Oxidative stress: does it play a role in the genesis of essential hypertension and hypertension of uraemia?

Reactive oxygen species: general aspects Reactive oxygen species, including superoxide radicals, hydrogenperoxide, nitric oxide, peroxynitrite, hydroxyl radicals andhypochlorous acid are by-products of normal metabolic processesin cells. Reactive oxygen species can be found in several cellsincluding macrophages and vascular smooth muscle cells. At lowconcentrations reactive oxygen species can act as physiologicalmediators of cellular responses whereas higher concentrationsmay cause cell damage [1,2]. The major sources of reactive oxygenspecies are leakages from the electron transport chains of mitochondriaand endoplasmic reticulum. Cellular energy metabolism is basedon the production of ATP through the electron transport reactionin which O₂ accepts electrons and H⁺ and then is eventuallyreduced to water. Only 1–2% of the electrons are leakedto generate superoxide radicals in reactions mediated by coenzymeQ and ubiquinone and its complexes. During ageing (and probablyin patients     

Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients.

BACKGROUND: Dyslipidaemia, inflammation and oxidative stress are prominent risk factors that potentially cause vascular disease in haemodialysis patients. Dialysis modalities affect uraemic dyslipidaemia, possibly by modifying oxidative stress, but the effects of dialyser flux and membrane material on atherogenic remnant particles and oxidized low-density lipoproteins (LDL) are unknown. METHODS: We performed a randomized crossover study in 36 patients on haemodialysis to analyse the effect of dialyser flux and membrane material on plasma lipids, apolipoproteins and markers of inflammation and oxidative stress. Stable patients on low-flux dialysis with polysulphone for >/=6 weeks were assigned to high-flux polysulphone or high-flux modified cellulose with similar dialyser surface area and permeability characteristics and crossed over twice every 6 weeks. RESULTS: Thirty patients completed the study per protocol. Treatments with high-flux polysulphone and modified cellulose lowered serum triglyceride (by 20% and 10%, respectively; P<0.05) and remnant-like particle cholesterol by 32% (P<0.001) and 11% (NS) after the first 6 weeks of treatment. Oxidized LDL decreased significantly with high-flux polysulphone, but not with modified cellulose. Apolipoproteins CII and CIII were reduced, whereas the ratio CII/CIII was increased (all P<0.05). Acute-phase proteins and LDL and high-density lipoprotein cholesterol remained unaffected. CONCLUSIONS: This randomized crossover study demonstrates a potent effect of high-flux haemodialysis on uraemic dyslipidaemia. Polysulphone membrane material showed superiority on oxidatively modified LDL, an indicator of oxidative stress in haemodialysis patients.     

Effect of psychotomimetics and some putative anxiolytics on stress-induced hyperthermia

Summary Stress-induced hyperthermia (SIH), which is seen in the last mice removed from the cage, is a novel animal model sensitive to anxiolytic drugs. SIH is antagonized by CL 218872 (25 and 50 mg/kg, os), by tracazolate (5 and 7.5 mg/kg, ip) and by 2-AP-5 (50 and 100 mg/kg, ip). At higher dose, CL 218872 (100 mg/kg, os) and tracazolate (12.5 mg/kg, ip) lose their activity.PK 9084 (5–40 mg/kg, ip) and CGS 9896 (2–20 mg/kg, both ip and os) were also ineffective in preventing SIH. The anti-hyperthermic effect of CL 218872 (25 mg/kg) and tracazolate (7.5 mg/kg) was blocked by the benzodiazepine antagonist Ro 15–1788 (15 mg/kg). CGS 9896 (10 mg/kg, os) also reversed the effect of CL 218872 (25 mg/kg) on SIH.Differently from anxiolytics, MK-801 (0.5–1 mg/kg, os), PCP (2.5 mg/kg, ip) and d-amphetamine (10 mg/kg, ip) evoked hyperthermia in the first set of mice and prevented a further stress-induced rise of body temperature in the last set of mice.     

Stress-Related Changes in β-Endorphin Processing: The Limitations of Slaughterhouse Material

In the sheep, unlike many other species, a significant proportion (>25%) of immunoreactive β-endorphin in the anterior pituitary is post-translationally modified to opioid-inactive, α-N-acetylated forms. In a study to determine the precise molecular nature of α-N-acetylated β-endorphin immunoreactivity, we noted a striking difference in high-performance liquid chromatography profiles of anterior pituitary extracts between sheep killed on the farm, and age-, sex- and strain-matched slaughterhouse animals. These altered patterns of a-N-acetylated β-endorphin processing were reproduced in farm animals by chronic (≤ 4 days) treatment with the synthetic glucocorticoid dexamethasone; in contrast dexamethasone had no effect on a-N-acetylated β-endorphin processing in hypothalamo-pituitary disconnected sheep. These data suggest that (1) the change in processing is a stress response, mediated by prolonged glucocorticoid exposure, (2) this effect is central, rather than a direct effect on the pituitary, and (3) the relative abundance of various peptide sequences in slaughterhouse-derived material may not reflect their abundance under more physiological conditions.     

损毁下丘脑不同脑区对折断腿骨所致血浆皮质酮变化的影响

清醒sprague-Dawley雄性大鼠64只,以折断胫腓骨造成应激。观察非内侧基底下丘脑脑区损毁对应激前(Bo)、后(Bs)血浆皮质酮变化的影响。以Bs/Bo及Bs-Bo的值衡量应激反应的大小。根据所损毁脑区的部位及范围将动物分为6组:假手术组、室旁核损毁组、室旁核部分损毁组、室旁核少量损毁组、下丘脑前部—视前区损毁组、下丘脑后部损毁组。用统计学方法比较了6组动物的Bs/Bo及Bs-B0值,以及根据4例室旁核完全损毁动物仍保持有应激反应的事实,我们得出结论:(1)在清醒大鼠的损伤性应激反应中,下丘脑室旁核较其他非基底内侧下丘脑区具有较重要的作用。(2)室旁核以外的促肾上腺皮质激素释放因子神经元可能也参与应激反应。     

Addition of sufentanil to bupivacaine in caudal block effect on stress responses in children

BACKGROUND: The aim of the present randomized study was to determine the effect of adding sufentanil to bupivacaine, compared with bupivacaine alone in caudal block, on the surgical stress response in children. METHODS: The children were premedicated with midazolam 0.5 mg/kg. All children received induction with nitrous oxide and sevoflurane. Anesthesia was maintained with the same volatile agents in the both groups. The children were randomly allocated to two groups. Group I received bupivacaine alone (n = 17) and group II received bupivacaine + sufentanil (n = 16). Caudal block was performed with 0.25% bupivacaine 2 mg/kg (group I) or 0.25% bupivacaine 2 mg/kg with sufentanil 0.5 microg/kg (group II) after induction of anesthesia. Blood samples were obtained after induction of anesthesia (T(0)) to measure baseline concentrations of cortisol, prolactin, glucose and insulin. Additional samples were obtained 30 min after the start of surgery (T(1)), and 60 min after the end of surgery (T(2)). RESULTS: All of the basal values (T(0)) were within the normal ranges of the authors' laboratory for children of this age group and there were no differences between the groups (P > 0.05). In both groups, glucose concentration increased at T(1), compared with T(0) and T(2) (P < 0.05). The glucose concentration was unchanged at T(2) compared with T(0) in both group (P > 0.05). In both groups, prolactin concentration increased at T(1), compared with T(0) and decreased at T(2), compared with T(1) (P < 0.05). Cortisol decreased at T(1) and T(2), compared with T(0) in both groups. (P < 0.05). Insulin concentration remained unchanged at T(0) and T(2), but increased slightly at T(1) in both groups (P > 0.05). There were no significant differences in plasma prolactin, cortisol, glucose and insulin levels between the two groups at T(1) and T(2) (P > 0.05). CONCLUSION: There is no advantage in adding 0.5 microg/kg sufentanil to bupivacaine over bupivacaine alone in the caudal block, with regard to the surgical stress response in children.     

Levels of Psychological Distress Experienced by Family Carers of Children and Adolescents with Intellectual Disabilities in an Urban Conurbation

Background The aim of the present study was to identify factors associated with the level of psychological distress reported by family carers of children with intellectual disability living in a large urban conurbation. Method Information was collected by postal questionnaire (or interview for family carers who did not have English as their first language) from the family carers of 408 children with intellectual disability (31% of all children within the area administratively identified as having an intellectual disability). Results Results indicated that 47% of primary carers scored above the threshold for psychological distress on the GHQ and that scoring above the threshold was strongly related to the emotional and behavioural needs of the index child and South‐Asian ethnicity and moderately associated with the severity of the child's delay in communication. Conclusions The rates of psychological distress (47% overall, 70% among South‐Asian carers) were markedly higher than that found in previous studies of carers supporting a child with intellectual disabilities. It is suggested that these elevated rates of psychological distress may be mediated by socio‐economic deprivation.     

Distension-induced gastric accommodation in functional dyspepsia: effect of autonomic manipulation

Functional dyspepsia (FD) is associated with impaired gastric accommodation and autonomic dysregulation. The aim of this study was to investigate the effects of autonomic manipulation on distension-induced gastric accommodation in subjects with and without FD, using a newly developed gastric barostat paradigm. Twelve healthy subjects (HS) and 18 subjects with FD had four barostat examinations each: no intervention, intravenous atropine (1 mg), vagal stimulation (mental relaxation with deep breathing) and acute stress stimulation (serial subtraction task). Intrabag pressure increased from 1 to 15 mmHg in 5 min (ramp phase), and was maintained at 15 mmHg for 5 min (tonic phase). Volume responses were analysed using predefined parameters. There were no significant group differences in accommodation variables between HS and subjects with FD. The FD group could be subdivided into two distinct subgroups: subgroup 1 (n = 7, 38%) with low maximum volume and accommodation rate, and subgroup 2 with normal accommodation (n = 11). In subgroup 1, but not in subgroup 2 atropine increased maximum volume and accommodation rate substantially. Neither mental stress nor mental relaxation changed any of the accommodation variables. In a subgroup of subjects with FD, impairment of distension-induced gastric accommodation can be improved by cholinergic blockade, but not by acute physiological autonomic manipulation.     

Lipid peroxidation in several brain regions during development of post-stress depressions in rats with different strategies of adaptive behavior

Lipid peroxidation in the brain cortex, striatum, hippocampus, and hypothalamus of rats of the KLA and KHA lines which were distinguished by their strategies of adaptive behavior was investigated following emotional-painful stress. Significant long-term changes in lipid peroxidation were shown to occur in the brain. These had a phase character and depended on the behavioral characteristics of the animals. The investigated brain regions were characterized by different reactions of lipid peroxidation to the stress. The induced depressive-like states (on the 21st day after the stress) in rats of the KLA and KHA lines were distinguished by the largest changes in lipid peroxidation in the striatum and hypothalamus and in the striatum and hippocampus, respectively. One could conclude on the basis of these results that both identical and different mechanisms of formation and development of depression existed in the animals with different behavioral strategies.