Eye colour: portals into pigmentation genes and ancestry

Several recent papers have tried to address the genetic determination of eye colour via microsatellite linkage, testing of pigmentation candidate gene polymorphisms and the genome wide analysis of SNP markers that are informative for ancestry. These studies show that the OCA2 gene on chromosome 15 is the major determinant of brown and/or blue eye colour but also indicate that other loci will be involved in the broad range of hues seen in this trait in Europeans.

A golden age of human pigmentation genetics

The zebrafish golden mutation is characterized by the production of small and irregular-shaped melanin granules, resulting in a lightening of the pigmented lateral stripes of the animal. The recent positional cloning and localization of the golden gene, combined with genotype-phenotype correlations of alleles of its human orthologue (SLC24A5) in African-American and African-Caribbean populations, provide insights into the genetic and molecular basis of human skin colour. SLC24A5 promotes melanin deposition through maturation of the melanosome, highlighting the importance of ion-exchange in the function of this organelle.

Diversity of pigmentation in cultured human melanocytes is due to differences in the type as well as quantity of melanin

Cultured human melanocytes differ tremendously in visual pigmentation, and recapitulate the pigmentary phenotype of the donor's skin. This diversity arises from variation in type as well as quantity of melanin produced. Here, we measured contents of eumelanin (EM) and pheomelanin (PM) in 60 primary human melanocyte cultures (51 neonatal and nine adults), and correlated some of these values with the respective activity and protein levels of tyrosinase, and the melanocortin-1 receptor (MC1R) genotype. Melanocytes were classified into four phenotypes (L, L+, D, D+) as depicted by visual pigmentation using light microscopy, and by the pigmentary phenotype of the donor's skin. There were large differences in total melanin (TM) and EM, which increased progressively for L, L+, D and D+ melanocytes. TM content, the sum of EM and PM, showed a good correlation with TM measured spectrophotometrically, and with the activity and protein levels of tyrosinase. Log EM/PM ratio did not correlate with MC1R genotype. We conclude that: (i) EM consistently correlates with the visual phenotype; (ii) lighter melanocytes tend to be more pheomelanic in composition than darker melanocytes; (iii) in adult melanocyte cultures, EM correlates with the ethnic background of the donors (African-American > Indian > Caucasian); and (iv) MC1R loss-of-function mutations do not necessarily alter the phenotype of cultured melanocytes.

Morbidity due to Schistosoma mansoni: an epidemiological assessment of distended abdomen syndrome in Ugandan school children with observations before and 1-year after anthelminthic chemotherapy

The objectives of this study were to determine the prevalence and distribution of distended abdomens among Ugandan school children across a range of eco-epidemiological settings and to investigate the relationship between distended abdomens and helminth infections, in particular Schistosoma mansoni, before and 1-year after anthelminthic treatment. A cross-sectional survey was conducted on 4354 school children across eight districts, with a longitudinal 1-year follow-up of 2644 children (60.7%). On both occasions, parasitological, biometrical and clinical data were collected for each child. Baseline prevalence of S. mansoni and hookworms was 44.3% and 51.8%, respectively. Distended abdomens, defined as an abdominal circumference ratio (ACR) >1.05, were observed in 2.5% of the sampled children, several of whom presented with particularly severe distensions necessitating hospital referral. ACR scores were highly overdispersed between districts and schools. Multivariate regression analysis revealed that S. mansoni infection accounted for only a small fraction of ACR variation, suggesting that either single point prevalence and intensity measures failed to reflect this more chronically evolved morbidity and/or that other interacting factors were involved, e.g. malnutrition and malaria. At 1-year follow-up, ACR scores showed an overall trend of regression towards the mean, potentially indicative of amelioration following chemotherapy, but geographic overdispersion still remained. © 2006 Royal Society of Tropical Medicine and Hygiene.

Cone photoreceptor oil droplet pigmentation is affected by ambient light intensity

The cone photoreceptors of many vertebrates contain spherical organelles called oil droplets. In birds, turtles, lizards and some lungfish the oil droplets are heavily pigmented and function to filter the spectrum of light incident upon the visual pigment within the outer segment. Pigmented oil droplets are beneficial for colour discrimination in bright light, but at lower light levels the reduction in sensitivity caused by the pigmentation increasingly outweighs the benefits generated by spectral tuning. Consequently, it is expected that species with pigmented oil droplets should modulate the density of pigment in response to ambient light intensity and thereby regulate the amount of light transmitted to the outer segment. In this study, microspectrophotometry was used to measure the absorption spectra of cone oil droplets in chickens (Gallus gallus domesticus) reared under bright (unfiltered) or dim (filtered) sunlight. Oil droplet pigmentation was found to be dependent on the intensity of the ambient light and the duration of exposure to the different lighting treatments. In adult chickens reared in bright light, the oil droplets of all cone types (except the violet-sensitive single cones, whose oil droplet is always non-pigmented) were more densely pigmented than those in chickens reared in dim light. Calculations show that the reduced levels of oil droplet pigmentation in chickens reared in dim light would increase the sensitivity and spectral bandwidth of the outer segment significantly. The density of pigmentation in the oil droplets presumably represents a trade-off between the need for good colour discrimination and absolute sensitivity. This might also explain why nocturnal animals, or those that underwent a nocturnal phase during their evolution, have evolved oil droplets with low pigment densities or no pigmentation or have lost their oil droplets altogether.

Endothelin 3 induces skin pigmentation in a keratin-driven inducible mouse model

Endothelin 3 (Edn3) is a ligand important to developing neural crest cells (NCC). Some NCC eventually migrate into the skin and give rise to the pigment-forming melanocytes found in hair follicles. Edn3's effects on NCC have been largely explored through spontaneous mutants and cell culture experiments. These studies have shown the Endothelin receptor B/Edn3 signaling pathway to be important in the proliferation/survival and differentiation of developing melanocytes. To supplement these investigations I have created doxycycline-responsive transgenic mice which conditionally over-express Edn3. These mice will help us clarify Edn3's role during the development of early embryonic melanoblasts, differentiating melanocyte precursors in the skin, and fully differentiated melanocytes in the hair follicle. The transgene mediated expression of Edn3 was predominantly confined to the roof plate of the neural tube and surface ectoderm in embryos and postnatally in the epidermal keratinocytes of the skin. Relative to littermate controls, transgenics develop increased pigmentation on most areas of the skin. My doxycycline-based temporal studies have shown that both embryonic and postnatal events are important for establishing and maintaining pigmented skin. The study of my Edn3 transgenic mice may offer some insight into the genetics behind benign dermal pigmentation and offer clues about the time periods important in establishing these conditions. This apparently abnormal development is echoed in a benign condition of human skin. Cases of dermal melanocytosis, such as common freckles, Mongolian spotting, and nevus of Ito demonstrate histological and etiological characteristics similar to those of the transgenic mice generated in this study.

Hipertensión intra-abdominal y síndrome abdominal compartamental prevalencia postlaparotomía por abdomen agudo, HVCM Cuenca 2010-2011 /

La hipertensión intra-abdominal (HIA) y el síndrome compartamental abdominal (SCA) son causa importante de morbi-mortalidad postoperatoria. Avances en su diagnóstico y tratamiento oportuno han proporcionado mejor sobrevida en estos pacientes. Objetivo. Determinar la prevalencia de HIA, SCA y asociarla con (hallazgos quirúrgicos, presión de perfusión Intra-abdominal (PPI), obesidad) intervenidos por abdomen agudo en el Departamento de Cirugía del Hospital Vicente Corral Moscoso de Cuenca. Metodología. Se realizó un estudio transversal analítico en pacientes mayores de 16 años que ameritaron laparotomía de septiembre de 2010 hasta agosto de 2011 y que cumplieron criterios de exclusión, la PIA fue medida mediante método indirecto y la información se recopilo en un formulario elaborado para el estudio. Resultados: 347 Pacientes fueron incluidos en el estudio, la media de edad se ubicó en 46.72 ± 22.30 años, presentaron sobrepeso el 5.2%, en el estadio pre-quirúrgico se encontró Hipertensión Intra-abdominal en 41.2% y 10.4% de síndrome compartamental; luego de la laparotomía la hipertensión intra-abdominal disminuyó a 37.7% y el síndrome compartamental a 8.4%. La PIA iguales o mayores a 12mmHg aumentan el riesgo de hipo-perfusión intestinal en 3.56 veces (IC 95%: 1.81-6.99), p menor que 0.05; la obesidad se comportó como factor de riesgo con un RP de 1.73 (1.451-2.13); los hallazgo quirúrgico encontrados fueron significativos para Abdomen agudo perforativo: 2.45 con IC 95% 1.91-3.13; Abdomen agudo hemorrágico 1.83 con IC 95% 1.46-2.30 y Abdomen agudo oclusivo intestinal 2.32 con IC 95% 2.05-2.64. Conclusión: La Hipertensión intra-abdominal disminuye progresivamente en el postoperatorio, mientras que en quienes se manifiesta el SCA permaneció elevado por mayor tiempo. Se evidencio que la Obesidad influye incrementando la PIA, la misma que produce disminución de la PPI prediciendo peor pronóstico; los hallazgos quirúrgicos representativos para el incremento de la PIA fueron el abdomen agudo perforativo y oclusivo .au

Valor diagnóstico y pronóstico de la medición de la presión intraabdominal transvesical en pacientes con abdomen agudo en el H.V.C.M. Cuenca febrero a septiembre del 2000

A 60 pacientes ingresados en emergencia y cirugía se realizó la medición de la presión intraabdominal [P.I.A.] por vía vesical a través de una sonda Foley. Clasificados en dos grupos de estudio: 30 del grupo de control; sin patología abdominal: 22 hombres y 8 mujeres con un promedio de edad 49 años, diagnosticados de; T.E.C., trauma raquimedular, meningitis, absceso cerebral y mal formación arteriovenoso, que necesitaban de sonda vesical. Obteníendose una media normal o valor referencial de normalidad de 2.7 cm. H20 o 1.98 mmHg. El segundo grupo experimental: 30 pacientes diagnosticados de abdomen agudo quirúrgico: 21 hombres y 9 mujeres, con un promedio de edad de 46 años, clasificados en 5 tipos de abdomen agudo: AAOI, AAT,AAP AAI. AAOV. se les mediÓ la presión intraabdominal transvesical, obteniéndose los siguientes resultados. P.I.A.: Prequirúrgico medio: 19.29 cm H20 [14.18 mmHg.]. P.IA.: Posquirúrgico media: 8.97 cm H20 [6.59 mmHg.]. Todos sometidos a laparotomía exploratoria. Mejorando 28 pacientes, uno empeoró y solicitÓ el alta, un paciente falleció. En el grupo de control los 30 pacientes presentaron la presiÓn intraabdominal en valores normales

Síndrome de VOMIT (Victim of Modern Imaging Technology) en pacientes con trauma de abdomen cerrado que consultaron en la Unidad de emergencia del Hospital General ISSS sometidos a LPE periodo Enero 2012 a Diciembre 2014

La tecnología se ha extendido a todas las áreas de la medicina, incluida la imagenología. El síndrome V.O.M.I.T “VICTIM OF MODERN IMAGING TECHNOLOGY”, describe el conjunto de consecuencias adversas secundarias a la mala aplicación e interpretación imagenológica, vinculadas al diagnóstico, tratamiento ó pronóstico de los pacientes politraumatizados que ingresan al Servicio de Emergencia. Es una entidad clínica en si misma dentro del capítulo de errores médicos y los servicios de emergencia son áreas de riesgo para que suceda. Sin duda, es imprescindible conocerlo, medirlo y plantear medidas preventivas. En nuestro medio la real incidencia de este problema se desconoce. Es por eso que la pregunta de nuestra investigación es: ¿Con que frecuencia la decisión de realizar una laparotomía exploradora en trauma cerrado de abdomen, con claras indicaciones clínicas se ve retrasada en espera de estudios de imageneologia?. Nuestra hipótesis era que la toma de conducta quirúrgica en trauma cerrado de abdomen en la unidad de emergencia del Hospital General del Seguro Social está siendo retrasada por el Síndrome de V.O.M.I.T. la cual fue verdadera. Es por esto que el objetivo general de nuestro estudio fue demostrar la presencia y frecuencia de este síndrome. Para ello recolectamos del libro de procedimientos de Sala de Operaciones de la Unidad de Emergencia del Hospital General (ISSS) los números de expedientes de los pacientes que fueron sometido a Laparotomía Exploradora con diagnóstico trauma cerrado de abdomen, en el periodo de Enero 2012 a Diciembre 2014 posteriormente se revisaron dichos expedientes y analizaron los datos.

Increasing Skin Pigmentation Following Severe Head Trauma: All That Glitters Is Not Gold!

We report the case of a 67-year-old man who was admitted to our Intensive Care Unit because of traumatic brain injury. During his prolonged hospitalization, gradual darkening of the skin all over his body was observed. An excess corticotropin (ACTH) production syndrome was considered. The patient’s hormone study showed high levels of ACTH (978 pg/ml) with normal cortisol levels. Extensive clinical and laboratory investigations revealed adenocarcinoma of the colon, which was likely the site of the ectopic ACTH production. This is a very rare manifestation of paraneoplastic syndrome during the course of colon adenocarcinoma. The most important feature of this case report is that this rare syndrome was accidentally discovered, in a patient hospitalized for unrelated reasons, by simple clinical investigation.

Estudio retrospectivo de caballos con síndrome de abdomen agudo diagnosticados con desplazamiento de colon dorsal derecho en el centro de veterinaria y zootecnia de La Universidad Ces durante el período 2005-2013

Tesis (Médico Veterinario). -- Universidad de La Salle. Facultad de Ciencias Agropecuarias. Programa de Medicina Veterinaria, 2014