WoundCur® Gel

Severe burns and scalds almost always result in unsightly hypertrophic scarring. Among the important processes involved in scarring are fibroblast formation and transformation of fibroblasts into myofibroblasts. Myofibroblasts contain α-smooth muscle actin which has contractile properties and can lead to wound contraction and hypertrophic scarring.

Phosphorylase kinase (PhK), expressed within 5 mins of injury, is among the earliest

enzymes released after tissue damage. It is responsible for activation of NF-kB, which in turn activates over 200 different genes related to inflammation, fibroblastic proliferation, myofibroblast conversion, and eventual scar tissue formation. The sequence and approximate timing of events following injury include the following: activation of PhK (5 mins), followed by appearance of neutrophils (30 mins), macrophages (hours to days), fibroblasts (1 week) and myofibroblasts (2 weeks). 

Cytokines and growth factors secreted by macrophages include fibroblast growth factor (FGF) and transforming growth factors α and β (TGFα and TGFβ). Fibroblast growth factor is responsible for fibroblastic proliferation, and TGFβ1 for conversion of fibroblasts into myofibroblasts. After thermal injury, the use of topical curcumin, a non-competitive, selective PhK inhibitor that blocks PhK activity upstream of NF-kB activation, was found to be associated with more rapid and improved skin healing, as well as less severe or absent scarring.

Phosphorylase kinase (PhK) is a unique enzyme in which the spatial arrangements of the specificity determinants can be manipulated to allow the enzyme to recognize substrates of different specificities. In this way, PhK is capable of transferring high energy phosphate bonds from ATP to serine/threonine and tyrosine moieties in serine/threonine kinases and tyrosine kinases, thus playing a key role in the activation of multiple signaling pathways.

Phosphorylase kinase is released within five minutes following injury and is responsible for activating inflammatory pathways in injury-activated scarring following burns. In photodamaged skin, PhK plays an important role in promoting photocarcinogenesis throughactivation of NF-kB-dependent signaling pathways with inhibition of apoptosis of photodamaged cells, thus promoting the survival of precancerous cells and allowing for subsequent tumor transformation. Curcumin, the active ingredient in the spice, turmeric, is a selective and non-competitive PhK inhibitor. By inhibition of PhK, curcumin targets multiple PhK-dependent pathways, with salutary effects on a number of skin diseases induced by injury. In this paper, we show that curcumin gel produces rapid healing of burns, with little or no residual scarring. Curcumin gel is also beneficial in the repair of photo-damaged skin, including pigmentary changes, solar elastosis, thinning of the skin with telangiectasia (actinic poikiloderma), and premalignant lesions such as actinic keratoses, dysplastic nevi, and advanced solar lentigines, but the repair process takes many months.

Background: Phosphorylase kinase (PhK) activity is induced by injurious stimuli, which is known to precipitate psoriasis.We had previously reported that elevated PhK activity in psoriatic epidermis correlated with increased psoriatic activity, and that suppression of PhK activity by its inhibitor, curcumin gel, correlated with disease resolution.

Objective: We evaluated the efficacy of a strategy of combining PhK inhibition by topical curcumin with elimination ofPhK-generating precipitating factors from various injurious stimuli in producing improvement of psoriatic activity, aiming at complete resolution. Patients and Methods: We studied a cohort of 647 consecutive patients with mild to severe psoriasis in a single center. Our therapeutic regimen consisted of curcumin gel, topical steroids, strict avoidance of contact allergens, avoidance of dairy products in lactose-intolerant patients, and treatment of infections to eliminate bacterial superantigens. Results: PASI scores at 0 wk was 24.7 +/– 17.1 (SD), n = 647. PASI scores improved significantly at 4 weeks to 11.5 +/– 8.1 (n = 638; p < 0.0001), at 8 weeks to 4.5 +/– 4.2 (n = 636, p < 0.0001), and at 16 weeks to 0.9 +/– 2.5 (n = 641, p < 0.0001). At 16 weeks, 72.2% of patients were completely clear of psoriatic activity (PASI = 0). Conclusion: Our results indicate that a regimen of PhK inhibition by topical curcumin with elimination of PhK-generating factors is effective in producing significant reduction of psoriatic activity at 16 weeks, with complete clearance of psoriasis in 72.2% of patients.

Recent advances in topical hyperbaric oxygen technology identified the use of low- pressure topical hyperbaric oxygen therapy in enhancing wound healing. This study prospectively examined the feasibility of technology transfer from university to Health Maintenance Organization personnel, using topical hyperbaric oxygen therapy to heal necrotic wounds. 

Fifteen patients with 24 gangrenous and/or necrotic wounds that did not improve or worsened after at least 6 weeks of standard wound care were treated with topical hyperbaric oxygen therapy by trained HMO personnel. Four patients underwent digital amputation for osteomyelitis and/or gangrene followed by topical hyperbaric oxygen therapy. Assessment parameters included wound healing and cost of wound care before and after topical hyperbaric oxygen therapy. Six of the six Level 2 wounds healed within 2 to 4 weeks, nine of the ten Level 3 wounds healed within 4 to 10 weeks, and seven of the eight Level 4 wounds healed within 4 to 12 weeks. The ulcers improved by a mean of 0.829 cm2 per day. T test (SSPS 7.5) showed significant improvement per day after topical hyperbaric oxygen therapy, t = 5.217, df = 24, P < 0.0001 (95% CI = 1.13 – 0.49). Wound healing with topical hyperbaric oxygen therapy was associated with decreased costs. The results of this support the feasibility of transfer of new wound healing technology from research to HMO personnel.