Complete recovery of filler-induced visual loss following subcutaneous hyaluronidase injection

The rise in popularity of hyaluronic acid (HA) dermal filler injection has caused an exceptional increase in the number of cases of reported irreversible blindness. Here, we reported a case of ischemic optic neuropathy and ophthalmoplegia following subcutaneous HA filler injection with complete visual recovery. A 31-year-old Chinese woman presented with sudden onset of right monocular visual impairment associated with diplopia. Patient had received a hyaluronic acid-containing ?ller injection for nasal dorsum augmentation twelve hours prior to presentation. Visual acuity of the right eye was counting finger. A right relative afferent pupillary defect was demonstrated with ophthalmoplegia. Humphrey visual field test disclosed a right inferior altitudinal field defect with impairment of colour vision. Computed tomography of the orbit revealed mild enlargement of the right medial and inferior recti muscles. Our patient showed a tremendous improvement of vision after a subcutaneous hyaluronidase injection with complete visual recovery within 2 weeks.     

透明质酸酶对大鼠双光气中毒性肺水肿治疗的初步观察

本实验初步现察了HA对双光气中毒性肺水肿早期的治疗作用。结果提示,早期应用HA能显著延长动物存活时间,而治疗组与对照组动物在肺体指数、肺湿干重量比及肺含水量等项指标则未见显著差别。     

Brief overview of selected approaches in targeting pancreatic adenocarcinoma

Introduction: Pancreatic adenocarcinoma (PDAC) has the worst prognosis of any major malignancy, with 5-year survival painfully inadequate at under 5%. Investigators have struggled to target and exploit PDAC unique biology, failing to bring meaningful results from bench to bedside. Nonetheless, in recent years, several promising targets have emerged.

Areas covered: This review will discuss novel drug approaches in development for use in PDAC. The authors examine the continued efforts to target Kirsten rat sarcoma viral oncogene homolog (KRas), which have recently been successfully abated using novel small interfering RNA (siRNA) eluting devices. The authors also discuss other targets relevant to PDAC including those downstream of mutated KRas, such as MAPK kinase and phosphatidylinositol 3-kinase.

Expert opinion: Although studies into novel biomarkers and advanced imaging have highlighted the potential new avenues toward discovering localized tumors earlier, the current therapeutic options highlight the fact that PDAC is a highly metastatic and chemoresistant cancer that often must be fought with virulent, systemic therapies. Several newer approaches, including siRNA targeting of mutated KRas and enzymatic depletion of hyaluronan with PEGylated hyaluronidase are particularly exciting given their early stage results. Further research should help in elucidating their potential impact as therapeutic options.     

Altered expression of hyaluronan synthase and hyaluronidase mRNA may affect hyaluronic acid distribution in keloid disease compared with normal skin

Keloid disease (KD) is a fibroproliferative disorder characterised partly by an altered extracellular matrix (ECM) profile. In fetal scarring, hyaluronic acid (HA) expression is increased, but is reduced in KD tissue compared with normal skin (NS). The expression of Hyaluronan Synthase (HAS) and hyaluronidase (HYAL) in KD and NS tissue were investigated for the first time using a range of techniques. Hyaluronan synthase and HYAL mRNA expression were significantly increased in NS tissue compared with KD tissue (P < 0.05). Immunohistological analysis of tissue indicated an accumulation of HAS and HYAL protein expression in KD compared with NS due to the thicker epidermis. No differences were observed in mRNA or protein expression in KD and NS fibroblasts. Reduced expression of HAS and HYAL may alter HA synthesis, degradation and accumulation in KD. Better understanding of the role of HA in KD may lead to novel therapeutic approaches to address the resulting ECM imbalance.     

透明质酸注射填充的不良反应及处理

作为最常用的注射用软组织填充剂,透明质酸可通过代替丢失的组织体积并填充、撑平粗糙的皱纹,以帮助恢复年轻的外貌。但在大量的临床实践中,难免会遇到注射相关的不良反应,甚至是血管栓塞等严重并发症。掌握透明质酸注射填充的不良反应及处理方法,在临床操作中具有重要的意义,本文将常见的不良反应及处理方法逐一进行总结,包括注射反应、丁达尔现象、结节和隆起、充填物迁移、感染、过敏反应、炎性肉芽肿和血管栓塞,并重点阐述了透明质酸酶在多种不良反应中的应用和血管栓塞的防治方法。     

Enhanced cognitive flexibility in reversal learning induced by removal of the extracellular matrix in auditory cortex

During brain maturation, the occurrence of the extracellular matrix (ECM) terminates juvenile plasticity by mediating structural stability. Interestingly, enzymatic removal of the ECM restores juvenile forms of plasticity, as for instance demonstrated by topographical reconnectivity in sensory pathways. However, to which degree the mature ECM is a compromise between stability and flexibility in the adult brain impacting synaptic plasticity as a fundamental basis for learning, lifelong memory formation, and higher cognitive functions is largely unknown. In this study, we removed the ECM in the auditory cortex of adult Mongolian gerbils during specific phases of cortex-dependent auditory relearning, which was induced by the contingency reversal of a frequency-modulated tone discrimination, a task requiring high behavioral flexibility. We found that ECM removal promoted a significant increase in relearning performance, without erasing already established—that is, learned—capacities when continuing discrimination training. The cognitive flexibility required for reversal learning of previously acquired behavioral habits, commonly understood to mainly rely on frontostriatal circuits, was enhanced by promoting synaptic plasticity via ECM removal within the sensory cortex. Our findings further suggest experimental modulation of the cortical ECM as a tool to open short-term windows of enhanced activity-dependent reorganization allowing for guided neuroplasticity.Structural remodeling and stabilization of synaptic networks are key mechanisms underlying learning in the adult brain. During early life, high structural and functional plasticity is required for the experience-shaped development of basic neuronal circuits (1). With brain maturation, juvenile plasticity of so-called critical or sensitive periods is decreased and is accompanied by the appearance of the brain’s extracellular matrix (ECM) and its specialized compact form named “perineuronal net” (PNN) enwrappping cell bodies and synaptic contacts (2, 3). Enzymatic degradation of the ECM in adult animals has been demonstrated to restore such forms of developmental (juvenile) plasticity with respect to topographical map plasticity in the visual cortex (4), fear-response–mediating circuits in the amygdala (5), spinal cord injuries (6, 7), and song learning circuits of zebra finches (8). In addition, enzymatic ECM removal altered several forms of synaptic plasticity in vitro and in vivo (9–12). However, even though structural stability of networks acquired during developmental phases is essential for neuronal efficiency, mechanisms allowing synaptic remodeling are key events during learning and memory formation throughout life (13). We recently demonstrated that endogenous proteases moderately digesting specific components of the ECM are regulated in an activity-dependent manner (2, 14) and ECM removal modulates synaptic short-term plasticity by synaptic exchange of postsynaptic glutamate receptors (10, 15). Further, ECM modulation enhances synaptic short-term plasticity by affecting voltage-dependent calcium channels (9). These findings challenge the view of the purely stabilizing role of ECM in the brain and indicate a potential regulatory switch for plastic network adaptations within the adult brain at the level of individual synapses by modulating the extracellular space (16). However, it remains open to what extent ECM modulations influence learning-related plasticity in the adult brain and its specific effects on behavior during a cognitive task.In the present study, we aimed at evaluating the potential role of experimental ECM removal within the auditory cortex (ACx) of Mongolian gerbils, which has been found to be particularly rich in ECM (17), during a cognitively demanding auditory go/no go shuttle-box task. We selected discrimination and reversal learning of frequency-modulated (FM) tones as a cognitive task, which necessarily requires ACx plasticity (18, 19). Injections of the ECM-degrading enzyme hyaluronidase (HYase) into the ACx after the first acquisition phase significantly enhanced subsequent reversal learning compared with sham-treated animals (injection of 0.9% saline). Particularly, after ECM degradation, animals abandoned the inappropriate discrimination strategy from the initial acquisition phase faster and thus promoted successful discrimination performance of the new contingency during reversal learning. ECM removal did not further influence the initial acquisition learning or interfere with already established—that is, learned—capacities in later learning stages, suggesting an enhanced activity-dependent neuroplastic reorganization of established synaptic networks in ACx during reversal learning.Our findings suggest that experimental degradation of the ECM in sensory cortex, although not affecting general sensory learning, does, however, enhance the cognitive flexibility that can build on the learned behaviors. Thereby, ECM degradation could be used as a tool for guided neuroplasticity, which might also bear therapeutic potential.     

Cross‐linked hyaluronic acid filler hydrolysis with hyaluronidase: Different settings to reproduce different clinical scenarios

Skin necrosis is the most severe complication arising from hyaluronic acid (HA) injection. To avoid skin necrosis, hyaluronidase should be injected along the course of the involved artery, to allow blood flow restoration. We evaluated the ability of hyaluronidase to degrade a HA filler in two simulated clinical situations—a compression case and an embolization case—to identify differences in the hyaluronidase injection. In the compression case, a bolus of HA filler was directly soaked in hyaluronidase solution; in the embolization case, a vein harvested from a living patient was filled with the same HA filler and then soaked in hyaluronidase. We then evaluated the quantity of HA remaining after 2 hr. While we found hydrolysis of HA in both cases, in the compression case, we detected almost complete hydrolysis, whereas in the embolization case we observed a reduction of the 60%. Our results support the hypothesis that vessel compression can be resolved with only one injection of hyaluronidase, while in the case of vascular embolization, repeated perivascular injections should be performed owing to the reduction of hyaluronidase activity.     

Use of hyaluronidase to prevent perineal trauma during spontaneous delivery: a pilot study

Our objective was to compare the frequency, degree, and location of perineal trauma during spontaneous delivery with or without perineal injections of hyaluronidase (HAase). This was a randomized, controlled pilot study, conducted in a midwife‐led hospital birth center in São Paulo, Brazil. Primiparous women (N = 139) were randomly assigned to an intervention group (HAase injection, n = 71) or to a control group (no injection, n = 68). Significant differences were noted between the two groups in frequency of perineal trauma (intervention, 39.4%; control, 76.5%), degree of spontaneous laceration (intervention, 0.0%; control, 82.4%), and laceration located in the posterior region of the perineum (intervention, 54.2%; control, 84.3%). When episiotomy and second‐degree lacerations were considered together and women with intact perineum were excluded from the analysis, the difference between the groups was no longer significant. With the use of the HAase enzyme, the relative risk was 0.5 for perineal trauma and 0.0 for second‐degree lacerations. The present findings suggest that perineal injection of HAase prevented perineal trauma. These findings provide strong rationale for a larger follow‐up study.     

Studies on hyaluronidase, chondroitin sulphatase, proteinase and phospholipase secreted by Candida species

Summary. We studied the ability of different Candida species to produce, at the same time, hyaluronidase, chondroitin sulphatase, proteinase, and phospholipase to assess whether they could be related to Candida pathogenicity. Only C. albicans was able to produce the four enzymes tested (73%) and was highly virulent to mice. Strains, that lack the capacity to produce one or more of the enzymes assayed, seemed less virulent or avirulent, similarly to the spontaneous hyaluronidase, chondroitin sulphatase, phospholipase and proteinase-deficient C. albicans strain FCF 14,1 which was non-pathogenic to mice. Among the other Candida species tested, none of them produced the four enzymes simultaneously, being less virulent in intravenously inoculated mice.
Zusammenfassung. Es wurde die Fähigkeit mehrerer Candida -Arten, gleichzeitig Hyaluronidase-, Chondroitinsulfatase-, Proteinase- und Phospholipase-Aktivität auszubilden, untersucht und deren Bedeutung als Candida -Pathogenitäts-merkmal bewertet. Nur C. albicans -Stämme waren in der Lage, die vier Enzyme zu bilden und waren für Mäuse hochvirulent. Stämme, welchen die Fähigkeit fehlte, eines oder mehrere dieser Enzyme zu produzieren, schienen weniger virulent oder avirulent zu sein, ähnlich wie der C. albicans -Stamm FCF 14,1, der spontan defizient für alle vier Enzyme war und der sich als nichtpathogen für Mäuse erwies. Von allen übrigen getesteten Candida -Arten produzierte keine gleichzeitig alle vier Enzyme, und diese erwiesen sich bei intravenöser Infektion als weniger virulent für Mäuse.