Inhibition of aggregation

Freedman and others (2001) determined the effects of purple grape juice and its main flavonoids on the functionality of platelets and the production of NO. They observed that incubation of platelets with diluted grape juice resulted in the inhibition of aggregation, increased production of NO, and decreased production of superoxide. To confirm the relevance of these findings, 20 healthy subjects were supplemented with 7 mL of black grape juice/kg/day for 14 days. The inhibition of platelet aggregation was also observed ex vivo there was an increase in the production of NO from 3.5 1.2 to 6.0 1.5 pmol/108 platelets and a decrease in the release of superoxide, from 29.5 5.0 to 19.2 3.1 arbitrary units. Under these conditions the antioxidant capacity of protein-free plasma increased by 50% (Freedman and others 2001). 

Recently, Strivastava [137] has suggested a mechanism for the vitamin s anti-aggregatory action in platelets that does not involve the arachidonic acid cascade system. The author proposed that the inhibition of aggregation could be due to inhibition of intracellular mobilization of Ca2 + from the dense tubular system of the cytoplasm. 

IC50 values are determined from the non-linear curve fitting of concentration-effect relationships. IC50 is defined as the concentration of test drug for half maximal inhibition of aggregation. 

ED50 values are determined from the dose-response curves. ED50 is defined as the dose of drug leading to 50 % inhibition of aggregation in the animals. 

Figure 4 Inhibition of aggregation of bovine growth hormone (BGH) by a peptide fragment comprising residues 96-133 of the hormone. A 1.75 m ml solution of the protein was initially incubated at 3.5 M guanidine hydrochloride (conditions that populate the associated intermediate) and subsequently was diluted at 0.18 m ml and 0.8 M guanidine hydrochloride (conditions that induce aggregation). Turbidity was monitored by the absorbance at 450 nm. The top curve represents the kinetics of turbidity formation in the absence of the peptide, and in descending order from the top, formation of turbidity in the presence of 1, 3, 5, 7-fold molar excess of the peptide. The peptide was present from the initial conditions that populate the intermediate. (3.5 M guanidine hydrochloride). From Brems, (26) reproduced with permission.

For example, the cobalt(II) complex for phthalocyanine tetrasodium sulfonate (PcTs) catalyzes the autoxidation of thiols, such as 2-mercaptoethanol (Eq. 1) [4] and 2,6-di(t-butyl)phenol (Eq. 2) [5]. In the first example the substrate and product were water-soluble whereas the second reaction involved an aqueous suspension. In both cases the activity of the Co(PcTs) was enhanced by binding it to an insoluble polymer, e.g., polyvinylamine [4] or a styrene - divinylbenzene copolymer substituted with quaternary ammonium ions [5]. This enhancement of activity was attributed to inhibition of aggregation of the Co(PcTs) which is known to occur in water, by the polymer network. Hence, in the polymeric form more of the Co(PcTs) will exist in an active monomeric form. In Eq. (2) the polymer-bound Co(PcTs) gave the diphenoquinone (1) with 100% selectivity whereas with soluble Co(PcTs) small amounts of the benzoquinone (2) were also formed. Both reactions involve one-electron oxidations by Co(III) followed by dimerization of the intermediate radical (RS or ArO ). 

Beretz A, Cazenave J-P, Anton A. Inhibition of aggregation and secretion of human platelets by quercetin and other flavonoids structure-activity relationships. Agent Action 1982 12 382-387. 

Grimm, L.J., Knapp, D.R., Senator, D. and Halushka, P. (1981). Inhibition of platelet thromboxane synthesis by 7-(l-imidazolyl) heptanoic acid dissociation from inhibition of aggregation. Thrombosis Res., 24, 307-317... 

An extract of cardamom inhibited aggregation in human blood platelets treated with the agonists ADP, epinephrine, collagen, and calcium ionophore A 23187. No inhibition of aggregation was observed in platelets treated with ristocetin (Suneetha and Krishnakantha 2005). 

In human platelet-rich plasma, inhibition of aggregation induced by collagen, ADP, adrenaline, and arachidonic acid was observed after treatment with the compound rutaecarpine (40-200 pM) (Sheu et al. 1996). 

In pig blood platelets, application of phenolic compounds, including fr ns-3,3, 5,5 -tetrahydroxy-4 -metho-xystilbene and yuccaols A and C, as a pretreatment slightly reduced platelet aggregation stimulated by ADP. With thrombin-induced platelet aggregation, the selected compounds exhibited significant inhibition of aggregation (Olas et al. 2002). 

Documented effects The alkaloid protopine (fumarine) caused narcosis in amphibians and, in mammals, caused paralysis of sensory nerve endings and increased reflex excitability. The alkaloid slightly increased the effects of analeptics and induced catalepsy (Chen-Gu 1957 Cheney 1963). In acute experiments with animals under narcosis, reduced heart rate and increased heartbeat amplitude occurred and, for a short time, decreased blood pressure was observed. Protopine has antiarrhythmic action with better effects than novocainamide and quinidine (Sadritdinov and Kurmukov 1980). In a screen to determine effects on platelet aggregation, extracts of this species showed complete inhibition of aggregation. This result was found to be caused by protopine (Sener 1994). Extracts of the dried plant displayed high rates of inhibition against the enzymes acetylcholinesterase and butyrylcholinesterase, which are associated with Alzheimer s disease (Orhan et al. 2004). 

The main role of stabilizers (surfactants or polymers) is to provide a steric or an electrostatic barrier between particles, thereby preventing inhibition of aggregation. Furthermore, stabilizers play an essential role in the control of both size and shape of nanoparticles. Generally, polymers are recommended as stabilizers for metal colloids due to their transparent, permeable, and nonconductive properties and also because they do not influence the optical, electrical, and catalytic properties of the nanoparticles. In addition, investigation of polymer-stabilized MNPs appears as a suitable way for solving the stability of MNPs. For this reason, great attention has been focused on the incorporation of MNPs into a polymer matrix, a procedure based on the synthesis of nanometer-sized metallic filler particles (Giannazzo et al. 2011). 

Prolonged use of nitroprusside may lead to hypothyroidism because of interference with the iodine uptake of the thyroid (147 ). Nitroprusside is both in vivo and in vitro a potent inhibitor of platelet function. In the presence of nitroprusside, platelets show blockage of ADP and serotonin release and inhibition of aggregation in response to ADP, collagen and epinephrine. Platelets from patients receiving nitroprusside also... 

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