Caffeine prevents high-intensity exercise-induced increase in enzymatic antioxidant and Na+-K+-ATPase activities and reduction of anxiolytic like-behaviour in rats

Objective: Here we investigated the impact of chronic high-intensity interval training (HIIT) and caffeine consumption on the activities of Na⁺-K⁺-ATPase and enzymes of the antioxidant system, as well as anxiolytic-like behaviour in the rat brain.

Methods: Animals were divided into groups: control, caffeine (4?mg/kg), caffeine (8?mg/kg), HIIT, HIIT plus caffeine (4?mg/kg) and HIIT plus caffeine (8?mg/kg). Rats were trained three times per week for 6 weeks, and caffeine was administered 30 minutes before training. We assessed the anxiolytic-like behaviour, Na⁺-K⁺-ATPase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) in the brain.

Results and discussion: HIIT-induced anxiolytic-like behaviour increased Na⁺-K⁺-ATPase and GPx activities and TBARS levels, altered the activities of SOD and CAT in different brain regions, and decreased GSH levels. Caffeine, however, elicited anxiogenic-like behaviour and blocked HIIT effects. The combination of caffeine and HIIT prevented the increase in SOD activity in the cerebral cortex and GPx activity in three brain regions. Our results show that caffeine promoted anxiogenic behaviour and prevented HIIT-induced changes in the antioxidant system and Na⁺-K⁺-ATPase activities.     

静脉注射乌拉地尔与硝酸甘油微泵对高血压患者拔牙术中血压及心率的影响

目的:探讨静脉注射乌拉地尔与硝酸甘油微泵对高血压患者拔牙术中血压及心率(HR)的影响。方法:选择自2015年1月到2016年10月在我院进行心电监护拔牙的高血压患者116例纳入本次研究,根据随机数字表法将患者分成观察组以及对照组各58例,对照组给予硝酸甘油加泵静点维持,观察组给予乌拉地尔加泵静点维持,对比两组术前、麻醉时、麻醉后10min、术中及术后10min收缩压(SBP)、舒张压(DBP)以及HR的变化,并对比两组不良反应情况。结果:两组术中及术后10min的SBP和DBP水平均分别明显低于术前,观察组术中的SBP和DBP水平均分别明显低于对照组,差异均有统计学意义(P0.05);对照组术中及术后10min的HR均明显高于术前,且观察组均明显低于对照组,差异均有统计学意义(P0.05)。观察组不良反应的总发生率是6.90%(4/58),与对照组的10.34%(6/58)相比,差异无统计学意义(P0.05)。结论:静脉注射乌拉地尔对高血压患者在拔牙术中血压及HR的影响较小,安全性较好,值得推广。     

主动脉球囊反搏器植入术治疗急性左心衰的应用价值

目的:探讨主动脉球囊反搏器植入术治疗急性左心衰的应用价值。方法:收集我院2013年2月-2016年1月收治的急性左心衰患者102例作为本次研究对象,根据随机信封抽签的方法将患者分为观察组和对照组,每组51例。对照组给予常规药物治疗,观察组在常规药物治疗的基础上加用主动脉球囊反搏器植入术,记录与观察两组患者的临床结局。结果:观察组的总有效率为96.1%,显著高于对照组的总有效率84.3%(P0.05)。治疗后,观察组与对照组的LVEF值分别为65.22±4.52%和58.20±5.31%,都明显高于治疗前的45.29±5.14%和45.20±4.89%,且观察组的LVEF值明显高于对照组(P0.05)。观察组治疗后随访6个月的死亡、顽固性缺血、恶性心律失常等近期主要终点事件发生率为5.9%,对照组为21.6%,观察组明显低于对照组(P0.05)。结论:主动脉球囊反搏器植入术治疗急性左心衰能促进左心室功能的改善,提高治疗效果,减少近期主要终点事件的发生。     

透明质酸钠预防微波消融术后局部粘连的实验研究

目的:通过实验探讨透明质酸钠预防微波消融术后局部组织粘连的效果。方法:120只健康SD大鼠随机分为三组,每组40只,分别为微波消融组(A组,对照组)、微波消融加透明质酸钠组(B组)、微波消融加生理盐水组(C组)。通过对大鼠背部肌肉进行微波消融建立术后局部粘连模型,并在该模型基础上应用透明质酸钠,术后3 d、1 w、2 w、4 w分别对背部组织进行粘连分级、HE染色及免疫组化观察和分析。结果:消融术后3 d、1 w、2 w,B组在粘连分级方面A、B及C 3组间水平差异具有统计学意义P0.05);4 w时A、B、C组间的差异无统计学意义(P=0.458)。两两比较,A、C两组在四个时间点水平差异无统计学差异(P均0.05),而B组在消融术后3 d、1 w和2 w时,粘连分级明显优于A、C组,P=0.029(3 d)、P=0.011(1W)、P=0.004(2W),水平差异显著,有统计学意义;4 w时,P=0.391,无统计学意义。消融术后A、C组HE染色及免疫组化染色光镜下观察,淋巴细胞、巨噬细胞等炎症浸润情况及成纤维细胞数目均较B组多,且A、C组胶原纤维沉积明显多于B组。结论:透明质酸钠能够有效减轻微波消融术后发生的局部组织粘连。     

Mineralocorticoids modulate the expression of the β-3 subunit of the Na+, K+-ATPase in the renal collecting duct

Renal sodium reabsorption depends on the activity of the Na⁺,K⁺-ATPase α/β heterodimer. Four α (α_1–4) and 3 β (β_1–3) subunit isoforms have been described. It is accepted that renal tubule cells express α₁/β₁ dimers. Aldosterone stimulates Na⁺,K⁺-ATPase activity and may modulate α₁/β₁ expression. However, some studies suggest the presence of β₃ in the kidney. We hypothesized that the β₃ isoform of the Na⁺,K⁺-ATPase is expressed in tubular cells of the distal nephron, and modulated by mineralocorticoids. We found that β₃ is highly expressed in collecting duct of rodents, and that mineralocorticoids decreased the expression of β₃. Thus, we describe a novel molecular mechanism of sodium pump modulation that may contribute to the effects of mineralocorticoids on sodium reabsorption.     

Evolution to environmental contamination ablates the circadian clock of an aquatic sentinel species

Environmental contamination is a common cause of rapid evolution. Recent work has shown that Daphnia pulex, an important freshwater species, can rapidly evolve increased tolerance to a common contaminant, sodium chloride (NaCl) road salt. While such rapid evolution can benefit organisms, allowing them to adapt to new environmental conditions, it can also be associated with unforeseen tradeoffs. Given that exposure to environmental contaminants can cause circadian disruption, we investigated whether the circadian clock was affected by evolving a tolerance to high levels of road salt. By tracking the oscillations of a putative clock gene, period, we demonstrated that D. pulex express per mRNA with approximately 20‐hr oscillations under control conditions. This putative circadian rhythm was ablated in response to high levels of salinity; populations adapted to high NaCl concentrations exhibited an ablation of period oscillation. Moreover, we showed that while gene expression is increased in several other genes, including clock, actin, and Na⁺/K⁺‐ATPase, upon the adaptation to high levels of salinity, per expression is unique among the genes we tracked in that it is the only gene repressed in response to salt adaptation. These results suggest that rapid evolution of salt tolerance occurs with the tradeoff of suppressed circadian function. The resultant circadian disruption may have profound consequences to individuals, populations, and aquatic food webs by affecting species interactions. In addition, our research suggests that circadian clocks may also be disrupted by the adaptation to other environmental contaminants.     

A minimalistic tetrapeptide amphiphile scaffold for transmembrane pores with a preference for sodium

Synthetic channels or pores that are easy to synthesize, stable and cation-selective are extremely attractive for the development of therapeutics and materials. Herein, we report a pore developed from a small tetrapeptide scaffold that shows a preference for sodium over lithium/potassium. The sodium selectivity is attributed to the appended oligoether tail at the C-terminus. A peptide dimer is proposed as the predominant cation-transporting pore. Such pyridine containing stable pores can be potentially utilized for the pH modulated ion transport.     

Metabolic constraints on the evolution of antibiotic resistance

Despite our continuous improvement in understanding antibiotic resistance, the interplay between natural selection of resistance mutations and the environment remains unclear. To investigate the role of bacterial metabolism in constraining the evolution of antibiotic resistance, we evolved Escherichia coli growing on glycolytic or gluconeogenic carbon sources to the selective pressure of three different antibiotics. Profiling more than 500 intracellular and extracellular putative metabolites in 190 evolved populations revealed that carbon and energy metabolism strongly constrained the evolutionary trajectories, both in terms of speed and mode of resistance acquisition. To interpret and explore the space of metabolome changes, we developed a novel constraint‐based modeling approach using the concept of shadow prices. This analysis, together with genome resequencing of resistant populations, identified condition‐dependent compensatory mechanisms of antibiotic resistance, such as the shift from respiratory to fermentative metabolism of glucose upon overexpression of efflux pumps. Moreover, metabolome‐based predictions revealed emerging weaknesses in resistant strains, such as the hypersensitivity to fosfomycin of ampicillin‐resistant strains. Overall, resolving metabolic adaptation throughout antibiotic‐driven evolutionary trajectories opens new perspectives in the fight against emerging antibiotic resistance.     

Sodium meta-arsenite induced reactive oxygen species in human red blood cells: impaired antioxidant and membrane redox systems,haemoglobin oxidation,and morphological changes

Arsenic (As) is an air and water toxicant that causes cancer in multiple organs. Humans are exposed to As through contaminated water. We have examined the cytotoxicity of sodium meta-arsenite (SA), an As(III) compound, in human red blood cells (RBC) under in vitro conditions. Haemolysates were prepared from human RBC treated with different concentrations of SA (0.1–5.0?mM) for 5?h at 37?°C. SA treatment of RBC caused significant increase in methaemoglobin formation, protein and lipid oxidation, and nitric oxide levels. It also resulted in decrease in glutathione levels, methaemoglobin reductase activity and plasma membrane redox system. SA exposure also inhibited the pathways of glucose metabolism while increasing AMP deaminase and glyoxalase-I. It impaired the enzymatic and non-enzymatic antioxidant defence systems which resulted in decreased antioxidant power and a compromised ability to quench free radicals. SA exposure also damaged the membrane since it decreased the activity of membrane bound enzymes, increased the osmotic fragility of treated cells and induced gross morphological changes. This cytotoxicity was the result of oxidative damage since the production of reactive oxygen species (ROS) was increased in SA treated erythrocytes. Thus As(III) causes extensive damage to RBC which impairs their antioxidant system and alters the major cellular metabolic pathways. All this has the potential to lower the oxygen carrying capacity of RBC and reduce their lifespan in blood.