OBJECTIVETo study the potential function and mechanism of heme oxygenase-1 (HO-1) in regulating platelet reactivity and arterial thrombosis.

METHODSHO-1-deficient (HO-1(-/-)) mice were generated by gene knock-out technique, and the genotyping of the mice was performed by PCR analysis of tail DNA. Thrombus formation was induced by applying FeCl(3) to the exposed carotid artery, and the occlusion time was monitored for each animal. Western blot and chemical assays were used to detect HO-1 and cGMP levels in platelets. Platelet aggregation induced by ADP was also studied.

RESULTSThe difference between mean occlusion time of wild-type mice [(15.56 +/- 1.25) min, n = 16] and HO-1(-/-) mice [(12.85 +/- 0.55) min, n = 14] was not statistically significant. However, after challenge with hemin, which induces HO-1 expression, mean occlusion time was significantly longer in wild-type mice [(16.25 +/- 1.20) min, n = 15] than in HO-1(-/-) mice [(11.96 +/- 0.98) min, n = 19; P < 0.05]. Hemin administration which induced oxidative stress could markedly elevate HO-1 level and cGMP concentration in platelet, while suppress ADP induced platelet aggregation in wild type mice.

CONCLUSIONUnder conditions that stimulate HO-1 production, platelet-dependent thrombus formation is inhibited by HO-1 through the pathway of cGMP expression. It suggests that enhanced platelet HO-1 expression in response to physiological stress may represent an adaptive response mechanism to down-regulate platelet activation under pro-thrombotic conditions.

Animals ; Blood Platelets ; metabolism ; physiology ; Cyclic GMP ; blood ; Female ; Heme Oxygenase-1 ; blood ; genetics ; physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxidative Stress ; physiology ; Platelet Aggregation ; Thrombosis ; metabolism ; physiopathology

INTRODUCTION: Oral ivermectin is an approved first-line option to topical permethrin in Europe and Japan for the treatment of classic scabies, while combination oral ivermectin and topical permethrin is used in clinical practice for extensive or recurrent cases. There is unclear evidence on comparative efficacy and safety.

OBJECTIVES: To review the evidence on efficacy and safety of oral ivermectin versus topical permethrin or its combination in the treatment of classic scabies.

METHODS: We searched PubMed from January 1, 2016 up to August 7, 2021 for systematic reviews that included RCTs comparing oral ivermectin versus topical permethrin or its combination in the clinical treatment of scabies. We described the characteristics of included studies, assessed reporting quality, and summarized results and conclusion.

RESULTS: We included five systematic reviews. Permethrin did not differ from oral ivermectin in cure rate at the 3 to 6-week time point but had an earlier cure at 1-2 weeks. Adverse effects did not significantly diff er and were few, mild, and transient with both treatments. The evidence ranged widely from low to high certainty and mainly came from three moderate-to-high quality systematic reviews. Combination oral ivermectin and topical permethrin was ranked higher in efficacy but lower in safety compared to either drug alone in one moderate validity network meta-analysis.

CONCLUSION: There is varying certainty of evidence suggesting comparable efficacy and safety of oral ivermectin versus topical permethrin. Limited evidence suggest higher efficacy and lower safety of combination oral ivermectin and topical permethrin compared to either drug alone. An updated systematic review and network meta-analysis is warranted.

KEYWORDS: scabies, ivermectin, permethrin, effectiveness, efficacy, safety