bluuebunny/crossref_metadata_2025 huggingface dataset:
Occurrence of Periodic Sleep Spindles within and across Non-REM Sleep Episodes
Authors: Himanen Sari-Leena , Virkkala Jussi , Huupponen Eero , Niemi Jukka , Hasan Joel
Published: December 2003

Sleep spindles have been reported to occur both as single events and periodically in sequences. However, there is no systematic description about the occurrence of spindles in sequences in relation to time of night. The aim of the present study was to examine the temporal occurrence of periodic sleep spindles during the night. Sleep spindles of 19 healthy subjects were selected visually. A minimum of three consecutive spindles was required to form a spindle sequence. A 5-second upper time interval limit was applied as the longest duration between spindles belonging to a spindle sequence. The number of spindles and time occupied by spindle sequences increased from the first to the fourth non-REM (NREM) sleep episode. Within NREM sleep episodes, the number of spindles and spindle sequences dominated at the beginning. In the first two NREM sleep episodes with high slow-wave activity (SWA), there were few spindle sequences and they decreased with increasing SWA. In the third and fourth NREM sleep episode with less SWA, there were more spindle sequences and they were more evenly distributed. It is possible that in the first NREM sleep episodes, hyperpolarization of the thalamocortical cells deepens so rapidly that the NREM sleep level, where spindle sequences arise, is passed and spindle sequences are not formed. Spindle sequences could be regarded as markers of the evolution of the NREM sleep process and their lack or excess in relation to time of night and NREM sleep episode can hopefully be used to indicate changes in brain mechanisms behind NREM sleep.
Valproic-Acid-Induced Thrombocytopenia and Hepatotoxicity: Discontinuation of Treatment?
Authors: Lackmann Gerd-Michael
Published: December 2003

We report the case of a 4-year-old boy with long-term sodium valproate (valproic acid; VPA) therapy who suddenly developed clinically relevant thrombocytopenia and signs of hepatotoxicity. Reduction of the VPA dosage led to clinical and laboratory parameter improvement, while discontinuation of therapy was not necessary. The current practice of the management of VPA-induced side effects is discussed in view of the current recommendations from the literature.
Effects of Cariporide (HOE642) on Myocardial Infarct Size and Ventricular Arrhythmias in a Rat Ischemia/Reperfusion Model: Comparison with Other Drugs
Authors: Wajima Teruaki , Beguier Beatrice , Yaguchi Masafumi
Published: December 2003

The effects of pretreatment with cariporide on myocardial infarction and ventricular arrhythmias in a rat model of ischemia/reperfusion were compared with those of nicorandil, propranolol, and nifedipine. Each drug was administered intravenously before coronary occlusion. Cariporide at 0.1, 0.3, and 1 mg/kg significantly reduced the infarct size (infarct mass/risk mass) from 28 ± 4% (vehicle control value) to 9 ± 3, 9 ± 3, and 5 ± 2%, respectively. Propranolol at 2.5 mg/kg also significantly reduced the infarct size to 11 ± 1%. Neither nicorandil nor nifedipine was effective when given at 0.1 mg/kg. Cariporide dose dependently decreased the number of ischemia-induced ventricular premature beats (VPB), incidence and duration of ventricular tachycardia, and the number of reperfusion-induced VPB. Nicorandil was effective against only VPB after reperfusion, and propranolol reduced only postischemic arrhythmias, but nifedipine had no effect on either type of arrhythmia. In summary, cariporide reduced the infarct size and dose dependently suppressed arrhythmias induced by ischemia/reperfusion in rats. In contrast, in the present rat model, the doses of the other three drugs used in this study did not show comparable effects.
Assessment of Bleeding Propensity in Non-Human Primates by Combination of Selective Tissue Factor/VIIa Inhibition and Aspirin Compared to Warfarin and Aspirin Treatment
Authors: Salyers Anita K. , Szalony James A. , Suleymanov Osman D. , Parlow John J. , Wood Rhonda S. , South Michael S. , Nicholson Nancy S.
Published: December 2003

This study in non-human primates was designed to evaluate the bleeding propensity of a selective, small molecule inhibitor of tissue factor (TF)/VIIa in combination with acetylsalicylic acid (ASA) in comparison to the combination of ASA and warfarin. Bleeding time was increased by ASA but was not prolonged further by the addition of the TF/VIIa inhibitor, PHA-927, at doses that elevated the prothrombin time to 8-fold. In contrast, bleeding time was prolonged by warfarin alone and further exacerbated by the presence of ASA. Acute blood loss at the bleeding site, while not significantly increased by either warfarin or PHA-927, was increased substantially in several individuals treated with a combination of warfarin and ASA but not by the combination of TF/VIIa inhibitor and ASA. These data predict that TF/VIIa inhibition, in the presence of chronic aspirin therapy in patients with cardiovascular risk factors, will be a safe therapy for thrombotic disorders.
Gender-Related Differences in the Pharmacodynamics of Furosemide in Rats
Authors: Brandoni Anabel , Villar Silvina R. , Torres Adriana M.
Published: December 2003

The possibility of gender differences in the relationship between dose and efficacy of drugs has historically been limited. The aim of the present study was to evaluate the influence of sex on the pharmacodynamics of furosemide (FUR) in adult Wistar rats. Conventional renal clearance studies were performed in the absence and in the presence of a FUR dose necessary to produce identical urine excretion rates of FUR in both sexes. Fractional excretions of sodium, potassium, and water were similar in male and female rats in the absence of FUR. Natriuretic, kaliuretic, and diuretic responses to FUR, when expressed in fractional terms, were significantly increased in female rats. Diuretic, natriuretic, and kaliuretic efficiencies of FUR were also higher in female rats as compared with males. This might be explained by the lower abundance of the Na-K-2Cl cotransporter observed in homogenates from the medullae of female kidneys as compared with male ones.
Pathology and Neurotransmitter Abnormalities of Dementia with Lewy Bodies
Authors: Duda John E.
Published: December 2003

The neuropathology of dementia with Lewy bodies (DLB) is characterized by the presence of Lewy bodies (LBs) and Lewy neurites (LNs) in specific systems throughout the brainstem, diencephalon, basal ganglia and neocortex. DLB shares many features with Parkinson’s disease (PD) with respect to LB distribution in the brainstem, and there is recent evidence that Lewy pathology (LP), which consists of LBs and LNs, may progress in a systematic fashion through the brain regardless of clinical phenotype. Increasing evidence supports a central role for LNs in Lewy neurodegeneration and engenders a ‘neuritic dystrophy hypothesis’ described herein. LP formation also occurs in Alzheimer’s disease (AD) and other dementias, and it is unclear whether there is a common underlying pathophysiology in these diseases or if the LP merely represents a common final pathway. Cholinergic deficits are evident in both DLB and AD, with reductions in acetylcholine and abnormalities in nicotinic and muscarinic receptor expression in both diseases. Cholinergic deficits are greater in DLB than in AD, although generally there is less brain atrophy in DLB. The lower neurodegeneration and preservation of cholinergic receptors in DLB has important therapeutic implications because patients with DLB (vs. AD) may receive greater benefits from cholinergic pharmacologic therapy. Patients with DLB who display parkinsonian signs have severe dopamine neurotransmitter deficiencies similar to those in patients with PD, although the manifestation of these deficiencies is different. Both groups have striatal dopamine transporter deficiencies, but the striatal dopamine D2 receptors are reduced in DLB patients compared with PD and control subjects. D2 receptor deficiencies in DLB may be the cause of the relative lack of response to levodopa treatment and the severe adverse reaction to neuroleptics in these patients.
Neuroimaging as a Diagnostic Tool in Dementia with Lewy Bodies
Authors: Small Gary W.
Published: December 2003

Due to similar presenting symptoms, many physicians find it difficult to distinguish cases of dementia with Lewy bodies (DLB) from Alzheimer’s disease or Parkinson’s disease with dementia. The pathologic diagnosis of DLB has improved because of the discovery of probes for α-synuclein, a protein found in Lewy bodies. However, pathologic diagnosis can be employed postmortem only, and therefore diagnostic techniques that can be employed to guide patient management are still needed. Consensus criteria have been developed for establishing a clinical diagnosis of DLB, but they lack sensitivity. Therefore, a review of the recent literature was conducted to establish whether neuroimaging studies are useful diagnostic tools to help differentiate these syndromes. At least six types of tests can be used to image the brain of patients with dementia. Structural studies (x-ray, magnetic resonance imaging and computerized tomography) can disclose the presence of stroke sequelae and other lesions, whereas functional studies (magnetic resonance spectroscopy, positron emission tomography and single-photon emission computed tomography) can disclose metabolic and blood flow alterations that may be characteristic for different types of dementia. Although more formal studies are needed to confirm that these imaging techniques are reliable diagnostic tools for DLB and permit the establishment of guidelines for their use, neuroimaging techniques currently are being employed in practice to differentiate dementia types as a guide to treatment.
Brain Magnetic Resonance Imaging White-Matter Lesions and Cerebrospinal Fluid Findings in Patients with Acute Intermittent Porphyria
Authors: Bylesjö Ingemar , Brekke Ole-Lars , Prytz Jan , Skjeflo Trine , Salvesen Rolf
Published: December 2003

Background: Case reports display similaritiesbetween multiple sclerosis and acute intermittent porphyria (AIP). This study examines whether patients with AIP in general demonstrate white-matter lesions on brain magnetic resonance imaging (MRI) and/or abnormalities in plasma and/or cerebrospinal fluid (CSF) when examined outside attacks. We looked particularly for the presence of oligoclonal bands (OB) of immunoglobulin (Ig) in liquor. Methods:Eight AIP gene carriers without previous episodes of porphyria, mean age 42.8 years (range 30–60), and 8 AIP gene carriers with previous episodes of porphyria, mean age 42.8 years (range 33–62), were examined with brain MRI, venous blood samples and lumbar punctures. Results: Two male AIP gene carriers with previous episodes of porphyria, 58 and 35 years of age, had multiple white-matter, high-signal lesions on T2- weighted MRI sequences. Two AIP gene carriers without previous episodes of porphyria, 1 male and 1 female, had less than 5 such lesions. No OB were seen in the CSF in any patient, but 1 carrier had an increased level of protein in the CSF. Seven of 16 subjects (44%) had increased levels of HbA1c (>6.0), suggesting protracted hyperglycemia, and 3 further subjects had borderline levels (5.9). Conclusion: T2-weighted MRI sequences demonstrated multiple white-matter, high-signal lesions in 4 out of 16 AIP gene carriers (25%). No carrier demonstrated OB of Ig in CSF, making it unlikely that demyelinating lesions play a pivotal role in the pathogenesis of CNS symptoms in AIP. Only 1 AIP gene carrier had an increased level of protein in CSF; this contrasts with studies during acute attacks of porphyria. Seven subjects (44%) had abnormally high levels of HbA1c, in spite of the fact that no patient had a previous diagnosis of diabetes mellitus.
Azathioprine and Interferon β1a in Relapsing-Remitting Multiple Sclerosis Patients: Increasing Efficacy of Combined Treatment
Authors: Lus Giacomo , Romano Felice , Scuotto Assunta , Accardo Catello , Cotrufo Roberto
Published: December 2003

Current treatments of relapsing-remitting multiple sclerosis (RRMS) with immunosuppressive or immunomodulatory drugs have been shown to modify the course of the disease in a significative number of patients. However, in many cases, the response to either interferon β (IFN-β) or azathioprine (AZA) treatments was not satisfactory and new therapeutic approaches are needed. We studied clinical and MRI efficacy, safety and tolerance of AZA and IFN-β1a combined therapy in 23 patients with clinically definite RRMS, who had not previously been responsive to either monotherapies. Our cases were divided into three subgroups: 8 previously untreated patients (subgroup A) with at least 2 years of natural course of the disease, 8 patients (subgroup B) previously treated with AZA for 2 years and 7 patients (subgroup C) previously treated with IFN-β1a for 2 years. The baseline Expanded Disability Status Scale (EDSS) ranged from 2 to 4 in all subgroups. All patients completed 2 years of combined treatment with a dose of AZA adjusted to reduce lymphocyte count down to 1,000 ± 100/µl in association with IFN-β1a at a dose of 6 MIU every other day. The mean number of relapses during the combined treatment period was significantly lower than that observed before combined therapy in all the three subgroups. Also, the mean ΔEDSS score was significantly lower during combined treatment than in monotherapy in subgroups B and C. Moreover, after 2 years of combined treatment, the number of new T1 hypointense lesions, the number and volume of proton density/T2 hyperintense lesions and the gadolinium enhancement of T1 hypointense lesions were significantly lower than before combined treatment. After 2 years of treatment, this combination therapy appears to be safe and well tolerated and no serious side effects were reported. Despite some limitations of our study design, the information regarding efficacy, safety and tolerance of the association of AZA and IFN-β is most encouraging.
High Frequency of Primary Sjögren’s Syndrome in Taiwanese Patients Presenting as Relapsing-Remitting Multiple Sclerosis
Authors: Wang Yuh-Jen , Tsai Kwang-Yang , Fuh Jong-Ling , Tsai Ching-Piao , Wang Shuu-Jiun
Published: December 2003

Primary Sjögren’s syndrome (PSS) with central nervous system involvement may mimic the manifestations of multiple sclerosis (MS). The prevalence of PSS in MS patients varies in the published literature (0–16.6%), but has not yet been investigated in Asia, having a much lower MS prevalence than Western countries. Twelve consecutive patients presenting with a relapsing-remitting MS-like syndrome were recruited to assess the presence of PSS according to the American-European consensus group criteria. Six patients (50%) fulfilled the diagnostic criteria of PSS. The preliminary result suggests that PSS is an important differential diagnosis in patients with MS-like syndrome in Taiwan. The prevalence of ‘pure MS’ in Taiwan might be even lower than expected. A further large-scale study is warranted to confirm this finding in Taiwan as well as other Asian countries.
Clinical and [99mTc]TRODAT-1/[123I]IBZM SPECT Imaging Findings in Dopa-Responsive Dystonia
Authors: Hwang Wen-Juh , Yao Wei-Jen , Wey Shiaw-Pyng , Ting Gann
Published: December 2003

We report the clinical and dopamine transporter/D2 receptor single-photon emission computed tomographic (SPECT) imaging findings in a 39-year-old woman with a 24-year history of dopa-responsive dystonia (DRD). The SPECT imaging of the dopamine transporter with [99mTc]TRODAT-1 is helpful in differentiating DRD from early-onset idiopathic parkinsonism. In the later clinical course, the [123I]IBZM SPECT is also helpful in differentiating these two conditions. The patient showed a dramatic and sustained response to levodopa, and needed a smaller dose of levodopa for symptom control in the later course.
POLymorphisms and Risk of Ischemic Stroke (POLARIS) Study: Rationale and Design
Authors: Pruissen D.M.O. , Kappelle L.J. , Algra A.
Published: December 2003

Twin and family-based studies indicate that genetic factors might be involved in the risk of transient ischemic attack (TIA) and ischemic stroke (IS). Identification of genetic risk factors for new vascular events after cerebral ischemia may target secondary prevention. The overall aim of POLARIS is to study which polymorphisms predispose to new vascular events after TIA/IS and to assess their predictive value. Patients who have had a TIA or IS of presumed arterial origin are included. The study design is twofold. In part one the prevalences of polymorphisms will be compared between 300 long-term survivors of the Dutch TIA Trial (average follow-up 10 years) and 820 patients with recent TIA/IS. In part two a cohort of 820 patients with recent TIA/IS will be followed for the occurrence of vascular events for an average of 3.5 years. Several polymorphisms of interest will be genotyped, including factor V Leiden, prothrombin 20210A, 5,10-methylenetetrahydrofolate reductase, HR2 haplotype factor V and factor XIII Val34Leu.
Effect of Interleukin-7 and -15 on Activation of Purified Umbilical Cord Blood and Adult Peripheral Blood CD4+ T Cells
Authors: Lin Syh-Jae , Cheng Po-Jen
Published: December 2003

We investigated the effect of two IL-2 receptor gamma chain (IL-2R-γc)-signaling cytokines, IL-7 and IL-15, on the activation of purified CD4+ lymphocytes from umbilical cord blood (CB) and adult peripheral blood (APB) by assessing the expression of the IL-2 receptor-α (CD25) and Fas (CD95) on CD45RA+ (naïve) and CD45RO+ (memory) CD4+ subsets. Induced CD40L (CD154) expression following phorbol 12-myristate 13-acetate and ionomycin (P+I) stimulation was also examined on cultured CB CD4+ cells. Incubation with IL-15 at 10 ng/ml resulted in a significant increase in the mean fluorescence intensity (MFI) of CD25 on CB CD4+/CD45RA+ cells (exceeding those of APB) without affecting the percentage of CD25-expressing CD45RA+ cells (%CD25/CD45RA). In contrast, both CD25 MFI and %CD25/CD45RA were enhanced on IL-15-treated APB CD4+ cells. CD95 expression (both percent expression and MFI) on CB CD4+/CD45RA+ cells were also enhanced by IL-15, but to a lesser extent compared to the response of ABP. IL-7, used at a concentration equivalent to IL-15, had little effect on APB CD25/CD95 and CB CD25 expression, but did enhance %CD95 expression on CB CD4+/CD45RA+ cells. Both IL-7 and IL-15 could augment the P+I-induced CD40L expression on CB CD4+/CD45RA+ T cells. However, the enhancing effect of IL-15 on CB CD40L/CD45RA expression was more sustained than that of IL-7. Thus, our study demonstrated differential activation of CB CD4+/CD45RA+ cells in response to IL-7 and IL-15 compared to adult counterparts, and the different T-enhancing function between IL-15 and IL-7.
Inter- and Intraobserver Agreement for Gastroesophageal Reflux Detection in Infants Using Multiple Intraluminal Impedance
Authors: Peter Corinna S. , Sprodowski Nadine , Ahlborn Viola , Wiechers Cornelia , Schlaud Martin , Silny Jiri , Poets Christian F.
Published: December 2003

The multiple intraluminal impedance (MII) technique is a new method that allows pH-independent gastroesophageal reflux detection via changes in impedance caused by a liquid bolus inside the esophagus. We wanted to know whether this technique yields objective and reproducible results. Twenty 3- to 6-hour recordings of MII from 19 preterm infants (median gestational age at birth 30 weeks, range 24–34 weeks; age at study 26 days, range 13–93 days) were divided into 23-second segments and analyzed for reflux episodes by three investigators; one investigator analyzed the data set twice. Observer agreement was assessed using kappa statistics. Each investigator analyzed 16,627 23-second segments, with a median of 854 (range 486–979) segments per recording. Median kappa values for the 20 recordings were 0.79, 0.83, and 0.83 for the three pairs of investigators and 0.84 for the repeated scoring procedure. MII recordings could be analyzed with a high level of inter- and intraobserver agreement.
Does Sucrose Analgesia Promote Physiologic Stability in Preterm Neonates?
Authors: Boyer Kristina , Johnston Celeste , Walker Claire-Dominique , Filion Françoise , Sherrard Adam
Published: December 2003

A double-blind, randomized controlled trial was conducted with infants born <31 weeks of gestational age and recruited within 48 h of life. The infants were randomized to receive up to three doses of 0.1 ml of either 24% sucrose or sterile water (placebo) for every painful procedure during the 1st week of life. The purpose of this study was to test the efficacy of treating all procedural pain with sucrose on overall physiological stability. The hypotheses were that infants who received 24% sucrose for all painful procedures would be less stressed as measured by salivary cortisol, and more physiologically stable as measured by pulse rate variability than those who received placebo. Salivary cortisol was measured before and 30 min after a painful procedure, whereas the pulse rate was continuously recorded, from second to second, from a pulse oximeter. There were no group differences in the cortisol response to a painful stimulus or in pulse rate variability over time. There was, however, a significant correlation between standard deviation of pulse rate and number of doses of sucrose only in the group who received high doses of sucrose.
Mechanics of Breathing after Surgical Ligation of Patent Ductus arteriosus in Newborns with Respiratory Distress Syndrome
Authors: Szymankiewicz Marta , Hodgman Joan E. , Siassi Bijan , Gadzinowski Janusz
Published: December 2003

The aim of the study was to detect changes in pulmonary function following ligation of a patent ductus arteriosus (PDA). Pulmonary function was recorded in 16 newborns (birth weight 1,081 ± 166 g, gestational age 27.6 ± 1.7 weeks) before and after ligation. No change in resistance of airways or mean airway pressure was observed. We found an increase in dynamic compliance (Cdyn) of 77% (p < 0.01), in tidal volume (TV) of 29% (p = 0.004), and in minute ventilation (MV) of 17% (p < 0.01) after the procedure. We demonstrated that pulmonary function improves after surgical ligation of the PDA. Because of considerable variation in intubated and spontaneously breathing premature newborns, we recommend the analysis of three main parameters: Cdyn, TV and MV for estimation of pulmonary mechanics in these infants.
Calcium, Sodium and Potassium Urinary Excretion during the First Five Days of Life in Very Preterm Infants
Authors: Bert Sophie , Gouyon Jean-Bernard , Semama Denis S.
Published: December 2003

Background: Hypercalciuria has been associated with the risk of nephrocalcinosis and renal stones in both adults and children. Renal calcifications are frequently encountered in preterm infants because this particular population presents most of the risk factors of increased urinary calcium excretion. Urinary calcium excretion has been shown to correlate with sodium and potassium excretions in adult patients, but these correlations have not been demonstrated in the early neonatal period yet. Objective: To define the relationship between calcium urinary excretion and sodium or potassium excretions in the first 5 days of life in preterm babies. Methods: A prospective study was conducted in 16 preterm infants born before 32 weeks of gestation (body weight 1,373 ± 310 g; gestational age 29.1 ± 1.6 weeks). Fifteen consecutive 8-hour urine collections were performed for each infant from the 8th hour of life. A plasma sample was obtained at the end of each urine collection. Sodium, potassium, calcium and creatinine were measured in urine and blood samples as often as possible. Results: (1) Urine sodium excretion was 6.56 ± 4.35 mmol/kg per day. (2) Urinary calcium excretion was 5.9 ± 5.4 mg/kg per day and the urinary calcium/creatinine ratio was 0.48 ± 0.39 mg/mg. (3) Urinary calcium and sodium excretion were positively correlated (r = 0.65, p = 0.0001), while an inverse correlation was found between calcium and potassium excretion (r = 0.31, p = 0.004). Conclusion: The mean values of urinary calcium excretion and calcium/creatinine ratio observed in our population were higher than 4 mg/kg per day and 0.4 mg/mg, respectively, i.e. boundary values previously associated with an increased risk of nephrocalcinosis. We hypothesize that an increase in urinary sodium excretion in this population may facilitate calcium excretion.
Transient Decrease in the CD45RA Expression on T Lymphocytes in Neonates with Fetal Distress
Authors: Mizobe Naoki , Sugita Kanji , Tezuka Toru , Sakamoto Mihoko , Fukada Yukihito , Hoshi Kazuhiko , Nakazawa Shinpei
Published: December 2003

To determine the expression of CD45 isoforms on T lymphocytes in neonates with fetal distress and to evaluate its diagnostic accuracy, peripheral blood samples were examined in 53 neonates who were classified into one of three groups: group I: ‘control’ group (n = 23), group II: ‘mild distress’ group (n = 15), and group III: ‘moderate distress’ group (n = 15). The expression of CD3 (mean ± SD 24.2 ± 10.1%), CD4 (23.0 ± 5.7%), and CD45RA (27.3 ± 9.6%) on total lymphocytes and the expression of CD45RA on CD4+ T lymphocytes (13.7 ± 4.7%) in group III were significantly lower than in the other two groups 0–3 days after birth. Sensitivity and specificity of the CD45RA expression on CD4+ T lymphocytes for discrimination of group III were calculated as 0.79 and 1.0, respectively, when the cutoff value was 22.7%. The low CD3, CD4, and CD45RA expression returned to normal levels 10 days and more after birth. There were no differences in the CD8 and CD45RO expression between the groups. We conclude that CD4+ T lymphocytes from neonates with fetal distress show a transient decrease in the CD45RA expression without an increase in the CD45RO expression, and, therefore, analysis of the CD45 isoform expression is useful for laboratory evaluation of fetal distress.
Gene-Teratogen Interactions in Chemically Induced Congenital Malformations
Authors: Giavini Erminio , Menegola Elena
Published: December 2003

Exposure of the embryo to environmental chemicals can result in congenital malformations or abortion. Although experimental teratology data are considered sufficient for risk assessment, only knowledge of their mechanisms of action permits a justifiable extrapolation of animal data to humans. Mechanistic studies of some teratogenic agents such as retinoic acids, valproic acid, diethylstilbestrol, and cyclopamine provided evidence of interference with regulation of genes controlling the embryonic development. The new genomic technologies are important tools in this field and may represent a real improvement in understanding the mechanisms of action of chemical teratogens.
Antenatal Glucocorticoids Attenuate Activation of the Inflammatory Reaction and Clotting in Preterm Lambs
Authors: Jaarsma Anneke S. , Braaksma Margriethe A. , Geven Wil B. , van Oeveren Wim , Bambang-Oetomo Sidarto
Published: December 2003

Recently we have shown that activation of inflammatory reaction and clotting can be found immediately after delivery in preterm lambs ventilated for respiratory distress syndrome (RDS). To investigate whether antenatal glucocorticoids would attenuate postnatal activation of the inflammatory reaction and clotting, we studied ventilated preterm lambs delivered by cesarean section, 24 h after antenatal administration of betamethasone or placebo. Blood was sampled before clamping the cord, 5, 10, and 15 min after delivery, and 2-hourly afterwards. Blood was used to determine oxygenation index, alveolar – arterial partial O2 difference (AaDO2), AP50 titer (see text), polymorphonuclear leukocytes (PMNs), β-glucuronidase, thrombin inhibition, activated partial thromboplastin time, and clot lysis time. Bronchoalveolar lavage fluid was sampled before clamping the cord and 30 min and 1, 2, 4, 6 and 8 h after delivery and was analyzed for elastase, thrombin, and protein. After removal of the lungs, static compliance and water content of the lungs were determined. We found that betamethasone-treated lambs had lower oxygenation index and AaDO2 than controls. At birth, PMN levels were higher, and the β-glucuronidase level was lower after betamethasone treatment. PMNs and β-glucuronidase did not change in betamethasone-treated lambs, in contrast to controls. Thrombin inhibition, activated partial thromboplastin time, and clot lysis time did not change in betamethasone-treated lambs, in contrast to controls. In both groups, elastase and protein levels in bronchoalveolar lavage fluid increased; the thrombin level increased in controls. The static compliance was better, and the water content of the lung was lower in the betamethasone-treated lambs. We conclude that early systemic activation of inflammatory reaction and clotting in preterm lambs with RDS are attenuated by antenatal betamethasone administration. Whether this is a direct effect of betamethasone on the inflammatory reaction or a result of a reduced ventilatory support because of less severe RDS after antenatal betamethasone treatment remains to be elucidated.
Reduced Apoptosis in Newborn Compared to Adult Rat Intestine after Ischemia-Reperfusion Injury
Authors: Luo Chih-Cheng , Shih Hsiang-Hung , Chiu Cheng-Hsun , Ma Wei-Chun , Chung Hui-Ying
Published: December 2003

The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury has been considered to be a major contributing factor. More recent reports have noted that apoptosis is a significant and perhaps the principal contributor to cell death after I/R. Some reports revealed that infants with NEC and perforated bowel can completely recover with drainage alone. This study aims to assess the ability of newborn rat intestine to resist apoptosis after I/R injury compared with adult rat intestine. Intestines from 10 groups of rats (n = 6 for each study group) were studied: (1) normal control group; (2) ischemia group, receiving vascular occlusion for 60 min; (3) I/R groups receiving vascular occlusion for 60 min and reperfusion for 15, 30, and 60 min, respectively. Apoptosis was quantified by TUNEL methods. Statistical analysis was performed using ANOVA with Dunn’s test. TUNEL-positive cells per 10 crypts were significantly increased in the ischemia and I/R groups compared to the control group. The peak number of positive cells by TUNEL was recognized 30 min after reperfusion in adult and newborn rats and then reduced gradually. The newborn rats had significantly less TUNEL-positive cells per 10 crypts than adult rats subjected to I/R injury (p < 0.05). We demonstrated that the activation of apoptosis occurred after intestinal I/R injury, especially during the reperfusion phase. The newborn intestine was more resistant to I/R injury and thus may have significant clinical application.
A Newborn Rat Model for the Study of Cerebral Hemodynamics by Near-Infrared Spectroscopy and Laser-Doppler Flowmetry in the Immature Brain
Authors: Fumagalli Monica , Mosca Fabio , Moos Knudsen Gitte , Greisen Gorm
Published: December 2003

An animal model for the study of cerebrovascular physiology in the immature brain was developed. Twelve 3- to 5-day-old rat pups were maintained on spontaneous breathing under light anesthesia for either 1 or 2 h. Transcutaneous carbon dioxide tension and arterial oxygen saturation were monitored. Continuous infusion of doxapram limited respiratory acidosis. Cerebral blood flow (CBF) and volume (CBV) could be monitored by near-infrared spectroscopy (NIRS) and laser-Doppler flowmetry (LDF) in spite of some movement artifacts. CBV and CBF were 6.0 ± 0.3 SE ml/100 g and 36.3 ± 3.1 SE ml/100 g/min, respectively, and remained stable during the study. Cerebrovascular responses, as monitored by LDF and NIRS, to hypoxic and hypercapnic gas mixtures were consistent.
Association of Lipid Peroxidation with Antenatal Betamethasone and Oxygen Radical Disorders in Preterm Infants
Authors: Weinberger Barry , Anwar Mujahid , Henien Samir , Sosnovsky Ana , Hiatt Mark , Jochnowitz Nina , Witz Gisela , Hegyi Thomas
Published: December 2003

Introduction: Premature infants are highly susceptible to ‘oxygen radical diseases’ (ORD), including bronchopulmonary dysplasia, intraventricular hemorrhage/white matter injury, retinopathy of prematurity, and necrotizing enterocolitis. The incidence of ORD is reduced following antenatal treatment with betamethasone. Oxidant-mediated injury is characterized at the cellular level by peroxidation of lipid membranes. This results in the generation of malondialdehyde (MDA), which can be quantified indirectly by measurement of thiobarbituric acid-reacting substances (TBARS). There is currently no effective way to quantify the risk for ORD. In this study, we analyzed the correlation of early urinary MDA and TBARS with prenatal betamethasone administration and with the development of ORD. Methods: Preterm infants (<30 weeks gestation, n = 25) born at St. Peter’s University Hospital were enrolled. Urine samples were collected during the first 10 days of life and stored at –70°C for 0–21 days. TBARS were quantified by spectrophotometric assay, and malondialdehyde levels measured by HPLC. Subjects were screened for the subsequent development of ORD. Betamethasone administration was defined as one or more doses ≧24 h prior to delivery. Results: Urinary MDA levels increased on days 2–3 and 5–10 relative to day 1 from birth. Maximal urinary MDA concentrations were significantly higher in the ORD group compared to controls, and there was a trend toward increased urinary TBARS in the presence of ORD. Infants receiving prenatal betamethasone demonstrated higher maximal urinary TBARS values during the first 10 days of life than control infants. The length of sample storage from 0 to 3 weeks at –70°C did not significantly affect TBARS measurements. Conclusions: Elevated urinary MDA measurements in the first 10 days are correlated with the risk for ORD. Urinary TBARS concentrations, which are correlated with MDA measurements, can be quantified rapidly and are stable for short-term storage. Our findings suggest that urinary TBARS may be adaptable as a practical tool for assessing the risk for ORD in neonatal intensive care unit patients, allowing clinicians to optimize the use of preventive strategies. Antenatal betamethasone is associated with increased urinary TBARS in the first 10 days of life, indicating that the protective effects of corticosteroids are not mediated through reductions in oxidant-mediated lipid peroxidation.
Erythropoietin Concentrations in Cerebrospinal Fluid of Nonhuman Primates and Fetal Sheep following High-Dose Recombinant Erythropoietin
Authors: Juul Sandra E. , McPherson Ronald J. , Farrell Francis X. , Jolliffe Linda , Ness Dana J. , Gleason Christine A.
Published: December 2003

Erythropoietin (Epo) decreases neuronal injury and cell death in vitro and in vivo. To lay the groundwork for use of Epo as a potential therapy for brain injury, we tested the hypothesis that systemic dosing of high-dose recombinant Epo (rEpo) would result in neuroprotective rEpo concentrations in the spinal fluid of adult and developing animals. This report characterizes the pharmacokinetics of high-dose rEpo in the blood and spinal fluid of juvenile and adult nonhuman primates (n = 7) and fetal sheep (n = 37) following a single injection. Timed blood and spinal fluid samples were collected following rEpo injection. Epo accumulation in spinal fluid was dependent on peak serum concentration and time following injection. We demonstrate that high-dose rEpo was well tolerated and results in neuroprotective concentrations in spinal fluid of adult and developing animal models by 2–2.5 h after injection.
Modified Exercise Test in Screening for Mitochondrial Myopathies – Adjustment of Workload in Relation to Muscle Strength
Authors: Hammarén Elisabet , Rafsten Lena , Kreuter Margareta , Lindberg Christopher
Published: December 2003

The aim of this study was to evaluate the usefulness of a modification of the bicycle ergometer test, the subanaerobic threshold exercise test (SATET), as a screening test for patients with mitochondrial myopathies. Since the original SATET is frequently found to be strenuous for weak patients, a new variable (relative muscle strength) was added to the workload formula. Plasma lactate levels were recorded at rest, then after 5 and 15 min of cycling on an ergometer, with constant workload. Nine patients with mitochondrial myopathy, 10 patients with other neuromuscular diseases and 9 healthy but sedentary volunteers undertook the test. An upper reference limit after exercise for plasma lactate was settled at 2.9 mmol/l. The modified SATET showed a sensitivity of 78% and a specificity compared to the healthy subjects of 100%. Compared to patients with other neuromuscular diseases, the specificity was lower (60%). All subjects completed the test without severe fatigue or pain.
Abnormal Intestinal Histology in Neonates with Congenital Anomalies of the Gastrointestinal Tract
Authors: Condino Adria A. , Barleycorn Aaron A. , Lu Wenge , Maheshwari Akhil , Christensen Robert D. , Calhoun Darlene A.
Published: December 2003

In animal models, when swallowing is experimentally prevented in utero, bowel length and weight are reduced, and villus height, crypt depth, and villus function are retarded. Little is known about the intestinal histology in infants with gastrointestinal (GI) tract anomalies. We examined the histological architecture of the intestine in neonates with GI anomalies in comparison to that of normal fetuses. Villus height, area, and length and crypt depth of normal fetuses were quantified in the proximal small bowel (n = 11) and measurements compared to those of surgical specimens of neonates with congenital anomalies of the GI tract (n = 16). Villus height and area and lamina propria height and area increased linearly from 8 to 24 weeks of gestation. In infants with anomalies of the GI tract, the villi were blunted and lacked normal histological architecture, the crypts were disorganized, and the crypt depth was significantly decreased (p = 0.004). Enterocyte height and area were significantly greater in neonates with congenital anomalies of the GI tract. The intestinal histology in neonates with congenital anomalies of the GI tract differs significantly from that of normal fetuses.
Elevated Blood Levels of Endogenous Ouabain-Like Factor in Preterm versus Mature Newborns at Birth
Authors: Göõz Monika , Vakkuri Olli , de Châtel Rudolf , Szalay Katalin S. , Tóth Miklós
Published: December 2003

Compared to healthy adults, elevated levels of endogenous ouabain-like factor (OLF) have already been shown in the cord blood, and a role of OLF in the maintenance of high Na+ excretion by reducing tubular sodium reabsorption during intrauterine life was suggested. In this study, we aimed to measure OLF cord blood levels of premature and mature newborns to provide further data on the possible physiological significance of this compound in neonates. OLF was assessed in the cord blood of newborns (28–41 weeks) and in the blood of healthy adults using ouabain radioimmunoassay. HPLC was employed to isolate endogenous OLF. Newborns had about twelve times higher OLF levels than healthy adults (41.96 ± 4.64 vs. 3.1 ± 1.1 pg/ml, p < 0.001). Further, there was a highly significant correlation (p < 0.004) between maturity and OLF concentration; OLF level increased with gestational age, however there was a rapid drop in its concentration at week 39 (43.26 ± 7 vs. 35.47 ± 1.84 pg/ml, p = NS). Further studies are needed to evaluate the physiological relevance of higher OLF in preterm versus mature newborns.
Obesity Indices and Major Components of Metabolic Syndrome in Young Adult Arab Subjects
Authors: Al-Shayji Iqbal A.R. , Akanji Abayomi O.
Published: December 2003

Background: The major components of metabolic syndrome are atherogenic dyslipidaemia (AD) and insulin resistance (IR), and both predict risk for atherosclerotic cardiovascular disease even in healthy individuals. Aims: To assess if, in a group of healthy young adult Arab subjects, a simple classification in high and normal scores on waist-hip ratio (WHR), body mass index (BMI) and waist circumference (WC) scales could predict atherogenic parameters for metabolic syndrome (AD, IR). Subjects and Methods: The subjects [n = 177 (72 M, 105 F), aged 29.7 ± 8.4 (SD) years], underwent physical evaluation, BP measurement and anthropometry [height (m), weight (kg), waist (WC) and hip circumference (HC, cm)]. The cut-off points for normal/high scores on the indices were: (1) BMI: 30 kg/m2 (M and F); (2) WHR: 0.80 F, 0.95 M, and (3) WC: 90 cm F, 100 cm M). The biochemical indices measured on fasting serum were: (1) AD: total cholesterol (TC), triglycerides (TG), HDL, LDL, apo B, HDL/TC ratio, and (2) IR: insulin, urate, insulin/glucose ratio (IGR). Results and Discussion: In the whole group of subjects, and in women separately considered, those with high indices (BMI, WHR, WC) had significantly increased levels of glucose, LDL, apo B, urate, mean BP, TG, insulin and IGR and lower values for HDL/TC ratio (all p < 0.05). In men, only urate, insulin and IGR levels were increased (p < 0.01) in the high-score groups. None of the indices showed any special superiority in describing the risk of AD or IR. Conclusion: In women, BMI, WHR and WC appeared equally good in identifying individuals at high risk of AD and IR while in men, these indices satisfactorily described the risk of IR but not of AD. It is important to re-emphasise the need to indicate gender distinctions in using anthropometry for CHD risk assessment.
Comparative Effects of the Addition of Meat from Beef, Chicken, Mullet and Hake to a Bean Seed Ragout on Iron Metabolism and Iron Status in Growing Rats
Authors: Hamdaoui M.H. , Chabchoub S.E. , Hédhili A.
Published: December 2003

Aims: The objective was to study the comparative effects of the addition of meat from beef, chicken, mullet and hake to a bean seed ragout (BSR) on iron metabolism and iron status in growing rats. Methods: The iron metabolism and the iron status were investigated through the exploration of the total iron in the blood and the reserve of iron stored in the liver, spleen, intestine, heart and tibia. Results: Our findings showed that the iron concentration in total blood significantly increased only in the BSR + beef group by 23% (p < 0.006) as compared to the control group (BSR). However, it significantly decreased in the BSR + chicken group by 19.3% (p < 0.002). The reserve of iron stored in the liver significantly increased in the BSR + beef and the BSR + hake groups by 69.5% (p < 0.003) and 160% (p < 2.5·10–7) respectively, as compared to the control group. The effect of hake was more pronounced than beef. However, in the BSR + chicken and the BSR + mullet groups, the reserve of iron stored in the liver did not significantly differ from the control group. The reserve of iron stored in the spleen increased significantly in all groups. The increase has reached 370% in the BSR + hake group (p < 1·10–7). In the intestine, the reserve of iron was significantly enhanced only in the group fed BSR + beef by 120% (p < 0.01). In contrast, this reserve was lower in the rats fed BSR + mullet than in the other groups, a reduction of 64% (p < 1·10–5) as compared to the control group. In the heart, iron concentration significantly increased between 36.5 and 50%, as compared to the control group. The iron stored in the tibia significantly increased only in the beef and the hake groups by 88% (p < 0.05) and 57.4% (p < 0.02) respectively. Conclusions: Our findings demonstrated that beef, chicken, mullet and hake did not have the same effect on iron metabolism and iron status in growing rats fed BSR diets. The rats fed BSR + beef have a better iron status than those fed BSR + hake, BSR + chicken or BSR + mullet in descending order.
Influence of Dietary Triacylglycerol Structure and Level of n–3 Fatty Acids Administered during Development on Brain Phospholipids and Memory and Learning Ability of Rats
Authors: Sommer Hartvigsen Merete , Mu Huiling , Sørig Hougaard Karin , Lund Søren Peter , Xu Xuebing , Høy Carl-Erik
Published: December 2003

Objective: The objective of this study was to examine the effects of triacylglycerol (TAG) structure and level of n–3 fatty acids on fatty acid profile of brain phospholipids (PL) of dams and offspring, and the memory and learning ability of the offspring, when administered during initial development of the nervous system. Methods: Pregnant rats were fed experimental diets from the 8th day of pregnancy throughout lactation. After weaning and until 13 weeks of age, the pups were fed the same diet as their dams. The experimental diets contained either a structured oil, a linseed oil, or a fish oil. In the structured oil, α-linolenic acid (18:3n–3) was predominantly located in the sn-2 position of the triacylglycerols and the level of 18:3n–3 was 2 mol or 10 mol%. In the linseed oil diets the level of 18:3n–3 was 2 mol or 10 mol% as well. Finally, the fish oil diet contained 18:3n–3 as well as 20:5n–3 and 22:6n–3 adding up to a total of 2 mol% n–3 fatty acids. The effects of the experimental diets were compared to the effect of a chow diet. Results: The amount of 22:6n–3 in brain phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS) of dams and offspring (3 and 13 weeks of age) was not affected by the six different diets. 18:2n–6, but not 18:3n–3, was detected in brain PL, suggesting a specificity of the tissues in the metabolism of n–3 and n–6 fatty acids. The level of monounsaturated fatty acids (MUFA) increased with increasing age of the pups, indicating an enhanced myelinization. No considerable differences between groups were found when memory or learning was tested in the Morris water maze. Conclusion: The results suggest that extreme diet modifications are needed in order to observe significant effects on the memory and learning ability in rats.
Smoking and High Plasma Triglyceride Levels as Risk Factors for Oxidative DNA Damage in the Korean Population
Authors: Park Eunju , Kang Myung-Hee
Published: December 2003

Aims: To investigate the effects of factors including dietary habits, lifestyle, anthropometric characteristics, plasma lipid profiles, and antioxidants on DNA damage among the Korean population. Methods: Blood samples were collected from 109 healthy Korean volunteers, aged 19–28 years, of whom 34% were smokers. Epidemiological information was collected by personal interviews, and anthropometric characteristics were measured directly. Oxidative DNA damage was quantified using the Comet assay; tail length (TL) and tail moment (TM) were measured. Results: Statistically significant (p < 0.05) positive correlations were observed between DNA damage (TM or TL) and smoking habits expressed as cigarettes smoked per day and number of packs smoked over time (r = 0.332 and 0.370, respectively, for TM; r = 0.266 and 0.304 for TL, respectively). There were also significant and positive correlations between DNA damage parameters and waist-hip ratio (r = 0.352 for TM and r = 0.226 for TL), but this significance disappeared after data were adjusted to account for smoking effects. Higher plasma triglyceride levels were associated with increased damage to DNA (r = 0.234 for TM and r = 0.271 for TL). Conclusions: Our results indicate that cigarette smoking and high plasma triglyceride levels significantly increase DNA damage to peripheral lymphocytes in a sample of Koreans.