keratolytic agents


Summary: Agents that soften, separate, and cause desquamation of the cornified epithelium or horny layer of skin. They are used to expose mycelia of infecting fungi or to treat corns, warts, and certain other skin diseases.

Top Publications

  1. Ming A, Happle R, Grzeschik K, Fischer G. Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome due to mutation of the gene MBTPS2 in a large Australian kindred. Pediatr Dermatol. 2009;26:427-31 pubmed publisher
    ..We describe the clinical features and discuss the differential diagnosis of IFAP. Our proband has benefited from treatment with acitretin...
  2. Fluhr J, Cavallotti C, Berardesca E. Emollients, moisturizers, and keratolytic agents in psoriasis. Clin Dermatol. 2008;26:380-6 pubmed publisher
    Emollients, moisturizers, and keratolytic agents are essential in the topical treatment of psoriasis. They are adjuvants for classic treatments and help to reduce the scale load of individual patients...
  3. Kang S, Fisher G, Voorhees J. Photoaging: pathogenesis, prevention, and treatment. Clin Geriatr Med. 2001;17:643-59, v-vi pubmed
    ..This article summarizes evidence mainly from studies of human volunteers that provide the basis for the current model of photoaging and the effects of tretinoin. ..
  4. Machtinger L, Kaidbey K, Lim J, Loven K, Rist T, Wilson D, et al. Histological effects of tazarotene 0.1% cream vs. vehicle on photodamaged skin: a 6-month, multicentre, double-blind, randomized, vehicle-controlled study in patients with photodamaged facial skin. Br J Dermatol. 2004;151:1245-52 pubmed
    ..001). Treatment of photodamaged skin with tazarotene is associated with an amelioration of keratinocytic and melanocytic atypia, an improvement in epidermal polarity, and an increase in epidermal thickness. ..
  5. Kang S, Bergfeld W, Gottlieb A, Hickman J, Humeniuk J, Kempers S, et al. Long-term efficacy and safety of tretinoin emollient cream 0.05% in the treatment of photodamaged facial skin: a two-year, randomized, placebo-controlled trial. Am J Clin Dermatol. 2005;6:245-53 pubmed
    ..0074). Long-term treatment with tretinoin emollient cream 0.05% is safe and effective in subjects with moderate to severe facial photodamage. ..
  6. Khandpur S, Bhat R, Ramam M. Ichthyosis follicularis, alopecia and photophobia (IFAP) syndrome treated with acitretin. J Eur Acad Dermatol Venereol. 2005;19:759-62 pubmed
    ..A moderate response to acitretin therapy (1 mg/kg) administered for 6 months was observed, with improvement in cutaneous features and corneal erosions and no change in alopecia or photophobia...
  7. Roth M, Connett J, D Armiento J, Foronjy R, Friedman P, Goldin J, et al. Feasibility of retinoids for the treatment of emphysema study. Chest. 2006;130:1334-45 pubmed
  8. Iulianella A, Lohnes D. Contribution of retinoic acid receptor gamma to retinoid-induced craniofacial and axial defects. Dev Dyn. 1997;209:92-104 pubmed
    ..5 dpc, suggesting that RAR alpha and/or RAR beta isoforms may substitute for certain RAR gamma functions, and that RAR gamma may elicit its normal effects on vertebral morphogenesis at this developmental stage. ..
  9. Cockayne E. The EVERT (effective verruca treatments) trial protocol: a randomised controlled trial to evaluate cryotherapy versus salicylic acid for the treatment of verrucae. Trials. 2010;11:12 pubmed publisher
    ..The primary analysis will be intention to treat. It is planned that recruitment will be completed by December 2009 and results will be available by June 2010. Current Controlled Trials ISRCTN18994246. ..

More Information


  1. Eichenfield L, Matiz C, Funk A, Dill S. Study of the efficacy and tolerability of 0.04% tretinoin microsphere gel for preadolescent acne. Pediatrics. 2010;125:e1316-23 pubmed publisher
    ..04% TMG pump was effective and safe for the treatment of acne vulgaris in this 8- to 12-year-old population, and the treatment was generally well tolerated. Additional studies in this population are recommended, to confirm these results. ..
  2. Kumari R, Thappa D. Comparative study of trichloroacetic acid versus glycolic acid chemical peels in the treatment of melasma. Indian J Dermatol Venereol Leprol. 2010;76:447 pubmed publisher
    ..Melasma is a common cause of facial hyperpigmentation with significant cosmetic deformity. Many modalities of treatment are available, but none is satisfactory...
  3. Kircik L. Salicylic Acid 6% in an ammonium lactate emollient foam vehicle in the treatment of mild-to-moderate scalp psoriasis. J Drugs Dermatol. 2011;10:270-3 pubmed
    ..Salicylic acid 6% emollient foam provides a useful option in the treatment of psoriasis that is highly effective, well tolerated and acceptable to patients. ..
  4. Pederiva F, Martinez L, Tovar J. Retinoic acid rescues deficient airway innervation and peristalsis of hypoplastic rat lung explants. Neonatology. 2012;101:132-9 pubmed publisher
    ..If deficient airway innervation contributing to dysmotility and pulmonary hypoplasia can be pharmacologically rescued, new relatively simple prenatal interventions could be envisioned. ..
  5. Tippmann F, Hundt J, Schneider A, Endres K, Fahrenholz F. Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J. 2009;23:1643-54 pubmed publisher
    ..The results of this study may have clinical relevance because acitretin has been approved for the treatment of psoriasis since 1997 and found generally safe for long-term use in humans. ..
  6. Carraway R, Dobner P. Zinc pyrithione induces ERK- and PKC-dependent necrosis distinct from TPEN-induced apoptosis in prostate cancer cells. Biochim Biophys Acta. 2012;1823:544-57 pubmed publisher
    ..The enhanced sensitivity of PCa cells to ZP and the apparent ability of ZP and TPEN to kill quiescent and rapidly dividing cells in a p53-independent manner suggest that ZP/TPEN might be used to develop adjunct treatments for PCa. ..
  7. Masmoudi A, Abdelmaksoud W, Ghorbel S, Amouri H, Mseddi M, Bouassida S, et al. [Impetigo herpetiformis (two cases)]. J Gynecol Obstet Biol Reprod (Paris). 2008;37:804-7 pubmed publisher
    ..They also show the importance of local steroid associated with UVB which constitute another therapeutic alternative in the treatment of hepetiformis impetigo. ..
  8. Mavrogianni P, Fallidas E, Nicolaidou E, Villias K, Stefanaki I, Katsambas A, et al. Therapeutic combination of radiofrequency surgical dissection and oral acitretin in the management of perianal Buschke-Lowenstein tumour: a case report. Int J STD AIDS. 2012;23:362-4 pubmed publisher
    ..The concurrent use of oral acitretin for the treatment of erythrodermic psoriasis led to elimination of the remaining disease. The patient remains free of disease 26 months after the end of treatment. ..
  9. Nomura T, Moriuchi R, Takeda M, Suzuki S, Kikuchi K, Ito T, et al. Low-dose etretinate shows promise in management of punctate palmoplantar keratoderma type 1: Case report and review of the published work. J Dermatol. 2015;42:889-92 pubmed publisher
    ..Thus, this study clearly provides further evidence that PPKP1 is caused by AAGAB mutations and that systemic retinoids are the most promising current treatment for PPKP1. ..
  10. Balci D, Serarslan G, Sangun O, Homan S. Acitretin for Papillon-Lefevre syndrome in a five-year-old girl. Indian J Dermatol Venereol Leprol. 2008;74:71-3 pubmed
  11. Borska L, Andrys C, Krejsek J, Palicka V, Vorisek V, Hamakova K, et al. Influence of dermal exposure to ultraviolet radiation and coal tar (polycyclic aromatic hydrocarbons) on the skin aging process. J Dermatol Sci. 2016;81:192-202 pubmed publisher
    ..However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP. ..
  12. Takeichi T, Sugiura K, Nakamura Y, Fujio Y, Konohana I, Akiyama M. Darier's Disease Complicated by Schizophrenia Caused by a Novel ATP2A2 Mutation. Acta Derm Venereol. 2016;96:993-994 pubmed publisher
  13. Situm M, Kolić M, Bolanca Z, Ljubicić I, Misanović B. Melasma--updated treatments. Coll Antropol. 2011;35 Suppl 2:315-8 pubmed
    ..Combining topical agents like hydroquinone, tretinoin and a corticosteroid in addition to sun avoidance, regular use of sunscreen throughout the year and patient education is the best treatment in this difficult to treat condition. ..
  14. Lai W, Hsiao Y, Chung J, Wei Y, Cheng Y, Yang J. Synergistic phototoxic effects of glycolic acid in a human keratinocyte cell line (HaCaT). J Dermatol Sci. 2011;64:191-8 pubmed publisher
    ..The synergistic photo-toxicity may be related to cell cycle arrest and apoptosis in UVB-treated HaCaT cells. These results highlight the potential adverse effects of GA-containing cosmetic agents on human skin. ..
  15. Chiewchanvit S, Chuamanochan M, Mahanupab P, Baosoung V. Reactive neutrophilic dermatoses associated with nontuberculous mycobacterial infection in adult-onset immunodeficiency syndrome responded well to acitretin: four cases report. J Med Assoc Thai. 2013;96:1609-16 pubmed
    ..Acitretin, a second-generation retinoid, can be used for the treatment of reactive pustular lesions in the syndrome of adult-onset immunodeficiency due to its good response, being well tolerated, and without immunosuppression. ..
  16. El Darouti M, Gawdat H, Hegazy R, Tawdy A, Fawzy M, Abdel Halim D. Crude Coal Tar and Ultraviolet (UV) A radiation (Modified Goeckerman Technique) in Treatment of Psoriasis. Acta Dermatovenerol Croat. 2015;23:165-70 pubmed
    ..1% of patients achieved 26-50% reduction. No serious side effects were reported in any of the patients. Modified GT is a safe and effective therapeutic option for patients with moderate and severe psoriasis. ..
  17. El Khayat R, Hague J. Use of acitretin in the treatment of resistant viral warts. J Dermatolog Treat. 2011;22:194-6 pubmed publisher
    ..A case of extensive periungual viral warts in an immunocompetent patient that failed to respond to standard treatments over a 10-year period is reported. A rapid and complete response to treatment was achieved with oral acitretin. ..
  18. Karapolat S, Sanli A, Onen A, Acikel U, Sivrikoz O. Effects of retinoic acid on compensatory lung growth. J Cardiothorac Surg. 2008;3:37 pubmed publisher
    ..A significant rise in the mean dimension and average wall thickness of the alveolar structure were determined in Group C. Retinoic acid contributes to the compensatory growth of the residual lung tissue. ..
  19. Werner B, Bresch M, Brenner F, Lima H. Comparative study of histopathological and immunohistochemical findings in skin biopsies from patients with psoriasis before and after treatment with acitretin. J Cutan Pathol. 2008;35:302-10 pubmed publisher
    ..Basal cell layer is expanded in psoriasis. Langerhans' cells were less frequent after treatment, and that finding has to be investigated further to determine its role in acitretin mechanism of action. ..
  20. van Steensel M. Emerging drugs for ichthyosis. Expert Opin Emerg Drugs. 2007;12:647-56 pubmed
    ..Treatment presently consists primarily of topical keratolytic agents, aimed at removing the ichthyotic scales, and emollients...
  21. Zhang X, Luo Q, Li C, He Y, Xu X. Clinical investigation of acitretin in children with severe inherited keratinization disorders in China. J Dermatolog Treat. 2008;19:221-8 pubmed publisher
    ..No previous investigation had been made on a negative effect on the growth and development of such children. Acitretin showed a satisfactory therapeutic effect on severe inherited disorders of keratinization in children. ..
  22. Meziane M, Chraibi R, Kihel N, Hassam B, Senouci K. Linear Darier disease. Dermatol Online J. 2008;14:11 pubmed
    ..The linear form of this disease is rare and could result from genetic mosaicism in this autosomal dominant disorder. We report a case of linear Darier disease that involved the right lower limb with a zosteriform distribution. ..
  23. Abdallah M, El Khateeb E, Abdel Rahman S. The influence of psoriatic plaques pretreatment with crude coal tar vs. petrolatum on the efficacy of narrow-band ultraviolet B: a half-vs.-half intra-individual double-blinded comparative study. Photodermatol Photoimmunol Photomed. 2011;27:226-30 pubmed publisher
    ..05) in favor of petrolatum. The pretreatment of psoriatic plaques with either petrolatum or crude coal tar may enhance the therapeutic outcome of NB-UVB, which appeared to favor petrolatum. ..
  24. Gajinov Z, Matić M, Duran V, Vuckovic N, Prcić S, Vujanović L. Drug-related pityriasis rubra pilaris with acantholysis. Vojnosanit Pregl. 2013;70:871-3 pubmed
    ..In management of rare inflammatory skin disease, such as PRP, we have to carefully observe and evaluate not only diagnostic features but possible external influences on its course also. ..
  25. Herbig M, Evers D. Correlation of hydrotropic solubilization by urea with logD of drug molecules and utilization of this effect for topical formulations. Eur J Pharm Biopharm. 2013;85:158-60 pubmed publisher
    ..For logD values below 2 or above 5, only EF<5 were found. For some compounds, e.g., diclofenac (pH 4) and prednicarbate could achieved only EF>5 at 5% urea and EF>250 at 20% urea. ..
  26. Moncada B, Castillo Martinez C, Arenas E, León Bejarano F, Ramírez Elías M, Gonzalez F. Raman spectroscopy analysis of the skin of patients with melasma before standard treatment with topical corticosteroids, retinoic acid, and hydroquinone mixture. Skin Res Technol. 2016;22:170-3 pubmed publisher
    ..We believe it will eventually help to decide the treatment of melasma in clinical dermatology. ..
  27. Anwar M, Iftikhar N, Hasnain S, Ishaq B. Pseudoainhum in acute psoriasis. J Coll Physicians Surg Pak. 2012;22:786-8 pubmed publisher
    ..The report herein, describes the rare presentation of pseudoainhum occurring concomitantly in acute psoriasis. Timely recognition of such rare disease entities by physicians is imperative to avoid unnecessary complications...
  28. Dong J, He Y, Zhang X, Wang Y, Tian Y, Wang J. Clinical efficacy of flumetasone/salicylic acid ointment combined with 308-nm excimer laser for treatment of psoriasis vulgaris. Photodermatol Photoimmunol Photomed. 2012;28:133-6 pubmed publisher
    ..The combination therapy can increase effectiveness and decrease the total laser dose, thus potentially reducing side effects. ..
  29. Leithead J, Simpson K, Macgilchrist A. Fulminant hepatic failure following overdose of the vitamin A metabolite acitretin. Eur J Gastroenterol Hepatol. 2009;21:230-2 pubmed publisher
    ..Given the known association between psoriasis and depression, and the possible association of acitretin with psychiatric illness, this is an important potential adverse event. ..
  30. Vieux Rochas M, Bouhali K, Baudry S, Fontaine A, Coen L, Levi G. Irreversible effects of retinoic acid pulse on Xenopus jaw morphogenesis: new insight into cranial neural crest specification. Birth Defects Res B Dev Reprod Toxicol. 2010;89:493-503 pubmed publisher
    ..Our findings provide a conceptual framework to understand the origin of individual facial features and the evolution of different craniofacial morphotypes. ..
  31. Seite S, Paries J, Reygagne P, Hamidou Z, Jouanique C, Perez Pala G, et al. A lipohydroxyacid-containing shampoo improves scalp condition and quality of life in patients with seborrheic dermatitis and light-to-moderate scalp psoriasis. J Cosmet Dermatol. 2009;8:108-13 pubmed publisher
  32. Pohl D, Andrys C, Borska L, Fiala Z, Hamáková K, Ettler K, et al. CC and CXC chemokines patterns in psoriasis determined by protein array method were influenced by Goeckerman's therapy. Acta Medica (Hradec Kralove). 2009;52:9-13 pubmed
    ..It could be the cause for decreased proangiogenic activity which is described after GT of psoriasis. ..
  33. Höpker L, Ribeiro C, Oliveira L, Moreira A. Ichthyosis follicularis, alopecia and photophobia syndrome (IFAP): report of the first case with ocular and cutaneous manifestations in Brazil with a favorable response to treatment. Arq Bras Oftalmol. 2011;74:55-7 pubmed
    ..After three months using systemic retinoid (Acitretina) and posterior amniotic membrane transplantation in the left eye, there was a significant improvement of photophobia, corneal erosions and neuropsychomotor development. ..
  34. Takenaga M, Ohta Y, Tokura Y, Hamaguchi A, Shudo K, Okano H, et al. The effect of Am-80, a synthetic retinoid, on spinal cord injury-induced motor dysfunction in rats. Biol Pharm Bull. 2009;32:225-31 pubmed
    ..Its efficacy may be partly ascribed to promotion of cell viability and differentiation of neural stem cells through increased TrkB expression. ..
  35. Aubry E, Odermatt A. Retinoic acid reduces glucocorticoid sensitivity in C2C12 myotubes by decreasing 11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor activities. Endocrinology. 2009;150:2700-8 pubmed publisher
    ..Disturbances of the nutrient and hormonal regulation of glucocorticoid action in skeletal muscles might be relevant for metabolic diseases. ..
  36. Abdel Daim M, Funasaka Y, Kamo T, Ooe M, Matsunaka H, Yanagita E, et al. Effect of chemical peeling on photocarcinogenesis. J Dermatol. 2010;37:864-72 pubmed publisher
    ..These results indicate that chemical peeling with glycolic acid, salicylic acid and trichloroacetic acid could serve tumor prevention by removing photo-damaged cells. ..
  37. Ishida Yamamoto A. Erythrokeratodermia variabilis et progressiva. J Dermatol. 2016;43:280-5 pubmed publisher
    ..Low-dose systemic retinoid may be beneficial. Novel therapies targeting connexin hemichannels and gap junctions may become available in the future. ..
  38. Mitra A, Wu Y. Topical delivery for the treatment of psoriasis. Expert Opin Drug Deliv. 2010;7:977-92 pubmed publisher
    ..New topical formulations have the potential to achieve better efficacy with improved safety profile. ..
  39. Sardana K, Relhan V, Garg V, Khurana N. An observational analysis of erythromelanosis follicularis faciei et colli. Clin Exp Dermatol. 2008;33:333-6 pubmed publisher
    ..To our knowledge, this is the first case series of EFFC from India, and we believe that EFFC is a common but infrequently reported condition. ..
  40. Jeong S, Shin J, Yeo U, Kim W, Kim I. Low-fluence Q-switched neodymium-doped yttrium aluminum garnet laser for melasma with pre- or post-treatment triple combination cream. Dermatol Surg. 2010;36:909-18 pubmed publisher
    ..There were no significant adverse effects with the laser treatments. Laser treatment after topical TC cream was found to be safer and more effective than the post-treatment use of topical agents. ..
  41. Rudolf E, Cervinka M. Zinc pyrithione induces cellular stress signaling and apoptosis in Hep-2 cervical tumor cells: the role of mitochondria and lysosomes. Biometals. 2010;23:339-54 pubmed publisher
    ..The use of specific inhibitors as well as siRNA technology suggest a crucial role of MT-IIA in trafficking of free zinc into mitochondria or lysosomes and regulation of apoptotic or necrotic cell demise. ..
  42. Chao P, Cheng Y, Chung M. Generalized pustular psoriasis in a 6-week-old infant. Pediatr Dermatol. 2009;26:352-4 pubmed publisher
    ..Acitretin was initiated at 1 mg/kg/day with marked improvement on her psoriasis, and titrated to 0.4 mg/kg/day in the subsequent 6 months without flare. Acitretin proved to be an effective therapeutic option for young infants with GPP. ..
  43. Ichiyama S, Funasaka Y, Otsuka Y, Takayama R, Kawana S, Saeki H, et al. Effective treatment by glycolic acid peeling for cutaneous manifestation of familial generalized acanthosis nigricans caused by FGFR3 mutation. J Eur Acad Dermatol Venereol. 2016;30:442-5 pubmed publisher
    ..We diagnosed our cases as familial generalized AN caused by heterozygous c.1949A>C (p.K650T) mutation of FGFR3. We propose that GA peeling is a useful and safe therapeutic option to treat familial AN. ..
  44. Beránek M, Fiala Z, Kremlacek J, Andrys C, Hamakova K, Chmelarová M, et al. Genetic polymorphisms in biotransformation enzymes for benzo[a]pyrene and related levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts in Goeckerman therapy. Toxicol Lett. 2016;255:47-51 pubmed publisher
    ..026). Our data suggest that CYP1B1/EPHX1 genotyping could help to predict the risk of DNA damage and to optimize doses of coal tar and UVR exposure in psoriatic patients in whom GT was applied. ..
  45. Quarles F, Brody H, Johnson B, Badreshia S. Chemical peels in richly pigmented patients. Dermatol Ther. 2007;20:147-8 pubmed
  46. Gouveia R, Connon C. The effects of retinoic acid on human corneal stromal keratocytes cultured in vitro under serum-free conditions. Invest Ophthalmol Vis Sci. 2013;54:7483-91 pubmed publisher
    ..These findings contribute to our understanding of corneal stromal biology in health and disease, and may prove useful in optimizing keratocyte cultures for applications in tissue engineering, cell biology, and medicine. ..
  47. Tirado Sanchez A, Espíndola Y, Ponce Olivera R, Bonifaz A. Efficacy and safety of adapalene gel 0.1% and 0.3% and tretinoin gel 0.05% for acne vulgaris: results of a single-center, randomized, double-blinded, placebo-controlled clinical trial on Mexican patients (skin type III-IV). J Cosmet Dermatol. 2013;12:103-7 pubmed publisher
    ..Adapalene 0.3% and tretinoin 0.05% are comparable in efficacy, and adapalene 0.1% offers a better safety profile in Mexican patients. ..
  48. Rajouria E, Amatya A, Karn D. Comparative study of 5 % potassium hydroxide solution versus 0.05% tretinoin cream for Molluscum Contagiosum in children. Kathmandu Univ Med J (KUMJ). 2011;9:291-4 pubmed
    ..The side effects could be minimized if applied as stated above. On the other hand, tretinoin showed delayed response and even some of lesion extended beyond 4 week but the side effect were less, and hence can be used in recurrent cases. ..
  49. Bhatia A, Singh B, Amarji B, Negi P, Shukla A, Katare O. Novel stain-free lecithinized coal tar formulation for psoriasis. Int J Dermatol. 2011;50:1246-8 pubmed publisher
    ..The study revealed the distinct non-staining potential of the LCT formulation. This LCT formulation lacks the propensity to stain hair and thus has excellent potential to be exploited in the treatment of scalp psoriasis. ..
  50. Kircik L. Comparative efficacy and safety results of two topical combination acne regimens. J Drugs Dermatol. 2009;8:624-30 pubmed
    ..While both regimens were safe and effective, regimen BPO/C+RAM yielded a more rapid onset of effect versus regimen CPT+BPO against both non-inflammatory and inflammatory lesions. Both treatment regimens were well-tolerated. ..
  51. Kleinpenning M, Kanis J, Smits T, van Erp P, van de Kerkhof P, Gerritsen R. The effects of keratolytic pretreatment prior to fluorescence diagnosis and photodynamic therapy with aminolevulinic acid-induced porphyrins in psoriasis. J Dermatolog Treat. 2010;21:245-51 pubmed publisher
    ..Salicylic acid in petrolatum and a hydrocolloid dressing prior to FDAP and PDT induce improvement of hyperkeratosis. Thus, a hydrocolloid dressing is a good alternative to the current keratolytic pretreatment regime. ..
  52. Ergin S, Ersoy Evans S, Sahin S, Ozkaya O. Acitretin is a safe treatment option for infantile pustular psoriasis. J Dermatolog Treat. 2008;19:341-3 pubmed publisher
    ..Herein, a 2.5-month-old infant with IPP is presented, who was successfully treated with systemic retinoid therapy, which appears to be a safe and effective option for this challenging pustular eruption of childhood. ..
  53. Joshi S, Boone S, Alam M, Yoo S, White L, Rademaker A, et al. Effectiveness, safety, and effect on quality of life of topical salicylic acid peels for treatment of postinflammatory hyperpigmentation in dark skin. Dermatol Surg. 2009;35:638-44; discussion 644 pubmed publisher
    ..Salicylic acid peels are safe in this population. Although patients rated them as clinically effective, blinded raters found a brief series of peels to have less efficacy. Measured quality of life improved nominally. ..