bluuebunny/crossref_metadata_2025 huggingface dataset:
24-Hour national dietary survey data: how do we interpret them most effectively?
Authors: Mackerras Dorothy , Rutishauser Ingrid
Published: October 2005

Objective

To illustrate the effect of common mistakes when using 24-hour national dietary survey data to estimate the prevalence of inadequate nutrient intakes.

Design

Raw data on nutrient intake from the Australian 1995 National Nutrition Survey were adjusted for within-person variance using standard techniques and corrected for underreporting using the criteria of Goldberg et al. The distributions for six nutrients were compared with current dietary reference values from the UK, USA and Australia.

Setting

A national sample of the Australian population with a 61.4% response rate.

Results

Adjusting for within-person variance reduced the range of nutrient intakes to 66–80% of the raw data range and the proportion with intakes below the estimated average requirement (EAR) by up to 20%. Excluding underreporters further reduced the proportion below the EAR by up to 10%. Using the dietary reference values from different countries also resulted in some markedly different estimates. For example, the prevalence of low folate intakes ranged from <1 to 92% for adult women depending on the reference used. Except for vitamin A and protein, the prevalence of low intakes was invariably higher for women than for men.

Conclusions

Estimates of the prevalence of low nutrient intakes based on raw 24-hour survey data are invariably misleading. However, even after adjustment for within-person variance and underreporting, estimates of the prevalence of low nutrient intakes may still be misleading unless interpreted in the light of the reference criteria used and supported by relevant biochemical and physiological measures of nutritional status.
Type of kindergarten and other potential determinants of overweight in pre-school children
Authors: Rapp K , Schick KH , Bode H , Weiland SK
Published: October 2005

Objective

The study aimed to assess the relationship of various types of kindergarten differing in length of care and food availability with the development of overweight in pre-school children.

Design, setting and subjects

A cross-sectional study was carried out in 2002 in Stuttgart, Germany, as part of the school entrance examination. Height and weight of 2140 children (participation 70.2%) were measured and information on type of kindergarten and other potential determinants of overweight was collected by a parental questionnaire. Change in relative body mass index (BMI) position between the ages of 4 and 6 years was assessed using medical records.

Results

The prevalence of overweight or change in relative BMI position did not differ according to the type of kindergarten. For the prevalence of overweight in German children, adjusted odds ratios (OR) comparing institutions that open only in the morning with those opening in the morning and afternoon or for the full day were 0.86 (95% confidence interval (CI) 0.40, 1.83) and 0.63 (95% CI 0.25, 1.58), respectively. Parental BMI and duration of television watching were positively associated, and maternal educational status and duration of breast-feeding were negatively associated, with overweight and/or change in relative BMI position. The prevalence of overweight was substantially higher among non-German than among German children (adjusted OR 2.17 (95% CI 1.53, 3.07)).

Conclusions

These data show no association between different types of kindergarten and the development of overweight in early childhood. Duration of television watching and breast-feeding, as well as the relatively high prevalence of overweight in ethnic minorities, deserve further attention.
AIDS, drought, and child malnutrition in southern Africa
Authors: Mason John B , Bailes Adam , Mason Karen E , Yambi Olivia , Jonsson Urban , Hudspeth Claudia , Hailey Peter , Kendle Andrea , Brunet Dominique , Martel Pierre
Published: October 2005

Objective

To investigate trends in child malnutrition in six countries in southern Africa, in relation to the HIV epidemic and drought in crop years 2001/2 and 2002/3.

Design

Epidemiological analysis of sub-national and national surveys with related data.

Setting

Data from Lesotho, Malawi, Mozambique, Swaziland, Zambia and Zimbabwe, compiled and analysed under UNICEF auspices.

Subjects

Secondary data: children 0–5 years for weight-for-age; HIV prevalence data from various sources especially antenatal clinic surveillance.

Results

Child nutritional status as measured by prevalence of underweight deteriorated from 2001 onwards in all countries except Lesotho, with very substantial increases in some provinces/districts (e.g. from 5 to 20% in Maputo (Mozambique, 1997–2002), 17 to 32% in Copperbelt (Zambia, 1999–2001/2) and 11 to 26% in Midlands province (Zimbabwe, 1999–2002)). Greater deterioration in underweight occurred in better-off areas. Areas with higher HIV/AIDS prevalences had (so far) lower malnutrition rates (and infant mortality rates), presumably because more modern areas – with greater reliance on trade and wage employment – have more HIV/AIDS. Areas with higher HIV/AIDS showed more deterioration in child nutrition. A significant area-level interaction was found of HIV/AIDS with the drought period, associated with particularly rapid deterioration in nutritional status.

Conclusions

First, the most vulnerable may be households in more modern areas, nearer towns, to whom resources need to be directed. Second, the causes of this vulnerability need to be investigated. Third, HIV/AIDS amplifies the effect of drought on nutrition, so rapid and effective response will be crucial if drought strikes again. Fourth, expanded nutritional surveillance is now needed to monitor and respond to deteriorating trends. Finally, with or without drought, new means are needed of bringing help, comfort and assistance to the child population.
Dietary intake and the insulin-like growth factor system: effects of migration in two related populations in India and Britain with markedly different dietary intake
Authors: Heald AH , Sharma R , Anderson SG , Vyas A , Siddals K , Patel J , Bhatnagar D , Prabharkaran D , Rudenski A , Hughes E , Durrington P , Gibson JM , Cruickshank JK
Published: October 2005

Background

The insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease.

Objective

We report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate.

Design, subjects and setting

Dietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n = 205) compared with people still resident in the same villages of origin in India (n = 246). Fasting IGF-I, IGF-binding protein (IGFBP)-1 and IGFBP-3, insulin and glucose (0 and 2-hour) were measured.

Results

Total energy and total fat intake were higher in UK migrants, as were IGFBP-3 and IGF-I (mean (95% confidence interval): 145.9 (138.1–153.6) vs. 100.9 (94.6–107.3) ng ml-1; F = 76.6, P < 0.001). IGFBP-1 was lower in UK migrants (29.5 (25.9–33.0) vs. 56.5 (50.6–62.5) μg l-1; F = 48.4, P < 0.001). At both sites, IGF-I correlated positively with total energy (Spearman's ρ = 0.45, P < 0.001) and total fat (ρ = 0.44, P < 0.001) as did IGFBP-3 with total energy (ρ = 0.21, P < 0.05) and fat (ρ = 0.26, P < 0.001). Conversely, in Indian Gujaratis, IGFBP-1 fell with increasing total energy (ρ = -0.27, P < 0.001) and fat intake (ρ = -0.26, P < 0.01) but not in UK Gujaratis. Multiple linear regression modelling showed that increasing quartiles of fat intake were associated with higher IGF-I (β = 0.42, P = 0.007) independent of age, body mass index, plasma insulin, fatty acids and 2-hour glucose.

Conclusion

In these genetically similar groups, migration to the UK and adoption of a different diet is associated with marked changes in the IGF system, suggesting that environmental factors profoundly modulate serum concentrations and actions of IGFs.
Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection
Authors: Glass William G. , Lim Jean K. , Cholera Rushina , Pletnev Alexander G. , Gao Ji-Liang , Murphy Philip M.
Published: October 2005

The molecular immunopathogenesis of West Nile virus (WNV) infection is poorly understood. Here, we characterize a mouse model for WNV using a subcutaneous route of infection and delineate leukocyte subsets and immunoregulatory factors present in the brains of infected mice. Central nervous system (CNS) expression of the chemokine receptor CCR5 and its ligand CCL5 was prominently up-regulated by WNV, and this was associated with CNS infiltration of CD4+ and CD8+ T cells, NK1.1+ cells and macrophages expressing the receptor. The significance of CCR5 in pathogenesis was established by mortality studies in which infection of CCR5−/− mice was rapidly and uniformly fatal. In the brain, WNV-infected CCR5−/− mice had increased viral burden but markedly reduced NK1.1+ cells, macrophages, and CD4+ and CD8+ T cells compared with WNV-infected CCR5+/+ mice. Adoptive transfer of splenocytes from WNV-infected CCR5+/+ mice into infected CCR5−/− mice increased leukocyte accumulation in the CNS compared with transfer of splenocytes from infected CCR5−/− mice into infected CCR5−/− mice, and increased survival to 60%, the same as in infected CCR5+/+ control mice. We conclude that CCR5 is a critical antiviral and survival determinant in WNV infection of mice that acts by regulating trafficking of leukocytes to the infected brain.
The Scurfy mutation of FoxP3 in the thymus stroma leads to defective thymopoiesis
Authors: Chang Xing , Gao Jian Xin , Jiang Qi , Wen Jing , Seifers Nick , Su Lishan , Godfrey Virginia L. , Zuo Tao , Zheng Pan , Liu Yang
Published: October 2005

The Scurfy mutation of the FoxP3 gene (FoxP3sf) in the mouse and analogous mutations in human result in lethal autoimmunity. The mutation of FoxP3 in the hematopoietic cells impairs the development of regulatory T cells. In addition, development of the Scurfy disease also may require mutation of the gene in nonhematopoietic cells. The T cell–extrinsic function of FoxP3 has not been characterized. Here we show that the FoxP3sf mutation leads to defective thymopoiesis, which is caused by inactivation of FoxP3 in the thymic stromal cells. FoxP3 mutation also results in overexpression of ErbB2 in the thymic stroma, which may be involved in defective thymopoiesis. Our data reveal a novel T cell–extrinsic function of FoxP3. In combination, the T cell–intrinsic and –extrinsic defects provide plausible explanation for the severity of the autoimmune diseases in the scurfy mice and in patients who have immunodysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome.
Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis
Authors: Mariathasan Sanjeev , Weiss David S. , Dixit Vishva M. , Monack Denise M.
Published: October 2005

Francisella tularensis is a highly infectious gram-negative coccobacillus that causes the zoonosis tularemia. This bacterial pathogen causes a plague-like disease in humans after exposure to as few as 10 cells. Many of the mechanisms by which the innate immune system fights Francisella are unknown. Here we show that wild-type Francisella, which reach the cytosol, but not Francisella mutants that remain localized to the vacuole, induced a host defense response in macrophages, which is dependent on caspase-1 and the death-fold containing adaptor protein ASC. Caspase-1 and ASC signaling resulted in host cell death and the release of the proinflammatory cytokines interleukin (IL)-1β and IL-18. F. tularensis–infected caspase-1– and ASC-deficient mice showed markedly increased bacterial burdens and mortality as compared with wild-type mice, demonstrating a key role for caspase-1 and ASC in innate defense against infection by this pathogen.
CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor–β–dependent manner
Authors: Ghiringhelli François , Ménard Cédric , Terme Magali , Flament Caroline , Taieb Julien , Chaput Nathalie , Puig Pierre E. , Novault Sophie , Escudier Bernard , Vivier Eric , Lecesne Axel , Robert Caroline , Blay Jean-Yves , Bernard Jacky , Caillat-Zucman Sophie , Freitas Antonio , Tursz Thomas , Wagner-Ballon Orianne , Capron Claude , Vainchencker William , Martin François , Zitvogel Laurence
Published: October 2005

Tumor growth promotes the expansion of CD4+CD25+ regulatory T (T reg) cells that counteract T cell–mediated immune responses. An inverse correlation between natural killer (NK) cell activation and T reg cell expansion in tumor-bearing patients, shown here, prompted us to address the role of T reg cells in controlling innate antitumor immunity. Our experiments indicate that human T reg cells expressed membrane-bound transforming growth factor (TGF)–β, which directly inhibited NK cell effector functions and down-regulated NKG2D receptors on the NK cell surface. Adoptive transfer of wild-type T reg cells but not TGF-β−/− T reg cells into nude mice suppressed NK cell–mediated cytotoxicity, reduced NKG2D receptor expression, and accelerated the growth of tumors that are normally controlled by NK cells. Conversely, the depletion of mouse T reg cells exacerbated NK cell proliferation and cytotoxicity in vivo. Human NK cell–mediated tumor recognition could also be restored by depletion of T reg cells from tumor-infiltrating lymphocytes. These findings support a role for T reg cells in blunting the NK cell arm of the innate immune system.
Fat meets the cholinergic antiinflammatory pathway
Authors: Tracey Kevin J.
Published: October 2005

The cholinergic antiinflammatory pathway is a neural mechanism that is controlled by the vagus nerve and inhibits local cytokine release, thereby preventing the damaging effects of cytokine overproduction. A new study now shows that dietary fat can activate this pathway, a finding that may help explain the immune system's failure to react to food antigens and commensal bacteria. Here we discuss this new data and its potential implications for dietary intervention in the treatment of inflammatory diseases.
Detection of Consciousness by Electroencephalogram and Auditory Evoked Potentials
Authors: Schneider Gerhard , Hollweck Regina , Ningler Michael , Stockmanns Gudrun , Kochs Eberhard F.
Published: October 2005

Background

A set of electroencephalographic and auditory evoked potential (AEP) parameters should be identified that allows separation of consciousness from unconsciousness (reflected by responsiveness/unresponsiveness to command).

Methods

Forty unpremedicated patients received anesthesia with remifentanil and either sevoflurane or propofol. With remifentanil infusion (0.2 microg . kg . min), patients were asked every 30 s to squeeze the investigator's hand. Sevoflurane or propofol was given until loss of consciousness. After intubation, propofol or sevoflurane was stopped until patients followed the command (return of consciousness). Thereafter, propofol or sevoflurane was started again (loss of consciousness), and surgery was performed. Return of consciousness was observed after surgery. The electroencephalogram and AEP from immediately before and after the transitions were selected. Logistic regression was calculated to identify models for the separation between consciousness and unconsciousness. For the top 10 models, 1,000-fold cross-validation was performed. Backward variable selection was applied to identify a minimal model. Prediction probability was calculated. The digitized electroencephalogram was replayed, and the Bispectral Index was measured and accordingly analyzed.

Results

The best full model (prediction probability 0.89) contained 15 AEP and 4 electroencephalographic parameters. The best minimal model (prediction probability 0.87) contained 2 AEP and 2 electroencephalographic parameters (median frequency of the amplitude spectrum from 8-30 Hz and approximate entropy). The prediction probability of the Bispectral Index was 0.737.

Conclusions

A combination of electroencephalographic and AEP parameters can be used to differentiate between consciousness and unconsciousness even in a very challenging data set. The minimal model contains a combination of AEP and electroencephalographic parameters and has a higher prediction probability than Bispectral Index for the separation between consciousness and unconsciousness.
High-frequency Components of Auditory Evoked Potentials Are Detected in Responsive but Not in Unconscious Patients
Authors: Scheller Bertram , Schneider Gerhard , Daunderer Michael , Kochs Eberhard F. , Zwissler Bernhard
Published: October 2005

Background

The dose-dependent suppression of midlatency auditory evoked potentials by general anesthetics has been proposed to measure depth of anesthesia. In this study, perioperatively recorded midlatency auditory evoked potentials were analyzed in a time-frequency space to identify significant changes induced by general anesthesia.

Methods

Perioperatively recorded auditory evoked potentials of 19 patients, recorded at varying levels of anesthesia, were submitted to a multiscale analysis using the wavelet analysis. Energy contents of the signal were calculated in frequency bands 0-57.1 Hz, 57.1-114.3 Hz, 114.3-228.6 Hz, and 228.6-457.1 Hz. A Friedman test and a Dunn multiple comparisons test were performed to identify significant differences.

Results

Statistical evaluation showed a highly significant decrease of the wavelet energies for the frequency bands 57.1-114.3 Hz (P < 0.0001), 114.3-228.6 Hz (P < 0.0001), and 228.6-457.1 Hz (P < 0.0001) for the measuring points representing deep general anesthesia. This decrease is accompanied by a decrease in the wavelet energy of the frequency band 0-57.1 Hz of no statistical significance (P = 0.021) (level of significance set to P = 0.01). The changes are most prominent in the poststimulus interval between 10 and 30 ms.

Conclusions

This study describes the presence of high-frequency components of the auditory evoked potential. The amount of these components is higher during responsiveness when compared to unconsciousness. Temporal localization of the high-frequency components within the auditory evoked potential shows that they represent a response to the auditory stimulus. Further studies are required to identify the source of these high-frequency components.
What Is the Driving Performance of Ambulatory Surgical Patients after General Anesthesia?
Authors: Chung Frances , Kayumov Leonid , Sinclair David R. , Edward Reginald , Moller Henry J. , Shapiro Colin M.
Published: October 2005

Background

Ambulatory surgical patients are advised to refrain from driving for 24 h postoperatively. However, currently there is no strong evidence to show that driving skills and alertness have resumed in patients by 24 h after general anesthesia. The purpose of this study was to determine whether impaired driver alertness had been restored to normal by 2 and 24 h after general anesthesia in patients who underwent ambulatory surgery.

Methods

Twenty patients who underwent left knee arthroscopic surgery were studied. Their driving simulation performance, electroencephalographically verified parameters of sleepiness, subjective assessment of sleepiness, fatigue, alertness, and pain were measured preoperatively and 2 and 24 h postoperatively. The same measurements were performed in a matched control group of 20 healthy individuals.

Results

Preoperatively, patients had significantly higher attention lapses and lower alertness levels versus normal controls. Significantly impaired driving skills and alertness, including longer reaction time, higher occurrence of attention lapses, and microsleep intrusions, were found 2 h postoperatively versus preoperatively. No significantly differences were found in any driving performance parameters or electroencephalographically verified parameters 24 h postoperatively versus preoperatively.

Conclusions

Patients showed lower alertness levels and impaired driving skills preoperatively and 2 h postoperatively. Based on driving simulation performance and subjective assessments, patients are safe to drive 24 h after general anesthesia.
Oxygen and Carbon Dioxide in the Cerebral Circulation during Progression to Brain Death
Authors: Stocchetti Nino , Zanier Elisa Roncati , Nicolini Rita , Faegersten Emelie , Canavesi Katia , Conte Valeria , Gattinoni Luciano
Published: October 2005

Background

The authors propose that for a moderate reduction of perfusion during progressive irreversible ischemia, oxygen extraction increases to maintain aerobic metabolism, and arteriojugular oxygen difference (AJDo2) increases. Because of reduced carbon dioxide washout, venoarterial difference in carbon dioxide tension (DPco2) increases, with no change in the DPco2/AJDo2 ratio. With further reduction of cerebral perfusion, the aerobic metabolism will begin to decrease, AJDo2 will decrease while DPco2 will continue to increase, and the ratio will increase. When brain infarction develops, the metabolism will be abated, no oxygen will be consumed, and no carbon dioxide will be produced.

Methods

The authors studied 12 patients with acute cerebral damage that evolved to brain death and collected intermittent arterial and jugular blood samples.

Results

Four patterns were observed: (1) AJDo2 of 4.1 +/- 0.7 vol%, DPco2 of 6.5 +/- 1.9 mmHg, and a ratio of 1.55 +/- 0.3 with cerebral perfusion pressure of 62.5 +/- 13.4 mmHg; (2) a coupled increase of AJDo2 (5.8 +/- 0.7 vol%) and DPco2 (10.1 +/- 1.0 mmHg) with no change in ratio (1.92 +/- 0.14) and cerebral perfusion pressure (57.9 +/- 5.8 mmHg); (3) AJDo2 of 4.7 +/- 0.4 vol% with an increase in DPco2 (11.8 +/- 1 mmHg) and correspondingly higher ratio (2.7 +/- 0.2); in this phase, cerebral perfusion pressure was 39.7 +/- 10.5 mmHg; (4) immediately before diagnosis of brain death (cerebral perfusion pressure, 17 +/- 10.4 mmHg), there was a decrease of AJDo2 (1.1 +/- 0.1 vol%) and of DPco2 (5.3 +/- 0.6 mmHg) with a further ratio increase (5.1 +/- 0.8).

Conclusions

Until compensatory mechanisms are effective, AJDo2 and DPco2 remain coupled. However, when the brain's ability to compensate for reduced oxygen delivery is exceeded, the ratio of DPco2 to AJDo2 starts to increase.
Effect of Nutritional Status on Oxidative Stress in an Ex Vivo Perfused Rat Liver
Authors: Stadler Michaela , Nuyens Vincent , Seidel Laurence , Albert Adelin , Boogaerts Jean G.
Published: October 2005

Background

Normothermic ischemia-reperfusion is a determinant in liver injury occurring during surgical procedures, ischemic state, and multiple organ failure. The preexisting nutritional status of the liver might contribute to the extent of tissue injury and primary nonfunction. The aim of this study was to determine the role of starvation on hepatic ischemia-reperfusion injury in normal rat livers.

Methods

Rats were randomly divided into two groups: one had free access to food, the other was fasted for 16 h. The portal vein was cannulated, and the liver was removed and perfused in a closed ex vivo system. Two modes of perfusion were applied in each series of rats, fed and fasting. In the ischemia-reperfusion mode, the experiment consisted of perfusion for 15 min, warm ischemia for 60 min, and reperfusion during 60 min. In the nonischemia mode, perfusion was maintained during the 135-min study period. Five rats were included in each experimental condition, yielding a total of 20 rats. Liver enzymes, potassium, glucose, lactate, free radicals, i.e., dienes and trienes, and cytochrome c were analyzed in perfusate samples. The proportion of glycogen in hepatocytes was determined in tissue biopsies.

Results

Transaminases, lactate dehydrogenase, potassium, and free radical concentrations were systematically higher in fasting rats in both conditions, with and without ischemia. Cytochrome c was higher after reperfusion in the fasting rats. Glucose and lactate concentrations were greater in the fed group. The glycogen content decreased in both groups during the experiment but was markedly lower in the fasting rats.

Conclusions

In fed rats, liver injury was moderate, whereas hepatocytes integrity was notably impaired both after continuous perfusion and warm ischemia in fasting animals. Reduced glycogen store in hepatocytes may explain reduced tolerance.
Isoflurane Postconditioning Prevents Opening of the Mitochondrial Permeability Transition Pore through Inhibition of Glycogen Synthase Kinase 3β
Authors: Feng Jianhua , Lucchinetti Eliana , Ahuja Preeti , Pasch Thomas , Perriard Jean-Claude , Zaugg Michael
Published: October 2005

Background

Postischemic administration of volatile anesthetics activates reperfusion injury salvage kinases and decreases myocardial damage. However, the mechanisms underlying anesthetic postconditioning are unclear.

Methods

Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. Anesthetic postconditioning was induced by 15 min of 2.1 vol% isoflurane (1.5 minimum alveolar concentration) administered at the onset of reperfusion. In some experiments, atractyloside (10 microm), a mitochondrial permeability transition pore (mPTP) opener, and LY294002 (15 microm), a phosphatidylinositol 3-kinase inhibitor, were coadministered with isoflurane. Western blot analysis was used to determine phosphorylation of protein kinase B/Akt and its downstream target glycogen synthase kinase 3beta after 15 min of reperfusion. Myocardial tissue content of nicotinamide adenine dinucleotide served as a marker for mPTP opening. Accumulation of MitoTracker Red 580 (Molecular Probes, Invitrogen, Basel, Switzerland) was used to visualize mitochondrial function.

Results

Anesthetic postconditioning significantly improved functional recovery and decreased infarct size (36 +/- 1% in unprotected hearts vs. 3 +/- 2% in anesthetic postconditioning; P < 0.05). Isoflurane-mediated protection was abolished by atractyloside and LY294002. LY294002 inhibited isoflurane-induced phosphorylation of protein kinase B/Akt and glycogen synthase kinase 3beta and opened mPTP as determined by nicotinamide adenine dinucleotide measurements. Atractyloside, a direct opener of the mPTP, did not inhibit phosphorylation of protein kinase B/Akt and glycogen synthase kinase 3beta by isoflurane but reversed isoflurane-mediated cytoprotection. Microscopy showed accumulation of the mitochondrial tracker in isoflurane-protected functional mitochondria but no staining in mitochondria of unprotected hearts.

Conclusions

Anesthetic postconditioning by isoflurane effectively protects against reperfusion damage by preventing opening of the mPTP through inhibition of glycogen synthase kinase 3beta.
Effect of Halothane on Gαi-3and Its Coupling to the M2Muscarinic Receptor
Authors: Jin Fang , Wang Shuyan , Spencer Joshua D. , Penheiter Sumedha G. , Streiff John H. , Penheiter Alan R. , Warner David O. , Jones Keith A.
Published: October 2005

Background

Halothane is an effective bronchodilator and inhibits airway smooth muscle contraction in part by inhibiting intracellular signaling pathways activated by the M2 muscarinic receptor and its cognate inhibitory heterotrimeric guanosine-5'-triphosphate (GTP)-binding protein (G protein), Gi. This study hypothesized that halothane inhibits nucleotide exchange at the alpha isoform-3 subunit of Gi (Galphai-3), but only when regulated by the M2 muscarinic receptor.

Methods

GTP hydrolysis by Galphai-3 and the Galphai-3beta1gamma2HF heterotrimer expressed in Spodoptera frugiperda cells was measured using a phosphohydrolase assay with [gammaPi]-labeled GTP. Anesthetic binding to Galphai-3 was measured by saturation transfer difference nuclear magnetic resonance spectroscopy. Galphai-3 nucleotide exchange was measured in crude membranes prepared from COS-7 cells transiently coexpressing the M2 muscarinic receptor and Galphai-3. A radioactive analog of GTP, [S]GTPgammaS, was used as a reporter for Galphai-3 nucleotide exchange.

Results

Although spectroscopy demonstrated halothane binding to Galphai-3, this binding had no effect on [gammaPi]-labeled GTP hydrolysis by the Galphai-3beta1gamma2HF heterotrimer expressed in Spodoptera frugiperda cells, nor basal Galphai-3 nucleotide exchange measured in crude membranes when the muscarinic receptor agonist acetylcholine was omitted from the assay. Conversely, halothane caused a concentration-dependent inhibition of Galphai-3 nucleotide exchange with acetylcholine included in the assay.

Conclusion

These data indicate that despite halothane binding to Galphai-3, halothane has no direct inhibitory effect on the intrinsic activity of the Galphai-3beta1gamma2HF heterotrimer but inhibits M2 muscarinic receptor regulation of the heterotrimer. This novel effect is consistent with the ability of halothane to inhibit airway smooth muscle contraction and bronchoconstriction induced by acetylcholine.
Dural Puncture with a 27-Gauge Whitacre Needle as Part of a Combined Spinal–Epidural Technique Does Not Improve Labor Epidural Catheter Function
Authors: Thomas John A. , Pan Peter H. , Harris Lynne C. , Owen Medge D. , D’Angelo Robert
Published: October 2005

Background

This prospective, double-blind, randomized study was designed to examine whether the combined spinal-epidural technique without subarachnoid drug administration improved epidural catheter function when compared with the traditional epidural technique.

Methods

After institutional review board approval and informed consent, 251 healthy laboring parturients were randomly assigned to either group DP (combined spinal-epidural technique with 27-gauge Whitacre needle dural puncture but without subarachnoid drug administration) or group NoDP (traditional epidural technique). Patient-controlled epidural analgesia was initiated with 0.11% bupivacaine and 2 microg/ml fentanyl. Top-up doses in 5-ml increments of 0.25% bupivacaine were administered if needed. Previous power analysis revealed that a sample size of 108 patients/group was needed to show a clinically useful reduction of the catheter manipulation rate from 32% to 15%.

Results

In groups DP and NoDP, 107 and 123 evaluable patients, respectively, completed the study. Demographics and outcome variables measured, including epidural catheter manipulation and replacement rate, sacral sparing, unilateral block, number of top-up doses, average hourly epidural drug usage, highest sensory blockade level, and labor analgesia quality, were not different between groups. A subgroup of 18 patients without cerebral spinal fluid return during dural puncture had a higher catheter replacement rate than those of groups DP and NoDP, but it did not reach statistical significance.

Conclusions

Dural puncture with a 27-gauge Whitacre needle without subarachnoid drug administration during combined spinal-epidural labor analgesia did not improve epidural labor analgesia quality or reduce catheter manipulation or replacement rate when compared with a traditional epidural technique.
Physiologic and Antinociceptive Effects of Intrathecal Resiniferatoxin in a Canine Bone Cancer Model
Authors: Brown Dorothy Cimino , Iadarola Michael J. , Perkowski Sandra Z. , Erin Hardam , Shofer Frances , Laszlo Karai J. , Olah Zoltan , Mannes Andrew J.
Published: October 2005

Background

Resiniferatoxin is a potent capsaicin analog. Intrathecal administration leads to selective, prolonged opening of the transient receptor potential V1 ion channel, which is localized mainly to C-fiber primary afferent nociceptive sensory neurons. Following work in laboratory animals, the authors explored the use of intrathecal resiniferatoxin to control spontaneous bone cancer pain in companion (pet) dogs.

Methods

Normal canine population: Behavioral testing was performed to establish baseline paw withdrawal latency; subsequently, general anesthesia was induced and resiniferatoxin was administered intrathecally while hemodynamic parameters were recorded. Behavior testing was repeated for 12 days after administration of resiniferatoxin. Clinical canine population: Twenty companion dogs with bone cancer pain were recruited. The animal's baseline level of discomfort and analgesic use were recorded. Resiniferatoxin was administered intrathecally and hemodynamic parameters were monitored while the dogs were under general anesthesia. Dogs were reevaluated up to 14 weeks after resiniferatoxin administration.

Results

Normal canine population: In the first minutes after resiniferatoxin injection, there were significant (P < 0.05) increases in mean arterial blood pressure and heart rate from baseline. Two days after injection, limb withdrawal latencies increased to the point of cutoff in the dogs that received at least 1.2 microg/kg resiniferatoxin. Clinical canine population: From baseline, there were significant (P < 0.05) increases in mean arterial blood pressure and heart rate after resiniferatoxin injection. Comfort scores were significantly improved at 2, 6, 10, and 14 weeks after resiniferatoxin administration (P < 0.0001). There was decreased or discontinued use of supplemental analgesics in 67% of the dogs 2 weeks after resiniferatoxin administration.

Conclusions

Intrathecal resiniferatoxin elicits transient hemodynamic effects. In controls, a profound and sustained blockade of thermal stimuli is produced in a dose-dependent fashion. Similar administration in dogs with bone cancer produces a prolonged antinociceptive response.
Adenosine Reduces Glutamate Release in Rat Spinal Synaptosomes
Authors: Li Xinhui , Eisenach James C.
Published: October 2005

Background

A1 adenosine receptor activation reduces hypersensitivity in animal models of chronic pain, but intrathecal adenosine does not produce analgesia to acute noxious stimuli. Here, the authors test whether increased inhibition by adenosine of glutamate release from afferents after injury accounts for this difference.

Methods

Synaptosomes were prepared from the dorsal half of the lumbar spinal cord of normal rats or those with spinal nerve ligation. Glutamate release evoked by the TRPV-1 receptor agonist, capsaicin, was measured. Adenosine with or without adenosine A1 and A2 receptor antagonists was applied to determine the efficacy and mechanism of adenosine to reduce capsaicin-evoked glutamate release.

Results

Capsaicin produced a concentration-dependent glutamate release similarly in normal and nerve-injured rats. Capsaicin-evoked glutamate release was inhibited by adenosine or R-PIA (R-N6-(2- phenylisopropyl)-adenosine) in a concentration-dependent manner, with a threshold of 10 nm in both normal and nerve-ligated synaptosomes. Blockade of capsaicin-evoked glutamate release by adenosine was reversed similarly in synaptosomes from normal and spinal nerve-ligated animals by an A1 adenosine receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) but not by an A2 adenosine receptor antagonist DMPX (3'7-dimethyl-1-proparaglyxanthine). Capsaicin-evoked glutamate release, as well as its inhibition by adenosine, did not differ between synaptosomes prepared from tissue ipsilateral and contralateral to spinal nerve ligation.

Conclusion

These observations confirm previous neurophysiologic studies that presynaptic adenosine A1 receptor activation inhibits glutamate release from primary afferents. This effect is unaltered after peripheral nerve injury and thereby is unlikely to account for the enhanced analgesic efficacy of intrathecal adenosine in this setting.
Efficacy of Postoperative Patient-controlled and Continuous Infusion Epidural Analgesia versus Intravenous Patient-controlled Analgesia with Opioids
Authors: Wu Christopher L. , Cohen Seth R. , Richman Jeffrey M. , Rowlingson Andrew J. , Courpas Genevieve E. , Cheung Kristin , Lin Elaina E. , Liu Spencer S.
Published: October 2005

The authors performed a meta-analysis and found that epidural analgesia overall provided superior postoperative analgesia compared with intravenous patient-controlled analgesia. For all types of surgery and pain assessments, all forms of epidural analgesia (both continuous epidural infusion and patient-controlled epidural analgesia) provided significantly superior postoperative analgesia compared with intravenous patient-controlled analgesia, with the exception of hydrophilic opioid-only epidural regimens. Continuous epidural infusion provided statistically significantly superior analgesia versus patient-controlled epidural analgesia for overall pain, pain at rest, and pain with activity; however, patients receiving continuous epidural infusion had a significantly higher incidence of nausea-vomiting and motor block but lower incidence of pruritus. In summary, almost without exception, epidural analgesia, regardless of analgesic agent, epidural regimen, and type and time of pain assessment, provided superior postoperative analgesia compared to intravenous patient-controlled analgesia.
Transcriptional feedback control of insulin receptor by dFOXO/FOXO1
Authors: Puig Oscar , Tjian Robert
Published: October 2005

The insulin signaling pathway, which is conserved in evolution from flies to humans, evolved to allow a fast response to changes in nutrient availability while keeping glucose concentration constant in serum. Here we show that, both in Drosophila and mammals, insulin receptor (InR) represses its own synthesis by a feedback mechanism directed by the transcription factor dFOXO/FOXO1. In Drosophila, dFOXO is responsible for activating transcription of dInR, and nutritional conditions can modulate this effect. Starvation up-regulates mRNA of dInR in wild-type but not dFOXO-deficient flies. Importantly, FOXO1 acts in mammalian cells like its Drosophila counterpart, up-regulating the InR mRNA level upon fasting. Mammalian cells up-regulate the InR mRNA in the absence of serum, conditions that induce the dephosphorylation and activation of FOXO1. Interestingly, insulin is able to reverse this effect. Therefore, dFOXO/FOXO1 acts as an insulin sensor to activate insulin signaling, allowing a fast response to the hormone after each meal. Our results reveal a key feedback control mechanism for dFOXO/FOXO1 in regulating metabolism and insulin signaling.
Recruitment of host functions suggests a repair pathway for late steps in group II intron retrohoming
Authors: Smith Dorie , Zhong Jin , Matsuura Manabu , Lambowitz Alan M. , Belfort Marlene
Published: October 2005

Retrohoming of group II introns occurs by a mechanism in which the intron RNA reverse splices directly into one strand of a DNA target site and is then reverse transcribed by the associated intron-encoded protein. Host repair enzymes are predicted to complete this process. Here, we screened a battery of Escherichia coli mutants defective in host functions that are potentially involved in retrohoming of the Lactococcus lactis Ll.LtrB intron. We found strong (greater than threefold) effects for several enzymes, including nucleases directed against RNA and DNA, replicative and repair polymerases, and DNA ligase. A model including the presumptive roles of these enzymes in resection of DNA, degradation of the intron RNA template, traversion of RNA-DNA junctions, and second-strand DNA synthesis is described. The completion of retrohoming is viewed as a DNA repair process, with features that may be shared by other non-LTR retroelements.
Replication of mitochondrial DNA occurs by strand displacement with alternative light-strand origins, not via a strand-coupled mechanism
Authors: Brown Timothy A. , Cecconi Ciro , Tkachuk Ariana N. , Bustamante Carlos , Clayton David A.
Published: October 2005

The established strand-displacement model for mammalian mitochondrial DNA (mtDNA) replication has recently been questioned in light of new data using two-dimensional (2D) agarose gel electrophoresis. It has been proposed that a synchronous, strand-coupled mode of replication occurs in tissues, thereby casting doubt on the general validity of the “orthodox,” or strand-displacement model. We have examined mtDNA replicative intermediates from mouse liver using atomic force microscopy and 2D agarose gel electrophoresis in order to resolve this issue. The data provide evidence for only the orthodox, strand-displacement mode of replication and reveal the presence of additional, alternative origins of lagging light-strand mtDNA synthesis. The conditions used for 2D agarose gel analysis are favorable for branch migration of asymmetrically replicating nascent strands. These data reconcile the original displacement mode of replication with the data obtained from 2D gel analyses.
Surfing with the tunicates into the post-genome era
Authors: Satoh Nori , Levine Mike
Published: October 2005

This year is the centenary of Edward G. Conklin's signal findings in embryology: the elucidation of complete cell lineages and the discovery of localized maternal determinants. Conklin used ascidian embryos to elucidate universal principles in embryology. A century later, ascidians, or sea squirts, have not only entered the post-genome era, but in many ways are leading the way to the promise of a “systems-level” understanding of complex processes such as notochord formation, neurogenesis, and even behavior.
A core promoter element downstream of the TATA box that is recognized by TFIIB
Authors: Deng Wensheng , Roberts Stefan G.E.
Published: October 2005

We have defined a core promoter element downstream of the TATA box that is recognized by TFIIB. This involves a DNA-binding domain in TFIIB that is distinct from the helix–turn–helix motif (which recognizes an element upstream of the TATA box). The TFIIB recognition element we describe regulates transcription in a manner that is promoter context-dependent, particularly with respect to the TFIIB recognition element that is located upstream of the TATA box. Thus TFIIB can recognize two distinct sequence elements that flank the TATA box, employing independent DNA-binding motifs and cooperating in the regulation of transcription.
The microtubule plus-end-tracking protein CLIP-170 associates with the spermatid manchette and is essential for spermatogenesis
Authors: Akhmanova Anna , Mausset-Bonnefont Anne-Laure , van Cappellen Wiggert , Keijzer Nanda , Hoogenraad Casper C. , Stepanova Tatiana , Drabek Ksenija , van der Wees Jacqueline , Mommaas Mieke , Onderwater Jos , van der Meulen Hans , Tanenbaum Marvin E. , Medema Rene H. , Hoogerbrugge Jos , Vreeburg Jan , Uringa Evert-Jan , Grootegoed J. Anton , Grosveld Frank , Galjart Niels
Published: October 2005

CLIP-170 is a microtubule “plus-end-tracking protein” implicated in the control of microtubule dynamics, dynactin localization, and the linking of endosomes to microtubules. To investigate the function of mouse CLIP-170, we generated CLIP-170 knockout and GFP-CLIP-170 knock-in alleles. Residual CLIP-170 is detected in lungs and embryos of homozygous CLIP-170 knockout mice, but not in other tissues and cell types, indicating that we have generated a hypomorphic mutant. Homozygous CLIP-170 knockout mice are viable and appear normal. However, male knockout mice are subfertile and produce sperm with abnormal heads. Using the knock-in mice, we followed GFP-CLIP-170 expression and behavior in dissected, live testis tubules. We detect plus-end-tracking GFP-CLIP-170 in spermatogonia. As spermatogenesis proceeds, GFP-CLIP-170 expression increases and the fusion protein strongly marks syncytia of differentiated spermatogonia and early prophase spermatocytes. Subsequently GFP-CLIP-170 levels drop, but during spermiogenesis (post-meiotic development), GFP-CLIP-170 accumulates again and is present on spermatid manchettes and centrosomes. Bleaching studies show that, as spermatogenesis progresses, GFP-CLIP-170 converts from a mobile plus-end-tracking protein to a relatively immobile protein. We propose that CLIP-170 has a structural function in the male germline, in particular in spermatid differentiation and sperm head shaping.
The Arabidopsis synaptonemal complex protein ZYP1 is required for chromosome synapsis and normal fidelity of crossing over
Authors: Higgins James D. , Sanchez-Moran Eugenio , Armstrong Susan J. , Jones Gareth H. , Franklin F. Chris. H.
Published: October 2005

The duplicated Arabidopsis genes ZYP1a/ZYP1b encode closely related proteins with structural similarity to the synaptonemal complex (SC) transverse filament proteins from other species. Immunolocalization detects ZYP1 foci at late leptotene, which lengthen until at pachytene fluorescent signals extending the entire length of the fully synapsed homologs are observed. Analysis of zyp1a and zyp1b T-DNA insertion mutants indicates that the proteins are functionally redundant. The SC is not formed in the absence of ZYP1 and prophase I progression is significantly delayed suggesting the existence of an intraprophase I surveillance mechanism. Recombination is only slightly reduced in the absence of ZYP1 such that the chiasma frequency at metaphase I is ∼80% of wild type. Moreover cytological analysis indicates that chiasma distribution within zyp1 bivalents is indistinguishable from wild type, providing evidence that the SC is not required for the imposition of interference. Importantly in the absence of ZYP1, recombination occurs between both homologous and nonhomologous chromosomes suggesting the protein is required to ensure the fidelity of meiotic chromosome associations.
Lower urinary tract symptoms in middle‐aged women – prevalence and attitude towards mild urinary incontinence. A community‐based population study
Authors: Teleman Pia , Lidfeldt Jonas , Nerbrand Christina , Samsioe Göran , Mattiasson Anders
Published: October 2005

Objective.  To investigate the prevalence and perceived bother of lower urinary tract symptoms (LUTS) in middle‐aged women with and without self‐reported urinary incontinence.

Patients and methods.  In the Women's Health In the Lund Area study (WHILA 1995–2000), 32% of the participating 6917 women, 50–59 years, reported urinary incontinence defined as involuntary urinary leakage causing a social and/or hygienic problem. Out of these, 1500 women with (INCONT) and 1500 without incontinence (CONT) received the Bristol Female lower urinary tract symptoms (LUTS) questionnaire in January 2001.

Results.  A total of 2682 (89%) women were included. Most common LUTS in the INCONT and CONT groups, respectively, were any urinary leakage (93.8% vs. 53.3%, P < 0.001), urgency (86.2% vs. 62.5%, P < 0.001), stress incontinence (85.1% vs. 41%, P < 0.001), and frequency (86.9% vs. 35.6%, P < 0.001). The two groups differed significantly in the degree of reported bother by infrequently occurring stress and urge incontinence. Urinary leakage more than once a week was reported as bothersome by 97.5%. The prevalence of self‐reported urinary incontinence increased from 32% to estimated 66% if the demand for social and/or hygienic bother was omitted from the definition.

Conclusion.  The prevalence of self‐reported urinary incontinence increased from 32% to estimated 66%, if the demand for social and/or hygienic bother was omitted from the definition. LUTS other than incontinence are common in middle‐aged women, with a significantly higher prevalence in women with self‐reported incontinence than in continent women. The attitude towards stress‐ and urge incontinence varied widely when the symptoms occurred infrequently. Urinary leakage more than once a week was considered bothersome by 97.5%.