Safety assessment and toxicological profiling of a novel combinational sunprotective dermal formulation containing melatonin and pumpkin seed oil

Ultraviolet (UV) radiation exposure has been known to cause irreparable damages to human skin. The daunting risk of UV radiation exposure faced by military personnel led to the development of a sunscreen formulation which has superior sun protection factor combined with the ability to counteract reactive oxygen species. The present work deals with the preclinical safety evaluation of the sunscreen formulation comprising of four US FDA approved UV filters; namely avobenzone, octinoxate, oxybenzone, titanium dioxide along with melatonin and pumpkin seed oil, via OECD protocols of assessing acute oral and dermal toxicity; skin sensitizing; skin irritating; ocular irritating and genotoxic potential. Both oral and dermal LD₅₀ values were found to be ˃2000 mg/kg body weight in adult Wistar albino rats using acute dermal and oral toxicity tests. The sunscreen formulation was found to be non-sensitizing to the skin of guinea pigs and non-irritating to both skin and eyes of rabbits. The sunscreen formulation was also found to be non-mutagenic which was affirmed by a battery of genotoxicity and muagenicity assays. The results obtained from this preclinical study indicated that the sunscreen formulation is non toxic and safe in animal models. This study along with additional preclinical evaluations may serve as a basis for considering the formulation as a potential candidate for further trials to establish its efficacy, tolerability and applicability.     

Using Geometry for the Dorsiflexory Wedge Osteotomy of the First Metatarsal

Dorsiflexory wedge osteotomy is indicated for the correction of structural and irreducible first metatarsal deformity to effectively shorten and elevate a plantar flexed first ray. This is most commonly due to fixed forefoot valgus deformity, the cavovarus foot type, and diabetic foot pathologic features involving an ulceration or preulcerative area on the plantar aspect of the first metatarsal head. Surgeons can subjectively judge the amount of correction, such as by restoring the frontal plane alignment of the forefoot, or objectively by returning Meary's angle to a parallel relationship on a weightbearing lateral radiograph. With this tip, we propose an objective measurement, with calculation and use of Meary's angle, to preoperatively quantify the amount of desired correction. In the present study, we applied basic geometric principles based on triangles to calculate the relationship between the width of the excised wedge and the angular degrees of achieved dorsiflexion. We hope these data will provide both objective and reasonable estimates for reconstructive foot and ankle surgeons working with these deformities and with this procedure.     

MRI assessment of the intra‐carotid route for macrophage delivery after transient cerebral ischemia

The broad aim underlying the present research was to investigate the distribution and homing of bone marrow‐derived macrophages in a rodent model of transient middle cerebral artery occlusion using MRI and ultrasmall superparamagnetic iron oxide (USPIO) to magnetically label bone marrow‐derived macrophages. The specific aim was to assess the intra‐carotid infusion route for bone marrow‐derived macrophage delivery at reperfusion. Fifteen Sprague–Dawley rats sustained 1 h of middle cerebral artery occlusion. USPIO‐labeled bone marrow‐derived macrophages were slowly injected for 5 min immediately after reperfusion in ischemic animals (n = 7), 1 h after the end of surgery in sham animals (n = 5) and very shortly after anesthesia in healthy animals (n = 3). Multiparametric MRI was performed at day 0, just after cell administration, and repeated at day 1. Immunohistological analysis included Prussian blue for iron detection and rat endothelial cell antigen‐1 for endothelium visualization. Intra‐carotid cell delivery brought a large number of cells to the ipsilateral hemisphere of the brain, as seen on both MRI and immunohistology. However, it was associated with high mortality (50%). The study of sham animals demonstrated that intra‐carotid cell delivery could induce ischemic lesions and may thus favor additional brain damage. The present study highlights severe drawbacks to the intra‐carotid delivery of macrophages at the time of reperfusion in this rodent model of transient cerebral ischemia. Multiparametric MRI appears to be a method of choice to monitor longitudinally the effects of cell infusion, allowing the assessment of both cell fate with the help of magnetic labeling and of potential tissue damage. Copyright © 2012 John Wiley & Sons, Ltd.