Mircea Tampa

Finasteride adverse effects in subjects with androgenic alopecia: A possible therapeutic approach according to the lateralization process of the brain

Abstract Nowadays, finasteride is a relatively frequently prescribed drug in the therapeutic management of male androgenic alopecia. The reported adverse effects are notable in some patients, consisting in signs and symptoms that are encountered both during finasteride administration and after treatment cessation. Clinical and imagistic data show that cognition and sexuality are two distinct but interrelated environmental functions, most probable due to lateralization process of the brain. Specific for our topic, relatively recent published studies found that frequency and severity of finasteride adverse effects could be interrelated with hand preference and sexual orientation of the respective subjects. This paper tries to explain/support this interrelation through a psychophysiologic approach, to suggest how this premise could be further proved in dermatological practice, and to highlight its relevance in respect to therapeutic approach of male androgenic alopecia. As a possible therapeutic application, subjects having preference for a certain sexual orientation and/or predisposition for a given dominant hand could be advised before finasteride administration, that present an increased risk/sensitivity to develop adverse effects. Finally, even if finasteride and post-finasteride symptoms overlap to a large extent they should be, however, viewed as distinct physiopathologic entities, which could require perhaps different therapeutic approaches.

Are Hand Preference and Sexual Orientation Possible Predicting Factors for Finasteride Adverse Effects in Male Androgenic Alopecia

Sexual side effects of finasteride seem to be redoubtable, being encountered not only during therapy but also after treatment cessation. Consequently, any possible clinical/paraclinical elements that might predict these adverse effects would be useful in the selection of a therapeutic strategy for male androgenic alopecia. Previous published studies show that some compounds that interfere with sexual hormones can decrease sexual activation and response, according to hand preference (as reported for finasteride and tamoxifen) and according to sexual orientation (as noted for bicalutamide). Our preliminary published data and the arguments presented here suggest that these two individual parameters might be used by dermatologists in the therapeutic approach of male androgenic alopecia, so as to alert specific subsets of men, prior to treatment, of the potential increased risk for developing adverse effects to finasteride.

Protein microarray for complex apoptosis monitoring of dysplastic oral keratinocytes in experimental photodynamic therapy.

BackgroundPhotodynamic therapy is an alternative treatment of muco-cutaneous tumors that uses a light source able to photoactivate a chemical compound that acts as a photosensitizer. The phthalocyanines append to a wide chemical class that encompasses a large range of compounds; out of them aluminium-substituted disulphonated phthalocyanine possesses a good photosensitizing potential.ResultsThe destructive effects of PDT with aluminium-substituted disulphonated phthalocyanine are achieved by induction of apoptosis in tumoral cells as assessed by flow cytometry analysis. Using protein microarray we evaluate the possible molecular pathways by which photodynamic therapy activates apoptosis in dysplastic oral keratinocytes cells, leading to the tumoral cells destruction. Among assessed analytes, Bcl-2, P70S6K kinase, Raf-1 and Bad proteins represent the apoptosis related biomolecules that showed expression variations with the greatest amplitude.ConclusionsUp to date, the intimate molecular apoptotic mechanisms activated by photodynamic therapy with this type of phthalocyanine in dysplastic human oral keratinocytes are not completely elucidated. With protein microarray as high-throughput proteomic approach a better understanding of the manner in which photodynamic therapy leads to tumoral cell destruction can be obtained, by depicting apoptotic molecules that can be potentially triggered in future anti-tumoral therapies.BACKGROUND Photodynamic therapy is an alternative treatment of muco-cutaneous tumors that uses a light source able to photoactivate a chemical compound that acts as a photosensitizer. The phthalocyanines append to a wide chemical class that encompasses a large range of compounds; out of them aluminium-substituted disulphonated phthalocyanine possesses a good photosensitizing potential. RESULTS The destructive effects of PDT with aluminium-substituted disulphonated phthalocyanine are achieved by induction of apoptosis in tumoral cells as assessed by flow cytometry analysis. Using protein microarray we evaluate the possible molecular pathways by which photodynamic therapy activates apoptosis in dysplastic oral keratinocytes cells, leading to the tumoral cells destruction. Among assessed analytes, Bcl-2, P70S6K kinase, Raf-1 and Bad proteins represent the apoptosis related biomolecules that showed expression variations with the greatest amplitude. CONCLUSIONS Up to date, the intimate molecular apoptotic mechanisms activated by photodynamic therapy with this type of phthalocyanine in dysplastic human oral keratinocytes are not completely elucidated. With protein microarray as high-throughput proteomic approach a better understanding of the manner in which photodynamic therapy leads to tumoral cell destruction can be obtained, by depicting apoptotic molecules that can be potentially triggered in future anti-tumoral therapies.

Androgenetic alopecia; drug safety and therapeutic strategies

ABSTRACT Introduction: Androgenetic alopecia (AGA) is a benign condition with variable psychosocial impact, with some individuals adapting well while others needing therapeutic support. Although 5α-reductase inhibitors like finasteride and dutasteride have proven effective in ameliorating AGA, their use/selection is currently a subject of debate. Areas covered: Treatment of AGA with 5α-reductase inhibitors lead to variable adverse effects and relatively unstable results (therapeutic efficacy ending with treatment cessation), so the choice of optimal therapy is not straightforward. This paper presents a general perspective regarding AGA based on studies listed in PubMed, to better understand/appreciate the opportunity for long term use of medication for a biological condition having non-life threatening implications. Studies focussed on adverse effects suggest that finasteride should be used with caution in AGA, due to considerable and persistent side effects induced in some men. In contrast, efficacy data indicate that dutasteride (a stronger inhibitor) presents superior therapeutic results compared to finasteride. Expert opinion: This paper argues that finasteride should be preferred to dutasteride in the treatment of AGA. Thus, finasteride preserves important physiological roles of dihydrotestosterone (unrelated to AGA) and, in addition, its adverse effects seem to be (at least in part) predictable.

A case of disseminated cutaneous Kaposi sarcoma in an immunocompetent patient

Background Kaposi’s sarcoma (KS) is a tumor derived from the endothelial cell lineage caused by Kaposi sarcomaassociated virus (KSHV), also known as human herpes virus 8 (HHV-8). Four subtypes of KS have been described: classical KS, African endemic KS, immunosuppression-associated KS and AIDS-associated KS. Over 95% of the lesions have been found to be infected with HHV-8, regardless of the clinical subtype. Classical KS usually occurs in elderly men from the Mediterranean region. It is a chronic, slowly progressing disorder, usually confined to the skin, which only rarely affects other organs.

Post-Finasteride Adverse Effects in Male Androgenic Alopecia: A Case Report of Vitiligo

Finasteride has proved to be relatively safe and effective in the therapeutic management of male androgenic alopecia. However, literature data report several endocrine imbalances inducing various adverse effects, which often persist after treatment cessation in the form of post-finasteride syndrome. Here we present the case of a 52-year-old man receiving finasteride (1 mg/day) who developed an uncommon adverse effect represented by generalized vitiligo 2 months after finasteride discontinuation. Associated adverse effects encountered were represented by mild sexual dysfunction (as determined by the International Index of Erectile Function, IIEF) and moderate depressive symptoms (according to DSM-V criteria), all of these manifestations aggregating within/as a possible post-finasteride syndrome. Further studies should develop and compare several therapeutic approaches, taking into account not only compounds that decrease the circulating dihydrotestosterone level but also those that could block the dihydrotestosterone receptors (if possible, compounds with selective tropism towards the skin). In addition, the possibility of predicting adverse effects of finasteride (according to hand preference and sexual orientation) should be taken into account.

Toxicological and efficacy assessment of post-transition metal (Indium) phthalocyanine for photodynamic therapy in neuroblastoma.

Metallo-phthalocyanines due to their photophysical characteristics as high yield of triplet state and long lifetimes, appear to be good candidates for photodynamic therapy (PDT). Complexes with diamagnetic metals such as Zn2+, Al3+ Ga3+ and In3+meet such requirements and are recognized as potential PDT agents. Clinically, Photofrin® PDT in neuroblastoma therapy proved in pediatric subjects diagnosed with progressive/recurrent malignant brain tumors increased progression free survival and overall survival outcome. Our study focuses on the dark toxicity testing of a Chloro-Indium-phthalocyanine photosensitizer (In-Pc) upon SH-SY5Y neuroblastoma cell line and its experimental in vitro PDT. Upon testing, In-Pc has shown a relatively high singlet oxygen quantum yield within the cells subjected to PDT (0.553), and 50 μg/mL IC50. Classical toxicological and efficacy assessment were completed with dynamic cellular impedance measurement methodology. Using this technology we have shown that long time incubation of neuroblastoma cell lines in In-Pc (over 5 days) does not significantly hinder cell proliferation when concentration are ≤ 10 μg/mL. When irradiating neuroblastoma cells loaded with non-toxic concentration of In-Pc, 50% of cells entered apoptosis. Transmission electron microscopy has confirmed apoptotic characteristics of cells. Investigating the proliferative capacity of the in vitro treated cells we have shown that cells that “escape” the irradiation protocol, present a reduced proliferative capacity. In conclusion, In-Pc represents another photosensitizer that can display sound PDT properties enhancing neuroblastoma therapy armentarium.

Capsaicin: Friend or Foe in Skin Cancer and Other Related Malignancies?

Capsaicin is the main pungent in chili peppers, one of the most commonly used spices in the world; its analgesic and anti-inflammatory properties have been proven in various cultures for centuries. It is a lipophilic substance belonging to the class of vanilloids and an agonist of the transient receptor potential vanilloid 1 receptor. Taking into consideration the complex neuro-immune impact of capsaicin and the potential link between inflammation and carcinogenesis, the effect of capsaicin on muco-cutaneous cancer has aroused a growing interest. The aim of this review is to look over the most recent data regarding the connection between capsaicin and muco-cutaneous cancers, with emphasis on melanoma and muco-cutaneous squamous cell carcinoma.

Muco-cutaneous manifestations in HIV infection/AIDS

The HIV/AIDS infection is an important public health problem in Romania. The aim of this study was to evaluate the main muco-cutaneous manifestations and their frequency in patients with HIV infection/AIDS in Romania. The study was performed beginning 1988 among 400 patients with HIV infection/AIDS who attended Scarlat Longhin Clinical Hospital for Dermatology, Victor Babes Clinical Hospital of Infectious Diseases and Matei Bals National Institute for Infectious Diseases Bucharest, Romania. The patients were clinically examined; mycological examination (KOH exam, cultures) was necessary in 216 cases and histological examination was performed in 32 cases. The subjects were classified in all stages of disease. The age of patients included in the study ranged from 6 months to 82 years. Muco-cutaneous manifestations were present in 76% of patients. The main muco-cutaneous manifestations registered were infections - 283 cases (oral and/or genital candidiasis - 179 cases; molluscum contagiosum - 53 cases; warts - 37 cases; tinea - 36 cases; sexually transmitted infections - 107 cases: herpes simplex genitalis - 33 cases, urethritis - 31 cases, condylomata acuminata - 29 cases, syphilis - 17 cases; herpes zoster - 28 cases; scabies - 12 cases; intertrigo - 11 cases; hairy leukoplakia - 4 cases; acute retroviral infection - 2 cases; disseminated cryptococcosis - 2 cases; bacillary angiomatosis, ganglionar tuberculosis - 1 case each), xerosis - 172 cases, papular eruptions - 87 cases, seborrheic dermatitis - 57 cases, atopic dermatitis - 24 cases, drug reactions - 21 cases, cancers - 20 cases (Kaposi sarcoma - 16 cases, basal cell carcinoma - 4 cases), psoriasis - 7 cases. Muco-cutaneous manifestations in HIV infection/AIDS are frequent and polymorphous. They can occur at any point in time, but their frequency and severity are increasing as HIV infection progresses. Dermatological examination is an important step in evaluation of patients HIV-positive.

The seroprevalence of several infections in urticaria

Results Serology for hepatitis B was found to be positive in 8 patients (3.38%) in the acute spontaneous urticaria group, in 9 patients (5.35%) in the chronic spontaneous urticaria group and in 5 subjects (2.27%) in the control group. Antibodies to HCV were identified in 3 patients (1.27%) with acute spontaneous urticaria, in 4 patients with chronic spontaneous urticaria (2.38%) and in one subject (0.45%) in the control group. Antibodies to Helicobacter pylori were present in 139 acute spontaneous urticaria patients (58.89%), in 107 chronic spontaneous urticaria patients (63.69%) and in 124 (56.36%) controls.