Effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor-1 and fibrinogen in hyperlipidaemic patients

Evaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects. A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent. We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen. Although both fibrates effectively lowered triglyceride and cholesterol levels, no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment. However, both fibrates influenced plasma fibrinogen levels, albeit in a different way. Fibrinogen antigen levels were elevated by 17.6% (p <0.05) and 24.3% (p <0.001) with gemfibrozil after six and twelve weeks, respectively, whereas with ciprofibrate there was no effect. Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point, no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment. However, after twelve weeks, gemfibrozil enhanced functional fibrinogen levels by 7.2% (p <0.05) as assessed by the Clauss mechanical assay, but decreased functional fibrinogen levels by 12.5% (p <0.0001) when a Clauss assay based on turbidity was used. After six or twelve weeks of ciprofibrate treatment, functional fibrinogen levels were decreased by 10.1% (p <0.001) and 10.5% (p <0.0001), respectively on the basis of Clauss mechanical and by 14.2% (p <0.001) and 28.2% (p <0.0001), respectively with the Clauss turbidimetric assay. A remarkable and consistent finding with both fibrates was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen (determined by either of the two Clauss assays) to fibrinogen antigen. Taken together, our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates, by differences in treatment period and/or by the different outcomes of various assay systems. Interestingly, the two fibrates tested both reduced the functionality of fibrinogen.     

Apolipoprotein E-associated risk for Alzheimer's disease in the African-American population is genotype dependent

As a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE epsilon4 allele frequency was significantly increased in AD patients compared with controls. The age-adjusted odds ratio (OR) for AD in epsilon4 homozygotes was 4.83 (95% confidence interval [CI], 1.71-13.64) compared with the epsilon3/epsilon3 genotype, but the OR for AD with the epsilon3/epsilon4 genotype did not reach significance (1.20; 95% CI, 0.58-2.45). These findings suggest that the association between ApoE epsilon4 and AD is weaker in African Americans than in whites.     

The directional effects of passive eye movement on the directional visual responses of single units in the pigeon optic tectum

We have investigated the visual responses of 184 single units located in the superficial layers of the optic tectum (OT) of the decerebrate, paralysed pigeon. Visual responses were similar to those reported in non-decerebrate preparations; most units responded best to moving visual stimuli, 18% were directionally selective (they had a clear preference for a particular direction of visual stimulus movement), 76% were plane-selective (they responded to movement in either direction in a particular plane). However, we also found that a high proportion of units showed some sensitivity to the orientation of visual stimuli. We examined the effects of extraocular muscle (EOM) afferent signals, induced by passive eye movement (PEM), on the directional visual responses of units. Visual responses were most modified by particular directions of eye movement, although there was no unique relationship between the direction of visual stimulus movement to which an individual unit responded best and the direction of eye movement that caused the greatest modification of that visual response. The results show that EOM afferent signals, carrying information concerning the direction of eye movement, reach the superficial layers of the OT in the pigeon and there modify the visual responses of units in a manner that suggests some role for these signals in the processing of visual information.     

Comparison of responses to T-kinin and bradykinin in the mesenteric vascular bed of the cat

Responses to T-kinin and bradykinin were compared in the mesenteric vascular bed of the cat. Under constant-flow conditions, injection of T-kinin and bradykinin into the perfusion circuit induced similar dose-related decreases in perfusion pressure. Responses to T-kinin and bradykinin were inhibited by the kinin B2 receptor antagonist Hoe-140, but were not altered by the B1 receptor antagonist des-Arg9-[Leu8]-BK, the histamine H1 antagonist pyrilamine, the histamine H2 receptor antagonist cimetidine, or the H3 receptor antagonist thioperamide. Vasodilator responses to T-kinin and bradykinin were attenuated by the nitric oxide synthase inhibitor, N omega Nitro-L-arginine methyl ester (L-NAME), but were not altered by the cyclooxygenase inhibitor, sodium meclofenamate, or the K+ ATP channel antagonist, U37883A. These data suggest that vasodilator responses to T-kinin and bradykinin are mediated by kinin B2 receptor stimulated release of nitric oxide from the endothelium, but that the activation of kinin B1 receptors, the release of vasodilator prostaglandins, or the opening of K+ ATP channels are not involved in the response to T-kinin in the mesenteric vascular bed of the cat.     

Changes in brain-derived neurotrophic factor immunoreactivity in rat dorsal root ganglia, spinal cord, and gracile nuclei following cut or crush injuries

In the present study, we evaluated changes in brain-derived neurotrophic factor (BDNF) immunoreactivity in the rat lumbar (L) 5 dorsal root ganglion (DRG) and areas where afferents from the DRG terminate, the L5 spinal cord and gracile nuclei, following unilateral sciatic nerve transection or crush. From 3 days to 4 weeks following cut or crush injury, the percentage of medium and large BDNF-immunoreactive neurons in the ipsilateral DRG increased significantly compared with those on the contralateral side. Following cut injury, there was no significant change in the percentage of small BDNF-immunoreactive neurons in the ipsilateral DRG; however, the intensity of immunoreactivity of these cells decreased. Following crush injury, however, both the percentage and intensity of small BDNF-immunoreactive neurons in the ipsilateral DRG significantly increased. Following cut injury, the expression of BDNF-immunoreactive axonal fibers decreased markedly in the ipsilateral superficial laminae of the L5 spinal cord and increased significantly in the ipsilateral deeper laminae of the spinal cord and gracile nuclei. Crush injury induced a marked increase in the expression of BDNF-immunoreactive axonal fibers in the superficial laminae of the spinal cord and gracile nuclei. These differences in BDNF response in the DRG and spinal cord after cut or crush injuries may reflect differences in trophic support to the injured DRG neurons and altered neuronal activity in the spinal cord and gracile nuclei following different types of peripheral nerve injury.     

Portal hypotensive effects of DL-028 and prazosin on portal hypertensive rats

The portal hypotensive effects of prazosin and DL-028 (chem- ical name: 3-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]- 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one(27b)), a synthetic alpha1-adrenoceptor antagonist, were assessed in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Two weeks after ligation, when the hyperdynamic state was stabilized the rats were anesthetized after an overnight fast and cannulated for measuring mean arterial pressure (MAP), portal venous pressure (PVP), cardiac index (CI) and heart rate (HR). Both DL-028 and prazosin (1, 3.3 and 10 microgram/kg) induced dose-dependent decreases of PVP and MAP after intravenous infusion, with effects lasting for longer than 30 min. The maximum percentage reduction of PVP after DL-028 was 10, 10 and 15%, respectively, for the dosages given (1, 3.3 and 10 microgram/kg), and 5, 12 and 25%, respectively, after prazosin. CI was not changed by either drug. HR was not changed by either drug except DL-028 at 10.0 microgram/kg with a bradycardiac effect. Our results showed that both DL-028 and prazosin reduced PVP in portal hypertensive rats.     

Klebsiella pneumoniae panophthalmitis: a possible complication of endoscopic variceal injection sclerotherapy

Complication of endoscopic variceal injection sclerotherapy for esophageal variceal hemorrhage is not unusual. However, sclerotherapy complicated panophthalmitis was never reported before. We report such an unusual complication and discuss its possible mechanism and treatment.     

Hunting by male lions: ecological influences and socioecological implications

In the Kruger National Park, male lions, Panthera leo, acquire most of their food by hunting rather than scavenging. This study, the most intensive to date of male lion ecology, showed that in savanna woodlands, with high buffalo, Syncerus caffer, densities, male lions were frequent and successful hunters. The main prey species of all male group types, but particularly nonterritorial males, was buffalo. By contrast, females preyed more frequently on the most abundant medium-sized ungulates, such as wildebeest, Connochaetes taurinus, and zebra, Equus burchelli. Thus intraspecific prey selection separation was based primarily on intersexual and, to a lesser extent, social differences. Furthermore, both nonterritorial males and pride females located their favoured prey, buffalo and medium-sized ungulates, respectively, more often than other prey. We investigated the influence of several ecological variables on the socioecology of male lions, particularly as we had determined that territorial males spent little time with their pride females and tended to hunt by themselves in their respective male coalitions. Further analysis showed that in a range of ecosystems in southern and eastern Africa the proportion of time territorial males spent with, and thus scavenged from, their pride females was strongly influenced by vegetation structure, and therefore probably by the assemblage of available ungulates. In open systems, territorial males were, therefore, likely to be encountered with pride females, whereas in more wooded areas they were likely to be encountered away from their pride females. We suggest that this is because vegetation structure influences food/prey availability and hunting success and influences territory maintenance and/or cub defence. (c) 1998 The Association for the Study of Animal Behaviour.     

Vitamin E supplementation attenuates myointimal proliferation of the abdominal aorta after balloon injury in diet-induced hypercholesterolemic rabbits

The effects of vitamin E supplementation in a dose of 450 mg/1000 g chow on the myointimal proliferation of the abdominal aorta after balloon injury were studied in 4 groups of rabbits (24 each). The animals were fed regular diet, regular diet plus vitamin E, 1% cholesterol-enriched diet, and 1% cholesterol-enriched diet plus vitamin E. Each animal underwent a balloon injury of the abdominal aorta and left common iliac artery after 2 weeks of feeding. The animals remained on their respective diets thereafter. In 8 balloon-injured and 8 sham-operated animals of each group, the abdominal aortas were harvested 3 days after the procedure for the analysis of prostacyclin and thromboxane A2 synthesis, thiobarbituric acid reactive substances (TBARS) levels, enzyme activities of glutathione reductase (GR) and glutathione peroxidase (GP) as well as reduced (GSH) and oxidized (GSSG) glutathione levels, 3H-thymidine uptake, cholesterol as well as vitamin E contents. In the other 8 balloon-injured rabbits of each group, the tissue was harvested 3 weeks later for the morphometric study. In dependent of high cholesterol feeding, the vitamin E-treated rabbits had lower aortic production of thromboxane B2, higher 6-keto-PGF1 alpha and higher 6-keto-PGF1 alpha/thromboxane B2 ratios in both procedures. The aortic TBARS levels of the rabbits treated high cholesterol alone were significantly higher than the other three groups in both procedures. Balloon injury had a trend to increase TBARS levels and had significantly higher 3H-thymidine uptake (each p < 0.001) than sham operation in each group. Vitamin E supplement to high cholesterol diet or regular chow reduced aortic TBARS levels (p < 0.005 and 0.01, respectively) and 3H-thymidine uptake (p < 0.05 and 0.01, respectively), as well as attenuated myointimal proliferation of the abdominal aorta and left common iliac artery after balloon injury; but only supplement to high cholesterol diet reached statistical significances (both p < 0.05 compared to rabbits fed high cholesterol alone). These results suggest that vitamin E supplement changes prostanoid metabolism to a favorable pattern and reduces lipid peroxidation of the abdominal aortic wall, thus attenuates myointimal proliferation after balloon injury; these presentations are particularly obvious in diet-induced hypercholesterolemic rabbits.