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Biomedical subjects

A A Dogterom

Publications and source records attributed to A A Dogterom.

13 recordsLinked to original sources

Pharmacokinetics and pharmacodynamics of a single dose of recombinant human growth hormone after subcutaneous administration by jet-injection: comparison with conventional needle-injection.

The pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) were studied after a single subcutaneous dose given by jet-injection, and have been compared with the results obtained after conventional needle-injection. Twelve healthy male volunteers completed an open label, randomised, two-way crossover study, with a 7-day washout period between the two single sc doses. Pharmacokinetic parameters were derived from rhGH concentrations in blood samples collected regularly over 24 h after dosing on Day 1 of each period. To investigate the pharmacodynamics, additional samples were taken for the analysis of somatomedin C (IGF-I) and free fatty acids (FFA). A higher and earlier Cmax was found after jet-injection (ratio (%) jet-injected/needle-injected 124; 90%-confidence interval 108-142). The AUC0-infinity for rhGH were similar (ratio (%) jet-injected/needle-injected 98; 90%-confidence interval 93-103). Both treatments were associated with a significant and similar rise in IGF-I. Both administrations of rhGH were associated with identical rhythmical changes in FFA. The study indicates that jet-injected and needle-injected rhGH are bioequivalent with respect to the amount absorbed. The criterion for bioequivalence is not met for the rate of absorption. It is unlikely that the latter finding will influence the pharmacodynamics of rhGH, since bioequipotency was established for the effect on IGF-I generation. Jet-injection was safe in use and was generally well tolerated.

Adult↗

Rapid reduction of uterine leiomyomas with monthly injections of D-Trp6-GnRH.

Ten women with intramural leiomyomas were treated with the microencapsulated GnRH analogue Decapeptyl for 24 weeks. Four (4) mg Decapeptyl was injected, starting on day 21 of the menstrual cycle, and injections were repeated every 4 weeks for a total of 24 weeks. All patients showed a marked reduction in uterine size: before treatment it measured 284 +/- 57 cm3, after 8 weeks 122 +/- 33 cm3, and after 24 weeks 89 +/- 14 cm3. LH and estradiol decreased significantly; FSH decreased but not significantly; prolactin remained almost unaltered. Serum calcium, phosphate, alkaline phosphatase and osteocalcin increased, but, since calcium excretion (and hydroxyproline excretion) remained unaltered, these changes were considered to reflect increased bone turnover rather than bone loss. From these data it is concluded that Decapeptyl is very effective in reducing uterine fibroids, that treatment can be shorter than 6 months and that measurable bone loss did not occur.

Adult↗

Matrix depletion of young and old human articular cartilage by cultured autologous synovium fragments: a chondrocyte-independent effect.

Human articular cartilage of different ages was cultured for 8 days and proteoglycan (PG) release into the medium was measured. Retinol and synovial co-culture increased the PG release of cartilage of all ages. The effect of retinol was dose-dependent. Synovium increased also the PG release of dead cartilage, whereas retinol did not. The increased PG release by synovial co-culture is therefore mainly the result of synovial enzymes acting directly on the matrix rather than of a factor inducing chondrocyte-mediated breakdown.

Age Factors↗

Some properties of carbonic anhydrase from mineralizing hamster molars.

Carbonic anhydrase (CA) activity in mineralizing hamster molars was determined with a radiochemical assay. Hamster molar CA appeared to be very similar to CA from other sources. No pH optimum could be determined; the KM was 13.6 mM and CA was strongly inhibited by acetazolamide. EDTA and F- had almost no effect on the CA activity. This lack of fluoride effect suggests strongly that the protective effect of fluoride on dental mineral is not mediated by CA.

Acetazolamide↗

Carbonic anhydrase in developing hamster molars.

Carbonic anhydrase (CA) activity decreased slightly in hamster molars from one to four d after birth. It was inhibited by low concentrations of acetazolamide. Histochemically, the stratum intermedium and stellate reticulum showed an intense staining for CA, whereas ameloblasts increased and odontoblasts decreased their CA activity with age.

Ameloblasts↗

An improved method for embedding hard tissue in polymethyl methacrylate.

An improved routine method for embedding tissue, especially hard tissue, in polymethyl methacrylate (pMMA) is described. The improvements were: the final dehydration step before MMA infiltration was performed with methanol in a Soxhlet apparatus; the stabilizer hydroquinone was not extracted from the monomer (MMA), and more important, the commonly used polymerization initiator, benzoyl peroxide (bpo), was replaced by the initiator, bis (4-tert-butylcyclohexyl)peroxydicarbonate (bbpd). Bbpd is preferred to bpo because it is not explosive, far less is needed and it has a suitable half life. Moreover, bbpd, as obtained from the manufacturer, needs no further purification, in contrast to bpo. Temperatures during bbpd initiated polymerization did not exceed 48 C. In bbpd initiated pMMA, bubbles were almost never generated.

Benzoyl Peroxide↗

Carbonate incorporation and carbonic anhydrase activity in developing hamster molars in vitro.

Hamster molar tooth germs were tested in vitro for their capacity to incorporate 45Ca, 32PO4 and H14CO3 into their mineral. Concomitantly, the activities of alkaline phosphatase and carbonic anhydrase were measured in the cultured tooth germs. Incorporation of calcium and phosphate into the dental mineral increased with time in culture (0-10 days), whereas carbonate incorporation decreased slightly. Alkaline phosphatase and carbonic anhydrase increased with time. These results suggest that carbonic anhydrase is probably not involved in carbonate deposition, but in carbonate depletion of the dental mineral, carbonate being probably replaced by phosphate.

Alkaline Phosphatase↗

Studies of alkaline phosphatase inhibition by p-bromotetramisole in non-mineralizing and mineralizing neonatal hamster tooth germs in vitro.

The effects of l and d-, p-bromotetramisole (pBTM) on alkaline phosphatase were studied in relation to 45Ca2+, 32phosphate and 3H-thymidine uptakes in non-mineralizing second (M2) and mineralizing first (M1) maxillary hamster molar tooth germs under the conditions of organ culture. At the concentration used in culture (10(-3)M), l-pBTM completely inhibited alkaline phosphatase activity in tooth germ homogenates. About 30% of the enzyme activity was inhibited by d-pBTM at the same concentration. In culture, there were no significant differences between the effects of l and d-pBTM isomers on all the parameters measured. In the non-mineralized M2 molars, l and d-pBTM significantly reduced both TCA-soluble and TCA-insoluble 32phosphate uptakes but not 45Ca2+. However, 3H-thymidine uptake was also significantly decreased. In M1 molars, the pBTM isomers significantly reduced the uptake of TCA-soluble 32phosphate and 45Ca2+ but not TCA-insoluble 32phosphate. Ouabain, a specific inhibitor of Na+-K+-ATPase (but not alkaline phosphatase), also significantly reduced 3H-thymidine uptake to the same extent as the pBTM isomers in the non-mineralizing M2 molars, but it did not significantly affect either 32phosphate (TCA-soluble and TCA-insoluble) or 45Ca2+ uptake. Although this inhibitor significantly reduced both 45Ca2+ and TCA-soluble 32phosphate uptake in the mineralizing M1 molars, this effect was much less dramatic than was the case with the pBTM isomers. The reduced 45Ca2+ uptake in the M1 molars is probably a consequence of reduced mineralization since in the non-mineralizing M2 molars calcium uptake was not significantly affected by the pBTM isomers.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

A hormone dependent calcium-binding protein in the mantle edge of the freshwater snail Lymnaea stagnalis.

By means of gel filtration and ion exchange chromatography on calcium-saturated Chelex-100, a calcium-binding fraction was isolated from the mantle edge of the freshwater snail lymnaea stagnalis. This fraction was not present in other tissues. Treatment with trypsin caused a disappearance of the calcium-binding capacity, proving that the active substance in this fraction is a protein (calcium-binding protein; CaBP). Removal of the growth hormone-producing neuroendocrine light green cells resulted in a strong decrease of the amount of CaBP. It is concluded that L. stagnalis possesses a hormone-dependent CaBP, probably responsible for the maintenance of a high calcium concentration in that part of the mantle that produces the outer crystalline layer of the shell.

Animals↗