Potential therapeutic effects of exercise to the brain.

Exercise is a well-recognized facet of modern living; however, the threat of sedentary lifestyle is ever increasing with the arrival of the technological period. Although the beneficial effects of exercise to the health and function of the brain have been accepted by the scientific and medical community, much remains to be achieved to understand its mechanisms of action. With the advent of modern investigative tools, several more key molecular and cellular players have been implicated in the above process. Such include the family of neurotrophins (e.g. NGF and BDNF) and their receptors, some pro-inflammatory cytokines (L-1beta, IL-6, TNF-alpha, IFN-gamma), microglia and astrocytes, and the cholinergic neuronal cells in the forebrain. While experiments based on the voluntary exercise paradigm has been the preferred approach to studying the brain, less is known about the forced paradigm. We will discuss in this review how molecular players may feature differently in the context of exercise and more importantly how their actions converged to impact the structure, and function (learning and memory) of the CNS.

Cytokine changes in the horizontal diagonal band of Broca in the septum after running and stroke: a correlation to glial activation.

The relationship between running, glial cell activation and pro-inflammatory cytokines was studied in the context of neuroprotection against ischemic stroke induced by middle cerebral artery occlusion (MCAO). This was investigated in four groups of rats, namely, (1) nonrunner, (2) runner after 12 weeks of treadmill running, (3) nonrunner with MCAO and (4) runner with MCAO. The horizontal diagonal band of Broca (HDB) in the septum was scrutinized for qualitative cum quantitative changes in the microglia and astrocytes. Reverse transcription-polymerase chain reaction and immunoblot work were carried out in the forebrain homogenate to determine, respectively, the gene and protein expression of several pro-inflammatory cytokines. Our results indicated that the runner exhibited less immunoreactivity and reduced numbers of glial cells within the HDB compared with the nonrunner. Interestingly, the mRNA and protein levels of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and interferon-gamma, were significantly downregulated in the runner. Our data also suggest albeit with some inconsistency that the runner/MCAO rats had benefited from running. These observations suggest that running can result in changes to the microenvironment, in which the microglia and astrocytes exist in a state of quiescence concomitant with a reduced expression of pro-inflammatory cytokines, that may lead to beneficial effects seen in ischemic stroke induced by MCAO.

Neuroprotection associated with running: is it a result of increased endogenous neurotrophic factors?

The possible neuroprotective effect of physical exercise was investigated in rats after middle cerebral artery occlusion (MCAO), a focal stroke model. It was found that physical exercise in the form of a 12-week treadmill running programme reduced the volume of infarction caused by MCAO. At the molecular level, reverse transcription polymerase chain reaction revealed that the runner had increased gene expression for nerve growth factor (NGF) over the nonrunner with or without MCAO. Expression of the NGF receptors, p75, was increased only in the absence of MCAO. In addition, runners showed a significantly higher number of cholinergic neurons, which constitutively expressed p75, in the horizontal diagonal band of Broca. The present findings suggest that neuroprotection after physical exercise may be a result of an increase in an endogenous neurotrophic factor nerve growth factor and the proliferation of its receptive cholinergic neurons.

Voluven, a lower substituted novel hydroxyethyl starch (HES 130/0.4), causes fewer effects on coagulation in major orthopedic surgery than HES 200/0.5.

UNLABELLED: Hydroxyethyl starch (HES) solutions are effective plasma volume expanders. Impairment of coagulation occurs with large HES volumes infused perioperatively. Therefore, a lower substituted novel HES (Voluven; Fresenius Kabi, Bad Homburg, Germany) was developed to minimize hemostatic interactions, and was compared with HAES-steril (Fresenius Kabi) (pentastarch) regarding safety and efficacy. We performed a prospective, randomized, double-blinded study in 100 major orthopedic surgery patients. Because the 95% confidence interval (-330 mL; +284 mL) for the treatment contrast Voluven-HAES-steril was entirely included in the predefined equivalence range (+/- 500 mL), comparable efficacy was established. Voluven interfered significantly less than HAES-steril with coagulation factor VIII levels and partial thromboplastin time postoperatively. Total amounts of red blood cells transfused were comparable between the Voluven and HAES-steril groups, but a significantly reduced need for homologous red blood cells was observed in the Voluven group. We conclude that in large-blood-loss surgery, Voluven has a comparable efficacy with HAES-steril and may reduce coagulation impairment, possibly leading to a smaller number of allogeneic blood transfusions. IMPLICATIONS: Hydroxyethyl starches are common plasma volume expanders, but may interfere with coagulation at large doses. We tested a novel hydroxyethyl starch specification (Voluven; Fresenius Kabi, Bad Homburg, Germany) which was developed to reduce hemostatic interactions while preserving its efficacy in restoring plasma volume in comparison to HAES-steril (pentastarch; Fresenius Kabi) in major orthopedic surgery.

Identification of pairwise interactions in the alpha-neurotoxin-nicotinic acetylcholine receptor complex through double mutant cycles.

alpha-Neurotoxins are potent inhibitors of the nicotinic acetylcholine receptor (nAChR), binding with high affinity to the two agonist sites located on the extracellular domain. Previous site-directed mutagenesis had identified three residues on the alpha-neurotoxin from Naja mossambica mossambica (Lys27, Arg33, and Lys47) and four residues on the mouse muscle nAChR alpha-subunit (Val188, Tyr190, Pro197, and Asp200) as contributing to binding. In this study, thermodynamic mutant cycle analysis was applied to these sets of residues to identify specific pairwise interactions. Amino acid variants of alpha-neurotoxin from N. mossambica mossambica at position 33 and of the nAChR at position 188 showed strong energetic couplings of 2-3 kcal/mol at both binding sites. Consistently smaller yet significant linkages of 1.6-2.1 kcal/mol were also observed between variants at position 27 on the toxin and position 188 on the receptor. Additionally, toxin residue 27 coupled to the receptor residues 190, 197, and 200 at the alphadelta binding site with observed coupling energies of 1.5-1.9 kcal/mol. No linkages were found between toxin residue Lys47 and the receptor residues studied here. These results provide direct evidence that the two conserved cationic residues Arg33 and Lys27, located on loop II of the toxin structure, are binding in close proximity to the alpha-subunit region between residues 188-200. The toxin residue Arg33 is closer to Val188, where it is likely stabilized by adjacent negative or aromatic residues on the receptor structure. Lys27 is positioned closer to Tyr190, Pro197, and Asp200, where it is likely stabilized through electrostatic interaction with Asp200 and/or cation/pi interactions with Tyr190.

Carbon dioxide recruitment threshold as a predictor of successful weaning in chronic obstructive pulmonary disease patients: a pilot study.

Several methods have been used to predict successful weaning and extubation among chronic obstructive pulmonary disease (COPD) patients. The objective of this study is to determine whether carbon dioxide recruitment threshold (PCO2RT) can be used as adjunct to conventional weaning parameters to predict early weaning and successful extubation. Twelve COPD patients who were ready to be extubated based on conventional weaning parameters were divided into group A (n = 7) and group B (n = 5). Group A were those patients with better weaning parameters and hence a higher probability of successful extubation as compared to group B. Carbon dioxide apnoeic threshold (PCO2AT) was obtained by hyperventilating the patient using an increment of two breaths per min until apnoea occurs. At this point, the PCO2AT or the PaCO2 during said apnoeic period was recorded. A dead space of 150 cc is then added to the circuit until the patient starts to breathe as evidenced by the sensitivity trigger indicator. The PCO2 obtained at this period is termed PCO2RT. After weaning for 30 min on a T-tube, another arterial blood gas is determined and this is called the PCO2SB or the CO2 level after 30 min on spontaneous breathing. If the PCO2SB-PCO2RT difference is high with a sensitivity of 85.71% and specificity of 100% vs sensitivity of 57.14% and specificity of 60% using the conventional weaning parameters. Thus an increase in PCO2SB at 30 min T-tube is indicative of impending respiratory pump failure and that other causes of failure to wean must be investigated.

Hepatic blood flow in humans during isoflurane-N2O and halothane-N2O anesthesia.

Hepatic blood flow (HBF) (assessed by plasma clearance and hepatic extraction of indocyanine green), cardiac index, and hepatic venous oxygen saturation were measured in patients before and after induction of anesthesia with thiopental, fentanyl, and N2O, and again during halothane (1 MAC)-N2O (n = 5) or isoflurane (1 MAC)-N2O (n = 6) anesthesia before the start of surgery. Induction of anesthesia decreased HBF and cardiac index. Before administration of volatile anesthetics, both groups had similar values of HBF, cardiac index, and hepatic venous oxygen saturation. During anesthesia cardiac index remained stable in both groups, whereas HBF increased significantly with isoflurane but did not change significantly with halothane. Hepatic venous oxygen saturation was also significantly greater during isoflurane than during halothane anesthesia. We conclude that isoflurane increases HBF in anesthetized patients and is associated with a higher hepatic venous oxygen saturation than is halothane.

[Postoperative analgesia: epidural injection of dexamethasone sodium phosphate]. / Analgésie postopératoire: injection péridurale de phosphate sodique de dexaméthasone.

Epidural administration of steroids has been suggested for the prevention of postoperative epidural fibrosis after lumbar lamino-arthrectomy. In order to assess the efficacy of this technique on pain occurring after such surgery, the demand of pentazocine during the first 24 postoperative hours was studied in 39 patients randomly assigned to two groups. Pain intensity was assessed by a five-point verbal scale (0: none; 1: poor; 2: moderate; 3: severe; 4: very severe) at five intervals (0-4, 5-8, 9-12, 13-16 and 17-24 h). The patients in group T (n = 20) did not receive any steroid, whereas those in group C (n = 19) were given, just after the end of surgery, a single dose of dexamethasone (4 mg) via an epidural lumbar catheter previously inserted by the surgeon. In group T, 18 patients required one or several intramuscular injections of pentazocine, whereas only three patients of group C (p less than 0.001) did so. Patients in group T expressed more severe pain (4 moderate, 12 severe, 3 unbearable) than those patients who had received steroids (1 moderate, 1 severe, 1 unbearable). As a consequence, they requested more pain killer (30 injections vs 8 injections, respectively; p less than 0.001) and sooner than patients of the steroid group (8 h vs 12 h; p less than 0.05). It was concluded that epidural administration of dexamethasone was helpful in preventing postoperative pain after lumbar lamino-arthrectomy.

Clinical significance of anti-nDNA antibodies in ANA-positive systemic lupus erythematosus: comparison of the Farr radioimmunoassay and the Crithidia luciliae immunofluorescent technique.

To evaluate the clinical applicability of anti-native DNA antibodies (anti-nDNA) in systemic lupus erythematosus (SLE), two conventional methods--the Farr radioimmunoassay (Farr assay) and the Crithidia luciliae immunofluorescent technique (CL-IF assay)--were compared in 180 sera of antinuclear antibody (ANA)-positive systemic lupus erythematosus (85 active and 95 inactive), 31 sera of ANA-positive non-SLE rheumatic diseases and 40 sera from healthy subjects. The results further appraised the clinical significance of anti-nDNA antibodies in the diagnosis of systemic lupus erythematosus, especially those patients with nephritis. The CL-IF assay was found less sensitive in the detection of anti-nDNA than the Farr assay. As a tool for differentiating SLE from non-SLE rheumatic diseases, the CL-IF assay is not as sensitive as the Farr assay (sensitivity of CL-IF and Farr assay = 38.3% versus 60.0%). But the CL-IF test is much more convenient and efficient in the detection of active stage SLE and lupus nephritis than the Farr assay. The efficiency of anti-nDNA tests by the CL-IF and Farr assays for diagnosing active SLE were 85.8% versus 79.6%, for lupus nephritis were 76.1% versus 64.4% and finally for both conditions were 81.7% versus 62.2%. As an index of disease activity during the course of treatment, titers of anti-nDNA antibodies by Farr assay proved much more reliable than those by Crithidia luciliae assay. For the detection of anti-nDNA antibodies, simultaneous utilization of these two methods for fresh cases and using the Farr assay alone during the course of treatment are recommended.

Continuous axillary brachial plexus block--a clinical and anatomical study.

In order to decrease both the failure rate and inadvertent arterial puncture rate that may be associated with continuous axillary brachial plexus block, a new technique of insertion of the catheter in the axilla was studied in 52 patients and in 12 fresh cadavers. With the arm abducted, externally rotated, and flexed at the elbow, an 80-mm long catheter was inserted under the skin at a site located 40-mm below the axilla and medial to the biceps muscle. Injection of lidocaine and bupivacaine produced sensory and motor blockades of the median, radial, ulnar, and musculocutaneous nerves in 98% of the patients. Arterial puncture occurred in one. The catheter was left in situ up to 9 days without complications. In the anatomical study, injection of dye and molding solutions showed that the tip of the catheter lay not in the perivascular sheath, but in a virtual cavity that was very superficial, under the skin, and surrounding the perivascular space. The technique used was safe and had a high success rate. It is particularly useful in patients undergoing long operations and in patients in whom pain would otherwise prevent postoperative physiotherapy of the upper arm.