent nitric oxide system activation were important the result would be a reduction in the frequency of ischemic heart disease, stroke, diabetes mellitus, and cancer – all nitric oxide sensitive processes. There were 77,375 deaths in mainland Panama and 558 deaths in the San Blas. In mainland Panama, as anticipated, cardiovascular disease was the leading cause of death (83.4 ± 0.70 age adjusted deaths/100,000) and cancer was second (68.4 ± 1.6). In contrast, the rate of CVD and cancer among island-dwelling Kuna was much lower (9.2 ± 3.1) and (4.4 ± 4.4) respectively. Similarly deaths due to diabetes mellitus were much more common in the mainland (24.1 ± 0.74) than in the San Blas (6.6 ± 1.94). This comparatively lower risk among Kuna in the San Blas from the most common causes of morbidity and mortality in much of the world, possibly reflects a very high flavanol intake and sustained nitric oxide synthesis activation. However, there are many risk factors and an observational study cannot provide definitive evidence.. It is well known that coronary artery disease (CAD) is a multifactorial chronic disease, whose morbidity and mortality remain high worldwide [1-3]. Dislipidemia has been shown to play a prominent role in the process of CAD and it accounts for ~50% of the population attributable risk of developing CAD [4]. Based upon the results of recent studies, which had demonstrated that dislipidemia is a distinct complex trait resulted from multiple environmental and genetic factors as well as their interactions [5-7]. In twin and family studies, it was surveyed that plasma lipid levels were estimated to range from 0.28-0.78 with heritability [8]. However, the genetic architecture of serum lipid profiles is assumed to be intricate and continues to be poorly understood.. myomectomy group.

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