Ahmet Akar

Topical cannabinoid antinociception: synergy with spinal sites

Analgesic effects of cannabimimetic compounds have been known to be related to their central effects. Cannabinoid receptors also exist in the periphery but their role in pain perception has been remained to be clarified. Therefore, we assessed topical antinociceptive effects of WIN 55, 212‐2, a mixed CB1 and CB2 receptors agonist, in mice using tail‐flick test. Immersion of the tail of mouse into the WIN 55, 212‐2 solution produced dose‐dependent antinociception. This antinociceptive activity was limited to the portion of the tail exposed to WIN 55, 212‐2. The antinociceptive response was dependent on duration of exposure to WIN 55, 212‐2 solution. The topical antinociceptive effects of WIN 55, 212‐2 were dose dependently blocked by topical pretreatment of CB1 receptor‐selective antagonist, AM 251. Thus, topical antinociceptive action of WIN 55, 212‐2 involve CB1 receptors. Intrathecal (i.th.) administration of WIN 55, 212‐2 produced a dose‐dependent antinociceptive effect. Interestingly, ineffective i.th. doses of WIN 55, 212‐2 produced a marked antinociception when combined with topical application of WIN 55, 212‐2 and topical antinociceptive effect was potentiated. The dose–response curve of i.th. WIN 55, 212‐2 was shifted to the left 15‐fold by topical WIN 55, 212‐2. This finding suggests that there is an antinociceptive synergy between peripheral and spinal sites of cannabinoid action and it also implicates that local activaton of cannabinoid system may regulate pain initiation in cutaneous tissue. Our findings support that cannabinoid system participates in buffering the emerging pain signals at the peripheral sites in addition to their spinal and supraspinal sites of action. In addition, an antinociceptive synergy between topical and spinal cannabinoid actions exists. These results also indicate that topically administered cannabinoid agonists may reduce pain without the dysphoric side effects and abuse potential of centrally acting cannabimimetic drugs.

Body dysmorphic disorder in patients with acne

There is growing evidence that the prevalence of body dysmorphic disorder (BDD) is significantly higher in specially selected populations as compared to the general population. The goal of the current study was to evaluate prevalence of BDD in Turkish patients with mild acne presenting to a dermatologist for treatment. This study was the first empirical investigation of BDD in acne patients in Turkey. One hundred fifty-nine outpatients diagnosed with acne who consulted to the dermatology clinic were included in the study. The diagnosis of BDD was based on DSM-IV criteria and the Structured Clinical Interview for DSM-IV (SCID-I). A study-specific questionnaire was administered to document and investigate the demographic and clinical characteristics of the cases. Fourteen (8.8%) patients were diagnosed with BDD. Three (21.4%) patients with acne and BDD also had concomitant psychiatric diagnoses. All of the patients were psychiatric management-naive, never received any psychological or physical treatments. BDD was a common psychiatric condition in acne cases. We suggest that dermatologists should routinely explore symptoms and screen such patients for BDD.

Antioxidant enzymes and lipid peroxidation in the scalp of patients with alopecia areata

Alopecia areata (AA) is an autoimmune inflammatory disease. However, little is known about the alterations in lipid peroxidation and antioxidant enzymes in the scalp of patients with AA. Therefore, the aim of this study was to investigate the status of oxidative stress in the scalp of patients with AA. We measured the levels of thiobarbituric acid reactive substances (TBARS) as lipid peroxidation status, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as antioxidant enzymes in the scalp of ten patients with AA and ten control subjects. The levels of TBARS in scalp of patients with AA (3654.1+/-621.2 nmol/g tissue) were significantly higher than those of controls (1210.2+/-188.8 nmol/g tissue) (P=0.002). The levels of SOD (134.8+/-23.8 U/g tissue) and GSH-Px (332.7+/-66.2 U/g tissue) in scalp of patients with AA were also significantly higher than those of controls (63.2+/-8.8 U/g tissue, 112.0+/-18.4 U/g tissue, respectively) (P=0.019, P=0.002, respectively). The mean levels of TBARS, SOD and GSH-Px in early phase of disease were increased 2-fold as compared with late phase of the disease. These results indicate that oxidative status is affected in AA. Lipid peroxidation and antioxidant enzymes may be involved in the pathogenesis of AA. Furthermore, we found high SOD and GSH-Px activities in the scalp of patient with AA. These high levels could not protect the patients against the reactive oxygen species, because lipid peroxidation could not be lowered in AA patients.

An open, randomized, prospective, comparative study of topical pimecrolimus 1% cream and topical ketoconazole 2% cream in the treatment of seborrheic dermatitis

Background: Seborrheic dermatitis (SD) is a chronic inflammatory disorder that mainly affects the seborrheic region. While ketoconazole is often used, pimecrolimus has been used successfully in SD. Objective: To compare the efficacy and tolerability of pimecrolimus in comparison with ketoconazole in the treatment of SD. Methods: A total of 48 patients with SD were included in the study. Patients were randomized into two groups: 23 and 25 patients in the pimecrolimus and ketoconazole groups, respectively. Clinical measures were assessed by erythema, scaling and infiltration, which were evaluated using a four-point scale (0 to 3) at 2, 6, and 12 weeks. Results: Of these 48 patients, 38 completed the study (18 and 20 patients in the pimecrolimus and ketoconazole groups, respectively). The mean percentage decrease in clinical severity scores from baseline to the last follow-up period was 86.2% and 86.1% in the pimecrolimus and ketoconazole groups, respectively. Both pimecrolimus and ketoconazole were effective in SD. Differences between the two groups were not statistically significant. Side effects were observed more frequently with pimecrolimus than with ketoconazole and this difference was statistically significant. Conclusion: Our study showed that pimecrolimus had a comparable efficacy profile with that of ketoconazole, but side effects appeared more frequently in the pimecrolimus group than in the ketoconazole group.

An open, randomized, comparative study of oral fluconazole, itraconazole and terbinafine therapy in onychomycosis

OBJECTIVE: In this open, randomized and comparative study, the safety and efficacy of systemic fluconazole, itraconazole and terbinafine was investigated in 50 patients with distal subungual toenail onychomycosis diagnosed clinically and mycologically. The patients with positive mycology and also the patients with positive microscopy and negative culture were investigated. METHODS: The treatment duration was 3 months, and the follow-up period was 6 months. Patients were randomly assigned: 16 patients received 150 mg fluconazole once weekly, 18 patients received 200 mg itraconazole twice daily with meals during the first week of each month, and 16 patients received 250 mg/day terbinafine during the treatment period. RESULTS: In a clinical evaluation, at the endpoint of the follow-up period, the clinical cure rates were 81.3% (13/16) in the terbinafine group, 77.8% (14/18) in the itraconazole group, and 37.5% (6/16) in the fluconazole group. The mycological cure rates were 75% (12/16), 61.1% (11/18) and 31.2% (5/16), respectively. The overall assessment rates were 62.5% (10/16), 61.1% (11/18) and 31.2% (5/16), respectively. Statistically significant intra-group reductions from baseline symptom severity values were seen at the endpoint of treatment and at the endpoint of the follow-up period for all three treatment groups in onycholysis, subungual hyperkeratosis, affected-area percentage score and total score parameters (p < 0.001). At the endpoint of the follow-up period, statistically significant differences between the treatment groups were seen in clinical, mycological and overall assessment (p < 0.05). However, while no statistically significant difference between the terbinafine and itraconazole groups was seen, there was a clinical and statistical difference between the other groups and the fluconazole group. Treatment was not stopped for side effects such as mild gastrointestinal and central nervous system symptoms. These effects were noted in four patients in the fluconazole group (25%), five patients in the itraconazole group (27.8%), and three patients in the terbinafine group (18.75%). The clinical laboratory data on all three drug groups did not show any statistically or clinically significant intra-group changes from baseline values at the endpoint (p > 0.05). CONCLUSION: This comparative study of systemic fluconazole, itraconazole and terbinafine showed that all three drugs were effective and safe in the treatment of onychomycosis. However, fluconazole, at these doses and treatment durations, was the least effective. With regard to cost-effectiveness, side effects and the cure rates, terbinafine could be the drug of choice in the short-term treatment of toenail onychomycosis.

Skin problems in amputees : a descriptive study

Background  Skin problems are common in amputee patients. These problems may restrict the normal use of a prosthetic limb. We aimed to determine the range, incidence, causes and patterns of dermatological problems seen in a population of amputees.

Association of human leukocyte antigen class II alleles with pemphigus vulgaris in a Turkish population

Pemphigus vulgaris (PV) is a severe autoimmune blistering skin disorder that is strongly associated with major histocompatibility complex class II alleles. Human leukocyte antigen (HLA) subtypes vary with racial/ethnic backgrounds. The purpose of this study was to determine the association of HLA class II alleles and haplotypes with PV in Turkish patients. Twenty‐five patients with PV and 113 healthy transplant donors were genotyped for HLA class II alleles. HLA DNA typing was performed by the polymerase chain reaction/sequence specific primer method. The frequency of HLA DRB1*04 allele was 68.00% in patients compared to 30.97% in controls (P = 0.0012) and the frequency of HLA DRB1*14 allele was 32.00% in the patient group compared to 8.85% in the control group (P = 0.0054). Also, the frequency of HLA DRB1*04/DQB1*03 and HLA DRB1*14/DQB1*05 haplotypes in PV patients was significantly higher than controls (32.0% vs 6.2%, χ2 = 28.142, P < 0.001; and 16% vs 2.7%, χ2 = 15.143, P = 0.001, respectively). A preventive allele or haplotype for the manifestation of PV has not been identified in this study. Our findings suggest that HLA DRB1*04 and DRB1*14 alleles, and HLA DRB1*04/DQB1*03 and HLA DRB1*14/DQB1*05 haplotypes are genetic markers for general susceptibility to PV in the Turkish population.

Broadband targeted UVB phototherapy for localized vitiligo: a retrospective study

Phototherapy with ultraviolet B (UVB) or PUVA has been used in the treatment of vitiligo for many years. The aim of this study was to analyze retrospectively the efficacy and safety of targeted broadband UVB phototherapy in patients with localized vitiligo. Thirty‐two patients (14 male, 18 female), aged 18–65 years, were treated with Daavlin T500x High Dose Targeted Phototherapy System. Patients were treated twice or thrice weekly, totaling 20 to 60 sessions. Out of 32 total patients, only four patients (12.5%) showed visible repigmentation. In two patients, repigmentation was more than 75%. Other two patients showed mild repigmentation (less than 25%). All the lesions responsive to treatment were facial lesions. Mild adverse events recorded in 3 of 32 patients. Although safety of targeted broadband UVB phototherapy in the treatment of localized vitiligo is good, its therapeutic effectiveness is limited and depends on the locations of vitiligo lesions.

The effect of oral cyclosporine in the treatment of severe alopecia areata.

Abstract Context: Alopecia areata (AA) is a common non-scarring hair loss condition with an unpredictable and relapsing disease course. T-cell mediated autoimmune process is mainstay of the pathogenesis of AA, therefore immunosuppressive therapies are widely used in the treatment of AA. Objective: The aim of the study was to evaluate efficacy of oral cyclosporine therapy and reveal effects of prognostic factors in the treatment of severe AA. Materials and methods: We evaluated case histories of patients who were admitted to our department between December 2004 and September 2011 for the treatment of severe AA. A total of 25 patients were included in the study. Patients’ data that included sex, age, alopecia type, alopecia duration, family history, atopic history, previous treatments, treatment dosage, treatment duration, adverse events and clinical response were retrieved from patients’ records. Twelve patients had multifocal AA, nine patients had alopecia universalis and four patients had alopecia totalis. Patients were treated with 2.5–6 mg/kg/d doses of oral cyclosporine for 2–12 months. Results: The mean age of patients was 21.92 ± 3.56 (range: 19–34) years. All patients were male. The mean duration of disease was 8.3 ± 6.48 (range: 0.5–21) years. Four patients had positive family history and three patients had atopy history. Three of 25 (16%) patients discontinued treatment due to adverse events. Of remaining 22 patients, significant hair growth was observed in 10 (45.4%) patients; five patients with multifocal AA, three patients with alopecia universalis and two patients with alopecia totalis. In addition to this, six of nine patients with less than four years disease duration showed significant hair growth. But in patients with more than four years disease duration, only 4 of 13 patients showed significant hair growth. Conclusion: This study indicates that oral cyclosporine treatment may be a beneficial treatment option for severe AA. In addition to this, disease duration is an important prognostic factor that influences efficacy of oral cyclosporine treatment.

Lack of efficacy of topical imiquimod in the treatment of patchy alopecia areata

They reported a 29-year-old man with Henoch-Schönlein purpura (HSP), and skin biopsy showed leukocytoclastic vasculitis with perivascular dense neutrophilic infiltration and stomach biopsy demonstrated extravasation of erythrocytes with mononuclear cell infiltration in the stroma. He was treated with oral prednisolone, carbazochrome sodium sulfonate, tranexamic acid and ascorbic acid. Regarding the histopathological findings of HSP, vessel wall granulocytes on biopsy has been a major diagnostic criterion according to the American College of Rheumatology criteria. 2 Recently, however, EULAR/PReS (European League against Rheumatism/Pediatric Rheumatology European Society) endorsed consensus criteria for HSP included “predominant IgA deposition” in the definition of the criterion describing “biopsy”, 3 because IgA deposition is a main pathogenesis of HSP and it can differentiate HSP from hypersensitivity vasculitis (leukocytoclastic vasculitis without IgA deposits). Cutaneous manifestations of hypersensitivity vasculitis are similar to those of HSP and, abdominal pain, arthralgia and renal involvement can also be present. 3,4 However, patients with hypersensitivity vasculitis recover completely and it does not lead to chronic renal failure in children. 3,5