Anaphylactic shock due to recombinant human insulin: follow-up of a desensitization protocol by basophil activation test

Introduction

Despite the occurrence of a severe allergic reaction including an anaphylactic shock, a drug may remain essential and impossible to replace. This may be the case of insulin in a diabetic patient. We describe the case of an anaphylactic shock to human insulin in whom a desensitization protocol was successfully achieved.

Case report

A 50-year-old type 2 diabetic man presented one year after initiation of the insulin therapy an anaphylactic shock following the subcutaneous administration of a human insulin containing protamine (Insulatard^®). A desensitization protocol to human insulin was performed and allowed to use two human insulin analogues containing no protamine (asparte and glargine), with a two-year event-free follow-up. Positive skin tests with insulin and protamine, and the presence of insulin specific IgE were evidenced of an IgE-mediated mechanism. Desensitization was monitored by skin tests, Maunsell's test, measurement of specific IgE and IgG4, and the basophil activation test. The decrease of basophil sensitivity to insulin is an early marker for tolerance induction.

Conclusion

The effectiveness of the desensitization to human insulin underlines the importance to define the modalities of such desensitization protocol and of the monitoring of the tolerance induction.     

便携式薄膜太阳能光伏野外多功能应急电源的设计

目的:介绍一种在野外临时断电或无市电可利用的紧急情况下能够正常使用的便携光伏型野外多功能应急电源。方法:将目前最先进、实际光电转换效率高、弱光性强的铜铟镓铟(CIGS)薄膜太阳能电池片镶嵌在纤维基布上,制作成柔软的"薄膜太阳能光伏布",使用时展开与控制电源箱相连对其供电;不用时折叠包装后放入电源控制箱内。整个电源以太阳能光伏输入为主,以市电、发电机或汽车发动机等为辅,经过DC/AC、DC/DC、AC/DC等各种变换和系统控制后,产生直流为混合超级电容电池充电储能,最后输出直流和交流电源。结果:经过野外测试,该电源采用多种形式输入,多种途经输出,交流稳定,负载范围大,功能多,便携可满足常规设备的使用。同时质量轻、组合简单,便于野外携行、搬运。结论:该研究设计对薄膜太阳能电池光伏在移动应急电源应用方面意义重大。     

Impact of gene expression noise on organismal fitness and the efficacy of natural selection

Gene expression noise is a universal phenomenon across all life forms. Although beneficial under certain circumstances, expression noise is generally thought to be deleterious. However, neither the magnitude of the deleterious effect nor the primary mechanism of this effect is known. Here, we model the impact of expression noise on the fitness of unicellular organisms by considering the influence of suboptimal expressions of enzymes on the rate of biomass production and the energetic cost associated with imprecise amounts of protein synthesis. Our theoretical modeling and empirical analysis of yeast data show four findings. (i) Expression noise reduces the mean fitness of a cell by at least 25%, and this reduction cannot be substantially alleviated by gene overexpression. (ii) Higher sensitivity of fitness to the expression fluctuations of essential genes than nonessential genes creates stronger selection against noise in essential genes, resulting in a decrease in their noise. (iii) Reduction of expression noise by genome doubling offers a substantial fitness advantage to diploids over haploids, even in the absence of sex. (iv) Expression noise generates fitness variation among isogenic cells, which lowers the efficacy of natural selection similar to the effect of population shrinkage. Thus, expression noise renders organisms both less adapted and less adaptable. Because expression noise is only one of many manifestations of the stochasticity in cellular molecular processes, our results suggest a much more fundamental role of molecular stochasticity in evolution than is currently appreciated.     

Effects of anti-oxidant treatment on sciatic nerve dysfunction in streptozotocin-diabetic rats; comparison with essential fatty acids

Summary In Study 1, the effects of treatment of streptozotocin-diabetic rats with the antioxidants, probucol or vitamin E were compared. Untreated diabetic rats showed a reduction of 45% (p<0.01) in nerve laser Doppler flux, which was used as an index of nerve blood flow. In diabetic rats treated with either probucol or vitamin E nerve Doppler flux was reduced by only 13 or 16%, respectively (p<0.01 for either compared to untreated diabetic rats). A second study examined the effects of treatment with evening primrose oil either alone or in combination with probucol. Reduced nerve Doppler flux was reproduced in untreated diabetic rats (47%; p<0.01). In parallel diabetic groups, nerve Doppler flux was reduced by only 14% with evening primrose oil alone and by 8% with evening primrose oil plus probucol (both p<0.01 vs untreated diabetic rats). Both treatments were also associated with marked attenuation of motor and sensory nerve conduction velocity deficits. Measurements on plasma from rats showed normalisation of triglyceride levels by probucol treatment without an effect on those of cholesterol in Study 1. In Study 2, the converse was true for evening primrose oil treatment, whilst the combined treatment lowered both plasma triglycerides and cholesterol. This work indicates similar effects of antioxidants and evening primrose oil against reduced nerve Doppler flux and conduction velocity in diabetic rats, with dissimilar actions on plasma triglycerides and cholesterol.Abbreviations STZ streptozotocin     

不同血液净化方法对慢性肾衰竭维持性血液透析患者血清β2-微球蛋白的影响

目的 探讨不同血液净化方法对慢性肾衰竭维持性血液透析(MHD)患者血清β2-微球蛋白(β2-MG)的清除效果.方法 将40例慢性肾衰竭MHD患者随机分为四组:血液透析(HD)组,高通量血液透析(HFD)组,血液透析滤过(HDF)组,HD+血液吸附(AP)组,每组各10例.记录患者治疗前后血清β2-MG测得值并进行组内和组间统计学比较.结果 HD组第1次血液净化后β2-MG测得值[(53.49±1.15)mg/L]较第1次血液净化前(基线值)[(49.10±2.31)ms/L]上升但差异无统计学意义(P>0.05),6个月血液净化后β2-MG测得值[(55.63±1.30)mg/L]较基线值上升且差异有统计学意义(P<0.05).HFD组、HDF组和HD+AP组第1次血液净化后及6个月血液净化后β2-MG测得值较基线值均有明显下降趋势(P<0.05).并且HD+AP组6个月血液净化后β2-MG测得值较HFD组和HDF组下降趋势更为明显(P<0.05).结论 HD对β2-MG无清除效果,HFD、HDF和HD+AP能有效清除β2-MG,并且6个月后HD+AP清除β2-MG效果更佳.     

Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules

Purpose  The maximum flux of solutes penetrating the epidermis has been known to depend predominantly on solute molecular weight. Here we sought to establish the mechanistic dependence of maximum flux on other solute physicochemical parameters. Methods  Maximum fluxes, stratum corneum solubilities and estimated diffusivities through human epidermis were therefore determined for 10 phenols with similar molecular weights and hydrogen bonding but varying in lipophilicity. Results  Maximum flux and stratum corneum solubilities of the phenolic compounds both showed a bilinear dependence on octanol-water partition coefficient (P), with solutes having a maximum solubility in the stratum corneum when 2.7<log P<3.1. In contrast, lag times and diffusivities were relatively independent of P. Stratum corneum-water partition coefficients and epidermal permeability coefficients were consistent with previously reported data. Conclusion  A key finding is that the convex dependence of maximum flux on lipophilicity arises primarily from variations in stratum corneum solubility, and not from diffusional or partitioning barrier effects at the stratum corneum–viable epidermis interface for the more lipophilic phenols. Our data support a solute structure-skin transport model for aqueous solutions in which permeation rates depend on both partitioning and diffusivity: partitioning is related to P, and diffusivity to solute size and hydrogen bonding. (199 words)     

Neonatal exposure to low-dose domoic acid lowers seizure threshold in adult rats

Exposing Sprague–Dawley rat pups to very low, sub-convulsant doses of domoic acid (DOM) during perinatal development has been previously shown to result in seizure-like activity in adulthood similar to partial complex epilepsy in humans, and to produce cellular and molecular changes in the dentate gyrus and area CA-3 of the hippocampus. To further these investigations we recorded electroencephalographical and behavioural activity in DOM and control rats following a normally sub-convulsant dose (25 mg/kg) of pentylenetetrazol. During this exposure, 50% of DOM-treated rats experienced a Stage V (tonic-clonic) seizure (X²₍₁₎=5.33, P=0.021), indicating a lowering of generalized seizure threshold in these animals. In a separate experiment we explored focal seizure (afterdischarge) threshold as well as seizure propagation rates in treated rats, using a 25 consecutive day standard amygdala kindling paradigm. We report that the afterdischarge threshold for DOM-treated rats was significantly lower than controls (F_(1,27)=7.117, P=0.013). No difference between groups was found in seizure progression as measured by afterdischarge duration, latency to first Stage V seizure, or latency to reach a fully kindled state (defined as five consecutive Stage V seizures). Timm staining to assess mossy fibre sprouting (MFS) in the hippocampus revealed a significant MFS increase relative to sham at the ventral level in both left and right inner molecular layer of the dentate gyrus for all DOM-treated animals, as well as in the dorsal stratum oriens of CA3 contralateral to electrode placement, and these increases were further enhanced by the kindling procedure. We conclude that perinatal exposure to subconvulsive doses of DOM results in permanent changes in neuronal excitability in the adult rat, as demonstrated by a lowering of both generalized seizure and focal afterdischarge threshold, and produces increased MFS following kindling.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Carbon dioxide fixation as a central redox cofactor recycling mechanism in bacteria

The Calvin-Benson-Bassham cycle (Calvin cycle) catalyzes virtually all primary productivity on Earth and is the major sink for atmospheric CO₂. A less appreciated function of CO₂ fixation is as an electron-accepting process. It is known that anoxygenic phototrophic bacteria require the Calvin cycle to accept electrons when growing with light as their sole energy source and organic substrates as their sole carbon source. However, it was unclear why and to what extent CO₂ fixation is required when the organic substrates are more oxidized than biomass. To address these questions we measured metabolic fluxes in the photosynthetic bacterium Rhodopseudomonas palustris grown with ¹³C-labeled acetate. R. palustris metabolized 22% of acetate provided to CO₂ and then fixed 68% of this CO₂ into cell material using the Calvin cycle. This Calvin cycle flux enabled R. palustris to reoxidize nearly half of the reduced cofactors generated during conversion of acetate to biomass, revealing that CO₂ fixation plays a major role in cofactor recycling. When H₂ production via nitrogenase was used as an alternative cofactor recycling mechanism, a similar amount of CO₂ was released from acetate, but only 12% of it was reassimilated by the Calvin cycle. These results underscore that N₂ fixation and CO₂ fixation have electron-accepting roles separate from their better-known roles in ammonia production and biomass generation. Some nonphotosynthetic heterotrophic bacteria have Calvin cycle genes, and their potential to use CO₂ fixation to recycle reduced cofactors deserves closer scrutiny.     

Prolonged hypoxia modulates platelet activating factor receptor-mediated responses by fetal ovine pulmonary vascular smooth muscle cells

Hypoxia augments PAF receptor (PAFr) binding and PAFr protein expression in venous SMC (SMC-PV). We compared effect of acute and prolonged hypoxia (pO₂ < 40 torr) on PAFr-mediated responses in arterial SMC (SMC-PA) and SMC-PV. Cells were studied for 30 min (acute) or for 48 h (prolonged) hypoxia and compared to normoxic (pO₂ ~ 100 torr) conditions. PAF binding was quantified in fmol/10⁶ cells (mean ± SEM). PAF binding in normoxia were SMC-PA, 5.2 ± 0.2 and in SMC-PV, 19.3 ± 1.1; values in acute hypoxia were SMC-PA, 7.7 ± 0.4 and in SMC-PV, 27.8 ± 1.7. Prolonged hypoxia produced 6-fold increase in binding in SMC-PA, but only 2-fold increase in SMC-PV, but binding in SMC-PV was still higher. Acute hypoxia augmented inositol phosphate release by 50% and 40% in SMC-PA and SMC-PV, respectively. During normoxia, PAFr mRNA expression by both cell types was similar, but expression in hypoxia by SMC-PA was greater. In SMC-PA, hypoxia and PAF augmented intracellular calcium flux. Re-exposure of cells to 30 min normoxia after 48 h hypoxia decreased binding by 45–60%, suggesting immediate down-regulation of hypoxia-induced PAFr-mediated effects. We speculate that re-oxygenation immediately reverses hypoxia effect probably due to oxygen tension-dependent reversibility of PAFr activation and suggest that exposure of the neonate to prolonged state of hypoxia will vilify oxygen exchange capacity of the neonatal lungs.     

高通量透析对维持性血液透析患者全身状况的影响

目的 评价高通量透析对维持性血液透析患者的伞身状况及各种并发症的影响.方法 对中途转入我院血液透析中心32例患者使用高通量膜透析器,观察患者一般身体状况及各种并发症的改善,观察时间为半年.结果 32例患者自我感觉明显改善(100%),各种并发症均得到纠正或改善.结论 全身状况明显改善,高磷血症等并发症均得到有效控制.