Topobiology of Human Pigmentation: P-Cadherin Selectively Stimulates Hair Follicle Melanogenesis.

P-cadherin serves as a major topobiological cue in mammalian epithelium. In human hair follicles (HFs), it is prominently expressed in the inner hair matrix that harbors the HF pigmentary unit. However, the role of P-cadherin in normal human pigmentation remains unknown. Since patients with mutations in the gene that encodes P-cadherin show hypotrichosis and fair hair, we explored the hypothesis that P-cadherin may control HF pigmentation. When P-cadherin was silenced in melanogenically active organ-cultured human scalp HFs, this significantly reduced HF melanogenesis and tyrosinase activity as well as gene and/or protein expression of gp100, stem cell factor, c-Kit, and microphthalmia-associated transcription factor (MITF), both in situ and in isolated human HF melanocytes. Instead, epidermal pigmentation was unaffected by P-cadherin knockdown in organ-cultured human skin. In hair matrix keratinocytes, P-cadherin silencing reduced plasma membrane beta-catenin, while glycogen synthase kinase 3 beta (GSK3beta) and phospho-beta-catenin expression were significantly upregulated. This suggests that P-cadherin-GSK3beta/Wnt signaling is required for maintaining expression of MITF to sustain intrafollicular melanogenesis. Thus, P-cadherin-mediated signaling is a melanocyte subtype-specific topobiological regulator of normal human pigmentation, possibly via GSK3beta-mediated canonical Wnt signaling.Journal of Investigative Dermatology accepted article preview online, 18 January 2013; doi:10.1038/jid.2013.18

Cisto ovariano em vacas de leite: incidência, resposta à aplicação de GnRH e desempenho reprodutivo Ovarian cysts in lactating dairy cows: incidence, response to GnRH, and reproductive performance

A incidência de cistos ovarianos, a resposta ao tratamento com GnRH e os efeitos da ocorrência de cisto no desempenho reprodutivo e na taxa de descarte foram determinados em vacas lactantes da raça Holandesa. Vacas lactantes (n=333) foram avaliadas semanalmente por ultrassonografia a partir da quarta semana pós-parto, visando à detecção de corpos lúteos (CL) e de folículos ovarianos maiores que 10mm. Na sétima semana pós-parto, as vacas foram classificadas: em ciclando (n=248; presença de CL em um dos exames ultrassonográficos); em anestro (n=54; ausência de CL e de folículos >25mm) e com cisto (n=31; ausência de CL e presença de estruturas >25mm), quando foram distribuídas em: grupo-controle (n=16; sem tratamento) e grupo-tratamento (n=15; vacas que receberam uma aplicação de GnRH). A taxa de cura foi de 60,0% no grupo das vacas tratadas e de 87,5% no grupo-controle. As vacas com cistos apresentaram maior intervalo parto-primeira inseminação artificial (P<0,05; 91,4±8,3 vs. 77,8±2,5), maior número de serviços por concepção (P<0,05; 4,4±1,2 vs. 3,6±1,5), maior intervalo parto-concepção (P<0,05; 214,8±25,9 vs. 174,9±7,7) e maior taxa de descarte (P<0,05; 41,2 vs. 21,8%) do que as vacas ciclando. Vacas diagnosticadas com cisto na sétima semana pós-parto apresentaram recuperação espontânea, embora o intervalo parto-concepção e a taxa de descarte tenham sido maiores para essas vacas.<br>The incidence of ovarian cysts, response to GnRH treatment, and effects on reproductive performance and culling rate of Holstein cows were determined. Ovaries of lactating cows (n=333), were weekly monitored by ultrasound, beginning at fourth week postpartum, to determine the presence of corpus luteum (CL) and follicles greater than 10mm. In the seventh week the cows were classified as cycling (n=248; presence of corpus luteum (CL) in one of the ultrasound evaluations); anovulatory (n=54; absence of CL and follicles less than 25mm), and cystic (n=31; absence of CL and presence of structures greater than 25mm). The cysts cows were distributed in two groups in the seventh week: control group (n=16; without treatment) and treatment group (n=15; cows received one GnRH injection). The recovery rate was 60.0% in treated cows and 87.5% in control cows. The cystic cows had longer average interval from parturition to first AI (P<0.05; 91.4±8.3 vs. 77.8±2.5), higher number of services per conception (P<0.05; 4.4±1.2 vs. 3.6±1.5), longer interval parturition to conception (P<0.05; 214.8± 25.9 vs. 174.9±7.7), and higher percentage of culled cows (P<0.05; 41.2% vs. 21.8%), than cycling cows. Cystic cows without treatment had the same recovery rate as cows treated with GnRH. Cystic cows had longer intervals from parturition to conception, and higher culling rate

Avaliação do uso de haste bloqueada e bloqueio transcortical no reparo de fraturas diafisárias de fêmur em felinos Evaluation of the use of interlocking nail and transcortical blockade for the repair of diaphyseal fractures of the femur in cats

As hastes bloqueadas além de permitirem estabilização rígida de fraturas, possuem vantagens biomecânicas quando comparadas a outras técnicas de imobilização, por atuar ao longo do eixo mecânico central do osso, além de preservar os conceitos de padrões biológicos de osteossíntese . O uso limitado de hastes bloqueadas em gatos se atribui ao fato da cavidade intramedular ser pequena, limitando o tamanho e diâmetro dos pinos. Relatam-se casos de 10 felinos que apresentavam fraturas fechadas simples ou múltiplas da diáfise femoral. Os animais pesavam entre 3,5 e 5 kg, o que permitiu a utilização de hastes de 4,0mm e 4,7mm de diâmetro. Para inserção da haste, adotou-se a via retrógrada ou a normógrada e foram realizados bloqueios com quatro parafusos de titânio de 2,0 mm de diâmetro. Complicações intra-operatórias não ocorreram, entretanto um animal sofreu fratura de colo femoral e fratura transversa distal ao implante, três dias após o ato cirúrgico, devido a novo trauma. Os animais foram submetidos a exames radiográficos até quatro meses após a intervenção, evidenciando-se formação de calo ósseo secundário e consolidação óssea em período de 61-89 dias. Clinicamente, ocorreu esporadicamente alteração na marcha por leve claudicação de apoio definida por escala de claudicação, entretanto os animais iniciaram o apoio adequado entre três e oito dias após o ato operatório. Complicações pósoperatórias ocorreram referentes ao animal que sofreu novo trauma, entretanto notou-se consolidação do foco primário tratado pelo implante com 61 dias e consolidação da nova fratura num período total de 150 dias do início do tratamento conservativo por penso esparadrapado e tala. Conclui-se que o uso de haste bloqueada em felinos foi adequado uma vez que houve consolidação óssea em todos os casos, com retorno precoce da função do membro, permitindo a deambulação.<br>Interlocking nails allow rigid fracture stabilization and present biomechanical advantages when compared to other immobilization techniques. It acts along the central mechanical axis of the bone and preserves biological concept standards for osteosynthesis. The use of interlocking nail in cats is limited because the intramedullary space is relatively small for the available nail sizes. We reported 10 cases of cats that had simple or multiple closed fractures of the femoral diaphysis. The animals weighed 3.5 to 5 kg , which allowed using nails of 4.0mm and 4.7mm in diameter. For the nail insertion, retrograde and normograde routs were used, and four 2mm titanium screws were used to lock all the perforations. No trans-surgical complication occurred, however, due to a new trauma, one of the animals suffered femoral neck fracture and transversal distal fracture to the nail, three days after surgery. Radiographies were made up to four months after surgery, and in most cases secondary bone formation was seen, showing bone consolidation in 61-89 days, excluding the animal who suffered new trauma, who presented bone healing in 150 days. Clinically, occasional lameness occurred; however, except for the animal that had new trauma, all animals initiated adequate limb support in 3 to 8 days after surgery. In conclusion, the use of 4.0mm and 4.7mm interlocking nails in felines was adequate, with bone healing in all cases, and also return of good limb function after surgery