Quantification of myocardial fibrosis using noninvasive T2-mapping magnetic resonance imaging: Preclinical models of aging and pressure overload

Noninvasive imaging of cardiac fibrosis is important for early diagnosis and intervention in chronic heart diseases. Here, we investigated whether noninvasive, contrast agent-free MRI T₂-mapping can quantify myocardial fibrosis in preclinical models of aging and pressure overload. Myocardial fibrosis and remodeling were analyzed in two animal models: (i) aging (15-month-old male CF-1 mice vs. young 6- to 8-week-old mice), and (ii) pressure overload (PO; by transverse aortic constriction in 4- to 5-month-old male C57BL/6 mice vs. sham-operated for 14 days). In vivo T₂-mapping was performed by acquiring data during the isovolumic and early diastolic phases, with a modified respiratory and ECG-triggered multiecho TurboRARE sequence on a 7-T MRI. Cine MRI provided cardiac morphology and function. A quantitative segmentation method was developed to analyze the in vivo T₂-maps of hearts at midventricle, apex, and basal regions. The cardiac fibrosis area was analyzed ex vivo by picro sirius red (PSR) staining. Both aged and pressure-overloaded hearts developed significant myocardial contractile dysfunction, cardiac hypertrophy, and interstitial fibrosis. The aged mice had two phenotypes, fibrotic and mild-fibrotic. Notably, the aged fibrotic subgroup and the PO mice showed a marked decrease in T₂ relaxation times (25.3 ± 0.6 in aged vs. 29.9 ± 0.7 ms in young mice, p = 0.002; and 24.3 ± 1.7 in PO vs. 28.7 ± 0.7 ms in shams, p = 0.05). However, no significant difference in T₂ was detected between the aged mild-fibrotic subgroup and the young mice. Accordingly, an inverse correlation between myocardial fibrosis percentage (FP) and T₂ relaxation time was derived (R² = 0.98): T₂ (ms) = 30.45 – 1.05 × FP. Thus, these results demonstrate a statistical agreement between T₂-map–quantified fibrosis and PSR staining in two different clinically relevant animal models. In conclusion, T₂-mapping MRI is a promising noninvasive contrast agent-free quantitative technique to characterize myocardial fibrosis.     

Treatment of thalassaemia: a review of the new approaches on transfusion safety and the novel therapeutics

Lifetime red cell concentrate (RCC) transfusions still account for significant iron overload‐related morbidity and mortality despite chelation therapy in thalassaemia. The cumulative risk of transfusion‐transmitted infections is substantial for thalassaemia patients. Pathogen reduction technologies for RCC may imply a proactive approach against new/re‐emerging pathogens and may be an ultimate safeguard for transfusion safety in the developing countries. Red cell alloimmunization may become a significant clinical challenge in thalassaemia. The availability of high‐throughput molecular blood group antigen typing in the donors may allow perfect match transfusion, beyond ABO‐D and CEK antigen‐matched transfusions. Allogeneic stem cell transplantation (A‐SCT) is the only available curative therapy in thalassaemia, but carries a substantial risk of serious adverse events and mortality. Gene addition therapy for correction of the α‐globin chain imbalance overcomes the problems of donor availability and immunological complications of A‐SCT. Gene editing by either gene disruption or correction emerged as a potential alternative to gene addition therapy in beta‐thalassaemia. A new era of novel therapeutics targeting α/β imbalance, ineffective erythropoiesis or iron dysregulation is unfolding in thalassaemia management, and a number of those now have agents in preclinical and clinical development. Hydroxyurea (HU) may improve globin chain imbalance and be beneficial for reducing or omitting transfusion requirement. Ruxolitinib has allowed steady decrease in spleen volume that may serve for avoiding splenectomy in beta‐thalassaemia. Luspatercept may restore normal erythroid differentiation and improve anaemia. Hepcidin mimetics or TMPRSS6 inhibitors may modulate ineffective erythropoiesis by iron restriction and improve anaemia and organ iron loading.     

单侧液压脑损伤对大鼠双侧海马GFAP表达和CA1区突触传递的影响

目的研究单侧液压脑损伤(FPI)对大鼠双侧海马区胶质纤维酸性蛋白(GFAP)表达和CA1区突触传递的影响。方法建立大鼠单侧液压脑损伤模型,脑标本分为对照组(包括正常对照和假手术对照)、FPI损伤同侧组和FPI损伤对侧组。免疫组化法检测海马水平切片GFAP表达,对海马CA1区锥体神经元进行细胞内记录。结果FPI大鼠双侧海马齿状回门区和CA1区GFAP表达均比对照组明显增强。FPI损伤同侧组兴奋性输入-输出关系曲线的斜率比其他两组显著增大(P<0.05);FPI损伤同侧组和对侧组双脉冲易化(PPF)比值和抑制性突触后电位(IPSP)幅值均比对照组显著减小(P<0.05);FPI损伤同侧组和对侧组双脉冲抑制(PPD)比值均比对照组显著增大(P<0.05)。结论大鼠单侧液压脑损伤对双侧海马均可产生影响,导致双侧海马CA1区兴奋性突触传递增强,抑制性突触传递减弱。     

未控制出血性休克与TNF—a的关联性及不同液体复苏的作用

目的 研究未控制出血性休克时不同液体复苏的作用以及，INF—a的变化规律，以期阐明限制性液体复苏降低未控制出血性休克的死亡率和改善预后的相关机制。方法采用改良后的Krausz方法建立重度脾创伤未控制出血性休克大鼠模型。采用随机分组的原则将大鼠分为假处理组、限制输液组、常规输液组、不输液组。观察各组动物的出血量、输液量、存活率、存活时间及各时间点的血压、血细胞比容（Hct）和TNF—a的变化情况。结果①限制输液组的输液量明显少于常规输液组（P〈0．05），出血量也明显少于常规输液组（P〈0．05）。②限制输液组Hct明显高于常规输液组（P〈0．05）。②限制输液组的存活时间比常规输液组及不输液组明显延长（P均〈0．05）。限制输液组在72h内的存活率明显高于常规输液组和不输液组。但低于假处理组（P均〈0．1）。④除假处理组外其余各组在伤后90min和180min血TNF—a水平均较伤前均有明显升高（P均〈0．05）；常规输液组，TNF—a水平明显高于限制输液组（P〈0．05）。⑤死亡者TNF—a水平明显高于生存者。结论本研究结果表明，在重度未控制出血条件下，限制性液体复苏可明显降低出血量，提高存活率。未控制性出血休克时的TNF—a水平与预后密切相关，TNF—a高预后不良，而限制性液体复苏时TNF—a水平明显降低。     

心钠素对心肌血管钙超载的影响

提要本研究是在大鼠VD_3+Nicotine引起的心血管钙超载模型上观察心钠素(ANF)治疗(10ug ·kg~-1/d),对钙超载的影响。结果发现,钙超载组动物主动脉、心肌组织钙含量较对照组分别增高24倍(54.4±2.2vs 2.3±0.04fumol/gww)和9倍(16.9±2.1vs1.8±0.1umol/gww)。ANF治疗能显著抑制钙超载的发生,主动脉和心肌组织钙含量较钙超载组分别降低92％(3.8±0.4 umol/gww)和66％(5.6±0.6umol/gww)。离体滋流的钙超载血管环较对照组对去甲肾上腺素收缩反应增强;对乙酰胆碱舒张反应减弱,对硝普钠舒张反应无影响。ANF能显著改善钙超载所致的血管反应性障碍。实验结果表明,ANF具有显著的防治心血管钙超载的作用。     

Neuronal plasticity in memory and learning abilities: Theoretical position and selective review

Neural plasticity of modality-nonspecific and modality-specific memory and learning abilities pertains to fluid intelligence and crystallized intelligence, respectively. The limbic system with the novelty neurons of the hippocampus interacts with the prefrontal cortex optimization of the orienting reflex and voluntary attention. Brain-derived neurotrophic factor produced by novelty neurons of the hippocampus contributes to long-term memory formation and improves learning abilities in a wide range of disciplines. Synergistic combination of stimulation with “analytical-specific visual perceptual patterns” and “optimally high” physiological activation of the bilateral electrodermal system optimizes the limbic system and prefrontal cortex activity as demonstrated by enhanced prefrontal N450 ERPs to a memory workload paradigm. This is accompanied by improvements in auditory retention tasks, word memorization, higher school achievement and marks, and an amelioration of “analytical-specific perceptual skills” as measured by the Mangina-Test. Intracerebral ERPs to a memory workload paradigm contributed to the elucidation of limbic structures and neocortical sites involved in memory workload processes. The progressive degeneration of these same structures causes the gradual decline of memory functions observed in early Alzheimer's disease. Research findings indicate that ERPs elicited by a memory workload paradigm are sensitive markers for diagnosis, treatment and clinical follow-up of early Alzheimer's patients. In addition, ERPs provide objective measurement of cholinergic medication effects on cerebral functions involved in memory processes through neuropsychophysiological parameters.     

Evidence for motility and pinocytosis in ramified microglia in tissue culture

Ramified microglial cells were investigated in primary cultures of dissociated cerebral cortical tissue from rats. The identification of these cells was confirmed through immunohistochemical staining with 7 monoclonal antibodies selective for microglia. While there was significant variation in staining intensity with different antibodies, all stained the identified ramified cells; the antibodies OX-42 and ED1 yielded the most intense immunoreactivity. Based on distinctive morphological features, the microglia could be identified in living cultures where they were monitored using time-lapse video recording. This technique revealed extremely dynamic features of cellular plasticity and motility. Ramified microglia exhibited constant and rapid alterations in the size and shape of their cell body with an associated extension and retraction of processes; concomitantly, the cells moved about in a circumscribed area. These features of plasticity and motility were unique to this cell type, and correlated with OX-42 immunostaining. The microglia also possessed a differentially high level of pinocytotic activity; this too was correlated with OX-42 staining. From the nature of their morphological plasticity and motility, high pinocytosis, and cellular distribution, it is hypothesized that the ramified microglia specifically function as a system of fluid cleansing in normal brain tissue.     

Perioperative specific management of blood volume loss in craniosynostosis surgery

Accurate assessment and replacement of blood loss and fluid–electrolyte deficit during craniosynostosis repair is difficult owing to patient size and the diversity of surgical technique. Forty-three patients undergoing primary craniosynostosis repair over a 10-year period were studied retrospectively to determine blood loss and fluid deficit and to assess blood transfusion practices during both intraoperative and postoperative periods. Blood loss was calculated on the basis of estimated red cell mass (ERCM) and fluid-electrolyte imbalance was investigated with blood samplings. Blood transfusion was considered appropriate if the postoperative or posttransfusion ERCM was within 12% of the preoperative value. Estimated fluid requirement (EFR) was used in 4 ml kg^–1 h^–1 except for neonates. Intraoperatively, 80% of all patients were appropriately managed with respect to blood transfusion and EFR. Postoperatively only 20% of the patients receiving transfusions were transfused appropriately. In 23.3% of these patients (10/43) unexpected respiratory distress developed immediately after their recovery from the anesthesia. With the measurement of estimated blood volume and allowable blood loss, appropriate transfusion could be achieved for the successful treatment of the primary craniosynostosis. Received: 16 February 1998