bluuebunny/crossref_metadata_2025 huggingface dataset:
Macrophages are not the source of injurious interleukin-18 in ischemic acute kidney injury in mice
Authors: He Zhibin , Dursun Belda , Oh Dong-Jin , Lu Lawrence , Faubel Sarah , Edelstein Charles L.
Published: January 2009

We previously reported in ischemic acute kidney injury (AKI) in mice that caspase-1-mediated production of interleukin-18 (IL-18) is pathogenic and that macrophage depletion by liposome-encapsulated clodronate (LEC) is protective. Therefore, our aim was to determine whether macrophages are a source of IL-18 in ischemic AKI in mice. On immunofluorescence staining of the outer stripe of outer medulla, the number of macrophages double stained for CD11b and IL-18 was significantly increased in AKI and significantly decreased by LEC. Adoptive transfer of RAW 264.7 cells, a mouse macrophage line that constitutively expresses IL-18 mRNA, reversed the functional protection against AKI in both LEC-treated wild-type and caspase-1 −/− mice. To test whether IL-18 in macrophages is necessary to cause AKI, we adoptively transferred macrophages in which IL-18 was inhibited. Peritoneal macrophages isolated from wild-type mice, IL-18 binding protein transgenic (IL-18 BP Tg) mice, and IL-18 −/− mice were used. IL-18 BP Tg mice overexpress human IL-18 BP and exhibit decreased biological activity of IL-18. Adoptive transfer of peritoneal macrophages from wild-type as well as IL-18 BP Tg and IL-18 −/− mice reversed the functional protection against AKI in LEC-treated mice. In summary, adoptive transfer of RAW cells, that constitutively express IL-18, reverses the functional protection in macrophage-depleted wild-type and caspase-1 −/− mice with AKI. However, adoptive transfer of peritoneal macrophages in which IL-18 function was inhibited also reverses the functional protection in macrophage-depleted mice. In conclusion, IL-18 from adoptive transfer of macrophages is not sufficient to cause ischemic AKI.
Nonselective NOS inhibition blunts the sweat response to exercise in a warm environment
Authors: Welch Garrett , Foote Kristopher M. , Hansen Crystelle , Mack Gary W.
Published: January 2009

The role of nitric oxide synthase (NOS) inhibition in modulating human thermoregulatory control of sweating and cutaneous dilation was examined in 10 subjects (5 men and 5 women). Three intradermal microdialysis probes were placed in nonglabrous skin of the dorsum of the forearm. The control site was perfused with 0.9% saline, while the two remaining sites were perfused with a nonselective NOS inhibitor: 10 mM NG-nitro-l-arginine (l-NAME) or 10 mM NG-monomethyl-l-arginine (l-NMMA). Local sweat rate (SR) and skin blood flow (laser-Doppler velocimetry) were monitored directly over the path of the intradermal microdialysis probe while arterial blood pressure was measured in the opposite arm noninvasively. Thermoregulatory responses were induced by cycle ergometer exercise (60% peak oxygen consumption) in a warm environment (30°C). Esophageal temperature increased 1.5 ± 0.2°C during the 30 min of exercise. The cutaneous dilator response between 5 and 30 min of exercise in the heat was attenuated by both 10 mM l-NAME and 10 mM l-NMMA ( P < 0.05). However, 10 mM l-NAME was more effective in blunting the rise in cutaneous vascular conductance during exercise than l-NMMA ( P < 0.05). NOS inhibition also reduced the rise in local SR between 10 and 30 min of exercise ( P < 0.05). In this case, 10 mM l-NMMA was more effective in limiting the increase in local SR than 10 mM l-NAME ( P < 0.05). We conclude that local production of nitric oxide in the skin or around the sweat gland augments local SR and cutaneous dilation during exercise in the heat.
Endurance exercise activates matrix metalloproteinases in human skeletal muscle
Authors: Rullman Eric , Norrbom Jessica , Strömberg Anna , Wågsäter Dick , Rundqvist Helene , Haas Tara , Gustafsson Thomas
Published: January 2009

In the present study, the effect of exercise training on the expression and activity of matrix metalloproteinases (MMPs) in the human skeletal muscle was investigated. Ten subjects exercised one leg for 45 min with restricted blood flow and then exercised the other leg at the same absolute workload with unrestricted blood flow. The exercises were conducted four times per week for 5 wk. Biopsies were taken from the vastus lateralis muscles of both legs at rest before the training period, after 10 days and 5 wk of training, and 2 h after the first exercise bout for analysis of MMP and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA, enzyme activity, and protein expression. Levels of MMP-2, MMP-14, and TIMP-1 mRNA in muscle tissue increased after 10 days of training regardless of blood flow condition. MMP-2 mRNA level in laser-dissected myofibers and MMP-2 activity in whole muscle increased with training. The level of MMP-9 mRNA and activity increased after the first bout of exercise. Although MMP-9 mRNA levels appeared to be very low, the activity of MMP-9 after a single bout of exercise was similar to that of MMP-2 after 10 days of exercise. MMP-2 and MMP-9 protein was both present throughout the extracellular matrix of the muscle, both around fibers and capillaries, but MMP-2 was also present within the skeletal muscle fibers. These results show that MMPs are activated in skeletal muscle in nonpathological conditions such as voluntary exercise. The expression and time pattern indicate differences between the MMPs in regards of production sites as well as in the regulating mechanism.
Multiple pathological events in exercised dystrophic mdx mice are targeted by pentoxifylline: outcome of a large array of in vivo and ex vivo tests
Authors: Burdi Rosa , Rolland Jean-François , Fraysse Bodvael , Litvinova Karina , Cozzoli Anna , Giannuzzi Viviana , Liantonio Antonella , Camerino Giulia Maria , Sblendorio Valeriana , Capogrosso Roberta Francesca , Palmieri Beniamino , Andreetta Francesca , Confalonieri Paolo , De Benedictis Leonarda , Montagnani Monica , De Luca Annamaria
Published: January 2009

The phosphodiesterases inhibitor pentoxifylline gained attention for Duchenne muscular dystrophy therapy for its claimed anti-inflammatory, antioxidant, and antifibrotic action. A recent finding also showed that pentoxifylline counteracts the abnormal overactivity of a voltage-independent calcium channel in myofibers of dystrophic mdx mice. The possible link between workload, altered calcium homeostasis, and oxidative stress pushed toward a more detailed investigation. Thus a 4- to 8-wk treatment with pentoxifylline (50 mg·kg−1·day−1 ip) was performed in mdx mice, undergoing or not a chronic exercise on treadmill. In vivo, the treatment partially increased forelimb strength and enhanced resistance to treadmill running in exercised animals. Ex vivo, pentoxifylline restored the mechanical threshold, an electrophysiological index of calcium homeostasis, and reduced resting cytosolic calcium in extensor digitorum longus muscle fibers. Mn quenching and patch-clamp technique confirmed that this effect was paralleled by a drug-induced reduction of membrane permeability to calcium. The treatment also significantly enhanced isometric tetanic tension in mdx diaphragm. The plasma levels of creatine kinase and reactive oxygen species were both significantly reduced in treated-exercised animals. Dihydroethidium staining, used as an indicator of reactive oxygen species production, showed that pentoxifylline significantly reduced the exercise-induced increase in fluorescence in the mdx tibialis anterior muscle. A significant decrease in connective tissue area and profibrotic cytokine transforming growth factor-β1 was solely found in tibialis anterior muscle. In both diaphragm and gastrocnemius muscle, a significant increase in neural cell adhesion molecule-positive area was instead observed. This data supports the interest toward pentoxifylline and allows insight in the level of cross talk between pathogenetic events in workloaded dystrophic muscle.
Onset responses of ventilation and cerebral blood flow to hypercapnia in humans: rest and exercise
Authors: Ogoh Shigehiko , Ainslie Philip N. , Miyamoto Tadayoshi
Published: January 2009

The respiratory and cerebrovascular reactivity to changes in arterial Pco2 ([Formula: see text]) is an important mechanism that maintains CO2 or pH homeostasis in the brain. It remains unclear, however, how cerebrovascular CO2 reactivity might influence the respiratory chemoreflex. The purpose of the present study was therefore to examine the interaction between onset responses of the respiratory chemoreflex and middle cerebral artery (MCA) mean blood velocity ( Vmean) to hypercapnia (5.0% CO2-40% O2-balance N2) at rest and during dynamic exercise (∼1.0 l/min O2 consumption). Each onset response was evaluated using a single-exponential regression model consisting of the response time latency [CO2-response delay ( t0)] and time constant (τ). At rest, t0 and τ data indicated that the MCA Vmean onset response was faster than the ventilatory (V̇e) response ( P < 0.001). In contrast, during exercise, t0 of V̇e and MCA Vmean onset responses were decreased. In addition, despite the enhanced [Formula: see text] response to CO2 administration ( P = 0.014), τ of MCA Vmean tended to increase during exercise ( P = 0.054), whereas τ of V̇e decreased ( P = 0.015). These findings indicate that 1) at rest, faster washout of CO2 via cerebral vasodilation results in a reduced activation of the central chemoreflex and subsequent reduced V̇e onset response, and 2) during exercise, despite higher rates of increasing [Formula: see text], the lack of change in the onset response of cerebral blood flow and reduced washout of CO2 may act to augment the V̇e onset response.
Bitter-Responsive Gustatory Neurons in the Rat Parabrachial Nucleus
Authors: Geran Laura C. , Travers Susan P.
Published: January 2009

Bitterness is a distinctive taste sensation, but central coding for this quality remains enigmatic. Although some receptor cells and peripheral fibers are selectively responsive to bitter ligands, central bitter responses are most typical in broadly tuned neurons. Recently we reported more specifically tuned bitter-best cells (B-best) in the nucleus of the solitary tract (NST). Most had glossopharyngeal receptive fields and few projected to the parabrachial nucleus (PBN), suggesting a role in reflexes. To determine their potential contribution to other functions, the present study investigated whether B-best neurons occur further centrally. Responses from 90 PBN neurons were recorded from anesthetized rats. Stimulation with four bitter tastants (quinine, denatonium, propylthiouracil, cycloheximide) and sweet, umami, salty, and sour ligands revealed a substantial proportion of B-best cells (22%). Receptive fields for B-best NST neurons were overwhelmingly foliate in origin, but in PBN, about half received foliate and nasoincisor duct input. Despite convergence, most B-best PBN neurons were as selectively tuned as their medullary counterparts and response profiles were reliable. Regardless of intensity, cycloheximide did not activate broadly tuned acid/sodium (AN) neurons but did elicit robust responses in B-best cells. However, stronger quinine activated AN neurons and concentrated electrolytes stimulated B-best cells, suggesting that B-best neurons might contribute to higher-order functions such as taste quality coding but work in conjunction with other cell types to unambiguously signal bitter-tasting ligands. In this ensemble, B-best neurons would help discriminate sour from bitter stimuli, whereas AN neurons might be more important in differentiating ionic from nonionic bitter stimuli.
Bipartite Toughness and k‐Factors in Bipartite Graphs
Authors: Liu Guizhen , Qian Jianbo , Sun Jonathan Z. , Xu Rui
Published: January 2009

We define a new invariant tB(G) in bipartite graphs that is analogous to the
toughness t(G) and we give sufficient conditions in term of tB(G) for the existence of k‐factors in bipartite graphs. We also show that these results are sharp.
Studies on Calcium Ion Selectivity of ZnO Nanowire Sensors Using Ionophore Membrane Coatings
Authors: Asif M. H. , Nur O. , Willander M. , Yakovleva M. , Danielsson B.
Published: January 2009

Zinc oxide nanorods with 100 nm diameter and 900 nm length were grown on the surface of a silver wire (0.25 mm in diameter) with the aim to produce electrochemical nanosensors. It is shown that the ZnO nanorods exhibit a Ca2+‐dependent electrochemical potentiometric behavior in an aqueous solution. The potential difference was found to be linear over a large logarithmic concentration range (1 μM to 0.1 M) using Ag/AgCl as a reference electrode and the response time was less than one minute. In order to adapt the sensors for calcium ion measurements in biological fluids with sufficient selectivity and stability, plastic membrane coatings containing ionophores were applied. These functionalized ZnO nanorods sensors showed a high sensitivity (26.55 mV/decade) and good stability.
Differences of Composition Operators on the Space of Bounded Analytic Functions in the Polydisc
Authors: Fang Zhong-Shan , Zhou Ze-Hua
Published: January 2009

This paper gives some estimates of the essential norm for the
difference of composition operators induced by φ and
ψ acting on the space, , of bounded analytic functions
on the unit polydisc , where φ
and ψ are holomorphic self‐maps of . As a consequence,
one obtains conditions in terms of the Carathéodory distance
on that characterizes those pairs of holomorphic self‐maps
of the polydisc for which the difference of two composition
operators on is compact.
Fecal and Salivary Cortisol Concentrations in Woolly(Lagothrix ssp.)and Spider Monkeys(Ateles spp.)
Authors: Ange-van Heugten Kimberly D. , van Heugten Eric , Timmer Saskia , Bosch Guido , Elias Abahor , Whisnant Scott , Swarts Hans J. M. , Ferket Peter , Verstegen Martin W. A.
Published: January 2009

Detrimental physiological effects due to stressors can contribute to the low captive success of primates. The objective of this research was to investigate the potential impact of diet composition on cortisol concentrations in feces and saliva in woolly (n=27) and spider monkeys (n=61). The research was conducted in three studies: the first investigated spider monkeys in the United States, the second investigated spider monkeys within Europe, and the third investigated woolly monkeys within Europe. Fecal cortisol in spider monkeys in US zoos varied (P=.07) from 30 to 66 ng/g. The zoo with the highest fecal cortisol also had the highest salivary cortisol (P≤.05). For European zoos, fecal cortisol differed between zoos for both spider and woolly monkeys (P≤.05). Spider monkeys had higher fecal cortisol than woolly monkeys (P≤.05). Zoos with the highest dietary carbohydrates, sugars, glucose, and fruit had the highest cortisol. Cortisol was highest for zoos that did not meet crude protein requirements and fed the lowest percentage of complete feeds and crude fiber. Differences among zoos in housing and diets may increase animal stress. The lifespan and reproductive success of captive primates could improve if stressors are reduced and dietary nutrients optimized.
Neuropsychological Functioning in Schizophrenia Patients with First-Rank (Passivity) Symptoms
Authors: Waters Flavie A.V. , Badcock Johanna C. , Dragović Milan , Jablensky Assen
Published: January 2009

Background: In this study, we conducted a broad investigation of neuropsychological functioning in schizophrenia patients with first-rank (passivity) symptoms (FRS) using standardized cognitive tests. We focused on 3 neuropsychological domains, partly informed by 3 broad hypotheses concerning the pathogenesis of FRS. We tested predictions that patients with FRS would show: (i) memory deficits consistent with abnormalities in medial temporal lobe functioning; (ii) reduced cerebral lateralization on tasks of motor and language functions, and (iii) deficits on tasks of executive functions as a measure of the integrity of the prefrontal cortex for supporting self-monitoring processes. Sampling and Methods: In 2 parallel studies, we administered a range of neuropsychological tests to patients with FRS (sample A = 17, sample B = 15) and without FRS (sample A = 28, sample B = 20) and to healthy controls (sample A = 109, sample B = 22). Results: The results showed reduced cerebral lateralization in patients with FRS, but there were no memory deficits or executive dysfunctions relative to patients without FRS. An unexpected finding was that, on many cognitive tasks, the performance of the patients with FRS was relatively spared compared to that of the patients without FRS. These results could not be accounted for by demographic features or medication effects. Conclusions: Our results provide qualified support for the reduced lateralization hypothesis. Analyses of performance across neuropsychological domains showed that generalized deficit is not a sufficient explanation for the occurrence of FRS.
Influence of Occult Hepatitis B Virus Coinfection on the Incidence of Fibrosis and Hepatocellular Carcinoma in Chronic Hepatitis C
Authors: Matsuoka Shunichi , Nirei Kazushige , Tamura Akinori , Nakamura Hitomi , Matsumura Hiroshi , Oshiro Shuu , Arakawa Yasuo , Yamagami Hiroaki , Tanaka Naohide , Moriyama Mitsuhiko
Published: January 2009

We examined prospectively the influence of occult hepatitis B virus (HBV) infection on the histopathological features and clinical outcome of HCV RNA-positive chronic hepatitis (CH-C) and detected hepatitis B core (HBc) particles in hepatocytes. The subjects were 468 patients with CH-C or liver cirrhosis (LC) who were negative for serum hepatitis B surface antigen (HBsAg) by enzyme-linked immunosorbent assay. HBV DNA was detected in serum by nested PCR. HBsAg and HBc antigen (HBcAg) in liver were investigated using immunohistochemical techniques and light (LM) and electron microscopy (EM). Serum HBV DNA was detected in 43.6% of the patients studied. There were no significant differences between HBV DNA-positive and DNA-negative patients in terms of their clinical profiles. For HBV DNA-positive patients, the degree of inflammatory cell infiltration and irregular regeneration of hepatocytes was significantly greater than for HBV DNA-negative patients. The cumulative probability of development of hepatocellular carcinoma (HCC) was significantly higher for HBV DNA-positive patients than for HBV DNA-negative patients. HBV DNA positivity was a risk factor for the occurrence of HCC according to multivariate analysis. HBsAg and HBcAg were detected in 8.5 and 72.3%, respectively, of the livers of serum HBV DNA-positive individuals. Core particles were detected in the nuclei of the hepatocytes by IEM. The histopathological features and long-term outcome of CH-C or LC could be affected by occult HBV infection.
Enhanced Interferon-γ Gene Expression in T Cells and Reduced Ovalbumin-Dependent Lung Eosinophilia in Hypoxia-Inducible Factor-1-α-Deficient Mice
Authors: Guo Jia , Lu Wenju , Shimoda Larissa A. , Semenza Gregg L. , Georas Steve N.
Published: January 2009

Background: There is growing evidence that hypoxia-inducible transcription factors are involved in the pathophysiology of asthma. Hypoxia-inducible factor-1α (HIF-1α) in particular controls the expression of many hypoxia regulated genes, but whether HIF-1α directly contributes to allergen-driven immune responses is not known. Methods: Partially HIF-1α-deficient mice (HIF-1α+/–) or wild-type littermate controls were used in all experiments. Spleen CD4+ T cells were stimulated with anti-CD3 plus anti-CD28 antibodies and cytokine secretion was measured in vitro. Mice were sensitized by intraperitoneal injection of ovalbumin (Ova) plus alum, and then challenged by intranasal Ova followed by bronchoalveolar lavage (BAL) and isolation of spleen cells. BAL cells were counted and the differential determined using cytospin, and splenocytes were incubated with Ova to measure recall cytokine production. Results: Interferon-γ secretion was significantly higher in anti-CD3 plus anti-CD28 stimulated CD4+ T cells obtained from HIF-1α+/– mice compared to wild-type controls. HIF-1α+/– mice were protected from lung eosinophilia 72 h after allergen challenge, in association with enhanced secretion of interferon-γ in recall responses of splenocytes. Conclusions: HIF-1α contributes to allergic immune responses and lung eosinophilia in a mouse model of asthma.
Atopic Dermatitis, Dry Skin and Serum IgE in Children in a Community in Japan
Authors: Wakamori Takeshi , Katoh Norito , Hirano Shinya , Kishimoto Saburo , Ozasa Kotaro
Published: January 2009

Background: Long-term, prospective studies investigating the prevalence, serum IgE and the natural history of atopic dermatitis (AD) in a community are lacking. Methods: In a Japanese community, the skin of primary school children and junior high school students was examined and a questionnaire was given to their parents; their serum total IgE, and house dust mite (HDM)- and Japanese cedar pollen (JCP)-specific IgE levels were also assessed once a year for 9 years. Results: The median AD prevalence in all students (492 in 1998 and 380 in 2004) was 7.6% (6.1–10.4%). The prevalence and the area of skin eruptions of AD decreased with growth. Serum total and HDM-specific IgE levels were high in AD patients, and significant differences were noted for both levels between children with and without later remission of skin eruptions at the time of primary school entry. IgE level increases were noted in the following order: healthy skin < dry skin < AD. In children presenting only with dry skin without atopic disorders, such as AD, asthma and allergic rhinitis, levels of total HDM- and JCP-specific IgE were significantly higher than in children with healthy skin. Conclusions: The infantile IgE level serves as a prognostic index, and sensitization to inhalant allergens may be easily established in individuals with clinically dry skin, even when AD is not present, and this may lead to the development of atopic disorders.
Co-Delivery of Ovalbumin and CpG Motifs into Microparticles Protected Sensitized Mice from Anaphylaxis
Authors: San Román Beatriz , Irache Juan M. , Gómez Sara , Gamazo Carlos , Espuelas Socorro
Published: January 2009

Background: Two major drawbacks of current subcutaneous specific immunotherapy are the risk to induce severe anaphylactic reactions and the need of multiple injections of the allergen to reduce IgE-mediated hypersensitivity. The sustained release of allergens over time provided by poly(lactide-co-glycolide) microparticles (MP) could mimic the current therapeutic schedule and decrease their allergenicity. Moreover, MP could also co-deliver Th1 immunoadjuvants, such as CpG motifs. Methods: Ovalbumin (OVA)-sensitized BALB/c mice were treated intradermally with OVA or OVA plus CpG containing MP. OVA-specific IgG1 and IgG2a as well as IgE total levels and cytokine production were assessed throughout the experiment. The protection exerted by the MP against allergen challenge was estimated with body temperature changes, mortality and other symptoms. Results: Microparticulated treatments, irrespective of the presence of CpG motifs, elicited a lower IgE/IgG2a ratio than those induced by the allergen in solution (free or with adjuvants). However, after induction of the anaphylactic shock, only mice treated with MP co-encapsulating OVA plus CpG showed a significant lower decrease in body temperature and were totally protected from death. Mice that were injected with OVA plus CpG in solution or with Alum displayed a marked fall of temperature accompanied by high mortality rates (70–100%). Conclusion: MP encapsulating both OVA, as an allergen model, and CpG sequences, as a pro-Th1 adjuvant, decreased the risk for OVA sensitization (IgE induction) and protected sensitized mice from anaphylactic shock after allergen provocation. Therefore, the combination of allergens and CpG sequences into MP could perform a safer alternative to current specific immunotherapy.
Pimecrolimus Reduces Eosinophil Activation Associated with Calcium Mobilization
Authors: Plager Douglas A. , Henke Susan A. , Matsuwaki Yoshinori , Madaan Arvind , Squillace Diane L. , Dierkhising Ross A. , Kita Hirohito
Published: January 2009

Background: Pimecrolimus is a calcineurin inhibitor that inhibits T cell and mast cell activation and effectively treats atopic dermatitis. However, its effects on eosinophils, a cell type implicated in allergic disease pathology, are unknown. Therefore, we examined the effects of pimecrolimus on eosinophil superoxide anion production, degranulation and survival. Methods: Purified eosinophils from normal or atopic donors were incubated with serial dilutions of pimecrolimus (μM to nM) and then stimulated with platelet activating factor (PAF), interleukin 5 (IL5), secretory immunoglobulin A (sIgA) or Alternaria alternata (Alt) fungus extract. Eosinophil activation was monitored by cytochrome c reduction resulting from superoxide anion production and by a 2-site immunoassay for eosinophil-derived neurotoxin (EDN) in cellular supernatants, as a marker of degranulation. Eosinophil survival was measured by propidium iodide exclusion using flow cytometry after 4 days in culture. Results: Normal and atopic eosinophil superoxide anion production induced by PAF, and associated with increased intracellular calcium, was inhibited up to 37% with 1 μM pimecrolimus. However, superoxide anion production induced by IL5 and sIgA was not consistently inhibited. EDN release, which ultimately depends on calcium, was inhibited about 30% with PAF, IL5 and sIgA stimulation for normal and atopic donor eosinophils. Furthermore, calcium-dependent Alt-induced EDN release was inhibited up to 49% with nanomolar pimecrolimus. Finally, increased eosinophil survival promoted by IL5 and sIgA was not influenced by pimecrolimus. Conclusion: Pimecrolimus moderately inhibits eosinophil superoxide anion production and EDN release associated with calcium mobilization, which may contribute to its efficacy in treating atopic dermatitis.
Increases in Urinary 9α,11β-Prostaglandin F2 Indicate Mast Cell Activation in Wine-Induced Asthma
Authors: Misso Neil L.A. , Aggarwal Shashi , Thompson Philip J. , Vally Hassan
Published: January 2009

Background: Wine-induced asthmatic symptoms may be caused by sulphite additives. Prostaglandin (PG)D2 and cysteinyl leukotrienes (cysLT) are important mediators of asthmatic responses. To determine whether the sulphite additives in wine alter the production of PGD2 and cysLT, asthmatic patients with compelling histories of wine sensitivity were challenged with high- and low-sulphite wines; the urinary metabolites of PGD2 and cysLT were measured before and after challenge. Methods: Eight self-reporting wine-sensitive asthmatic patients completed double-blind challenges with high- and low-sulphite wines on separate days. Urine samples were collected before and after consumption of 150 ml of wine. Urinary concentrations of 9α,11β-PGF2 and leukotriene (LT)E4 were measured by enzyme immunoassay. Results: Urinary 9α,11β-PGF2 concentrations increased in all subjects following challenge with high-sulphite wine, and the median concentration increased 1.6-fold (p < 0.01). Urinary 9α,11β-PGF2 also increased 1.5-fold after low-sulphite wine challenge, although this did not reach statistical significance (p = 0.08). The median difference in 9α,11β-PGF2 concentration after high-sulphite wine challenge was not significantly different compared with that after low-sulphite wine challenge. Median urinary LTE4 concentrations did not change significantly after either wine challenge. Conclusions: Increased urinary 9α,11β-PGF2 concentrations following wine challenge suggest mast cell activation as a possible mechanism for wine-induced asthma, although this did not appear to be related to the sulphite additives in wine. Urinary 9α,11β-PGF2 may warrant further assessment as a potential biomarker of reactivity to wine in asthmatic subjects.
Association between Obesity and Atopy in Chinese Schoolchildren
Authors: Leung Ting Fan , Kong Alice P.S. , Chan Iris H.S. , Choi Kai Chow , Ho Chung Shun , Chan Michael H.M. , So Wing Yee , Lam Christopher W.K. , Wong Gary W.K. , Chan Juliana C.N.
Published: January 2009

Background: Despite parallel increases in asthma and obesity prevalence, there is little data on obesity as a risk factor for atopy. The latter is an important phenotype in asthmatic patients. This study investigates the association between asthma traits, atopy and obesity-related markers in Chinese adolescents. Methods: 486 schoolchildren were recruited among participants of our population-based study on the epidemiology of obesity, and their allergy status was ascertained using a standardized questionnaire. Subjects’ anthropometry was recorded on-site, and fasting blood was collected for allergen-specific immunoglobulin E (IgE), lipids and systemic inflammatory biomarkers. Results: 98 (20.2%) subjects were classified as overweight or obese. Obesity status was not associated with asthma, allergic rhinitis or eczema (p > 0.25). Atopy was not associated with age-adjusted body mass index (BMI) or waist circumference. Atopy and presence of allergen-specific IgE did not differ between overweight or obese children and those with normal BMI (p > 0.25), although subgroup analysis suggested that cockroach sensitization was more common among males who were obese or overweight (p = 0.045). White cell count (WCC) was higher among atopic than nonatopic children (mean values 6.5 × 109/l vs. 6.2 × 109/l, p = 0.006). Logistic regression revealed WCC to be the only risk factor for atopy (OR 18.97, p = 0.004). Conclusions: Obesity is not associated with asthma or atopy in Chinese children. High WCC is an important risk factor for atopy in both males and females. Gender does not exert any consistent effect on the association between obesity and allergen sensitization in children.
Nasal Challenge with LPS Stimulates the Release of Macrophage Inflammatory Protein 1α
Authors: Ekman Anna-Karin , Fransson Mattias , Rydberg Camilla , Adner Mikael , Cardell Lars-Olaf
Published: January 2009

Background: Bacterial infections can cause a variety of airway diseases. Toll-like receptors (TLRs) directly respond to the presence of microbes and partake in the innate immune defense. TLR4 is activated by lipopolysaccharide (LPS), and has been detected in sinonasal tissue, epithelial cells and various inflammatory cells. Macrophage inflammatory protein 1α (MIP-1α) is a chemokine released during the inflammatory process. The present study investigated the potential role and regulation of MIP-1α in LPS-induced nasal inflammation. Methods: Thirty-two healthy individuals were intranasally challenged with LPS or vehicle. Nasal lavage was performed, followed by a nasal biopsy. Inflammatory cells were counted, MIP-1α levels analyzed and expression of MIP-1α mRNA in biopsies quantified. Neutrophils isolated from peripheral blood were treated with LPS and effects on MIP-1α release, cell survival, and the involved signal pathways, were investigated. Results: LPS challenge caused an increase of MIP-1α in nasal lavage. No corresponding change in mRNA expression was seen in nasal biopsies, suggesting the increase was not due to epithelial synthesis. Neutrophil numbers increased after LPS provocation. Treatment of isolated neutrophils with LPS delayed neutrophil apoptosis and resulted in a time- and concentration-dependent release of MIP-1α, which was reduced by inhibitors of transcription and of nuclear factor (NF)-κB, protein kinase C (PKC) and p38 MAPK pathways. Conclusions: Nasal LPS challenge results in release of MIP-1α. The release most likely originates from recruited neutrophils, via NF-κB-, PKC- and p38 MAPK-dependent pathways. LPS stimulation delayed neutrophil apoptosis. MIP-1α may constitute an important mediator in neutrophilic airway disease.
Analysis of Signaling Pathways Involved in Peptidoglycan-Induced RANTES Production from Murine Langerhans Cells
Authors: Matsui Katsuhiko , Wirotesangthong Mali , Nishikawa Akemi
Published: January 2009

Background: Our previous study showed that percutaneous application of peptidoglycan from Staphylococcus aureus induced eosinophil infiltration in murine skin through production of CCL5/RANTES (regulated upon activation in normal T cells expressed and secreted) from epidermal Langerhans cells. Although it is well known that peptidoglycan is an agonist of Toll-like receptor (TLR)-2, it is unclear whether other TLR agonists are able to induce RANTES production from Langerhans cells. Methods: Langerhans cells were purified from murine epidermal cells by the panning method using anti-IAd monoclonal antibody. RANTES production by Langerhans cells was investigated by RT-PCR and ELISA. Analysis of the signaling pathways responsible for RANTES production by Langerhans cells was performed by ELISA using N-acetyl-L-cysteine, SP600125, SB203580 and PD98059, which are specific inhibitors of NF-κB activation, JNK, p38 MAPK and ERK, respectively, and was finally confirmed by Western blot analysis. Results: Peptidoglycan, poly(I:C), lipopolysaccharide and CpG DNA, which signal through TLR-2, TLR-3, TLR-4 and TLR-9, respectively, were found to strongly induce RANTES production. Treatment with N-acetyl-L-cysteine inhibited all TLR agonist-induced RANTES production. However, treatment with SP600125 did not inhibit CpG DNA-induced RANTES production. Furthermore, treatment with SB203580 inhibited only peptidoglycan- and lipopolysaccharide-induced RANTES production and the inhibition was correlated with that of p38 MAPK phosphorylation. Conclusion: These results suggest that the signaling pathway of RANTES production from murine Langerhans cells induced by different TLR stimuli is not necessarily the same, and that inhibition of p38 MAPK may be a more specific therapeutic target for eosinophilic inflammation in patients with atopic dermatitis associated with S. aureus colonization.
Desensitization in Interferon-β1a Allergy: A Case Report
Authors: Kalpaklioglu Ayse Fusun , Baccioglu Kavut Ayse , Erdemoglu Ali Kemal
Published: January 2009

We report a 41-year-old patient with multiple sclerosis (MS) who was successfully desensitized after she developed non-injection-site urticaria and angioedema due to interferon (IFN)-β1a. Although a few cases of urticaria and anaphylaxis have been reported in the literature, to our knowledge this is the first report of a successful desensitization with IFN-β1a. Desensitization with IFN-β1a allowed us to continue with the administration of interferon-β, which is a mainstay in treatment for MS.
Oxidative Imbalance in Nonstimulated X-Adrenoleukodystrophy-Derived Lymphoblasts
Authors: Uto Takuhiro , Contreras Miguel A. , Gilg Anne G. , Singh Inderjit
Published: January 2009

X-Adrenoleukodystrophy (X-ALD) is a peroxisomal disorder characterized by accumulation of very-long-chain (VLC) fatty acids, which induces inflammatory disease and alterations in cellular redox, both of which are reported to play a role in the pathogenesis of the severe form of the disease (childhood cerebral ALD). Here, we report on the status of oxidative stress (NADPH oxidase activity) and inflammatory mediators in an X-ALD lymphoblast cell line under nonstimulated conditions. X-ALD lymphoblasts contain nearly 7 times higher levels of the C26:₀ fatty acid compared to controls; these levels were downregulated by treatment with sodium phenylacetate (NaPA), lovastatin or the combination of both drugs. In addition, free-radicals synthesis was elevated in X-ALD lymphoblasts, and protein levels of the NADPH oxidase gp91PHOX membrane subunit were significantly upregulated, but no changes were observed in the p47PHOX and p67PHOX cytoplasmic subunits. Unexpectedly, there was no increase in gp91PHOX mRNA levels in X-ALD lymphoblasts. Furthermore, X-ALD lymphoblasts produced higher levels of nitric oxide (NO) and cytokines (tumor necrosis factor-α and interleukin 1β), and treatment with NaPA or lovastatin decreased the synthesis of NO. Our data indicate that X-ALD lymphoblasts are significantly affected by the accumulation of VLC fatty acids, which induces changes in the cell membrane properties/functions that may, in turn, play a role in the development/progression of the pathogenesis of X-ALD disease.
Low Levels of Corticotropin-Releasing Hormone during Early Pregnancy Are Associated with Precocious Maturation of the Human Fetus
Authors: Class Quetzal A. , Buss Claudia , Davis Elysia Poggi , Gierczak Matt , Pattillo Carol , Chicz-DeMet Aleksandra , Sandman Curt A.
Published: January 2009

Elevation in placental corticotropin-releasing hormone (pCRH) during the last trimester of pregnancy has been associated with an increased risk for preterm delivery. Less is known about the consequences for the human fetus exposed to high levels of pCRH early in pregnancy. pCRH levels were measured in 138 pregnant women at least once at 15, 20 and 25 weeks of gestation. At 25 weeks of gestation, fetal heart rate (FHR) responses to a startling vibroacoustic stimulus (VAS) were recorded as an index of maturity. pCRH levels at 15 weeks of gestation, but at no later point, predicted FHR responses to the VAS. Fetuses exposed to the lowest concentrations of pCRH at 15 weeks of gestation exhibited a distinguishable response to the VAS, whereas fetuses exposed to higher levels of pCRH did not respond. The findings suggest that exposure to low levels of pCRH early in gestation may be optimal and associated with a response pattern indicating greater maturity.
Impact of Age and Medical Comorbidity on the Effectiveness of Implantable Cardioverter-Defibrillators for Primary Prevention
Authors: Chan Paul S. , Nallamothu Brahmajee K. , Spertus John A. , Masoudi Frederick A. , Bartone Cheryl , Kereiakes Dean J. , Chow Theodore
Published: January 2009

Background—

Although implantable cardioverter-defibrillators (ICDs) reduce mortality in primary prevention patients with left ventricular systolic dysfunction, recent studies have questioned their overall role in clinical practice, especially in older patients and those with major comorbid conditions.

Methods and Results—

In a prospective cohort of 965 patients with ischemic and nonischemic cardiomyopathies (ejection fraction ≤35%) and no prior ventricular arrhythmias, we compared long-term mortality in patients who did (n=494 [51%]) and did not receive ICDs over a mean follow-up period of 34�16 months. Using a landmark analysis, multivariable Cox proportional hazards models that included propensity scores for ICD implantation assessed the relationship between ICD therapy and mortality in the entire cohort and by age and the presence of major comorbid conditions. Data from these analyses were then used as inputs in a Markov model to generate incremental cost-effectiveness ratios for ICD therapy. Patients who received ICDs were similar in age and prevalence of most major comorbid conditions, including symptomatic heart failure. After multivariable adjustment, ICD therapy was associated with a 31% lower risk for all-cause mortality (adjusted hazard ratio, 0.69; 95% CI, 0.50 to 0.96;
P
=0.03). The relationship between ICD therapy and lower all-cause mortality was consistent after stratification by age (<65, 65 to 74, and ≥75), ischemic etiology, ejection fraction (>25% versus ≤25%), and the presence of major comorbid conditions (probability values for all interactions >0.05). Incremental cost-effectiveness ratios for ICD therapy were similar between patients aged ≥75 years and younger patients but rose slightly in those with multiple comorbid conditions.

Conclusions—

Routine use of ICDs in primary prevention patients with left ventricular systolic dysfunction was associated with lower all-cause mortality, even among older patients and those with major comorbid conditions. Although their use needs to be individualized, our findings suggest that these groups should not be routinely excluded from ICD treatment.
Stress Reduction Prolongs Life in Women With Coronary Disease
Authors: Orth-Gomér Kristina , Schneiderman Neil , Wang Hui-Xin , Walldin Christina , Blom May , Jernberg Tomas
Published: January 2009

Background—

Psychosocial stress may increase risk and worsen prognosis of coronary heart disease in women. Interventions that counteract women’s psychosocial stress have not previously been presented. This study implemented a stress reduction program for women and investigated its ability to improve survival in women coronary patients.

Methods and Results—

Two hundred thirty-seven consecutive women patients, aged 75 years or younger, hospitalized for acute myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention were randomized to a group-based psychosocial intervention program or usual care. Initiated 4 months after hospitalization, intervention groups of 4 to 8 women met for a total of 20 sessions that were spread over a year. We provided education about risk factors, relaxation training techniques, methods for self-monitoring and cognitive restructuring, with an emphasis on coping with stress exposure from family and work, and self-care and compliance with clinical advice. From randomization until end of follow-up (mean duration, 7.1 years), 25 women (20%) in the usual care and 8 women (7%) in the stress reduction died, yielding an almost 3-fold protective effect of the intervention (odds ratio, 0.33; 95% CI, 0.15 to 0.74;
P
=0.007). Introducing baseline measures of clinical prognostic factors, including use of aspirin, β-blockers, angiotensin-converting enzyme inhibitors, calcium-channel blockers, and statins into multivariate models confirmed the unadjusted results (
P
=0.009).

Conclusions—

Although mechanisms remain unclear, a group-based psychosocial intervention program for women with coronary heart disease may prolong lives independent of other prognostic factors.
Impact of Depression on Sex Differences in Outcome After Myocardial Infarction
Authors: Parashar Susmita , Rumsfeld John S. , Reid Kimberly J. , Buchanan Donna , Dawood Nazeera , Khizer Saadia , Lichtman Judith , Vaccarino Viola
Published: January 2009

Background—

Women have an unexplained worse outcome after myocardial infarction (MI) compared with men in many studies. Depressive symptoms predict adverse post-MI outcomes and are more prevalent among women than men. We examined whether depressive symptoms contribute to women’s worse outcomes after MI.

Methods and Results—

In a prospective multicenter study (PREMIER), 2411 (807 women) MI patients were enrolled. Depressive symptoms were assessed with the Patient Health Questionnaire. Outcomes included 1-year rehospitalization, presence of angina using the Seattle Angina Questionnaire, and 2-year mortality. Multivariable analyses were used to evaluate the association between sex and these outcomes, adjusting for clinical characteristics. The depressive symptoms score was added to the models to evaluate whether it attenuated the association between sex and outcomes. Depressive symptoms were more prevalent in women compared with men (29% versus 18.8%,
P
<0.001). After adjusting for demographic factors, comorbidities, and MI severity, women had a mildly higher risk of rehospitalization (hazard ratio, 1.20; 95% CI, 1.04 to 1.40), angina (odds ratio, 1.32; 95% CI, 1.00 to 1.75), and mortality (hazard ratio, 1.27; 95% CI, 0.98 to 1.64). After adding depressive symptoms to the multivariable models, the relationship further declined toward the null, particularly for rehospitalization (hazard ratio, 1.14; 95% CI, 0.98 to 1.34) and angina (odds ratio, 1.22; 95% CI, 0.91 to 1.63), whereas there was little change in the estimate for mortality (hazard ratio, 1.24; 95% CI, 0.95 to 1.62). Depressive symptoms were significantly associated with each of the study outcomes with a similar magnitude of effect in both women and men.

Conclusions—

A higher prevalence of depressive symptoms in women modestly contributes to their higher rates of rehospitalization and angina compared with men but not mortality after MI. Our results support the recent recommendations of improving recognition of depressive symptoms after MI.
Acute Pancreatitis—Complicating Hepatitis E Virus Infection in a 7-Year-Old Boy With Glucose 6 Phosphate Dehydrogenase Deficiency
Authors: Thapa Rajoo , Biswas Biswajit , Mallick Debkrishna , Ghosh Apurba
Published: January 2009

The association of viral hepatitis and acute pancreatitis is well described in the literature. Most of the cases occur in conjunction with fulminant hepatitis A and hepatitis B virus infections. The recent literature reports increasing number of cases of this complication secondary to hepatitis E virus (HEV) infection, mostly in young adults in regions endemic for the virus. Till date, to the authors' knowledge, there are 14 well-documented cases of HEV-associated acute pancreatitis in the literature. This study reports on a 7-year-old boy from India deficient in glucose 6 phosphate dehydrogenase (G6PD) with moderately severe pancreatitis, manifesting during the course of nonfulminant acute HEV infection. He developed extremely high serum bilirubin levels, probably attributed to the concomitant viral infection and his G6PD status. He recovered completely with conservative therapy. The present child is the youngest ever reported case till date with this complication secondary to HEV infection.
Evolving Function
Authors: Johnston Norman
Published: January 2009

This article explores the usages of imprisonment, both de facto and de jure, from its earliest recorded use 3,000 years ago down to recent times. Early scattered use, unreflected in the statutes, was followed by houses of correction for minor offenders and later, displacing capital punishment, for major crimes. Serious reform in England and Pennsylvania and the subsequent battle between two systems developed in Pennsylvania and New York states and their ultimate demise are described. The origins of special prisons for women, youth, and other categories are traced, and early prison labor and schooling are described.
A Historical Review of Mother and Child Programs for Incarcerated Women
Authors: Craig Susan C.
Published: January 2009

Programs for incarcerated mothers and their children have received little scholarly attention over the years. This article presents a historical review and discussion of programs for incarcerated mothers and their children in the United States. Recurring themes in the history of these programs include the pervasive effects of race and class, the state's attempt to regulate and control women's minds and bodies, and the persistent dilemmas posed by the presence of mothers in prison. The article begins with an examination of historical influences from England and continues with an overview of programs in the United States from the early 1800s to the present. A discussion and recommendations for further research are provided.
Rapid Conversion of Persistent Atrial Fibrillation to Sinus Rhythm by Intravenous AZD7009
Authors: Geller J. Christoph , Egstrup Kenneth , Kulakowski Piotr , Rosenqvist Mårten , Jansson Maria Aunes , Berggren Anders , Edvardsson Nils , Sager Philip , Crijns Harry J.
Published: January 2009

This randomized, double‐blind trial compared cardioversion rates between AZD7009 infusion (15‐minute 3.25 mg/min, 15‐minute 4.4 mg/min, or 30‐minute 3.25 mg/min) and placebo infusion (15 or 30 minutes) in patients with atrial fibrillation (AF) scheduled for DC cardioversion. One hundred sixty‐eight patients were randomized, 167 received study treatment, and 159 were included in per‐protocol analyses. The mean duration of current AF episode was 47 days (range, 0.8–92). In the AZD7009 30‐minute 3.25 mg/min group, 21 of 42 patients converted within 90 minutes, compared with 7 of 39, 7 of 36, and 0 of 42 patients in the 15‐minute 3.25 mg/min, 15‐minute 4.4 mg/min, and combined placebo groups, respectively. Patients not converted within 90 minutes underwent DC cardioversion. In patients with AF episodes ≤30 days, conversion rates with AZD7009 30‐minute 3.25 mg/min and after placebo followed by DC cardioversion were 82% and 83%, respectively. AZD7009 was generally well tolerated. Mean QTc increased by 15% to 20% in the AZD7009 treatment groups. One patient experienced a ventricular tachyarrhythmia of 7 beats, with features of torsades de pointes. AZD7009 was associated with a 50% conversion rate in the best‐dose group. In patients with AF episodes ≤30 days, the conversion rates after AZD1305 and placebo followed by DC cardioversion were observed to be similar.