Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. Description based on print version record. Includes bibliographical references (leaves 173-180).

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Acne is a common, chronic disorder that affects many adolescents. The most effective acne medication is systemic isotretinoin. It provides a permanent cure for many patients, but has various side effects. A South African Acne Treatment Guideline was introduced in 2005. Adherence to this guideline could lead to safer, more effective acne management. The primary aim of this study was to investigate the appropriateness of medications prescribed in the treatment of acne in South Africa, and to evaluate the safety and efficacy of systemic isotretinoin utilised by patients in the Nelson Mandela Metropole (NMM). A drug utilisation study (including 18 803 South African acne patients’ chronic prescription data between 2000 and 2005) and a patient questionnaire survey (including information from 57 patients in the NMM who used systemic isotretinoin) were conducted. Basic descriptive and interferential statistics were calculated. The drug utilisation study revealed that systemic antibiotics were the acne treatment prescribed to most (43.3 percent) patients, followed by 42.1 percent of patients on systemic isotretinoin, 33.2 percent on hormonal therapy and 18.9 percent on topical therapy. Topical retinoids were underused. The questionnaire survey indicated a lack of compliance by prescribers with guideline recommendations regarding the prescription (and accompanying counselling and monitoring) of isotretinoin. Incorrect cumulative doses were frequently prescribed, and a lack of proper implementation of pregnancy prevention measures was evident. The majority of isotretinoin patients reported a high efficacy of isotretinoin in clearing their acne.

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The purpose of this research was to determine the effects of retinoic acid on bovine papillomavirus (BPV) transformed cells. Since BPV transformed cells are able to form colonies in agar and their untransformed counterparts are not, of particular interest was the effect of retinoic acid on this marker. Retinoic acid inhibited the growth of colony forming cells, but the extent of inhibition varied among several cloned cell lines. Retinoic acid inhibited the proliferation of BPV transformed cells and the extent of this inhibition also varied. The copy number of the virus was determined for each of three cell lines by liquid reassociation experiments. The copy number did not change when the cells were treated with RA for a prolonged period of time. Gel electrophoresis and Southern blotting of extrachromosomal DNA from the cell lines revealed the presence of unit length BPV DNA in all three transformed cell lines. The amount of BPV DNA per cell was decreased when the cells were treated with 10⁻⁵ M RA for three days.

This investigation evaluated the potential protective role of Zn, through modulation of MT, against the teratogenic effects of isotretinoin (ITR), a dermatological drug which causes oxidative damage, in CD-1 mouse embryos. Significant induction of MT by Zn supplementation was observed in mouse embryos both in vivo and in vitro. On gestational day (GD) 6.5, pregnant mice received a subcutaneous Zn injection of 0 (saline), 20 and 40 mg/kg, resulting in embryonic MT concentrations of 12.5, 54.5 and 93.4 $ mu$g/g protein, respectively, after 48h. Embryos were extracted at GD 8.5 and incubated with 0 (saline) and 15 $ mu$M Zn for 48h. There was a six-fold increase in MT expression in the Zn treatment group, resulting in MT concentration of 688 $ mu$g/g protein. Pre-induction of MT by Zn exposure was found to offer protection against subsequent exposure to ITR in vivo and in vitro. Zn injections of 40 and 20 mg/kg to pregnant mice on GD 8.5 and 9.5, respectively, alleviated fetal damage caused by three intragastric intubations of 100 mg ITR/kg on GD 10.5. Zn pre-treatment significantly increased fetal and placental masses, totally eliminated the incidence of cleft palate and lessened the frequency of post-partum mortality by 74%. Pre-treatment of GD 8.5 embryos with a 24h culture period with 15 $ mu$M Zn improved growth and totally restored normal embryonic development altered by a 24h culture with 17 $ mu$M ITR. Zn decreased the frequencies of unfused mid brain and fore brain by 100%, and the incidence of abnormal flexion by 74%. A reduction in MT concentrations was observed in groups exposed to ITR, indicating that MT may have been oxidized by ITR-derived toxic FR. (Abstract shortened by UMI.)

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Akne eller finnar är en inflammatorisk hudreaktion som uppstår när talgkörtlar eller hårsäckar blir inflammerade. Denna hudreaktion syns som utslag på eller under huden, och involverar främst ansiktet. Akne är vanligast förekommande bland tonåringar, men kan drabba människor i alla åldrar. Akne anses vara en bidragande faktor till social isolering, dåligt självförtroende, depression och självmordstankar.  Under 1950-talet utvecklades ett nytt akneläkemedel innehållande den verksamma substansen isotretinoin. Läkemedlet började användas i början på 1980-talet och är idag det effektivaste läkemedlet vid behandling av svår akne.  - Isotretinoin är ett A-vitaminsyraderivat (13-cis-retonic-acid) som tillhör läkemedelsgruppen retonioder. Läkemedlet är avsett för behandling av svår ärrbildande akne, samt där behandling av akne med andra läkemedel som antibiotika eller lokalbehandling inte gett ett önskat resultat. Isotretinoin är ett effektivt läkemedel vid behandling av svår akne, men dessvärre även ett läkemedel som kan orsaka besvärliga samt allvarliga biverkningar. Eftersom läkemedlet passerar över blodhjärnbarriären, har det utförts studier för att undersöka om det finns ett samband mellan behandling med läkemedlet isotretionin och psykiska reaktioner. Då det föreligger hög förekomst av psykiatriska symptom och självmordstankar hos personer som lider av akne, är det svårt att skilja ifall de psykiska symptomen är läkemedelsrelaterade eller inte. Syftet med denna litteraturstudie var att undersöka om det kan finns ett samband mellan behandling av akne med läkemedlet isotretinion och uppkomst av psykiatriska symptom samt självmord. För att hitta relevanta artiklar till det här arbetet utfördes en sökning i databasen PubMed via Linnéuniversitetets bibliotek vilket resulterade i sex relevanta studier. För utvärdering av depression, ångest samt livskvalitet i valda studier användes olika självskattningsskalor. Resultaten av studierna är entydiga där ingen av studierna visar att det finns ett samband mellan förekomsten av psykiatriska symptom och självmordstankar vid behandling av akne med läkemedlet isotretinoin. Tvärtom indikerades det en förbättring av psykiatriska tillstånd som återspeglas till reducering av akne. Det finns dock otillräckliga bevis för att dessa resultat kan utesluta uppkomsten av psykiatriska symtom och självmordstankar under behandling med isotretinoin. / Acne or pimples is an inflammatory skin reaction that occurs when the sebaceous glands or hair follicles become inflamed. This skin reaction is seen as a rash on or under the skin and mainly involves the face. Acne is most common in adolescence but can affect people of all ages. Acne is considered a contributing factor to social isolation, low self-esteem, depression, and suicidal thoughts. During the 1950s, a new acne drug containing the active substance isotretinoin was developed. The drug began to be used in the early 1980s and is today the most effective drug in treating severe acne. Isotretinoin is a vitamin A acid derivative (13-cis-retonic-acid) that belongs to the drug group retinoids. Isotretinoin is intended for the treatment of severe scarring acne, as well as where the treatment of acne with other drugs such as antibiotics or topical treatment has not given the desired result. Isotretinoin is an effective drug in treating severe acne, but unfortunately also a drug that can cause troublesome and severe side effects. As isotretinoin crosses the blood-brain barrier, studies have been performed on whether there is a link between treatment with isotretinoin and mental reactions. There is a high incidence of psychiatric symptoms and suicidal ideation in people suffering from acne. It is difficult to distinguish whether the mental symptoms are drug-related or not. The purpose of this literature review was to investigate whether there may be an association between the treatment of acne with the drug isotretinoin and the onset of psychiatric symptoms as well as suicide. To find relevant articles for this work, a search was performed in the PubMed database through Linnaeus University's library, which resulted in six relevant studies. Different self-assessment scales evaluated depression, anxiety, and quality of life in selected studies. The results of the studies are unequivocal, where none of the studies showed a connection between the occurrence of psychiatric symptoms and suicidal thoughts when treating acne with the drug isotretinoin. On the contrary, it indicated an improvement in psychiatric conditions reflected in acne reduction. However, there is insufficient evidence that these results can rule out the emergence of psychiatric symptoms and suicidal thoughts during treatment.

Isotretinoin är en av de mest använda vid behandling av medelsvår till svår akne. Läkemedlet används främst när mildare behandlingar såsom lokalbehandling och antibiotika inte är tillräckligt aktiva vid behandling av akne. Nittio procent av alla tonåringar i världen lider av akne som kallas just för akne vulgaris. En tredjedel av tonåringar lider av just måttlig och svår akne och behöver därför behandlas med ett effektivt behandling. Flera vetenskapliga studier har bekräftat att standarddos (0,5 -1,0 mg/kg/dag) av isotretinoin är den mest effektiva behandling vid akne. Däremot har studierna bekräftat att behandlingen med standarddos isotretinoin leder till allvarliga biverkningar såsom teratogena effekter (fosterskador) och därför väljer en stor del av patienterna att inte behandlas med standarddos isotretinoin. Syftet med detta arbete var att undersöka om ersättning av standarddos isotretinoin (0,5-1,0 mg/kg/dag) med lågdos isotretinoin (0,2-0,4mg/kg/dag) som monoterapi eller i kombination med en annan behandling såsom laser som kan minska svårighetsgraden av akne och samtidigt minska av biverkningar.  Fem vetenskapliga studier som besvarar studiens frågeställningar har valts med hjälp av databasen Pubmed. Alla fem studier visade att lågdos isotretinoin är effektiv behandling vid måttlig till svår akne. Färre biverkningar noterades vid användning av lågdos isotretinoin (0,25-0,5 mg/kg/dag) jämfört med standarddoser (0,5-1 mg/kg/dag). Slutsatsen som dras från detta litteraturarbete är att lågdos isotretinoin (< 0,5 mg/kg/dag) är en effektiv och säker behandling vid mild till svår akne. Färre biverkningar noterades vid användning av låg dos isotretinoin jämfört med standard dos isotretinoin (0,5-1 mg/kg/dag) som ger allvarliga biverkningar. Lågdos isotretinoin, både som monoterapi och som kombinationsbehandling har visat sig vara lika effektiv som standarddos.

Orientador: Juliano Vilaverde Schmitt / Resumo: Fundamentos: Apesar da isotretinoína oral ser um tratamento eficaz para casos graves e persistentes de acne, existe significativa preocupação e controvérsia sobre seus efeitos adversos psicológicos. Por outro lado, a acne apresenta significativo impacto psicossocial nos portadores. Objetivos: Avaliar adolescentes e adultos jovens sob tratamento com isotretinoína oral para acne moderada a grave quanto a sintomas depressivos e suas relações com variáveis demográficas e clínicas. Métodos: Estudo tipo coorte com portadores de acne tratados com isotretinoína oral. Foram avaliados Cardiff Acne Disability Index (CADI), escala de depressão de Beck (EDB), gravidade da acne e cicatrizes e escore de efeitos adversos mucocutâneos (EEAM). Resultados: Foram incluídos 42 pacientes, 43% do sexo feminino, com idade mediana de 18 [1q-3q:16-21], seguidos por um período de 9 [6-9] meses. EDB passou de 7,5 [2-16] pré-tratamento para 1 [0-5] ao final do seguimento (p<0,01), sendo que 43% apresentavam pontuação para depressão leve ou superior pré-tratamento, contra 14% ao final do seguimento (RP=0,33 (IC 95%: 0,15 a 0,76); p<0,01). EDB pré-tratamento associou-se à presença de antecedentes psiquiátricos, menor renda familiar e maior CADI (p<0,05), enquanto durante o tratamento associou-se à maior duração prévia da acne, a maiores EEAM, à menor dose acumulada e a maiores EDB iniciais (p<0,05). Limitações: Perdas de seguimento, não apresentar grupos controle, monocêntrico. Conclusões: Há melhora nos e... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Despite the effectiveness of oral isotretinoin for severe and persistent acne, there is concern and controversy about its possible psychological adverse effects. On the other hand, acne causes significant psychosocial impact on patients. Objective: Assess treatment with oral isotretinoin for moderate to severe acne in adolescents and young adults regarding depressive symptoms and their relationships with demographic and clinical variables. Methods: Cohort study with patients with acne under treatment with oral isotretinoin. Four aspects were considered: Cardiff Acne Disability Index (CADI), Beck Depression Inventory (BDI), acne and scars severity and Mucocutaneous Adverse Effects Score (MAES). Results: Forty-two participants were included, 43% were female, median age 18 years old [1q-3q:16-21], followed up for 9 [6-9] months. The BDI went from 7.5 [2- 16] before the treatment to 1 [0-5] after the follow up (p<0.01). 43% had score for mild depression or worse before treatment – the number dropped to 14% in the end of the study (RP=0.33 (IC 95%: 0.15 to 0.76); p<0.01). The BDI before treatment correlates to psychiatric history, lower family income and higher CADI (p<0.05), while during the treatment it correlates to the duration of acne, higher MAES, lower cumulative dose and higher initial BDI (p<0.05). Study Limitations: Loss of follow-up, lack of a control group, monocentric. Conclusion: There is improvement on the depression scores when acne vulgaris is treated ... (Complete abstract click electronic access below) / Mestre