Platelet function, depression

Hematologic- Eosinophilia transient neutropenia leukocytosis leukopenia thrombocythemia thrombocytopenia agranulocytosis granulocytopenia hemolytic anemia bone marrow depression pancytopenia decreased platelet function anemia aplastic anemia hemorrhage. 

Tuomisto and Tukiainen 33 studied the platelet 5-HT uptake system in a well-defined study and found that 5-HT uptake in platelets from depressed patients had one-half the initial uptake value and Vmax of normals Kins were the same for both groups. Following antidepressant treatment, the Vmax moved towards normal, and the Km remained the same. These results were interpreted to mean that there are less 5-HT transport molecules or some inactive ones in membranes of depressed patients, but those 5-HT transport molecules which are there are completely functional, as demonstrated by the constant Km. Clinical improvement was accompanied by a return of Vmax to normal. Of most interest was the finding that imipra-mine added in vitro to the platelets increased the Km but had no effect on the Vmax. 

Such difficulties prompted research workers to look for some other index of NT function in humans. These range from studies on platelets, such as abnormalities in their amine uptake and MAO activity in depressed patients, to changes in the secretion of a hormone known to be controlled by a particular NT. Thus if NA controls growth hormone release, and the secretion of the hormone is changed in depressed patients, does that confirm a role for NA in the mediation of depression ... 

It has been hypothesized that depression could arise from a pathological enhancement of 5-HT2 receptor function. This view would concur with the observations that the functional activity of 5-HT2 receptors on the platelet membrane is enhanced in depression and the increase in the density of 5-HT2 receptors in the frontal cortex of brains from suicide victims. It is possible that enhanced 5-HT2 receptor function is associated primarily with anxiety, a common feature of depression, and that the increased activity of the 5-HT2 receptors results in an attenuation of the functioning of S-HT receptors thereby resulting in the symptoms of depression. Whether this change in the activity of S-HT receptors is due to direct effects of the altered 5-HT2 receptor function is uncertain. There is evidence that hypercortisolaemia, which is a characteristic feature of depression, reduces the activity of these receptors probably through central glucocorticoid type 2 receptors. Clearly further research is needed to determine the precise interaction between the 5-HT2 and 5-HTi receptor types. 

The role of serotonin (5-hydroxytryptamine, 5-HT) has also been extensively studied in depressed patients. Whereas the overall psycho-physiological effects of noradrenaline in the CNS appear to be linked to drive and motivation, 5-HT is primarily involved in the expression of mood. It is not surprising therefore to find that the serotonergic system is abnormal in depression. This is indicated by a reduction in the main 5-HT metabolite, 5-hydroxy indole acetic acid (5-HIAA), in the cerebrospinal fluid of severely depressed patients and a reduction in 5-HT and 5-HIAA in the limbic regions of the brain of suicide victims. The 5-HT receptor function also appears to be abnormal in depression. This is indicated by an increase in the density of cortical 5-HT2a receptors in the brains of suicide victims and also on the platelet membrane of depressed patients. Platelets may be considered as accessible models of the nerve terminal. 

Thus when the results of the studies on platelets, lymphocytes, changes in cerebrospinal fluid metabolites of brain monoamines and the post-mortem studies are taken into account it may be concluded that a major abnormality in both noradrenergic and serotonergic function occurs in depression, and that such changes could be causally related to the disease process. 

Newman ME, Drummer D, Lerer B Single and combined effects of desimipramine and lithium on serotonergic receptor number and second messenger function in rat brain. J Pharmacol Exp Ther 252 826-831, 1990 Newman ME, Lerer B, Lichtenberg P, et al Platelet adenylate cyclase activity in depression and after clomipramine and lithium treatment. Psychopharmacology 109 231-234, 1992... 

In keeping with the S deficiency hypothesis of depression, different manipulations of adenosine transmission in the basal forebrain show that favoring A i adenosiner-gic transmission promotes SWS, while decreasing it, for instance with agents that block Ai receptors such as caffeine, inhibits SWS and increases wakefulness [88], However, straight indications of a decrease adenosine transmission in depressive disorders are not found in the literature. A blunted platelet A2A receptor function was described in depressed patients [105], as well as a decreased serum activity of adenosine deaminase [106],... 

Berk M, Plein H, Ferreira D, Jersky B (2001) Blunted adenosine A2a receptor function in platelets in patients with major depression. EurNeuropsychopharmacol 11 183-186... 

Figure 15. Dose dependently c-GMP inhibits PDE or activates PKG, thereby mediating its effects on the vasculature, platelets and myocytes. The cardiac interstitial NO concentration during early ischemia and early reperfusion is increased. The increase in NO concentration is derived from activated NO synthase (NOS) isoforms (species specific) and from NOS independent pathways. Cardiac c-GMP concentration during ischemia is somewhat increased while upon reperfusion is decreased. NO seems to mediate protective as well as deleterious effects which are critically dependent on the specific experimental conditions. NO at lower concentrations preserves blood flow and attenuates platelet aggregation and neutrophil-endothelium interaction following ischemia and reperfusion. In small amounts might also be beneficial by nitration of the cardioprotective PKCe. Furthermore, NO increases cardiomyocyte function. Figure 16. At higher concentrations, NO depresses cardiomyocyte function, mediates inflammatory processes following ischemia and reperfusion, impairs mitochondrial respiration...

Tremendous efforts have been put into surface modification of polyurethane biomaterials to promote cell adhesion [41] and/or depress platelet adhesion [42,43], biofihn formation [44], or protein adsorption [45]. CA is the quickest indirect evidence of confirming these surface modifications. Cooper et al. [41] prepared a series of polyurethanes with surfaces functionalized with three hexapeptides to improve cell adhesion. The polar peptides on the surface increase the hydrophilicity and thus decreased CAs were observed. Again, CA is only an indirect proof of a successful surface modification since there are many factors that contribute to a change in CA. Many other surface characterization techniques must be combined to obtain a fuU picture of the surface properties of polyurethane biomaterials. 

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