Crusted scabies in a pediatric renal transplant recipient on immunosuppressants.

BACKGROUND: Crusted scabies (CS) is a rare, severe and highly contagious form of scabies, which has been reported in immunosuppressed patients. A high index of suspicion and awareness of CS is essential to treat this infestation. CASE: A 13-year-old boy presented with pruritic hyperkeratotic squamous plaques located on both inner wrists, the web spaces of both his hands and his feet, and the genital area of 12 months duration. He was diagnosed with focal segmental glomerulosclerosis at the age of 5 and received a kidney transplant at the age of 9. He has been on a maintenance dose of prednisone (5 mg/d) and mycophenolate mofetil (250 mg/d) for the past 2 years. He had a contact history with a school friend with similar lesions. A skin punch biopsy demonstrated the presence of multiple mites in the stratum corneum confirming the diagnosis of CS. Ivermectin, the recommended drug of choice for crusted scabies, is not available in South Africa. The patient was commenced on topical benzoyl benzoate lotion but discontinued its use because of intolerable irritation. We subsequently prescribed the daily application of topical 5% sulfur in petrolatum to which his pruritus subsided significantly after 2 weeks with resolution of all skin lesions at the end of 8 weeks. CONCLUSION: This case is the first documented report of CS in a pediatric renal transplant patient. Our management highlights that classic formularies of magistral drugs are still effective treatment options and can be used especially when standard therapies cannot be tolerated or when optimum treatments are not available.

The long-term effect of oral isotretinoin therapy on macula ganglion cell complex thickness.

PURPOSE: To evaluate the long-term effect of oral isotretinoin therapy on macula ganglion cell complex (GCC) thickness by spectral domain optical coherence tomography (SD-OCT). MATERIALS AND METHODS: Newly diagnosed cystic acne patients who received low dose for a long time systemic isotretinoin therapy were included in this study. Thorough ophthalmic evaluation and GCC thickness analysis by using SD-OCT were performed at baseline, and at 1, 3, 6, and 12 months of treatment. RESULTS: Forty-eight eyes of 24 patients (15 females, 9 males) were included in the study. The mean age of patients was 19.37 ± 2.74 years (range 14-25 years). The full ophthalmologic examination was normal in all eyes before treatment. During the treatment there were no change in visual acuity, refractive error, intraocular pressure and tear break-up time. The mean GCC thicknesses were 81.45 ± 4.91, 81.45 ± 5.12, 81.81 ± 4.68, 81.87 ± 4.91 and 81.64 ± 5.09 µm at pretreatment and at 1, 3, 6, and 12 months of treatment, respectively (p = 0.803). CONCLUSION: One-year systemic use of isotretinoin had no significant effect on the thickness of macula ganglion cell. Macular ganglion cell analysis is useful for determining and following the toxic effects of systemic drugs on the retina. However, it is more rational to consider it as an adjunct to electrophysiological testing rather than used alone.

Evaluation of Diagnostic Accuracy and Therapeutic Approach of Dermatologists and Plastic Surgeons To Non-Melanocytic Skin Lesions By Using Telemedicine.

Introduction: In the new circumstances of coronavirus disease 2019 pandemic, tele-dermatology and tele-dermoscopy have become more important in daily practice for departments for which visuality is at the forefront as dermatology and plastic and reconstructive surgery. Objectives: This study was aimed to determine diagnostic accuracy and treatment approaches of non-melanocytic skin lesions between 2 clinics by store and forward tele-dermatology method and to evaluate the contribution of tele-dermoscopy to the diagnostic accuracy for dermatologists. Methods: A total of 26 patients with non-melanocytic skin lesions were included in the study. Clinical images of the lesions were sent by email to 3 plastic surgeons and 3 dermatologists. The accuracy of the diagnoses was evaluated by comparing tele-dermatology with histopathology. Diagnosis and treatment approaches were recorded for both clinics. Dermatologists also defined their diagnosis with tele-dermoscopic images. Results: The mean percentage of diagnostic accuracy among dermatologists was 74.3% and among plastic surgeons was 61.5%. There was no significant difference in diagnostic accuracy between departments (P = 0.625). There was a statistically significant difference between the departments for diagnostic and treatment approaches (P values respectively P = 0.002, P < 0.001). Plastic surgeons preferred to confirm their pre-diagnosis histopathologically more than dermatologists. Plastic surgeons recommended surgical procedures for 25 lesions (96.2%) while dermatologists for 14 (53.8%) ones. Tele-dermoscopy increased the rate of diagnostic accuracy of dermatologists from 74.3% to 82.0% (P = 0.02). Conclusions: Tele-dermatology is an effective method for non-melanocytic skin lesions with high diagnostic accuracy. Adding dermoscopy to tele-dermatology increases diagnostic accuracy of dermatologists on non-melanocytic skin lesions.

Childhood pityriasis rosea.

Pityriasis rosea (PR) is an acute, self-limiting papulosquamous disorder of unknown etiology. Published studies of childhood PR are scarce and most are reviews. The aim of this study was to determine the demographic and clinical features of childhood PR.

de novo Histoid leprosy: an expatriate case recently diagnosed in Johannesburg.

Histoid leprosy (HL) is a rare variant of lepromatous leprosy with unique clinical, histopathological, and microbiological features. A 32-year-old man from Malawi who immigrated to Johannesburg 1-year-ago, presented with a 4-month history of flesh-colored nodules on the face and trunk and hyperpigmented plaques on the chest and limbs. Skin slit smears confirmed multibacillary leprosy, and skin punch biopsies showed proliferation of spindled cells containing a large number of acid-fast bacilli. The prevalence of de novo HL is increasing in the era of leprosy elimination. HL cases may act as reservoirs and negatively affect the global control of leprosy.

Subcutaneous nodules of cysticercosis as a sign of asymptomatic neurocysticercosis in an HIV positive patient.

Cysticercosis is caused by the hematogenous dissemination of the larval form (cysticercus) of Taenia solium. It can affect any organ or tissue in the body but commonly affects the subcutaneous tissue, central nervous system, eyes, and skeletal muscle. Skin lesions can assist as a marker in the diagnosis of asymptomatic neurocysticercosis in endemic areas. A 49-year-old HIV positive man presented with multiple cutaneous nodules confirmed as cysticercomas which led to the diagnosis of asymptomatic neurocysticercosis. He was successfully treated with albendazole and steroids at recommended doses with no adverse effects.

High-Resolution Computed Tomography and Pulmonary Function Findings of Occupational Arsenic Exposure in Workers.

BACKGROUND: The number of studies where non-malignant pulmonary diseases are evaluated after occupational arsenic exposure is very few. AIMS: To investigate the effects of occupational arsenic exposure on the lung by high-resolution computed tomography and pulmonary function tests. STUDY DESIGN: Retrospective cross-sectional study. METHODS: In this study, 256 workers with suspected respiratory occupational arsenic exposure were included, with an average age of 32.9±7.8 years and an average of 3.5±2.7 working years. Hair and urinary arsenic levels were analysed. High-resolution computed tomography and pulmonary function tests were done. RESULTS: In workers with occupational arsenic exposure, high-resolution computed tomography showed 18.8% pulmonary involvement. In pulmonary involvement, pulmonary nodule was the most frequently seen lesion (64.5%). The other findings of pulmonary involvement were 18.8% diffuse interstitial lung disease, 12.5% bronchiectasis, and 27.1% bullae-emphysema. The mean age of patients with pulmonary involvement was higher and as they smoked more. The pulmonary involvement was 5.2 times higher in patients with skin lesions because of arsenic. Diffusing capacity of lung for carbon monoxide was significantly lower in patients with pulmonary involvement. CONCLUSION: Besides lung cancer, chronic occupational inhalation of arsenic exposure may cause non-malignant pulmonary findings such as bronchiectasis, pulmonary nodules and diffuse interstitial lung disease. So, in order to detect pulmonary involvement in the early stages, workers who experience occupational arsenic exposure should be followed by diffusion test and high-resolution computed tomography.

In vitro and in vivo pharmacological characterization of the nociceptin/orphanin FQ receptor ligand Ac-RYYRIK-ol.

It was recently reported that the hexapeptide Ac-RYYRIK-ol binds with high affinity nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptors and competitively antagonizes N/OFQ actions in the mouse vas deferens assay. Here we further describe the in vitro and in vivo pharmacological features of this NOP receptor ligand. In mouse brain homogenate the degradation half life of Ac-RYYRIK-ol (2.48 min) was significantly higher than that of the parent compound Ac-RYYRIK-NH2 (1.20 min). In the electrically stimulated mouse vas deferens, Ac-RYYRIK-ol (10-1000 nM) competitively antagonized the inhibitory effect of N/OFQ (pA2=8.46), while in the isolated mouse colon the hexapeptide mimicked N/OFQ contractile effects thus behaving as a NOP receptor agonist (pEC50=9.09). This latter effect was no longer evident in colon tissues taken from mice knock out for the NOP receptor gene (NOP-/-). In vivo in mice, similarly to N/OFQ, Ac-RYYRIK-ol (dose range 0.001-1 nmol) produced: i) pronociceptive effects after intracerebroventricular (i.c.v.) administration and antinociceptive actions when given intrathecally (i.t.) in the tail withdrawal assay; ii) inhibition of locomotor activity and iii) stimulation of food intake after supraspinal administration. Finally, in the forced swimming test, Ac-RYYRIK-ol was inactive per se, but reversed the antidepressant-like effects elicited by the NOP receptor selective antagonist UFP-101 ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH2). Thus, in all these in vivo assays Ac-RYYRIK-ol mimicked the actions of N/OFQ showing however higher potency. In conclusion, Ac-RYYRIK-ol displayed a complex pharmacological profile which is likely due to the low efficacy agonist nature of this novel ligand of the NOP receptor. The high potency, selectivity of action, and in vivo effectiveness make Ac-RYYRIK-ol a useful pharmacological tool for future studies in the field of N/OFQ and its NOP receptor.

Comparison of European Standard Patch Test Results of 330 Patients from an Occupational Diseases Hospital.

Background and Aim. Contact dermatitis (CD) is the most prevalent occupational skin disease with a significant impact on quality of life. Patch testing is used for the identification of responsible allergens which may improve protective and preventive measures in the workplace. Herein, we aim to identify the demographic characteristics and occupation of patients with early diagnosis of occupational CD and compare patch test results. Materials and Methods. The study included 330 patients referred to our clinic between April 2009 and April 2011 and who were patch-tested with 28-allergen European Standard Test. Results. 126 (38%) patients were female and 204 (62%) were male with a mean age of 36.12 (±13.13) years. Positive allergic reactions were observed in 182 (55%) patients. Nickel sulphate (41/126) and potassium dichromate (39/204) were significantly the most common allergens in women and men, respectively (P < 0.005). Additionally, the most common occupation in women was household activities (83/126) and in men was manufacturing (80/204). Conclusion. The allergens to which people become sensitized differ according to their working environment and occupation. Classification of occupations is important for identification of sensitization risks and monitoring of changes in allergen distribution of different occupations.

Slowly Growing Nodule on the Trunk: Cutaneous Granular Cell Tumor.

Granular cell tumor (GCT) is a rare benign neoplasm of the skin that accounts for 0.5% of all soft-tissue tumors. The tumor mostly presents with a symptomatic slowly growing solitary nodule and overlying normal skin; therefore, it is not always considered in the differential diagnosis. Here, we report a 58-year-old female patient who presented with a 4-year history of a slowly growing mass, with a dimension of 5 × 4 cm on her left waist, diagnosed as a GCT at the histopathological examination. The neoplastic cells had centrally located nuclei and granular eosinophilic cytoplasm and stained positively for S100, neuron-specific enolase, and CD68 antibodies. Fifteen months after surgery, the patient still showed no signs of local recurrence or metastases. Although a large diameter is a feature of malignant GCT, our case with cutaneous GCT was localized on the trunk and did not present malignant features clinically and histopathologically.

Synthesis and biological studies of nociceptin derivatives containing the DTPA chelating group for further labeling with therapeutic radionuclides.

Nociceptin is an endogenous anti-opiate heptadecapeptide primarily interacting with the nociceptin (NOP) receptor. This neuropeptide-receptor system is involved in pain regulation, tolerance to and dependence on opiates as well as many other physiological and pathophysiological events. The role and mechanisms of nociceptin in pathological conditions is not clearly known yet. In an attempt to have a radiopharmaceutical labeled either with 99mTc or (111)In, we incorporated diethylenetriaminepentaacetic acid (DTPA) as chelator into the structure of [Arg14,Lys15]nociceptin(1-17)-NH2 at the epsilon-amino group of Lys15. Such a radiopeptide may be useful in imaging for diagnostical purposes. Preparation of the peptide ligands was carried out by solid phase synthesis. Two peptides containing DTPA were obtained and purified. The products were [Arg14,Lys(DTPA)15]nociceptin(1-17)-NH2 and its cross-linked dimer on the basis of mass spectrometric analysis. In (115)In3+ binding experiments the conjugates exhibited preserved indium ion chelating properties, indicating the potential use of radiolabeled DTPA-nociceptin derivatives as radiopharmaceutical. Biological properties of these compounds were studied in rat brain membrane preparations by radioligand binding, functional biochemical [35S]GTPgammaS binding assays and mouse vas deferens (MVD) bioassay. Besides the similar in vitro binding characteristics to nociceptin receptor, both of the DTPA-chelated compounds were more potent and efficient than nociceptin in functional biochemical and mouse vas deferens bioassays. Our further aim is to radiolabel these compounds in order to get a radiopharmaceutical which can be used diagnostically.

de novo Histoid leprosy: an expatriate case recently diagnosed in Johannesburg

Abstract: Histoid leprosy (HL) is a rare variant of lepromatous leprosy with unique clinical, histopathological, and microbiological features. A 32-year-old man from Malawi who immigrated to Johannesburg 1-year-ago, presented with a 4-month history of flesh-colored nodules on the face and trunk and hyperpigmented plaques on the chest and limbs. Skin slit smears confirmed multibacillary leprosy, and skin punch biopsies showed proliferation of spindled cells containing a large number of acid-fast bacilli. The prevalence of de novo HL is increasing in the era of leprosy elimination. HL cases may act as reservoirs and negatively affect the global control of leprosy.

Nociceptin antagonism: probing the receptor by N-acetyl oligopeptides.

In search for effective antagonist structures for the nociceptin (NOP) receptor, a number of N-acylated oligopeptides, including N-acyl tetra- and pentapeptides selective for the kappa-opioid receptor, as well as N-acyl hexapeptides bearing the Ac-Arg-Tyr-Tyr-Arg-Ile-Lys (Ac-RYYRIK) core sequence originally isolated from combinatorial chemical libraries, were synthesized and studied in radioreceptor binding assays, [(35)S]GTPgammaS functional tests and in mouse vas deferens (MVD) bioassays. The properties of the novel antagonist candidates were compared to known antagonists. A new antagonist structure with a reduced, primer alcohol C-terminus, Ac-Arg-Tyr-Tyr-Arg-Ile-lysinol (Ac-RYYRIK-ol) was described in the mouse vas deferens tests, showing an equilibrium inhibitory constant value (K(e)) of 2.44 nM, and no agonist effect at 10 microM ligand concentration. Schild-analysis indicated a clearly competitive interaction at the NOP receptor, whereas the peptide did not affect the action of the delta-opioid receptor agonist [D-Ala(2),D-Leu(5)]enkephalin. Ac-RYYRIK-ol also exhibited a high affinity in [(3)H]nociceptin-NH(2) binding competition assays using rat brain membranes. Agonist-induced G-protein activation via NOP receptors was studied in [(35)S]GTPgammaS binding stimulation assays by the use of both native brain tissue preparations and membranes from cultured CHO cells expressing recombinant nociceptin receptors. Ac-RYYRIK-ol displayed only weak intrinsic agonist activity, whereas it effectively inhibited the stimulation generated by nociceptin. The results support the high potency and antagonist nature of Ac-RYYRIK-ol and reveal important roles for both the N- and the C-terminal region of the molecule.

Could thoracoscopic sympathicotomy for hyperhidrosis also improve acne vulgaris?

INTRODUCTION: The aim of this study is to emphasize the therapeutic effect of thoracoscopic sympathicotomy performed at our clinic for facial/scalp hyperhidrosis or blushing on coincidental facial acne vulgaris based on previous reports indicating an association between the sympathetic nerve stimulus, epithelial melanocyte system and sebogenesis. MATERIAL AND METHODS: The possible therapeutic effects of sympathicotomy on facial acne vulgaris were analyzed in a study design of retrospective review with prospective collection of the data from March 2005 to March 2013. RESULTS: Forty-two patients were operated on at our clinic due to facial/scalp hyperhidrosis or blushing and 30 of these also had facial acne vulgaris. However, none harbored a systemic co-morbidity. The patients' medical history indicated that they had used several medical therapies including topical or systemic antibiotherapies to treat their acne for several years but this had met with limited success and the treatment was stopped in all patients an average of 8 ± 2.4 months prior to the operations. Furthermore, the patients with acne vulgaris also underwent a thoracoscopic sympathicotomy procedure at the second costal head (R2) for hyperhidrosis or blushing. All 30 patients showed marked improvement of their acne grade at the first postoperative month (p < 0.01). CONCLUSIONS: In this study, the patients' facial acne vulgaris grade significantly improved after undergoing a sympathicotomy. This can be explained by the possible effect the nervous system had on the epithelial melanocyte system and sebogenesis. However, prospective studies with an increased number of patients are needed to verify our findings.

Comparison of growth hormone receptor, igf-1r and igfbp-3 between tumoral and non-tumoral areas in non-melanoma skin cancers.

OBJECTIVE: A relationship between the pathogenesis of some cancers and growth hormone, insulin-like growth factor-1 and insulin-like growth factors binding protein-3 has been shown. Our aim was to evaluate the expression of growth hormone receptor, insulin-like growth factor-1 receptor and insulin-like growth factors binding protein-3 in actinic keratosis, basal cell carcinoma and squamous cell carcinoma, and to compare the expression patterns of tumoral areas with normal epidermis and skin appendages. MATERIAL AND METHOD: The formalin-fixed, paraff in-embedded tissues of 40 patients which were diagnosed as 15 actinic keratosis, 15 basal cell carcinoma and 15 squamous cell carcinoma were analyzed for growth hormone receptor, insulin-like growth factor-1 receptor and insulin-like growth factors binding protein-3 with the immunohistochemical method using the streptavidin-biotin-peroxidase technique. RESULTS: There was no difference between tumoral areas of actinic keratosis, basal cell carcinoma and squamous cell carcinoma in expression of growth hormone receptor and insulin-like growth factors binding protein-3 (P > 0.05). However, a significantly higher expression of insulin-like growth factor-1 receptor was observed in tumoral areas of squamous cell carcinoma (P < 0.01). In basal cell carcinoma, a significantly lower intensity of immunostaining with growth hormone receptor, insulin-like growth factor-1 receptor and insulin-like growth factors binding protein-3 in tumoral areas than skin appendages was seen (P < 0.01). In squamous cell carcinoma, higher expressions of growth hormone receptor, insulin-like growth factor-1 receptor and insulin-like growth factors binding protein-3 in tumoral areas than peritumoral epidermis was found (P =0.06, P < 0.01 and P =0.02, respectively). CONCLUSION: Our study points out that, growth hormone receptor, insulin-like growth factor-1 receptor and insulin-like growth factors binding protein-3 have a role in the pathogenesis of non-melanoma skin cancers, especially squamous cell carcinoma.

Subcutaneous nodules of cysticercosis as a sign of asymptomatic neurocysticercosis in an HIV positive patient

Abstract Cysticercosis is caused by the hematogenous dissemination of the larval form (cysticercus) of Taenia solium. It can affect any organ or tissue in the body but commonly affects the subcutaneous tissue, central nervous system, eyes, and skeletal muscle. Skin lesions can assist as a marker in the diagnosis of asymptomatic neurocysticercosis in endemic areas. A 49-year-old HIV positive man presented with multiple cutaneous nodules confirmed as cysticercomas which led to the diagnosis of asymptomatic neurocysticercosis. He was successfully treated with albendazole and steroids at recommended doses with no adverse effects.

Trichostasis spinulosa confirmed by standard skin surface biopsy.

Trichostasis spinulosa (TS) is a common but rarely diagnosed disease. For diagnosis, it's sufficient to see a bundle of vellus hair located in a keratinous sheath microscopically. In order to obtain these vellus hair settled in comedone-like openings, Standard skin surface biopsy (SSSB), a non-invasive method was chosen. It's aimed to remind the differential diagnosis of TS in treatment-resistant open comedone-like lesions and discuss the SSSB method in diagnosis. A 25-year-old female patient was admitted with a complaint of the black spots located on bilateral cheeks and nose for 12 years. In SSSB, multiple vellus hair bundles in funnel-shaped structures were observed under the microscope, and a diagnosis of 'TS' was made. After six weeks of treatment with tretinoin 0.025% and 4% erythromycin jel topically, the appearance of black macules was significantly reduced. Treatment had to be terminated due to her pregnancy, and the lesions recurred within 1 month. It's believed that TS should be considered in the differential diagnosis of treatment-resistant open comedone-like lesions, and SSSB might be an inexpensive and effective alternative method for the diagnosis of TS.

Selective and high affinity labeling of neuronal and recombinant nociceptin receptors with the hexapeptide radioprobe [(3)H]Ac-RYYRIK-ol.

The synthetic hexapeptide Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-ol (Ac-RYYRIK-ol) represents a highly potent and selective partial agonist ligand for the nociceptin/orphanin FQ (N/OFQ) peptide receptor (nociceptin receptor, NOPr). Ac-RYYRIK-ol has been labeled with tritium yielding [(3)H]Ac-RYYRIK-ol with exceptionally high specific radioactivity of 94Ci/mmol. The radioprobe is chemically stable even at 24 degrees C in ethanol solution for at least 4 days. No significant decomposition of the [(3)H]ligand occurred under the condition of the binding experiments indicating a fine enzymatic stability of the peptide. Radioreceptor binding studies were conducted using native neuronal NOPr preparation of rat brain membrane fractions and recombinant human nociceptin receptor ((h)NOPr) preparations from cultured Chinese Hamster Ovary (CHO) cells stably expressing (h)NOPr. Specific binding of the compound was reversible, saturable and of high affinity. No cross-reaction with the opioid receptors was observed suggesting superior NOPr selectivity of the ligand. Monophasic isotherm curves obtained in radioligand binding saturation and homologous displacement experiments indicated the presence of single binding sites in both preparations. Average densities of the [(3)H]Ac-RYYRIK-ol recognition sites were 237 and 749fmol/mg protein in rat brain and transfected cells, respectively. Equilibrium affinity values (K(d)s) were determined by three independent way providing identical results. In rat brain membranes K(d)s of 0.3-1.3nM were found depending upon the assay type. In homologous competition studies performed on (h)NOP-CHO cell membranes almost the same binding affinities were measured for Ac-RYYRIK-ol either with [(3)H]Ac-RYYRIK-ol (K(i) 2.8nM) or with [(3)H](Leu(14))nociceptin (2.3nM). A number of NOPr and opioid ligands were screened in heterologous displacement experiments and displayed a rank order of affinity profile being consistent with fairly good NOPr selectivity of the sites labeled by [(3)H]Ac-RYYRIK-ol. Taken together, the high molar activity, improved chemical and biological stability and the capability of the selective and high affinity labeling make this novel radioprobe available for further exploring the biochemical pharmacology and receptor-ligand interaction of the NOP receptor.

In vitro binding and functional studies of Ac-RYYRIK-ol and its derivatives, novel partial agonists of the nociceptin/orphanin F/Q receptor.

Following the discovery of nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) and its endogenous ligand, an extensive search has started to find selective agonists and antagonists targeting this novel receptor-ligand system due to their therapeutic potentials. By the help of the combinatorial chemistry a series of hexapeptides with a general formula of Ac-RYY-R/K-W/I-R/K-NH(2) having high NOP receptor affinity and selectivity were identified. On the basis of this information we developed a number of novel compounds. The detailed structure-activity studies on the partial agonist Ac-RYYRIK-NH(2) are reported in this communication. Besides the modifications on N- and C-terminal, Arg-Cit exchange was performed on the template structure. The novel hexapeptides were analyzed in radioligand binding, functional biochemical [(35)S]GTPgammaS binding assays by using membranes from rat brains and Chinese hamster ovary cells expressing human NOP receptor. The agonist/antagonist properties were also tested on in the mouse vas deferens bioassay. C-terminal modification yielded a high affinity, selective and potent NOP ligand (Ac-RYYRIK-ol) with a partial agonist property. Several analogs of this compound were synthesized. The presence of the positively charged arginine residue at the first position turned out to be crucial for the biological activity of the hexapeptide. The N-terminal modifications with various acyl groups (ClAc, pivaloyl, formyl, benzoyl, mesyl) decreased the affinity of the ligand towards the receptor and the intrinsic activity for stimulating the G-protein activation was also decreased. The structure-activity studies on the hexapeptide derivatives provided some basic information on the structural requirements for receptor binding and activation.