Renova Retin-A
Differences in the lipoprotein distribution of free and liposome-associated all-trans-retinoic acid in human, dog, and rat plasma are due to variations in lipoprotein lipid and protein content.

Wasan KM, Ramaswamy M, Ng SP, Wong W, Parrott SC, Ojwang JO, Wallace T, Cossum PA.

Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada. Kwasan unixg.ubc.ca

The objective of the proposed study was to determine the distribution in plasma lipoprotein of free all-trans retinoic acid (ATRA) and liposomal ATRA (Atragen; composed of dimyristoyl phosphatidylcholine and soybean oil) following incubation in human, rat, and dog plasma. When ATRA and Atragen at concentrations of 1, 5, 10, and 25 micrograms/ml were incubated in human and rat plasma for 5, 60, and 180 min, the majority of the tretinoin was recovered in the lipoprotein-deficient plasma fraction. However, when ATRA and Afragen were incubated in dog plasma, the majority of the tretinoin (> 40%) was recovered in the high-density lipoprotein (HDL) fraction. No differences in the plasma distribution between ATRA and Atragen were found. These data suggest that a significant percentage of tretinoin associates with plasma lipoproteins (primarily the HDL fraction) upon incubation in human, dog, and rat plasma. Differences between the lipoprotein lipid and protein profiles in human plasma and in dog and rat plasma influenced the plasma distribution of ATRA and Atragen. Differences in lipoprotein distribution between ATRA and Atragen were not observed, suggesting that the drug's distribution in plasma in not influenced by its incorporation into these liposomes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9660998&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Arsenic trioxide: new preparation. Acute promyelocytic leukaemia: encouraging results but persistent doubts.

[No authors listed]

(1) Acute promyelocytic leukaemia is a rare disease. There is a high remission rate after combination treatment with tretinoin and anthracycline, but there is no established treatment for refractory or relapsed disease. Further treatment with tretinoin, combined with intensive cytotoxic chemotherapy, seems to give the best results in patients who qualify for this treatment, but assessment is limited. (2) Arsenic trioxide has now been approved for induction of remission and consolidation in patients with refractory or relapsed acute promyelocytic leukaemia. (3) The clinical evaluation dossier that supported the application contains data from two non comparative trials including 12 and 40 patients. A complete haematological response was obtained in 45 (87%) of the 52 patients, and the survival rate among patients in first relapse was 77% after a median follow-up of two years. These results are similar to those previously obtained with tretinoin plus intensive cytotoxic chemotherapy. (4) All the patients treated with arsenic trioxide experienced adverse events. This was to be expected given the acute and chronic toxicity of arsenicals. Most events included fatigue, gastrointestinal disturbances, peripheral neuropathies, prolongation of the QT interval; and biochemical disturbances (hypokalaemia, hyperglycaemia, elevated transaminase activity). (5) Like tretinoin, arsenic trioxide can provoke a potentially severe leukocyte activation syndrome. (6) In practice, these encouraging data justify further assessment of arsenic trioxide. This drug is already an option for patients with refractory or relapsed disease who cannot receive tretinoin plus intensive chemotherapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15532137&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Comparison of topical therapy for striae alba (20% glycolic acid/0.05% tretinoin versus 20% glycolic acid/10% L-ascorbic acid).

Ash K, Lord J, Zukowski M, McDaniel DH.

Department of General Surgery, Naval Medical Center, Portsmouth, Virginia, USA.

BACKGROUND: Topical treatment of striae rubra with 0.1% tretinoin and laser treatment of striae rubra and alba with the 585-nm pulsed dye laser are proven therapeutic options. However, little efficacy has been shown for treatment of striae alba topically, and the laser is currently not a suitable treatment option for darker ethnic skin types. OBJECTIVE: The purpose of this study was to demonstrate that selected commercial topical agents can improve the appearance of striae alba. METHODS: Ten patients of varying skin types (I-V) having straie distensae alba on the abdomen or thighs were selected to evaluate the effectiveness of two topical treatment regimens. Patients were placed on daily topical application of 20% glycolic acid (MD Forte) to the entire treatment area. In addition, the patients applied 10% L-ascorbic acid, 2% zinc sulfate, and 0.5% tyrosine to half to the treatment area and 0.05% tretinoin emollient cream (Renova) to the other half of the treatment area. The creams were applied on a daily basis for 12 weeks. Improvement was evaluated at 4 and 12 weeks in an objective unblinded fashion at the follow-up visits, a objective blinded fashion by visual grading at the conclusion of the study, and in an objective blinded fashion with profilometry. Additionally, histopathologic analysis was performed. RESULTS: Analysis of these data reveals: 1) both regimens can improve the appearance of stretch marks; 2) these topical therapy regimens are safe and effective in study patients with minimal irritation; 3) elastin content within the reticular and papillary dermis can increase with topical 20% glycolic acid combined with 0.05% tretinoin emollient cream therapy; 4) both regimens increased epidermal thickness and decreased papillary dermal thickness in treated stretch marks when compared with untreated stretch marks; 5) combined epidermal and papillary dermal thickness in stretch marks treated with either topical regimen approaches that of normal skin; and 6) profilometry can objectively measure differences in skin texture associated with striae treatments when compared to controls, however, it is not sensitive enough to justify comparison or quantitative improvements between similarly effective treatments.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9723049&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Inhibition of ribonuclease P activity by retinoids.

Papadimou E, Georgiou S, Tsambaos D, Drainas D.

Department of Biochemistry, School of Medicine, University of Patras, 26500 Patras, Greece.

The effect of two naturally occurring (retinol and all-trans retinoic acid) and two synthetic (isotretinoin and acitretin) analogs of vitamin A (retinoids) on tRNA biogenesis was investigated employing the RNase P of Dictyostelium discoideum as an in vitro experimental system. RNase P is an ubiquitous and essential enzyme that endonucleolytically cleaves all tRNA precursors to produce the mature 5' end. All retinoids tested revealed a dose-dependent inhibition of RNase P activity, indicating that these compounds may have a direct effect on tRNA biogenesis. Detailed kinetic analysis showed that all retinoids behave as classical competitive inhibitors. The Ki values determined were 1475 microM for retinol, 15 microM for all-trans retinoic acid, 20 microM for isotretinoin, and 8.0 microM for acitretin. On the basis of these values acitretin is a 184, 2.5, and 1.9 times more potent inhibitor, as compared with retinol, isotretinoin, and all-trans retinoic acid, respectively. Taking into account that retinoids share no structural similarities to precursor tRNA, it is suggested that their kinetic behavior reflects allosteric interactions of these compounds with hydrophobic site(s) of D. discoideum RNase P.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9733726&dopt=Abstract tretinoin Retin-A Renova