Understanding Kerion Celsi in Children: Diagnosis and Therapeutic Guidelines Through an Algorithm.

Kerion celsi (KC), known as scalp ringworm, is the most common dermatophytosis in children. In Mexico, it ranks fourth among dermatophytoses, with a frequency of 4%-10%. KC is the inflammatory variety of tinea capitis (TC), with the most common causative agents being Microsporum canis and Trichophyton mentagrophytes. We present the clinical case of a six-year-old male diagnosed with KC. Direct examination stained with chlorazol black and cultures were performed, yielding negative results. Histopathological study revealed spores and short hyphae within and surrounding the hair shaft. Treatment with itraconazole was initiated based on suspicion of Microsporum spp. from the trichoscopy findings. We propose a diagnostic and therapeutic algorithm for kerion celsi.

Pilomatrixomas: 31 years of experience in population under and over 18 years of age.

BACKGROUND: Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a benign cutaneous neoplasm that demonstrates differentiation towards the matrix portion of hair follicles. It is the most common benign cutaneous neoplasm in childhood and youth, although it can occur at any age. With a general incidence ranging from 0.001% to 0.0031% of all cutaneous tumors. There is a slight predilection for females, with a female-to-male ratio of 1.15:1. METHODS: Observational, descriptive, retrospective, and cross-sectional study conducted using the electronic database of the dermatopathology department of Dr. Manuel Gea González General Hospital, from January 1992 to July 2023. Only cases with a histopathological diagnosis of pilomatrixoma, pilomatricoma, and Malherbe's calcifying epithelioma were included. RESULTS: A total of 200 pilomatrixomas were recorded in 177 patients. The tumor predominantly affected females in the pediatric age group, with an average age of 22.98 years in the studied population. The most common location was the head (periorbital region), followed by the upper extremities and trunk. Upon separating the population into pediatric and adult groups, 111 and 89 cases were identified, respectively. CONCLUSIONS: We present a detailed study on pilomatrixomas with a comprehensive overview of the demographic, clinical, and epidemiological characteristics of this benign cutaneous neoplasm. The results revealed robust statistical data highlighting the distribution by age, gender, topography, morphology, accompanying symptoms, and frequency of clinical differential diagnoses. This study significantly contributes to the existing knowledge of pilomatrixomas and serves as a valuable reference for future research and clinical practice.

INTRODUCCIÓN: El pilomatrixoma o epitelioma calcificado de Malherbe es una neoplasia cutánea benigna que muestra diferenciación hacia la porción de la matriz de los folículos pilosos. Es la neoplasia cutánea benigna más frecuente en la infancia y la juventud, aunque puede ocurrir a cualquier edad. Tiene una incidencia general que oscila entre el 0.001% y el 0.0031% de todos los tumores cutáneos. Se reporta una ligera predilección por el sexo femenino, con una relación mujer: hombre de 1.15:1. MÉTODOS: Estudio observacional, descriptivo, retrospectivo y transversal en el que se utilizó la base de datos electrónica del departamento de dermatopatología del Hospital General Dr. Manuel Gea González, entre enero de 1992 y julio de 2023. Para la búsqueda de los casos solo se incluyeron aquellos con diagnóstico histopatológico de pilomatrixoma, pilomatricoma o epitelioma calcificado de Malherbe. RESULTADOS: Se registraron 200 pilomatrixomas en 177 pacientes. El tumor predominó en mujeres de edad pediátrica; el promedio de edad de la población estudiada fue 22.98 años. La topografía más frecuente fue la cabeza (región periorbitaria), seguida de las extremidades superiores y el tronco. Al separar la población en pediátricos y adultos, se encontraron 111 y 89 casos, respectivamente. CONCLUSIONES: Presentamos un estudio detallado sobre pilomatrixomas con una visión exhaustiva de las características demográficas, clínicas y epidemiológicas de esta neoplasia cutánea benigna. Los resultados revelaron datos estadísticos sólidos, destacando la distribución por edades, sexo, topografía, morfología, síntomas acompañantes y frecuencia de diagnósticos diferenciales clínicos. Este estudio contribuye significativamente al conocimiento existente sobre los pilomatrixomas y sirve como una referencia valiosa para futuras investigaciones y para la práctica clínica.

Longitudinal findings of a U.S. preventive evidence-based family intervention tested among youth in Ecuador: Familias Unidas.

Interventions that address adolescent conduct problems are essential for decreasing negative risk behaviors and promoting positive protective factors among youth. Although interventions have been developed and tested in the United States, preventive evidence-based interventions (EBIs) are less available in Latin American countries such as Ecuador. Therefore, the purpose of this study was to evaluate the efficacy of an evidence-based, parent-centered intervention, Familias Unidas, in preventing/reducing conduct problems, across time, among youth in Guayaquil, Ecuador. Ecuadorian youth (ages 12 through 14) and their respective primary caregiver were recruited from two public schools and randomized to either Familias Unidas or Community Practice. A series of latent growth models were run to test for differences between Familias Unidas and Community Practice on conduct disorder symptoms across three timepoints covering 6 months. Ecuadorian mental health professionals were trained to deliver the evidence-based intervention. Findings indicate no direct relationship between condition and average change in conduct problems at 6 months post baseline. However, indirect effects favoring Familias Unidas over Community Practice were found through improvements in family functioning. Findings highlight that Familias Unidas was efficacious in an international setting and indicate the viability of successfully delivering preventive EBIs in Ecuador.

Carotid intima-media thickness in patients with psoriasis with and without metabolic syndrome / Grosor de intima-media carotídea en pacientes con psoriasis con y sin síndrome metabólico

Abstract Introduction: Patients with psoriasis have an increased prevalence of cardiovascular risk factors as well as cardiovascular disease. Objective: To determine if patients with psoriasis and metabolic syndrome (MS) have a higher frequency of subclinical atherosclerosis compared with those with psoriasis without MS. Materials and Methods: A cross-sectional study was conducted in patients with psoriasis; MS was defined according to ATP III criteria. Demographic, clinical, and anthropometric data were obtained. Blood chemistry, high sensitive C-reactive protein (hs-CRP), and insulin were measure. Subclinical atherosclerosis was defined as high carotid intima-media thickness (CIMT) by Mode B ultrasound. Results: 92 patients with psoriasis were included, 67 (72.8%) with MS and 25 (27.2%) without MS. Subjects with psoriasis and MS had significantly higher weight, body mass index, waist circumference, systolic blood pressure, glucose, insulin, triglycerides, insulin resistance, hs-CRP, and lower level of high-density lipoprotein cholesterol, compared with subjects without MS. High CIMT was greater in patients with psoriasis and MS than in those without MS. Age and MS were independent predictors of increased CIMT after multiple linear regression analysis. Conclusions: MS is associated with greater inflammation and subclinical atherosclerosis in patients with psoriasis.

Resumen Introducción: Los pacientes con psoriasis tienen prevalencia incrementada de factores de riesgo y enfermedad cardiovascular. Objetivo: Determinar si los pacientes con psoriasis y síndrome metabólico (SM) tienen mayor frecuencia de ateroesclerosis subclínica comparados con pacientes con psoriasis y sin SM. Material y Métodos: Estudio transversal, en pacientes con psoriasis; SM fue definido con base en criterios ATP III. Se obtuvieron datos demográficos, clínicos y antropométricos. Se realizó química sanguínea, proteína C reactiva de alta sensibilidad (PCR-hs) e insulina. Ateroesclerosis subclínica fue definida como grosor de íntima-media carotídeo (GIMC) elevado, medido por ultrasonido tipo B. Resultados: Se incluyeron 92 pacientes con psoriasis, 67 (72.8 %) con SM y 25 (27.2 %) sin SM. Los sujetos con psoriasis y SM tuvieron valores significativamente más elevados de peso, índice de masa corporal, circunferencia de cintura, tensión arterial sistólica, glucosa, insulina, triglicéridos, resistencia a insulina, PCR-hs y menores niveles de colesterol de alta densidad, comparados con sujetos sin SM. El GIMC fue mayor en pacientes con psoriasis y SM. La edad y el SM fueron predictores independientes de mayor GIMC después de realizar múltiples análisis de regresión lineal. Conclusiones: Síndrome metabólico está asociado con mayor inflamación y ateroesclerosis subclínica en pacientes con psoriasis.

Carotid intima-media thickness in patients with psoriasis with and without metabolic syndrome.

INTRODUCTION: Patients with psoriasis have an increased prevalence of cardiovascular risk factors as well as cardiovascular disease. OBJECTIVE: To determine if patients with psoriasis and metabolic syndrome (MS) have a higher frequency of subclinical atherosclerosis compared with those with psoriasis without MS. MATERIALS AND METHODS: A cross-sectional study was conducted in patients with psoriasis; MS was defined according to ATP III criteria. Demographic, clinical, and anthropometric data were obtained. Blood chemistry, high sensitive C-reactive protein (hs-CRP), and insulin were measure. Subclinical atherosclerosis was defined as high carotid intima-media thickness (CIMT) by Mode B ultrasound. RESULTS: 92 patients with psoriasis were included, 67 (72.8%) with MS and 25 (27.2%) without MS. Subjects with psoriasis and MS had significantly higher weight, body mass index, waist circumference, systolic blood pressure, glucose, insulin, triglycerides, insulin resistance, hs-CRP, and lower level of high-density lipoprotein cholesterol, compared with subjects without MS. High CIMT was greater in patients with psoriasis and MS than in those without MS. Age and MS were independent predictors of increased CIMT after multiple linear regression analysis. CONCLUSIONS: MS is associated with greater inflammation and subclinical atherosclerosis in patients with psoriasis.

Propiedades psicométricas del Profile of Mood States (POMS) en personas con demencia y su aplicación en la evaluación de los efectos de la danza creativa terapéutica / Psychometric properties of Profile of Mood States (POMS) in people with dementia and its application in the evaluation of the effects of therapeutic creative dance

Introducción. Existe una creciente necesidad de estudios científicos e instrumentos que permitan evaluar los efectos en el plano afectivo de algunas terapias no farmacológicas para personas con demencia, como la danza creativa terapéutica. Objetivos. Determinar la validez y fiabilidad del Profile of Mood States (POMS) en personas con demencia y analizar las posibles diferencias en las puntuaciones de los participantes antes y después de sesiones de danza creativa terapéutica. Pacientes y métodos. El POMS se administró a 36 personas con demencia antes y después de cuatro sesiones grupales de danza creativa terapéutica. Para comprobar la validez de constructo se administraron dos cuestionarios autoinformados (PANAS y STAXI-2). Resultados. El POMS presentó una buena consistencia interna para cada factor y excelente para la escala total. La estabilidad temporal fue media-alta. Los resultados de validez convergente apoyan la validez de constructo. Después de las sesiones de danza creativa terapéutica, los factores tensión, depresión y confusión del POMS se redujeron, mientras que el factor vigor aumentó significativamente. No hubo ningún efecto sobre la fatiga y la cólera. Conclusiones. Se ha demostrado la validez y fiabilidad del POMS en una población con demencia. La danza creativa terapéutica puede ofrecer beneficios emocionales para personas con demencia

Introduction. There is a growing need for scientific studies and tools that allow the evaluation of the effects at an affective level of some non-pharmacological therapies for people with dementia such as the creative therapeutic dance. Aims. To explore the validity and reliability of the Profile of Mood States (POMS) in people with dementia and to analyse the possible differences in the scores of the participants before and after sessions of creative therapeutic dance. Patients and methods. POMS was administered to 36 people with dementia before and after four group sessions of creative therapeutic dance. To verify the construct validity, PANAS and STAXI-2 were also administered. Results. The POMS presented a good internal consistency for each factor and an excellent one for the total scale. The temporal stability was medium-high. Convergent validity results support construct validity. After the creative therapeutic dance sessions, POMS factors tension, depression and confusion were reduced, while vigour increased significantly. There was noeffect on fatigue and anger.Conclusions. The validity and reliability of POMS have been demonstrated in a population with dementia. Creative therapeutic dance can offer emotional benefits for people with dementia

Beneficios del psicoballet cubano en el tratamiento de enfermos de Alzheimer. Validación psicométrica / Os benefícios do psychoballet cubano no tratamento de pacientes com doença de Alzheimer. Validação psicométrica / The benefits of Cuban psychoballet in the treatment of patients with Alzheimer's disease. Psychometric validation

Introducción: existe necesidad de estudios con rigor científico que evalúen los beneficios del psicoballet en personas con demencia y también un vacío de estudios que midan directamente el estado emocional del paciente y no a través de un observador. Objetivo: analizar las posibles diferencias en las puntuaciones de los participantes antes y después de las sesiones de psicoballet a través del Profile of Mood States (POMS). Método: es un diseño casi experimental. El POMS se administró a 36 personas con demencia antes y después de cuatro sesiones de psicoballet. Resultados: después de las sesiones de psicoballet los factores tensión, depresión y confusión del POMS se redujeron, mientras que vigor aumentó significativamente. El tamaño del efecto variaba de pequeño a moderado-alto. No hubo ningún efecto sobre fatiga y cólera. Conclusiones: los resultados indican que el psicoballet puede ser una terapia no farmacológica beneficiosa para personas con Alzheimer u otras demencias(AU)

Introduction: there is a need for studies with scientific rigor that evaluate the benefits of psychoballet in people with dementia and also a vacuum of studies that directly measure the emotional state of the patient and not through an observer. Objective: to analyze the possible differences in the scores of the participants before and after the sessions of psicoballet through the Profile of Mood States (POMS). Method: it is a quasi-experimental design. The POMS was administered to 36 people with dementia before and after four psychoballet sessions. Results: after the psychoballet sessions, the Tension, Depression and Confusion factors of the POMS were reduced, while vigor increased significantly. The size of the effect varied from small to moderate-high. There was no effect on Fatigue and Cholera. Conclusions: the results indicate that psychoballet can be a beneficial non-pharmacological therapy for people with Alzheimer's or other dementias(AU)

Introdução: há a necessidade de estudos com rigor científico que avaliem os benefícios do psychoballet em pessoas com demência e também um vácuo de estudos que meçam diretamente o estado emocional do paciente e não através de um observador. Objetivo: analisar as possíveis diferenças nos escores dos participantes antes e após as sessões de psicobalética por meio do Profile of Mood States (POMS). Método: é um desenho quase experimental. O POMS foi administrado a 36 pessoas com demência antes e depois de quatro sessões de psychoballet. Resultados: após as sessões de psicobalônia, os fatores estresse, depressão e confusão do POMS foram reduzidos, enquanto o vigor aumentou significativamente. O tamanho do efeito variou de pequeno a moderado-alto. Não houve efeito sobre fadiga e raiva. Conclusões: os resultados indicam que o psychoballet pode ser uma terapia não farmacológica benéfica para pessoas com Alzheimer ou outras demências(AU)

Myopericytoma in an unusual location.

Myopericytoma is a soft-tissue tumor of perivascular cells (pericytes). It is slow-growing, usually asymptomatic, and generally benign, although a malignant variant has been described. The etiology is unknown, but it has been associated with local trauma. The most common location is on the distal extremities. Histologically, it is characterized by a well-circumscribed, non-encapsulated proliferation of spindle shaped cells similar to myofibroblasts with oval nuclei and eosinophilic cytoplasm, arranged in perivascular concentric rings. There are few mitoses and no necrosis is reported. The immunohistochemical analysis is positive for smooth muscle actin and negative or weakly positive for desmin. A low Ki-67 proliferation index is typical. Treatment is surgical excision with free margins. Recurrences after adequate excision are uncommon. We describe a 48-year-old woman with a myopericytoma in an unusual location (next to the inner corner of her left eye) who was treated with surgical excision; there has been no recurrence after 5 years of follow up.

Molecular sensitization patterns and influence of molecular diagnosis in immunotherapy prescription in children sensitized to both grass and olive pollen.

BACKGROUND: The overlapping grass and olive pollen seasons in Spain and the phenomenon of cross-reactivity can make it difficult to determine the true causative agent of seasonal allergic rhinitis when only skin prick tests with whole extracts are used. The aim of the GRAMOLE study was to determine sensitization patterns to the major grass and olive pollen allergens detected using specific recombinant IgE and to explore how this knowledge affected physicians' choice of allergen-specific immunotherapy. METHODS: Epidemiological, observational, multicenter, cross-sectional study. Results from children under 18 years of age diagnosed with seasonal allergic rhinitis by positive skin prick tests to olive and grass pollen were analyzed. Specific IgE to Phl p 1+5, Ole e 1, and Phl p 7+12 was determined. Investigators specified the optimal composition of allergen immunotherapy before and after knowing the results of the molecular diagnosis. RESULTS: A total of 281 patients with a mean age of 13.4 years were included. Double sensitization to both major allergens was found in vitro in 76% of children for an IgE cutoff point of 0.35 kU/L. When the molecular diagnosis results were known, specialists changed the composition of the prescribed immunotherapy in 52.87% of cases. CONCLUSIONS: Double sensitization to grass and olive pollen is common in Spain and also occurs in the pediatric population. Molecular diagnosis using specific IgE may help improve immunotherapy selection in polysensitized patients.

Short-Term Effects on Family Communication and Adolescent Conduct Problems: Familias Unidas in Ecuador.

Familias Unidas, a Hispanic/Latino-specific, parent-centered intervention, found to be efficacious in improving family functioning and reducing externalizing behaviors among youth in the USA, was recently adapted and tested for use in Ecuador. This study examined the short-term efficacy of Familias Unidas in Ecuador on parent-adolescent communication, parental monitoring of peers, and youth conduct problems. Two hundred thirty-nine youths (ages 12-14 years) and their primary care givers were randomized to either Familias Unidas or Community Practice and assessed pre- and post-intervention. There was a significant difference between Familias Unidas and Community Practice in conduct problems at 3 months (standardized ß = -.101, p = .001, effect size = .262). A significant indirect intervention effect was also detected, indicating that Familias Unidas predicted conduct problems at 3 months through parent-adolescent communication at 3 months (standardized ß = -.036, p = .016, CI 95% [-.066, -.007], effect size = .265). Familias Unidas was efficacious in reducing conduct problems through improved parent-adolescent communication, relative to Community Practice. Future assessments will determine whether Familias Unidas also has an impact on substance use and sexual risk behaviors at later time points, as demonstrated in past Familias Unidas trials. The short-term effects of the intervention, family engagement, and facilitator skill in the Ecuadorian adaptation of Familias Unidas are promising. This study implies that an intervention developed for Hispanics/Latinos in the USA and culturally adapted and implemented for use by Hispanics/Latinos in a Latin American country can be efficacious in improving family functioning and reducing youth conduct problems. TRIAL REGISTRATION: MSP-DIS-2015-0055-0, Ministry of Public Health (MSP), Ecuador.

Familias Unidas for high risk adolescents: Study design of a cultural adaptation and randomized controlled trial of a U.S. drug and sexual risk behavior intervention in Ecuador.

BACKGROUND: Developing, testing and implementing evidence-based prevention interventions are important in decreasing substance use and sexual risk behavior among adolescents. This process requires research expertise, infrastructure, resources and decades of research testing, which might not always be feasible for low resource countries. Adapting and testing interventions proven to be efficacious in similar cultures might circumvent the time and costs of implementing evidence-based interventions in new settings. This paper describes the two-phase study, including training and development of the research infrastructure in the Ecuadorian university necessary to implement a randomized controlled trial. METHODS/DESIGN: Familias Unidas is a multilevel parent-centered intervention designed in the U.S. to prevent drug use and sexual risk behaviors in Hispanic adolescents. The current study consisted of Phase 1 feasibility study (n=38) which adapted the intervention and study procedures within a single-site school setting in an area with a high prevalence of drug use and unprotected sexual behavior among adolescents in Ecuador, and Phase 2 randomized controlled trial of the adapted intervention in two public high schools with a target population of families with adolescents from 12 to 14 years old. DISCUSSION: The trial is currently in Phase 2. Study recruitment was completed with 239 parent-youth dyads enrolling. The intervention phase and the first follow-up assessment have been completed. The second and third follow-up assessments will be completed in 2016. This project has the potential of benefitting a large population of families in areas of Ecuador that are disproportionally affected by drug trafficking and its consequences. TRIAL REGISTRATION: MSP-DIS-2015-0055-0, Ministry of Public Health (MSP), Quito, Ecuador.

[Hidradenoma papilliferum. Report of two cases and review of literature]. / Hidradenoma papilífero. Reporte de dos casos y revisión de la bibliografía.

We bring two cases of hidradenoma papilliferum, rare injury. We describe the clinical, histopathological and a review of the available literature on the condition.

Diet for the prevention of asthma and allergies in early childhood: Much ado about something?

In the last decades there has been an increase in allergic disease throughout the world, particularly in children. Attempts have been made to identify the causes of this ‘‘allergy epidemic’’ in environmental changes and changes in population hygiene, lifestyle, socio economic level, and eating habits that would exert epigenetic effects. Dietetic hypotheses have been mainly focussed in long-chain polyunsaturated fatty acids, vitamin D, antioxidants, Mediterranean diet, and fruits, vegetables and fish consumption. Although the data suggest a certain association between diet and the development of asthma/allergy, there is no evidence that diet has an impact upon the prevalence of such diseases after early infancy. If indeed there is such an impact, it is likely to be confined to the prenatal period and the first months of life-when it is still possible to modulate the development of the respiratory, digestive and immune systems. Thus, once the most appropriate preventive measures have been defined, these should be implemented during pregnancy and lactation. The existing scientific evidence is unable to recommend any primary preventive measure in the general population or in different population subgroups. Special or restrictive diets in pregnantor nursing women are not indicated. Exclusive breastfeeding for six months is questioned, since solid foods should begin to be introduced at around four months of age. Once the atopic process has started, no nutritional strategies have been found to be effective as secondary or tertiary preventive measures. Longitudinal studies in cohorts of pregnant women or new born infants could help clarify these issues(AU)

Diet for the prevention of asthma and allergies in early childhood: much ado about something?

In the last decades there has been an increase in allergic disease throughout the world, particularly in children. Attempts have been made to identify the causes of this "allergy epidemic" in environmental changes and changes in population hygiene, lifestyle, socioeconomic level, and eating habits that would exert epigenetic effects. Dietetic hypotheses have been mainly focussed in long-chain polyunsaturated fatty acids, vitamin D, antioxidants, Mediterranean diet, and fruits, vegetables and fish consumption. Although the data suggest a certain association between diet and the development of asthma/allergy, there is no evidence that diet has an impact upon the prevalence of such diseases after early infancy. If indeed there is such an impact, it is likely to be confined to the prenatal period and the first months of life - when it is still possible to modulate the development of the respiratory, digestive and immune systems. Thus, once the most appropriate preventive measures have been defined, these should be implemented during pregnancy and lactation. The existing scientific evidence is unable to recommend any primary preventive measure in the general population or in different population subgroups. Special or restrictive diets in pregnant or nursing women are not indicated. Exclusive breastfeeding for six months is questioned, since solid foods should begin to be introduced at around four months of age. Once the atopic process has started, no nutritional strategies have been found to be effective as secondary or tertiary preventive measures. Longitudinal studies in cohorts of pregnant women or newborn infants could help clarify these issues.

Cyclic analogs of alpha-melanocyte-stimulating hormone (alphaMSH) with high agonist potency and selectivity at human melanocortin receptor 1b.

Alpha-melanotropin (alphaMSH), Ac-Ser1-Tyr2-Ser3-Met4-Glu5-His6-Phe7-Arg8-Trp9-Gly10-Lys11-Pro12-Val13-NH2,(1) has been long recognized as an important physiological regulator of skin and hair pigmentation in mammals. Binding of this peptide to the melanocortin receptor 1 (MC1R) leads to activation of tyrosinase, the key enzyme of the melanin biosynthesis pathway. In this study, interactions of the human MC1bR (an isoform of the receptor 1a) with the synthetic cyclic analogs of alphaMSH were studied. These ligands were analogs of MTII, Ac-Nle4-cyclo-(Asp5-His6-D-Phe7-Arg8-Trp9-Lys10)-NH2, a potent pan-agonist at the human melanocortin receptors (hMC1,3-5R). In the structure of MTII, the His6-D-Phe7-Arg8-Trp9 segment has been recognized as "essential" for molecular recognition at the human melanocortin receptors (hMC1,3-5R). Herein, the role of the Trp9 in the ligand interactions with the hMC1b,3-5R has been reevaluated. Analogs with various amino acids in place of Trp9 were synthesized and tested in vitro in receptor affinity binding and cAMP functional assays at human melanocortin receptors 1b, 3, 4 and 5 (hMC1b,3-5R). Several of the new peptides were high potency agonists (partial) at hMC1bR (EC50 from 0.5 to 20 nM) and largely inactive at hMC3-5R. The bulky aromatic side chain in position 9, such as that in Trp, was found not to be essential to agonism (partial) of the studied peptides at hMC1bR.

Analogs of alpha-melanocyte stimulating hormone with high agonist potency and selectivity at human melanocortin receptor 1b: the role of Trp(9) in molecular recognition.

alpha-Melanocyte stimulating hormone (alphaMSH), Ac-Ser(1)-Tyr(2)-Ser(3)-Met(4)-Glu(5)-His(6)-Phe(7)-Arg(8)-Trp(9)-Gly(10)-Lys(11)-Pro(12)-Val(13)-NH(2), is an endogenous agonist for the melanocortin receptor 1 (MC1R), the receptor found in the skin, several types of immune cells, and other peripheral sites. Three-dimensional models of complexes of this receptor with alphaMSH and its synthetic analog NDP-alphaMSH, Ac-Ser(1)-Tyr(2)-Ser(3)-Nle(4)-Glu(5)-His(6)-D-Phe(7)-Arg(8)-Trp(9)-Gly(10)-Lys(11)-Pro(12)-Val(13)-NH(2), have been previously proposed. In those models, the 6-9 segment of the ligand was considered essential for the ligand-receptor interactions. In this study, we probed the role of Trp(9) of NDP-alphaMSH in interactions with hMC1bR. Analogs of NDP-alphaMSH with various amino acids in place of Trp(9) were synthesized and tested in vitro in receptor affinity binding and cAMP functional assays at human melanocortin receptors 1b, 3, 4, and 5 (hMC1b,3-5R). Several new compounds displayed high agonist potency at hMC1bR (EC(50) = 0.5-5 nM) and receptor subtype selectivity greater than 2000-fold versus hMC3-5R. The Trp(9) residue of NDP-alphaMSH was determined to be not essential for molecular recognition at hMC1bR.