Dermostyx (IB1) - High efficacy and safe topical skin protectant against percutaneous toxic agents.

Prevention of the penetration of toxic agents through the skin is crucial for both military troops and civilian populations. We have developed a novel topical skin protectant (TSP), coded as IB1 and commercially available as Dermostyx protective solution (Rekah Pharm, Israel). The formulation afforded significant protection against chemical warfare agents such as sulfur mustard (SM) and VX (2LD50), pesticides such as parathion and irritants such as acrolein.

Beneficial effects of activated macrophages on sulfur mustard-induced cutaneous burns, an in vivo experience.

Objective: Macrophages are known to have key functions in almost every stage of wound healing and there is evidence for their beneficial effects in treating decubital ulcers and deep sternal wound infections in human. This study aimed to investigate the efficacy of a treatment with activated macrophages on ameliorating acute and long-term sulfur mustard (SM) induced skin injuries in the hairless guinea pig (HGP) model.

Methods: HGP were exposed to SM vapor and treated with either a single or multiple intra-dermal injections of human activated macrophages in suspension (hAMS) into the wound bed.

Anti-VEGF therapy (bevacizumab) for sulfur mustard-induced corneal neovascularization associated with delayed limbal stem cell deficiency in rabbits.

Purpose: To investigate the involvement of VEGF in corneal neovascularization (CNV) following sulfur mustard (SM) exposure and to test the therapeutic effects of bevacizumab (Avastin) in respect to dose, route of administration and timing.

Materials And Methods: Topical bevacizumab (6 or 25 mg/ml, ×2/day) was applied to rabbit eyes, before or after appearance of NV, following SM vapor exposure, and was compared with subconjunctival injection (25 mg/ml, ×2/week) and topical dexamethasone (1%, ×4/day). Treatments were given for 3 weeks.

Endothelial cell damage following sulfur mustard exposure in rabbits and its association with the delayed-onset ocular lesions.

Objective: Ocular injuries following exposure to the toxic agent sulfur mustard (SM) are characterized by acute corneal erosions and inflammation of the anterior segment that may be followed by delayed corneal injuries, expressed clinically by neovascularization and epithelial defects. The present study aimed to investigate the effects of SM on corneal endothelium (CE) during the acute and delayed phase in relation to the development of the long-term pathology.

Methods: Rabbit eyes were exposed to SM vapor.

Characterization of acute and long-term pathologies of superficial and deep dermal sulfur mustard skin lesions in the hairless guinea pig model.

Sulfur mustard induces severe acute and prolonged damage to the skin and only partially effective treatments are available. We have previously validated the use of hairless guinea pigs as an experimental model for skin lesions. The present study aimed to characterize a model of a deep dermal lesion and to compare it with the previously described superficial lesion.

Delayed loss of corneal epithelial stem cells in a chemical injury model associated with limbal stem cell deficiency in rabbits.

Purpose: Ocular injuries following exposure to the chemical agent sulfur mustard (SM) are characterized by acute corneal erosions and inflammation of the anterior segment that may be followed by delayed Partial Limbal Stem Cell Deficiency (LSCD), expressed clinically by corneal neovascularization and epithelial defects. LSCD may derive from direct destruction of limbal stem cells or indirectly from altered limbal stromal niche. The aim of this study was to investigate the mechanism underlying LSCD in SM injuries, focusing on the effects of the chemical on limbal epithelium.

Characterization of acute and long-term sulfur mustard-induced skin injuries in hairless guinea-pigs using non-invasive methods.

Background/purpose: Skin exposure to sulfur mustard (HD) results in erythema, edema and severe injury, which take long time to heal and might impose a heavy burden on the health system. Despite many years of research, there is no treatment that prevents the development of the cytotoxic effects of HD causing acute and prolonged damage to the skin. Therefore, it is of great importance to develop treatments that will ameliorate the extent of injury and improve as well as shorten the healing process.

Ocular injuries following sulfur mustard exposure--pathological mechanism and potential therapy.

Sulfur mustard (SM) is a potent vesicant, known for its ability to cause incapacitation and prolonged injuries to the eyes, skin and respiratory system. The toxic ocular events following sulfur mustard exposure are characterized by several stages: photophobia starting a few hours after exposure, an acute injury phase characterized by inflammation of the anterior segment and corneal erosions and a delayed phase appearing following a clinically silent period (years in human). The late injury appeared in part of the exposed eyes, expressed by epithelial defects and corneal neovascularization (NV), that lead to vision deficits and even blindness.

Subcellular alterations of protein kinase C isozymes in the rat brain after organophosphate poisoning.

The protein kinase C (PKC) signaling pathway has been associated with modulation of N-metyl-D-aspartate receptor activity, motor behavior, learning, and memory, all of which are severely impaired in organophosphate (OP) intoxication. Nevertheless, the role of PKC in OP intoxication is largely unknown. The present study attempted to characterize alterations in the immunoreactivity levels of PKC isozymes expressed in different brain areas in the rat following exposure to the nerve agent sarin (1x LD(50)).

Amelioration of sulfur mustard skin injury following a topical treatment with a mixture of a steroid and a NSAID.

The ability to ameliorate sulfur mustard (HD)-induced oedema by treatment with anti-inflammatory drugs was reported previously after screening four steroids and four non-steroidal anti-inflammatory drugs (NSAIDs) using the mouse ear vesicant model. Following the screening study, one steroid and one NSAID (Adexone and Voltaren) were selected as the most effective, and a mixture of the two was chosen for the present more extensive research. The effect of the combined treatment on clinical, biochemical and histopathological parameters following HD insult was studied.

A topical skin protectant against chemical warfare agents.

Background: Sulfur mustard and VX are potent chemical warfare agents that penetrate rapidly through the skin, causing severe prolonged injuries and sometimes death.

Objectives: To develop a topically applied pretreatment that will act as a barrier and prevent the absorption of these agents through the skin, reducing morbidity and saving life.

Methods: Several formulations were developed and tested in preclinical animal studies in pigs.