Biomedical subjects

F A Muskiet

Publications and source records attributed to F A Muskiet.

At least 37 records · Page 2Linked to original sources

PubMed1999

Does supplementation of formula with evening primrose and fish oils augment long chain polyunsaturated fatty acid status of low birthweight infants to that of breast-fed counterparts?

We investigated whether formulae with evening primrose and fish oils raise long chain polyunsaturated fatty acids (LCPUFA) in plasma cholesterol esters (CE), erythrocytes (RBC) and platelets (PLT) to levels encountered in breast-fed infants. Low birthweight infants (< or =2500 g) received LCP1 formula (n = 16; 0.31% 18:3 omega6, 0.17% 20:5 omega3 and 0.20% 22:6 omega3) or LCP2 formula (n = 13; 0.32% 18:3 omega6, 0.34% 20:5 omega3 and 0.43% 22:6 omega3). Fatty acids were measured days 10+/-2, 20+/-3 and 42+/-3. The formulae raised CE, RBC and PLT 20:5 omega3 and 22:6 omega3 dose-dependently (P<0.01), to exceed levels of breast-fed babies (n = 18) day 42 (P<0.05). CE, RBC and PLT 20:3 omega6 was comparable with, and CE, RBC, PLT 20:4 omega6 were below, that of breast-fed infants (P<0.05). Dietary 20:5 omega3 and 22:6 omega3 related with CE, RBC and PLT 20:5 omega3 and 22:6 omega3 (n = 47; P< or =0.01). Dietary 20:5 omega3 and LCPUFA omega3 related inversely with CE, RBC and PLT 20:4 omega6 and LCPUFA omega6 (P< or =0.002). LCP1 and LCP2 fed infants had similar LCPUFA omega6 status day 42. Added 18:3 omega6 does not correct 20:4 omega6 to that of breast-fed infants, but improves 20:3 omega6 status. Fish oil dose-dependently raises 20:5 omega3 and 22:6 omega3, but decreases 20:4 omega6 and other LCPUFA omega6.

Breast Feeding↗

PubMed1999

Development of low-birthweight infants at 19 months of age correlates with early intake and status of long-chain polyunsaturated fatty acids.

We investigated the influence of early nutrition with and without long-chain polyunsaturated fatty acids (LCP) on later development of < or = 2500 g newborns receiving preterm formula without LCP (n=75), preterm formula with 18:3omega6 and LCPomega3 (at two doses; n=26) or their mother's own milk (n=27). All diets were given from birth to day 42. Erythrocytes (RBC) fatty-acid compositions were determined on day 42. Bayley's mental development (MDI) and psychomotor development (PDI) indices were assessed at 19 months. Multivariate regression analysis revealed that PDI was most strongly related to RBC 22:6omega3 in the cohort of 101 infants who received formula. The most consistent correlations were between development and early LCPomega3 intake, and between development and parameters of RBC LCPomega3 status day 42, in infants who received formula with 18:3omega6 and LCPomega3. Development of formula-fed low-birthweight infants seems positively influenced by early dietary LCPomega3.

Child Development↗

PubMed1999

Umbilical vessels of preeclamptic women have low contents of both n-3 and n-6 long-chain polyunsaturated fatty acids.

BACKGROUND: Preeclampsia is characterized by enhanced platelet aggregation and vasoconstriction and is related to an elevated ratio of thromboxane A2 to prostacyclin I2. OBJECTIVE: We investigated whether altered eicosanoid production in preeclamptic women could be explained by the fatty acid composition of umbilical vessel walls and platelets. DESIGN: The fatty acid composition of maternal and umbilical platelets and of umbilical arteries and veins in 27 preeclamptic women and 24 normotensive women was determined. Between-group differences were analyzed with linear discriminant analysis, the Kruskal-Wallis test, or analysis of covariance with gestational age as the covariate. RESULTS: Platelets of preeclamptic women contained lower amounts of 20:5n-3 and a higher ratio of 20:4n-6 to 20:5n-3 than did platelets of normotensive women. Additionally, linear discriminant analysis revealed higher amounts of 20:4n-6 in platelets of preeclamptic women. Umbilical arteries and veins in preeclamptic women contained lower amounts of long-chain polyunsaturated fatty acids (PUFAs) of the n-3 series, n-6 long-chain PUFAs, and 20:3n-6 than did umbilical arteries and veins of normotensive women. Umbilical arteries also had lower amounts of 20:4n-6, higher amounts of 20:3n-9, and a higher ratio of 20:3n-9 to 20:4n-6. CONCLUSIONS: Low amounts of long-chain n-3 and n-6 PUFAs in umbilical vessels of preeclamptic women with adequate n-6 status may indicate insufficient transplacental transfer of long-chain PUFAs. The low amounts of 20:4n-6, high amounts of 20:3n-9, and high ratio of 20:3n-9 to 20:4n-6 in umbilical arteries may unfavorably affect local prostacyclin production. Low amounts of 20:3n-6 in umbilical arteries and veins and low amounts of 20:5n-3 in maternal platelets may contribute to the dominance of eicosanoids derived from 20:4n-6.

Blood Platelets↗

PubMed1999

Predictive value of cord blood hematological indices and hemoglobin Barts for the detection of heterozygous alpha-thalassemia-2 in an African-Caribbean population.

BACKGROUND: Cord blood hemoglobin Barts (HbBarts) and hemocytometric indices may be used for classification of newborns into those without alpha-thalassemia-2 (alphaalpha/alphaalpha) and with heterozygous alpha-thalassemia-2 (-alpha(3.7)/alphaalpha). We investigated by logistic regression analysis whether the combination of HbBarts and hemocytometric indices improves classification compared with classification based on a single analyte. METHODS: HbBarts percentages and hemocytometric indices were determined in cord blood of 208 consecutive newborns in Curaçao (Netherlands Antilles). Of these, 157 had alphaalpha/alphaalpha and 51 had -alpha(3.7)/alphaalpha, as established by DNA analysis. RESULTS: Between-group differences were significant for erythrocytes, mean cell volume, mean cell hemoglobin (MCH), mean cell hemoglobin concentration, platelets, hemoglobin F(0) (HbF(0)), and HbBarts. The Logit equation of the logistic regression model, using MCH (pg) and HbBarts (%), was: 42.7164 + 5.7916(HbBarts) - 1.3110(MCH). A sensitivity of 100% was reached at a Logit value of -3.70. The corresponding specificity was 62.2%, and the predictive value of a positive test (PV+) was 46.3% (95% confidence interval, 37.0-55.7%). The relative information gains were as follows: 88% for the HbBarts-MCH combination, 26% for MCH (not significant), and 0% for HbBarts compared with the 24.6% -alpha(3.7)/alphaalpha prevalence. CONCLUSION: Combined use of cord blood HbBarts and MCH improves classification compared with classification based on single hemocytometric indices.

Black People↗

PubMed1998

In vivo manipulation of L1210 cell cycle phase distribution with alpha-difluoromethylornithine, 4-amidinoindan-1-one 2'-amidinohydrazone and N1-acetylspermine.

We investigated whether the in vivo growth inhibitory effect of the combination of 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) and alpha-difluoromethylornithine (DFMO) is reversible by treatment with N1-acetylspermine (N1-acSp). DBA-2 mice were inoculated with 10(5) L1210 cell i.p. on day 0. From day 1 they received 2.50 mg CGP 48664A/kg i.p. once daily and 500 mg DFMO/kg i.p. twice daily. On day 5 they received 3 x 2500 nmol N1-acSp i.p. with 15-min intervals. L1210 cell numbers, S-phase percentage and polyamine contents, and liver and spleen polyamine contents were monitored in the following 48 h. Four days treatment with CGP 48664A/DFMO reduced L1210 cell numbers, S-phase, and spermidine. N1-acSp treatment increased L1210 spermidine from < or = 8 h and percentage S-phase from 12 h. Maxima for spermidine and S-phase were reached at < or = 8 and 18 h, respectively. These were below levels of untreated controls. Decreases were noted from 12 and 18 h, respectively. N1-acSp was detectable in L1210 from 0-18 h. Liver spermidine was decreased by CGP 48664A/DFMO. After N1-acSp treatment, liver N1-acSp and N1-acSd increased from < or = 8 h, reached maxima at < or = 8 and 10 h, respectively, and were undetectable from 15 h. We conclude that the in vivo growth inhibitory effect of CGP 48664A/DFMO is reversible by N1-acSp treatment. The liver is probably involved in N1-acSp terminal catabolism. The effect of the polyamine depletion-repletion scheme on S-phase cell numbers may be much more profound than present estimates from 5-bromo-2'-deoxyuridine incorporation.

Amidines↗

PubMed1998

In vitro manipulation of L1210 cell cycle kinetics with 4-amidinoindan-1-one 2'-amidinohydrazone, alpha-difluoromethylornithine and N1-acetylspermine.

We investigated whether in vitro L1210 growth inhibition by alpha-difluoromethylornithine (DFMO; 740 microM) and 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A; 1.7 microM) is reversible with N1-acetylspermine (N1-acSp). Influences of N1-acSp dose (1-100 microM), time (0-12 h at 100 microM), aminoguanidine (AG, 1 mM) and cell numbers (at 1 microM N1-acSp) on percentage S-phase, polyamine contents and viability were determined. DFMO/CGP 48664A decreased percentage S-phase from 58 to 26%, decreased spermidine (Sd) and spermine (Sp) contents 3-fold, but did not affect viability. With increasing N1-acSp dose, S-phase percentage and Sd contents increased concomitantly, reaching plateau values that were comparable with those of untreated controls. S-phase and Sd content increased from 4-6 h after N1-acSp administration, reaching plateau values from 11 and 6 h, respectively. N1-acSp content was dose dependent and increased linearly to reach plateau values from 8 h. AG did not affect any of these parameters. Addition of 1 microM N1-acSp to decreasing numbers of DFMO/CGP 48664A-treated cells caused increasing S-phase percentage, Sd and N1-acSp contents. We conclude that cell cycle kinetics of cultured L1210 cells can be manipulated by the induction of growth inhibition with DFMO/CGP 48664A and its subsequent abolishment with N1-acSp. N1-acSp accumulation rate and its subsequent conversion to Sd is relatively slow compared with intracellular Sd needs. The data support the notion that Sd is the most important polyamine for growth.

Amidines↗

PubMed1998

[Recommended dietary allowance of folic acid is insufficient for optimal homocysteine levels].

OBJECTIVE: To determine the effect of short term supplementation of vitamin B6 (pyridoxine) followed by folic acid in apparently healthy volunteers on the fasting plasma homocysteine concentrations (hyperhomocysteinaemia is an independent risk factor for premature atherosclerosis). DESIGN: Prospective, descriptive. SETTING: Academic Hospital Groningen, the Netherlands. METHODS: Apparently healthy Dutch volunteers, aged 20-75 years, were supplemented with vitamin B6 1 mg/kg/day during 7 days followed by folic acid 5 mg/day during another 7 days. On days 0, 7 and 14 the fasting plasma homocysteine concentrations were measured. A change of an individual's plasma homocysteine level was considered statistically significant if the change in percentage exceeded 2.8 times the sum of the analytical and the intraindividual biological variation. RESULTS: There were 103 participants, 45 males and 58 females, with average ages of 43 and 44 years, respectively (on day 7, data were available on 101 participants). Baseline folic acid concentrations of all participants were above the lower limit of the reference range. Eight and two of them had vitamin B6 and vitamin B12 concentrations below the reference range, respectively. Plasma homocysteine was inversely related to plasma levels of folic acid and vitamin B12 at that moment. During vitamin B6 supplementation the mean plasma homocysteine level did not change; one participant exhibited a significant plasma homocysteine decrease. During folic acid supplementation the mean plasma homocysteine decreased from 11.7 mumol/l (SD: 5.6) to 9.1 (SD: 3.4); 40 participants (40%) exhibited significant plasma homocysteine decreases. At the end of the study plasma homocysteine was still related to plasma vitamin B12. CONCLUSION: The folic acid status of the participants at baseline was not associated with the lowest plasma homocysteine levels. Since atherosclerosis risk may increase continuously with increasing plasma homocysteine, it may be wise to keep plasma homocysteine levels as low as possible. To reach this goal, the recommended dietary allowance of folic acid may have to be increased.

Adult↗

PubMed1998

New concepts in assessing sickle cell disease severity.

Vasoocclusion leads to pain, chronic organ damage, and a decreased life expectancy in patients with sickle cell disease. Therapeutic options for sickle cell disease have usually been evaluated according to their capacity for reducing the frequency of vasoocclusive crises requiring clinical attention. However, the frequency of vasoocclusive crises is not representative for the rate of accumulating organ damage in most sickle cell patients. This implies that the frequency of vasoocclusive crises needn't correlate with disease severity and, although being of importance, cannot solely serve as a parameter of treatment efficacy. Therefore, additional new objective parameters are needed to effectively study the vasoocclusive process in sickle cell disease. Several studies show that intricate adhesive interactions between (red) blood cells, plasma components, and endothelium play a crucial role in the pathophysiology of sickle cell vasoocclusion, offering new potential parameters to effectively assess disease severity as well as new therapeutical targets in the near future. Whether these adhesive mechanisms involve the causes or the effects of vasoocclusion will be determined if their inhibition, by interventive measures, results in therapeutic benefits.

Anemia, Sickle Cell↗

PubMed1998

Elevated homocysteine levels indicate suboptimal folate status in pediatric sickle cell patients.

We investigated whether pediatric patients with sickle cell disease (SCD) (9 +/- 4 years; 27 homozygous SCD [HbSS]; 19 sickle-C disease [HbSC]) have different folate status compared with age-, sex-, and race-matched normal hemoglobin (HbAA) controls (n = 20), and whether their folate status can be improved by folate supplementation. The patients were supplemented with vitamins B6 and B12 during one week and with folate during the following week. Circulating folate, homocysteine, vitamin B6 and vitamin B12 levels were measured at baseline (patients and controls), after one week and after two weeks (patients). The patients had similar folate, vitamin B6, and vitamin B12, but higher homocysteine levels compared with HbAA controls (12.7 +/- 4.5 vs. 10.9 +/- 3.5 micromol/l; P = 0.04). Vitamin B6 and B12 supplementation did not change their homocysteine levels, but folate supplementation caused a 53% reduction (to 5.7 +/- 1.6). We conclude that patients with SCD have adequate vitamin B6 and B12 status, but suboptimal folate status, leading to elevated plasma homocysteine levels. They may therefore benefit from folate supplementation to reduce their high risk for endothelial damage.

Adolescent↗

PubMed1998

Long-chain polyunsaturated fatty acid status and early growth of low birth weight infants.

UNLABELLED: We correlated arachidonic acid (AA) and docosahexaenoic acid (DHA) status with anthropometric measures and growth rates in a group of low birth weight infants (< or = 2500 g; gestational ages 30-41 weeks; n = 143). AA and DHA status were measured in erythrocytes (RBC) and plasma cholesterol esters (CE) during days 10 to 42. Infants received preterm formula without long-chain polyunsaturated fatty acids (LCP; n = 81), with LCP (n = 29) or maternal milk (n = 33). RBC AA contents on day 10 were correlated (P < 0.05) with birth weight in breast-fed infants and all formula-fed infants, with on day 10 a standard deviation score (SDS) for weight, length and occipito-frontal circumference in all formula-fed infants, and with on day 10 an SDS for length in breast-fed infants. Brain weight was related to RBC DHA and CE DHA contents on both day 10 and day 42 in formula-fed infants. Of the variances of brain growth parameters on day 42, 21-34% were explained by DHA status on day 42 and protein intake from days 10-42. CONCLUSION: We conclude that parameters of early neonatal AA status are related to intra-uterine rather than to post-natal growth. Parameters of post-natal brain growth are related to RBC DHA and CE DHA contents on day 42, and to dietary protein intake. These results point to the importance of dietary DHA for brain growth in the first 6 post-natal weeks.

Anthropometry↗

PubMed1998

Influence of fasting on circulating levels of alpha-tocopherol and beta-carotene. Effect of short-term supplementation.

We investigated the influence of fasting on the levels of alpha-tocopherol in plasma, erythrocytes and platelets, and on plasma beta-carotene. Six apparently healthy adults were subjected to 17-h feed-fasting experiments at various days before, during and after supplementation with alpha-tocopherol (455 mg/day, 41 days) and beta-carotene (25 mg/day, 24 days). Adipose tissue alpha-tocopherol and beta-carotene were measured at regular intervals. Supplementation increased alpha-tocopherol and beta-carotene in all compartments, except for beta-carotene in adipose tissue. Discontinuation caused a rapid return to baseline, except for adipose tissue alpha-tocopherol and plasma beta-carotene. Fasting caused linear increases of free fatty acids, consistent (but small) increases of plasma alpha-tocopherol and inconsistent increases of plasma beta-carotene. There were no fasting-related changes in other compartments. We conclude that fasting is unable to increase alpha-tocopherol and beta-carotene in circulating lipoproteins and cells to a considerable extent, both at baseline levels and after short-term supplementation. Maintenance of high levels may necessitate regular high oral intakes.

Adult↗

PubMed1998

Gamma-linolenic acid does not augment long-chain polyunsaturated fatty acid omega-3 status.

Augmentation of long chain polyunsaturated omega3 fatty acid (LCPUFA omega3) status can be reached by consumption of fish oil or by improvement of the conversion of alpha-linolenic acid (ALA) to LCPUFA omega3. Since gamma-linolenic acid (GLA) might activate the rate-limiting delta-6 desaturation, we investigated whether GLA augments LCPUFA omega3 status. Eight adults received 1.4 g GLA for 4 weeks and subsequently 2.2 g ALA+1.4 g GLA daily during another 4 weeks. Another seven adults received a daily oral dose of 2.2 g ALA for 4 weeks, and subsequently 2.2 g ALA+1.4 g GLA during another 4 weeks. ALA, or ALA+GLA, did not significantly augment EPA and DHA contents. We conclude that the LCPUFA omega3 status can not be improved by supplementation of low dose GLA, neither by co-supplementation of ALA. Poor conversion of ALA to LCPUFA omega3 may be caused by preferential beta-oxidation of ALA, negative feedback of arachidonic acid from the omnivorous diet, or by the low dietary ALA/LA ratio.

Adult↗

PubMed1998

Rat adipose tissue rapidly accumulates and slowly releases an orally-administered high vitamin D dose.

We investigated the effect of oral high-dose cholecalciferol on plasma and adipose tissue cholecalciferol and its subsequent release, and on plasma 25-hydroxyvitamin D (25(OH)D). Female Wistar rats (n 126) received 37.5 micrograms cholecalciferol/d for 14 d and were subsequently studied for a further 88 d. Two subgroups of eighteen rats each were fasted for 3 d immediately after treatment (days 14-17) and at the end of the study (days 98-101). During treatment, plasma cholecalciferol increased rapidly to reach a steady-state. Plasma 25(OH)D and adipose tissue cholecalciferol increased linearly for 1-2 d after treatment. Serum Ca and inorganic phosphate also increased. Subsequently half-lives of plasma cholecalciferol and 25(OH)D, and perirenal and subcutaneous adipose tissue were: 1.4, 22.5, 97.5 and 80.9 d respectively. Fasting, as compared with ad libitum feeding, caused increased plasma free fatty acids, weight loss up to 14% and increased adipose tissue cholecalciferol (nmol/g wet weight). It did not affect plasma cholecalciferol immediately after cholecalciferol treatment, but raised plasma 25(OH)D. Fasting at the end of the study decreased plasma cholecalciferol and increased plasma 25(OH)D. We conclude that orally-administered cholecalciferol rapidly accumulates in adipose tissue and that it is very slowly released while there is energy balance. Fasting causes preferential loss of triacylglycerols from adipose tissue, as opposed to cholecalciferol, but nevertheless augments plasma 25(OH)D. Adipose tissue may act as a 'buffer to functional vitamin D status' by preventing, to a certain extent, unregulated production of 25(OH)D from dietary vitamin D, and by slowly releasing vitamin D under fasting conditions.

Adipose Tissue↗

PubMed1998

Polychlorinated biphenyls in adipose tissue, liver, and brain from nine stillborns of varying gestational ages.

We analyzed polychlorinated biphenyls (PCBs) in s.c. adipose tissue, liver, and brain of nine fetuses who died in utero. Their median (range) gestational ages and birth weights were 34 (17-40) wk and 2050 (162-3225) g. Three fetuses were small for gestational age. The levels of PCB congener nos. 118, 138, 153, and 180, and the sum of these (sigmaPCB), were calculated in terms of tissue total fat content (ng/g fat). The median (range) sigmaPCB (in ng/g fat) amounted to adipose tissue 235 (97-768), liver 198 (67-362), and brain 50 (22-122). Median (range) sigmaPCB levels in liver and brain were 0.8 (0.4-0.9) and 0.2 (0.1-0.3) times, respectively, as high as the sigmaPCB levels in adipose tissue. There were strong relations between sigmaPCB in adipose tissue and sigmaPCB in liver (r=0.98; p < 0.01), and between sigmaPCB in adipose tissue and sigmaPCB in brain (r=0.91; p < 0.01). Adipose tissue, liver, and brain did not show differences in the distribution of congeners 118, 138, 153, and 180, and there was no statistically significant association between tissue PCB levels and gestational age (r varied between 0.22 and 0.47). Median sigmaPCB levels in fetal adipose tissue proved to be comparable with our previously established sigmaPCB levels in mature breast milk of 93 Dutch women (median 414; range 158-969 ng/g of fat). The PCB congeneric distribution of fetal adipose tissue was not different from that of human milk. We conclude that maternal PCBs have a tendency to accumulate notably in fetal tissues with high triglyceride contents. They are easily transferred across the placenta and seem to become equilibrated among the apolar parts of maternal and fetal lipids.

Adipose Tissue↗

PubMed1998

Plasma folic acid cutoff value, derived from its relationship with homocyst(e)ine.

We established the cutoff value for plasma folic acid, using plasma homocyst(e)ine as the functional marker. To do this, we investigated the relationship of the plasma folic acid of 103 apparently healthy adults with their fasting plasma homocyst(e)ine and with their plasma homocyst(e)ine 6 h after oral methionine challenge (100 mg/kg). We also studied the relationship of their plasma folic acid with the decline of fasting plasma homocyst(e)ine after 7 days of folic acid supplementation (5 mg/day). The three approaches suggested a cutoff value of 10 nmol/L. The chances of individuals to significantly (P <0.05) lower their plasma homocyst(e)ine after folic acid supplementation proved significantly higher at plasma folic acid concentrations < or = 10 nmol/L, as compared with folic acid concentrations above this value (odds ratio, 5.02; 95% confidence interval, 1.87-13.73). We suggest adopting a 10 nmo/L plasma folic acid cutoff value on functional grounds.

Adult↗

PubMed1997

Simultaneous determination of polyamines, N-acetylated polyamines and the polyamine analogues BE-3-3-3 and BE-4-4-4-4 by capillary gas chromatography with nitrogen-phosphorus detection.

We describe a method for the profiling of polyamines, N-acetylated polyamines and the polyamine analogues N1,N11-bis(ethyl)norspermine (BE-3-3-3) and 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) in L1210 murine leukaemia cells by capillary gas chromatography with nitrogen-phosphorus detection. The method makes use of four intemal standards. Prepurification comprises deproteinization, isolation with Sep-Pak silica at pH 9.0, conversion to heptafluorobutyryl derivatives and postderivatization organic fluid extraction. Within- and between-series precisions (given as CV.s) for analysis of 1-2x10(6) cells were: putrescine 5.5 and 29.4%; spermidine 1.6 and 7.1%; and spermine 3.2 and 7.6%, respectively. Recoveries relative to the respective internal standards, were in the 70.6-104.7% range. Accuracy and precision of measurements of BE-4-4-4-4 can probably be improved by the introduction of a separate pentamine internal standard. We conclude that the method can be used for studying the effect of BE-3-3-3 and BE-4-4-4-4, and possibly their metabolites, on polyamine homeostasis (biosynthesis, retroconversion, transport, terminal catabolism) and polyamine function.

Acetylation↗

PubMed1997

4-Amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) exerts in vitro growth inhibitory effects that are not only related to S-adenosylmethionine decarboxylase (SAMdc) inhibition.

The competitive S-adenosylmethionine decarboxylase (SAMdc; EC 4.1.1.50) inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) inhibits growth more effectively than the irreversible SAMdc inhibitor 5'-[[(Z)-4-amino-2-butenyl]methylamino]-5'-deoxyadenosine (AbeAdo), while having similar effects on polyamine contents. We hypothesized that growth inhibition by CGP 48664A is not merely accomplished by SAMdc inhibition. Concentration-related growth inhibitory effects of AbeAdo, CGP 48664A and methylglyoxal bis(guanylhydrazone) (MGBG) were investigated in L1210 cells that were additionally exposed to 10 microM AbeAdo. This concentration causes maximal growth inhibition, profound SAMdc inhibition and plateau polyamine contents. Almost complete inhibition of functional SAMdc activity by 10 microM AbeAdo was confirmed by demonstration of poor conversion of tetradeuterated spermidine to tetradeuterated spermine by gas chromatography-mass spectrometry. Increasing AbeAdo did not affect L1210 cell numbers, viability, nor polyamine contents. MGBG proved highly toxic. CGP 48664A did not affect L1210 polyamine contents, but cell numbers and viability decreased dose-dependently to 50% and 70% of control, respectively. We conclude that CGP 48664A inhibits L1210 growth not only through SAMdc inhibition, but also by an as yet poorly understood second effect with higher IC50. The alleged second effect of CGP 48664A appears important for its potent antitumor effect.

Adenosylmethionine Decarboxylase↗

PubMed1997

Catecholaminergic development of fetal rat ventral mesencephalon: characterization by high-performance liquid chromatography with electrochemical detection and immunohistochemistry.

We determined dopamine (DA), noradrenaline (NA), and adrenaline (A), as well as immunohistochemically stained tyrosine hydroxylase (TH) and DA in dissected rat ventral mesencephalon (VM) tissue from Embryonic Day (ED) 14 to Postnatal Day (P) 17. Whole VM tissue DA, NA, and A contents increased with advancing age. VM DA/protein increased from ED15 to ED16, whereas NA/protein increased from ED15 to ED16 and from ED20 to P4. VM DA/NA ratio increased from ED14 to ED15 and decreased from ED18 to P4. VM cell suspensions exhibited higher DA/NA ratios than whole VM tissue. Washed cell suspensions had higher DA/NA than unwashed counterparts. We conclude that data from both VM immunohistochemistry and catecholamine assays relate to VM development. VM DA is contained mainly in cells, whereas VM NA is located in fibers that channel at the dorsal side of the VM. Determination of tissue catecholamine contents may be helpful for the biochemical characterization of tentatively identified VM grafts.

Animals↗