Upstream thrombus growth impairs downstream thrombogenesis in non-anticoagulated blood: effect of procoagulant artery subendothelium and non-procoagulant collagen

In the present experiments we have investigated the influence of wall shear rate and axial position on platelet and fibrin deposition which results when flowing human non-anticoagulated blood is exposed to either non-procoagulant fibrillar collagen (human type III) or procoagulant subendothelium (rabbit aorta). Platelet adhesion, thrombus volume and fibrin deposition were morphometrically evaluated at axial positions of 1 and 13 mm following perfusions for 5 min at shear rates of 100, 650 and 2,600 s-1. An axially-dependent decrease of platelet adhesion (34-57%, p less than 0.01-0.05) and thrombus volume (57-80%, p less than 0.05) was observed on collagen at all shear rates. On subendothelium, an axially-dependent decrease was observed for platelet adhesion only at 100 s-1 (29%; p less than 0.01) and for thrombus volume at shear rates of 650 s-1 and above (49-58%, p less than 0.01). Deposition of fibrin on subendothelium was axially decreased (16-42%, p less than 0.05) at all shear rates, while no significant axial differences were seen on collagen. However, substantially more fibrin was deposited on the subendothelium (p less than 0.05), and the upstream platelet adhesion and thrombus volume were lower than on collagen (p less than 0.05) at 100 s-1 and 650 s-1. The axially-dependent phenomena on the two surfaces are consistent with the concept of rapid-growing upstream thrombi which deplete the blood layer streaming adjacent ot the surface of platelets, leading to decreased platelet deposition further downstream.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multidrug transport in human glioblastoma cells is inhibited by transforming growth factors type beta 1, beta 2, and beta 1.2

The transforming growth factors type beta 1, beta 2, and beta 1.2 suppress multidrug transport in human pat-1 glioblastoma cells and even in cells that strongly over-express mdr genes and are resistant to inhibition of multidrug transport by chemosensitizers. Thus, inhibition of multidrug transport by cytokines might be a new approach to increase cellular accumulation of chemotherapeutic agents in multidrug resistant glial tumor cells. Interestingly, a member of the more distantly related decapentaplegic subgroup of transforming growth factors, the bone morphogenetic protein BMP 2, did not inhibit multidrug transport.     

Evaluation of 2,3,5-triphenyltetrazolium chloride staining to delineate rat brain infarcts.

BACKGROUND AND PURPOSE: Accurate and reproducible determination of the size and location of cerebral infarcts is critical for the evaluation of experimental focal cerebral ischemia. The purpose of this study was to compare intracardiac perfusion of 2,3,5-triphenyltetrazolium chloride with immersion of brain tissue in 2,3,5-triphenyltetrazolium chloride to delineate brain infarcts in rats. METHODS: After 6, 24, or 48 hours of ischemia induced by permanent middle cerebral artery occlusion, some rats were perfused with 2,3,5-triphenyltetrazolium chloride; other rats were given an overdose of barbiturates, after which brain sections were immersed in 2,3,5-triphenyltetrazolium chloride. Coronal sections were taken 4, 6, and 8 mm from the frontal pole, and infarct areas in perfused and immersed sections were compared; subsequently, the same sections were stained with hematoxylin and eosin. RESULTS: In rats subjected to 24 or 48 hours of occlusion, areas of infarction were clearly defined with both 2,3,5-triphenyltetrazolium chloride staining techniques, and the infarct sizes correlated well with the results of hematoxylin and eosin staining (r = 0.85-0.94). CONCLUSIONS: These results demonstrate that intracardiac perfusion of 2,3,5-triphenyltetrazolium chloride is an accurate, inexpensive, and efficient staining method to detect infarcted tissue 24 and 48 hours after the onset of ischemia in rats.     

Diurnal patterns of serotonin, 5-hydroxyindoleacetic acid, tryptophan and fibrinolytic activity in blood of depressive patients and healthy volunteers.

Diurnal changes of serotonin-related factors in whole blood and fibrinolytic activity were determined in depressed patients and healthy controls. Whole blood serotonin concentration of depressed patients showed marked changes throughout daytime, with maximum values in the evening and lowest values in the morning, whereas its metabolite 5-HIAA followed a contrary pattern. The circadian rhythm of 5-HT and 5-HIAA in the control group was quite different from depressed patients. Plasma levels of tPA decreased from 12:30 to 16:30. Concentrations of free plasminogen activator inhibitor (PAI-1) and complex of tPA-PAI-1 decreased from 8:30 to 16:30. Plasma levels of total PAI-1 decreased from 8:30 to 16:30. Plasma levels of the fibrinolytic parameters may be lower in depressive patients than in normal controls. These results support the changes in the circadian rhythm of serotonin and its related substances in the blood of depressive patients.     

Cerebral perfusion scintigraphy in patients with cerebrovascular disease by using 99mTc-ECD: comparative study with 123I-IMP SPECT

99mTc-ECD SPECT was performed in 19 patients with cerebrovascular disease, and location, extent, and severity of the lesions on 99mTc-ECD SPECT were compared with those on 123I-IMP SPECT. The initial brain uptake was 5.5 +/- 0.7% of the injected dose at 10 minutes after injection, 5.3 +/- 1.3% at 90 minutes, and clearance from the brain is slow. The distribution in the brain was changed, especially washout from the thalamus was slower than that from other regions. The count ratio of perfusion defect to normal area (D/N) on 99mTc-ECD SPECT was unchanged over the time, and had no significant differences from that on 123I-IMP SPECT. 99mTc-ECD SPECT was superior in detection of the lesion in the basal ganglia, and showed the images with superior spatial resolution due to physical characteristics of 99mTc. However, mild ischemic lesion and peri-infarct area was not clearly visualized, while 123I-IMP SPECT could demonstrate these lesions with better contrast.     

What can the additional diagnosis contribute in sudden deafness?

100 patients suffering from sudden hearing loss were examined with regard to cardiovascular risk factors and compared with a control group without ear diseases. Hypercholesterinaemia and hypertriglyceridaemia were significantly more often seen in patients with sudden hearing loss. No accumulation of pathological findings in neurological, orthopaedic or ophthalmological examinations was observed in patients with sudden hearing loss.     

Blood transfusions and the development of cytotoxic antibodies in dialyzed patients

In our work we investigated factors which can influence the alloimmunization and especially the ranges of cytotoxic antibodies that develop in patients on dialysis awaiting their first graft. Up to 15 liters of administered blood the proportion of immunized patients is rather stabile, not exceeding 50%. After further transfusions the percentage of immunized patients is growing rapidly reaching about 85%. Hyperimmunization, marked by cytotoxic antibodies with more than 80% panel reactivity is significantly more frequent in patients who obtained 15 and more liters of blood. In females the hyperimmunization is about 4 times more frequent than in males.     

Effects of galanin on insulin and glucagon secretion in the rat

Galanin-like immunoreactivity has been visualized in nerve fibers in the islets of Langerhans, suggesting an involvement of galanin in the neural regulation of islet function. In this study, we investigated the effects of galanin on basal and stimulated insulin and glucagon secretion by infusing the peptide at three different dose rates in rats. We also studied the direct effect of galanin on insulin secretion from freshly isolated rat islets. At 320 pmol/kg/min, but not at 20 or 80 pmol/kg/min, galanin lowered basal plasma insulin levels. In contrast, basal plasma glucagon levels were lowered by galanin already at 20 and 80 pmol/kg/min. Furthermore, galanin inhibited both glucose- and arginine-induced insulin release at all three dose levels, whereas arginine-induced glucagon release was not affected by galanin. Glucose-stimulated insulin secretion from isolated rat islets was dose-dependently suppressed by galanin (10^-6-10^-8M). Therefore, it is concluded that galanin in rats inhibits insulin secretion, both in vivo and in vitro, and that at lower dose levels, the peptide also inhibits basal glucagon release.     

Adult body height, self perceived health and mortality in the Swedish population.

STUDY OBJECTIVE: The purpose of the study was to examine adult body height as an indicator of general health. DESIGN: The study was a survey of a randomly selected sample of the adult Swedish population obtained by the Swedish National Central Bureau of Statistics. PARTICIPANTS: The sample studied was identified in 1980-81 and comprised 14,757 persons aged 16-74. Of these, 12,695 (86%) consented to interview. MEASUREMENTS AND MAIN RESULTS: Information was obtained on adult height, socioeconomic status in childhood and adult life, self perceived health, self reported longstanding illness, and mortality during a six year follow up. The numbers of people in three height groups who considered their general health as bad, who reported any longstanding illness or who died during the follow up were compared with the expected numbers in the same groups. The number of persons with reduced health and the number of deaths was larger than expected in the shortest height group. The excess risk of dying in the shortest group (about 20% higher compared to the tallest group) was reduced but not eliminated when present and childhood socioeconomic group was taken into account. Coronary heart disease mortality in particular was linked to height. The shortest group of men and women reported the largest proportion with bad general health and longstanding illness. For the latter the differences between height groups disappeared after controlling for present socioeconomic status. CONCLUSIONS: There is a detectable excess risk of morbidity and mortality from being short. Assuming that the childhood environment is an important determinant of adult stature it is also important for adult health.     

Flecainide versus quinidine in the prevention of paroxysms of atrial fibrillation

We compared the efficacy of flecainide versus quinidine in preventing paroxysms of atrial fibrillation in a randomized open crossover study. Twenty-six patients with weekly attacks of atrial fibrillation during the last 3 months, objectified by 24-h holter monitoring or 12-lead electrocardiogram (ECG) were treated for a period of 3 months with flecainide 100 mg b.i.d. or quinidine 500 mg b.i.d. Efficacy was assessed by 24-h holter monitoring and a questionnaire at the end of each month. Dosage was adjusted to flecainide 100 mg t.i.d. or quinidine 500 mg t.i.d. if patients still had symptomatic paroxysms of atrial fibrillation according to a questionnaire or on holter monitoring. In 46% of the patients, flecainide 100 mg b.i.d. caused total abolition of supraventricular tachycardia; after dose adjustment it caused 50% total abolition. For quinidine, the figures are 16% (p less than 0.05) and 32% (NS), respectively. Side effects occurred with flecainide only after dose adjustment (23%), but on quinidine they occurred before (8%) and after dose adjustment (20%). We conclude that flecainide suppresses paroxysms of atrial fibrillation significantly more often as compared with quinidine in the lower dosage regimen. Optimal treatment dosage of flecainide is 100 mg b.i.d. After quinidine dose adjustment, the difference in efficacy is no longer significant. However, side effects necessitating discontinuation of quinidine developed in 20% of the patients as compared to none in patients treated with flecainide 100 mg b.i.d.