Peripheral analgesic activities of peptides related to alpha-melanocyte stimulating hormone and interleukin-1 beta 193-195.

1. The hyperalgesic effects of interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2) were measured in rats. 2. Hyperalgesic responses to IL-1 beta were inhibited in a dose-dependent manner by alpha-melanocyte stimulating hormone (alpha-MSH)-related peptides with the following order of potency: [N1(4),D-Phe7]alpha-MSH greater than alpha-MSH greater than Lys-D-Pro-Val greater than Lys-Pro-Val greater than Lys-D-Pro-Thr greater than D-Lys-Pro-Thr. 3. Hyperalgesic responses to PGE2 were not inhibited by Lys-D-Pro-Thr and D-Lys-Pro-Thr but were inhibited in a dose-dependent manner by the other peptides with the same order of potency as against IL-1 beta. 4. The potencies of [N1(4), D-Phe7]alpha-MSH and alpha-MSH were greatly diminished by deletion of their C-terminal tripeptide, Lys11-Pro-Val13. 5. Nor-binaltorphimine (Nor-BNI) largely reversed the analgesic effects of alpha-MSH, [N1(4), D-Phe7]alpha-MSH, Lys-Pro-Val and Lys-D-Pro-Val indicating that kappa-opioid receptors mediated the analgesic activity of these peptides. 6. Nor-BNI did not antagonize the inhibition by Lys-D-Pro-Thr and D-Lys-Pro-Thr of IL-1 beta evoked hyperalgesia indicating that these peptides were not acting via kappa-opioid receptors.     

A leg ulcer as manifestation of metastatic squamous cell vaginal carcinoma

Cutaneous metastasis of vaginal carcinoma is extremely rare. So far, the total number of reported skin metastasis of vaginal carcinoma is only one. We present another case with an unusual manifestation of vagina carcinoma metastasis: skin metastasis presenting as a leg ulcer on the lower leg.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.