Analysis of Pfmdr 1 gene in mefloquine-resistant Plasmodium falciparum.

Drug resistance in Plasmodium falciparum is a serious problem in most endemic areas. Recent studies have suggested the potential involvement of genes in the MDR gene family in resistance to quinoline-containing compounds in P. falciparum. In our present studies, a molecular analysis of pfmdr 1 in isolate strain of P. falciparum, 523a R, from Japanese mefloquine-resistant patient was done to determine the reported association of pfmdr 1 intragenic alleles and mefloquine resistance, and to examine the antimalarial activities of several antimalarial agents against the P. falciparum strain. The antimalarial activities against the strain was decreased susceptibility to mefloquine, artemisinin and halofantrine, in contrast increased susceptibility to chloroquine. The DNA sequence analysis of pfmdr 1 gene in a strain reveled no association of intragenic alleles with mefloquine resistance. Furthermore, the overexpression of pfmdr1 mRNA have been observed and it is about 7.2 times higher than sensitive strain. Our data shows that overexpression of pfmdr1 gene may be associated in mefloquine-resistance mechanism.

Ciliary neurotrophic factor immunoreactivity in rat intramuscular nerve during reinnervation through a silicone tube after severing of the rat sciatic nerve.

The immunoreactivity of ciliary neurotrophic factor (CNTF) and S100 was studied in the degenerating and regenerating intramuscular nerves after the sciatic nerve was severed. The sciatic nerves of male Wistar rats were transected at the midpoint of the thigh, and silicone tubing was used to obtain effective reinnervation. The strong immunoreactivity of CNTF and S100 was observed in the Schwann cell cytoplasm of intramuscular nerves (IMN) and at the neuromuscular junction (NMJ) on the control sections. The CNTF immunoreactivity gradually became weak and indistinct in the Schwann cell cytoplasm after the operation. However, it was recognized again in the IMN at 4 weeks after the operation. On the other hand, the S100 immunoreactivity was continuously observed except at the NMJ through the denervating and reinnervating period. At 12 weeks after the operation, the strong immunoreactivity of both CNTF and S100 was observed again. These findings suggest that the amount of CNTF protein decreased in Schwann cells of the IMN and NMJ during the denervating period and increased during the reinnervating period in proportion to the number of remyelinated Schwann cells after severing of the sciatic nerve. They also suggest that CNTF was more highly correlated than the S100 protein with the reinnervation activity of Schwann cells.