Biomedical subjects

Paul Rice

Publications and source records attributed to Paul Rice.

6 recordsLinked to original sources

PubMed2003

Ricin poisoning.

Ricin is a naturally occurring toxin derived from the beans of the castor oil plant Ricinus communis. It is considered a potential chemical weapon. Ricin binds to cell surface carbohydrates, is internalised then causes cell death by inhibiting protein synthesis. Oral absorption is poor and absorption through intact skin most unlikely; the most hazardous routes of exposure being inhalation and injection. Features of toxicity mainly reflect damage to cells of the reticuloendothelial system, with fluid and protein loss, bleeding, oedema and impaired cellular defence against endogenous toxins. It has been estimated that in man, the lethal dose by inhalation (breathing in solid or liquid particles) and injection (into muscle or vein) is approximately 5-10 micrograms/kg, that is 350-700 micrograms for a 70 kg adult. Death has ensued within hours of deliberate subcutaneous injection. Management is supportive. Prophylactic immunisation against ricin toxicity is a developing research initiative, although presently not a realistic option in a civilian context.

Animals↗

PubMed2003

Sulphur mustard injuries of the skin. Pathophysiology and management.

Sulphur mustard is a vesicant (blistering agent), which produces chemical burns with widespread blistering. It was used extensively as a chemical warfare agent in the First World War, and has allegedly been employed in a number of conflicts since then, most recently by Iraq against Iran (1984-1987). The potential further use of mustard in military conflicts and by terrorists remains a significant threat that if realised in practice would result in a large number of casualties with severely incapacitating, partial thickness burns. Such injuries clearly present a huge potential wound care problem. The development and healing of mustard-induced cutaneous injuries has not only been observed in human casualties, but has been studied recently at the microscopic and ultrastructural levels in several animal models. Vesication generally begins on the second day after exposure, and may progress for up to 2 weeks. Wound healing is considerably slower than for a comparable thermal burn, and patients often require extended hospital treatment. The current management strategy is essentially symptomatic and supportive. Recently, two techniques for removing damaged tissue and improving wound healing have been investigated. Mechanical dermabrasion and laser debridement ('lasablation') both produced an increased rate of wound healing in animal models, and may be of benefit in a clinical context.

Animals↗

PubMed2003

Abrin poisoning.

Abrin is a toxic protein obtained from the seeds of Abrus precatorius (jequirity bean), which is similar in structure and properties to ricin. Abrin is highly toxic, with an estimated human fatal dose of 0.1-1 microgram/kg, and has caused death after accidental and intentional poisoning. Abrin can be extracted from jequirity beans using a relatively simple and cheap procedure. This satisfies one criterion of a potential chemical warfare agent, although the lack of large scale production of jequirity seeds means that quantity is unavailable for ready mass production of abrin for weapons. This contrasts with the huge cultivation of Ricinus seeds for castor oil production. At the cellular level, abrin inhibits protein synthesis, thereby causing cell death. Many of the features observed in abrin poisoning can be explained by abrin-induced endothelial cell damage, which causes an increase in capillary permeability with consequent fluid and protein leakage and tissue oedema (the so-called vascular leak syndrome). Most reported cases of human poisoning involve the ingestion of jequirity beans, which predominantly cause gastrointestinal toxicity. Management is symptomatic and supportive. Experimental studies have shown that vaccination with abrin toxoid may offer some protection against a subsequent abrin challenge, although such an approach is unlikely to be of benefit in a civilian population that in all probability would be unprotected.

Abrin↗

PubMed2002

Chemical weapons.

Explore the source record for details and available documents.

Chemical Warfare Agents↗

PubMedDate not supplied

Examination of changes in connective tissue macromolecular components of large white pig skin following application of Lewisite vapour.

The aim of this study was to provide information about the degradative processes that occur in major connective tissue components in skin following exposure of large white pigs to Lewisite vapour. Of particular interest were alterations in glycoproteins, which are known to mediate dermo-epidermal attachment (laminin and type IV collagen) and the main collagen found in the dermis (type III collagen). The immunostaining of transfer blots from skin extracts run on sodium dodecyl sulphate polyacrylamide gel electrophoresis gels revealed no evidence of cross-linking of laminin or of type III or IV collagen. However, there was evidence of a very considerable degradation of laminin and, to a lesser extent, of type IV collagen. Type III collagen did not appear to be degraded in skin exposed to Lewisite. These degradative processes appeared to be more severe than found in previous studies in Yucatan mini-pigs percutaneously exposed to sulphur mustard, in which only laminin was found to undergo partial cleavage rather than wholesale degradation. The results suggest that damage to macromolecular components in the sub-epidermal basement membrane in skin which mediate dermo-epidermal separation processes may be a common feature in the mechanism of action of vesicating agents such as Lewisite and sulphur mustard. It is of interest that the damage to laminin in this study appeared to be more severe than that previously found for sulphur mustard. This suggests that skin can suffer substantial damage yet, in the case of Lewisite exposure, recover relatively quickly. However, Lewisite is not an alkylating agent. Sulphur mustard, in contrast, generates characteristically slow healing lesions, most probably because of its ability to alkylate cell types that normally would be involved in skin regenerative processes.

Animals↗

PubMedDate not supplied

Evaluation of barrier creams against sulphur mustard. I. In vitro studies using human skin.

The purpose of this study was to assess the effectiveness of a range of passive and reactive barrier cream formulations against the chemical warfare agent sulphur mustard (SM) using an in vitro diffusion cell system containing human skin. In general, proprietary formulations were relatively effective under occluded conditions, but ineffective under unoccluded conditions. For example, SM skin absorption rates through occluded control and Stokoderm pre-treated skin were 538 +/- 193 and 200 +/- 51 microg x cm(-2) x h(-1), respectively (p < 0.05). Under unoccluded conditions, control and Stokoderm pre-treated skin absorption rates were 4.41 +/- 1.90 and 36.84 +/- 15.19 microg x cm(-2) x h(-1) (p < 0.05). Novel (perfluorinated) barrier creams were generally more effective under unoccluded conditions; pre-treatment with one formulation led to an 18-fold reduction in skin absorption rate and reduced the total amount of SM penetrated by 95% of the applied dose. Several proprietary formulations also had adverse effects on the effectiveness of the skin decontaminant fuller's earth. The rate (Jss) and total amount (percentage of dose) of SM absorbed through the skin were deemed to be independent parameters of barrier cream performance. These data indicate that (1) perceived conditions of use, (2) compatibility with existing protective equipment and (3) the rate and extent of SM skin absorption must all be taken into account when evaluating barrier creams in vitro.

Administration, Cutaneous↗