DaiS: <<I am out of my mind not being able to read the AUA abstracts. AUA told me they will be on the site later in the month, and Dr Christ is away at present so I cannot check with him.>>
DaiS: Here is a copy of Dr. Christ's abstracts.
BigKNY3
806
GENE THERAPY WITH K CHANNELS PRESERVES ERECTILE CAPACITY IN THE FACE OF DIMINISHED NEURONAL INNERVATION FOLLOWING 12-16 WEEKS OF EXPERIMENTAL DIABETES IN RATS.
George J. Christ, William L. Smith, Cristian Santizo, Yoshi Sato, Weixin Zhao, Nancy S. Day, Mira Valcic, Teresa Sclafani, Jamil Rehman, Ron Bakal & Arnold Melman, Bronx, NY 10461. (Presented by Dr. Christ)
INTRODUCTION AND OBJECTIVES: A recent publication (Christ et al., Am. J. Physiol., 1998) indicates that low efficiency gene transfer is an attractive therapeutic option for the treatment of erectile dysfunction. Since more than 50% of impotent men are diabetic, the goal of the current investigation was to determine if gene-based strategies could be utilized to ameliorate the well-documented decline in erectile capacity observed following induction of experimental diabetes with streptozotocin (STZ).
METHODS: 47 Fisher-344 rats were made diabetic by a single subcutaneous injection of STZ (35 mg/kg). Two months after the diabetic state was established (when significant neuropathy is known to occur), all animals received a single intracorporal injection of naked pcDNA/hSlo cDNA (100 mg in 200 ml final volume). The ICP response to cavernous nerve stimulation was studied 1-2 months later, and the results are displayed below for several levels of current stimulation. Synaptophysin (SN) immunostaining was used to confirm the diabetic neuropathy as described (Rehman et al., Am. J. Physiol., 1997).
RESULTS: SN immunostaining confirmed the presence of significant diabetic neuropathy in the STZ-treated rats. The ICP data are reviewed below.
Table 1. Mean amplitude of the ICP response following cavernous nerve stimulation in STZ-diabetic and hSlo transfected animals, respectively.
CONCLUSIONS: These studies clearly document that K gene therapy can restore the STZ-induced decline in erectile capacity in rats in vivo, and thus, bode well for the use of a similar strategy in man. This work was supported in part by a grant from VIVUS, Inc.
807
THE EXPRESSION OF HSLO TRANSCRIPT IS LARGELY LOCALLY RESTRICTED FOLLOWING INTRACAVERNOUS INJECTION.
Nancy S. Day, Arnold Melman, William L. Smith, Cristian Santizo, Yoshi Sato, Weixin Zhao, Michele E. Day, Frank C. Chen, Mira Valcic, Jamil Rehman, Ron Bakal and George J. Christ, Bronx, NY (Presented by Dr. Christ).
INTRODUCTION AND OBJECTIVES: Previous studies in a rat model have indicated the potential utility of somatic gene therapy for the treatment of erectile dysfunction. A major concern, however, is the disposition and distribution of the recombinant gene. The goal of this study was to examine the time course of expression and the tissue distribution of the recombinant gene product of the pcDNA/hSlo cDNA following a single intracavernous injection in the rat in vivo.
MATERIALS AND METHODS: Rats received a single intracavernous injection of naked pcDNA/hSlo cDNA (100 mg in 100 ml final volume). Tissues were harvested 1, 8, 24 and 48 hours post injection, as well as 1 and 2 weeks, and 1 month after injection. Steady-state levels of the recombinant KCa transcripts were evaluated using RT-PCR. The primer sets for PCR amplification were the code for the first 6 amino acids of hSlo (5'-GCCGCCACCATTTGCAT-3') and the T7 promoter (5'-CCCTATAGTGAGTCGTATTA-3').
RESULTS: Table 1. Tissue distribution of recombinant KCa transcript. The presence of a symbol indicates the detection of transcript in that tissue(s). Distinct symbols represent observations on distinct animals
CONCLUSIONS: Although no attempt was made to restrict blood flow out of the penis, the intracavernous injection of recombinant KCa results in transcript expression that is largely locally confined to the original tissue injection at time points > 24 hours after injection. Supported by a grant from VIVUS, Inc. |
