Pharmacological observations on phyllomedusin.
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Biomedical subjects
Publications and source records attributed to A Anastasi.
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1. The South American amphibian Phyllomedusa sauvagei contains in its skin large amounts of a polypeptide closely resembling caerulein in its pharmacological actions. This polypeptide, called phyllocaerulein, was obtained in a pure form, and upon acid hydrolysis, enzymic digestion and end-group determination experiments it proved to be a nonapeptide of the following composition Pyr-Glu-Tyr(SO(3)H)-Thr-Gly-Trp-Met-Asp-Phe-NH(2)It may be seen that caerulein and phyllocaerulein have in common the C-terminal heptapeptide and the N-terminal pyroglutamyl residue.2. Phyllocaerulein is indistinguishable from caerulein even in parallel bioassay. However, the former polypeptide seems to be somewhat more potent than the latter on all the preparations tested.3. In different batches of Phyllomedusa sauvagei skin the phyllocaerulein content ranged between 150 and 600 mug/g of fresh tissue.Phyllocaerulein or similar polypeptides occur also in the skin of several other Phyllomedusa species, among which are Phyll. burmeisteri, Phyll. dachnicolor, Phyll, helenae, Phyll. annae, Phyll. callidryas and Phyll. bicolor.4. The qualitative identification and quantitative estimation of caerulein-like polypeptides in crude skin extracts may be complicated by the concomitant occurrence of other active polypeptides. These, however, are poorly effective on some test preparations which seem to respond selectively to caerulein.5. Like that of caerulein, the biological significance of phyllocaerulein is completely obscure.
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The levels of expression of histocompatibility antigens on the cell membrane and their gene expression in non-metastatic and in highly metastatic Friend leukemia cells (FLC) were measured and the levels of expression of these antigens were correlated with the different in vivo behaviour of the tumor cells. Highly metastatic in vivo passaged FLC (either interferon-sensitive 745 or interferon alpha/beta-resistant 3Cl-8 cells) expressed higher levels of class I H-2K and H-2D antigens on their cell membrane with respect to the non-metastatic in vitro passaged counterparts. The increased expression of H-2 class I antigens was associated with an increased transcription of H-2K and H-2D genes. As both in vitro and in vivo passaged FLC have been shown to be resistant in vitro to the natural killer (NK) cell activity, we tried to correlate the levels of expression of histocompatibility antigens with the in vivo clearance of [125I]UDR-labeled FLC. However, no correlation was found between the levels of expression of H-2 antigens and the in vivo clearance of tumor cells. In fact, in vivo passaged FLC (tested either after 1 or after 15 in vitro passages) expressed virtually identical levels of H-2 antigens; however, the freshly explanted in vivo passaged FLC exhibited markedly lower levels of clearance from the lung, spleen and liver (when injected i.v. in DBA/2 mice) with respect to the corresponding FLC cultivated for several passages in vitro. Pretreatment of in vitro passaged 745 FLC with either interferon alpha/beta or interferon gamma resulted in the acquisition of some metastatic potential of FLC to the liver when interferon-treated FLC were subsequently injected i.v. in DBA/2 mice; such in vitro treatments resulted in a 2-3-fold increase in the expression of H-2K antigens versus the control untreated FLC. We suggest that such increases could represent some advantages for the homing properties of tumor cells and/or for the tumor progression, by mechanisms different from the resistance to the NK cells.
Surgical treatment of familial adenomatous polyposis (FAP) is still controversial. From 1984 we carried out a prospective evaluation of total colectomy with ileorectal anastomosis (IRA) and restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) to determine differences in postoperative complications, functional results, occurrence of desmoids, and recurrence of polyps in the rectal stump. IRA was performed below the peritoneal reflection and was indicated in the absence of rectal cancer and in the presence of fewer than 10 polyps or minute polyposis in the last 10 cm of the rectal mucosa. IRA patients underwent a regular endoscopic follow-up and prolonged sulindac administration (100 mg twice daily). When criteria for IRA were absent, IPAA was performed adopting a manual anastomosis at the pectinate line. Fourteen patients were operated with IRA and 24 with IPAA. There was no difference in sex and age between the two groups of patients. The number of rectal polyps was significantly different in the two groups. Immediate postoperative complications were observed in only five IPAA patients, three of whom (12%) required reoperation. Late postoperative complications occurred more frequently in IRA patients (14%) than in IPAA patients (4%). Desmoids developed in both groups (five in the IRA group and four in IPAA group). The number of bowel movements was similar in both groups, but 25% of IPAA patients complained of nocturnal fecal soiling. Fulguration or polypectomy for recurrent polyps was necessary in all but two IRA patients at follow-up. The rectal stump was easily eradicated by polyps in all but four patients with minute polyps at surgery. In the latter patients a diffuse or carpeting rectal polyposis occurred. IPAA can give optimum control of colorectal polyposis in FAP patients with an acceptable incidence of postoperative complications and satisfactory functional results. This type of surgical procedure is indicated in most FAP patients, and IRA should be reserved for patients without polyps or with fewer than 10 polyps in the rectal stump; otherwise growth of polyps cannot be adequately controlled.
Restorative proctocolectomy with ileal-anal anastomosis can induce a duodenal stenosis due to the compression between superior mesenteric artery (SMA) and aorta when the ileum is pulled-down to the anus stretching the SMA. This situation may require prolonged nasogastric intubation or even surgery. In our experience this occurred in 10% of pts. Aiming to avoid this complication we have performed an intestinal derotation just before ileal-anal anastomosis abolishing any possibility of duodenal compression. Comparing this latter group of patients to those who didn't receive intestinal derotation, we observed a significant reduction of nasogastric tube drainage and of the nasogastric intubation time. We think that intestinal derotation could be effective in preventing SMA syndrome after restorative proctocolectomy and ileal-anal anastomosis.