Renova Retin-A
Effect of isotretinoin on tooth germ and palate development in mouse embryos.

Balducci-Roslindo E, Silverio KG, Jorge MA, Gonzaga HF.

Discipline of Histology, Faculty of Dentistry of Araraquara, UNESP, Araraquara, SP, Brazil. eleny black.foar.unesp.br

Vitamin A and its derivatives, retinoic acid, tretinoin and isotretinoin, are currently used in dermatological treatments. The administration of high doses of this vitamin provokes congenital malformations in mice: cleft palate, maxillary and mandibular hypoplasia and total or partial fusion of the maxillary incisors. This study compares the tooth germs of the first maxillary and mandibular molars of fetal mice submitted to isotretinoin during organogenesis. Twelve 60-day-old female Mus musculus were divided into two groups on the 7th day of pregnancy: treated group--1 mg isotretinoin per kg body weight, dissolved in vegetable oil, was administered from the 7th to the 13th day of pregnancy; control group--vegetable oil in equivalent volume was administered orally for the same period. On the 16th day of pregnancy, the females were sacrificed, the fetuses were removed and their heads amputated. After standard laboratory procedures, 6-micron thick serial slices were stained with hematoxylin and eosin for optical microscopy examination. The results showed that both groups had closed palates with no reminiscence of epithelial cells; however, the first molar germs of the isotretinoin-treated animals showed delayed development compared to the control animals.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11445913&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Tretinoin and cutaneous photoageing: new preparation. Guaranteed adverse effects!

[No authors listed]

(1) A cream containing 0.05% of tretinoin is approved in France for the treatment of sun-induced skin damage ("photoageing"). (2) Three comparative trials versus the excipient show that the effects of the tretinoin cream are at best limited and slow to occur; furthermore, they disappear on treatment cessation, necessitating long-term use. (3) The 0.05% tretinoin cream has poor local tolerability: most subjects develop irritation and fragile skin, necessitating a longer interval between each application. Systemic adverse effects can occur in some circumstances. (4) There are persistent doubts over safety during pregnancy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11503837&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Liposomes with tretinoin: a physical and chemical evaluation.

Brisaert M, Gabriels M, Matthijs V, Plaizier-Vercammen J.

Laboratory of Pharmaceutical Technology and Physical Pharmacy, Free University of Brussels, Pharmaceutical Institute, Laarbeeklaan 103, 1090, Brussels, Belgium. apobrimy yahoo.com

The comedolytic activity of tretinoin, incorporated in liposomes, is five to ten times higher compared to the conventional preparations and also the local tolerability is much better. This implies the big interest of a study on tretinoin in liposomes. First, the encapsulation capacity of tretinoin in the liposomes was determined. Therefore, a series of liposomes was prepared with different concentrations of tretinoin (1-6 mg/ml buffer) and lipids (100-300 mg/ml buffer) (egg phosphatidyl choline/cholesterol) with buffers pH=5 and 7. These series of liposomes were evaluated microscopically on the presence of tretinoin crystals outside the liposomes. The highest incorporation capacity was obtained using 2 mg of tretinoin and 300 mg of lipids per milliliter of buffer pH=5. The chemical stability of tretinoin in the liposomes, evaluated during 1 year, revealed no remarkable loss in tretinoin content, even when stored at 25 degrees C. The photo-degradation of tretinoin in the liposomes was about two times slower than in castor oil, but tretinoin degraded to approximately 25% of its initial content. The chemical evaluation of the lipid fraction showed no oxidative degradation of the polyunsaturated fatty acids in EPC because the determined concentration of conjugated dienes and hydroperoxides, two oxidative degradation products, was <1%, which is negligible. Finally, the in-vitro release of tretinoin from the liposomes, evaluated with a dialysis technique, was very low, but this is not a problem for topical use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11600303&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Effects of retinoids on the TGF-beta system and extracellular matrix in experimental glomerulonephritis.

Morath C, Dechow C, Lehrke I, Haxsen V, Waldherr R, Floege J, Ritz E, Wagner J.

Department of Nephrology, University of Heidelberg, Heidelberg, Germany.

Transforming growth factor-beta1 (TGF-beta 1) overexpression plays a key role in the glomerular accumulation of extracellular matrix proteins in renal disease. Retinoids have previously been shown to significantly limit glomerular damage in rat experimental glomerulonephritis. Therefore, the effects of all-trans retinoic acid and isotretinoin on the components of the TGF-beta system and extracellular matrix proteins in anti-Thy1.1-nephritis (Thy-GN) were investigated. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans retinoic acid or 40 mg/kg body wt isotretinoin (n = 9 per group) either with a pretreatment (day -2 through 8) or posttreatment protocol (day +3 through 8), i.e., starting before or after induction of Thy-GN, respectively. Urinary TGF-beta 1 excretion was 60% lower in all-trans retinoic acid-treated animals with Thy-GN (P < 0.025). The increase of cortical TGF-beta 1 gene expression in Thy-GN rats was significantly attenuated with all-trans retinoic acid and even more with isotretinoin treatment as compared with untreated animals (P < 0.025). Cortical expression of TGF receptor II, but not receptor I gene expression, was significantly lower in animals treated with all-trans retinoic acid or isotretinoin (P < 0.05). In all-trans retinoic acid-treated animals with Thy-GN, the increase of glomerular TGF-beta 1 protein (P < 0.008) and TGF-beta 1 (P < 0.025) and TGF receptor II mRNA (P < 0.015) was significantly less. Immunohistochemistry revealed less glomerular staining for TGF-beta 1 and TGF receptor II in the presence of all-trans retinoic acid. TGF-beta 1 immunostaining was not restricted to monocytes and macrophages, as indicated by double-staining. Glomerular staining for collagen IV and collagen III was less in animals treated with isotretinoin (P < 0.02 for both) in contrast to all-trans retinoic acid, whereas fibronectin remained unchanged. It was concluded that the beneficial effects of retinoids on glomerular damage are presumably due to a marked reduction in renal TGF-beta 1 and TGF receptor II expression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11675406&dopt=Abstract tretinoin Retin-A Renova