[Determinants of the elevated factor VIII activity in patients following venous thromboembolism]. / Czynniki determinujace wysoka aktywnosc czynnika VIII u pacjentów po przebytej zylnej chorobie zakrzepowo-zatorowej.

INTRODUCTION: Activity of factor VIII (FVIII) increased above 150% of reference range predisposes to venous thromboembolism (VTE). The aim of this study was to identify predictors of increased FVIII activity in patients following VTE. MATERIALS AND METHODS: 241 (38% men) patients presented due to objectively documented VTE episode at least 3 months ago were included in this study. FVIII activity was measured using a clotting assay on the analyzer BCS XP. RESULTS: Among 241 patients with VTE, activity of FVIII above 150% (FVIII ≥ 150%) was observed in 96 (40%). These patients were older (p = 0.035) and their concentrations of fibrinogen and C-reactive protein (CRP) were higher by 12% and 88% (p < 0.001), respectively, compared with other patients. There was a positive correlation between FVIII and fibrinogen (r = 0.34; p < 0.001), FVIII and CRP (r = 0.30; p < 0.001). Type of treatment, time from the VTE episode and type of VTE were not associated with FVIII. Twenty patients (8%) had activity of FVIII increased above 200% (FVIII > 200%) and this group was also older (p = 0.015), more patients in that group had obesity (p = 0.015), idiopathic VTE (p = 0.043), less of them had positive family history (p = 0.010) and they were characterized by fibrinogen and CRP increased by 28% (p < 0.001) and 102% (p = 0.004), respectively, compared with patients with FVIII between 150-200%. Independent predictors of FVIII ≥ 150% were: fibrinogen (p < 0.001), bilirubin (p = 0.002), hemoglobin (p = 0.016), glucose (p = 0.040), CRP (p = 0.023), total homocysteine (p = 0.032). Fibrinogen was the only independent predictor of FVIII > 200% (p = 0.016). CONCLUSIONS: The activity of FVIII in patients after VTE episode is influenced by age, concentration of fibrinogen, bilirubin, hemoglobin, glucose, CRP and homocysteine. Our results suggest the role of environmental factors, mainly inflammatory response in maintaining elevated FVIII activity following VTE.

Differential regulation of cortical NMDA receptor subunits by sensory learning.

NMDA receptor is an important player in neuronal plasticity, including cortical reorganization. In the adult cerebral cortex, the receptor properties are regulated by relative expression of NR2A and NR2B subunits. We have previously found that 3 days of sensory conditioning, in which stimulation of whiskers was paired with a tail shock, induce NMDA-receptor-dependent expansion of metabolically labeled cortical representations of the stimulated vibrissae. Here, we examined the effect of learning-induced cortical reorganization upon expression of NR2A and NR2B NMDA receptor subunits. An increase in NR2A mRNA expression in the barrel of the "trained" row of vibrissae was observed with in situ hybridization 24 h after sensory conditioning. NR2B mRNA expression level did not change. Protein level of both regulatory subunits and obligatory NR1 subunit were examined in P2 fraction. NR2A protein level was found elevated 1 h and 24 h after the sensory conditioning, but not in controls which received only whisker stimulation, signifying that the change was associated with cortical map reorganization. NR2B protein level was transiently elevated in both trained and stimulated control groups. NR1 protein level did not change. The results show that simple sensory learning induces a change in expression of regulatory NMDA receptor subunits, indicating a potential for receptor channel properties modification.

Learning-induced plasticity of cortical representations does not affect GAD65 mRNA expression and immunolabeling of cortical neuropil.

Two forms of glutamic acid decarboxylase (GAD) are present in inhibitory neurons of the mammalian brain, a 65-kDa isoform (GAD65) and a 67-kDa isoform (GAD67). We have previously found that GAD67 is upregulated during learning-dependent plasticity of cortical vibrissal representations of adult mice. After sensory conditioning involving pairing stimulation of vibrissae with a tail shock, the increase in mRNA expression and density of GAD67-immunoreactive neurons was observed in barrels representing vibrissae activated during the training. In the present study, using the same experimental model, we examined GAD65 mRNA and protein levels in the barrel cortex. For this purpose, we used in situ hybridization and immunohistochemistry. No changes in the level of GAD65 mRNA expression were detected after the training. The pattern of GAD65 mRNA expression was complementary to that observed for GAD67. Immunocytochemical analysis found no changes in immunolabeling of neuropil of the barrels representing the vibrissae activated during the training. The results show that, in contrast to GAD67, cortical plasticity induced by sensory learning does not affect the expression of GAD65.