Effectiveness of the repurposed drug isotretinoin in an experimental murine model of Chagas disease.

Benznidazole and nifurtimox are the drugs currently used for the treatment of Chagas disease, however its side effects may affect patient adherence. In the search for new alternative therapies, we previously identified isotretinoin (ISO), an FDA-approved drug widely used for the treatment of severe acne through a drug repurposing strategy. ISO shows a strong activity against Trypanosoma cruzi parasites in the nanomolar range, and its mechanism of action is through the inhibition of T. cruzi polyamine and amino acid transporters from the Amino Acid/Auxin Permeases (AAAP) family. In this work, a murine model of chronic Chagas disease (C57BL/6 J mice), intraperitoneally infected with T. cruzi Nicaragua isolate (DTU TcI), were treated with different oral administrations of ISO: daily doses of 5 mg/kg/day for 30 days and weekly doses of 10 mg/kg during 13 weeks. The efficacy of the treatments was evaluated by monitoring blood parasitemia by qPCR, anti-T. cruzi antibodies by ELISA, and cardiac abnormalities by electrocardiography. No parasites were detected in blood after any of the ISO treatments. The electrocardiographic study of the untreated chronic mice showed a significant decrease in heart rate, while in the treated mice this negative chronotropic effect was not observed. Atrioventricular nodal conduction time in untreated mice was significantly longer than in treated animals. Mice treated even with ISO 10 mg/kg dose every 7 days, showed a significant reduction in anti-T. cruzi IgG levels. In conclusion, the intermittent administration of ISO 10 mg/kg would improve myocardial compromise during the chronic stage.

Isotretinoin and Thalidomide Down-Regulate c-MYC Gene Expression and Modify Proteins Associated with Cancer in Hepatic Cells.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. The number of cases is increasing and the trend for the next few years is not encouraging. HCC is usually detected in the advanced stages of the disease, and pharmacological therapies are not entirely effective. For this reason, it is necessary to search for new therapeutic options. The objective of this work was to evaluate the effect of the drugs isotretinoin and thalidomide on c-MYC expression and cancer-related proteins in an HCC cellular model. The expression of c-MYC was measured using RT-qPCR and western blot assays. In addition, luciferase activity assays were performed for the c-MYC promoters P1 and P2 using recombinant plasmids. Dose-response-time analyses were performed for isotretinoin or thalidomide in cells transfected with the c-MYC promoters. Finally, a proteome profile analysis of cells exposed to these two drugs was performed and the results were validated by western blot. We demonstrated that in HepG2 cells, isotretinoin and thalidomide reduced c-MYC mRNA expression levels, but this decrease in expression was linked to the regulation of P1 and P1-P2 c-MYC promoter activity in isotretinoin only. Thalidomide did not exert any effect on c-MYC promoters. Also, isotretinoin and thalidomide were capable of inducing and repressing proteins associated with cancer. In conclusion, isotretinoin and thalidomide down-regulate c-MYC mRNA expression and this is partially due to P1 or P2 promoter activity, suggesting that these drugs could be promising options for modulating the expression of oncogenes and tumor suppressor genes in HCC.

Effects of oral isotretinoin therapy on the nasal cavities / Efeitos nasais da terapia com isotretinoína oral

Abstract Introduction Isotretinoin (13 cis-retinoic acid) is the most effective treatment for acne vulgaris and is the only treatment option that can provide either remission or a permanent cure. Objective The aim of this study was to use both subjective and objective methods to assess the nasal complaints of patients with severe acne who received oral isotretinoin therapy. Methods Fifty-four subjects were enrolled in the study. All the subjects were assessed with subjective (NOSE and VAS questionnaires) and objective (rhinomanometry and saccharine) tests to determine the severity of their nasal complaints. Results The mean severity scores (min: 0; max: 100) for nasal dryness/crusting and epistaxis were 0.47 ± 1.48 (0-5); 0.35 ± 1.30 (0-5) at admission, 3.57 ± 4.45 (0-10); 2.26 ± 4.71 (0-20) at the first month, and 4.28 ± 6 (0-20); 2.26 ± 4.71 (0-20) at the third month of the treatment respectively. Total nasal resistance of 0.195 ± 0.079 (0.12-0.56) Pa/cm3/s at admission, 0.21 ± 0.084 (0.12-0.54) Pa/cm3/s at the first month, and 0.216 ± 0.081 (0.14-0.54) Pa/cm3/s at the third month. Conclusion Oral isotretinoin therapy can cause the complaint of nasal obstruction. In addition, nasal complaints, such as dryness/crusting and epistaxis, significantly increase in patients during the therapy schedule.

Resumo Introdução A isotretinoína (ácido-13 cis-retinóico) é o tratamento por via oral mais eficaz para acne vulgar e é a única opção de tratamento que pode produzir remissão ou cura permanente. Objetivo Usar métodos subjetivos e objetivos para avaliar as queixas nasais de pacientes com acne grave que receberam terapia com isotretinoína oral. Método Foram incluídos no estudo 54 indivíduos. Todos os indivíduos foram avaliados por meio de testes subjetivos (questionários NOSE e escala EVA) e objetivos (rinomanometria e teste de sacarina) para determinar a gravidade de suas queixas nasais. Resultados Os escores médios de gravidade (min: 0; max: 100) para ressecamento/crostas e epistaxe nasal foram de 0,47 ± 1,48 (0-5); 0,35 ± 1,30 (0-5) no início, 3,57 ± 4,45 (0-10); 2,26 ± 4,71 (0-20) no primeiro mês e 4,28 ± 6 (0-20); 2,26 ± 4,71 (0-20) no terceiro mês do tratamento, respectivamente. A resistência nasal total foi de 0,195 ± 0,079 (0,12 a 0,56) Pa/cm3/s no início, 0,21 ± 0,084 (0,12 a 0,54) Pa/cm3/s no primeiro mês e 0,216 ± 0,081 (0,14 a 0,54) Pa/cm3/s no terceiro mês. Conclusão A terapia com isotretinoína por via oral pode resultar em queixa de obstrução nasal. Além disso, queixas nasais, tais como ressecamento/formação de crostas e epistaxe, aumentam significativamente nos pacientes durante o esquema terapêutico.

Effects of oral isotretinoin therapy on the nasal cavities.

INTRODUCTION: Isotretinoin (13 cis-retinoic acid) is the most effective treatment for acne vulgaris and is the only treatment option that can provide either remission or a permanent cure. OBJECTIVE: The aim of this study was to use both subjective and objective methods to assess the nasal complaints of patients with severe acne who received oral isotretinoin therapy. METHODS: Fifty-four subjects were enrolled in the study. All the subjects were assessed with subjective (NOSE and VAS questionnaires) and objective (rhinomanometry and saccharine) tests to determine the severity of their nasal complaints. RESULTS: The mean severity scores (min: 0; max: 100) for nasal dryness/crusting and epistaxis were 0.47±1.48 (0-5); 0.35±1.30 (0-5) at admission, 3.57±4.45 (0-10); 2.26±4.71 (0-20) at the first month, and 4.28±6 (0-20); 2.26±4.71 (0-20) at the third month of the treatment respectively. Total nasal resistance of 0.195±0.079 (0.12-0.56)Pa/cm3/s at admission, 0.21±0.084 (0.12-0.54)Pa/cm3/s at the first month, and 0.216±0.081 (0.14-0.54)Pa/cm3/s at the third month. CONCLUSION: Oral isotretinoin therapy can cause the complaint of nasal obstruction. In addition, nasal complaints, such as dryness/crusting and epistaxis, significantly increase in patients during the therapy schedule.

Effects of isotretinoin on the olfactory function in patients with acne.

BACKGROUND:: Isotretinoin is a synthetic analog of vitamin A. Recent studies support a role for retinoic acid in the recovery of olfactory function following injury in mice. OBJECTIVE:: This study aimed at determining the effect of isotretinoin on olfactory function in patients who have acne and are otherwise healthy. METHODS:: Forty-five patients (aged 25-40 years) with acne were included in the study. All patients underwent a rhinological examination. Olfactory function was assessed by the Sniffin' Sticks Test. The test was assessed at baseline and in the third month of isotretinoin treatment. RESULTS:: Isotretinoin improved the performance of patients in the olfactory test. The SST score increased from 8.7±1.09 to 9.5±1.19 (p<0.001), prevalence of hyposmia decreased from 40% to 24% and normosmia increased from 60% to 75% (p=0.059). The percentage of patients whose olfactory function was categorized as "good" increased from 6% to 21.3%. This increase was statistically significant (p<0.05). STUDY LIMITATIONS:: Absence of a control group is one of the limitations of this study. Also, we did not evaluate patients with smell test after stopping isotretinoin treatment. CONCLUSION:: We examined the effect of systemic isotretinoin on olfactory function. It can be concluded from the present investigation that isotretinoin therapy improves the sense of smell.

Trypanocidal Effect of Isotretinoin through the Inhibition of Polyamine and Amino Acid Transporters in Trypanosoma cruzi.

Polyamines are essential compounds to all living organisms and in the specific case of Trypanosoma cruzi, the causative agent of Chagas disease, they are exclusively obtained through transport processes since this parasite is auxotrophic for polyamines. Previous works reported that retinol acetate inhibits Leishmania growth and decreases its intracellular polyamine concentration. The present work describes a combined strategy of drug repositioning by virtual screening followed by in vitro assays to find drugs able to inhibit TcPAT12, the only polyamine transporter described in T. cruzi. After a screening of 3000 FDA-approved drugs, 7 retinoids with medical use were retrieved and used for molecular docking assays with TcPAT12. From the docked molecules, isotretinoin, a well-known drug used for acne treatment, showed the best interaction score with TcPAT12 and was selected for further in vitro studies. Isotretinoin inhibited the polyamine transport, as well as other amino acid transporters from the same protein family (TcAAAP), with calculated IC50 values in the range of 4.6-10.3 µM. It also showed a strong inhibition of trypomastigote burst from infected cells, with calculated IC50 of 130 nM (SI = 920) being significantly less effective on the epimastigote stage (IC50 = 30.6 µM). The effect of isotretinoin on the parasites plasma membrane permeability and on mammalian cell viability was tested, and no change was observed. Autophagosomes and apoptotic bodies were detected as part of the mechanisms of isotretinoin-induced death indicating that the inhibition of transporters by isotretinoin causes nutrient starvation that triggers autophagic and apoptotic processes. In conclusion, isotretinoin is a promising trypanocidal drug since it is a multi-target inhibitor of essential metabolites transporters, in addition to being an FDA-approved drug largely used in humans, which could reduce significantly the requirements for its possible application in the treatment of Chagas disease.

Effects of isotretinoin on the olfactory function in patients with acne

Abstract: Background: Isotretinoin is a synthetic analog of vitamin A. Recent studies support a role for retinoic acid in the recovery of olfactory function following injury in mice. Objective: This study aimed at determining the effect of isotretinoin on olfactory function in patients who have acne and are otherwise healthy. Methods: Forty-five patients (aged 25-40 years) with acne were included in the study. All patients underwent a rhinological examination. Olfactory function was assessed by the Sniffin' Sticks Test. The test was assessed at baseline and in the third month of isotretinoin treatment. Results: Isotretinoin improved the performance of patients in the olfactory test. The SST score increased from 8.7±1.09 to 9.5±1.19 (p<0.001), prevalence of hyposmia decreased from 40% to 24% and normosmia increased from 60% to 75% (p=0.059). The percentage of patients whose olfactory function was categorized as "good" increased from 6% to 21.3%. This increase was statistically significant (p<0.05). Study limitations: Absence of a control group is one of the limitations of this study. Also, we did not evaluate patients with smell test after stopping isotretinoin treatment. Conclusion: We examined the effect of systemic isotretinoin on olfactory function. It can be concluded from the present investigation that isotretinoin therapy improves the sense of smell.

Isotretinoin Use in Thick-Skinned Rhinoplasty Patients.

One of the characteristics of mestizo patients can be the thick sebaceous skin associated with a poor osteocartilaginous underlying nasal structure. In spite of using a proper structural approach where grafts and sutures are used to define the nasal tip, frequently the results are suboptimal. Surgical techniques have been described to reduce the thickness of the skin-soft tissue envelope, but these frequently give unreliable results. The monitored use of isotretinoin given orally as a complement after performing a rhinoplasty can adequately control the production of the sebaceous glands and thin the skin-subcutaneous tissue envelope in a uniform fashion without compromising the underlying bony and cartilaginous structures of the nose. Patients ideally should be treated jointly with a dermatologist and be followed closely to monitor hepatic function. Follow-up after 2 years with pre- and postoperative pictures shows improved definition of the nasal tip and dramatic improvement on sebaceous gland production.

Effect of retinoic acid on aquaporin 3 expression in keratinocytes.

To explore the possible mechanism of the third-generation retinoic acid drugs (isotretinoin, acitretin, adapalene) in inducing skin and mucosa dryness and rhagades; specifically, mechanism by which these drugs influence keratinocyte cell culture models in vitro (HaCaT) and aquaporin channel (AQP3) protein expression was investigated. Isotretinoin, acitretin, and adapalene were applied to human keratinocyte HaCaT cells. Immunohistochemistry, reverse transcriptase polymerase chain reaction, and western blotting were used to detect their effects on AQP3 expression in HaCaT cells at different concentrations (0.000, 0.001, 0.010, 0.060, and 0.100 mg/mL) or different at times (0, 6, 12, 24, and 48 h). At 0.010 mg/mL, maximal AQP3 expression was observed in HaCaT cells; this was significantly higher than the expressions at the other concentrations (P < 0.05). After treatment with isotretinoin, acitretin, or adapalene at 0.010 mg/mL for 12 h, the expression of AQP3 was the highest in the isotretinoin group, followed by the acitretin group, with the lowest expression in the adapalene group. However, the differences were not statistically significant (P > 0.05). Retinoic acid can increase AQP3 expression in HaCaT cells, with significant effects observed with 0.010 mg/mL isotretinoin treatment for 12 h. The side effects, namely skin and mucosa dryness caused by retinoic acid might be related to its effects on AQP3 expression.

Isotretinoin effect on alveolar repair after exodontia--a study in rats.

OBJECTIVES: To evaluate isotretinoin effect on alveolar repair after tooth extraction of maxillary incisor and serum calcium levels in rats. STUDY DESIGN: Wistar rats (60-day-old) were assigned to control (CG, n = 12) and experimental (EG, n = 20) groups. EG received daily isotretinoin (7.5 mg/kg) for 30 days before surgery and until euthanasia, 7, 21, 28, or 90 days after tooth extraction. Blood was collected in the EG to analyze serum calcium levels before isotretinoin administration and at euthanasia. Right hemimaxillae underwent histological examination, and the slides were stained with HE and analyzed by descriptive light microscopy. RESULTS: There was acceleration in the process of alveolar repair in the EG at all time points when compared to controls. Serum calcium levels showed a statistically significant decrease between first and second blood collection at days 21, 28, and 90. CONCLUSIONS: Daily isotretinoin in a dose corresponding to the treatment of cystic acne accelerated alveolar repair.

Specific gel-cream as adjuvant to oral isotretinoin improved hydration and prevented TEWL increase--a double-blind, randomized, placebo-controlled study.

BACKGROUND: Hydrating and emollient products are often recommended to patients under isotretinoin therapy to control the most frequent mucocutaneous side effects and to improve adherence to treatment. AIMS: To assess, using noninvasive biophysical tests, the clinical and instrumental effectiveness of a hydrating gel-cream compared with placebo as an adjuvant to isotretinoin for treatment of facial skin in patients with inflammatory acne. METHODS: Prospective, double-blind, randomized study, using MULTI SKIN MC750, on the adjuvant effect of a hydrating gel-cream for acne (active product) vs. a gel-cream without active substances (placebo). Follow-up lasted 3 months. RESULTS: Sixty-six patients were included. Thirty-four were administered the active product, and 32 placebo. Though the number of lesions fell significantly in both groups, the mean number of papules on day 30 was significantly lower in the active product group. The active product group showed a significant increase in hydration, while the placebo group showed a significant increase in transepidermal water loss (TEWL). Seborrhoea decreased significantly in both groups; there were no differences between them. CONCLUSIONS: Compared with placebo, the specific gel-cream with active products as an adjuvant to oral isotretinoin improved hydration, prevented TEWL increase, and reduced inflammatory acne lesions after 30 days.

Oral isotretinoin in photoaging: clinical and histopathological evidence of efficacy of an off-label indication.

BACKGROUND: Despite evidences of the beneficial clinical effects of oral isotretinoin in the treatment of cutaneous photoaging, scientific evidences are still scarce, mainly supported by histopathological and morphometric studies. OBJECTIVES: To analyse possible clinical and morphological changes resulting from the treatment of photoaging with oral isotretinoin. METHODS: Thirty female patients, aged 40 to 55 years, phototypes II to IV, with moderate to severe photoaging were randomly assigned to two groups of 15 each. Group I (G I) patients were treated with 10 mg of isotretinoin and group II (G II) with 20 mg of oral isotretinoin thrice a week for 3 months. Skin biopsies were performed before and after the end of therapy, and the various sections were submitted to specific staining for collagen and elastic fibres. To analyse the changes, morphometric studies were performed, and the results obtained were analysed by Student's t-test (paired and non-paired). Clinical results of therapy regarding texture, colouring and aspect of the wrinkles were assessed by both physician and patient. RESULTS: The increase in the amount of collagen fibres was statistically significant with both dosage regimens (mean, 37.8%, increasing to 44.4%; P = 0.029 with the 10-mg dosage; and mean, 36.6%, increasing to 41.9%; P = 0.01 with the 20-mg dosage). A pattern pointing toward a decrease in the number of elastic fibres was found (mean, 15.3-12%; P = 0.014 with the 10-mg dosage; mean, 15.5-14%; P = 0.125 with the 20-mg dosage). Additionally, there was improvement in the general aspect of the skin, regarding texture, wrinkles depth and skin coloration. LIMITATIONS: Despite ethical considerations, a lack of a control group using placebo may render the results less accurate. CONCLUSION: Low dosages of oral isotretinoin seem to be an effective therapeutic option for cutaneous photoaging.

Cytotoxic effect induced by retinoic acid loaded into galactosyl-sphingosine containing liposomes on human hepatoma cell lines.

Two retinoids, ATRA and 13cisRA, were incorporated into liposomes of different composition and charge and added to two hepatoma cell lines with different degree of transformation to measure cytotoxicity by MTT assay. Retinoid-free cationic liposomes were more toxic than the other kinds (anionic and made only of PC) but were also the best delivery system for retinoic acid to induce specific cytotoxic effects on these tumor hepatoma cell lines. Galactosyl-sphingosine containing cationic liposomes increased the cytotoxic effect induced by ATRA on Hep3B cells when compared to glucosyl-sphingosine cationic liposomes, but did not improve the effect induced by free retinoid or ATRA loaded into liposomes without glycolipids. This suggests that in this cell line, ATRA is being incorporated by a mechanism mediated by the asialoglycoprotein receptor, but at the same time, non-specific sugar-independent capture is also taking place as well as free diffusion of ATRA directly through the membrane. Galactose-specific effect was not observed in HepG2 cells treated with ATRA or both cell lines treated with 13cisRA. In fact, treatment of HepG2 cells with retinoids entrapped into liposomes likely induces proliferation instead of cytotoxicity, a result that interferes with the measurement of cell death by MTT. Compared to the specific effect of ATRA entrapped into cationic liposomes, vesicles made only by PC, did not mediate a specific mechanism, since differences between ATRA in galactosyl- and glucosyl-shpingosine PC-liposomes were not statistically significant. The specific mechanism was not present in the myoblastic cell line C2C12, where ATRA incorporated into galactosyl- and glucosyl-sphingosine containing cationic and PC-liposomes, was able to induce cytotoxicity at the same extent. Micelles containing ATRA and galactosyl-sphingosine had a significantly more toxic effect than the retinoid administered together with glucosyl-sphingosine, in Hep3B cells. Also, micelles containing ATRA were more toxic than glycolipid-containing liposomes with ATRA, for both kinds of sphingosines. The same effect was not observed in C2C12 cells, where glycolipid-containing liposomes worked better than micelles, and a sugar-specific mechanism was not seen. This suggests that, even though galactose-containing cationic liposomes could be a promising approach, a galactose-specific emulsion system could be the best strategy to specifically deliver retinoic acid to liver tumor cells, since it shows tissue specificity (perhaps induced by ASGPR-mediated internalization) and a stronger cytotoxic effect than the retinoid incorporated into liposomes.

Epidermal effects of tretinoin and isotretinoin: influence of isomerism.

The efficacy of tretinoin is well established in the treatment of acne and photoaged skin, however as a typical side effect of tretinoin treatment most patients develop a low-grade irritant dermatitis. Since isotretinoin topical treatment usually shows much lower incidence and intensity of adverse effects than tretinoin topical treatment, histological studies are needed to scientifically evaluate the effects of isotretinoin application on epidermis and also to assess if it can be used in anti-aging products as an alternative to tretinoin. Thus, the aim of this study was to compare the effects of topical use of tretinoin or isotretinoin on hairless mice epidermis, using appropriate histopathological and histometric techniques, in order to evaluate the influence of isomerism on skin effects. For this, gel cream formulations containing or not 0.05% tretinoin or 0.05% isotretinoin were applied in the dorsum of hairless mice, once a day for seven days. Histopathological evaluation, viable epidermal and horny layer thicknesses as well as the number of epidermal cell layers were determined. Our results showed that tretinoin and isotretinoin were effective in the enhancement of viable epidermis thickness and number of epidermal cell layers, suggesting that they could be used for stimulation of cellular renewal. However isomerism influenced skin effects since isotretinoin had more pronounced effects than tretinoin in viable epidermis. In addition only isotretinoin treatment enhanced horny layer thickness when compared to the gel cream treatment.

Effects of isotretinoin on the metabolism of triglyceride-rich lipoproteins and on the lipid profile in patients with acne.

Isotretinoin treatment alters the plasma lipid levels but the mechanisms and the effects on the metabolism of triglyceride-rich lipoproteins such as chylomicrons and very-low-density lipoproteins remain unclear. We investigated the effect of isotretinoin on the plasma kinetics of emulsion models of triglyceride-rich lipoproteins and the lipid profile. Ten patients with acne were treated with 0.8 mg/kg of isotretinoin over 4 weeks for comparison with non-treated acne patients. In both groups the plasma kinetic study of a triglyceride-rich emulsion double-labeled with 14C-cholesterol oleate and 3H-triolein was performed after intravenous injection of the emulsion and radioactive counting in plasma samples collected over 60 min. Patients using isotretinoin showed decreased removal from the plasma of the 3H-triglyceride (median 0.019 min-1 TG) compared with controls (median 0.044 min-1, P=0.007), and the removal of the emulsion 14C-cholesterol oleate also tended to be decreased (treatment: 0.011 min-1; controls: 0.024 min-1, P=0.06). The values of total and LDL cholesterol and triglycerides were increased post-treatment (P<0.03). In conclusion, while increasing the fasting plasma concentration of VLDL and LDL, which are traditional risk factors for atherosclerosis, isotretinoin treatment also slows down the metabolism of triglyceride-rich lipoproteins such as chylomicrons, as tested by the emulsion model, an effect that is also increasingly recognized as atherogenic.

Apoptotic events induced by naturally occurring retinoids ATRA and 13-cis retinoic acid on human hepatoma cell lines Hep3B and HepG2.

Two hepatoma cell lines were incubated for 72 h with ATRA and its analog 13cisRA and according to MTT assay, Hep3B cells were highly susceptible whereas HepG2 cells were more resistant to the treatment. At the high concentration of 166 microM, retinoids were able to induce apoptosis in both cell lines and the highest effect was observed in HepG2 cells treated with ATRA. TUNEL-based photometric ELISA showed that at the same retinoid concentration tested by flow cytometry, both cell lines showed apoptosis whereas plasma membranes were not significantly disrupted. Inhibitors of apoptosis Bcl-xL and survivin were downregulated in Hep3B cells by treatment with both retinoids. Bax, a pro-apoptotic protein, was not significantly upregulated in Hep3B cells, but was slightly increased in HepG2 cells treated with 13cisRA. Both procaspase-3 and procaspase-8 were cleaved in Hep3B cells, suggesting apoptosis could be triggered through the extrinsic pathway. In the case of HepG2 cells, lack of caspase activation suggests a mechanism dependent on other kind of proteases.

Acne vulgar / Acne vulgaris

A acne vulgar é afecçäo inflamatória crônica da unidaded pilossebáceca, dee etiologia multifatorial, sendo particularmente comum entre adolescentes e adultos jovens.Pode levar a importante morbidade física e psicológica, devendo-se atentar para o tratamento mais adequado, considerando-se também a prevençäo de sequelas. O tratamento combinado constitui alternativa comum, principalmente nos casos masi avançados da doença. O tratamento tópico envolve agentes queratolíticos, como os retinóides, o ácido azeláico e os alfa-hidroxiacidos e os bactericidas, incluindo antibióticos como clindamicina e eritromicina, além do peróxido de benzoíla. Já a terapia oral está centrada no uso da isotretinoína, principalmente na acne severa e resistente a tratamentos anteriores, pela excelente melhora do quadro e segurança no uso, comprovados ao longo de mais de 20 anos de estudo. Antibióticos sistêmicos, ,anticoncepcionais orais e antiandrogênicos também constituem alternativas eficazes na terapia oral. Cicatrizes também podem ser tratadas por técnicas mais recentes, como o resurfacing com laser dee CO2 e o preenchimento, além da dermabrasäo e do uso do punch. Diante do enorme arsenal terapêutico, cabe ao dermatologista a escolha do melhor método a seu paciente, o que constitui hoje o grande desafio no tratamento da acne vulgar.(au)

Isotretinoína: perfis farmacológico, farmacocinético e analítico / Isotretinoin: pharmacological, pharmacokinetic and analytical profiles

A isotretinoína quimicamente conhecida como ácido-13-cis-retinóico, faz parte do amplo grupo de compostos relacionados à vitamina A. É empregada particularmente no tratamento da acne cística e nodular e como inibidor da proliferação de células neoplásicas, por exercer efeito regulador sobre a diferenciação celular. Os efeitos adversos envolvendo o uso de isotretinoína estãrelacionados à pele e membranas mucosas, sistemas nervoso, músculo esquelético, linfático, gastrintestinal, cardiorespiratório e geniturinário. A isotretinoína é um composto termo e fotossensível e, por assim se apresentar, desperta o interesse pelo estudo de sua estabilidade...