No abstract

Platelets and fibrin play an important role in the coagulation process, where they are involved in the maintenance of hemostasis. Fibrin dysfunction is associated with the development of vascular complications, while proneness to the formation of tight and rigid fibrin networks is independently associated with thrombotic disease. Here we investigate the ultrastructure of human, rabbit, and mouse platelets and fibrin networks, using the scanning electron microscope. Human and rabbit fibrin and platelets, with regards to morphology as well as size of major and minor fibers compare well with each other. However, mouse fibers are much thinner and form a flimsy branching network. Platelet aggregate morphology of all three species compare well with each other. We conclude that rabbit platelet and fibrin networks could be used successfully when studying the effect of pharmaceutical products in preclinical trials, when looking at the effects of these products on morphology and ultrastructure.

The coagulation process, including thrombin, fibrin, as well as platelets, plays an important role in hemostasis, contributing to the general well-being of humans. Fibrin formation and platelet activation are delicate processes that are under the control of many small physiological events. Any one of these many processes may be influenced or changed by external factors, including pharmaceutical or nutritional products, e.g., the sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester). It is known that phenylalanine is present at position P 9 and aspartate at position P 10 of the α-chain of human fibrinogen, and plays an important role in the conversion of fibrinogen to fibrin by the catalyst -thrombin. The authors investigate the effect of aspartame on platelet and fibrin ultrastructure, by using the rabbit animal model and the scanning electron microscope. Animals were exposed to 34 mg/kg of aspartame 26× during a 2-month period. Aspartame-exposed fibrin networks appeared denser, with a thick matted fine fiber network covering thick major fibers. Also, the platelet aggregates appeared more granular than the globular control platelet aggregates. The authors conclude by suggesting that aspartame usage may interfere with the coagulation process and might cause delayed fibrin breakup after clot formation. They suggest this, as the fibrin networks from aspartame-exposed rabbits are more complex and dense, due to the netlike appearance of the minor, thin fibers. Aspartame usage should possibly be limited by people on anti-clotting medicine or those with prone to clot formation.

Platelets and fibrin play an important role in the coagulation process where they are involved in the maintenance of haemostasis. Fibrin dysfunction is associated with the development of vascular complications, while proneness to the formation of tight and rigid fibrin networks is independently associated with thrombotic disease. Rabbits have long been used successfully as animal models, and are often the species of choice for models of antithrombotic efficacy. It was previously shown that rabbit and human platelet and fibrin morphology are very similar in ultrastructure and fibrin fibre thickness. It was also previously reported that the thin minor fibres forms a thick fine network cover over the major fibres during pregnancy. According to research, white blood cell counts also changes during pregnancy and stays changed for up to 6 weeks post-partum; where the number of neutrophils increased, and the number of lymphocytes, basophils and eosinophils decreased. Here, we show that the same ultrastructure and white blood cell count changes occur in lactating rabbits (4 weeks post-partum). We therefore suggest that a rabbit morphology model studying platelet and fibrin morphology can be used successfully, either to study the effect of pharmaceutical products to be used during lactation and pregnancy in humans, or used in veterinary research. Furthermore, the effects of pharmaceutical products on immunology and white blood cell counts can possibly also be used successfully.

The issue of aspartame safety has been controversial since approval by FDA, many years ago. It seems as if there are two points of views, either supporting the use of aspartame, or suggesting its dangers. Numerous research articles raised concerns regarding the adverse effects and particularly related to the metabolic components. The comments of JD Fernstrom will now be addressed in Box 1.From the comments made by JD Fernstrom, it appears that he does not trust research suggesting that aspartame may be detrimental to human health. We believe that there are numerous well-researched papers by key researchers that prove the negative effects of this sweetener. Can we as researchers really take the responsibility of the health of millions of consumers by ignoring research? Can we sit back ), and we acknowledge the fact that there are articles that propagate the fact that aspartame is safe, it was the focus of the article to discuss possible adverse effects of the consumption of aspartame. Formate is not converted to diketopiperazine (abstract) Sentence in the abstract of Humphries et al. (2007) is as follows: methanol, which forms 10% of the broken down product, is converted in the body to formate, which can either be excreted or can give rise to formaldehyde, diketopiperazine (a carcinogen) and a number of other highly toxic derivatives. This sentence does not imply that formate is converted to diketopiperazine, but that diketopiperazine is a breakdown product of methanol. (Prodolliet and Bruelhart, 1993;Lin and Cheng, 2000). The authors are incorrect in stating that tyrosine cannot be synthesized in brain from phenylalanine. This statement is not true; under the heading 'Effects of phenylalanine', the sentence reads 'A large number of compounds, including phenylalanine and tyrosine compete with each other for a binding site on the NAAT, seeing that it is the only manner in which these compounds can cross the BBB. Importantly, tyrosine cannot be synthesised in the brain, thus have to enter the BBB via NAAT (Figure 2c) for production'. For more clarity, the sentence could also have read 'Importantly, dopamine cannot be synthesized in the brain unless tyrosine is carried over the BBB via NAAT for production'. Despite the authors' statement, even very large increases in phenylalanine levels produced by aspartame administration to rats do not suppress catecholamine synthesis rate (Dow-Edwards et al., 1989) Reference: There are papers that disagree with the statement of JD Fernstrom: Yokogoshi and Wurtman (1986), which states 'Phenylalanine has been described as both a substrate (Kaufman S, personal communication) and an inhibitor (McKean, 1972;Gibson and Wurtman, 1977) of tyrosine hydroxylase, the enzyme that catalyzes the rate-limiting step in converting tyrosine to catecholamines'. 'The effect of TPT (tryptophan, phenylalanine and tyrosine) depletion on the ratio between the monoamine precursors and other LNAA that compete for active transport into the brain correspond to an 87-90% decrease. Neuro-imaging, cerebro...