研究报告: 实验性自身免疫性葡萄膜炎模型中肝脏免疫系统紊乱的研究

葡萄膜炎是一种反复发作的炎症性疾病,可导致免疫系统功能障碍和多器官损伤．然而,葡萄膜炎是否导致肝功能损害尚不十分清楚．本文通过运用流式分析技术和激光共聚焦成像技术,研究了实验性自身免疫葡萄膜炎模型的肝脏病理和功能变化．结果显示肝损伤可出现在葡萄膜炎的炎症后期并与眼损伤程度相关．并且CD3⁺ CD4⁺ T细胞、CD3^- NK1.1⁺ DX5^- NK细胞、和CD11b⁺ F4/80^- ly6c⁺ 细胞在感染的眼睛和肝脏中增加．将CD3⁺ CD4⁺ T细胞回输给炎症的小鼠后,眼睛和肝脏的病理损伤加重．此外,在炎症的小鼠中可见血管扩张,大量淋巴细胞浸润到炎症的眼和肝脏的血管周围．总之,我们的研究结果提示,肝损伤可以发生在小鼠葡萄膜炎模型中,这种损伤可能与通过外周循环浸润到肝脏的CD3⁺ CD4⁺ T细胞有关．     

Effects of single low-temperature sauna bathing in patients with severe motor and intellectual disabilities

We have previously reported that thermal vasodilation following warm-water bathing and low-temperature sauna bathing (LTSB) at 60 degrees C for 15 min improves the cardiac function in patients with congestive heart failure. Through a comparative before-and-after study, we studied the hemodynamic and clinical effects of single exposure to LTSB in cerebral palsy (CP) patients who usually suffer from chilled extremities and low cardiac output. The study population comprised 16 patients ranging between 19 and 53 years with severe motor and intellectual disabilities. Noninvasive methods were used to estimate the systemic and peripheral circulatory changes before and after LTSB. Using blood flow velocity analysis, the pulsatile and resistive indexes of the peripheral arteries of the patients' lower limbs were calculated. Following LTSB, the patients' deep body temperature increased significantly by 1 degrees C. Their heart rates increased and blood pressure decreased slightly. The total peripheral resistance decreased by 11%, and the cardiac output increased by 14%. There was significant improvement in the parameters that are indicative of the peripheral circulatory status, including the skin blood flow, blood flow velocity, pulsatile index, and resistive index. Numbness and chronic myalgia of the extremities decreased. There were no adverse side effects. Thus, it can be concluded that LTSB improves the peripheral circulation in CP patients.     

扶正活血祛瘀法治疗慢性足底溃疡的临床疗效观察

目的观察扶正活血祛瘀法治疗慢性足底溃疡的临床疗效。方法采用四妙勇安汤加减内服,红萝卜加马齿苋煎液浸泡外洗溃疡处,外敷呋喃西林纱布保护伤口的综合治疗方法。结果36例中治愈27例,占75．0％;好转6例,占16．7％;无效3例,占8．3％．姑论以扶正活血祛痰法内服为主,结合红萝卜加马齿苋煎液浸泡外洗与呋喃西林纱布外敷治疗慢性足底溃疡有较好的临床疗效．     

Live optical projection tomography

Optical projection tomography (OPT) is a technology ideally suited for imaging embryonic organs. We emphasize here recent successes in translating this potential into the field of live imaging. Live OPT (also known as 4D OPT, or time-lapse OPT) is already in position to accumulate good quantitative data on the developmental dynamics of organogenesis, a prerequisite for building realistic computer models and tackling new biological problems. Yet, live OPT is being further developed by merging state-of-the-art mouse embryo culture with the OPT system. We discuss the technological challenges that this entails and the prospects for expansion of this molecular imaging technique into a wider range of applications.     

Adenosine receptor-mediated coronary vascular protection in post-ischemic mouse heart

This study evaluated the ability of A1 and A3 adenosine receptor (AR) agonism, and A1, A2A, A2B and A3AR antagonism (revealing "intrinsic" responses), to modify post-ischemic coronary dysfunction in mouse heart. Vascular function was assessed before and after 20 min global ischemia and 30-45 min reperfusion in Langendorff perfused C57/Bl6 mouse hearts. Ischemic insult impaired coronary sensitivity to the endothelial-dependent dilators ADP (pEC50=6.8+/-0.1 vs. 7.6+/-0.1, non-ischemic) and acetylcholine (pEC50=6.1+/-0.1 vs. 7.3+/-0.1 in non-ischemic), and for the mixed endothelial-dependent/independent dilator 2-chloroadenosine (pEC50=7.5+/-0.1 vs. 8.4+/-0.1, non-ischemic). Endothelium-independent dilation in response to nitroprusside was unaltered (pEC50=7.0+/-0.1 vs. 7.1+/-0.1 in non-ischemic). Pre-treatment with a selective A1AR agonist (50 nM CHA) failed to modify coronary dysfunction, whereas A1AR antagonism (200 nM DPCPX) worsened the effects of I/R (2-chloroadenosine pEC50=6.9+/-0.1). Conversely, A3AR agonism (100 nM Cl-IB-MECA) did reduce effects of I/R (pEC50s=8.0+/-0.1 and 7.3+/-0.1 for 2-chloroadenosine and ADP, respectively), whereas antagonism (100 nM MRS1220) was without effect. While A2AAR agonism could not be assessed (due to pronounced vasodilatation), A2AAR antagonism (100 nM SCH58261) was found to exert no effect, and antagonism of A2BARs (50 nM MRS1754) was also ineffective. The protective actions of A3AR agonism were also manifest as improved reactive hyperemic responses. Interestingly, post-ischemic coronary dysfunction was also limited by: Na+-H+ exchange (NHE) inhibition with 10 or 50 microM BIIB-513 (2-chloroadenosine pEC50s=7.8+/-0.1, either dose), an effect not additive with A3AR agonism; Ca2+ antagonism with 0.3 microM verapamil (2-chloroadenosine pEC50=7.9+/-0.1); and Ca2+ desensitization with 5 mM BDM (2-chloroadenosine pEC50=7.8+/-0.1). In contrast, endothelin antagonism (200 nM PD142893) and anti-oxidant therapy (300 microM MPG+150 U/ml SOD+600 U/ml catalase) were ineffective. Our data collectively confirm that ischemia selectively impairs endothelial function and reactive hyperemia independently of blood cells. Vascular injury is intrinsically limited by endogenous (but not exogenous) activation of A1ARs, whereas exogenous A3AR activation further limits dysfunction (improving post-ischemic vasoregulation). Finally, findings suggest this form of post-ischemic coronary injury is unrelated to endothelin or oxidant stress, but may involve modulation of Ca2+ overload and/or related ionic perturbations.     

Enhanced global mathematical model for studying cerebral venous blood flow

Here we extend the global, closed-loop, mathematical model for the cardiovascular system in Müller and Toro (2014) to account for fundamental mechanisms affecting cerebral venous haemodynamics: the interaction between intracranial pressure and cerebral vasculature and the Starling-resistor like behaviour of intracranial veins. Computational results are compared with flow measurements obtained from Magnetic Resonance Imaging (MRI), showing overall satisfactory agreement. The role played by each model component in shaping cerebral venous flow waveforms is investigated. Our results are discussed in light of current physiological concepts and model-driven considerations, indicating that the Starling-resistor like behaviour of intracranial veins at the point where they join dural sinuses is the leading mechanism. Moreover, we present preliminary results on the impact of neck vein strictures on cerebral venous hemodynamics. These results show that such anomalies cause a pressure increment in intracranial cerebral veins, even if the shielding effect of the Starling-resistor like behaviour of cerebral veins is taken into account.     

Numerical modelling of large-scale circulation in Lakes Onega and Ladoga

The results of numerical modelling of large-scale circulation in Lakes Onega and Ladoga are presented, with primary emphasis on the temporal variability of currents with time scales of days. Some typical circulation patterns have been inferred from model calculations. They reflect the existence of different dynamic regimes in the lakes, namely, forced and free circulation regimes. The forced circulation regime is the well-known wind-induced double-gyre circulation accompanied by coastal upwelling and downwelling. A case of double-gyre circulation in Lake Onega was investigated in particular detail. The second dynamic regime is a free response (or a relaxation) of the stratified lake to wind cessation, and is connected closely with the evolution of wind-induced upwelling and thermal front propagation. Diagnostic calculations demonstrate that the regime of relaxation supports the restoration of cyclonic circulation in Lake Onega. Barotropic circulation patterns in Lake Ladoga were calculated with the emphasis on prevailing winds from west to south-east. Our calculations show that the bottom relief of Lake Ladoga causes asymmetry in the double-gyre circulation patterns. In particular, approximately equal cyclonic and anticyclonic circulation cells appearing in the case of southerly wind transform to a single dominant cyclonic cell and several small anticyclonic cells in the case of westerly wind. We also found especially strong sensitivity of the sense of rotation of the largest gyre to the east-west components of the wind vector.     

Acute responses of regional vascular conductance to oral ingestion of fructose in healthy young humans

Background

Recently, it was reported in healthy young subjects that fructose containing drinks increased blood pressure acutely, without any apparent change in total vascular conductance (TVC). However, because it is well known that the splanchnic vasculature is dilated by oral fructose ingestion, it is assumed to be the concomitant vasoconstriction in other peripheral region(s) that is responsible for this finding. Thus, the purpose of this study was to determine the acute response of regional VC to oral fructose ingestion in young healthy humans.

Results

In 12 healthy young subjects, mean arterial blood pressure (MAP), heart rate, cardiac output, and blood flow (BF) in the superior mesenteric (SMA), brachial (BA), and popliteal (PA) arteries, in addition to forearm skin BF, were measured continuously for 2 h after ingestion of 400 ml fructose solution (containing 50 g fructose). Regional VC was calculated as BF/MAP. MAP increased for 120 min after fructose ingestion without any change in TVC. While VC in the SMA was elevated after ingestion, VC in BA and PA and forearm skin decreased.

Conclusions

While TVC was apparently unchanged during the 2 h after fructose ingestion, there were coincident changes in regional VCs in the peripheral circulation, but no net change in TVC.     

Nitrogen deposition in tropical forests from savanna and deforestation fires

We used satellite‐derived estimates of global fire emissions and a chemical transport model to estimate atmospheric nitrogen (N) fluxes from savanna and deforestation fires in tropical ecosystems. N emissions and reactive N deposition led to a net transport of N equatorward, from savannas and areas undergoing deforestation to tropical forests. Deposition of fire‐emitted N in savannas was only 26% of emissions – indicating a net export from this biome. On average, net N loss from fires (the sum of emissions and deposition) was equivalent to approximately 22% of biological N fixation (BNF) in savannas (4.0 kg N ha^?1 yr^?1) and 38% of BNF in ecosystems at the deforestation frontier (9.3 kg N ha^?1 yr^?1). Net N gains from fires occurred in interior tropical forests at a rate equivalent to 3% of their BNF (0.8 kg N ha^?1 yr^?1). This percentage was highest for African tropical forests in the Congo Basin (15%; 3.4 kg N ha^?1 yr^?1) owing to equatorward transport from frequently burning savannas north and south of the basin. These results provide evidence for cross‐biome atmospheric fluxes of N that may help to sustain productivity in some tropical forest ecosystems on millennial timescales. Anthropogenic fires associated with slash and burn agriculture and deforestation in the southern part of the Amazon Basin and across Southeast Asia have substantially increased N deposition in these regions in recent decades and may contribute to increased rates of carbon accumulation in secondary forests and other N‐limited ecosystems.