RANK deletion in neuropeptide Y neurones attenuates oestrogen deficiency‐related bone loss

The RANKL pathway is known to be an important aspect of the pathogenesis of oestrogen deficiency‐induced bone loss. RANK deletion specifically in neuropeptide Y (NPY) neurones has been shown to enhance the ability of the skeleton to match increases in body weight caused by high‐fat diet feeding, likely via the modulation of NPY levels. In the present study, we used ovariectomy in female mice to show that RANK deletion in NPY neurones attenuates bone loss caused by long‐term oestrogen deficiency, particularly in the vertebral compartment. Ovariectomy led to a reduction in NPY expression levels in the arcuate nucleus of NPY^cre/+;RANK^lox/lox mice compared to NPY^cre/+;RANK^lox/+ controls. Because NPY deficient mice also displayed a similar protection against ovariectomy‐induced bone loss, modulation of hypothalamic NPY signalling is the likely mechanism behind the protection from bone loss in the NPY^cre/+;RANK^lox/lox mice.     

Reverse Peroneal Artery Flap—A Workhorse Flap for Reconstruction of Large,Distal Defects of Ankle and Foot

Background  Reconstruction of large foot and ankle defects is a difficult task due to less available local soft tissue and more critical from functional point of view. To overcome the limitations associated with locoregional flaps and free flaps, reverse peroneal artery (RPA) flap was selected and its usefulness in reconstruction of distal large defects of the ankle and foot and its complications were studied. Materials and Methods  This is a prospective observational study done in 20 patients treated as cohort within 2 years and 8 months from January 2018 to August 2020. Large defects of foot and ankle were reconstructed with RPA flap and evaluated for its usefulness. Three cases were evaluated with computed tomography angiography postoperatively, to assess the vascular pattern. Conclusion  RPA flap is a versatile and very reliable flap for the reconstruction of large and distal defects of foot and ankle. It is safely done in children and in acute trauma without any major complications.     

影响小鼠视网膜检查的突发性可逆性晶状体混浊

目的:评价氯胺酮/甲苯噻嗪麻醉对小鼠晶状体的影响。方法:用氯胺酮(60mg/kg)/甲苯噻嗪(10mg/kg)腹腔注射,分别麻醉4,8,12和16wk的Kimba小鼠(n=10)和野鼠(n=8)。托吡卡胺眼液(25g/L)扩大瞳孔后用HRA+OCT检查晶状体状态和视网膜病变。结果:所有的Kimba小鼠和野鼠都出现严重的眼球突出,眨眼反射消失,角膜干燥和晶状体混浊。最早的晶状体混浊发生在麻醉后的21±6min,晶状体混浊可持续150±24min。结论:氯胺酮/甲苯噻嗪麻醉可导致暂时性晶状体混浊,晶状体混浊与氯胺酮/甲苯噻嗪的副作用有关。     

Characterization of a Mouse Model of Hyperglycemia and Retinal Neovascularization

One of the limitations of research into diabetic retinopathy is the lack of suitable animal models. To study how the two important factors—hyperglycemia and vascular endothelial growth factor—interact in diabetic retinopathy, the Akimba mouse (Ins2^AkitaVEGF^+/−) was generated by crossing the Akita mouse (Ins2^Akita) with the Kimba mouse (VEGF^+/+). C57Bl/6 and the parental and Akimba mouse lines were characterized by biometric measurements, histology, immunohistochemistry, and Spectralis Heidelberg retinal angiography and optical coherence tomography. The Akimba line not only retained the characteristics of the parental strains, such as developing hyperglycemia and retinal neovascularization, but developed higher blood glucose levels at a younger age and had worse kidney-body weight ratios than the Akita line. With aging, the Akimba line demonstrated enhanced photoreceptor cell loss, thinning of the retina, and more severe retinal vascular pathology, including more severe capillary nonperfusion, vessel constriction, beading, neovascularization, fibroses, and edema, compared with the Kimba line. The vascular changes were associated with major histocompatibility complex class II⁺ cellular staining throughout the retina. Together, these observations suggest that hyperglycemia resulted in higher prevalences of edema and exacerbated the vascular endothelial growth factor-driven neovascular and retinal changes in the Akimba line. Thus, the Akimba line could become a useful model for studying the interplay between hyperglycemia and vascular endothelial growth factor and for testing treatment strategies for potentially blinding complications, such as edema.Diabetes is widely recognized as one of the leading causes of death and disability and is the fifth-leading cause of death by disease in the United States.¹ Diabetes is associated with long-term complications that affect almost every part of the body, often leading to blindness, cardiovascular disease, kidney failure, and nerve damage.The Ins2^Akita (Akita) mouse^2,3,4 is a naturally occurring diabetes model that carries a dominant mutation in the Mody4 locus on chromosome 7 in the insulin 2 gene. The heterozygous male mice develop hyperglycemia and hypoinsulinemia at 4 weeks postnatal and progress to develop the well-known signs of diabetes. They exhibit signs similar to early pathophysiological changes of diabetic complications,^{5,6,7,8,9,10,11} but fail to develop any of the advanced stages of these complications. Analysis of retinae of Ins2^Akita mice⁵ showed early neuronal changes, increased vascular permeability, a modest increase in acellular capillaries, increased leukostasis, a thinner inner plexiform layer, and amacrine and ganglion cell loss.¹² Although these changes are associated with the early stages of diabetic retinopathy (DR), they fall short of the proposed target for a DR animal model, which should have capillary and neuronal loss, capillary obliteration and dropout, retinal edema, and preretinal neovascularization (pre-RNV; Animal Models of Diabetic Complications Consortium, http://www.amdcc.org/shared/retinopathyvalidation.aspx; last accessed on August 23, 2010).The trVEGF029 (Kimba) mouse model, in which photoreceptors transiently overexpress human vascular endothelial growth factor (hVEGF),^13,14 has a slower and less destructive form of neovascularization¹⁵ than previously described models.¹⁶ The Kimba model features hVEGF production, which peaks at around 10 days postnatal and gradually decreases to an only slightly elevated level by 6 weeks postnatal.^14,15 Despite transient hVEGF up-regulation, the short-term presence of elevated hVEGF induces vascular permeability, capillary nonperfusion/dropout, microaneurysms, RNV, and occasional hemorrhages.^15,17 The Kimba model has several vascular changes associated with DR but, crucially, this model is not on a hyperglycemic background.To date, other rodent diabetes models, whether transgenic, naturally occurring or induced, have failed to develop advanced stages of retinal complications regardless of the age of onset or the duration of hyperglycemia. Thus, generation of a model that develops retinal vascular changes similar to those presented in DR would represent a significant advance for DR research. This article describes the generation of a mouse model that presents with RNV on a hyperglycemic background. We crossbred the Akita with our Kimba mice^13,15 resulting in a model that allows investigation into the interplay between high blood glucose levels (BGLs) and VEGF-induced retinal pathology.