The effects of biotin supplementation on serum and liver tissue biotinidase enzyme activity and alopecia in rats which were administrated to valproic acid.

Valproic acid (VPA) is a widely used and well-tolerable antiepileptic drug in epileptic patients. However, VPA has many side effects dose-dependent or non-dose-dependent. It is reported that VPA treatment may lead to biotin deficiency and low serum and liver tissue biotinidase enzyme activity (BEA). Major clinical manifestations in biotin deficiency are seborrheic dermatitis, dry skin, fine and brittle hair, and alopecia. We aimed to investigate the effects of biotin supplementation on serum and liver tissue BEA and alopecia during VPA therapy. Rats were randomly divided into 4 groups, each consisted of 15 rats (VPA-B1, VPA-B2, VPA, and control). Except the control group, all groups were administrated VPA dose of 600 mg/kg/d per oral (PO) for 60 days with 12h intervals two divided doses. VPA-B1 was administrated biotin dose of 6 mg/kg/d and VPA-B2 was administrated biotin dose of 0.6 mg/kg/d. In the third week of the study, we determined alopecia in the study groups. Alopecia was seen in the subjects of 13.3% of VPA-B1 (n=2), 13.3% of VPA-B2 (n=2), and 40% of VPA (n=6). But statistical significant effect on alopecia by biotin supplementation was not able to be determined between the study groups. In the control group, alopecia was not observed. The ratios of alopecia in the study groups were statistically higher than the control group (p=0.028). Itchiness was more obvious in the study groups compared with the control group. Serum biotin levels of the biotin supplemented groups (VPA-B1 and VPA-B2) were higher than the other groups (VPA and control group). Serum biotin levels of the VPA group were lower than the control group. There were significant decreases in the levels of serum and liver tissue BEA of the study groups compared with the control group. In conclusion we showed that VPA usage reduced the serum and liver tissue BEA and impaired the biotin utilization by affecting the liver. Partial biotinidase deficiency may lead to alopecia. It might be prevented by biotin supplementation in the patients receiving VPA therapy. We considered that further studies are necessary to find out the effective and safe biotin dose.

Evaluation of bone mineral density in children with cerebral palsy.

In the present study, bone mineral density of 40 children with cerebral palsy (study group) and the effects of various risk factors on bone mineralization in these children were investigated by comparing with 40 age-matched healthy children (control group). Weight, height, skinfold thickness, body-mass index measurements, and serum levels of calcium, phosphorus, alkaline phosphatase and 25 OH vitamin D were not significantly different between the study and control groups (p>0.05). The mean bone mineral density value of the study group measured by dual-energy X-ray absorptiometry method at L2-L4 levels of lumbar vertebrae was significantly lower than that of the control group (p<0.05). When the patients in the study group were assessed with respect to ambulation status, pattern of involvement, calcium and energy intakes, and whether or not they had taken and/or were taking a regular physical therapy program, there was a significant difference only between the hemiplegic and tetraplegic patients (p<0.05), while there were no significant differences among the patients who were ambulant versus non-ambulant, who had sufficient versus insufficient calcium and energy intakes, and who did and did not take a regular physical therapy (p>0.05). Although the ambulatory status, quantity of calcium and energy intakes, and the presence or absence of a physical therapy program had no effects on bone mineral density values of the children with cerebral palsy in this study, the exact factors and mechanisms responsible for the reduced bone mineral density in children with cerebral palsy should be investigated in further large-scale studies considering the increased risk of pathological fractures in these patients.