Therapeutic Strategies to Reduce Burn Wound Conversion.

Burn wound conversion refers to the phenomenon whereby superficial burns that appear to retain the ability to spontaneously heal, convert later into deeper wounds in need of excision. While no current treatment can definitively stop burn wound conversion, attempts to slow tissue damage remain unsatisfactory, justifying the need for new therapeutic interventions. To attenuate burn wound conversion, various studies have targeted at least one of the molecular mechanisms underlying burn wound conversion, including ischemia, inflammation, apoptosis, autophagy, generation of reactive oxygen species, hypothermia, and wound rehydration.

Metal chelation attenuates oxidative stress, inflammation, and vertical burn progression in a porcine brass comb burn model.

Oxidative stress and inflammation may mediate cellular damage and tissue destruction as the burn wound continues to progress after the abatement of the initial insult. Since iron and calcium ions play key roles in oxidative stress, this study tested whether topical application of a metal chelator proprietary lotion (Livionex Formulation (LF) lotion), that contains disodium EDTA as a metal chelator and methyl sulfonyl methane (MSM) as a permeability enhancer, would prevent progression or reduce burn wound severity in a porcine model. We have reported earlier that in a rat burn model, LF lotion reduces thermal injury progression.

Thermal injury induces early blood vessel occlusion in a porcine model of brass comb burn.

Burn wound progression is an important determinant of patient morbidity and mortality after injury. In this study, we used the brass comb contact burn to determine burn wound vertical injury progression with a focus on blood vessel occlusion and endothelial cell death. Class A 3-month-old Yorkshire pigs received a brass comb contact burn.

Metal chelation reduces skin epithelial inflammation and rescues epithelial cells from toxicity due to thermal injury in a rat model.

Background: One of the most pervasive complications of burn injury is wound progression, characterized by continuous tissue destruction in untreated wounds, which leads to wound infection, inflammation, oxidative stress and excessive scar formation. We determined whether additional tissue destruction could be attenuated with Livionex formulation (LF) lotion, which contains a metal-chelating agent and reduces inflammation in burn wounds.

Methods: We subjected male Sprague Dawley rats to a 2% total body surface area (TBSA) burn using a brass comb model and topically applied LF lotion (containing ethylenediaminetetraacetic acid and methyl sulfonyl methane) to the affected area every 8 hours over 3 days.

Amelioration of Endotoxin-Induced Inflammatory Toxic Response by a Metal Chelator in Rat Eyes.

Purpose: Metal ions play a key role in exacerbating toxicity associated with oxidative stress and inflammation. This study examines the effects of a formulation containing the metal chelator ethylenediaminetetraacetic acid (EDTA) and permeability enhancer methyl sulfonyl methane (MSM) on the early course of inflammation in endotoxin-induced uveitis (EIU). The proprietary MSM/EDTA formulation of Livionex, Inc.

Febrile ulceronecrotic Mucha-Habermann disease in an 8-year-old boy responding to methotrexate.

Background: Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare fulminant variant of pityriasis lichenoides et varioliformis acuta (PLEVA) characterized by a rapidly progressive course with predominant ulceronecrotic lesions associated with fever and systemic manifestations. First described by Degos in 1966, it carries a high morbidity and is potentially fatal. The exact pathogenesis is not clear, but it is proposed to be the result of hypersensitivity reaction to an infection.

Aneurysm in a Large Sporadic Renal Angiomyolipoma.

Angiomyolipomas (AMLs) are the most common mesenchymal renal neoplasms and are classified as neoplasms of perivascular epithelioid cells (PEComa). AML is usually a benign neoplasm arising most often in the kidney although it has been described in a wide variety of sites. Most patients are adults, and one-third suffer from tuberous sclerosis.

Attenuation of p38α MAPK stress response signaling delays the in vivo aging of skeletal muscle myofibers and progenitor cells.

Functional competence and self-renewal of mammalian skeletal muscle myofibers and progenitor cells declines with age. Progression of the muscle aging phenotype involves the decline of juvenile protective factorsi.e.

Topically applied metal chelator reduces thermal injury progression in a rat model of brass comb burn.

Unlabelled: Oxidative stress may be involved in the cellular damage and tissue destruction as burn wounds continues to progress after abatement of the initial insult. Since iron and calcium ions play key roles in oxidative stress, this study tested whether topical application of Livionex formulation (LF) lotion, that contains disodium EDTA as a metal chelator and methyl sulfonyl methane (MSM) as a permeability enhancer, would prevent or reduce burns.

Methods: We used an established brass comb burn model with some modifications.

4-Hydroxynonenal in the pathogenesis and progression of human diseases.

Metastable aldehydes produced by lipid peroxidation act as 'toxic second messengers' that extend the injurious potential of free radicals. 4-hydroxy 2-nonenal (HNE), a highly toxic and most abundant stable end product of lipid peroxidation, has been implicated in the tissue damage, dysfunction, injury associated with aging and other pathological states such as cancer, Alzheimer, diabetes, cardiovascular and inflammatory complications. Further, HNE has been considered as a oxidative stress marker and it act as a secondary signaling molecule to regulates a number of cell signaling pathways.

Antidiabetic drug metformin suppresses endotoxin-induced uveitis in rats.

Purpose: To investigate the therapeutic effects of metformin, a commonly used antidiabetic drug, in preventing endotoxin-induced uveitis (EIU) in rats.

Methods: EIU in Lewis rats was developed by subcutaneous injection of lipopolysaccharide (LPS; 150 μg). Metformin (300 mg/kg body weight, intraperitoneally) or its carrier was injected either 12 hours before or 2 hours after LPS induction.

Differential diagnosis of malignant epithelial tumours in the liver: an immunohistochemical study on liver biopsy material.

Introduction: A variety of primary and secondary malignant tumours may present in the liver. In clinical practice the most commonly encountered hepatic tumours are primary hepatocellular carcinoma, metastatic carcinoma and primary cholangiocarcinoma, each with its separate prognostic and management implications. When these tumours are poorly differentiated and the biopsy size is limited to a needle core, the distinction can be extremely difficult.

Preventive effects of ethyl pyruvate on endotoxin-induced uveitis in rats.

Purpose: Recent studies indicate that ethyl pyruvate (EP) exerts anti-inflammatory properties; however, the effect of EP on ocular inflammation is not known. The efficacy of EP in endotoxin-induced uveitis (EIU) in rats was investigated.

Methods: EIU in Lewis rats was developed by the subcutaneous injection of lipopolysaccharide (LPS; 150 μg).

Aldose reductase inhibition suppresses oxidative stress-induced inflammatory disorders.

Oxidative stress-induced inflammation is a major contributor to several disease conditions including sepsis, carcinogenesis and metastasis, diabetic complications, allergic asthma, uveitis and after cataract surgery posterior capsular opacification. Since reactive oxygen species (ROS)-mediated activation of redox-sensitive transcription factors and subsequent expression of inflammatory cytokines, chemokines and growth factors are characteristics of inflammatory disorders, we envisioned that by blocking the molecular signals of ROS that activate redox-sensitive transcription factors, various inflammatory diseases could be ameliorated. We have indeed demonstrated that ROS-induced lipid peroxidation-derived lipid aldehydes such as 4-hydroxy-trans-2-nonenal (HNE) and their glutathione-conjugates (e.

Topical metal chelation therapy ameliorates oxidation-induced toxicity in diabetic cataract.

Oxidative stress plays a critical role in cataractogenesis, the leading cause of blindness worldwide. Since transition metals generate reactive oxygen species (ROS) formation, metal chelation therapy has been proposed for treatment of cataracts. However, the effectiveness of most chelators is limited by low tissue penetrability.

Primary pulmonary botryomycosis presenting with septic shock and acute lung injury.

Botryomycosis is a rare chronic suppurative bacterial infection involving mostly subcutaneous tissues and less frequently other organs. It can be diagnosed by histological examination and culture of the granules. Botryomycosis is mostly caused by Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa but the exact pathogenesis remains uncertain.

[Metabolism and detoxification of the lipid derived aldehyde, 4-Hydroxynonenal in diabetic cataractogenesis in rat].

Objective: To study the metabolism of 4-hydroxynonenal (HNE), one of lipid derived aldehydes (LDAs), in diabetic rat lens and its role in diabetic cataract formation.

Methods: Experimental research. A factor design was used to set up the experiment statistically upon two factors: diabetic and normal control as treatment factors; day 30, 45 and 70 as the time factors.

Assessment of methylsulfonylmethane as a permeability enhancer for regional EDTA chelation therapy.

Pharmacologic chelators do not effectively penetrate cell membranes and blood-brain barrier. This study assesses methylsulfonylmethane (MSM) as a permeability enhancer and an excipient to facilitate EDTA transport across biologic membranes, and to make possible localized, regional chelation. Topical application of MSM with C(14)EDTA onto the rat cornea led to uptake of the C(14)EDTA in all tested ocular tissues.

Molecular cloning and oxidative modification of human lens ALDH1A1: implication in impaired detoxification of lipid aldehydes.

Earlier studies showed that human lens ALDH1A1 plays a critical role in protection against oxidative stress-induced cytotoxicity in human lens epithelial cells (HLEC), and opacification of rat and mouse lens. The complete coding sequence of ALDH1A1 was cloned from human lens cDNA library by using PCR methods and expressed it in Escherichia coli. The cloned human lens ALDH1A1 cDNA encodes a 501-amino-acid protein (molecular mass = 54.

Regulation of CD95 (Fas) expression and Fas-mediated apoptotic signaling in HLE B-3 cells by 4-hydroxynonenal.

The Fas (apo/CD95) receptor which belongs to the TNF-alpha family is a transmembrane protein involved in the signaling for apoptosis through the extrinsic pathway. During this study, we have examined a correlation between intracellular levels of 4-HNE and expression of Fas in human lens epithelial (HLE B-3) cells. Our results show that in HLE B-3 cells, Fas is induced by 4-HNE in a concentration- and time-dependent manner, and it is accompanied by the activation of JNK, caspase 3, and the onset of apoptosis.

Pathogenesis of balls in mature ovarian cystic teratoma. Report of 3 cases and review of literature.

Ovarian cystic teratomas with intracystic balls are rare, and only 11 cases have been reported since 1946. We present 2 new cases and review the literature for the clinical presentation and morphological appearances of the cysts and balls. We also present our histology findings on a third case reported in the international literature.