Differential Effects of Anesthetics on Mitochondrial KATP Channel Activity and Cardiomyocyte Protection

Background: Mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels play a pivotal role in mediating cardiac preconditioning. The effects of intravenous anesthetics on this protective channel have not been investigated so far, but would be of importance with respect to experimental as well as clinical medicine.

Methods: Live cell microscopy was used to visualize and measure autofluorescence of flavoproteins, a direct reporter of mitoKATP channel activity, in response to the direct and highly selective mitoKATP channel opener diazoxide, or to diazoxide following exposure to various anesthetics commonly used in experimental and clinical medicine. A cellular model of ischemia with subsequent hypoosmolar trypan blue staining served to substantiate the effects of the anesthetics on mitoKATP channels with respect to myocyte viability.

Results: Diazoxide-induced mitoKATP channel opening was significantly inhibited by the anesthetics R-ketamine, and the barbiturates thiopental and pentobarbital. Conversely, urethane, 2,2,2-trichloroethanol (main metabolite of [alpha]-chloralose and chloral hydrate), and the opioid fentanyl potentiated the channel-opening effect of diazoxide, which was abrogated by coadministration of chelerythrine, a specific protein kinase C inhibitor. S-ketamine, propofol, xylazine, midazolam, and etomidate did not affect mitoKATP channel activity. The significance of these modulatory effects of the anesthetics on mitoKATP channel activity was substantiated in a cellular model of simulated ischemia, where diazoxide-induced cell protection was mitigated by R-ketamine and the barbiturates, while urethane, 2,2,2-trichloroethanol, and fentanyl potentiated myocyte protection.     

Diagnosis of Ewing sarcoma of the thoracic spine--differential diagnostic difficulties

Spinal Ewing's sarcomas are rare and cause problems in differential diagnosis. The radiologic, nuclear medicine and CT findings in two children with histologically proven Ewing's sarcoma are presented and problems in differential diagnosis discussed. Biopsy should be done early.     

Cerebrospinal Fluid Density Influences Extent of Plain Bupivacaine Spinal Anesthesia

Background: The attempts to explain the unpredictability of extent of spinal block provided by plain local anesthetic solutions have resulted in many clinical reports; however, causes of this uncertainty are as yet unknown. Recently, normal values of the human cerebrospinal fluid densities have been studied showing important interindividual variations, especially between females and males. The current study was designed to evaluate as primary endpoint the influence of cerebrospinal fluid density values on the extent of spinal block with plain bupivacaine. The ancillary endpoints were search of factors explaining the interindividual differences in cerebrospinal fluid density values reported and determination of the relation between upper extent and regression of spinal anesthesia.

Methods: Sixty-four consecutive patients undergoing peripheral orthopedic surgery with spinal block were enrolled. Spinal anesthesia was performed in the lateral decubitus position with the operated side upward. Two milliliters of cerebrospinal fluid was sampled before injection of 3 ml plain bupivacaine 0.5%. The patient was immediately turned supine and remained in the horizontal position until the end of the study. Maximal sensory block level and time to sensory regression to L4 were determined for each patient enrolled. Cerebrospinal fluid and bupivacaine densities as well as cerebrospinal proteins, glucose, sodium, and chloride concentrations were measured.

Results: A highly significant correlation between cerebrospinal fluid density and maximal sensory block level was found (P = 0.0004). However, this correlation was poorly predictive (R2 = 0.37). Cerebrospinal fluid density, proteins, and glucose concentrations were significantly higher in men than in women: 1.000567 +/- 0.000091 versus 1.000501 +/- 0.000109 g/ml (P = 0.014), 0.46 +/- 0.18 versus 0.32 +/- 0.13 g/l (P = 0.001), and 3.27 +/- 0.7 versus 2.93 +/- 0.5 mm (P = 0.023), respectively. A highly significant (P = 0.0004) and predictive (R2 = 0.73) inverse correlation was found between maximal upper sensory extent and sensory regression to L4.     

Growth hormone benefits children with 18q deletions

Most individuals with constitutional deletions of chromosome 18q have developmental delays, dysmyelination of the brain, and growth failure due to growth hormone deficiency. We monitored the effects of growth hormone treatment by evaluating 23 individuals for changes in growth, nonverbal intelligence quotient (nIQ), and quantitative brain MRI changes. Over an average of 37 months, the treated group of 13 children had an average nIQ increase of 17 points, an increase in height standard deviation score of 1.7, and significant change in T1 relaxation times in the caudate and frontal white matter. Cognitive changes of this magnitude are clinically significant and are anticipated to have an effect on the long-term outcomes for the treated individuals.     

P-selectin inhibition suppresses muscle regeneration following injury

This investigation sought to determine if P-selectin-mediated mechanisms contributed to macrophage localization in damaged muscle, an essential process for muscle regeneration. Mice were injected intravenously (i.v.) with soluble P-selectin glycoprotein ligand-1 (sPSGL-1) at 5, 50, or 200 microg/mouse or with 100 microl vehicle alone, and then, lengthening contractions were induced in hindlimb plantar-flexor muscles. The contractions caused fiber damage in soleus muscles, with maximal invasion by CD11b+ mononuclear cells at 24 h post-injury and substantial accumulation of CD11b+ mononuclear cells in the extracellular matrix up to 7 days post-injury. sPSGL-1 treatment caused a dose-dependent decrease in the number of regenerating fibers (P=0.021), as determined by developmental myosin heavy chain (dMHC) expression. This expression was reduced 93% at 7 days post-injury by the highest dose of sPSGL-1, which had no significant influence on intrafiber or extracellular accumulation of cells expressing CD11b, a general marker for phagocytic cells. Additional mice were injected i.v. with 20 microg anti-P-selectin or isotype-control immunoglobulin G and were then subjected to lengthening contractions as before. At 7 days post-injury, soleus muscles from anti-P-selectin-treated mice contained 48% fewer mononuclear cells that bound ER-BMDM1 (P=0.019), a marker for mature macrophages and dendritic cells, and 84% fewer fibers expressing dMHC (P = 0.006), compared with muscles from isotype-injected, control mice. The number of CD11b+ cells was not significantly different between groups. The results are consistent with the concept that P-selectin is involved in the recruitment, maturation, and/or activation of cells that are critical for muscle fiber regeneration.     

Obesity and asthma, what are the links?

PURPOSE OF REVIEW: Obesity is a major cause of morbidity accounting for approximately 300 000 deaths each year and about 7% of the health care budget with an economic impact greater than US dollar 100 billion annually in the United States. Obesity and its sequelae such as cardiovascular disease, diabetes, arthritis or cancer have been on the rise over the last decades. The parallel time trend with an increasing prevalence of asthma has induced a lively debate about a potential link between both conditions. RECENT FINDINGS: A number of prospective studies have shown that weight gain can antedate the development of asthma. Effect modification by sex may occur as some studies have shown effects of body mass index on asthma only among females. However, sex differences are not consistent. Several hypotheses have been proposed to explain the epidemiological associations including alterations in airway mechanics and immune responses, hormonal influences and genetic factors. SUMMARY: There is evidence that obesity and overweight are associated with the development of asthma. Yet, the mechanisms underlying this relation are unclear. Weight reduction among asthmatic patients can result in improvements of lung function demonstrating the potential clinical impact of the findings.     

Zur Frage der Hepatitishäufigkeit nach Austauschtransfusionen bei Neugeborenen

Zusammenfassung 63 Neugeborene wurden nach insgesamt 93 Austauschtransfusionen während eines Zeitraumes bis zu 6 Monaten auf das Risiko einer Transfusionshepatitis untersucht. Dabei wurden zusätzlich zur klinischen Beobachtung die Transaminasen und der Nachweis des Australia-Antigens als Kontrollkriterien gewertet. Klinisch wurde in keinem Fall eine Hepatitis beobachtet, eine SGPT-Erhöhung nach 3 Monaten in einem Fall könnte für eine anikterische Hepatitis sprechen. Ein Australia-Antigen-Nachweis konnte bei negativen Ausgangsbefunden bei Spendern und Empfängern nirgends in den Nachuntersuchungen erbracht werden. Demnach ist das Hepatitisrisiko einer Austauschtransfusion bei Wahrung der heute üblichen Spenderauslese praktisch nicht zu befürchten.     

Spatiotemporal analysis of event-related potentials to upright, inverted, and contrast-reversed faces: effects on encoding and recognition

In an n-back face recognition task where subjects responded to repeated stimuli, ERPs were recorded to upright, inverted, and contrast-reversed faces. The effects of inversion and contrast reversal on face encoding and recognition were investigated using the multivariate spatiotemporal partial least squares (PLS) analysis. The configural manipulations affected early processing (100-200 ms) at posterior sites: Inversion effects were parietal and lateral, whereas contrast-reversal effects were more occipital and medial, suggesting different underlying generators. A later reactivation of face processing areas was unique to inverted faces, likely due to processing difficulties. PLS also indicated that the "old-new" repetition effect was maximal for upright faces and likely involved frontotemporal areas. Marked processing differences between inverted and contrast-reversed faces were seen, but these effects were similar at encoding and recognition.     

CD34+ Cord Blood Cell-Transplanted Rag2−/− γc−/− Mice as a Model for Epstein-Barr Virus Infection

Recent studies suggest that Epstein-Barr virus (EBV) can infect naïve B cells, driving them to differentiate into resting memory B cells via the germinal center reaction. This hypothesis has been inferred from parallels with the biology of normal B cells but has never been proven experimentally. Rag2^−/− γ_c^−/− mice that were transplanted with human CD34⁺ cord blood cells as newborns were recently shown to develop human B, T, and dendritic cells, constituting lymphoid organs in situ. Here we used this model to better define the strategy of EBV infection of human B cells in vivo and to compare this model system with different conditions of EBV infection in humans. Our results support the model of EBV persistence in vivo in cases that were characterized by follicular hyperplasia and a relatively normal CD4⁺ and CD8⁺ T-cell distribution. Intriguingly, in cases that were characterized by nodular and diffuse proliferation with a preponderance of CD8⁺ T cells, similar to infectious mononucleosis, EBV still infects naïve B cells but also induces clonal expansion and ongoing somatic mutations without germinal center reactions. Our results reveal different strategies of EBV infection in B cells that possibly result from variations in the host immune response. Future experiments might allow understanding of the mechanisms responsible for persistent EBV infection and provide targets for more highly tailored therapeutic interventions.