Search PubMed⌕ Search

Biomedical subjects

O Eriksson

Publications and source records attributed to O Eriksson.

At least 55 records · Page 3Linked to original sources

Repetitive dosing of artemisinin and quinine against Plasmodium falciparum in vitro: a simulation of the in vivo pharmacokinetics.

Plasmodium falciparum (F32) parasites were exposed to artemisinin and quinine for 3 and 4 h, respectively, once or twice daily and for 3, 5 or 7 days. Between the peaks the parasites were exposed to trough concentrations. Continuous drug exposure was also assessed for comparison. After drug exposure, the cultures were extended for an observation period of up to 30 days to assess the viability of the parasites remaining after drug exposure. For artemisinin, a critical threshold concentration of 3 x 10(-8) M was required for growth inhibition. Dosing twice daily for at least 5 days was also critical. Prolonging the duration of drug exposure to 7 days further increased the efficacy. For quinine the results were quite different. The concentration dependency of the efficacy was more gradual. On the other hand dosing once daily appeared to be nearly as effective as twice daily and radical clearance was obtained even after 3 days of exposure at peak concentrations of 10(-5) M. A concentration of 10(-6) M provided the same effect if the duration was extended to 7 days. There was a strong similarity between estimated concentrations of free unbound drug required for radical clearance in vitro and those empirically required for clinical efficacy in vivo. This suggests that the in vitro model represents an appropriate model for estimating drug efficacy and pharmacodynamics if the in vitro system is adapted to simulate in vivo pharmacokinetics.

Animals↗

The paradoxical effect of smoking in preeclamptic pregnancies: smoking reduces the incidence but increases the rates of perinatal mortality, abruptio placentae, and intrauterine growth restriction.

OBJECTIVES: Smoking is associated with a reduced risk of preeclampsia, but what is the outcome of pregnancy when preeclampsia develops in women who smoke? STUDY DESIGN: Single births in Sweden from 1987 through 1993 to nulliparous women aged 15 to 34 years (N = 317,652) were included. Poisson regression analyses were used to calculate adjusted relative risks and rates of adverse pregnancy outcomes. RESULTS: Maternal smoking was associated with significantly reduced risks of mild and severe preeclampsia (relative risks = 0.6 and 0.5, respectively). In pregnancies with severe preeclampsia, smoking at least 10 cigarettes per day was associated with increased rates of perinatal mortality (from 24 to 36 per 1000), abruptio placentae (from 31 to 67 per 1000), and being small for gestational age (from 28% to 68%), whereas the corresponding smoking-related increases in rates in nonhypertensive pregnancies were considerably less. CONCLUSIONS: Smokers in whom preeclampsia develops have very high risks of perinatal mortality, abruptio placentae, and small-for-gestational-age infants.

Abruptio Placentae↗

Vitamin A exerts potential therapeutic effects in the endotoxaemic pig.

BACKGROUND: Pretreatment with an injection of vitamin A has beneficial effects on cardiac and pulmonary functions in normally bred endotoxaemic pigs. The present study was performed in order to elucidate whether the response of an ongoing infusion of E. coli can be modulated by a single injection of vitamin A. METHODS: Sixteen healthy (not vitamin A-depleted) pigs were anaesthetized, monitored, mechanically ventilated and subjected to an infusion of E. coli endotoxin (10 micrograms.kg-1.h-1). This infusion resulted within 30 min in a progressive haemodynamic derangement. When the mean pressure in the pulmonary artery was twice the baseline value, vitamin A (460 IU.kg-1) or a corresponding volume of vehicle was injected intravenously. After sacrificing the animals, the right lung was excised and weighed, and biopsy specimens were taken from the left lung for microscopical examination. RESULTS: Mean arterial blood pressure was significantly less affected (P < 0.01) between the 1st and 6th hour in endotoxaemic pigs treated with vitamin A than in those given vehicle. The mean lung weight in the vitamin A-treated pigs was significantly lower than that in the vehicle group (164 +/- 5.3 vs 199 +/- 19.8 g; P < 0.01). Microscopical examination showed significantly less oedema (0.93 +/- 0.17 vs 2.00 +/- 0.26; P < 0.01) and microatelectasis (0.56 +/- 0.17 vs 1.75 +/- 0.31; P < 0.01) in the vitamin A group. Endotoxaemia was also accompanied by an initial, steep decline in neutrophil counts in all animals; this decrease was significantly less pronounced (P < 0.05) in vitamin A-injected pigs than in the vehicle-injected group. The major difference was a more rapid restitution in the vitamin A group. CONCLUSION: Several manifestations of endotoxaemia were expressed less in the vitamin A group. Thus, vitamin A may turn out to be a tool in the management of endotoxaemia.

Animals↗

Analysis of total lipid extracts from human liver by 13C and 1H nuclear magnetic resonance spectroscopy.

Lipid extracts of liver tissue from normal donors and from patients with acute liver failure were analyzed by 13C NMR and 1H NMR at 9.4 T. The spectra allowed estimation of (i) the free fatty acid to total fatty acid chains ratio, (ii) the polyunsaturated to monounsaturated lipids ratio, (iii) the glycerophospholipids to triacylglycerols ratio, (iv) the total cholesterol to total fatty acids molar ratio, (v) the acylcholesterol to cholesterol ratio, (vi) the phosphatidylcholine to phosphatidylethanolamine molar ratio, and (vii) the unsaturation ratio of the fatty acid chains. The values obtained for normal livers agree with literature data on lipid composition obtained by other techniques. The two pathologic livers differ from the normal in the composition of some lipids and show a higher free fatty acid to total fatty acid chains ratio and a lower polyunsaturated to monounsaturated lipid ratio, a lower acylcholesterol to cholesterol ratio, and a lower phosphatidylcholine to phosphatidylethanolamine ratio, whereas the ratio of total cholesterol to fatty acids and the unsaturation ratio remained unchanged. The detailed assignment of the 13C NMR spectra of lipid extracts from normal and pathologic human liver may contribute to direct future research programs on 13C NMR spatially localized spectroscopy of the liver in vivo.

Cholesterol↗

Beneficial effects of pre-treatment with vitamin A on cardiac and pulmonary functions in endotoxaemic pigs.

BACKGROUND: Septic shock is associated with high mortality despite the development of new antibiotics. Since Vitamin A has an immunomodulating ability and is able to lower the concentrations of endotoxin and some cytokines, we decided to study whether supplementation with vitamin A may have a beneficial effect in experimental endotoxaemia. METHODS: A porcine model was used, in which normally bred (i.e., not vitamin A depleted) animals were anaesthetised, monitored and injected intramuscularly with a non-toxic dose of vitamin A (230 IU.kg-1) (n = 9) or the corresponding volume of vehicle (n = 9) 1 hour before an infusion of purified E. coli endotoxin was given in a dose of 10 micrograms.kg-1.h-1 over 6 hours. Another 3 pigs also injected with vitamin A, but not endotoxin, served as controls. RESULTS: Vitamin A- and endotoxin-injected pigs were significantly less affected in several circulatory and respiratory variables as compared to vehicle-and endotoxin-injected animals (e.g., blood pressure; heart rate; cardiac index; pulmonary capillary wedge pressure; left and right ventricular stroke work indices; pH; base excess; oxygen delivery; and oxygen extraction). Vitamin A did not per se significantly affect these variables. Hb increased significantly in the vehicle group, indicating a more pronounced capillary permeability. Urinary output or fluid supply did not differ between the groups. Myocardial production of metabolites of prostacyclin or thromboxane A2 did not differ between the groups. CONCLUSION: Pre-treatment with vitamin A had a beneficial effect on several variables, such as oxygen delivery and metabolic acidosis in the endotoxaemic pig. Improvement of these variables is associated with increased survival in septic shock and may indicate reduced tissue hypoxia. Thus, vitamin A may turn out to be useful as a prophylactic agent in conditions where septic shock is apt to occur.

6-Ketoprostaglandin F1 alpha↗