Biomedical subjects

P Vuorela

Publications and source records attributed to P Vuorela.

26 records · Page 2Linked to original sources

PubMed1998

High-performance liquid chromatography methods for the separation and quantitation of spironolactone and its degradation products in aqueous formulations and of its metabolites in rat serum.

HPLC assays have been developed for the determination of spironolactone and its degradation products 7 alpha-thiospirolactone and canrenone in aqueous solutions of beta-cyclodextrins and for the determination of spironolactone and its metabolites 7 alpha-thiospirolactone, 7 alpha-thiomethylspirolactone, 6 beta-hydroxy-7 alpha-thiomethylspirolactone and canrenone in rat serum samples. Both methods were well suited for their respective applications, i.e., studying the stability of spironolactone in liquid formulations of beta-cyclodextrins and the oral absorption of spironolactone in rats. The HPLC method developed for spironolactone and its metabolites in rat serum requires very small volumes of serum making it possible to take several blood samples over a period of time.

Animals↗

PubMed1998

Endothelial tie receptor antigen in maternal and cord blood of healthy and preeclamptic subjects.

OBJECTIVE: To measure the vascular endothelial receptor tyrosine kinase Tie, essential in the process of angiogenesis, in blood from healthy and preeclamptic pregnant women, in umbilical cord blood from both, and in blood from nonpregnant women. METHODS: A total of 143 women participated in four arms of the study. Blood samples were collected from 54 healthy nonlaboring pregnant women (gestational weeks 14-41). Samples were collected immediately prepartum and postpartum from another 40 healthy women (15 delivered vaginally and 25 by cesarean) and 15 preeclamptic women (all delivered by cesarean). Arterial and venous cord samples were collected, when possible, from infants born by cesarean. Single blood samples were drawn from 34 nonpregnant controls. Of these, weekly samples from 11 were drawn during one menstrual cycle. A time-resolved fluoroimmunoassay was developed for the detection of the soluble extracellular domain of Tie. RESULTS: Maternal serum Tie levels decreased with advancing gestational age after 26 weeks (r = .6, P < .001). They were significantly higher in healthy women at term (median 233 ng/mL, range 152-414 ng/mL) compared with nonpregnant controls (median 173 ng/mL, range 107-333 ng/mL, P < .001) or with preeclamptic women at term (median 152 ng/mL, range 90-372 ng/mL, P < .05). This difference between healthy and preeclamptic women persisted on the first postpartum day (median 221 ng/mL, range 128-343 and median 152 ng/mL, range 90-372 ng/mL, respectively, P < .05). The highest levels of serum Tie receptor were observed in umbilical arterial and venous blood (median 240 ng/mL, range 174-474 ng/mL and median 340 ng/mL, range 245-690 ng/mL, respectively). In nonpregnant women, serum Tie levels did not vary with menstrual cycle. CONCLUSION: The high levels of the extracellular domain of Tie in healthy term maternal and cord blood may indicate a role for Tie in the vascular development of human fetuses and placentas.

Adult↗

PubMed1998

Optimization of selectivity in high-performance liquid chromatography using desirability functions and mixture designs according to PRISMA.

A computer program for the mobile phase optimization of high-performance liquid chromatography (HPLC) is described. The desirability function technique combined to the prisma mixture design was employed to enhance the quality of HPLC separations. The use of statistical models to predict the behaviour of retention times (tR) and band broadening at the different eluent compositions obtained by prisma was examined for dansyl amides and coumarins. The study showed that the dependence between the eluent composition and tR values of dansyl amides and coumarins can be expressed using quadratic regression models with a high degree of accuracy. Band broadening given by means of the band width at half-height (wh) was described by a linear regression model. Both models were used in calculating and predicting the resolution (Rs) in various solvent combinations. The desirability function converted the calculated (Rs) value into the desirability value (D), and the overall optimum was then defined by means of the overall desirability. The optimal eluent mixtures for the separation of compounds were easily read from the contour plot inside the horizontal plane of the prisma model. A good separation was achieved using the optimized solvent combination. Depending on the aims of the optimal separation, the program allows either optimization of critical pairs or achieving the overall optimum giving a reasonable separation for as many compounds as possible.

Chromatography, High Pressure Liquid↗

PubMed1997

Isolation and immunomodulatory effect of flavonol glycosides from Epimedium hunanense.

The ethyl acetate and n-butanol fractions from aerial parts of E. hunanense were initially screened to find active fractions with immunomodulatory activity. Nine compounds, tricin (1), luteolin (2), thalictoside (3), icariin I (4), baohuoside I (5), quercitrin (6), icariin (7), epimedin C (8), and B (9) were isolated from this species for the first time, and 3 was isolated for the first time from flavonoid extracts of the genus. Their structures were established by chemical and spectroscopic methods. The immunomodulatory effects of the n-butanol fraction and epimedin C isolated from the fraction were investigated. Hydrocortisone acetate (HCA) was used as an immunosuppressant to inhibit the immune response of mice. The n-butanol fraction and epimedin C significantly enhanced the response of spleen antibody-forming cells (SAFC) to near normal in the mice treated with HCA. They also significantly enhanced lymphocyte proliferation and caused a significant recovery of interleukin-2 (IL-2) production in the mice inhibited with HCA. In conclusion, they are active principles with immunoenhancing effects.

Adjuvants, Immunologic↗

PubMed1997

Expression of vascular endothelial growth factor and placenta growth factor in human placenta.

Normal development and function of the placenta requires invasion of the maternal decidua by trophoblasts, followed by abundant and organized vascular growth. Little is known of the significance and function of the vascular endothelial growth factor (VEGF) family, which includes VEGF, VEGF-B, and VEGF-C, and of placenta growth factor (PIGF) in these processes. In this study we have analyzed the expression of VEGF and PIGF mRNAs and their protein products in placental tissue obtained from noncomplicated pregnancies. Expression of VEGF and PIGF mRNA was observed by in situ hybridization in the chorionic mesenchyme and villous trophoblasts, respectively. Immunostaining localized the VEGF and PIGF proteins in the vascular endothelium, which was defined by staining for von Willebrand factor and for the Tie receptor tyrosine kinase, an early endothelial cell marker. VEGF-B and VEGF-C mRNAs were strongly expressed in human placenta as evidenced by Northern blot analysis. These data imply that VEGF and PIGF are produced by different cells but that both target the endothelial cells of normal human term placenta.

Blotting, Northern↗

PubMed1994

Bioactivity of certain Egyptian Ficus species.

The fruit extracts of Ficus sycomorus L., F. benjamina L., F. bengalensis L. and F. religiosa L. were screened for bioactivity. F. bengalensis and F. religiosa demonstrated activity in the brine shrimp test (Artemia salina) which indicates toxicity, whereas F. sycomorus and F. benjamina showed no activity. All the fruit extracts exhibited antitumor activity in the potato disc bioassay. None of the tested extracts showed any marked inhibition on the uptake of calcium into rat pituitary cells GH4C1. The extracts of the four tested Ficus species had significant antibacterial activity, but no antifungal activity. The results of this preliminary investigation support the traditional use of these plants in folk medicine for respiratory disorders and certain skin diseases.

Animals↗

PubMed1993

Differential inhibition of coumarin 7-hydroxylase activity in mouse and human liver microsomes.

Coumarin is 7-hydroxylated by the P450 isoform Cyp2a-5 in mice and CYP2A6 in humans. Various drugs, endogenous substances, plant substances and carcinogens, altogether about 90 chemicals, were evaluated as possible inhibitors of coumarin 7-hydroxylase (COH) activity in mouse microsomes. The effects of selected compounds on COH activity in human liver microsomes were also tested. The furanocoumarin derivatives methoxsalen (8-methoxypsoralen) and psoralen proved to be the most potent inhibitors of mouse COH activity (IC50 values 1.0 and 3.1 microM, respectively). The furanocoumarins bergapten (5-methoxypsoralen), isopimpinellin (5,8-dimethoxypsoralen), imperatorin and sphondin also effectively inhibited mouse COH activity (IC50 values 19-40 microM). Methoxsalen, isopimpinellin and metyrapone were also inhibitors in mice in vivo. Methoxsalen was a potent inhibitor of COH activity also in human liver microsomes, (IC50 value 5.4 microM), whereas bergapten, isopimpinellin and imperatorin had no effect. The imidazole antimycotic miconazole was a potent but non-specific inhibitor of COH activity. Several known substrates and inhibitors of members in the CYP1A, CYP2B, CYP2C, CYP2D and CYP3A subfamilies were poor inhibitors of COH activity. These results suggest that (i) the coumarin-type compounds in particular interact with the active sites of Cyp2a-5 and CYP2A6, and (ii) the active sites of Cyp2a-5 and CYP2A6 are structurally different, since a number of compounds inhibited mouse, but not human COH activity.

Animals↗

PubMedDate not supplied

In vitro assay for human toxicity of cereulide, the emetic mitochondrial toxin produced by food poisoning Bacillus cereus.

The in vitro boar spermatozoon test was compared with the LC ion trap MS analysis for measuring the cereulide content of a pasta dish, implemented in serious emetic food poisoning caused by Bacillus cereus. Both assays showed that the poisonous food contained approximately 1.6 microg of cereulide g(-1) implying the toxic dose in human as < or =8 microg kg(-1) body weight. The threshold concentration of cereulide provoking visible mitochondrial damage in boar sperm exposed in vitro was 2 ng of cereulide ml(-1) of extended boar sperm. The same threshold value was found for cereulide extracted from the food and from the cultured bacteria. This shows that other constituents of the food did not enhance or mask the effects of cereulide. Exposure of four human cell lines (HeLa, Caco-2, Calu-3 and Paju) to cereulide showed that the threshold concentration for the loss of mitochondrial membrane potential in human cells was similar to that observed in boar sperm. Human cells and boar sperm were equally sensitive to cereulide. The results show that boar spermatozoan assay is useful for detecting cereulide concentrations toxic to humans. Spermatozoa in commercially available extended fresh boar and cryopreserved bull semen were compared, boar sperms were 100 times more sensitive to cereulide than bull sperms.

Animals↗