Osteochondral defects in the ankle: why painful?

Osteochondral defects of the ankle can either heal and remain asymptomatic or progress to deep ankle pain on weight bearing and formation of subchondral bone cysts. The development of a symptomatic OD depends on various factors, including the damage and insufficient repair of the subchondral bone plate. The ankle joint has a high congruency. During loading, compressed cartilage forces its water into the microfractured subchondral bone, leading to a localized high increased flow and pressure of fluid in the subchondral bone. This will result in local osteolysis and can explain the slow development of a subchondral cyst. The pain does not arise from the cartilage lesion, but is most probably caused by repetitive high fluid pressure during walking, which results in stimulation of the highly innervated subchondral bone underneath the cartilage defect. Understanding the natural history of osteochondral defects could lead to the development of strategies for preventing progressive joint damage

Evolução histórica dos utensílios empregados para alimentar lactentes não amamentados Historical evolution of utensils used to feed non breastfed infants

O objetivo desse artigo de revisão é descrever os utensílios empregados ao longo da história para alimentar lactentes não amamentados. O levantamento bibliográfico foi realizado nas bases de dados MEDLINE, LILACS e SciELO, de 1966 a 2007. Para a análise documental, foram processadas buscas na Internet, em enciclopédias, livros de arte, história e museus. Utensílios manufaturados com materiais e formas variadas, dependendo da disponibilidade, poder aquisitivo e cultura, foram empregados desde os primórdios da história para alimentar bebês que, por diferentes motivos, deixaram de ser amamentados. Muitos objetos coexistiram na mesma época e local, outros em tempos e pontos geográficos distantes. A aceitação de uma nova alternativa ocorria sem evidência que comprovasse ou apontasse para os benefícios da mudança. Alguns utensílios voltaram a ser empregados embora a mortalidade infantil fosse elevada à época em que foram utilizados. No início do século XX, as mamadeiras assumiram a forma cilíndrica cônica. A tecnologia trouxe avanços no sentido de melhorar a higienização e possibilitar o controle da contaminação. O vidro deu lugar ao plástico e os bicos de borracha, aos de silicone, mas a mamadeira, como a conhecemos hoje, é a mesma de cem anos atrás.<br>The objective of this article is to describe the utensils used throughout history to feed non breastfed infants. The method used was article review, reference search on the MEDLINE, LILACS and SciELO databases from 1966 to 2007 and documental analysis based on data from the internet, encyclopedias, art and history books, and museums. Utensils manufactured in a variety of materials and shapes, depending on availability, purchasing power and culture have been used since early history to feed babies who for different reasons were not breastfed. Many objects coexisted at the same time and place, others at distant sites and times. New alternatives have been accepted without evidence to prove or point toward the benefits of the change. Some of these alternatives were adopted again, even if infant mortality was high at the time in which they were used at first. In the beginning of the 20th century, bottles became conic-cylindrical. Technology brought about progress as to improve hygiene and enable contamination control. Glass gave way to plastic, and rubber nipples to silicone ones, but the bottle as we know it today is still the same of a 100 years ago

Abnormal mGlu 5 Receptor/Endocannabinoid Coupling in Mice Lacking FMRP and BC1 RNA

Transcriptional silencing of the gene encoding the fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS). FMRP acts as a translational repressor at central synapses, and molecular and synaptic plasticity studies have shown that the absence of this protein alters metabotropic glutamate 5 receptors (mGlu5Rs)-mediated signaling. In the striatum of mice lacking FMRP, we found enhanced activity of diacylglycerol lipase (DAGL), the enzyme limiting 2-arachidonoylglicerol (2-AG) synthesis, associated with altered sensitivity of GABA synapses to the mobilization of this endocannabinoid by mGlu5R stimulation with DHPG. Mice lacking another repressor of synaptic protein synthesis, BC1 RNA, also showed potentiated mGlu5R-driven 2-AG responses, indicating that both FMRP and BC1 RNA act as physiological constraints of mGlu5R/endocannabinoid coupling at central synapses. The effects of FMRP ablation on DAGL activity and on DHPG-mediated inhibition of GABA synapses were enhanced by simultaneous genetic inactivation of FMRP and BC1 RNA. In double FMRP and BC1 RNA lacking mice, striatal levels of 2-AG were also enhanced compared with control animals and to single mutants. Our data indicate for the first time that mGlu5R-driven endocannabinoid signaling in the striatum is under the control of both FMRP and BC1 RNA. The abnormal mGlu5R/2-AG coupling found in FMRP-KO mice emphasizes the involvement of mGlu5Rs in the synaptic defects of FXS, and identifies the modulation of the endocannabinoid system as a novel target for the treatment of this severe neuropsychiatric disorder