Dionysios Tsambaos

Influence of chronic UV-light exposure on hepatic and cutaneous monooxygenases

Hairless female Ng/-mice were irradiated by UV-light for 16h daily over a period of 24 weeks. Monooxygenase activities were measured in liver and skin, and an induction of the aryl-hydrocarbon hydroxylase was detected in liver by both fluorometric and radiochemical methods, whereas no induction of this enzyme could be demonstrated in the skin.

Dipeptidyl Peptidase-4 Inhibitors Cause Bullous Pemphigoid in Diabetic Patients: Report of Two Cases

Bullous pemphigoid (BP) is an autoimmune disorder characterized by the production of autoantibodies against two antigens (BPAG1 and 2) and can be induced by drugs (1,2). Recently, the development of BP was reported in diabetic patients treated with dipeptidyl peptidase-4 inhibitors (gliptins) plus metformin (3). However, it remains unknown whether gliptins alone or in combination with metformin are responsible for the induction of BP. We report two diabetic patients who developed BP shortly after addition of vildagliptin to their metformin monotherapy. A 59-year-old woman and a 67-year- old man, both with type 2 diabetes that had been controlled with metformin for 6 and 3 years, respectively, presented with an 1- and 3-month history of pruritic …

Cutaneous sarcoidosis : Complete remission after oral isotretinoin therapy

We report a 31-year-old female patient with cutaneous sarcoidosis, who showed a complete remission of her single system skin disease after an 8-month therapy with oral isotretinoin (1 mg/kg/day). At 15-month follow-up, the patient still remained free of recurrence and visceral involvement.

Effects of oral thalidomide on rat liver and skin microsomal P450 isozyme activities and on urinary porphyrin excretion: interaction with oral hexachlorobenzene

Adult female Wistar rats (n=48) divided into four groups of 12 were treated orally with 3 mg/kg per day thalidomide, a 0.05% hexachlorobenzene (HCB) — containing diet, with both drugs together and with the vehicles (controls) over periods of 10 and 60 days. The protein and P450 contents and the activities of amino-pyrine-N-demethylase (ADM) and 7-ethoxyresorufine-O-deethylase (7-ERO-D) were determined in the liver microsomes. The activity of 7-ERO-D was also determined in the skin microsomes and total porphyrins were measured in the urine of the animals. Thalidomide increased the hepatic P450 content, caused distinct changes in the activities of the hepatic and cutaneous microsomal isozymes, modified their induction by HCB and inhibited the porphyriogenic activity of HCB. These findings indicate an interaction between thalidomide and HCB with regard to their effects on the P450 isozymes and the metabolism of porphyrins.

Neuromuscular adverse effects associated with systemic retinoid dermatotherapy: monitoring and treatment algorithm for clinicians.

Although neuromuscular adverse effects represent significant clinical manifestations of hypervitaminosis A syndrome, surprisingly little attention has been paid to the potential neuromuscular toxicity of vitamin A derivatives (retinoids). Since isotretinoin and acitretin are currently the two most commonly used oral retinoids in systemic dermatotherapy, this review focuses exclusively on their neuromuscular adverse effects and proposes a neuromuscular algorithm for appropriate monitoring of patients treated with these two compounds.The most frequent CNS adverse effect associated with oral isotretinoin is headache, either as an independent adverse effect or as part of benign intra-cranial hypertension, which is additionally characterized by nausea and visual changes. Isolated cases of stiff-person-like syndrome, epileptic seizures and generalized muscle stiffness syndrome, possibly or probably related to oral treatment with isotretinoin, have also been reported. In addition, oral isotretinoin has reportedly been associated with muscular adverse effects that most frequently manifest as myalgia and stiffness and, in rare cases, as true myopathy or rhabdomyolysis. Creatine phosphokinase, a specific marker of muscle destruction, has been found to be elevated, occasionally by up to 100 times the normal value (with or without muscular symptoms and signs), in a variable percentage of patients receiving isotretinoin treatment and particularly in those undergoing vigorous physical exercise.Oral acitretin has been found to cause peripheral nerve dysfunction, particularly of sensory fibres, which in rare cases leads to clinically evident sensory disturbances. Less clear is the causal relationship between acitretin and benign intracranial hypertension or myopathy, whereas an isolated case of cranial nerve IV (oculomotor) palsy and a further case of thrombotic stroke during treatment with oral acitretin have been reported.Systemic diseases with involvement of nervous and/or muscle tissue and neuromuscular disorders should be regarded as exclusion criteria for initiation of oral retinoid therapy. Additionally, intense physical exercise and concurrent treatment with neurotoxic or myotoxic drugs should be avoided during treatment with oral retinoids. In order to minimize the potential risk of neuromuscular adverse effects, a neuromuscular algorithm is suggested that may be useful for monitoring patients taking oral retinoids.

Inhibition of Ribonuclease P Activity by Retinoids

The effect of two naturally occurring (retinol and all-trans retinoic acid) and two synthetic (isotretinoin and acitretin) analogs of vitamin A (retinoids) on tRNA biogenesis was investigated employing the RNase P ofDictyostelium discoideum as an in vitroexperimental system. RNase P is an ubiquitous and essential enzyme that endonucleolytically cleaves all tRNA precursors to produce the mature 5′ end. All retinoids tested revealed a dose-dependent inhibition of RNase P activity, indicating that these compounds may have a direct effect on tRNA biogenesis. Detailed kinetic analysis showed that all retinoids behave as classical competitive inhibitors. The K i values determined were 1475 μmfor retinol, 15 μm for all-trans retinoic acid, 20 μm for isotretinoin, and 8.0 μmfor acitretin. On the basis of these values acitretin is a 184, 2.5, and 1.9 times more potent inhibitor, as compared with retinol, isotretinoin, and all-trans retinoic acid, respectively. Taking into account that retinoids share no structural similarities to precursor tRNA, it is suggested that their kinetic behavior reflects allosteric interactions of these compounds with hydrophobic site(s) ofD. discoideum RNase P.

Abnormalities of the Auditory Brainstem Response in Vitiligo

Accumulating evidence suggests that vitiligo is a systemic disease affecting the entire pigmentary system and possibly the melanin-containing cellular elements of the nervous system. In the present paper we comparatively study the auditory brainstem response (ABR) of 30 patients with active vitiligo and 50 healthy human subjects in order to detect possible subclinical abnormalities of the auditory system in this disorder. Our findings reveal a statistically significant (p < 0.01) decrease of the I peak latency and a statistically significant (p < 0.01) increase of the I-III interpeak latency in the patients as compared to the controls. The decrease of the first peak latency may be due to a numerical decrease of active melanocytes in the inner ear which results in an impairment of the ion exchange between the endolymph and perilymph. The increase of the I-III interpeak latency may be explained in terms of an abnormal synaptic activity and transmission of the action potential from the auditory nerve to the superior olive.

Detection of human papillomavirus DNA in nongenital seborrhoeic keratoses

The histological similarities of seborrhoeic keratoses and common warts led to the investigation of the possible occurrence of human papillomavirus DNA (HPV-DNA) in a large number of nongenital seborrhoeic keratoses using the in situ hybridization technique. All specimens derived from normal skin (n=173) were negative for the applied HPV-DNA probe, whereas the HPV genome was detected in 34 of 173 seborrhoeic keratosis specimens (19.65%). Of 34 HPV-positive specimens, 15 contained types 6/11 and 14 types 31/33/35, and 5 showed no positive reaction to the applied types. These results suggest that a considerable percentage of nongenital seborrhoeic keratoses may be related to an HPV infection.

Effects of oral isotretinoin on human auditory brainstem response.

BACKGROUND Accumulating evidence suggests that synthetic retinoids may be capable of affecting the differentiation and growth of nervous tissue in vivo and in vitro. On the other hand, adverse reactions concomitant with brainstem involvement definitely or probably related to oral retinoid therapy have been reported in a small number of patients. OBJECTIVE The purpose of the present study was to substantiate the possible effects of oral isotretinoin on the synaptic activity and propagation of action potentials along the nerve fibers. METHODS The auditory brainstem response of 33 patients with severe nodulocystic acne before and 3 weeks after the onset of oral isotretinoin administration was investigated using auditory evoked potentials. RESULTS The paired analysis of the response variables before and after treatment failed to reveal any statistically significant differences. However, a marked increase in latencies and interpeak latencies and a decrease in amplitudes for both ears were found in 3 patients after therapy. CONCLUSIONS It seems reasonable to suggest that these subclinical changes may be due to an isotretinoin-induced synaptic malfunction or to a conduction defect in the auditory nerve fibers.

TREATMENT OF CONDYLOMATA ACUMINATA WITH ORAL ISOTRETINOIN

PURPOSE The aim of our study was to evaluate the efficacy and safety of oral isotretinoin in the treatment of condylomata acuminata. MATERIALS AND METHODS A total of 56 male patients with a history of condylomata acuminata refractory to at least 1 standard therapeutic regimen was treated orally with isotretinoin (1 mg./kg. daily) during a 3-month period. RESULTS At the end of treatment 21 of the 53 evaluated patients (39.6%) had complete response, 7 (13.2%) had partial response and 25 (47.1%) had no response. A statistically significant inverse relationship was found between age and area of treated lesions and response to medication. Two complete responders (9.5%) revealed recurrence during the 1-year followup. CONCLUSIONS Oral isotretinoin may be regarded as an effective, fairly well tolerated and noninvasive alternative form of therapy for immature and small condylomata acuminata.