Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience. / Psoriasis moderada-grave en pacientes pediátricos y jóvenes: experiencia en el registro BIOBADADERM.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.

Association between xerostomia, oral and general health, and obesity in adults. A cross-sectional pilot study.

BACKGROUND: The objective of this study was to analyse the association between oral and general health variables and obesity indicators with the sensation of dry mouth or xerostomia as evaluated on the Xerostomia Inventory (XI). MATERIAL AND METHODS: A total of 354 randomly selected subjects participated in this cross-sectional pilot study and completed an anonymous questionnaire. Anthropometric, clinical, and xerostomic variables were evaluated. Kruskal-Wallis, ANOVA and Bonferroni test were used for multiple comparisons. ROC curves and multinomial logistic regression were used to determine the (OR) risk of xerostomia. RESULTS: A total of 30.7 % of respondents reported xerostomia based on XI. The dry mouth question, the XI taken as a "gold standard", showed a diagnostic sensitivity of 70.37 %, and a specificity of 83.27 % (AUC=0.768, p<0.001). Logistical regression showed the highest xerostomia OR was associated to patients with bad self-perceived health, 6.31 (CI 95% 2.89-13.80, p<0.001). In the model adjusted for tooth mobility, bone or respiratory diseases, and the consumption of anxiolytics and antidepressants, the OR was 3.46 (CI 95% 1.47-8.18, p=0.005). CONCLUSIONS: a high prevalence of xerostomia was found in this cross-sectional pilot study, which was significantly more frequent in women, and increased with age. Xerostomia was associated to several systemic diseases, psychological conditions, and oral functional disorders such as tooth mobility. These preliminary results can serve as the basis for developing guidelines for the application of innovative measures designed to improve the quality of life of individuals with xerostomia.

Changing Trends in Drug Prescription and Causes of Treatment Discontinuation of First Biologic Over Ten Years in Psoriasis in the Spanish Biobadaderm Registry. / Cambios en las tendencias de la prescripción y causas de la interrupción en los tratamientos biológicos indicados en la psoriasis durante los primeros 10 años. Datos obtenidos del registro español Biobadaderm.

BACKGROUND AND OBJECTIVES: Current psoriasis guidelines do not usually include recommendations about first line classical or biologic treatment. The objectives of this study were: to describe shifts in the prescription of the first biological treatment, and to compare treatment withdrawal and rates of adverse events over ten years. MATERIAL AND METHODS: Biobadaderm registry was analyzed to describe: first biological prescription in bio-naïve patients, adverse events rate and reasons for drug withdrawal comparing three periods of time (2008-2010, 2011-2014, 2015-2018). RESULTS: Anti-TNF drugs were the most prescribed biological drug from 2008 to 2010. Ustekinumab has become the most prescribed first biologic since 2014. The main reasons for drug discontinuation were adverse events, lack of efficacy and remission. In each period any treatment was less likely to be discontinued due to any of these three reasons comparing to the previous period. CONCLUSIONS: The present study identifies trends in prescription of the first biological antipsoriatic drug in clinical practice from 2008 to 2018. It suggests that we have become more comfortable with the safety profile and more exigent with the efficacy of the drugs.

Comorbidities in childhood associated with extrauterine growth restriction in preterm infants: a scoping review.

Extrauterine growth restriction (EUGR) is a frequent morbidity of preterm infants that can affect short- and long-term prognosis as it involves different EUGR-related alterations in growth and neurological development, as well as cardiometabolic risk. However, knowledge about the prognosis of EUGR is scarce. Thus, the objective of this study is to review the evidence regarding EUGR-related comorbidities in childhood by a systematic approach. This review was carried out using the Joanna Briggs Institute Reviewers' Manual Methodology and the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses)-Search Extension for scoping review. The MEDLINE and EMBASE databases were used to identify papers published until September 2017. Twenty-four publications were included and 19 examined cohort studies. EUGR is mainly associated with (1) lower weight, length, and head circumference measures in childhood; (2) poor neurodevelopment; and (3) alterations in cardiometabolic risk markers. The definition for EUGR and the populations studied differ among authors.Conclusion: EUGR is mainly associated with poor growth and neurodevelopment, as well as with cardiometabolic alterations in childhood. Evidence is based on observational studies with variability in the included populations due to the lack of consensus regarding the definition for EUGR. Finding a gold standard definition becomes paramount in order to select phenotypes at risk later in life. What is known? • EUGR is a frequent condition of preterm infants. Up to date little is known about the effect of the metabolic programming on prognosis. What is new? • The available evidence, which is based on observational studies with variability in the population and the existing different definitions for EUGR, do not enable appropriate data collection. EUGR is mainly associated with poor growth and neurodevelopment, as well as with cardiometabolic alterations in childhood.

Management options for low-dose methotrexate-induced oral ulcers: A systematic review.

BACKGROUND: Oral ulcers caused by methotrexate (MTX) at low doses are a known side effect of this drug. Although increasingly more patients are medicated with MTX, these painful ulcers, without traumatic origin and resistant to any type of treatment, are not usually identified by health professionals as a side effect of the medication. MATERIAL AND METHODS: In the absence of a consensus protocol for the effective treatment of oral lesions produced by MTX, the objective of this article was to review and analyse the information from articles related to oral ulcers produced by low-dose MTX and to record the clinical management performed and the MTX dose given to the patient. Data sources - Medline, Web of Science, and Cochrane Library. Participants - Patients treated with low-dose MTX (less than 25 mg/week). Interventions - Management of oral lesions caused by MTX. Study eligibility criterion, study appraisal and synthesis method: An initial search was carried out in the aforementioned databases with the terms 'methotrexate AND oral OR ulcer'. The search was carried out using both medical subject heading (MeSH) terms and a free search between January 2003 and January 2018. Of the results obtained, two independent researchers analysed abstracts that met the search criteria, that is, those that mentioned oral ulcers produced by MTX at low doses. Next, both researchers read the complete article and determined whether it met the following inclusion criteria: written in English, specified the dose of MTX prescribed for the patient and specified the protocol of action for the ulcers. A third investigator acted as a mediator in cases of dispute. Agreement was calculated using Cohen's kappa coefficient, with a k value of 0.82. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide for systematic reviews was used. RESULTS: The initial search resulted in a total of 66 articles, of which 30 were selected to assess their inclusion in this study. Finally, 16 met the inclusion criteria. Using the Pierson and Newcastle-Ottawa scales and Bradford Hill criteria modified for studies of case series and "in relation to a case", 2 were rated as high quality, 2 were rated as low quality and 12 were rated as medium quality. The limitations of this study are based on the fact that all of the articles available to carry out the systematic review were "in relation to a case or series of cases", with the heterogeneity of data that this implies. CONCLUSIONS: Evidence on the management of oral ulcers in the oral cavity produced by MTX at low doses is scarce due to the heterogeneity of data and the measures adopted in the selected studies. Therefore, it seems that this management is relegated to the perception of the clinician rather than to a specific protocol of action. Studies with a longer follow-up duration and larger sample size are needed to guide different health professionals on the management of these lesions.

Description of Patients Treated with Biologic Drugs as First-Line Systemic Therapy in the BIOBADADERM Registry Between 2008 and 2016. / Descripción de los pacientes que reciben biológicos como primer tratamiento sistémico en el registro BIOBADADERM durante el periodo 2008-2016.

INTRODUCTION AND OBJECTIVES: Biologic drugs are usually prescribed as second-line treatment for psoriasis, that is, after the patient has first been treated with a conventional psoriasis drug. There are, however, cases where, depending on the characteristics of the patient or the judgement of the physician, biologics may be chosen as first-line therapy. No studies to date have analyzed the demographics or clinical characteristics of patients in this setting or the safety profile of the agents used. The main aim of this study was to characterize these aspects of first-line biologic therapy and compare them to those observed for patients receiving biologics as second-line therapy. MATERIAL AND METHOD: We conducted an observational study of 181 patients treated in various centers with a systemic biologic drug as first-line treatment for moderate to severe psoriasis between January 2008 and November 2016. All the patients were registered in the Spanish Registry of Adverse Events Associated with Biologic Drugs in Dermatology. RESULTS: The characteristics of the first- and second-line groups were very similar, although the patients receiving a biologic as first-line treatment for their psoriasis were older. No differences were observed for disease severity (assessed using the PASI) or time to diagnosis. Hypertension, diabetes, and liver disease were all more common in the first-line group. There were no differences between the groups in terms of reasons for drug withdrawal or occurrence of adverse effects. CONCLUSIONS: No major differences were found between patients with psoriasis receiving biologic drugs as first- or second-line therapy, a finding that provides further evidence of the safety of biologic therapy in patients with psoriasis.

Cumulative exposure to biological therapy and risk of cancer in patients with psoriasis: a meta-analysis of Psonet studies from Israel, Italy, Spain, the U.K. and Republic of Ireland.

BACKGROUND: Cancer risk following long-term exposure to systemic immunomodulatory therapies in patients with psoriasis is possible. OBJECTIVES: To assess a dose-response relationship between cumulative length of exposure to biological therapy and risk of cancer. METHODS: Four national studies (a healthcare database from Israel, and prospective cohorts form Italy, Spain and the U.K. and Republic of Ireland) collaborating through Psonet (European Registry of Psoriasis) participated in these nested case-control studies, including nearly 60 000 person-years of observation. 'Cases' were patients who developed an incident cancer. Patients with previous cancers and benign or in situ tumours were excluded. Four cancer-free controls were matched to each case on year of birth, sex, geographic area and registration year. Follow-up for controls was censored at the date of cancer diagnosis for the matched case. Conditional logistic regression was performed by each registry. Results were pooled using random-effects meta-analysis. RESULTS: A total of 728 cases and 2671 controls were identified. After matching, differences between cases and controls were present for the Charlson Comorbidity Index in all three registries, and in the prevalence of previous exposure to psoralen-ultraviolet A and smoking (the British Association of Dermatologists Biologic Interventions Register only). The risk of first cancers was not significantly associated with cumulative exposure to biologics (adjusted odds ratio per year of exposure 1·02, 95% confidence interval 0·92-1·13). Results were similar if squamous and basal cell carcinomas were included in the outcome. CONCLUSIONS: Cumulative length of exposure to biological therapies in patients with psoriasis in real-world clinical practice does not appear to be linked to a higher risk of cancer after several years of use.

Adverse events associated with discontinuation of the biologics/classic systemic treatments for moderate-to-severe plaque psoriasis: data from the Spanish Biologics Registry, Biobadaderm.

BACKGROUND: Little is known about the adverse events (AEs) that lead to suspension of systemic treatments for psoriasis in clinical practice. OBJECTIVE: The study aimed to investigate AEs associated with discontinuation of systemic therapy in patients with psoriasis in a clinical setting (Biobadaderm). MATERIALS AND METHODS: Multicentre, prospective, cohort study of patients with moderate-to-severe plaque psoriasis receiving systemic therapies from January 2008 to November 2015, in 12 hospitals in Spain. The incidence rate (IR) was used to compare biologics and classic systemic therapies. RESULTS: A total of 4218 courses of treatment were given to 1938 patients. A total of 447 (11%) treatments were discontinued due to AEs. The IR of AE associated with discontinuation of systemic therapies was 13 events/100 patient-years (PY) (95% CI: 12.14-13.93), 9.34 events/100 PY (95% CI: 8.44-10.33) for biologics and 19.67 (95% CI: 17.9-21.6) events/100 PY for classics (P < 0.001). Of 810 discontinuation-related AEs, 117 (14%) were serious. The highest IRs were for cyclosporine [49.18/100 PY (95% CI: 41.91-57.72)] and infliximab [26.52/100 PY (95% CI: 20.98-33.51). Ustekinumab presented the lowest IR (2.6/100 PY (95% CI: 1.83-3.69). LIMITATIONS: Observational study with potential selection bias. CONCLUSION: Biologic therapies are associated with a lower rate of discontinuation-related AEs than are classic therapies in real clinical practice. Ustekinumab showed the lowest incidence.

Comparison of phenotype, comorbidities, therapy and adverse events between psoriatic patients with and without psoriatic arthritis. Biobadaderm registry.

BACKGROUND: There are a limited number of studies comparing psoriasis patients without psoriatic arthritis (PsA) to those with arthritis. Previous results are controversial. OBJECTIVES: To perform a comparative analysis of the phenotype, baseline comorbidities, therapeutic profile and incidence of adverse events (particularly overall adverse events, infections and infestations, malignancies and psychiatric disorders) among psoriatic patients with/without PsA. METHODS: All the patients on the Biobadaderm registry, a prospective inception cohort of psoriasis patients on systemic therapy, were included. Patients were divided into two groups: those with psoriasis without arthritis at the time of entry into the cohort (Pso group) and those with psoriasis and psoriatic arthritis (PsA group) at entry. Patients were followed until the censorship date (last visit in a lost-to-follow-up patient, or 10 November 2015, whichever occurred first). We excluded all the patients who developed any kind of signs and/or symptoms of joint involvement during the follow-up. A descriptive analysis was performed. We estimated incidence ratios (IRR) of adverse events during systemic treatment using a mixed-effects Poisson regression. RESULTS: We included 2120 patients: 1871 (88%) patients with psoriasis without arthritis and 249 (12%) with psoriasis and PsA. The follow-up time was 5020 patients-year in the Pso group and 762 patients-year in the PsA group. Patients with PsA had more comorbidities, particularly hypertension and liver disease; used a higher number of systemic therapies, particularly anti-TNFα drugs and combination therapy; and presented more adverse events (IRR adjusted = 1.29; 95% CI: [1.05-1.58]), particularly serious adverse events (IRR adjusted = 1.51; 95% CI: [1.01-2.26]) and infections/infestations (IRR adjusted = 1.88; 95% CI: [1.27-2.79]), independently of the associated comorbidities and present/past therapies. CONCLUSIONS: Given the differences between patients with psoriasis alone or with psoriasis associated with PsA, patients with psoriasis and PsA should be followed and managed more closely and with specific attention.

Management of Biologic Therapy in Moderate to Severe Psoriasis in Surgical Patients: Data From the Spanish Biobadaderm Registry. / Manejo de los tratamientos biológicos en pacientes con psoriasis moderada-grave sometidos a intervenciones quirúrgicas en el registro español Biobadaderm.

BACKGROUND AND OBJECTIVE: We now have considerable experience in the use of biologic agents to treat psoriasis, but doubts about management arise in certain clinical settings. Surgery is one of them. Although treatment guidelines advise that biologics be suspended before major surgery, data about actual clinical practices and associated complications are lacking. We aimed to analyze current practice in the clinical management of these cases. METHODS: Retrospective study of cases in the Biobadaderm database. We analyzed the management of biologic therapy in patients with psoriasis who underwent surgical procedures. RESULTS: Forty-eight of the 2113 patients registered in Biobadaderm underwent surgery. The largest percentage of procedures (31%) involved skin lesions. Biologic treatment was interrupted in 42% of the cases. No postsurgical complications were significantly related to treatment interruption. Likewise we detected no associations between treatment interruption and other variables, such as sex, age, or duration or severity of psoriasis. CONCLUSION: Continuity of biologic treatment and the risk of postsurgical complications were not associated in this study, although conclusions are limited by the small sample size.

Survival of classic and biological systemic drugs in psoriasis: results of the BIOBADADERM registry and critical analysis.

BACKGROUND: Few reported studies compare drug survival in moderate-to-severe psoriasis vulgaris. OBJECTIVES: To describe and compare drug survival of systemic drugs, including biologic agents (infliximab, etanercept, adalimumab and ustekinumab) and classical drugs (acitretin, ciclosporin and methotrexate) in moderate-to-severe psoriasis. METHODS: This was a multicenter, prospective, cohort study of patients receiving systemic therapies between 2008 and 2013 in 12 hospitals in Spain. Baseline data and drug discontinuation were collected. Drug survival is presented using Kaplan-Meier survival curves. We compared adjusted risk ratios of serious adverse events (AEs) with results of survival analysis for AEs. RESULTS: A total of 1956 patients were included for analysis (1240 exposed to biologics during follow-up and 1076 to classic therapies). Median follow-up time was 3.3 years (0.0-5.1 years). There were 2209 discontinuations out of 3640 therapy cycles started. The main reason for discontinuation was lack of efficacy (36.4%) and remission (27.2%). Biologics showed a higher drug survival than classics and the pattern of survival results for all outcomes (positive or negative) were very similar. Adjusted risk ratios of serious AEs did not agree with results of survival analysis. LIMITATIONS: A limitation is that this is an observational study with potential selection bias. CONCLUSION: Survival as a proxy measure of drug safety in psoriasis is inadequate.

Does the treatment ladder for systemic therapy in moderate to severe psoriasis only go up? The percentage of patients with severe psoriasis on biologics increases over time.

BACKGROUND: With the advent of biologic drugs in the management of moderate to severe psoriasis, there may have been a shift in therapeutic approach from rotational strategies to a unidirectional progression from topical treatments to the highest rung of the therapeutic ladder. We studied the frequency of switching from classic to biologic therapy and vice versa in a cohort of patients with psoriasis over a period of up to 5 years. METHODS: Patients are included in the BIOBADADERM prospective registry when they are first prescribed any specific conventional or biologic systemic treatment. The data for each patient refer to the follow-up period from the time they entered the cohort until October 2013. To describe the pattern of switches from classic to biologic therapy and vice versa, we used the data in the registry on the first day of every 365-day period following the date each patient was included in the cohort. RESULTS: In total, 47.3% of the patients (926/1956) were prescribed a classic systemic drug and 52.7% (1030/1956) a biologic agent on entry into the study. Of the 741 patients who accumulated 5 years of follow-up, 21.9% (155) were receiving nonbiologic drugs and 78.1% (553) were on biologic therapy on the first day of their 5th year of follow-up. CONCLUSIONS: The proportion of patients receiving biologic therapy increased with longer follow-up.

Safety of classic and biologic systemic therapies for the treatment of psoriasis in elderly: an observational study from national BIOBADADERM registry.

BACKGROUND: Psoriasis patients over 65 years-old (elderly) constitute a growing group, underrepresented in clinical trials, and likely to be more prone to adverse events. OBJECTIVE: To describe safety of systemic psoriasis therapy in patients over 65 years-old compared to younger patients. METHODS: Patients registered in Biobadaderm, a Spanish national registry of psoriasis patients treated with systemic therapy, were grouped in elderly (≥ 65 years old) and younger patients. Rates of adverse events were described by severity and type, and the risks compared in both groups, taking into account exposure to classic or biologic drugs, using Cox regression. RESULTS: 175 (9.8%) of 1793 patients were elderly. Overall risk of adverse events was not higher in elderly (drug group adjusted HR 1.09 (95%CI: 0.93-1.3)). Serious adverse events were more common in elderly (drug group adjusted HR 3.2 (95%CI: 2.0-5.1)). Age adjusted HR of all adverse events was lower for patients exposed to biologics compared to classic drugs in the whole sample (HR 0.7 (95%CI: 0.6-0.7)). Age did not seem to modify the effect of therapy (biologic vs. classic) in the risk of adverse events (likelihood ratio test for interaction, p = 0.12 for all adverse events, p = 0-09 for serious adverse events). CONCLUSIONS: Serious adverse events are more common in elderly patients, although they may be related to other variants that are associated with this age group and not due to the treatment itself. Use of biologics was associated with lower risk of adverse events in the whole group. We found no differences in this association between young and elderly. These results are reassuring, although uncontrolled confounding could not be excluded as an explanation for these findings, and the power of the study to detect differences was low.

Risk of adverse events in psoriasis patients receiving classic systemic drugs and biologics in a 5-year observational study of clinical practice: 2008-2013 results of the Biobadaderm registry.

BACKGROUND: Biobadaderm is the Spanish registry of psoriasis patients receiving systemic treatment in clinical practice. OBJECTIVE: To compare the safety of biologics and classic systemic treatment. METHODS: Prospective cohort of patients receiving biologics and classic systemic therapies between 2008 and 2013 in 12 hospitals are included. We registered demographic data, diagnoses, comorbidities, treatments and adverse events (AE). We obtained raw relative risks (RR) for specific AE. Multivariate analysis consisted of Cox models adjusting for age, gender, chronic hepatic disease and previous cancer. RESULTS: A total of 1030 patients received biologics (2061 AE in 3681 person-years), 926 patients classic systemic drugs (1015 AE in 1517 person-years). Ninety-three per cent of AE in both groups were non-serious, 6% serious and 0.003% fatal. The age- and gender-adjusted hazard ratio of AE was lower in the biologics group [hazard ratio 0.6 (95% CI: 0.5-0.7)].We found no differences in rates of serious and mortal AE. Some system organ class AE rates differed between both groups. As limitations: Prescription bias might affect the incidence of AE in both groups. Association of drug and AE was based on timing: associations might not be causal. CONCLUSION: Patients receiving biologics had lower risk of AE. We did not find differences in the risk of serious or fatal AE.

Chemopreventive potential of phenolic compounds in oral carcinogenesis.

OBJECTIVE: To evaluate the chemopreventive potential of phenolic compounds - potassium apigenin, cocoa, catechins, eriocitrin and rosmarinic acid in oral carcinogenesis induced in hamsters by means of the topical application of 7,12-dimethylbenz(a)anthracene(DMBA). STUDY DESIGN: An experimental study at the University of Murcia. METHODS: 50 male Syrian hamsters (Mesocricetus auratus) were divided into five groups of ten: Group I (control group): 0.5% DMBA; Group II: 0.5% DMBA+1.1mg/15ml potassium apigenin; Group III: 05% DMBA+2.5mg/15ml cocoa catechins; Group IV: 0.5% DMBA+6mg/15ml eriocitrin; Group V: 0.5% DMBA+1.3mg/15ml rosmarinic acid. The flavonoids were administered orally. All the animals were sacrificed after 12 weeks. Macroscopic, microscopic and immunohistochemical (PCNA and p53) analyses of the lesions were performed. RESULTS: All the groups treated with phenolic compounds showed lower incidences of tumour, greater differentiation and lower scores in the tumour invasion front grading system in comparison with the control group. Potassium apigenin and rosmarinic acid achieved the best results, the former considerably reduced the carcinoma tumour volumes developed and both significantly reduced the intensity and aggression of the tumours. Immunoexpression of PCNA and p53 were significantly altered during DMBA-induced oral carcinogenesis. CONCLUSIONS: Animals treated with phenolic compounds, particularly potassium apigenin and rosmarinic acid, showed a lower incidence of tumours.

Body mass index in patients with moderate-to-severe psoriasis in Spain and its impact as an independent risk factor for therapy withdrawal: results of the Biobadaderm Registry.

BACKGROUND: There are few data on the prevalence of obesity in the general psoriasis population and on the real impact of obesity on the management of psoriasis patients in the clinical setting. OBJECTIVES: To evaluate the prevalence of overweight and obesity in patients with moderate-to-severe psoriasis compared to the general population and to assess the relationship between Body Mass Index (BMI) and the risk of discontinuing treatment. METHODS: Patients registered on Biobadaderm, a prospective registry, were grouped according the different categories of BMI and compared to the general Spanish population. Drug survival was analysed considering only drug withdrawal due to lack of effectiveness, remission and adverse events. RESULTS: A total of 1162 moderate-to-severe psoriasis patients on systemic conventional or biological treatment were recruited. The prevalence of obesity was found to be significantly higher in psoriasis patients than in the general Spanish population (P < 0.001). In multivariate analysis a 5-unit increase in BMI, similar to a change in BMI category from normal weight to overweight and from overweight to obesity, was associated with a 12% increased risk of discontinuing therapy due to lack of effectiveness (HR 1.12, 95% CI: 1.01-1.24) and with a 17% increased risk of having an adverse event (HR 1.17, 95% CI: 1.02-1.36), both independently of the drug used. CONCLUSIONS: Patients with moderate-to-severe psoriasis had a higher prevalence of obesity than the general population. Increased BMI was associated with an increased risk of treatment discontinuation due to lack of effectiveness and a higher risk of adverse events.

Effect of the phenolic compounds apigenin and carnosic acid on oral carcinogenesis in hamster induced by DMBA.

OBJECTIVE: To investigate oral carcinogenesis in hamster induced by the topical application of 7,12-dimethyl benzanthracene (DMBA) to evaluate the different lesions produced and the possible preventive effects of the phenolic compounds apigenin (flavone) and carnosic acid (diterpene). MATERIALS AND METHODS: Thirty-two Syrian hamsters were divided into three groups: I: 0.5% DMBA (n = 12); II: 0.5% DMBA + potassium apigenin (n = 8); III: 0.5% DMBA + carnosic acid (n = 12). All the animals were sacrificed after 11 weeks, and a macroscopic and light microscopic study was made of the lesions. RESULTS: The largest number of neoplasms, showing the most aggressive biological behavior, corresponded to the control group. The group treated with potassium apigenin ranked second in tumor incidence, although the tumors were not very aggressive behavior. In the group treated with carnosic acid, only one malignancy was recorded, showing the smallest volume of all the recorded tumor lesions. CONCLUSIONS: Our findings indicate that both potassium apigenin and carnosic acid have chemoprotective effects against carcinogenesis induced by DMBA in hamster.