Solvent free vapor phase photografting of maleic anhydride onto poly(ethylene terephthalate) and surface coupling of fluorinated probes, PEG, and an RGD-peptide.

Poly(ethylene terephthalate) (PET) was photografted in a solvent free vapor of maleic anhydride and benzophenone. After hydrolysis of the initially grafted succinic anhydride groups, the carboxylic PET surfaces were modified by coupling reactions in organic and aqueous solutions. 2,2,2-Trifluoroethylamine and diamino PEGs of molecular weight 3400 and 2000 were reacted with acid chloride groups obtained by treating the PET-COOH surface with PCl(5). Furthermore, fluoro substituted thiols and a cystein terminated RGD containing peptide were bound to PET-COOH surfaces via a disulfide link by a three step coupling sequence. Coupling yields and surface concentrations of the fluoro substituted ligands were calculated from ESCA data. The RGD-peptide surfaces were evaluated by cultivation with rat smooth muscle cells.

Micro and nano-structured surfaces.

The study of cell reaction to micro and nanotopography is dependent on the method of manufacture available. Several methods of manufacture have been developed: polymer demixing, embossing and photolithography. Surfaces obtained with these different techniques, having micro and/or nanodomains, have been studied toward the same type of cells, i.e. human endothelial cells (HGTFN) and mouse fibroblasts (3T3). Polymer demixing of polystyrene (PS) and poly(4-bromostyrene) (PBrS) producing nanometrically islands of 18, 45 and 100 nm height, polycarbonate (PC) and polycaprolactone (PCL) grooved with grooves 450 nm wide and 190 high, the natural polysaccharide hyaluronic acid (Hyal) and its sulfated derivative (HyalS) photoimmobilized on silanized glass as grooves 250 nm high and 100, 50, 25 or 10 microm wide have been obtained. The morphology and polarization of the cells has been studied by optical microscopy and scanning electron microscopy. Cells respond in different way to the topography of the materials, but the surface chemistry is dominant in inducing different cell behavior.

Bioactive heparin surfaces from derivatization of polyacrylamide-grafted LLDPE.

Primary amine groups were introduced into polyacrylamide-LLDPE films, using the Hofmann degradation synthesis. The Hofmann degradation was studied at room temperature using sodium hypochlorite and sodium hydroxide at different concentrations. Diazotized heparin was covalently bound to the grafted LLDPE film via the primary amine groups. Surfaces were analysed with ESCA, ATR-IR, chloride titration and Toluidine Blue. Evaluation of the biological activity of the heparinized surfaces was made by measuring the capacity for binding antithrombin (AT) and inhibition of the activated coagulation factor XII (FXIIa). The heparinized surfaces were able to bind up to 3 pmol cm-2 of AT in solution with ionic strengths of I = 0.15 and I = 0.40. No activation of the adsorbed FXII was detected.

Acute effects of alcohol on regional cerebral blood flow in man.

Acute effects of alcohol in a low (0.7 g/kg) and a high dose (1.5 g/kg) on regional cerebral blood flow (rCBF) were measured with 133Xe inhalation technique at resting conditions in 13 normals. Mean hemisphere CBF increased globally by 12% at the lower dose and 16% at the higher dose. A normal hyperfrontal flow pattern was seen in both alcohol conditions. There were, however, significant regional differences in response to alcohol. The largest rCBF increase was observed in prefrontal regions at the lower dose, and in temporal regions at the higher. Expressed in relative values (% of the whole brain CBF), the temporal rCBF increased linearly with increasing alcohol dosage, while the prefrontal rCBF showed a increase at the lower dose followed by a decrease at the higher dose. It is concluded that alcohol has two types of acute effects on rCBF, a global vasodilatory effect and some regional effects, most clearly seen in prefrontal and temporal regions. The prefrontal flow augmentation following acute alcohol intake may be related to a transient arousal reaction, which has been reported by others. The temporal flow increase may be related to effects of alcohol on emotions and mood.

Neuropsychological performance differs between type 1 diabetic and normal men during insulin-induced hypoglycaemia.

Cerebral function was measured with a neuropsychological test battery before, during, and after insulin-induced hypoglycaemia (blood glucose approximately 2.0 mmol l-1) in 10 male Type 1 diabetic patients (age 20-43 years, duration of diabetes 14 (2-30) years) and in 12 normal men. There were no group differences in neuropsychological results at normal glucose levels. Significant effects of hypoglycaemia were found in reaction-time measures (p less than 0.001) and in other tests requiring speed and attention (p less than 0.001), in verbal fluency (p less than 0.05), and short-term memory (p less than 0.001). Significant group effects and interactions (p less than 0.05) revealed that the diabetic patients were generally more affected by hypoglycaemia than the normal subjects. This might have been partly due to the larger absolute decrease in blood glucose level in the diabetic patients, although the rate of glucose decrease was not related to performance in either group. Thus, the diabetic brain might be more vulnerable to hypoglycaemia, perhaps through the persistent impact of repeated hypoglycaemic episodes, although no neuropsychological deficit is demonstrable at normal blood glucose levels.

Quantified EEG and cortical evoked responses in patients with chronic traumatic frontal lesions.

Eighteen frontal trauma patients and 17 age-matched control subjects had quantified EEGs and measurements of sensory (SEP) and auditory evoked potentials (P300) using a Biologic Brain Atlas III system. The findings were compared to the conventional paper EEG, and to the frontal lesion volumes, severity of head injury, and outcome variables. The quantified EEG confirmed the pathological findings detected by visual inspection, but some regional abnormalities were more easily detected by topographic mapping. The regional distribution of pathological slowing corresponded well with the morphological lesions in most patients. The modal frequency of EEG correlated both with lesion volume and injury severity and with the outcome variables. There were no pathological findings in the SEPs, and all but one patient had clearly distinguishable P300 responses. There was a significant reduction in P300 amplitude in the frontal patients at the anterior, but not at the posterior electrodes. The topographical distribution of the P300 changes corresponded well with the morphological lesions. Our findings indicate that the P300 potential is, in part, dependent upon the prefrontal cortical areas. The present study thus supports P300 investigations which have shown amplitude reduction in other disorders (e.g., schizophrenia) with a presumed prefrontal dysfunction.

Exploring the connections between platelet monoamine oxidase activity and behavior. II. Impulsive personality without neuropsychological signs of disinhibition in air force pilot recruits.

Platelet monoamine oxidase (MAO) activity and serum levels of the adrenal androgen metabolite dehydroepiandrosterone sulfate (DHAS) were measured in 18 male air force pilot recruits and 19 randomly selected male conscripts. Personality scales from three inventories were given, and computerized neuropsychological tests were performed: finger tapping and alternation, reaction time, perceptual maze, perspective fluctuation and lexical decision. The pilot recruits had higher scores in sensation-seeking-related scales suggesting disinhibited behavior in the social sphere, interest in sports and activities involving some danger, and a need for change. They also had higher scores on an impulsivity scale which comprises sensation-seeking content. In the neuropsychological tasks, the pilot recruits were faster in finger-tapping alternation and performed more efficiently in the perceptual-maze test than the conscripts. In a linear discriminant analysis, neuropsychological-task performance discriminated significantly between the pilot and conscript groups. In the biochemical measures, the pilot recruits had higher DHAS levels but similar MAO activity levels compared to the conscripts, which is in contrast to what has been found in other sensation-seeking groups in comparison to controls. This result is in accordance with the normal scores in one of the impulsivity scales in the pilot recruits, and with the absence of signs of disinhibition in neuropsychological tasks. It is proposed that only some aspects of the impulsivity concept might be critical for the association with low MAO activity.

Volumes of chronic traumatic frontal brain lesions measured by MR imaging and CBF tomography.

The volumes (ml) of chronic traumatic frontal brain lesions were compared measured "morphologically" with MR imaging (T1 and T2 weighted images) and "functionally" with a tomographic rCBF technique (SPECT with 133Xe i.v.). The T1 volumes varied between 11 and 220 ml. The correlation between T1 and T2 volumes was 0.95, the T2 volumes being 33% larger than T1 volumes (p less than 0.001). The functional SPECT volumes were considerably larger (range 16-324 ml) than the MR volumes. The mean volume difference was 81% between T1 and SPECT images (p less than 0.001), and 35% between T2 and SPECT images (p less than 0.001). Correlations between the MR and SPECT volumes were also higher for T2 than T1 volumes. The volume difference is most likely explained by a functional decrease in regions around the lesion in which no morphologic change visible on MR images had taken place. MR and SPECT volume measurements were positively related to persistent lack of energy and personality changes, but only moderately related to duration of impaired consciousness and neuropsychologic outcome.

Differences in asymmetric perception of facial expression in free-vision chimeric stimuli and reaction time.

Two forms of a Chimeric Faces Free-Vision Task used to estimate cerebral asymmetry for perceiving facial expression were given to young male subjects, n = 60 in a first session and n = 40 in a retest session. Test-retest and split-half reliabilities were high. As expected from assumptions of right-hemisphere specialization for processing expression, faces with left-sided smiles were more frequently judged as looking happier than those with right-sided smiles in both forms. However, there were individual differences in direction and extent of bias, which were systematically related to reaction time, right visual field-biased subjects being slower. Differences in lateral bias as well as in reaction time are assumed to reflect individual patterns of hemispheric activation, whereas the average left bias in the present male group may reflect right-hemisphere specialization for processing of facial expression.

Exploring the connections between platelet monoamine oxidase activity and behavior: relationships with performance in neuropsychological tasks.

Platelet MAO activity has been found to have behavioral (psychiatric and personality) correlates. The purpose of the present study was to explore the nature of the connections between platelet MAO activity and behavior by analyzing performance in neuropsychological tasks in relation to platelet MAO activity, measured in 37 male subjects. The following neuropsychological tests were given: a finger tapping and alternation test, a reaction time test, a perceptual maze test, a perspective fluctuation task (the Necker cube), and a lexical decision task. The reaction time tasks comprised a motor disinhibition task, in which auditory stimuli given simultaneously with light stimuli were signals for response inhibition. Significant relationships were obtained between low MAO activity and short response times and small variations in response times to left-sided visual stimuli, suggesting a readiness for higher right hemisphere activation in low MAO subjects, and between low platelet MAO activity and many perspective reversals, in line with expectations. Furthermore, high MAO subjects had equal tapping speed for both hands, which has been found in schizophrenic patients. Of special interest in the present results is the strong negative relationship obtained between platelet MAO activity and number of failed inhibitions in the motor disinhibition task, which in a multiple regression analysis highly significantly contributed to the prediction of platelet MAO activity. This finding is in line with the poor passive avoidance performance associated with serotonergic deficiency and syndromes of disinhibition, and thus supports the assumption that platelet MAO activity may be considered as a genetic marker for some properties of the central serotonergic system.

Smooth pursuit eye tracking and neuro-psychological performance in healthy volunteers. Exploring a possible genetic marker for vulnerability to schizophrenia.

Eye movement dysfunction (EMD) has been repeatedly found in schizophrenics and their first-degree relatives. In the present study, smooth pursuit eye tracking was measured in healthy subjects and related to performance on computerized neuropsychological tasks assumed to involve frontal or frontoparietal functions: monitoring perspective fluctuations (Necker cube), finger tapping, trail making, reaction time (RT) and a perceptual maze test. Poor trackers performed worse on tasks requiring parallel processing (trail making with letters and digits and RT with random auditory signals for response inhibition) and made more errors and cancellations on the mazes. Results are in line with our earlier EMD results on schizophrenics, showing poor performance on frontal tasks. However, their deficiency was more pervasive, whereas the present healthy EMD subjects only had difficulties with more complex tasks. The results are of interest in view of the recent evidence that EMD may be a genetic marker for vulnerability to schizophrenia.

Prizidilol, a combined vasodilatory and beta-adrenoceptor blocking drug, in primary hypertension. A long-term efficacy, tolerance and pharmacokinetic study.

After an initial placebo period of four weeks 24 patients with primary hypertension were treated with prizidilol, a hydrazinopyridazine derivative with combined vasodilator and non-selective beta-adrenoceptor blocking actions, for a dose titration period of 14 weeks. Prizidilol 200 to 800 mg was given once daily to achieve a target supine diastolic blood pressure (BP) less than 90 mmHg. Supine and standing BP recorded 24-27 h after drug intake decreased from 172 +/- 17/106 +/- 6 mmHg (mean +/- SD) and 167 +/- 18/111 +/- 8 mmHg, respectively, after placebo to 159 +/- 16/99 +/- 8 and 154 +/- 18/101 +/- 9 mmHg after active treatment for six weeks (mean dose 447 mg), and to 154 +/- 16/97 +/- 7 and 148 +/- 14/97 +/- 7 mmHg after treatment for 14 weeks (mean dose 687 mg/day). A slight reduction in HR was seen after treatment for six weeks and in plasma renin activity and urinary methoxycatecholamine excretion after treatment for 14 weeks. A sustained decrease in BP was observed for 10 h after prizidilol 800 mg (n = 9), with a maximum antihypertensive effect (mean reduction in supine BP 33/18 mmHg) 2.5 h after dosing, which coincided with the mean peak plasma concentration. The plasma elimination half-life of the drug was 3.9 h (range 2.0-8.9 h). Changing to a twice daily regimen in 17 patients (mean daily dose 748 mg at six months) did not produce any further reduction in the BP (recorded 12-15 h after dosing) as compared to the once daily regimen at 14 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Prizidilol, an antihypertensive with precapillary vasodilator and beta-adrenoceptor blocking actions, in primary hypertension.

Single oral doses of 1.5, 3.0, 4.5 and 6.0 mg/kg prizidilol HCl, an antihypertensive with vasodilator and beta-adrenoceptor blocking actions, were given to 12 patients with primary hypertension on separate days. Systolic and diastolic blood pressure (BP) decreased after 4.5 and 6.0 mg/kg and systolic BP also after 3.0 mg/kg. The antihypertensive effect was evident in 1 to 2 hr with maximum effect in 4 to 5 hr (supine systolic BP 20 and diastolic 13 mm Hg after 6.0 mg/kg); the effect was sustained for more than 8 hr. An initial slight reduction in heart rate (HR) after 1 to 2 hr was followed by a slight rise after 6 to 8 hr. There were higher plasma drug levels and greater antihypertensive effects after the 6.0-mg/kg dose in slow acetylators (n = 5) than in rapid acetylators (n = 7). Due to its hydrazine moiety, prizidilol, like hydralazine, seems to be a substrate for the polymorphic N-acetyltransferase enzyme system.