Trauma exposure rather than posttraumatic stress disorder is associated with reduced baseline plasma neuropeptide-Y levels.

BACKGROUND: Exposure to uncontrollable stress reduces baseline plasma neuropeptide-Y levels in animals. We previously reported that baseline plasma neuropeptide-Y levels, as well as neuropeptide-Y responses to yohimbine, were lower in combat veterans with posttraumatic stress disorder, but we were unable to determine whether this was attributable to posttraumatic stress disorder or trauma exposure. The current report addresses this issue. METHODS: A) Baseline plasma neuropeptide-Y levels were measured in 8 healthy combat veterans compared to 18 combat veterans with posttraumatic stress disorder and 8 healthy nontraumatized subjects; and B) Baseline plasma neuropeptide-Y levels, trauma exposure, and posttraumatic stress disorder symptoms were assessed in 41 active military personnel. RESULTS: Plasma neuropeptide-Y was negatively associated with trauma exposure but not posttraumatic stress disorder symptoms in active duty personnel. Baseline neuropeptide-Y was reduced in combat veterans with and without posttraumatic stress disorder. CONCLUSIONS: Trauma exposure rather than posttraumatic stress disorder is associated with reduced baseline plasma neuropeptide-Y levels. Future studies must determine if neuropeptide-Y reactivity differentiates trauma-exposed individuals with and without posttraumatic stress disorder.     

Platelet adhesion to collagen in subtypes of type I von Willebrand's disease is dependent on platelet von Willebrand factor

Von Willebrand's disease type I, characterized by low levels of factor VIII coagulant activity (VIII: C), von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (RiCof) (1), can be subdivided on the basis of platelet von Willebrand factor into subtype platelet normal, platelet discordant, and platelet low (2). We have investigated the contribution of platelet von Willebrand factor in these various subtypes to platelet adhesion using the rectangular perfusion chamber of Sakariassen et al. (3) with fibrillar collagen or a fibroblast matrix as adhesive surfaces. Platelet adhesion to fibrillar collagen was decreased in all subtypes of von Willebrand's disease, but not as low as in severe von Willebrand's disease. A close correlation was observed between platelet adhesion to collagen and plasma vWF:Ag in severe von Willebrand's disease, subtype platelet low, subtype platelet discordant, and normal controls. The platelet adhesion in subtype platelet normal was higher than expected from the plasma vWF:Ag level. Perfusions in which washed platelets were added to a human albumin solution together with red blood cells gave similar adhesion values in subtype platelet normal and normal controls; adhesion was decreased in subtype platelet discordant, and the lowest values were found in subtype platelet low and in severe von Willebrand's disease. These data indicate that platelet von Willebrand factor may contribute to platelet adhesion, when plasma von Willebrand factor is low. Perfusion studies over a fibroblast matrix gave similar low adhesion values for subtype platelet low and platelet normal, indicating that the contribution of platelet von Willebrand factor can only be observed on a strongly activating surface such as fibrillar collagen.     

Immunologic studies in von Willebrand's disease: alteration of factor VIII/von Willebrand protein after transfusion with plasma concentrates in patients with von Willebrand's disease.

Two patients with a severe von Willebrand's disease characterized by no detectable factor VIII related antigen in their plasma received transfusions of cryoprecipitate. The bleeding time was corrected for a short period of time and returned to its pretransfusional value although the other parameters of the disease were still corrected. Electrophoretic and immunologic properties of factor VIII related antigen infused were determined serially after transfusion. Modifications of these properties occurred progressively after transfusion. The half disappearance time of F. VIII R.A. was determined and found to be considerably shorter than in hemophilic recipients. This study suggests an alteration in vivo of F. VIII R.A. infused into von Willebrand recipients.     

Effect of dextran 70 on factor VIII and platelet function in von Willebrand's disease.

Dextran given intravenously to two patients with mild von Willebrand's disease and two healthy controls impaired the factor VIII properties measured, i.e. it decreased the factor VIII-related antigen and the ristocetin co-factor activity. In the patients the variables fell from borderline to abnormally low levels accompanied by a prolongation of the bleeding time. Infusion of factor VIII concentrate reversed the dextran-induced impairment of factor VIII and the prolonged bleeding time. The findings lend support to the view that dextran induces a defective platelet function in vivo by interfering with the factor VIII molecular complex. They also show that patients with von Willebrand's disease should not be given dextran as it might potentiate their bleeding diathesis.     

Nocturnal agitation in Huntington disease is caused by arousal-related abnormal movements rather than by rapid eye movement sleep behavior disorder

BackgroundPatients with Huntington disease (HD) and their spouses often complain of agitation during sleep, but the causes are mostly unknown.ObjectiveTo evaluate sleep and nocturnal movements in patients with various HD stages and CAG repeats length.MethodsThe clinical features and sleep studies of 29 patients with HD were retrospectively collected (11 referred for genotype–phenotype correlations and 18 for agitation during sleep) and compared with those of 29 age- and sex-matched healthy controls. All patients had videopolysomnography, but the movements during arousals were re-analyzed in six patients with HD with stored video.ResultsThe patients had a longer total sleep period and REM sleep onset latency, but no other differences in sleep than controls. There was no correlation between CAG repeat length and sleep measures, but total sleep time and sleep efficiency were lower in the subgroup with moderate than milder form of HD. Periodic limb movements and REM sleep behavior disorders were excluded, although 2/29 patients had abnormal REM sleep without atonia. In contrast, they had clumsy and opisthotonos-like movements during arousals from non-REM or REM sleep. Some movements were violent and harmful. They might consist of voluntary movements inappropriately involving the proximal part of the limbs on a background of exaggerated hypotonia. Giant (>65 mcV) sleep spindles were observed in seven (24%) patients with HD and one control.ConclusionThe nocturnal agitation in patients with HD seems related to anosognostic voluntary movements on arousals, rather than to REM sleep behavior disorder and other sleep problems.     

In vivo and in vitro experiments show that betaxolol is a retinal neuroprotective agent

The aim of the study was to determine whether betaxolol is a neuroprotective agent and can therefore slow down the changes seen in the retina following ischaemia/reperfusion. Ischaemia was induced in one rat eye by raising the intraocular pressure for 45 min. Three days later electroretinograms were recorded from both eyes and the retinas were examined immunohistochemically for the localisation of calretinin and choline acetyltransferase (ChAT) immunoreactivities. The effect of glutamate agonists, hypoxia or experimental ischaemia was examined on the GABA immunoreactivity, lactate dehydrogenase (LDH) and internal calcium levels ([Ca²⁺]_i) of the isolated rabbit retina, rat cortical cultures and chick retinal cell cultures respectively. Betaxolol was tested to see whether it can attenuate the influence of the glutamate agonists, hypoxia or experimental ischaemia. Ischaemia for 45 min causes a change in the nature of the normal calretinin immunoreactivity, an obliteration of the ChAT immunoreactivity and a drastic reduction in the b-wave of the electroretinogram after 3 days of reperfusion. When betaxolol was injected i.p. into the rats before ischaemia and on the days of reperfusion the changes to the calretinin and ChAT immunoreactivities were reduced and the reduction of the b-wave was prevented. Rabbit retinas incubated in vitro in physiological solution lacking oxygen/glucose or containing the glutamate agonists kainate or NMDA caused a change in the nature of the GABA immunoreactivity. Inclusion of betaxolol partially prevented the changes caused by NMDA and lack of oxygen/glucose. Rat cortical cultures exposed to glutamate or hypoxia/reoxygenation resulted in a release of LDH. The release of the enzyme was almost completely attenuated when betaxolol was included in the culture medium. Kainate increased the [Ca²⁺]_i in chick retinal cultures, as measured with Indo-1. In a medium with sodium, this kainate-induced elevation of [Ca²⁺]_i was significantly reduced by betaxolol. The combined data show that betaxolol is a neuroprotective agent and attenuates the effects on the retina induced by raising the intraocular pressure to simulate an ischaemic insult as may occur in glaucoma.© 1997 Elsevier Science B.V. All rights reserved.     

The bleeding time in normal subjects is mainly determined by platelet von Willebrand factor and is independent from blood group.

Bleeding time (BT) is the most important test "in vivo" evaluating the primary hemostasis. No relationship between plasma von Willebrand factor (vWF) and BT has been found in normal subjects, whereas no data are available on the relationship between platelet vWF and blood group or BT in normal subjects. To clarify the reciprocal relationship between blood group, vWF and BT, we studied 177 normal subjects. The influence of blood group on BT was analyzed in 116 subjects and the distribution of platelet and plasma vWF between different blood groups in 111 subjects. Furthermore, in a subgroup of 50 subjects, a multivariate regression model, including age, platelet count, plasma and platelet vWF:Ag and Ristocetin Cofactor (RiCof), hematocrit, sex and O or non-O blood group was used to assess the joint influence of these variables on BT. BT was similar in O and non-O group (P = 0.310) and, although plasma vWF was significantly lower in O group (P less than 0.0001), platelet vWF content was similarly distributed (P = 0.873 vWF:Ag and P = 0.322 RiCof). Furthermore, platelet vWF was not correlated with plasma vWF (r = 0.06, P = 0.526). In the multivariate regression analysis, only platelet vWF, age and platelet count showed a significant, inverse correlation with BT (P = 0.004), explaining 25% of the total variation of this test. Platelet vWF resulted therefore the main determinant of BT.     

Striatal deficiency of L-pyroglutamic acid in Huntington's disease is accompanied by increased plasma levels

L-Pyroglutamic acid (L-PGA), a cyclized glutamate analogue, was measured in plasma, cerebrospinal fluid and brain tissue of patients with Huntington's disease (HD) and controls. In HD, plasma L-PGA was elevated and possibly reflects an increased requirement of cell membranes to be protected against peroxidative damage. L-PGA was decreased in caudate and putamen of HD patients. We suggest that striatal deficiency of L-PGA in HD is a consequence of neuronal loss which characteristically occurs in HD striatum.     

Platelet aggregability and in vivo platelet deposition in patients with ischemic cerebrovascular disease - evaluation by indium-111-platelet scintigraphy -

In ischemic cerebrovascular disease, it is not clear whether platelet function in vitro actually reflects the situation in vivo. Using indium-111 platelet scintigraphy as a method for detecting platelet activation in vivo, we tried to elucidate this problem. Twenty eight patients with chronic stage of ischemic cerebrovascular disease (CVD) and 17 control subjects were examined. Platelet scintigrams were positive in 9 of 28 patients in CVD, while all were negative in control. A comparison of the results obtained from qualitative platelet imaging and platelet aggregability was performed to evaluate whether threshold aggregation concentration (TAC) grade differed across the three groups(control, CVD patients without platelet deposition and CVD patients with platelet deposition). CVD patients with platelet deposition showed a higher TAC than those patients who did not show platelet deposition (P < 0.05) or control subjects without platelet deposition (P < 0.05). These results suggest that some patients in chronic stages of CVD may have active platelet deposition on carotid atheromatous lesions, and presence of platelet deposition in vivo could contribute to reduce platelet reactivity in peripheral blood.     

Variant Alzheimer's disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations

We describe 3 new families affected by Alzheimer's disease with spastic paraparesis. In affected individuals, including the earliest known patient with this clinical syndrome, neuropathological examination revealed large "cotton wool" plaques similar to those we have previously described in a Finnish family. In the families in which DNA was available, presenilin-1 mutations were observed. Transfection of cells with these mutant genes caused exceptionally large increases in secreted Abeta42 levels. Furthermore, brain tissue from individuals with this syndrome had very high amyloid-beta concentrations. These findings define the molecular pathogenesis of an important subgroup of Alzheimer's disease and have implications for the pathogenesis of the disease in general.     

Treatment of uremic anemia with recombinant erythropoietin also reduces the defects in platelet adhesion and aggregation caused by uremic plasma.

In the present study, uremic patients on chronic maintenance hemodialysis were treated with recombinant erythropoietin. Before and after 20 weeks of treatment, platelet adhesion and aggregation were studied with perfusions over a sprayed collagen surface and over matrix of cultured endothelial cells with high tissue factor activity. The influence of the erythropoietin induced raise in hematocrit on platelet transport and adhesion was excluded by performing the perfusions at a standard red blood cell concentration. The present study clearly demonstrates that erythropoietin treatment improves platelet adhesion and aggregation in addition to and independent of its effect on the hematocrit. Studies with control platelets resuspended in plasma of untreated patients showed that a uremic plasma factor reduced adhesion and thrombin- and collagen-dependent aggregation. Patient platelets resuspended in control plasma showed no defects. After erythropoietin treatment, the plasma-induced inhibition of adhesion and aggregation had almost completely disappeared from patient plasma. The beneficial effect of the erythropoietin treatment on uremic hemostasis is therefore twofold. The increase of the red blood cell mass improves transport of platelets, and thus adhesion to the vessel wall. The intrinsic defect due to the presence of an inhibitory toxin in uremic plasma is, in large part, corrected. Improved neutralization of uremic toxins by red blood cells or less production of toxins by better oxygenated tissue might play a role in the observed phenomena.