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Conradi-Hünermann-Happle syndrome (CHHS) is a rare genodermatosis resulting from mutations in the EBP (emopamil binding protein) gene. Dermatologic manifestations may include cicatricial alopecia, ichthyosis, follicular atrophoderma, pigmentary abnormalities, and nail dystrophy. In addition to genetic testing and clinical findings, trichoscopic findings may aid in the diagnosis. In this case report, we discuss the trichoscopic findings in a 3-year-old girl with CHHS and how these findings help us understand the pathophysiology of this disease.
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Condrodisplasia Punctata , Ictiose , Anormalidades da Pele , Feminino , Humanos , Pré-Escolar , Alopecia/diagnóstico , Alopecia/genética , Mutação , Condrodisplasia Punctata/diagnóstico , Condrodisplasia Punctata/genéticaRESUMO
Introducción. Un estilo de vida poco saludable (malos hábitos alimentarios y sedentarismo), deficiencia de vitamina D, y la ingesta inadecuada de calcio, pueden contribuir a desarrollar osteopenia grave en la infancia, condicionando el riesgo futuro a sufrir fracturas y osteoporosis. Materiales y métodos. Presentamos un caso de osteopenia en una niña blanca, hispana y premenárquica de 13 años quien completó la visita basal del estudio de MetA-Bone. Evaluamos el contenido de masa ósea, la densidad de masa ósea corporal total y de la columna y la composición corporal mediante densitometría ósea (DXA). Abarcamos el historial de salud, antecedentes familiares, desarrollo puberal, actividad física, sueño, ingesta de nutrientes, antropometría, biomarcadores óseos y metabólicos. Resultados. La niña tiene antecedentes familiares de osteoporosis y no reporta fracturas previas. Muestra una actividad moderada al aire libre <1 hora/día 3 veces/semana con 8 horas/día de sueño. El consumo de productos lácteos y vegetales fue <1 ración/día. Presenta deficiencia de vitamina D (25(OH)D: 9 ng/mL) e hiperfosfatemia (5,2 mg/dL). El Z-score del DXA fue -2,1 DE (indicativo de osteopenia por edad y sexo). La niña fue referida a un pediatra, quien confirmó los hallazgos e indicó un suplemento diario con 2000 UI de vitamina D y 1000 mg de calcio. Conclusiones. El aislamiento durante la pandemia de COVID pudo haber contribuido a la gravedad de los hallazgos. Por lo tanto, recomendamos realizar pruebas de detección de vitamina D, calcio y hábitos de vida a los niños que experimentaron crecimiento acelerado durante y después de la pandemia(AU)
Introduction. Poor lifestyle habits, vitamin D deficiency, and inadequate calcium intake, particularly during the COVID-19 pandemic, may contribute to severe osteopenia in childhood, increasing future fractures and osteoporosis risk. Materials and methodology. We here present a case of osteopenia in a 13-year-old white, Hispanic, premenarchal girl who completed the baseline visit of the MetA-Bone Trial during the COVID-19 pandemic. Using a dual-energy X-ray absorptiometry, we assessed bone mass content (BMC), total body and spine bone mass density (BMD), and body composition. We cover the girl's health history and family history, pubertal development, intensity, duration, and frequency of physical activity and sleep, and nutrient intake (calcium and vitamin D), as well as anthropometric parameters, and bone and metabolic biomarkers. Results. The girl has a family history of osteoporosis (maternal grandfather) but no previous fractures; moderate outdoor activity was <1 hour/day 3 times/week with 8 hours/day of sleep. Consumption of dairy products and vegetables was <1 serving/day. Lab blood tests confirmed vitamin D deficiency (serum 25(OH) D: 9 ng/ml) and hyperphosphatemia (5.2 mg/dL); other tests were normal. DXA scan Z-score was -2.1 SD (indicative of osteopenia by age and sex). The girl was referred to a pediatrician, who confirmed the results, and prescribed a daily supplement with 2000 IU of vitamin D and 1000 mg of calcium. Conclusions. Seclusion during the COVID pandemic may have contributed to the severity of the findings. Therefore, we recommend screening children undergoing growth spurts for vitamin D, calcium, and poor lifestyle habits during and after the pandemic(AU)
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Humanos , Feminino , Adolescente , Doenças Ósseas Metabólicas , Adolescente , BiomarcadoresRESUMO
Bacteria of the genera Xenorhabdus and Photorhabdus are symbionts of entomopathogenic nematodes. Despite their close phylogenetic relationship, they show differences in their pathogenicity and virulence mechanisms in target insects. These differences were explored by the analysis of the pangenome, as it provides a framework for characterizing and defining the gene repertoire. We performed the first pangenome analysis of 91 strains of Xenorhabdus and Photorhabdus; the analysis showed that the Photorhabdus genus has a higher number of genes associated with pathogenicity. However, biological tests showed that whole cells of X. nematophila SC 0516 were more virulent than those of P. luminescens HIM3 when both were injected into G. mellonella larvae. In addition, we cloned and expressed the GroEL proteins of both bacteria, as this protein has been previously indicated to show insecticidal activity in the genus Xenorhabdus. Among these proteins, Cpn60-Xn was found to be the most toxic at all concentrations tested, with an LC50 value of 102.34 ng/larva. Sequence analysis suggested that the Cpn60-Xn toxin was homologous to Cpn60-Pl; however, Cpn60-Xn contained thirty-five differentially substituted amino acid residues that could be responsible for its insecticidal activity.
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Los trastornos hipertensivos asociados al embarazo constituyen uno de los síndromes de mayor interés a escala mundial, cerca de 600 000 mujeres mueren anualmente por causas relacionadas. La Organización Mundial de la Salud considera que la incidencia de preeclampsia es siete veces mayor en los países en vías de desarrollo en comparación a los industrializados (2,8 % y 0,4 %, respectivamente). El estrés oxidativo es una de las principales causas asociadas a la preeclampsia, cuyo diagnóstico y manejo adecuado y oportuno son medidas eficaces para disminuir la tasa de morbimortalidad, por lo que diversos autores se han centrado en la búsqueda de biomarcadores predictores de estrés oxidativo entre los cuales encontramos: especies reactivas del ácido tiobarbitúrico, superóxido, catalasa, superóxido dismutasa y glutatión peroxidasa. El presente trabajo describe los principales biomarcadores de estrés oxidativo estudiados mediante la técnica espectrofotométrica debido a que es económica, rápida y precisa
Hypertensive disorders associated with pregnancy are one of the syndromes of greatest interest worldwide, nearly 600,000 women die annually from related causes. The World Health Organization considers that the incidence of preeclampsia is seven times higher in developing countries compared to industrialized ones (2.8% and 0.4%, respectively). Oxidative stress is one of the main causes associated with preeclampsia, whose proper and timely diagnosis and management are effective measures to reduce the morbidity and mortality rate, which is why various authors have focused on the search for predictive biomarkers of oxidative stress among which we find: reactive species of thiobarbituric acid, superoxide, catalase, superoxide dismutase and glutathione peroxidase. The present work describes the main biomarkers of oxidative stress studied by means of the spectrophotometric technique because it is cheap, fast and precise
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Pacientes , Pré-Eclâmpsia , Espectrofotometria , Mulheres , Estresse Oxidativo , Indicadores de Morbimortalidade , Morbidade , MétodosRESUMO
Growth Hormone-Releasing Peptide 6 (GHRP-6) (His-(D-Trp)-Ala-Trp-(D-Phe)-Lys-NH2) is an agonist of the growth hormone secretagogue receptor. GHRP-6 mimics the effect of ghrelin. The present study focuses on the immunomodulatory effects of GHRP-6 in tilapia with and without the presence of Pseudomonas aeruginosa infection. GHRP-6 up-regulated the transcription levels of three piscidin-like antimicrobial peptides (Oreochromicins I, II, and III) and granzyme in a tissue-dependent manner. Antimicrobial activity stimulation in serum (lysozyme and anti-protease activity) was also confirmed. Besides, GHRP-6 enhanced the in vitro antimicrobial activity against P. aeruginosa in tilapia gills mucus and serum samples and decreased the bacterial load in vivo after infection with this Gram-negative bacterium. Our results evidenced, for the first time, a direct link between a growth hormone secretagogue ghrelin mimetic in fish and the enhancement of antimicrobial peptides transcription, which suggests that this secretagogue is capable to lead the activation of microbicidal activity in tilapia. Thus, these results open new possibilities for GHRP-6 application in aquaculture to stimulate the teleost immune system as an alternative treatment against opportunistic bacteria.
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Anti-Infecciosos , Ciclídeos , Tilápia , Animais , Peptídeos Antimicrobianos , Grelina , Hormônio do Crescimento , SecretagogosRESUMO
The development of vaccines employing conserved protein antigens, for instance ribosomal protein P0, has as disadvantage the high degree of identity between pathogen and host proteins due to possible induction of tolerance or auto antibodies in the host organism. To overcome this drawback, peptide-based vaccines have been designed with a proved high efficacy. The use of defined peptides as antigens has the problem that they are generally poor immunogenic unless coupled to a carrier protein. Several studies have established the potential for promiscuous T cell epitopes incorporated into chimeric peptides to enhance the immunogenicity in mammals. On the contrary, studies about the role of these epitopes on teleost immune system are scarce. Therefore, the main objective of our present study was to evaluate the potential of promiscuous T cell epitopes to boost specific IgM immune response in teleost fish against a peptide antigen. With this aim, we used a peptide of 35 amino acids from the ribosomal P0 protein of Lepeophtheirus salmonis, an important parasite in salmon aquaculture. We fused this peptide to the C-terminal of T cell epitopes from tetanus toxin and measles virus and produced the chimeric protein in Escherichia coli. Following vaccination, IgM antibody production was monitored in different immunization schemes in Tilapia, African catfish and Atlantic salmon. The results demonstrated for first time that the addition of T cell epitopes at the N-terminal of a target peptide increased IgM specific response in different teleost species, revealing the potential of this approach to develop peptide-based vaccines for aquaculture. The results are also of great importance in the context of vaccine development against sea lice using ribosomal protein P0 as antigen taking into account the key role of P0 in protein synthesis and other essential physiological processes.
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Copépodes/imunologia , Ectoparasitoses/veterinária , Epitopos de Linfócito T/imunologia , Doenças dos Peixes/imunologia , Imunidade Inata/efeitos dos fármacos , Imunoglobulina M/imunologia , Animais , Proteínas de Artrópodes/imunologia , Peixes-Gato/imunologia , Ciclídeos/imunologia , Ectoparasitoses/imunologia , Peptídeos/imunologia , Proteínas Ribossômicas/imunologia , Salmo salar/imunologia , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
Swine influenza is a worldwide disease, which causes damage to the respiratory system of pigs. The H1N1 and H3N2 subtypes circulate mainly in the swine population of Mexico. There is evidence that new subtypes of influenza virus have evolved genetically and have been rearranged with human viruses and from other species; therefore, the aim of our study was to identify and characterize the genetic changes that have been generated in the different subtypes of the swine influenza virus in Mexican pigs. By sequencing and analyzing phylogenetically the eight segments that form the virus genome, the following subtypes were identified: H1N1, H3N2, H1N2 and H5N2; of which, a H1N1 subtype had a high genetic relationship with the human influenza virus. In addition, a H1N2 subtype related to the porcine H1N2 virus reported in the United States was identified, as well as, two other viruses of avian origin from the H5N2 subtype. Particularly for the H5N2 subtype, this is the first time that its presence has been reported in Mexican pigs. The analysis of these sequences demonstrates that in the swine population of Mexico, circulate viruses that have suffered punctual-specific mutations and rearrangements of their proteins with different subtypes, which have successfully adapted to the Mexican swine population.
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Genoma Viral , Vírus da Influenza A/genética , Infecções por Orthomyxoviridae/virologia , Doenças dos Suínos/virologia , Proteínas Virais/genética , Animais , Hemaglutininas/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/enzimologia , Vírus da Influenza A/isolamento & purificação , México , Neuraminidase/genética , Filogenia , Análise de Sequência de RNA/veterinária , Sus scrofa , SuínosRESUMO
Growth hormone (GH) release is a process that is well regulated by several factors, including GH secretagogues. GH can mediate the regulation of the fatty acid level and composition. The aim of this study was to determine the effect of a synthetic GH secretagogue peptide (A233) on the growth and fatty acid composition in tilapia (Oreochromis niloticus). To address this objective, we administrated a diet supplemented with A233 to juvenile tilapia for 60 days. The group fed with a diet supplemented with 600 µg of A233 per kg of feed increased in weight (4.81 ± 0.09 g) and specific growth rate (2.49 ± 0.03%/day) compared to the control diet group (3.63 ± 0.08 g, 2.07 ± 0.04%/day; respectively) (p < 0.001). In the muscle, the total lipids for the control diet group were higher than that in the group fed with 600 µg of A233 per kg feed; however, no differences were detected in the liver. In both tissues, the patterns of fatty acid composition and content were generally similar, with some exceptions. Tilapia fed with 600 µg of A233 per kg of feed showed, in liver and muscle, a significantly higher composition and content of n-3 polyunsaturated fatty acids (such as 20:5n-3, 22:5n-3, 22:6n-3) and n-3/n-6 PUFA than animals fed with the control diet. To our knowledge, this is the first report on the the effects of natural or synthetic GH secretagogues (GHS) on fatty acid composition, implying an increase in the nutritional quality of the tilapia.
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Ciclídeos/crescimento & desenvolvimento , Ciclídeos/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Fígado/efeitos dos fármacos , Músculos/efeitos dos fármacos , Hormônios Peptídicos/farmacologia , Secretagogos/farmacologia , Animais , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Fígado/metabolismo , Músculos/metabolismo , Hormônios Peptídicos/administração & dosagem , Hormônios Peptídicos/química , Secretagogos/administração & dosagem , Secretagogos/químicaRESUMO
Modern subunit vaccines have excellent safety profiles and improved tolerability, but do not elicit strong immune responses without the addition of adjuvants. Developing a safe and affective adjuvant remains a challenge for peptide-based vaccine design. Growth Hormone Releasing Peptide-6 (GHRP-6) is one of the earliest-developed, synthetic, peptidyl growth hormone secretagogue receptor agonists. These compounds mimic the effect of the endogenous ligand, ghrelin. In the present study, we evaluated the ability of GHRP-6 to enhance the humoral immune response against co-injected antigens in mice, tilapia and African catfish. This peptide was able to increase the antigen-specific antibody response using heterologous proteins and peptides as antigens, which were also formulated in "water in oil" emulsions (Freund and Montanide). As long as we know there is no previous report describing any ghrelin analogous as molecular immunomodulator stimulating a humoral immune response. Further studies will be conducted to evaluate the functionality of this humoral immune response in challenge trials.
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Anticorpos/imunologia , Peixes-Gato/imunologia , Ciclídeos/imunologia , Oligopeptídeos/imunologia , Tilápia/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Antígenos/imunologia , Feminino , Grelina/imunologia , Imunidade Humoral/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
BACKGROUND: Growth hormone secretagogues (GHS), among other factors, regulate the release of GH. The biological activity of the secretagogue peptide A233 as a promoter of growth and innate immunity in teleost fish has previously been demonstrated, but its role in the immune system of mammals is not well understood. METHODS: The effect of the peptide was investigated in J774A.2 macrophage cells using a comparative proteomics approach after 6 and 12 h of peptide stimulation. RESULTS: The functional analysis of differentially modulated proteins showed that A233 peptide treatment appears to promote activation and ROS-dependent cytotoxic functions in macrophages and enhanced expression of antiviral protein complexes such as MAVS. In accordance with this hypothesis, we found that A233 treatment enhanced superoxide anion production and the IFN-γ level in J774A.2 cells and mouse splenocytes, respectively, and reduced viral load in a dengue virus mouse model of infection. CONCLUSIONS: The growth hormone secretagogue A233 peptide promotes activation of ROS-dependent cytotoxic functions and exerts immunomodulatory effects that enable an antiviral state in a dengue virus mouse model. GENERAL SIGNIFICANCE: The increase of IFN-γ level and the differential modulation of antiviral proteins by the A233 peptide suggest that the molecule could activate an innate immune response with a possible further impact in the treatment of acute and chronic diseases.
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We have previously shown that the intrastriatal injection of the C-terminal domain of tetanus toxin (Hc-TeTx) protects the nigrostriatal-dopaminergic pathways and improves motor behavior in hemiparkinsonism-rat models caused by MPP(+) (1-methyl-4-phenylpyridinium). Here we have investigated the protective effects of the intramuscular application of the Hc-TeTx on motor asymmetry and neurodegeneration in the striatum of 6-hydroxydopamine (6-OHDA)-treated rats. Adult male rats were intramuscularly injected with the recombinant Hc-TeTx protein (0.1-20µg/kg, daily) 3days before the stereotaxic injection of 6-OHDA into the left striatum. Our results showed that the motor-improvement functions were extended for 4weeks in all Hc-TeTx-treated groups, obtaining the maximum performance with the highest dose of Hc-TeTx (20µg/kg). The improvements found were 97%, 87%, and 70% in the turning behavior, stepping test, and cylinder test, respectively. The striatal levels of dopamine and its metabolites did not vary compared to the control group. Moreover, the peripheral treatment with Hc-TeTx in rats prevents, for 30days, the neurodegeneration in the striatum caused by the toxicity of the 6-OHDA. Our results lead us to believe that the Hc-TeTx could be a potential therapeutic agent in pathologies caused by impairment of dopaminergic innervations such as Parkinson's disease.
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Corpo Estriado/metabolismo , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Oxidopamina/toxicidade , Transtornos Parkinsonianos/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Toxina Tetânica/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Astrócitos/patologia , Catecolaminas/metabolismo , Cromatografia Líquida de Alta Pressão , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Dopamina/metabolismo , Avaliação Pré-Clínica de Medicamentos , Injeções Intramusculares , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Atividade Motora/fisiologia , Músculo Esquelético , Degeneração Neural/induzido quimicamente , Degeneração Neural/prevenção & controle , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/induzido quimicamente , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Estrutura Terciária de Proteína , Ratos , Ratos Wistar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Toxina Tetânica/administração & dosagem , Toxina Tetânica/farmacologiaRESUMO
In teleosts fish, secretion of GH is regulated by several hypothalamic factors that are influenced by the physiological state of the animal. There is an interaction between immune and endocrine systems through hormones and cytokines. GH in fish is involved in many physiological processes that are not overtly growth related, such as saltwater osmoregulation, antifreeze synthesis, and the regulation of sexual maturation and immune functions. This study was conducted to characterize a decapeptide compound A233 (GKFDLSPEHQ) designed by molecular modeling to evaluate its function as a GH secretagogue (GHS). In pituitary cell culture, the peptide A233 induces GH secretion and it is also able to increase superoxide production in tilapia head-kidney leukocyte cultures. This effect is blocked by preincubation with the GHS receptor antagonist [d-Lys(3)]-GHRP6. Immunoneutralization of GH by addition of anti-tilapia GH monoclonal antibody blocked the stimulatory effect of A233 on superoxide production. These experiments propose a GH-mediated mechanism for the action of A233. The in vivo biological action of the decapeptide was also demonstrated for growth stimulation in goldfish and tilapia larvae (P<0.001). Superoxide dismutase levels, antiprotease activity, and lectin titer were enhanced in tilapia larvae treated with this novel molecule. The decapeptide A233 designed by molecular modeling is able to function as a GHS in teleosts and enhance parameters of the innate immune system in the fish larvae.