Increased Sensitivity to the Anticonvulsant Effect of Valproate in Aging BN/BiRij Rats

The aim of the present investigations was to study the influence of increasing age on the pharmacodynamics of valproate in BN/BiRij rats, applying a threshold for electrically induced localized seizure activity as a measure of the anticonvulsant effect. Seven groups of healthy male BN/BiRij rats were used, aged 3, 6, 12, 19, 25, 31, and 37 months. Individual plasma concentration versus anticonvulsant effect relationships were determined during a continuous intravenous infusion of sodium valproate at a rate of 5.5 mg/min/kg. The infusion was terminated when the anticonvulsant effect intensity had reached the maximum attainable level or at a total infusion time of three hours. A nonlinear relationship between valproate concentration and anticonvulsant effect intensity was observed with no maximal effect in the concentration range up to 1200 mg · L^–1. With increasing age a parallel shift in the concentration versus anticonvulsant effect relationships toward lower concentrations occurred. Thus increasing age appears to be associated with an increased sensitivity to the anticonvulsant effect of valproate.Suzanne Hovinga: Deceased January 30, 1991.     

Subacute (4-week) inhalation toxicity study of formaldehyde in male rats: 8-hour intermittent versus 8-hour continuous exposures

Male Wistar rats were exposed for 4 weeks, 5 days a week, to 0 (controls), 5 or 10 ppm formaldehyde continuously (8 hours a day), or to 10 or 20 ppm formaldehyde interruptedly (eight 30 min exposure periods separated by 30 min non-exposure periods). Histopathology and cell proliferation studies indicated that under the conditions of exposure used, concentration rather than the total dose of formaldehyde determined the severity of the cytotoxic effects on the nasal epithelium.     

Dipyridamole alone or combined with low-dose acetylsalicylic acid inhibits platelet aggregation in human whole blood ex vivo.

1. In a randomized, double-blind trial we compared the inhibition of the platelet-vessel wall interactions in whole blood ex vivo. There were four groups of 24 healthy volunteers each of whom were treated orally for 3.5 days with either 200 mg dipyridamole (sustained release preparation), 25 mg acetylsalicylic acid, both drugs combined or placebo twice daily. 2. The mean area of all platelets/aggregates was reduced by 6.2% +/- 4.2% (+/- s.e. mean) by placebo (n = 23), 19.8% +/- 6.7% by dipyridamole (n = 22), 53.7% +/- 4.9% by acetylsalicylic acid (n = 23) and 71.4% +/- 3.7% by the combination of both drugs (n = 24), when compared with total inhibition of aggregation by EGTA. Thus, low-dose acetylsalicylic acid inhibited aggregation (P less than 0.001). 3. Dipyridamole reduced the size of platelet aggregates (P less than 0.01, two-fold analysis of variance). The reduction was correlated with the individual dipyridamole plasma levels (P less than 0.05, analysis of covariance). The subgroup of large and very large thrombi being formed was also reduced by dipyridamole (P less than 0.05). 4. This ex vivo study demonstrates that dipyridamole alone inhibits formation of thrombi on subendothelial matrix and enhances the inhibitory effect of low dose acetylsalicylic acid in this model of thrombosis.     

Tetraspanins: molecular organisers of the leukocyte surface

Tetraspanins are a large superfamily of cell surface membrane proteins characterised by their four transmembrane domains. They are expressed in a wide variety of cell types and have functional roles in processes, such as cellular adhesion, motility, activation and tumour invasion. Leukocytes express 相似文献   

Klebsiella pneumonia today]

Analysis of incidence and morphology of Klebsiella pneumonia nowadays in the adults (10 observations), children (5 observations) and newborns (23 observations) is presented. The pneumonias account for 11.3% of total number of lobar pneumonias in the adults dying in 1979-1989. Klebsiella infection represent 16.1% of total number of autopsies a year according to the pediatric infection pathology department. Etiological role of Klebsiella is established in 21.5% of total number of autopsies of newborns for 1985-1988, pneumonia being 61% of total Klebsiella infections. Klebsiella pneumonias in the adults correspond in principle to the Friedl?nder's pneumonia studied in detail by V.D. Zinserling (1891-1960) and his students. Generalized forms of, as a rule, hospital Klebsiellosis with most grave lung damage, unknown up to now, are frequently observed in children. Klebsiellosis was combined practically in all cases both in the adults and children with other bacterial, viral and fungal infections. The degree of clinico-morphological manifestations may considerably vary.     

Partial dehiscence of a porcine prosthesis in association with aortic annular separation producing a false aneurysm of the ascending aorta

A 44-year-old man developed intermittent left bundle branch block followed by complete heart block 18 months after aortic valve replacement, and aortic insufficiency and hemolytic anemia 5 years postoperatively. These abnormalities were associated with operative findings (7 years after aortic valve replacement) of total disruption of the aorta at the level of the aortic annulus. Echocardiographic findings of an enlarged and unusually shaped "aortic root" and angiographic findings of abnormally high origin of the coronary arteries relative to the valve ring, which should have suggested the diagnosis 2 years prior to successful surgical repair, are presented.     

Restored hypoxic pulmonary vasoconstriction by peripheral chemoreceptor agonists in dogs

Hypoxic stimulation of the peripheral chemoreceptors inhibits hypoxic pulmonary vasoconstriction (HPV). On the other hand, almitrine, a peripheral chemoreceptor agonist, has been reported in some studies to enhance HPV. To further explore this apparent contradiction, we investigated the effects of two different low intravenous doses of almitrine on pulmonary arterial pressure (Ppa) versus cardiac index (Q) plots in 32 pentobarbital-anesthetized dogs ventilated alternatively in hyperoxia (FIO2, 0.4) and in hypoxia (FIO2 0.1). HPV, defined as a hypoxia-induced increase in Ppa over the entire range of Q studied, from 2 to 5 L/min/m2, was elicited in 16 dogs. In the first eight of these "responders," almitrine 2 micrograms/kg/min had no vascular effect, and in the other eight, almitrine 4 micrograms/kg/min inhibited HPV. In 16 other dogs, hypoxia did not affect Ppa over the entire range of Q. In these "nonresponders," almitrine 2 micrograms/kg/min (n = 8) as well as 4 micrograms/kg/min (n = 8) restored HPV. To answer the question whether the ability to restore HPV would be specific to almitrine, we administered intravenously the structurally unrelated chemoreceptor agonist doxapram at the dose of 20 micrograms/kg/min to an additional group of eight "nonresponders," and this treatment also restored HPV. Intravenous infusion of the malic acid solution solvent of almitrine had no effect on Ppa/Q plots in a final group of eight "nonresponders". We conclude that low dose almitrine and doxapram restore HPV in dogs with a naturally absent hypoxic pulmonary pressor response, probably by a direct effect at the pulmonary vessels.     

Regulating the gene: From genetic consumption to regulatory trust

In this article, we examine the changing terms on which genetics-based technologies in two areas agriculture (Genetically Modified Organism, GMOs) and health (genetic diagnostics) have been regulated. These are used to illustrate and examine the proposition that shifts in the politics of governance and regulation (associated in part with the advent of the negotiation state) have meant that the responsibility for the social management of new technology is increasingly shared between the state and the consumer. However, this redistribution of the social management of risk, we argue, fails to establish a sufficient basis for a legitimate regulatory trust. We suggest that trust will depend on embedding broad social values and a self-critical agenda within the regulatory regime itself.