bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermogenic side effects to migratory predisposition in shorebirds
Authors: Vézina François , Jalvingh Kirsten M. , Dekinga Anne , Piersma Theunis
Published: December 2006

In the calidrine sandpiper red knot ( Calidris canutus), the weeks preceding takeoff for long-distance migration are characterized by a rapid increase in body mass, largely made up of fat but also including a significant proportion of lean tissue. Before takeoff, the pectoral muscles are known to hypertrophy in preparation for endurance flight without any specific training. Because birds facing cold environments counterbalance heat loss through shivering thermogenesis, and since pectoral muscles represent a large proportion of avian body mass, we asked the question whether muscle hypertrophy in preparation for long-distance endurance flight would induce improvements in thermogenic capacity. We acclimated red knots to different controlled thermal environments: 26°C, 5°C, and variable conditions tracking outdoor temperatures. We then studied within-individual variations in body mass, pectoral muscle size (measured by ultrasound), and metabolic parameters [basal metabolic rate (BMR) and summit metabolic rate (Msum)] throughout a 3-mo period enclosing the migratory gain and loss of mass. The gain in body mass during the fattening period was associated with increases in pectoral muscle thickness and thermogenic capacity independent of thermal acclimation. Regardless of their thermal treatment, birds showing the largest increases in body mass also exhibited the largest increases in Msum. We conclude that migratory fattening is accompanied by thermoregulatory side effects. The gain of body mass and muscle hypertrophy improve thermogenic capacity independent of thermal acclimation in this species. Whether this represents an ecological advantage depends on the ambient temperature at the time of fattening.
Microinjection of DLH into the region of the caudal ventral respiratory column in the cat: evidence for an endogenous cough-suppressant mechanism
Authors: Poliacek Ivan , Corrie Lu Wen-Chi , Wang Cheng , Rose Melanie J. , Bolser Donald C.
Published: December 2006

The caudal ventral respiratory column (cVRC) contains premotor expiratory neurons that play an important role in cough-related expiratory activity of chest wall and abdominal muscles. Microinjection of d,l-homocysteic acid (DLH) was used to test the hypothesis that local activation of cVRC neurons can suppress the cough reflex. DLH (20–50 mM, 10–30 nl) was injected into the region of cVRC in nine anesthetized spontaneously breathing cats. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms (EMG) were recorded bilaterally from inspiratory parasternal and expiratory transversus abdominis (ABD) and unilaterally from laryngeal posterior cricoarytenoid and thyroarytenoid muscles. Unilateral microinjection of DLH (1–1.5 nmol) elicited bilateral increases in tonic and phasic respiratory ABD EMG activity, and it altered the respiratory pattern and laryngeal motor activities. However, DLH also decreased cough frequency by 51 ± 7% compared with control ( P < 0.001) and the amplitude of the contralateral (−35 ± 3%; P < 0.001) and ipsilateral (−34 ± 5%; P < 0.001) ABD EMGs during postinjection coughs compared with control. The cough alterations were much less pronounced after microinjection of a lower dose of DLH (0.34–0.8 nmol). No cough depression was observed after microinjections of vehicle. These results suggest that an endogenous cough suppressant neuronal network in the region of the cVRC may exist, and this network may be involved in the control of cough reflex excitability.
Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats
Authors: Tarasiuk Ariel , Segev Yael
Published: December 2006

The effect of upper airway loading on longitudinal bone growth and various components of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis has not been fully elucidated. In the present study, the effect of chronic resistive airway loading (CAL) in a prepubescent rat model on linear bone growth and weight gain was investigated. We hypothesize that CAL induced in prepubescent rats will lead to impaired longitudinal growth due to impairment in circulating and liver GH/IGF-I parameters. The tracheae of 22-day-old rats were obstructed by tracheal banding to increase inspiratory esophageal pressure. The GH/IGF-I markers were analyzed using ELISA, RT-PCR, and Western immunoblot analysis 14 days after surgery. Animals exhibited impaired longitudinal growth as demonstrated by reduction of tibia and tail length gains by 40% ( P < 0.0001) and body weight gain by 24% ( P < 0.0001). No differences were seen in total body energy balance, i.e., oxygen consumption, daily food intake, or arterial blood gases. Circulating GH, IGF-I, and IGF binding protein-3 (IGFBP-3) levels were reduced by 40% ( P = 0.037), 30% ( P < 0.006), and 27% ( P = 0.02), respectively, in the CAL group. Liver IGF-I mRNA level decreased by 20% ( P < 0.0002), whereas GH receptor mRNA and protein expression were unchanged. We conclude that impaired longitudinal growth in prepubescent CAL rats is related to a decrease in GH, IGF-I, and IGFBP-3 levels.
Carbohydrate ingestion augmentsl-carnitine retention in humans
Authors: Stephens Francis B. , Evans Claire E. , Constantin-Teodosiu Dumitru , Greenhaff Paul L.
Published: December 2006

Maintaining hyperinsulinemia (∼150 mU/l) during steady-state hypercarnitinemia (∼550 μmol/l) increases skeletal muscle total carnitine (TC) content by ∼15% within 5 h. The present study aimed to investigate whether an increase in whole body carnitine retention can be achieved through l-carnitine feeding in conjunction with a dietary-induced elevation in circulating insulin. On two randomized visits ( study A), eight men ingested 3 g/day l-carnitine followed by 4 × 500-ml solutions, each containing flavored water (Con) or 94 g simple sugars (glucose syrup; CHO). In addition, 14 men ingested 3 g/day l-carnitine followed by 2 × 500 ml of either Con or CHO for 2 wk ( study B). Carbohydrate ingestion in study A resulted in a fourfold greater serum insulin area under the curve when compared with Con ( P < 0.001) and in a lower plasma TC concentration throughout the CHO visit ( P < 0.05). Twenty-four-hour urinary TC excretion in the CHO visit was lower than in the Con visit in study A (155.0 ± 10.7 vs. 212.1 ± 17.2 mg; P < 0.05). In study B, daily urinary TC excretion increased after 3 days (65.9 ± 18.0 to 281.0 ± 35.0 mg; P < 0.001) and remained elevated throughout the Con trial. During the CHO trial, daily urinary TC excretion increased from a similar basal value of 53.8 ± 9.2 to 166.8 ± 17.3 mg after 3 days ( P < 0.01), which was less than during the Con trial ( P < 0.01), and it remained lower over the course of the study (P < 0.001). The difference in plasma TC concentration in study A and 24-h urinary TC excretion in both studies suggests that insulin augmented the retention of carnitine in the CHO trials.
Tracheal stenosis: a flow dynamics study
Authors: Brouns Mark , Jayaraju Santhosh T. , Lacor Chris , De Mey Johan , Noppen Marc , Vincken Walter , Verbanck Sylvia
Published: December 2006

Patients referred for treatment of tracheal stenosis typically are asymptomatic until critical narrowing of the airway occurs, which then requires immediate intervention. To understand how tracheal stenosis affects local pressure drops and explore how a dramatic increase in pressure drop could possibly be detected at an early stage, a computational fluid dynamics (CFD) study was undertaken. We assessed flow patterns and pressure drops over tracheal stenoses artificially inserted into a realistic three-dimensional upper airway model derived from multislice computed tomography images obtained in healthy men. Solving the Navier-Stokes equations (with a Yang-shih k-ε turbulence model) for different degrees of tracheal constriction located approximately one tracheal diameter below the glottis, the simulated pressure drop over the stenosis (ΔP) was seen to dramatically increase only when well over 70% of the tracheal lumen was obliterated. At 30 l/min, ΔP increased from 7 Pa for a 50% stenosis to, respectively, 46 and 235 Pa for 80% and 90% stenosis. The pressure-flow relationship in the entire upper airway model (between mouth and end of trachea) in the flow range 0–60 l/min showed a power law relationship with best-fit flow exponent of 1.77 in the absence of stenosis. The exponent became 1.92 and 2.00 in the case of 60% and 85% constriction, respectively. The present simulations confirm that the overall pressure drop at rest is only affected in case of severe constriction, and the simulated flow dependence of pressure drop suggests a means of detecting stenosis at a precritical stage.
Pharmacokinetics, Metabolism, and Oral Bioavailability of the DNA Methyltransferase Inhibitor 5-Fluoro-2′-Deoxycytidine in Mice
Authors: Beumer Jan H. , Eiseman Julie L. , Parise Robert A. , Joseph Erin , Holleran Julianne L. , Covey Joseph M. , Egorin Merrill J.
Published: December 2006

Purpose: In vivo, 5-fluoro-2′-deoxycytidine (FdCyd) is rapidly and sequentially converted to 5-fluoro-2′-deoxyuridine, 5-fluorouracil, and 5-fluorouridine. The i.v. combination of FdCyd and 3,4,5,6-tetrahydrouridine (THU), a cytidine deaminase (CD) inhibitor that blocks the first metabolic step in FdCyd catabolism, is being investigated clinically for its ability to inhibit DNA methyltransferase. However, the full effects of THU on FdCyd metabolism and pharmacokinetics are unknown. We aimed to characterize the pharmacokinetics, metabolism, and bioavailability of FdCyd with and without THU in mice.

Experimental Design: We developed a sensitive high-performance liquid chromatography tandem mass spectrometry assay to quantitate FdCyd and metabolites in mouse plasma. Mice were dosed i.v. or p.o. with 25 mg/kg FdCyd with or without coadministration of 100 mg/kg THU p.o. or i.v.

Results: The oral bioavailability of FdCyd alone was ∼4%. Coadministration with THU increased exposure to FdCyd and decreased exposure to its metabolites; i.v. and p.o. coadministration of THU increased exposure to p.o. FdCyd by 87- and 58-fold, respectively. FdCyd exposure after p.o. FdCyd with p.o. THU was as much as 54% that of i.v. FdCyd with i.v. THU.

Conclusions: FdCyd is well absorbed but undergoes substantial first-pass catabolism by CD to potentially toxic metabolites that do not inhibit DNA methyltransferase. THU is sufficiently bioavailable to reduce the first-pass effect of CD on FdCyd. Oral coadministration of THU and FdCyd is a promising approach that warrants clinical testing because it may allow maintaining effective FdCyd concentrations on a chronic basis, which would be an advantage over other DNA methyltransferase inhibitors that are currently approved or in development.
Inhibition of SARS-CoV Gene Expression by Adenovirus-Delivered Small Hairpin RNA
Authors: Zhang Xue , Wu Kailang , Yue Xin , Zhu Ying , Wu Jianguo
Published: December 2006

Objective: Severe acute respiratory syndrome (SARS) is a highly contagious and lethal disease caused by a new type of coronavirus, SARS-associated coronavirus (SARS-CoV). Currently, there is no efficient treatment and prevention for this disease. We constructed recombinant adenoviral vectors that can express shRNAs, which inhibited the expression of SARS-CoV genes effectively in mammalian cells. Methods: In this study, we designed several plasmids that express small hairpin RNA molecules (shRNA) specifically targeting to the genes encoding for the SARS-CoV nucleocapsid (N) protein and envelope (E) protein, respectively. Effective shRNA molecules to the viral genes were screened and identified, and then constructed into adenovirus vectors. The effects of adenovirus-delivered small hairpin RNA on SARS-CoV gene expression were determined by RT-PCR, Western blot, and luciferase activity assays. Results: The levels of viral mRNAs and viral proteins of the targets were significantly decreased or completely inhibited in cell lines after being infected with the recombinant adenoviruses that expressed specific shRNA molecules. Conclusions: Since many cell types can be efficiently infected by adenovirus, recombinant adenoviruses could serve as an alternative powerful tool for shRNA delivery and for gene suppression, especially when the targeted cells are resistant to transfection by DNA or RNA. With availability of high titers of adenoviruses and uniform and rapid infection, this approach would have foreseeable wide applications both in experimental biology and molecular medicine.
Human Coronavirus Infection among Children with Acute Lower Respiratory Tract Infection in Thailand
Authors: Theamboonlers Apiradee , Samransamruajkit Rujipat , Thongme Chittima , Amonsin Alongkorn , Chongsrisawat Voranush , Poovorawan Yong
Published: December 2006

Objective: This study was performed to further identify the previously uncharacterized human coronavirus 229E (hCoV-229E) and human coronavirus OC43 (hCoV-OC43) in Thailand by using the RT-PCR technique. In addition, we performed this study in order to delineate the prevalence, the potential clinical impacts and evaluation of the genetic characterization of this pathogen in young children who presented with acute lower respiratory tract infections (ALRI). Methods: We obtained nasopharyngeal secretions (NPs) from 226 children <5 years of age who were either attending the outpatient department or hospitalized with ALRI from March 2002 to July 2003. All clinical, laboratory, RT-PCR, direct sequencing and phylogenetic analysis data were collected and analyzed. Results: Of the 226 NPs samples from infants and young children presented with ALRI, 8 (3.54%) were positive for hCoV-229E, 2 (0.88%) were positive for hCoV-OC43, and 1 (0.44%) had co-infection. The following clinical presentations were noted: fever (100%), rhinitis (44%), acute bronchiolitis (44%), viral pneumonia (33%), viral pneumonia triggering asthma exacerbation (11%) as well as viral pneumonia causing BPD exacerbation (11%). All positive samples were subjected to direct sequencing. The amino acid sequences had 82–99% similarity to previous sequences stored in the GenBank database. Conclusion: The molecular technique we applied to detect human coronavirus appears justified as a valuable diagnostic approach to elucidate the prevalence, cause and clinical implications of ALRI among infants and young children.
Intra- and Intergenotypic Variations among Human Cytomegalovirus gB Genotypes
Authors: Chantaraarphonkun S. , Bhattarakosol P.
Published: December 2006

Objectives: To study genotypic variations among human cytomegalovirus (HCMV) gB genotypes in clinical samples of Thai patients. Methods: gB genotyping of 31 HCMV-DNA-positive clinical samples were determined by PCR-RFLP, gene cloning and DNA sequencing methods. Results: Eight gB1, 7 gB2, 7 gB3, 6 gB untype (UT1 and UT2) and 3 mixed gB genotypes were first identified by PCR-RFLP. All 3 mixed gB genotype samples and 1 gB2 sample were cloned and confirmed gB genotype by PCR-RFLP. Altogether, 57 strains (27 unique types and 30 transformants) were further analyzed by DNA sequencing method. Discordant results between PCR-RFLP and DNA sequencing methods were demonstrated in 5 samples and 1 clone. The gB UT1 and UT2 were all classified as gB1 except 1 sample of UT1 (9D), suggesting a new variant. Each genotype had a similarity of more than 97%, whereas strains of different genotypes had 77.71–92.75% homology. The most divergent type was gB3. Conclusions: Intra- and intergenotypic variations among strains were demonstrated either in individual or distinct patients. Intragenotypic variation in a person occurs possibly due mainly to a point mutation mechanism rather than reinfection of a new gB genotype.
Entry into and Production of the Japanese Encephalitis Virus from C6/36 Cells
Authors: Boonsanay Verawan , Smith Duncan R.
Published: December 2006

Objectives: The mosquito-borne Japanese encephalitis virus is a leading cause of encephalitis worldwide. However, few studies have investigated the kinetics of Japanese encephalitis virus internalization and production in mosquito cells, and fewer still have investigated the nature of the molecules involved in the binding of the virus to mosquito cells. Methods: Using the Aedes albopictus/Stegomyia albopicta-derived C6/36 cell line, Japanese encephalitis virus internalization and production were assayed by standard plaque assay, and virus binding was investigated through preinfection enzymatic treatment of cells and virus overlay protein-binding assay of membrane fractions in native and denaturing gels. Results: The internalization of the virus was nonlinear, and intracellular infective viruses were detected 8 h after infection and exported to the medium 10 h after infection. The internalization of the virus was primarily mediated by protein elements, and several bands were observed after overlay assay to membrane proteins, although mass spectroscopy was unable to identify candidate proteins. Soluble laminin produced a marginal, but dose-dependent inhibition of infection. Conclusions: These results suggest that the mechanism of Japanese encephalitis entry, production, attachment and receptor usage are distinct from those employed by the dengue viruses.
Immunologic Analysis Induced by DNA Vaccine Encoding E Protein of Beijing-1 Strain Derived from Japanese Encephalitis Virus
Authors: Feng Guo-he , Liu Ning , Zhou Yan , Zhai Yong-zhen , Li Xi-mei , Dou Xiao-guang
Published: December 2006

Objective: We have compared the gene expression and DNA immunization efficacy encoding prME and E proteins of a different strain (JaGAr-01) derived from Japanese encephalitis virus. This study aimed to construct a recombinant encoding E protein of the Beijing-1 strain derived from Japanese encephalitis virus and analyze the humoral, cellular and protective immunity induced by the above recombinant. Methods: The recombinant pJBE containing E (1,500 bps) gene from the Beijing-1 strain of Japanese encephalitis virus was constructed and then transfected into the HepG2 cell line by liposome fusion. The expression of E (about 53 kD) protein in transfected cells was analyzed by Western blot using a specific anti-JEV-E antibody. BALB/c mice were vaccinated with 3 µg of pJBE by the gene-gun technique. JaGAr-01 and Beijing-1 strains (105 PFU/100 µl) of Japanese encephalitis virus were given to BALB/c mice by intraperitoneal injection 3 weeks after double DNA immunization with a lethal virus challenge. BALB/c mice were observed for 21 days after challenge. An 80% plaque reduction neutralization test was performed to titrate the neutralization antibody before and after viral challenge. A lactate dehydrogenase activity release test was used to examine cytotoxic T lymphocyte activity after double DNA immunization. Results: The expression of about 53 kD protein associated with pJBE was determined in transfected HepG2 cells with specific anti-JEV-E antibody. A higher level of neutralization antibodies and the cytotoxicity effect were induced with pJBE immunization using the gene-gun technique, and were similar to those induced with inactivated vaccine derive from the Beijing-1 strain of Japanese encephalitis virus. Balb/c mice immunized with pJBE survived the challenge with the different strains of Japanese encephalitis virus; however, Balb/c mice immunized with inactivated vaccine did not survive the challenge with the JaGAr-01 strain of Japanese encephalitis virus at all. Conclusions: DNA vaccine containing the E protein gene derived from Japanese encephalitis virus can provide not only better efficacy including humoral and cellular immunity, but also cross-protection against infection with homologous and heterologous Japanese encephalitis virus.
Effects of Mitogen-Activated Protein Kinase Inhibitors on Tumor Necrosis Factor-α Gene Expression and Apoptosis Induction in Cultured Human Fetal Membrane Chorion Cells Infected with Influenza Virus
Authors: Uchide Noboru , Ohyama Kunio , Bessho Toshio , Toyoda Hiroo
Published: December 2006

Objectives: We investigated the involvement of p38 mitogen-activated protein (MAP) kinase in tumor necrosis factor (TNF)-α gene expression, apoptosis induction and virus replication in cultured human fetal membrane chorion cells infected with influenza virus. Methods: Influenza virus-infected chorion cells were incubated in the absence or presence of inhibitors of p38 MAP kinase, SB203580 and SB202190. TNF-α mRNA and hemagglutinin viral RNA (HA vRNA) were amplified with reverse transcriptase-polymerase chain reaction techniques. TNF-α protein concentrations were determined by enzyme-liked immunosorbent assay. The extent of apoptosis induction was estimated by DNA agarose gel electrophoresis. Pyrrolidine dithiocarbamate (PDTC) and ribavirin, which have been shown to inhibit apoptosis induction via the inhibition of viral gene replication, were used as positive control reagents. Results: PDTC and ribavirin inhibited the accumulation of TNF-α mRNA and HA vRNA in the virus-infected chorion cells, resulting in the suppression of TNF-α protein secretion. Both SB203580 and SB202190 suppressed TNF-α protein secretion, but not the accumulation of TNF-α mRNA as well as HA vRNA and the induction of apoptosis. Conclusions: These results suggest that p38 MAP kinase pathway is critical in TNF-α gene expression at a post-transcriptional level but not in the apoptosis induction and influenza virus replication in cultured chorion cells.
Taurine as a Marker for Foetal Wellbeing?
Authors: de Boo Hendrina A. , Harding Jane E.
Published: December 2006

Background: After placental embolisation in pregnant sheep, we found elevated plasma taurine concentrations in several foetuses. These animals also had higher morbidity and mortality than foetuses with normal taurine concentrations. We therefore re-analysed our foetal growth and metabolism data with embolised animals divided into subgroups with high taurine concentrations (EH) and low taurine concentrations (EL). Objective: To investigate the hypothesis that foetal plasma taurine concentrations may be used as a marker for foetal wellbeing. Methods: Growth, metabolic and endocrine parameters were measured in normally grown foetal sheep and in those who had EH or EL after placental embolisation. Results: EH animals were more compromised than the EL animals, as shown by reductions in foetal weight and hind limb length and a failure to increase growth rate (chest girth increment) after embolisation. EH foetuses were hypoxaemic, hypoglycaemic and had increased lactate concentrations. Kidney, liver and adrenal weights were increased and thymus weight was decreased in EH animals. Maternal amino acid concentrations were elevated in EL animals. Foetal amino acid concentrations were more reduced in EH animals than in EL animals. Maternal IGF-1 concentrations were increased in EL, but not EH animals. Conclusions: Animals with EH were less able to compensate for the effects of embolisation than animals with EL. Taurine may have been released by the tissues as a protective mechanism against hypoxia-induced inflammation, or in an attempt to maintain osmotic balance. The connection between taurine and foetal wellbeing deserves further investigation.
Efficacy and Tolerance of High-Dose Inhaled Ipratropium Bromide vs. Terbutaline in Intubated Premature Human Neonates
Authors: Fayon Michael , Tayara Nawar , Germain Christine , Choukroun Marie-Luce , Dumas De La Roque Eric , Chêne Geneviève , Breilh Dominique , Marthan Roger , Demarquez Jean-Louis
Published: December 2006

Background: There is insufficient data to reliably assess the benefit of bronchodilators in ventilated premature neonates. Objectives: To compare the efficacy/tolerance of inhaled ipratropium bromide (IB) vs. terbutaline (T) and to describe factors associated with their efficacy. Methods: A cross-over randomized controlled double-blind trial including intubated neonates with respiratory distress syndrome. Two puffs of IB or T were administered at 0, 20, 40 min. Passive respiratory system resistance (Rrs) and compliance (Crs) were measured at 0, 20, 40, 60 min. A positive response was defined as a >2 individual coefficients of variation decrease in Rrs or increase in Crs. Results: Twenty-one infants (gestational age (mean ± SD): 27.3 ± 1.6 weeks; birth weight: 947 ± 250 g; postnatal age: 20 ± 9 days) were included. At 60 min, no treatment effect for Rrs and Crs could be identified (cross-over analysis). Overall data (irrespective of order of administration) showed that after 6 puffs, the decrease in Rrs was greater in the IB vs. T group (–17.0 ± 22.2% vs. –11.3 ± 26.7%, respectively (NS)). Thirty-eight percent of infants responded to IB vs. 43% to T. However, in 19% of patients, decreased Crs was observed after 6 puffs of T. No marker of a positive or paradoxical response could be identified. Treatment was well-tolerated. Conclusion: High doses of bronchodilators are required in ventilated neonates, but the positive response rate was <50%. Their long-term benefit remains to be proven.
High-Sensitivity C-Reactive Protein in Umbilical Cord of Small-for-Gestational-Age Neonates
Authors: Trevisanuto Daniele , Doglioni Nicoletta , Altinier Sara , Zaninotto Martina , Plebani Mario , Zanardo Vincenzo
Published: December 2006

Background: Several epidemiological studies reported a significant correlation between low birth weight and cardiovascular disease in adult life. Recent studies showed that an inflammatory response has been associated with the development of atherosclerosis. High-sensitivity C-reactive protein (hs-CRP) has been demonstrated to be a sensitive marker of this inflammatory process giving prognostic information in apparently healthy general population as well as in patients with symptomatic atherosclerosis.We hypothesized that the chronic inflammatory process, involved in the future atherosclerotic injury, could be found during the fetal period. Objectives:To compare umbilical cord hs-CRP concentrations between small-for-gestational-age (SGA) and appropriate-for-gestational age (AGA) neonates. Methods: Concentrations of hs-CRP (Dade Boehring®) were measured in 35 SGA infants (gestational age: mean ± SD, 34.6 ± 3.0 weeks) and in 69 AGA neonates (34.2 ± 3.4 weeks). Neonates with a history of suspected or proven feto-maternal infection were excluded. Results: In SGA infants, hs-CRP concentrations were significantly higher than in AGA neonates: median (range); 0.06 mg/l (0.02–5.53) vs. 0.02 mg/l (0.02–0.55); p = 0.003. Concentrations of hs-CRP were higher than the detection limit (0.04 mg/l) in 25 (71.5%) SGA infants and in 28 (40.6%) AGA neonates (p = 0.002). Conclusions: In SGA infants, hs-CRP concentrations are higher than in AGA neonates suggesting the presence of an inflammatory process in this group of patients during the fetal life. This finding could be involved in the previously reported relationship between low birth weight and cardiovascular disease in adult life.
Sensitization of Cardiac Responses to Pain in Preterm Infants
Authors: Pineles Beth L. , Sandman Curt A. , Waffarn Feizal , Uy Cherry , Davis Elysia Poggi
Published: December 2006

Background: Preterm infants are repeatedly exposed to painful experiences as part of their care in the neonatal intensive care unit. There is evidence from both animal and human studies that exposure to pain during the neonatal period may have persisting consequences for development. Objective: To perform serial assessments of three heelstick blood draws to examine early changes both in physiological and behavioral responses to repeated exposure to painful stimuli in preterm infants. Methods: Heart rate and behavioral responses to three serially administered heelstick blood draws were evaluated in 22 medically stable preterm infants with less than 48 h of mechanical ventilation who were admitted to the neonatal intensive care unit. Results: Heart rate and behavioral agitation significantly increased during each heelstick as compared to baseline. The heart rate response was larger to the third heelstick as compared to the first two procedures. Behavioral responses did not change across the three assessments. Conclusions: Healthy preterm infants sensitize to heelstick-induced pain, as measured by their heart rate responses. These data suggest that greater attention to the effects of repeated pain for the neonate is needed.
The Added Value of Simultaneous EEG and Amplitude-Integrated EEG Recordings in Three Newborn Infants
Authors: de Vries Nathalie K.S. , ter Horst Hendrik J. , Bos Arend F.
Published: December 2006

Amplitude-integrated electroencephalograms (aEEGs) recorded by cerebral function monitors (CFMs) are used increasingly to monitor the cerebral activity of newborn infants with encephalopathy. Recently, new CFM devices became available which also reveal the original EEG signals from the same leads. To date it was unclear whether this single-lead EEG provides additional information towards interpreting the aEEG traces more accurately. Our report deals with three cases in which the single-lead EEG from the CFM device did indeed reveal important additional information not provided by the aEEG alone. In cases 1 and 3, the aEEGs showed drifting of the baseline to higher amplitudes. The single-lead EEG revealed that this was due to muscle artefacts, high-frequency oscillation ventilation and the electrocardiogram rather than to cerebral activity. Hence, without knowledge of the EEG, the aEEG trace might have been misinterpreted as being fairly normal. Case 2 showed paroxysmal elevation of the lower margin of the amplitude on the aEEG which looked like epileptic activity. However, additional information from the single-lead EEG revealed that it was due to muscle artefacts. Thus, simultaneously recorded EEG can help to interpret seizure-like episodes on the aEEG. Conclusion: Simultaneously recorded single-lead EEGs can help to interpret aEEG traces more accurately.
Tyramide Signal Amplification: An Enhanced Method for Immunohistochemistry on Methyl-Methacrylate-Embedded Bone Marrow Trephine Sections
Authors: Gaiser Timo , Bernhards Joachim
Published: December 2006

The detection of cellular antigens in bone marrow sections depends on the method of embedding, the nature of antigen and antibody, antigen retrieval techniques and the sensitivity of the immunohistochemical method. This study evaluated a fluorescyl-tyramide-enhanced immunostaining method on methyl-methacrylate-embedded bone marrow trephine biopsies. Compared with the standard immunostaining technique, fluorescyl-tyramide-enhanced immunostaining showed a superior signal intensity on methyl- methacrylate-embedded bone marrow trephines. Thus, the fluorescyl-tyramide-based immunostaining method, while retaining specificity, is highly sensitive and provides optimal staining results for a broad panel of antibodies commonly used for the routine diagnosis and classification of hematological disorders.
HHV-8-Associated Lymphoma: State-of-the-Art Review
Authors: Carbone Antonino , Gloghini Annunziata
Published: December 2006

During the first decade after the discovery of primary effusion lymphoma (PEL), sporadic and serial reports suggested that Kaposi-sarcoma-associated-herpesvirus/human-herpesvirus-8 (KSHV/HHV-8)-associated lymphomas in their liquid and solid presentation are clinically distinct, representing part of the spectrum of PEL. In HIV-seropositive patients with serous effusions, these solid lymphomas were reported before the development of an effusion lymphoma and following resolution of PEL. More recently, solid lymphomas not associated with lymphomatous effusion have been found in HIV-seropositive and HIV-seronegative patients. Despite the diversification in the clinical presentation of KSHV/HHV-8-associated lymphomas, most cases demonstrated a similar morphology, immunophenotype and KSHV/HHV-8 viral status.
Healthy Aging Is Associated with Unaltered Production of Immunoreactive Growth Hormone but Impaired Neuroimmunomodulation
Authors: Luz Clarice , Collaziol Diego , Preissler Thales , da Cruz Ivana M. , Glock Luiz , Bauer Moisés E.
Published: December 2006

Background: Both endocrine and immune systems are continuously remodeled during aging. Objective: Here, we investigated to what extent adrenal and somatosenescence are associated reciprocal changes in the immune system during strictly healthy aging. Methods: Forty-six elderly subjects and 33 young adults were recruited according to the health criteria of the SENIEUR protocol. Peripheral blood mononuclear cells were isolated and stimulated in vitro with lipopolysaccharide or phytohemagglutinin to assess the production of immunoreactive growth hormone (GH). Peripheral sensitivity to steroids was assessed in vitroby dexamethasone-, cortisol- or dehydroepiandrosterone (DHEA)-induced inhibition of T-cell proliferation. DHEA and GH levels were measured by radioimmunoassays. Results: Healthy elderly had lower salivary DHEA and serum GH levels (somatosenescence). They presented reduced T-cell sensitivity to dexamethasone but similar cellular sensitivities to cortisol and DHEA. Their cells produced similar levels of immunoreactive GH compared to the cells of young adults. Conclusions: These data indicate that healthy aging is associated with adrenal and somatosenescence as well as impaired neuroendocrine immunoregulation at the level of the lymphocyte. In addition, somatosenescence may not be associated with a reciprocal decline in immunoreactive GH.
A New Equation for Estimating Renal Function Using Age, Body Weight and Serum Creatinine
Authors: Virga Giovambattista , Gaspari Flavio , Thomaseth Karl , Cara Marilena , Mastrosimone Stefania , Rossi Vittorio
Published: December 2006

Background: Many formulas have been developed to estimate glomerular filtration rate (GFR). The aim of our study was to propose a new, more reliable equation. Methods: The study considered 530 subjects (training sample) with M/F 280/250, age 57.1 ± 17.4, creatinine clearance (CrCl) 55.2 ± 38.2 (range 2.1–144.0) for the development the new equation. A linear model was used to describe Cr production using serum Cr (sCr), age, and body weight (BW) as variables: (CrCl + b4) · sCr = b1 – (b2 · age) + (b3 · BW) subsequently estimating parameter values by linear least squares, with CrCl as the dependent variable, and 1/sCr, age/sCr, BW/sCr as independent variables. CrCl = {[69.4 – (0.59 · age) + (0.79 · BW)]/sCr} – 3.0 (males) and {[57.3 – (0.37 · age) + (0.51 · BW)]/sCr} – 2.9 (females). A 229-patient renal failure validation sample with M/F 166/63, age 53.0 ± 14.8, GFR 32.0 ± 14.3 (range 4.3–69.8), assessed using iohexol Cl, was considered to compare the Cockcroft-Gault (C-G) and MDRD formulas with the new equation for estimating GFR. Results: The mean % error in GFR estimated by the new equation (+2.3 ± 28.3%) was better than with the C-G and MDRD formulas (+5.2 ± 30.1% and –11.4 ± 25.9%, respectively, p < 0.0005 and p < 0.0001), and so was the mean absolute % error, bordering on statistical significance (19.8 ± 20.3 vs. 21.1 ± 22.0 and 22.4 ± 17.3, p = 0.08 and p < 0.005). The precision was also better (RMSE = 7.89 vs. 8.02 and 9.13). The Bland-Altman test showed no GFR over or underestimation trend (measured ± predicted GFR/2 vs. % error, R2 = 0.001). Conclusions: The new equation appears to be at least as accurate as the C-G and MDRD formulas for estimating GFR.
Glucocorticoid-Induced Diabetes Mellitus: Prevalence and Risk Factors in Primary Renal Diseases
Authors: Uzu T. , Harada T. , Sakaguchi M. , Kanasaki M. , Isshiki K. , Araki S. , Sugiomoto T. , Koya D. , Haneda M. , Kashiwagi A. , Yamauchi A.
Published: December 2006

Background/Aims: In patients with primary renal diseases the current knowledge of hyperglycemia associated with corticosteroid therapy is limited. We therefore examined the prevalence and risk factors of glucocorticoid-induced diabetes mellitus (DM) in primary renal diseases. Methods: Patients were recruited with primary renal diseases who were started on corticosteroids between April 2002 and June 2005. In patients with DM, an impaired fasting glucose level and/or positive urinary glucose analyses before corticosteroids therapy were excluded. Results: During corticosteroid therapy (initial dose: prednisolone 0.75 ± 0.10 mg/kg/day), DM was newly diagnosed in 17 (40.5%) of 42 patients. All of the 17 patients were diagnosed as having DM by postprandial hyperglycemia at 2 h after lunch, although they had normal fasting blood glucose levels. Age (OR 1.40, 95% CI 1.06–1.84) and body mass index (OR 1.87, 95% CI 1.03–3.38) were determined as independent risk factors for glucocorticoid-induced DM. Conclusion: Over 40% of patients with primary renal disease developed DM during treatment with corticosteroids. A high age and high body mass index are the independent risk factors for glucocorticoid-induced DM. 24-hour urinary glucose analyses and postprandial plasma glucose are useful for detecting glucocorticoid-induced DM.
Long-Term Outcome of Paediatric Renal Transplantation: Follow-Up of 300 Children from 1973 to 2000
Authors: Rees Lesley , Shroff Rukshana , Hutchinson Carol , Fernando Oswald N. , Trompeter Richard S.
Published: December 2006

Background/Aim: To report our experience of paediatric renal transplantation at Great Ormond Street and Royal Free Hospitals since the inception of the programme. Methods: Retrospective review of the patient and transplant survival and influencing factors in the 300 children transplanted between 1973 and 2000. Results: 300 children had received a total of 354 transplants; 56 were living-related donations. The median age at transplantation was 10.3 (range 1.4–17.9) years. Forty-four percent had congenital structural abnormalities of the urinary tract. Forty-six children required a second and 8 a third transplant before transfer to an adult unit. The overall patient survival at 5, 10, and 20 years was 97, 94, and 72%, respectively. In the overall cohort, the donor type (deceased donor or living-related donor) did not affect mortality, nor did age at transplantation, but those transplanted before 5 years of age had a significantly shorter post-transplant survival time (p < 0.0001). Transplant survival (first transplant) for deceased and living-related donors was 66 and 87% at 5 years (p < 0.01), 51 and 54% at 10 years, and 36% at 20 years (deceased-donor transplants only). Although the overall transplant survival was inferior in children transplanted before 2 years of age (p < 0.03), in the most recent cohort (1990–2000), age did not affect the outcome. On multiple regression analysis, the only predictor of transplant survival was the era of transplantation (p < 0.001). The median final height was within the normal range for males and females; 7 patients received growth hormone after transplantation. Conclusions: The outlook for successful transplantation is improving, and in the last decade was unaffected by age at transplantation. The survival of living-related donor transplants is superior to deceased-donor transplants for the first 5 years. From the above data, we can predict that a 10-year-old child receiving a renal transplant in 2000 and on ciclosporin-based immunosuppression can expect a transplant half-life of 13.1 years from a living-related donor and one of 10.8 years from a deceased-donor transplant.
Could Streptococcal Erythrogenic Toxin B Induce Inflammation prior to the Development of Immune Complex Deposits in Poststreptococcal Glomerulonephritis?
Authors: Mosquera Jesus , Romero Maritza , Viera Ninoska , Rincon Jaimar , Pedreáñez Adriana
Published: December 2006

Acute poststreptococcal glomerulonephritis (APSGN) is a consequence of the immune response to streptococcal antigens with further in situ antigen-antibody interaction and deposition of circulating immune complexes, resulting in the activation of complement and the inflammatory process. These events are related to a previous antibody response. However, early renal events, when circulating streptococcal antigens bind to the kidney during streptococcal infection, remain unknown. Cationic streptococcal erythrogenic toxin type B (ETB) and its precursor (ETBP) are largely produced by nephritogenic streptococci and have high affinity for anionic glomerular structures. Renal deposition of ETB/ETBP makes conceivable a possible interaction between these streptococcal proteins with intrinsic glomerular cells or infiltrating leukocytes. Since ETB/ETBP are chemotactic for leukocytes and capable of inducing proliferation, cytokine and chemokine production, expression of adhesion molecules and apoptosis in renal cells and leukocytes, the early presence of these proteins could be a relevant event before and during antigen-antibody interaction takes place in renal tissues.
Co-Administration of Acetyl-11-Keto-β-Boswellic Acid, a Specific 5-Lipoxygenase Inhibitor, Potentiates the Protective Effect of COX-2 Inhibitors in Kainic Acid-Induced Neurotoxicity in Mice
Authors: Bishnoi Mahendra , Patil C.S. , Kumar Anil , Kulkarni Shrinivas K.
Published: December 2006

Cyclooxygenase (COX) and lipoxygenase (LOX) are responsible for the metabolism of arachidonic acid into inflammatory metabolites, prostaglandins and leukotrienes, respectively. The upregulation of these enzymes in the central nervous system has been demonstrated to be responsible for the increased neuronal vulnerability to degeneration. Kainic acid, a glutamate receptor agonist and responsible for neuronal excitotoxicity and oxidative damage via different mechanisms, is capable of stimulating mRNA of both COX-2 and 5-LOX in the brain. The present study was designed to study the effects of COX inhibitors (indomethacin, nimesulide, rofecoxib) and a 5-LOX inhibitor (acetyl-11-keto-β-boswellic acid; AKBA) and the combination of these inhibitors (dual inhibition) on kainic acid induced excitotoxicity and oxidative and nitrosative damage in mice. The results from the present study indicated that AKBA, indomethacin, and nimesulide per se did not produce any change in the behavioural parameters after kainic acid administration; however, rofecoxib per seproduced a significant increase in the latency of clonic (seizure-like) movement and a decrease in mortality rate as compared with kainic acid treated animals. In combination studies AKBA, rofecoxib, and nimesulide produced a more pronounced effect than either of these drugs alone. Further, the effect of AKBA combined with rofecoxib was significantly more marked when compared with AKBA combined with nimesulide. Besides this, identical results were found for the effect of these agents and their combination against oxidative damage induced by kainic acid. These findings indicate the potential role of COX-2 inhibitors and also their combination with the 5-LOX inhibitor in kainic acid induced excitotoxicity and oxidative damage by virtue of their antioxidant effect and suggest the need for the development of dual inhibitors for the treatment of neuronal excitotoxicity.
Novel Approaches to Treatment of Autoimmune Neuroinflammation and Lessons for Drug Development
Authors: Nizri Eran , Irony-Tur-Sinai Michal , Grigoriadis Nikolaos , Abramsky Oded , Amitai Gabi , Brenner Talma
Published: December 2006

Drug development, and especially that intended for central nervous system (CNS) disorders, still poses a challenge. We investigated both the use of bifunctional compounds designed for multiple targeting and enhanced CNS permeability, and of recombinant α-fetoprotein (AFP), a natural pregnancy-associated immunomodulating protein for the treatment of CNS inflammation. Bifunctional compounds showed a novel pharmacokinetic profile due to the conjugation, yet retained, and even improved pharmacodynamics. AFP was well tolerated and decreased various aspects of neuroinflammation, including disease severity, axonal loss and damage, T-cell reactivity, and antigen presentation. Our results show that both strategies may serve as future drug modalities.
Risk Indicators of Pre-Eclampsia in North Jordan: Is Dental Caries Involved?
Authors: Khader Yousef , Jibreal Muna , Burgan Samar , Amarin Zouhair
Published: December 2006

Background: Despite a huge body of published research, understanding the basic pathology that leads to pre-eclampsia is still incomplete. This study was conducted among women in north Jordan to determine factors associated with pre-eclampsia and to determine if dental caries was involved. Methods: A case-control study was carried out among women who delivered at Princess Badea Teaching Hospital, Irbid, North Jordan, between September 1, 2004 and January 1, 2005. 115 women with pre-eclampsia and 230 normotensive controls were included in the study. Information regarding participants’ demographics, antenatal history and family history were collected through personal interviews. Several oral parameters were measured for each participant. Results: In multivariate analysis, factors found to be associated with increased odds of pre-eclampsia were age ≧35 years (adjusted OR 2.20; 95% CI 1.08, 4.48), nulliparity (adjusted OR 2.73; 95% CI 1.38, 5.39), emotional stress during pregnancy (adjusted OR 4.22; 95% CI 1.79, 9.90), maternal history of pre-eclampsia (adjusted OR 16.04; 95% CI 5.82, 44.22), family history of cardiovascular diseases (adjusted OR 2.82; 95% CI 1.22, 6.51), family history of pre-eclampsia (adjusted OR 23.26; 95% CI 5.07, 106.78), twin births (adjusted OR 37.79; 95% CI 4.22, 338.51), and Body Mass Index (BMI). In comparison with women with pre-pregnancy BMI <25, adjusted OR were 1.97, 95% CI 1.02, 3.81 for women with BMI from 25 to 29.9, and 3.31, 95% CI 1.36, 8.03 for women with BMI ≧30. Mean decayed teeth surface was found to be associated with increased odds of pre-eclampsia (adjusted OR 1.14, 95% CI 1.03, 1.27). Conclusion: This study demonstrated no difference to reported risk indicators of pre-eclampsia in other populations, but adds that dental caries may have an association with increased odds of pre-eclampsia.
Hypoxia Represses the Differentiation of Rcho-1 Rat Trophoblast Giant Cells
Authors: Takeda Takashi , Sakata Masahiro , Isobe Aki , Yamamoto Toshiya , Nishimoto Fumihito , Minekawa Ryoko , Okamoto Yoko , Tasaka Keiichi , Murata Yuji
Published: December 2006

Background: A hypoxic environment is known to be essential for early placentation. A low oxygen tension induces hypoxia-inducible factor-1 (HIF-1α) which may play an important role as a transcription factor in maintaining the proliferative and undifferentiated phenotype in human trophoblasts. Methods: We analyzed the effect of a low oxygen tension on the rat trophoblast giant cell differentiation pathway using Rcho-1 cells which were derived from rat choriocarcinomas and consist of trophoblast stem cells. Results: We found that a low oxygen tension suppressed the morphological changes and steroidogenesis during differentiation. The anticipated downregulation of the Id-1 transcription factor, a negative regulator of trophoblast giant cell differentiation, was not observed in the hypoxic environment. On the other hand, deferoxamine, which mimics hypoxia and induces HIF-1α, caused downregulation of Id-1 transcription factor and trophoblast giant cell differentiation. Conclusion: These results indicate that hypoxia represses rat trophoblast giant cell differentiation via an HIF-1α-independent pathway.