Oxidative damage to DNA in plaques of MS brains

To a number of nurse educators, the Internet is a new, innovative and exciting teaching and learning tool. Sadly, anecdotal evidence suggests that many educators remain largely unaware of these new technologies or their potential to assist in the process of learning. Such a situation is not surprising given the limited amount of literature detailing the use of the Internet in nurse education and a profound lack of educational research in the area. This paper will highlight some of the benefits of the Internet for nursing students and educators, provide an overview of a number of Internet technologies and suggest some practical applications of these technologies in nurse education. A glossary of Internet terms is included.     

Endothelial damage from intraocular lens insertion

Previous studies have shown that approximately 40 per cent of the corneal endothelial cells can be lost at the time of intraocular lens insertion. Momentary contact between the methacrylate surface and the endothelial cells causes an adhesion between these surfaces and results in extensive cell damage upon separation of the surfaces. This type of damage appears to be due to a biophysical interaction between these surfaces and may be avoidable by altering the surface of the lens.     

Extracorporeal support for intractable cardiorespiratory failure due to meningococcal disease

BACKGROUND: Meningococcal disease is still associated with considerable mortality, despite the use of early antibiotics and management in specialised intensive care units, due principally to early refractory myocardial depression and hypotension as well as severe acute respiratory distress syndrome. Extracorporeal membrane oxygenation (ECMO) is a complex technology that uses a modified "heart-lung" machine to provide temporary cardiac and respiratory support. We reviewed the UK and Australian experience of the use of ECMO in patients with refractory cardiorespiratory failure due to meningococcal disease. METHODS: The records from all 12 known patients supported with ECMO for meningococcal disease in the UK and Australia since 1989 were reviewed. FINDINGS: 12 patients (aged 4 months to 18 years, median 26 months) with meningococcal disease received ECMO over 8 years. In seven patients, ECMO was required early for cardiac support for intractable shock within 36 h of admission to intensive care. In the other five patients, ECMO was indicated for respiratory failure due to severe adult respiratory distress syndrome, which tended to occur later in the disease. The paediatric risk of mortality score ranged from 13 to 40 (median 29, median predicted risk of mortality 72%). Six of the 12 patients required cardiopulmonary resuscitation before ECMO and the other six were deteriorating despite maximal conventional therapy. Overall, eight of the 12 patients survived, with six leading functionally normal lives at a median of 1 year (range 4 months to 4 years) of follow-up. INTERPRETATION: ECMO might be considered to support patients with intractable cardiorespiratory failure due to meningococcal disease who are not responding to conventional treatment.     

Sleep state organization in the developing piglet during exposure to different thermal stimuli

Sleep state changes in response to different thermal stimuli were investigated in newborn piglets between 2 and 10 days of age. Test animals were exposed to cold air (7-12 degrees C) and warm air (27-33 degrees C) around the face, while the remainder of the body was kept at first warm (normothermic) then hyperthermic. A separate group of animals was studied under normothermic conditions (control) for the duration of the study. Piglets showed typical changes in sleep state patterns characteristic of rapid maturation over the first 10 days of development. It was found that both the amount of rapid eye movement (REM) sleep and, in some cases, the duration of REM episodes increased in response to facial cooling regardless of rectal temperature. However, hyperthermia with warm air exposure caused a significant decrease in the amount of REM sleep but not in the duration of REM episodes. It is suggested that an infant placed to bed in a cold room or exposed to a draft might also experience a greater amount of REM sleep than an infant placed to sleep in a warm draft-free room.     

Effect of propentofylline on free radical generation during cerebral hypoxia in the newborn piglet

The present study tests the hypothesis that propentofylline, an adenosine re-uptake inhibitor, will reduce free radical generation during cerebral hypoxia. Ten newborn piglets were pretreated with propentofylline (10 mg/kg), five of which were subjected to hypoxia, while the other five were maintained at normoxia. Five untreated control piglets underwent the same conditions. Hypoxia was induced through a decrease in FiO2 to 0.11 and documented biochemically by a decrease in ATP and phosphocreatine levels. Free radical formation in the cortex was detected directly using electron spin resonance spectroscopy with a spin trap technique. Results demonstrate that free radicals, corresponding to the alkoxyl radical, increased significantly following hypoxia, and that this increase was inhibited by pretreatment with propentofylline. Conjugated dienes, a lipid peroxidation product, also increased following hypoxia and were subsequently inhibited by propentofylline. The administration of propentofylline also significantly limited the hypoxia-induced decrease in tissue levels of ATP and phosphocreatine. These data demonstrate that pretreatment with propentofylline decreased free radical generation and lipid peroxidation as well as preserved high energy phosphates during cerebral hypoxia.     

Local transport kinetics of glucose during acute and chronic nicotine infusion in rat brains

Acute and chronic infusion of nicotine is known to result in a distinct increase in local cerebral glucose utilization (LCGU) in several brain structures. The present study addresses the question whether this increase in LCGU is paralleled by a local change in glucose transport in rat brain. Nicotine was infused either acutely for 3 hours or chronically by osmotic minipumps for one week. Local rate constants for glucose transport were measured in brain cryosections using the 3-O-[14C]methylglucose method. Local rate constants K1 and k2 were lower in part of the brain structures during acute (-10% to -20%) and in nearly all structures during chronic (-39% to -41%) nicotine. The finding of a decreased glucose transport during chronic nicotine was confirmed by additional experiments of 3-O-[14C]methylglucose transfer in an epithelial cell culture. It is concluded that acute and chronic nicotine infusion results in decreased glucose transport although LCGU is either unchanged or increased.     

Endothelial dysfunction in cerebral microcirculation during hypothermic cardiopulmonary bypass in newborn lambs

OBJECTIVES: Inflammatory stimuli or mechanical stresses associated with hypothermic cardiopulmonary bypass could potentially impair cerebrovascular function, resulting in inadequate cerebral perfusion. We hypothesize that hypothermic cardiopulmonary bypass is associated with endothelial or vascular smooth muscle dysfunction and associated cerebral hypoperfusion. Therefore we studied the cerebrovascular response to endothelium-dependent vasodilator, acetylcholine, endothelium-independent nitric oxide donor, sodium nitroprusside, and vasoactive amine, serotonin, in newborn lambs undergoing hypothermic cardiopulmonary bypass (nasopharygeal temperature = 18 degrees C). METHODS: Studies were performed on 13 newborn lambs equipped with a closed cranial window, allowing for direct visualization of surface pial arterioles. Six animals were studied while undergoing hypothermic cardiopulmonary bypass, whereas seven served as nonbypass, warm (37 degrees C) controls. Pial arteriolar caliber (range = 111 to 316 microm diameter) was monitored using video microscopy. RESULTS: Topical application of acetylcholine caused a dose-dependent increase in arteriolar diameter in the control group that was absent in animals undergoing hypothermic cardiopulmonary bypass. Hypothermic cardiopulmonary bypass did not alter the vasodilation in response to sodium nitroprusside. Furthermore, the contractile response to serotonin was fully expressed during hypothermic cardiopulmonary bypass. CONCLUSIONS: The specific loss of acetylcholine-induced vasodilation suggests endothelial cell dysfunction rather than impaired ability of vascular smooth muscle to respond to nitric oxide. It is speculated that loss of endothelium-dependent regulatory factors in the cerebral microcirculation during hypothermic cardiopulmonary bypass may enhance vasoconstriction, and impaired cerebrovascular function may be a basis for associated neurologic injury during or after hypothermic cardiopulmonary bypass.     

Acute hypoxemia depresses the cardiorespiratory response during phase I constant load exercise and unloaded cycling

The effects of acute inhalation of hypoxic gas mixtures on minute ventilation (VE), respiratory frequency (fR) and heart rate (HR) were studied in healthy subjects executing constant-load 100 W and 150 W hindlimb exercises (protocol 1) or unloaded (0 W) cycling (protocol 2). Attention was focussed on early changes in variables during phase I of constant load exercise, a period where neurogenic afferents from working muscles play a key role in adaptative cardiorespiratory response as they did also during 0 W cycling. In protocol 1, a 15% O2 gas mixture was used while in protocol 2, 15% and 10% O2 mixtures were tested. Compared to the variations of cardiorespiratory variables measured during room air breathing (normoxia), hypoxemia significantly and markedly depressed the rates of VE and fR changes during phase I exercise but did not affect the changes in HR. Reduced phase I ventilatory response was not accompanied by significant variations in rest values of PaCO2 and pHa associated with the response to hypoxia. The cardiorespiratory response to 0 W cycling was also lowered under hypoxemic conditions, the magnitude of VE and HR changes being inversely proportional to the fall in PaO2 level. Based on electrophysiological animal observations, the present results may be interpreted in terms of inhibitory influences of hypoxemia on proprioceptive muscle afferents.     

Endothelial cell markers in chronic uremia: relationship with hemostatic defects and severity of renal failure

The Read Codes are a hierarchically-arranged controlled clinical vocabulary introduced in the early 1980s and now consisting of three maintained versions of differing complexity. The code sets are dynamic, and are updated quarterly in response to requests from users including clinicians in both primary and secondary care, software suppliers, and advice from a network of specialist healthcare professionals. The codes' continual evolution of content, both across and within versions, highlights tensions between different users and uses of coded clinical data. Internal processes, external interactions and new structural features implemented by the NHS Centre for Coding and Classification (NHSCCC) for user interactive maintenance of the Read Codes are described, and over 2000 items of user feedback episodes received over a 15-month period are analysed.     

Oxidative damage during aging targets mitochondrial aconitase

The mechanisms that cause aging are not well understood. The oxidative stress hypothesis proposes that the changes associated with aging are a consequence of random oxidative damage to biomolecules. We hypothesized that oxidation of specific proteins is critical in controlling the rate of the aging process. Utilizing an immunochemical probe for oxidatively modified proteins, we show that mitochondrial aconitase, an enzyme in the citric acid cycle, is a specific target during aging of the housefly. The oxidative damage detected immunochemically was paralleled by a loss of catalytic activity of aconitase, an enzyme activity that is critical in energy metabolism. Experimental manipulations which decrease aconitase activity should therefore cause a decrease in life-span. This expected decrease was observed when flies were exposed to hyperoxia, which oxidizes aconitase, and when they were given fluoroacetate, an inhibitor of aconitase. The identification of a specific target of oxidative damage during aging allows for the assessment of the physiological age of a specific individual and provides a method for the evaluation of treatments designed to affect the aging process.     

Left ventricular function during respiratory failure

Indirect measures of left ventricular function were studied in seven patients with respiratory failure secondary to chronic obstructive pulmonary disease to determine if there were a relationship between left ventricular function and treatment of the pulmonary disease. All patients were studied during acute episodes while in respiratory failure having arterial Pco2 (Paco2) values greater than 49 torr with no clinical evidence of left ventricular failure. Indirect methods to evaluate left ventricular function included the use of the Swan-Ganz catheter for pulmonary capillary wedge pressure measurement, systolic time intervals, and cardiac output. There was improvement in left ventricular function with treatment of the respiratory failure manifested by decreases in the wedge pressure and pre-ejection period/left ventricular ejection time ratio, and an increase in the dp/dt/pulmonary capillary wedge pressure with treatment of the chronic obstructive pulmonary disease. The improvement in left ventricular function suggests that there is a depression of left ventricular function in respiratory failure. The depressed function improved with therapy of the lung disease without additional medication directed at cardiac function.     

Endothelial DNA synthesis in themicrovasculature of rat skin during the hair growth cycle

A method is described for the purification of human enterokinase from accumulated duodenal fluid by affinity chromatography using p-aminobenzamidine as the ligand. Resolution was greatest when glycylglycine was substituted as the spacer arm. Purification was not a one-step procedure, and some contamination, principally by the alpha-glucosidases, remained. Their removal was completed by immunoadsorption using antisera raised to enterokinase-free material containing these enzymes, prepared as a by-product of the purification procedure. The final preparation had an activity of 4260 nmol of trypsin/min per mg and was free of other enzymic activity tested. Amino acid and sugar analyses of the highly purified enzyme indicated an acidic glycoprotein containing 57% sugar (neutral sugars 47%, amino sugars 10%). The apparent mol.wts. and Stokes radii of human and pig enterokinase were 296 000 and 316 000, and 5.65 and 5.78 nm respectively. Two isoenzymes were identified for human enterokinase and three for the pig enzyme. Human enterokinase demonstrated a resistance to reduction of disulphide linkages and to sodium dodecyl sulphate binding, which may be related to the need for it to retain its integrity in the digestive environment of the upper small intestine. Antisera to highly purified pig and human enterokinases specifically inhibited enterokinase activity. Immuno-inhibition of intestinal aminopeptidase, maltase and glucoamylase by homologous antisera was not observed.