Effects of Nigella sativa and Lepidium sativum on cyclosporine pharmacokinetics.

The present study was conducted to investigate the effects of Nigella sativa and Lepidium sativum on the pharmacokinetics of cyclosporine in rabbits. Two groups of animals were treated separately with Nigella sativa (200 mg/kg p.o.) or Lepidium sativum (150 mg/kg p.o.) for eight consecutive days. On the 8th day, cyclosporine (30 mg/kg p.o.) was administered to each group one hour after herbal treatment. Blood samples were withdrawn at different time intervals (0.0, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, and 24 hrs) from marginal ear vein. Cyclosporine was analyzed using UPLC/MS method. The coadministration of Nigella sativa significantly decreased the C(max) and AUC(0-∞) of cyclosporine; the change was observed by 35.5% and 55.9%, respectively (P ≤ 0.05). Lepidium sativum did not produce any significant change in C(max) of cyclosporine, although its absorption was significantly delayed compared with control group. A remarkable change was observed in T(max) and AUC(0-t) of Lepidium sativum treated group. Our findings suggest that concurrent consumption of Nigella sativa and Lepidium sativum could alter the pharmacokinetics of cyclosporine at various levels.

Analysis of the SRY gene in two sex-reversed XY sisters identifies two new novel point mutations in the high mobility group box domain.

OBJECTIVE: To determine mutations in the SRY gene in two sisters with 46, XY karyotype. DESIGN: Case report. SETTING: Jamia Millia Islamia, New Delhi, and CSIRO Human Nutrition, Adelaide, Australia. PATIENT(S): Two sisters aged 23 and 27 years old with primary amenorrhea. INTERVENTION(S): Endocrine, mutations in the SRY gene, and DNA binding ability. MAIN OUTCOME MEASURE(S): LH, FSH, and testosterone levels, DNA sequence findings. RESULT(S): We found a new point mutation in the SRY gene in patient 1 at position +275 (A>T), which results in amino acid change (K92M). In patient 2, we found a double mutation in the SRY gene at two different loci. The first mutation is a substitution of C at +352, resulting in a change of amino acid (A118P), and second is deletion of T, resulting in a frame shift within a highly conserved DNA-binding motif-high mobility group box at +379 (T127IfsX179). Electrophoretic mobility shift assay showed that mutant K92M and A118P show reduced and greatly reduced binding ability, respectively. These mutations have the potential to interfere with protein-DNA binding activity and nuclear localization necessary for interactions of these proteins with DNA. CONCLUSION(S): Our results suggest involvement of the SRY gene in sex reversal, which supports the relationship between SRY alterations, gonadal dysgenesis, and/or primary infertility, and provides further evidence of a high-mobility group box significance in DNA-binding/-bending properties.