Anja Bohlmann - Academia.edu (original) (raw)

Papers by Anja Bohlmann

Research paper thumbnail of Biotransformation and toxicokinetics of the insect repellent IR3535® in male and female human subjects after dermal exposure

Toxicology Letters, Apr 1, 2013

The absorption and excretion of the insect repellent IR3535 ® was studied in human subjects after... more The absorption and excretion of the insect repellent IR3535 ® was studied in human subjects after dermal application. IR3535 ® was rapidly metabolized to the corresponding acid. Based on the recovery of IR3535 ® free acid, the skin penetration rate of IR3535 ® is 13.3% in humans after dermal application.

Research paper thumbnail of 5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women

The American Journal of Clinical Nutrition, Feb 1, 2002

Background: Elevated plasma total homocysteine (tHcy) is a risk factor for vascular disease and n... more Background: Elevated plasma total homocysteine (tHcy) is a risk factor for vascular disease and neural tube defects. The polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (FADH 2) (MTHFR) influences the tHcy concentration and the response to tHcy-lowering therapy. Supplementation with folic acid (FA) decreases plasma tHcy, but limited data are available on the effect of 5-methyltetrahydrofolate (MTHF). Objective: We evaluated the tHcy-lowering potential of lowdose FA and of MTHF with respect to the MTHFR genotype. Design: In this randomized, placebo-controlled, double-blind study, 160 women received 400 g FA, the equimolar amount of MTHF (480 g, racemic mixture), or a placebo daily during an 8-wk treatment period. Blood samples were collected at baseline and at 4 and 8 wk. Results: Changes in plasma tHcy concentration depended on the supplemented folate derivative and the MTHFR genotype. Supplementation with FA significantly decreased tHcy concentrations by ≥ 13% in women of all 3 genotypes after both 4 and 8 wk. The greatest decrease was 20% (P < 0.05) in the women with the TT genotype after 4 wk. MTHF supplementation also decreased tHcy, but only the women with the CT genotype had a significant decrease after 4 wk (7%; P < 0.05). The largest nonsignificant reduction (15%) occurred in the women with the TT genotype after 4 wk of MTHF supplementation. Conclusions: The response to tHcy-lowering therapy is influenced by MTHFR genotype. Women with the TT genotype seem to benefit the most from supplementation with either FA or MTHF. In women with the CT or CC genotype, FA is more effective than MTHF in lowering plasma tHcy.

Research paper thumbnail of Biotransformation and toxicokinetics of the insect repellent IR3535® in male and female human subjects after dermal exposure

Toxicology Letters, 2013

The absorption and excretion of the insect repellent IR3535(®) was studied in human subjects (fiv... more The absorption and excretion of the insect repellent IR3535(®) was studied in human subjects (five males and five females) after dermal application of approx. 3g of a formulation containing 20% IR3535(®), i.e. the amounts of IR3535(®) applied were between 1.94 and 3.4 mmol/person (418-731 mg/person). Blood and urinary concentrations of IR3535(®) and its only metabolite, IR3535(®)-free acid, were determined over time. In plasma, concentrations of the parent compound IR3535(®) were at or below the limit of quantification (0.037 μmol/L). IR3535(®)-free acid peaked in plasma samples 2-6h after dermal application. Cmax mean values were 5.7 μmol/L in males, 3.0 μmol/L in females and 4.2 μmol/L in all volunteers. Mean AUC values were 41.6, 24.5 and 33.9 μmolL(-1)h in males, females and all subjects, respectively. In urine samples from all human subjects, both IR3535(®) and IR3535(®)-free acid were detectable, however, only very small amounts of IR3535(®) were found. Concentrations of IR3535(®)-free acid were several thousand-fold higher than the parent compound and peaked at the first two sampling points (4h and 8h after dermal application). Overall, IR3535(®) and IR3535(®)-free acid excreted with urine over 48 h representing 13.3 ± 3.05% of the dose applied. Since IR3535(®) is rapidly and extensively metabolized, and IR3535(®)-free acid has a low molecular weight and high water solubility, it is expected that urinary excretion of IR3535(®)-free acid and IR3535(®) represents the total extent of absorption of IR3535(®) in humans. Based on the results of this study, the skin penetration rate of IR3535(®) is 13.3% in humans after dermal application.

Research paper thumbnail of 5,10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects

American journal of medical genetics, Jan 28, 1996

Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) h... more Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) have reduced enzyme activity and increased plasma homocysteine which can be lowered by supplemental folic acid. Thermolability of the enzyme has recently been shown to be caused by a common mutation (677C-->T) in the MTHFR gene. We studied 41 fibroblast cultures from NTD-affected fetuses and compared their genotypes with those of 109 blood specimens from individuals in the general population. 677C-->T homozygosity was associated with a 7.2 fold increased risk for NTDs (95% confidence interval: 1.8-30.3; p value: 0.001). These preliminary data suggest that the 677C-->T polymorphism of the MTHFR gene is a risk factor for spina bifida and anencephaly that may provide a partial biologic explanation for why folic acid prevents these types of NTD.

Research paper thumbnail of Biotransformation and toxicokinetics of the insect repellent IR3535® in male and female human subjects after dermal exposure

Toxicology Letters, Apr 1, 2013

The absorption and excretion of the insect repellent IR3535 ® was studied in human subjects after... more The absorption and excretion of the insect repellent IR3535 ® was studied in human subjects after dermal application. IR3535 ® was rapidly metabolized to the corresponding acid. Based on the recovery of IR3535 ® free acid, the skin penetration rate of IR3535 ® is 13.3% in humans after dermal application.

Research paper thumbnail of 5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women

The American Journal of Clinical Nutrition, Feb 1, 2002

Background: Elevated plasma total homocysteine (tHcy) is a risk factor for vascular disease and n... more Background: Elevated plasma total homocysteine (tHcy) is a risk factor for vascular disease and neural tube defects. The polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (FADH 2) (MTHFR) influences the tHcy concentration and the response to tHcy-lowering therapy. Supplementation with folic acid (FA) decreases plasma tHcy, but limited data are available on the effect of 5-methyltetrahydrofolate (MTHF). Objective: We evaluated the tHcy-lowering potential of lowdose FA and of MTHF with respect to the MTHFR genotype. Design: In this randomized, placebo-controlled, double-blind study, 160 women received 400 g FA, the equimolar amount of MTHF (480 g, racemic mixture), or a placebo daily during an 8-wk treatment period. Blood samples were collected at baseline and at 4 and 8 wk. Results: Changes in plasma tHcy concentration depended on the supplemented folate derivative and the MTHFR genotype. Supplementation with FA significantly decreased tHcy concentrations by ≥ 13% in women of all 3 genotypes after both 4 and 8 wk. The greatest decrease was 20% (P < 0.05) in the women with the TT genotype after 4 wk. MTHF supplementation also decreased tHcy, but only the women with the CT genotype had a significant decrease after 4 wk (7%; P < 0.05). The largest nonsignificant reduction (15%) occurred in the women with the TT genotype after 4 wk of MTHF supplementation. Conclusions: The response to tHcy-lowering therapy is influenced by MTHFR genotype. Women with the TT genotype seem to benefit the most from supplementation with either FA or MTHF. In women with the CT or CC genotype, FA is more effective than MTHF in lowering plasma tHcy.

Research paper thumbnail of Biotransformation and toxicokinetics of the insect repellent IR3535® in male and female human subjects after dermal exposure

Toxicology Letters, 2013

The absorption and excretion of the insect repellent IR3535(®) was studied in human subjects (fiv... more The absorption and excretion of the insect repellent IR3535(®) was studied in human subjects (five males and five females) after dermal application of approx. 3g of a formulation containing 20% IR3535(®), i.e. the amounts of IR3535(®) applied were between 1.94 and 3.4 mmol/person (418-731 mg/person). Blood and urinary concentrations of IR3535(®) and its only metabolite, IR3535(®)-free acid, were determined over time. In plasma, concentrations of the parent compound IR3535(®) were at or below the limit of quantification (0.037 μmol/L). IR3535(®)-free acid peaked in plasma samples 2-6h after dermal application. Cmax mean values were 5.7 μmol/L in males, 3.0 μmol/L in females and 4.2 μmol/L in all volunteers. Mean AUC values were 41.6, 24.5 and 33.9 μmolL(-1)h in males, females and all subjects, respectively. In urine samples from all human subjects, both IR3535(®) and IR3535(®)-free acid were detectable, however, only very small amounts of IR3535(®) were found. Concentrations of IR3535(®)-free acid were several thousand-fold higher than the parent compound and peaked at the first two sampling points (4h and 8h after dermal application). Overall, IR3535(®) and IR3535(®)-free acid excreted with urine over 48 h representing 13.3 ± 3.05% of the dose applied. Since IR3535(®) is rapidly and extensively metabolized, and IR3535(®)-free acid has a low molecular weight and high water solubility, it is expected that urinary excretion of IR3535(®)-free acid and IR3535(®) represents the total extent of absorption of IR3535(®) in humans. Based on the results of this study, the skin penetration rate of IR3535(®) is 13.3% in humans after dermal application.

Research paper thumbnail of 5,10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects

American journal of medical genetics, Jan 28, 1996

Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) h... more Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) have reduced enzyme activity and increased plasma homocysteine which can be lowered by supplemental folic acid. Thermolability of the enzyme has recently been shown to be caused by a common mutation (677C-->T) in the MTHFR gene. We studied 41 fibroblast cultures from NTD-affected fetuses and compared their genotypes with those of 109 blood specimens from individuals in the general population. 677C-->T homozygosity was associated with a 7.2 fold increased risk for NTDs (95% confidence interval: 1.8-30.3; p value: 0.001). These preliminary data suggest that the 677C-->T polymorphism of the MTHFR gene is a risk factor for spina bifida and anencephaly that may provide a partial biologic explanation for why folic acid prevents these types of NTD.