Current status and challenges of Additive manufacturing in orthopaedics: An overview

Additive manufacturing is a rapidly emerging technology which is being successfully implemented in the various field of medicine as well as in orthopaedics, where it has applications in reducing cartilage defects and treatments of bones. The technology helps through systematic collection of information about the shape of the "defects" and precise fabrication of complex 3D constructs such as cartilage, heart valve, trachea, myocardial bone tissue and blood vessels. In this paper, a large number of the relevant research papers on the additive manufacturing and its application in medical specifically orthopaedics are identified through Scopus had been studied using Bibliometric analysis and application analysis is undertaken. The bibliometric analysis shows that there is an increasing trend in the research reports on additive manufacturing applications in the field of orthopaedics. Discussions are on using technological advancement like scanning techniques and various challenges of the orthopaedic being met by additive manufacturing technology. For patient-specific orthopaedic applications, these techniques incorporate clinical practice and use for effective planning. 3D printed models printed by this technology are accepted for orthopaedic surgery such as revision of lumbar discectomy, pelvic surgery and large scapular osteochondroma. The applications of additive manufacturing in orthopaedics will experience a rapid translation in future. An orthopaedic surgeon can convert need/idea into a reality by using computer-aided design (CAD) software, analysis software to facilitate the manufacturing. Thus, AM provides a comprehensive opportunity to manufacture orthopaedic implantable medical devices.     

Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein of mumps virus vaccine strain Urabe AM9 is not a requirement for neurovirulence

The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence.     

Secretion of a chemotactic factor for neutrophils and eosinophils by alveolar macrophages from asthmatic patients

The studies presented in this article demonstrate the release of an IgE-dependent chemotactic factor for polymorphonuclear neutrophils (PMN) and eosinophils by alveolar macrophages (AMs) from normal subjects (n = 15) and allergic asthmatic patients (n = 15). A 60-minute incubation of normal AMs previously sensitized by 20% nonheated allergic sera with anti-human IgE antibody or the related allergen induced the release of a chemotactic activity (CA) for PMN and eosinophils in culture supernatants. When AMs were obtained from asthmatic patients, direct incubation with anti-IgE or the related allergen induced the same CA, whereas incubation with an unrelated allergen failed to produce CA (neutrophil CA after addition of anti-IgE, 22.5 +/- 3.5 cells per high power field; with related allergen, 15.8 +/- 3.6; with unrelated allergen, 0.7 +/- 1.8; p less than 0.0001). A partial characterization of the neutrophil chemotactic factor was carried out. Enzymatic treatment by trypsin or carboxypeptidase or by heating (56 degrees C for 3 hr) failed to abolish the neutrophil CA. After gel filtration the greater part of the neutrophil CA (80%) was recovered among low-molecular-weight components (300 to 1300 daltons). A preliminary deactivation of PMN by leukotriene B4 suppressed the CA of AM supernatants. These results indicate that IgE-dependent stimulation of AMs produces a neutrophil and eosinophil CA, present in a low-molecular-weight fraction possibly related to leukotrienes, and emphasizes the role of AMs in inflammatory lung processes during allergic asthma.     

Thermal gradients in microtitration plates. Effects on enzyme-linked immunoassay

Temperature studies of microtitration plates demonstrate that the use of a common bacteriology incubator for heating the plates can cause a phase lag of over 30 min for the fluid in the wells to reach 37°C from ambient temperature, and that a temperature gradient of as much as 1.6°C can exist between the peripheral and center wells. This gradient is a cause of the ‘rim’ or edge effect noted in enzyme immunoassay using microtitration plates. The problem is corrected by the use of a specially designed forced air microtitration plate incubator.     

Secretin dissipates red aridine orange fluoescence from pancreatic duct epithelium

This study was undertaken to elucidate whether duct cells in the pancreas contain acidic cytoplasmic compartments regulated by secretion. Microdissected pancreatic ducts from pigs were examined by acridibe orange (AO) and 2′, 7′-biscarboxyethyl-5(6)-carboxyfluorescein/tetraacetioxymethyl ester (BCECF/AM) epifluorescence microscopy. Estimated cytoplasmic pH using BCECF fluorescence was 7.43pL0.04 and was not changed by altering CO₂ tension in the incubation mdium. The epithelium of acridine orange incbated peripheral interlobular pancreatic ducts exhibited green and fluorescence was sen in resting pancreatic ducts and was greatly accentuated by raising CO₂ in the incubation medium with chloroqyuine or NH₄Cl or the protonophores carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or carbonyl cyanide M-chlorophenylhydrazone (CCCP), leaving uniform gren fluoresence. These findings suggest that pancreatic duct cells contain CO₂-dependent acidic compartments which vanishduring seceatin stimulation and which may be cytoplasmic tubulovesicles.     

On the role of agonist-evoked Ca2+ mobilization in sustaining the ongoing phosphoinositide hydrolysis

Stimulation of SK-N-BE(2) cells with 1 mM carbachol (Cch) elicited phosphoinositide (PPI) hydrolysis and a rapid elevation of cytosolic Ca²⁺ concentration ([Ca²⁺]_i) from 115 nM to about 500 nM, followed by a plateau around 200 nM. In myo [³H]inositol-labelled cells, Cch-evoked accumulation of [³H]inositol phosphates (IPs) was not affected when [Ca²⁺]_i was clamped at resting by cell loading with 10 M BAPTA/AM; under these conditions, maximal 1,4,5-inositol trisphosphate accumulation was not reduced either. When [Ca²⁺]_i was clamped around 700 nM by cell treatment with 600 nM ionomycin, Cch-evoked [³H]IPs accumulation was enhanced by less than 20%, but it was impaired by a 30% and a 55% after [Ca²⁺]_i reduction to about 70 nM and 35—50 nM, by cell loading with 20 M or 40 M BAPTA/AM, respectively. These results show that, in SK-N-BE(2) cells, Cch-activated PPI-specific phospholipase C is sensitive to [Ca²⁺]_i but it already operates under suboptimal conditions at resting [Ca²⁺]_i.     

Glutamate Toxicity: An Experimental and Theoretical Analysis

In slices of 8-day-old rat cerebellum, the lowest concentration of glutamate that induced toxicity (30 min exposure; 90 min recovery) was 100 microM, but the damage only occurred in the outermost regions. As the concentration was raised, the band of necrosis became progressively deeper until, at 3 mM, it was uniform across the slice thickness. At a test concentration of 300 microM, the width of the necrotic band did not change when either the exposure time or the recovery period was varied between 30 min and 3 h. These results are predicted by a theoretical model in which the diffusion of glutamate into brain tissue is countered by cellular uptake of the amino acid, and they argue against the idea that glutamate toxicity is inherently self-propagating. When slices were examined immediately after exposure (300 microM), a prominent swelling of glial cells was present at the slice surface. Swelling per se did not appear to compromise their uptake function, and the model predicts that cellular swelling, by reducing the rate of diffusion of glutamate, protects against glutamate toxicity. The damage produced by 3 mM glutamate, which was primarily exerted against granule cells, was prevented by N-methyl-d-aspartate (NMDA) receptor blockade, whereas antagonists acting at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors were ineffective. Under conditions of energy deprivation, the neurotoxic potency of glutamate was markedly enhanced and a normally non-toxic concentration (30 microM) became maximally toxic towards granule cells. Dark vacuolar degeneration of Purkinje cells was also present, and this could be inhibited by blocking AMPA receptors. The results and theoretical analysis suggest that intact brain tissue is remarkably resistant to glutamate toxicity, chiefly because of the formidable properties of the uptake system. However, under special circumstances, glutamate can become a potent neurotoxin and its toxicity can then involve both NMDA and AMPA receptors.     

黄芪抗γ射线辐射作用的研究

目的 :从免疫学方面探讨中药黄芪抗 γ射线辐射的作用。方法 :用 10 0 %黄芪水浸出液定期给小鼠灌胃 ,然后测定骨髓细胞增殖反应、淋巴细胞转化率、巨噬细胞吞噬功能。结果 :用药组对以上免疫学指标均有显著增强作用 ,与照射组相比有非常显著性差异 ( P<0 .0 1)。未见有副作用。结论 :口服黄芪有明显抗 γ射线辐射作用     

激光共聚焦显微镜比较观察甾体皂苷Trilliuo、Lc253、Lc239对培养心肌细胞内[Ca2+]i的作用

目的：薯蓣皂苷元的皂苷为许多抗心血管中药中的主要活性成分，具有重要研究价值。本研究以经人工合成获得的薯蓣皂苷元皂苷同系物甾体皂苷Trilliuo(署蓣皂苷元葡萄糖苷、Lc253[薯蓣皂苷鼠李糖(1→2)葡萄糖苷]、Lc239(薯蓣皂苷元[鼠李糖(1→2)，葡萄糖(1→3)]葡萄糖苷)为研究对象，通过考察它们对培养心肌细胞钙离子释放的影响，分析其构效关系。方法：利用激光共聚焦显微镜测定加入fluo3—AM培养的心肌细胞中的钙离子变化情况。结果：Lc253能明显增强心肌细胞节律性和呈浓度依赖性增加心肌细胞静息钙离子水平，加入CaCl2 10mmol/L or KCl 60 mmol/L后钙离子荧光峰强度仍维持在较高水平；而Trilliuo and Lc239在10^—5mmol/L浓度时，对心肌细胞静息钙离子水平作用不明显，在高浓度胞外Ca^2 或K^ 情况下，抑制心肌细胞内钙离子升高；其作用特点与verapamil相似，具有钙离子通道阻断作用。结论：研究结果显示三种甾体皂苷对细胞内钙离子浓度有所差异，结构中连接糖的数目与调孔钙内流的活性有重要的相关性。这些皂苷类化合物对钙离子通道的活性有潜在的开发价值。     

黄芪抗γ射线辐射对小鼠淋巴细胞增殖和IL-2的作用研究

目的 :从免疫学方面探讨中药黄芪对辐射损伤小鼠淋巴细胞增殖和 IL - 2的研究。方法 :用 10 0 %黄芪水浸出液定期给小鼠灌胃 ,行γ线照射后检测小鼠淋巴细胞增殖和 IL - 2的产生。结果 :用药组小鼠脾淋巴细胞增殖和 IL - 2产生有显著增强作用 ,与照射组相比均有非常显著性差异 (P<0 .0 1)。结论 :黄芪有明显抗 γ线辐射、促进小鼠淋巴细胞增殖和IL- 2产生的作用。