The lytic effects of detergent sclerosants on erythrocytes, platelets, endothelial cells and microparticles are attenuated by albumin and other plasma components in vitro.

OBJECTIVE: To investigate the lytic effects of sodium tetradecyl sulphate (STS) and polidocanol (POL) on erythrocytes, platelets, endothelial cells and platelet-derived microparticle (PDMP) formation in vitro and the potential protective effects of serum albumin and agents such as procaine. MATERIALS AND METHODS: The effects of sclerosants were studied in blood samples obtained from normal individuals. Absorbance densitometry was used to assess the lytic effects of sclerosants on blood cells and cultured human microvascular endothelial cells (HMEC) in plasma and in saline. PDMP were quantified by flow cytometry. RESULTS: Haemolysis occurred in whole blood at sclerosant concentrations greater than 0.25% for STS and above 0.45% for POL. Similar concentrations of both agents caused platelet and endothelial cell lysis. Both sclerosants released PDMP at low concentrations but destroyed PDMP at higher concentrations. Albumin significantly reduced the lytic effect of both sclerosants on all cells but had a greater inhibitory effect on POL. Protamine at 0.01% had a neutralising effect on STS, whereas procaine and lignocaine showed no such activity. CONCLUSIONS: Sclerosants at therapeutic concentrations lyse blood cells and endothelial cells in vitro. This effect is strongly reduced by serum albumin possibly contributing towards the low incidence of thromboembolic complications of sclerotherapy.

Responses of periphyton and invertebrates to a tetradecyl-pentadecyl sulfate mixture in stream mesocosms.

Alkyl sulfates (AS) are anionic surfactants widely used in household and personal cleansing applications. Aquatic toxicity of AS under laboratory conditions indicated effects at relatively low concentrations (50-230 microg/L) for some sensitive species. A comprehensive stream mesocosm study of an AS mixture composed of tetra- (C14) and pentadecyl (C15) chain lengths was conducted to better understand effects on microbial and macroinvertebrate populations and communities. A 56-d exposure of AS was performed at concentrations ranging from 57 to 419 microg/L (analytically confirmed exposures) and was accompanied by detailed investigations of periphyton community function (autotrophy, heterotrophy, and metabolism of test chemical), periphyton structure (algal population and community dynamics based on taxonomic identity), and invertebrate structure (benthic abundance, drift, and insect emergence patterns based on taxonomic identity). A no-observed-effect-concentration (NOEC) of 222 microg/L was concluded for several individual algal and invertebrate species based on univariate statistical analyses. An apparent energetic subsidy from C14-15AS at the highest concentrations of 222 to 419 microg/L was observed and tied to changes in microbial community processing of AS when added at these high concentrations. A multivariate analysis based on principal response curves (PRC) indicated that communities in streams exposed to 222 to 419 microg/L were significantly different from the controls leading to an overall (multivariate and univariate) conclusion that 106 microg/L was the ecosystem NOEC. Exposure to AS in the environment has been demonstrated to be in the range of 5 to 21 microg/L in 100% wastewater treatment plant effluent. Potential environmental effects are at least 5 to 20 times above worst-case environmental exposures; therefore, C14-15AS does not pose a risk to the aquatic environment due to normal use patterns.

Effect of intravenous and intraperivenous injections of sclerosants (sodium tetradecyl sulfate and hydroxy polyethoxy dodecan) on the rat femoral vein.

The sclerosant effect of injected tetradecyl sulfate of sodium (STS) and hydroxy polyethoxy dodecan (HPD) was studied in the rat femoral vein. Intravenous (i.v.) and intravenous plus perivenous (i.v. + p.v.) injections of both sclerosants and physiologic saline were compared as to vein lumen occlusion, fibrosis, phlogosis, and damage to the artery and surrounding nervous and muscular tissues. The study was carried out in 30 rats treated by STS, in 30 treated by HPD, and 15 animals were injected with saline. The neurovascular bundle and adjacent muscle were removed at 48 h, 7 and 30 days and examined histologically. I.v. injections of STS produced a solid occlusion of the vein in a significant number of cases, after 30 days (P less than 0.01). A statistically significant number of solid occlusions of the femoral vein resulted after i.v. + p.v. injection of STS and HPD, at 48 h, 7 and 30 days (P less than 0.05; P less than 0.01). There was no significant difference between STS and HPD after i.v. + p.v. injection. After i.v. + p.v. we recorded a marked inflammation of muscle with signs of focal necrosis, at 48 h and 7 days. Our study indicated that i.v. + p.v. injection of STS and HPD provided a high degree of efficacy as regards vein occlusion. On the other hand, i.v. + p.v. injection induced a severe inflammation and necrosis of the tissues surrounding the sclerosed vein. Extrapolating our results to the endoscopic sclerotherapy for esophageal variceal bleeding, we conclude that paravariceal injection of sclerosants is a dangerous procedure, even though efficacious to reduce variceal hemorrhage, owing to the high risk of iatrogenic ulcers and esophageal perforation caused by muscular and mucosal necrosis.

Chemical ablation of the canine kidney using sodium tetradecyl sulfate (Sotradecol). A histopathologic study.

We studied the histopathologic effect of intraarterial Sotradecol (Elkins-Sinn, Inc., Cherry Hill, NJ) on the kidney and examined the mechanism for destruction of renal parenchyma by Sotradecol. Sotradecol was injected into one renal artery distal to an occlusion balloon catheter in six dogs, and the kidneys were removed for histologic examination; four dogs within 20 minutes, and one each at 12 and 24 hours after embolization. The contralateral kidney of each dog underwent the same procedure but was injected with normal saline, and served as control. Histologic examination of the control kidneys was unremarkable. The embolized kidneys revealed extensive endothelial denudation and mural necrosis of the arteries and coagulation necrosis of the renal parenchyma. The changes were evident as early as 20 minutes after embolization, and necrosis became complete by 24 hours. The arteries were filled with red blood cell sludge. Sotradecol produces extensive tissue necrosis and complete renal parenchymal destruction through its direct cytotoxic action on the arterial wall, blood cell elements, and renal parenchyma.

An intravaginal contraceptive device for the delivery of an acrosin and hyaluronidase inhibitor.

A study was begun to develop a contraceptive delivery system that would free the user from precoital or daily administration and utilize a nonhormonal agent as the active ingredient. Testing of such a system in rabbits has led to the development of a device that will release a controlled level of an acrosin and hyaluronidase inhibitor into the vagina. This toroidal device is composed of a core of tetradecyl sodium sulfate (TDSS) incorporated in polyurethane surrounded by a rate-limiting membrane of polyurethane. Such devices had a sustained in vitro TDSS release rate of greater than or equal to 400 micrograms/day for over 30 days. These devices had a complete contraceptive effect in 15 rabbits bred weekly for 4 weeks. The contraceptive effect is due to release of the TDSS into the vagina and the subsequent binding of the TDSS to spermatozoa in the female reproductive tract. TDSS has a very low toxicity profile in the rat, dog, and rabbit.

PIP: A study was designed to determine whether tetradecyl sodium sulfate (TDSS), a potent inhibitor of both acrosin and hyaluronidase, would have a contraceptive effect in rabbits when a controlled level of TDSS was released from a vaginal delivery system over a 4-week period. The toroidal shaped delivery system was composed of a core of TDSS incorporated in polyurethane surrounded by a rate-limiting membrane of polyurethane. These devices were found to have a sustained in vitro TDSS release rate of equal to or greater than 400 mcg/day for over 30 days and had a complete contraceptive effect in 15 rabbits bred weekly for 4 weeks. No toxic effects were noted at 20 mg/day doses, but slight to moderate vaginal irritation was observed in the 50 and 100 mg/day groups. These results clearly demonstrate that TDSS is a useful intravaginal contraceptive agent when incorporated in a delivery system that continuously releases the compound into the vagina. 175 corpora lutea were found in the ovaries of the study rabbits, indicating that TDSS has no effect on ovulation. It remains unknown whether the TDSS binds to all the spermatozoa at the point of TDSS release in the vagina or whether some TDSS finds its way into the oviduct after release into the vagina and finally binds there to the few spermatozoa that reach this site. The vaginal delivery system shown in this study to be efficacious in rabbits could lead to the development of a similar device for human contraception. The advantages of this system are that it frees users from daily or postcoital administration, is capable of self-insertion, and uses a nonhormonal agent as the active ingredient.