Topical Simvastatin Research Articles

Topical application of simvastatin acid sodium salt and atorvastatin calcium salt in vitiligo patients. Results of the randomized, double-blind EVRAAS pilot study

Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are focused on systemic medications, while there is only a very limited number of reports on new topical treatment in vitiligo. With their pleiotropic activities statins turned out to be efficient in the treatment of various autoimmune/autoinflammatory disorders. The randomized, double-blind placebo-controlled study of topical administration of the active forms of simvastatin and atorvastatin has been designed to evaluate their efficacy in patients with vitiligo. The study was registered in clinicaltrials.gov (registration number NCT03247400, date of registration: 11th August 2017). A total of 24 patients with the active form of non-segmental vitiligo were enrolled in the study. The change of absolute area of skin lesions, body surface area and vitiligo area scoring index were evaluated throughout the 12 week application of ointments containing simvastatin and atorvastatin. Measurements were performed with planimetry and processed using digital software. Use of active forms of simvastatin and atorvastatin did not result in a significant repigmentation of the skin lesions throughout the study period. Within the limbs treated with topical simvastatin, inhibition of disease progression was significantly more frequent than in the case of placebo (p = 0.004), while the difference was not statistically significant for atorvastatin (p = 0.082). Further studies of topical simvastatin in vitiligo patients should be considered.

Formulation Optimization of Topical Simvastatin Emulgel by Box Behnken Method

Formulation Optimization of Topical Simvastatin Emulgel by Box Behnken Method

621 Topical simvastatin for porokeratosis ptychotropica: A randomized, single-blind, split-body, placebo-controlled investigator-initiated trial

621 Topical simvastatin for porokeratosis ptychotropica: A randomized, single-blind, split-body, placebo-controlled investigator-initiated trial

Topical Simvastatin Improves Lesions of Diffuse Normolipemic Plane Xanthoma by Inhibiting Foam Cell Pyroptosis.

Xanthoma pathogenesis is speculated to be associated with oxidized low-density lipoprotein (ox-LDL) deposition, although this remains unclear. Most patients with diffuse plane xanthomas present elevated blood lipid levels, and they benefit from treatment with oral lipid-lowering agents. However, there is no available treatment for diffuse normolipemic plane xanthoma (DNPX). In this study, for the first time, we used a topical simvastatin ointment to treat DNPX in three pediatric patients and observed favorable results. Immunofluorescence staining showed that the pyroptotic pathway was significantly attenuated after topical simvastatin application on the skin lesions of the patients. As ox-LDL deposition was observed in the lesions, we used ox-LDL to build a foam cell model in vitro. In the ox-LDL-induced foam cell formation, simvastatin consistently inhibited pyroptotic activation and inflammation in the macrophages. Additionally, the overexpression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) or 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase (HMGCR), the known target of statins, reversed the effects of simvastatin. Moreover, gasdermin D (GSDMD) or HMGCR knockdown inhibited ox-LDL-induced pyroptosis. Furthermore, the immunoprecipitation results confirmed the interaction between NLRP3 and HMGCR, and this interaction was inhibited by simvastatin. In conclusion, we demonstrated that topical application of simvastatin ointment might be a promising treatment for DNPX skin lesions and that this therapeutic effect may be related to pyroptosis inhibition via HMGCR inhibition in foam cells. Moreover, xanthoma pathogenesis might be associated with ox-LDL deposition and inflammation.

Preparation and Safety Evaluation of Topical Simvastatin Loaded NLCs for Vitiligo.

Purpose: Vitiligo is a long-term common autoimmune disease in which growing patches of skin lose their color. There is no FDA-approved treatment for vitiligo. However, recent studies have demonstrated an immunosuppressive effect on vitiligo lesions in mouse models by simvastatin. A topical formulation was prepared containing simvastatin-loaded nano lipid carriers (simNLCs) for vitiligo treatment followed by evaluating their physicochemical characteristics and clinical safety. Methods: Both the lipid phase and the aqueous phase were heated to 75°C separately, and then simvastatin was dispersed in the lipid phase added to the aqueous phase. The mixture was homogenized for 1 minute, then for Nanostructured Lipid Carriers (NLC) formation, the emulsion was sonicated using a probe sonicator. The simNLCs produced were evaluated for drug entrapment, particle size and morphology, zeta potential, polydispersity index, viscosity, drug content, in vitro drug release, in vivo skin safety test, and long-term stability studies. Results: Dynamic light scattering, transmission electron microscopy and differential scanning calorimetry techniques proved the formation of a stable formulation containing spherical particles with nanoscale size. The drug entrapment efficiency and the drug-loading capacity were determined to be 99.27% and 3.9%, respectively. Human safety results indicated that adding simvastatin to lipid nanoparticles did not cause any changes to skin biophysical parameters. Conclusion: The preparation method of simNLC developed in this study is a suitable method, and the nanoparticles fabricated were safe with acceptable long-term stability and drug entrapment.

Simvastatin combined with bone marrow mesenchymal stromal cells (BMSCs) improve burn wound healing by ameliorating angiogenesis through SDF-1α/CXCR4 pathway.

Objective(s):Chemokines are wound mediators that promote angiogenesis during wound healing. We hypothesized that Simvastatin in combination with the bone marrow mesenchymal stromal cells (BMSCs) improve burn wound healing by ameliorating angiogenesis via SDF-1α/CXCR4 pathway.Materials and Methods:Under general anesthesia, deep partial-thickness burns were created on the inter-scapular area of 48 male rats. Study groups were administrated with petroleum jelly (Simvastatin Vehicle), a single dose of intradermal BMSCs (1×106), topical Simvastatin (0.5 mg/kg) daily and combination of BMSCs and Simvastatin for 14 days. In this study, we used MTT assay, in vivo and in vitro wound closure, H&E and Trichorome staining, immunohistochemistry (IHC), real- time PCR, Western blot and tube formation assay.Results:A significant improvement in wound closure percentage, epithelial thickness, collagen remodeling, and up-regulation of stromal cell-derived factor 1 alpha (SDF1α), C-X-C chemokine receptor type 4 (CXCR4), protein kinase B (AKT), and phosphatidylinositol 3- kinase (PI3K), as well as CD31 and vascular endothelial growth factor (VEGF) expression were observed after treatment with simvastatin, BMSCs and combination of them compared to the vehicle group. However, the co-treatment group revealed considerable superiority in examined factors. BMSCs treated with Simvastatin showed the highest viability in the concentration of 0.5 and 1 Nanomolar (nM). Increment in proliferation and capillary vessels formation of BMSCs was observed in the 0.5 nM and 1 nM concentrations of Simvastatin in vitro. Conclusion:Treatment of deep partial-thickness of burns with co-treatment of BMSCs and Simvastatin resulted in improved burn wound healing through up-regulating of SDF-1α/CXCR4 pathway.

Effect of Topical Simvastatin Therapy on Patients with Psoriasis

Objective: Study the effect of simvastatin ointment on tissue expression of inflammatory mediators associated with pathogenesis of Psoriasis such as TNF-?, , IL-6 and ICAM-1. Background: Psoriasis is a common and complex inflammatory disease, which was described as the chronic systemic T-cell-mediated inflammatory condition characterized by the skin and joint manifestation. The patients with psoriasis are usually presented with a white-silvery scaly lesion covering various parts of the body. In psoriatic lesions, epidermal Keratinocytes produce a variety of inflammatory mediators, such as TNF-?, IL-6, ICAM-1 will stimulate the abnormal proliferation which will cause the psoriasis characteristics to appear. Simvastatin is an anti-hyperlipidemic agent that acts by competitive, reversible inhibition of the HMG-CoA, the rate-limiting step in cholesterol biosynthesis. Materials and Method: The study has been carried out on 44 patients suffering from mild to moderate chronic plaque psoriasis; patients with plaque psoriasis will be randomly divided into two groups, the first group was the Placebo group (n 22) whose patients have directed to have placebo plus topical steroid (Dermosalic ointment) ® ( Betamethasone dipropionate 0.5 mg /g and salicylic acid 30 mg /g) two times for a period of 8 weeks. The second group was the Simvastatin group (n-22) whose patients have been directed to have Simvastatin ointment 5% two times per day in addition to (Dermosalic ointment)® ( Betamethasone dipropionate 0.5 mg /g and salicylic acid 30 mg /g) for a period of 8 weeks. Before and after the eight weeks; The skin biopsy samples have been taken from patients in the two groups at baseline and after eight weeks of treatment used to measure concentrations of TNF-?, IL-6, and ICAM-1. Conclusion: The present study indicated the fact that Simvastatin ointment plus topical steroid improvement of psoriasis by reduce concentration of inflammatory mediators.

Evaluation of the effects of topically applied simvastatin on titanium implant osseointegration

ObjectiveThe aim of this study was to evaluate the effect of topical simvastatin on the osseointegration of machined-surface titanium implants. Material & methodsSixteen female Sprague–Dawley rats were used in this study in a 4-wk experimental trial. The rats were divided into two groups: a test group (n = 8), in which local simvastatin was applied, and a control group (n = 8). In each of the 16 animals, a machined-surface titanium implant was surgically integrated into the tibial metaphysis. Prior to integration of the implants, 100 μl of ethanol solution containing 5 mg of simvastatin was applied to the bone sockets. The implants were then immediately integrated into the bone sockets. No simvastatin treatment was applied in the control group. At the end of the 4-wk period, the rats were sacrificed, and the implants and surrounding bone tissue were removed. The bone–implant contact (BIC) and bone filling (BF) ratios of nondecalcified histological sections were then determined. The BIC ratio was defined as the ratio of the implant surface directly in contact with the bone to the total implant surface length. The BF ratio was determined by measuring the bone-filled area at a distance of 0.5 mm from implant. ResultsThere were no statistically significant differences in the BIC and BF ratios of the test group and control group in terms of implant osseointegration (p > 0.05). ConclusionWithin the limitations of this study, we conclude that topically applied simvastatin to implant surfaces does not affect osseointegration.

Bone Marrow-Derived Mesenchymal Stem Cells Combined With Simvastatin Accelerates Burn Wound Healing by Activation of the Akt/mTOR Pathway.

Burn wound healing is one of the most important problems in the field of medical science. Promising results have recently been reported by researchers who used bone marrow mesenchymal stem cells (BMSCs) to treat burn wounds. In this study, we investigated the effects of BMSC therapy in combination with simvastatin (SMV) on angiogenesis as well as on the activity of the Akt/mTOR signaling pathway during burn wound healing in rats. After creating second-degree burn wounds, 40 adult male Wistar rats were randomly divided into four treatment groups: the control, SMV, BMSCs, and the combination therapy group (BMSCs+SMV). Animals were killed 14 days after treatment initiation, and the wounds were removed for histological and molecular analyses. All in all, combination therapy produced better outcomes than individual therapy in terms of the wound closure area, epidermal regeneration level, collagen deposition intensity, and reepithelialization rate. In addition, the elevations of expression levels of Akt and mTOR genes, at both mRNA and protein levels, were more pronounced in the BMSCs+SMV group (P < .05, at least, for both qRT-PCR and western blot assessments). qRT-PCR findings also demonstrated that the wounds treated with the combination of BMSCs and SMV had the highest expression levels of CD31 and VEGF genes (P < .01 for all comparisons). These data suggest that the combined administration of BMSCs transplantation and topical SMV has a great potential in burn wound healing. According to the findings, the beneficial effects of the combination therapy are caused, at least in part, through stimulating Akt/mTOR signaling pathway.

Evaluating the Effects of Oral and Topical Simvastatin in the Treatment of Acne Vulgaris: A Double-blind, Randomized, Placebo-controlled Clinical Trial.

Acne vulgaris is a common dermatologic disorder which results in psychological consequences. Inflammatory responses play an important role in the development of inflammatory acne lesions. Recently, many studies have demonstrated anti-inflammatory effects of statins; thus, the aim of this study was to evaluate the efficacy of oral and topical Simvastatin as adjunct therapy in the treatment of acne vulgaris. A total of 76 patients with moderate to very severe acne vulgaris, all receiving oral azithromycin (250 mg, 3 times a week, orally) and topical benzoyl peroxide gel (5%, once daily) were assigned to three groups: 1) Oral group received 20mg/day of oral simvastatin and blank solution, 2) Topical group received simvastatin 1% topical solution and oral placebo, 3) Placebo group received oral placebo and blank solution. The severity of acne was determined by global acne grading system (GAGS) at baseline and after 8 weeks of treatment. Comparing the three groups showed that topical simvastatin was associated with greater decrease in acne severity as compared with those of oral and placebo groups. Moreover, the oral simvastatin appeared to be more efficacious as compared with placebo group (P value<0.001). Oral and topical simvastatin were well tolerated in almost all patients. Although preliminary, the results of this study showed that oral and topical statins, drugs with anti-inflammatory properties, can be considered as effective treatment for acne vulgaris as an adjunct to standard treatment. However, further studies with larger sample size, using improved formulations of topical simvastatin are needed to confirm these results.

Comparative Study of the Effects of Topically Used Insulin and Simvastatin on Thermal Induced Burn in Diabetic Albino Rats

AbstractBackground: Diabetic wound healing is a major compli-cation that may be delayed or impaired. This is resulting from abnormalities in inflammatory and oxidative stress responses, impaired growth factors production, angiogenic responses and collagen deposition.Aim of the Work: The aim of this work was to investigate and compare possible effects of topical insulin and simvastatin on the tissue repair capacity, their anti-inflammatory and anti-oxidant effects.Material and Methods: Sixty male Wister Albino rats were divided into 5 equal groups, group1 normal burned received vehicle, group 2 diabetic burned received vehicle, group 3 diabetic burned received insulin in vehicle, group 4 diabetic burned received simvastatin in vehicle and group 5 diabetic burned received insulin in saline all applied topically. At certain end recording points (3rd, 7th, 14th and 21st days post burning) wound contraction percentage % was calculated and serum tumor necrosis factor-a (TNF-a), blood reduced glutathione and serum malonaldialdehyde (MDA) levels were estimated and dissected burn specimens were prepared for histopathological and immunohistochemical staining for VEGF and a-SMA.Results: Insulin and simvastatin produced more than satisfactory results evidenced by significant improvement in the whole studied parameters.Conclusion: Insulin and simvastatin have anti–inflamma-tory, antioxidant and angiogenic effects improving the healing properties. Although they both in vehicle exhibited similar effectiveness in regard the investigated parameters, they exhibited superiority over insulin in saline.

Topical simvastatin gel as a novel therapeutic modality for palatal donor site wound healing following free gingival graft procedure

Objective: Autogenous soft-tissue grafting is a commonly used procedure nowadays in dentistry. However, the prolonged healing time needed for the donor site leads to increase the patient’s pain and discomfort. Statin has been observed to be beneficial in reducing bacterial burden, improving epithelization and wound healing. The aim of this study was to evaluate intra-oral topical application of simvastatin/chitosan gel (10 mg/mL) over the palatal donor site following free gingival graft (FGG) procedure.Material and methods: Subjects indicated for FGG procedure were divided into four groups. Group I: Simvastatin suspension (S), group II: simvastatin/chitosan gel (SC), group III: chitosan gel (C), group IV: petroleum gel (P). Treatment was applied three times/day for the following 7 days. Wound healing was evaluated at day 3, 7 and 14 post-surgery. A visual analogue scale (VAS) was used to measure the experienced discomfort at 1, 3, 5, 7 and 14 days.Results: Statistical significant reduction in wound-healing scores was observed after 3 and 7 days for group II compared to other groups (p = .015). A significant reduction was also observed in VAS score for group II compared to other groups at day 1, 3, 5 and 7.Conclusion: Topical application of S/C gel could be used as a novel therapeutic modality that improved healing and reduced pain in the palatal donor site following FGG procedure.

Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model

Background:We previously showed that intradermal injection of statins is a successful treatment for hypertrophic scarring. Topical application has many advantages over intradermal injection. In this study, we demonstrate the efficacy of topical statin treatment in reducing scar in our validated rabbit ear scar model.Methods:Twenty New Zealand White rabbits were divided into 2 study groups, with 6 rabbits receiving 10 μm pravastatin intradermally at postoperative days 15, 18, and 21, and 14 rabbits receiving 0.4%, 2%, and 10% simvastatin topical application at postoperative days 14–25. Four or 6 full-thickness circular dermal punches 7 mm in diameter were made on the ventral surface of the ear down to but not including the perichondrium. Specimens were collected at 28 days to evaluate the effects of statins on hypertrophic scarring.Results:Treatment with pravastatin intradermal administration significantly reduced scarring in terms of scar elevation index. Topical treatment with both medium- and high-dose simvastatin also significantly reduced scarring. High-dose simvastatin topical treatment showed a major effect in scar reduction but induced side effects of scaling, erythema, and epidermal hyperplasia, which were improved with coapplication of cholesterol. There is a dose response in scar reduction with low-, medium- and high-dose simvastatin topical treatment. High-dose simvastatin treatment significantly reduced the messenger ribonucleic acid (mRNA) expression of connective tissue growth factor, consistent with our previously published work on intradermally injected statins. More directly, high-dose simvastatin treatment also significantly reduced the mRNA expression of collagen 1A1.Conclusions:Topical simvastatin significantly reduces scar formation. The mechanism of efficacy for statin treatment through interference with connective tissue growth factor mRNA expression was confirmed.

Topical hydrogel matrix loaded with Simvastatin microparticles for enhanced wound healing activity

A prolonged release drug delivery system was developed by loading Simvastatin-chitosan microparticles into poly vinyl alcohol (PVA) hydrogels for enhanced wound healing efficiency. The microparticles prepared by ionic gelation method with varying composition of chitosan and surfactants (Tween 80/Pluronic F-127) were optimized for entrapment efficiency, morphology and drug-polymer interactions. Microparticles prepared with 0.3% between 80 and 0.5:5 chitosan: drug ratio showed maximum entrapment efficiency of 82% with spherical morphology and mild interaction between drug and chitosan. 5% PVA solutions loaded with pure drug and drug loaded microparticles at three different doses (2.5mg, 5mg and 10mg equivalent of drug) were chemically cross linked using gluteraldehyde and HCl. The formulated hydrogels were optimized for swelling, in vitro release behavior and in vivo wound healing effect. Hydrogels containing 2.5mg equivalent dose of Simvastatin microparticles exhibited maximum cumulative percentage drug release of 92% (n=3) at the end of 7days. The in vitro drug release data was supported by the higher swelling index of the low dose hydrogels. The in vivo wound healing study was performed using Wistar rats (n=30, 5 groups with 6 animals in each group) for the formulated hydrogels (at 3 doses) and compared with the untreated animals and the positive control group treated with conventional topical Simvastatin ointment (1%). The wound healing effect was comparable to the in vitro results, wherein the animals treated with low dose hydrogels (replaced every 7days) exhibited considerable reduction in the wound area compared to medium and high dose hydrogels. Statistically significant difference (P<0.05) was observed in the wound area of the animals treated with low dose hydrogels compared to 1% ointment and untreated animals, as estimated by two-way ANOVA. The histopathology images of the different groups of animals also displayed the comparative changes in the wound healing process. Hence, the incorporation of Simvastatin-chitosan microparticles in PVA hydrogels has demonstrated significant wound healing efficiency at optimum dose.

Topical Simvastatin as Host-Directed Therapy against Severity of Cutaneous Leishmaniasis in Mice.

We recently demonstrated that statins mediate protection against intracellular pathogens, Mycobacterium tuberculosis and Listeria monocytogenes in mice. Here, we investigated the immunomodulatory potential of simvastatin as a topical or systemic host-directed drug therapy in controlling inflammatory responses in an experimental mouse model of cutaneous leishmaniasis caused by Leishmania major (LV39). In an ear infection model, topical application of simvastatin directly on established lesions significantly reduced severity of the disease reflected by ear lesion size and ulceration. The host protective effect was further accompanied by decreased parasite burden in the ear and draining lymph nodes in both BALB/c and C57BL/6 mice. Pre-treatment of these mice on a low-fat cholesterol diet and systemic simvastatin also reduced footpad swelling, as well as parasite burdens and ulceration/necrosis in the more robust footpad infection model, demonstrating the prophylactic potential of simvastatin for cutaneous leishmaniasis. Mechanistically, following L. major infection, simvastatin-treated primary macrophages responded with significantly reduced cholesterol levels and increased production of hydrogen peroxide. Furthermore, simvastatin-treated macrophages displayed enhanced phagosome maturation, as revealed by increased LAMP-3 expression in fluorescent microscopy and Western blot analysis. These findings demonstrate that simvastatin treatment enhances host protection against L. major by increasing macrophage phagosome maturation and killing effector functions.

Effect of topical simvastatin (1.2 mg) on gingival crevicular fluid interleukin-6, interleukin-8 and interleukin-10 levels in chronic periodontitis – A clinicobiochemical study

ObjectivesThe impact of simvastatin (SMV), a cholesterol lowering drug, on bone metabolism appears to involve complex interaction with cholesterol metabolites, hormones, inflammatory mediators and growth factors, thus having direct influence on extent and severity of periodontitis. The present study aims to evaluate the in vivo effect of subgingivally delivered SMV gel (1.2mg) as a local drug-delivery agent on clinical parameters and on interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) levels in gingival crevicular fluid (GCF) of chronic periodontitis patients. Materials and methods50 patients were selected and categorized into two treatment groups: control (scaling and root planing) and test group (scaling and root planing with SMV gel). At initial appointment, clinical parameters were measured. Biochemical analysis of GCF samples was done to evaluate the amount of IL-6, IL-8 and IL-10. GCF sampling and clinical parameters were repeated at one and three months for both the groups. ResultsSMV has an inhibitory effect on pro-inflammatory cytokines (IL-6, IL-8) and stimulatory effect on anti-inflammatory cytokines (IL-10) in GCF of periodontitis patients and has significantly positive effect on all clinical parameters except relative attachment level (RAL). The addition of SMV, thereby, further alters the levels of cytokine that reflect enhanced antibacterial host defence activity at that site. ConclusionTopical SMV has a beneficial effect on periodontal health. Removal of the bacterial plaque and subgingival delivery of SMV significantly modulates the chemokines present in GCF. To summarize, SMV shows promising role in the management of periodontitis.

Topical simvastatin promotes healing of Staphylococcus aureus-contaminated cutaneous wounds.

Cutaneous wounds are prompt to be contaminated by bacteria, but the clinical benefits of applying antibiotics and antiseptics in wound management have not been proven. Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors commonly used to lower cholesterol levels. Studies indicated that statins, especially simvastatin, promote wound healing in experimental models. As Staphylococcus aureus is one of the most important microorganism responsible for wound infections, the aims of this study were to characterise the anti-staphylococcal activity of simvastatin and to evaluate the application of simvastatin as a topical therapy for S. aureus-contaminated wounds. In the present study, simvastatin was bacteriostatic against S. aureus at sub-inhibitory concentrations up to 8 hours after exposure. Further increased concentrations of simvastatin above the minimal inhibitory concentration (MIC) did not enhance the growth inhibitory effect. By contrast, the ability of simvastatin to inhibit S. aureus biofilm formation was concentration dependent. Topical application of simvastatin at its MIC against S. aureus accelerated the healing and bacterial clearance of S. aureus-contaminated wounds in an excisional mice wound model. This effective concentration is well below the safe concentration for topical use. Collectively, topical application of simvastatin has the potential as a novel modality for managing wound infections and promoting wound healing.

Efficacy of adding topical simvastatin to topical calcipotriol on improvement of cutaneous plaque psoriasis

Background:Psoriasis is a common dermatologic disorder, with fluctuating response to treatment. Considering the proven immunomodulatory effects of oral simvastatin in psoriasis, this trial study was enrolled to determine whether the topical form has also antipsoriatic effects. Vitamin D analogs known to be effective and are considered the first line of therapy in mild to moderate cases. In this study, the efficacy of topical calcipotriol 0.005% ointment (as a standard method of treatment for psoriasis) versus combination of calcipotriol plus topical simvastatin is compared in the treatment of psoriasis.Materials and Methods:A total of 80 subjects with symmetric psoriasis who had body surface involvement up to 20% were divided randomly into 2 groups. Group A were treated with calcipotriol 0.005% ointment twice daily and Group B with calcipotriol 0.005% ointment twice daily and simvastatin 3% ointment twice daily for 12 weeks. The results were evaluated by a Blind Dermatologist using psoriasis area severity index (PASI) score at baseline, 4th, 8th and 12th week of treatment. In a similar way, a subjective assessment performed by patients based on photo-evaluation at the end of the study.Results:Despite a continuous reduction in PASI score in both groups, according to both physician (P = 0.603) and patient (P = 0.243) assessment topical simvastatin was not statistically more effective than conventional treatment of psoriasis at the end of the study.Conclusion:This study indicates that topical simvastatin is not associated with significant impacts in the treatment of psoriasis as compared to oral form. This study indicates that psoriasis is a systemic disorder with variable skin manifestations.

Topical Application of Slow-Release Simvastatin as a Bone Substitute in Bone Defects in the Rat Tibia: A Pilot Study

It is hypothesized that local application of statins positively affects bone formation. The aim of this study was to evaluate the potential effect of topical slow-release simvastatin as a bone substitute on the healing of bone defects in rat tibia. Granules of slow-releasing hydroxypropyl methylcellulose, with or without simvastatin, were inserted into critical-size defects in the tibiae of 16 rats (8 in the study group, 8 in the control group). Bone static and dynamic histomorphometric variables were examined at 2, 4, 6, and 8 weeks postsurgery. All indices examined in the study group indicated improved healing relative to the control group, although statistical significance was not demonstrated for all variables. In the static histomorphometric analysis, osteoid thickness and volume were significantly higher in the study group, but the fraction of trabecular surface covered with active osteoblasts, the fraction of trabecular surface covered with osteoid, and total calcified bone volume were not significantly higher in the experimental group. In the dynamic histomorphometric analysis, the mineral apposition rate, determined by time-repeated calcein labeling, was significantly higher in the study group than in the control group. Experimental time and dosage effects were observed for most bone values in the study group. The findings indicate that topical application of simvastatin for the treatment of bone defects enhances the process of healing. Dosage and the methodology of administration require further calibration.

Topical simvastatin enhances tissue regeneration in full-thickness skin wounds in rat models.

Wounds and wound healing have always been one of the most important subjects that experimental researches were dedicated to. Simvastatin has been used for long as a common lipid lowering agent which was reported to have some pleiotropic effects such as antioxidation, anti-inflammation and immunomodulation. In this study we aimed to determine the effect of simvastatin on wound healing process in laboratory rats by means of stereological and histopathological analyses. 36 male Sprague-Dawley rats (220 ± 20 g) with a 1 cm(2) circular full-thickness wound on their back were divided into three groups: SS group that received a gel with 2% concentration of simvastatin; UW group that received no treatment but daily irrigation with normal saline; Base group that was treated with the gel base. Duration of the study was 12 days and at the end, wound closure rate, grade of inflammation, granulation-tissue formation, ulceration, epithelization, fibroblast proliferation, collagen-bundles synthesis, and vascularization were determined. Outcome of this study revealed that Simvastatin improves the wound healing by its anti-inflammatory and epithelization induction effect as well as statistically significant induction of fibroblast proliferation and collagen bundle synthesis which were reported by our stereological and histopathological investigations. Results of the present study demonstrated that topical Simvastatin enhances the wound healing process through affecting different aspects of tissue regeneration; however, further researches are needed to find the exact mechanism, advantages and disadvantages of this chemical agent.