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Brymonidyna na twarz - Tajemnicze Piękno Naturalnej Pielęgnacji
Biochemical Study
A total of 100 μL of plasma/urine study samples, calibrators, and QCs were added to 300 μL of IS working solution (acetonitrile containing IS 2 ng/mL for plasma sample processing and 100 ng/mL for urine sample processing). After centrifugation, supernatants were transferred into other tubes and then evaporated until dry. The residues were reconstituted with 100 μL of mobile phase and finally transferred into vials for UPLC-MS/MS analysis. Altogether, 10 μL of the sample was injected into the ion source. More details on the calibrator and quality control materials, sample preparation, and UPLC-MS/MS analysis are fully reported in the Supplementary Materials.
The UPLC/MS/MS analysis performed on the urine sample revealed 8.40 ng/mL brimonidine concentration levels, supporting the initial clinical suspicion. The chromatograph in Figure 2 clearly highlights the presence of brimonidine in the patient’s urine sample.
Chromatographic separation of (A) brimonidine (quantifier), (B) brimonidine (qualifier), and (C) internal standard brimonidine-d4 in urine sample of the study child.
The clinical suspicion was further supported by the analysis of the patient’s plasma sample with brimonidine concentration levels of 0.79 ng/mL, as shown in the chromatograph reported in Figure 3 .
Chromatographic separation of (A) brimonidine (quantifier), (B) brimonidine (qualifier), and (C) internal standard brimonidine-d4 in plasma sample of the study child.
INTRODUCTION
Brimonidine is a selective α2A‐adrenergic agonist (1) that is synthesized from a quinoxaline base (2) and exhibits diverse biological activities, such as neuroprotection (3), vasoconstriction (4) and anti‐inflammatory effects (4, 5). It is routinely used to lower intraocular pressure and has also been used to treat facial erythema in patients with rosacea (6) by reversing the vasodilation of superficial blood vessels in the skin (1, 7, 8, 9). Facial flushing, erythema and a burning sensation have all been described as adverse effects of the drug by patients with rosacea (1, 8, 9, 10).
Nizari et al. (3) confirmed the neuroprotective effect of brimonidine in different glaucoma‐related models and demonstrated that this effect is mediated by a soluble amyloid precursor protein. Piwnica et al. (4) used in vitro vascular and ex vivo human skin biopsy neuroinflammation models to show that brimonidine stimulated vasoconstriction of human subcutaneous arteries and vessels with diameters of
MATERIALS AND METHODS
Animals
Hairless female C3.Cg/TifBomTac immunocompetent mice (n = 125), aged 14–22 weeks at the beginning of the experiment, purchased from Taconic (Ry, Denmark) were used in this study. Mice were anesthetized with 0.05 mL of HypDorm (0.158 mg/mL fentanyl citrate, 5 mg/mL fluanisone, 2.5 mg/mL midazolam), tattooed with consecutive numbers on the abdomen and randomized into five groups. Each group was housed in an individual cage with access to water and a standard diet (Table 1 ) and maintained at 23–24°C under a 12‐h light‐dark cycle. This study followed recommendations described by national guidelines. All protocols were approved by national (permit number 2014‐15‐0201‐00096) and institutional ethical committees.
TABLE 1
Treatment schedule and median number of days until 50% of the mice had a first, second, and third tumor.
| Group | Treatment | Irradiation dose (SEDs) | Median days to first tumor (Q3–Q1) † | Median days to second tumor (Q3–Q1) † | Median days to third tumor (Q3–Q1) † |
|---|---|---|---|---|---|
| 1 | 1% brimonidine cream before UVR | 3 | 295 (302–288) | 302 (309–302) | 309 (316–302) |
| P‐value ‡ | 0.000006 | 0.000004 | 0.000001 | ||
| 2 | 0.33% brimonidine gel before UVR | 3 | 267 (295–254) | 281 (295–267) | 288 (295–274) |
| P‐value ‡ | 0.313 | 0.447 | 0.372 | ||
| 3 | 1% brimonidine cream after UVR | 3 | 274 (281–261) | 288 (295–274) | 295 (295–288) |
| P‐value ‡ | 0.252 | 0.172 | 0.080 | ||
| 4 | UVR, no drug treatment (UVR control) | 3 | 267 (274–254) | 274 (281–267) | 274 (288–267) |
| 5 | 1% brimonidine cream | NA | No tumor | No tumor | No tumor |