bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and characterization of a novel family of membrane magnesium transporters, MMgT1 and MMgT2
Authors: Goytain Angela , Quamme Gary A.
Published: December 2007

Magnesium is an essential metal, but few selective transporters have been identified at the molecular level. Microarray analysis was used to identify two similar transcripts that are upregulated with low extracellular Mg2+. The corresponding cDNAs encode proteins of 131 and 123 amino acids with two predicted transmembrane domains. The two separate gene products comprise the family that we have termed “membrane Mg2+ transporters” (MMgTs), because the proteins reside in the membrane and mediate Mg2+ transport. When expressed in Xenopus laevis oocytes, MMgT1 and MMgT2 mediate Mg2+ transport as determined with two-electrode voltage-clamp analysis and fluorescence measurements. Transport is saturable Mg2+ uptake with Michaelis constants of 1.47 ± 0.17 and 0.58 ± 0.07 mM, respectively. Real-time RT-PCR demonstrated that MMgT mRNAs are present in a wide variety of cells. Subcellular localization with immunohistochemistry determined that the MMgT1-hemagglutinin (HA) and MMgT2-V5 fusion proteins reside in the Golgi complex and post-Golgi vesicles, including the early endosomes in COS-7 cells transfected with the respective tagged constructs. Interestingly, MMgT1-HA and MMgT2-V5 were found in separate populations of post-Golgi vesicles. MMgT1 and MMgT2 mRNA increased by about threefold, respectively, in kidney epithelial cells cultured in low-magnesium media relative to normal media and in the kidney cortex of mice maintained on low-magnesium diets compared with those animals consuming normal diets. With the increase in transcripts, there was an apparent increase in MMgT1 and MMgT2 protein in the Golgi and post-Golgi vesicles. These experiments suggest that MMgT proteins may provide regulated pathways for Mg2+ transport in the Golgi and post-Golgi organelles of epithelium-derived cells.
Opposing effects of coupled and uncoupled NOS activity on the Na+-K+ pump in cardiac myocytes
Authors: White C. N. , Hamilton E. J. , Garcia A. , Wang D. , Chia K. K. M. , Figtree G. A. , Rasmussen H. H.
Published: December 2007

Pharmacological delivery of nitric oxide (NO) stimulates the cardiac Na+-K+ pump. However, effects of NO synthesized by NO synthase (NOS) often differ from the effects of NO delivered pharmacologically. In addition, NOS can become “uncoupled” and preferentially synthesize O2·−, which often has opposing effects to NO. We tested the hypothesis that NOS-synthesized NO stimulates Na+-K+ pump activity, and uncoupling of NOS inhibits it. To image NO, we loaded isolated rabbit cardiac myocytes with 4,5-diaminofluorescein-2 diacetate (DAF-2 DA) and measured fluorescence with confocal microscopy. l-Arginine (l-Arg; 500 μmol/l) increased DAF-2 DA fluorescence by 51% compared with control ( n = 8; P < 0.05). We used the whole cell patch-clamp technique to measure electrogenic Na+-K+ pump current ( Ip). Mean Ip of 0.35 ± 0.03 pA/pF ( n = 44) was increased to 0.48 ± 0.03 pA/pF ( n = 7, P < 0.05) by 10 μmol/l l-Arg in pipette solutions. This increase was abolished by NOS inhibition with radicicol or by NO-activated guanylyl cyclase inhibition with 1 H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. We next examined the effect of uncoupling NOS using paraquat. Paraquat (1 mmol/l) induced a 51% increase in the fluorescence intensity of O2·−-sensitive dye dihydroethidium compared with control ( n = 9; P < 0.05). To examine the functional effects of uncoupling, we measured Ip with 100 μmol/l paraquat included in patch pipette solutions. This decreased Ip to 0.28 ± 0.03 pA/pF ( n = 12; P < 0.001). The paraquat-induced pump inhibition was abolished by superoxide dismutase (in pipette solutions). We conclude that NOS-mediated NO synthesis stimulates the Na+-K+ pump, whereas uncoupling of NOS causes O2·−-mediated pump inhibition.
Adaptation to hypobaric hypoxia involves GABAA receptors in the pons
Authors: Hsieh Yee-Hsee , Dick Thomas E. , Siegel Ruth E.
Published: December 2007

Survival in low-oxygen environments requires adaptation of sympathorespiratory control networks located in the brain stem. The molecular mechanisms underlying adaptation are unclear. In naïve animals, acute hypoxia evokes increases in phrenic (respiratory) and splanchnic (sympathetic) nerve activities that persist after repeated challenges (long-term facilitation, LTF). In contrast, our studies show that conditioning rats to chronic hypobaric hypoxia (CHH), an environment characteristic of living at high altitude, diminishes the response to hypoxia and attenuates LTF in a time-dependent manner. Phrenic LTF decreases following 7 days of CHH, and both sympathetic and phrenic LTF disappear following 14 days of CHH. Previous studies demonstrated that GABA is released in the brain stem during hypoxia and depresses respiratory activity. Furthermore, the sensitivity of brain stem neurons to GABA is increased following prolonged hypoxia. In this study, we demonstrate that GABAA receptor expression changes along with the CHH-induced physiological changes. Expression of the GABAA receptor α4 subunit mRNA increases two-fold in animals conditioned to CHH for 7 days. In addition, de novo expression of δ and α6, a subunit normally found exclusively in the cerebellum, is observed after 14 days. Consistent with these changes, diazepam-insensitive binding sites, characteristic of GABAA receptors containing α4 and α6 subunits, increase in the pons. Immunohistochemistry revealed that CHH-induced GABAA receptor subunit expression is localized in regions of sympathorespiratory control within the pons. Our findings suggest that a GABAA receptor mediated-mechanism participates in adaptation of the sympathorespiratory system to hypobaric hypoxia.
AMPA receptors undergo channel arrest in the anoxic turtle cortex
Authors: Pamenter Matthew Edward , Shin Damian Seung-Ho , Buck Leslie Thomas
Published: December 2007

Without oxygen, all mammals suffer neuronal injury and excitotoxic cell death mediated by overactivation of the glutamatergic N-methyl-d-aspartate receptor (NMDAR). The western painted turtle can survive anoxia for months, and downregulation of NMDAR activity is thought to be neuroprotective during anoxia. NMDAR activity is related to the activity of another glutamate receptor, the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR). AMPAR blockade is neuroprotective against anoxic insult in mammals, but the role of AMPARs in the turtle's anoxia tolerance has not been investigated. To determine whether AMPAR activity changes during hypoxia or anoxia in the turtle cortex, whole cell AMPAR currents, AMPAR-mediated excitatory postsynaptic potentials (EPSPs), and excitatory postsynaptic currents (EPSCs) were measured. The effect of AMPAR blockade on normoxic and anoxic NMDAR currents was also examined. During 60 min of normoxia, evoked peak AMPAR currents and the frequencies and amplitudes of EPSPs and EPSCs did not change. During anoxic perfusion, evoked AMPAR peak currents decreased 59.2 ± 5.5 and 60.2 ± 3.5% at 20 and 40 min, respectively. EPSP frequency (EPSPƒ) and amplitude decreased 28.7 ± 6.4% and 13.2 ± 1.7%, respectively, and EPSCƒand amplitude decreased 50.7 ± 5.1% and 51.3 ± 4.7%, respectively. In contrast, hypoxic (Po2= 5%) AMPAR peak currents were potentiated 56.6 ± 20.5 and 54.6 ± 15.8% at 20 and 40 min, respectively. All changes were reversed by reoxygenation. AMPAR currents and EPSPs were abolished by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In neurons pretreated with CNQX, anoxic NMDAR currents were reversibly depressed by 49.8 ± 7.9%. These data suggest that AMPARs may undergo channel arrest in the anoxic turtle cortex.
Coherent Motor Unit Rhythms in the 6–10 Hz Range During Time-Varying Voluntary Muscle Contractions: Neural Mechanism and Relation to Rhythmical Motor Control
Authors: Erimaki Sophia , Christakos Constantinos N.
Published: December 2007

In quasi-sinusoidal (0.5–3.0 Hz) voluntary muscle contractions, we studied the 6- to 10-Hz motor unit (MU) firing synchrony and muscle force oscillation with emphasis on their neural substrate and relation to rhythmical motor control. Our analyses were performed on data from 121 contractions of a finger muscle in 24 human subjects. They demonstrate that coherent 6- to 10-Hz components of MU discharges coexist with carrier components and coherent modulation components underlying the voluntary force variations. The 6- to 10-Hz synchrony has the frequency of the tremor synchrony in steady contractions and is also widespread and in-phase. Its strength ranges from very small to very large (MU/MU coherence >0.50) among contractions; moreover, it is not related to the contraction parameters, in accord with the notion of a distinct 6- to 10-Hz synaptic input to the MUs. Unlike the coherent MU modulations and the voluntary force variations, the in-phase 6- to 10-Hz MU components are suppressed or even eliminated during ischemia, while the respective force component is drastically reduced. These findings agree with the widely assumed supraspinal origin of the MU modulations, but they also strongly suggest a key role for muscle spindle feedback in the generation of the 6- to 10-Hz synaptic input. They therefore provide important information for the study of generators of the 6- to 10-Hz rhythm which subserves the postulated rhythmical control and is manifested as force and movement components. Moreover, they argue for a participation of oscillating spinal stretch reflex loops in the rhythm generation, possibly in interaction with supraspinal oscillators.
Polarized Skylight Navigation in Insects: Model and Electrophysiology of e-Vector Coding by Neurons in the Central Complex
Authors: Sakura Midori , Lambrinos Dimitrios , Labhart Thomas
Published: December 2007

Many insects exploit skylight polarization for visual compass orientation or course control. As found in crickets, the peripheral visual system (optic lobe) contains three types of polarization-sensitive neurons (POL neurons), which are tuned to different (∼60° diverging) e-vector orientations. Thus each e-vector orientation elicits a specific combination of activities among the POL neurons coding any e-vector orientation by just three neural signals. In this study, we hypothesize that in the presumed orientation center of the brain (central complex) e-vector orientation is population-coded by a set of “compass neurons.” Using computer modeling, we present a neural network model transforming the signal triplet provided by the POL neurons to compass neuron activities coding e-vector orientation by a population code. Using intracellular electrophysiology and cell marking, we present evidence that neurons with the response profile of the presumed compass neurons do indeed exist in the insect brain: each of these compass neuron-like (CNL) cells is activated by a specific e-vector orientation only and otherwise remains silent. Morphologically, CNL cells are tangential neurons extending from the lateral accessory lobe to the lower division of the central body. Surpassing the modeled compass neurons in performance, CNL cells are insensitive to the degree of polarization of the stimulus between 99% and at least down to 18% polarization and thus largely disregard variations of skylight polarization due to changing solar elevations or atmospheric conditions. This suggests that the polarization vision system includes a gain control circuit keeping the output activity at a constant level.
Self-Monitoring of Blood Pressure and the Role of Community Pharmacists in Kuwait
Authors: Matowe Wandikayi C. , Abahussain Eman A. , Awad Abdelmoneim , Capps Phillip A.
Published: December 2007

Objective: To determine the types of devices for self-monitoring of blood pressure available to consumers in Kuwait and the pharmacists’ knowledge and level of information provided to consumers when purchasing such devices.Materials and Methods: It was possible to contact 196 of the 230 eligible pharmacies from five governorates in Kuwait. Ten of these were used to pretest the questionnaire and six declined to participate. Another six did not carry any blood pressure monitoring devices and hence were excluded. Data was then collected from pharmacists at the 174 remaining community pharmacies via face-to-face structured interview of the respondents at their work sites. Results: Of the 174 pharmacists, 173 (99.4%) claimed to offer or provide advice to clients at the time of purchasing devices, 117 (67.1%) of them stating that they did so even if the patients did not ask. Although 147 (84.5%) respondents correctly identified the mercury sphygmomanometer as the most reliable device for measuring blood pressure, less than half (86, 49.4%) claimed to know how to check the accuracy of the devices they sold. Only 25 (14.4%) pharmacists could actually identify the correct procedure for checking the accuracy of the devices and only 25 (14.4%) pharmacists could correctly identify cutoff points for systolic and diastolic blood pressure delineating clinical hypertension. Only 1 pharmacist could correctly name a reference source for blood pressure measurement. Conclusion: There is a need for improvement of community pharmacists’ competence in supporting patients and in providing them with information regarding devices for measuring blood pressure in Kuwait.
Spectrum of Cutaneous Vasculitis in Adult Patients from the Farwaniya Region of Kuwait
Authors: Al-Mutairi Nawaf
Published: December 2007

Objective: To determine the clinical profile, etiologic factors, disease associations, and the laboratory profile of adult patients with cutaneous leukocytoclastic vasculitis (LV) presenting to the Dermatology Department at Farwaniya Hospital, Kuwait. Subjects and Methods: The medical records of 57 adult patients (>18 years) with biopsy-proven cutaneous LV from January 2004 to June 2006 at Farwaniya Hospital were reviewed. Results: Of the 57 patients studied, 21 (36.8%) were classified as having primary cutaneous small vessel vasculitis. The most common type of skin lesions found was palpable purpura seen in 29 (50.9%) patients. No possible cause for the cutaneous vasculitis could be identified in 21 patients. Extracutaneous involvement was seen in 32 (56.1%) patients of which 29 had joint involvement. The most frequent laboratory abnormality was an elevated erythrocyte sedimentation rate (ESR). Altered laboratory evaluation in the form of leukocytosis, raised antistreptolysin O titers and urine abnormalities were found in association with systemic vasculitis. IgA deposits were present in 33 patients. Risk factors for chronicity of cutaneous LV were female sex, advanced age, unidentified etiology, absence of fever and presence of joint involvement. Conclusion: The commonest type of LV in Kuwait is primary cutaneous small vessel vasculitis. The most frequent laboratory abnormality associated with LV was increased ESR.
Spontaneous Rupture of a Giant Diaphragmatic Hydatid Cyst into the Intrapleural Space
Authors: Dervisoglu Erkan , Topcu Salih , Liman Serife Tuba , Yilmaz Ahmet
Published: December 2007

Objective: We report a case of giant diaphragmatic hydatid cyst which ruptured spontaneously into the intrapleural space in a patient with coexistent giant hepatic hydatid cyst. Clinical Presentation and Intervention: A 62-year-old female was admitted for dyspnea, nausea, vomiting, and right thoracic pain. Clinical findings, laboratory and radiological examinations including multislice computed tomography scan were consistent with the diagnosis of a giant diaphragmatic hydatid cyst which ruptured into the intrapleural space. Surgical intervention was performed through thoracotomy and phrenotomy in a one-stage operation for both cysts. Conclusion: This case shows that hydatid cysts of the diaphragm can rupture into the intrapleural space spontaneously. One-stage operation through thoracotomy may be successful for the surgical intervention for diaphragmatic hydatid cysts with coexistent hepatic cyst.
The Immune-Pineal Axis: A Shuttle between Endocrine and Paracrine Melatonin Sources
Authors: Markus Regina P. , Ferreira Zulma S. , Fernandes Pedro A.C.M. , Cecon Erika
Published: December 2007

The time course of the innate immunological response involves a pro-inflammatory phase followed by an anti-inflammatory phase. Pro-inflammatory responses serve as a defense against several stressor conditions, and sequential processes that shut down these responses are necessary to avoid exacerbation or the development of chronic diseases. In the present review, we put together recent data that show that the pineal gland is a player in bidirectional control of the inflammatory response. Healthy organisms stay in standby mode, ready to react. The nocturnal melatonin surge impairs the rolling and adherence of leukocytes to endothelial layers, limiting cell migration, and stimulates nocturnal production of IL-2 by T helper lymphocytes, exerting an immunostimulatory effect. Otherwise, the release of TNF-α from activated macrophages suppresses the nocturnal melatonin surge, allowing a full cell migration and inhibiting IL-2 production. In sequence, activated mononuclear and polymorphonuclear cells produce melatonin in a paracrine manner at the site of injury, which scavenges free radicals and collaborates to resolve the inflammatory response. The sequential diminution of TNF-α production is followed by the recovery of the nocturnal melatonin surge and IL-2 production. In summary, the immune-pineal axis, implicated in the sequential involvement of the melatonin produced by the pineal gland and immune-competent cells, is an integral participant of the innate immune response.
Matrix Metalloproteinase-9 Is Involved in the Development and Plasticity of Retinotectal Projections in Rats
Authors: Oliveira-Silva Priscilla , Jurgilas Patricia B. , Trindade Pablo , Campello-Costa Paula , Perales Jonas , Savino Wilson , Serfaty Claudio A.
Published: December 2007

Objective: During postnatal development, retinotectal projections undergo a process of misplaced axon elimination, leading to a topographical matching between the retinal surface and the superior colliculus. Matrix metalloproteinases (MMPs) have been implicated in the development and plasticity of the nervous system. We studied the expression and role of MMPs during normal development of retinotectal projections and after monocular enucleation-induced plasticity. Material and Methods: Lister hooded rats at different postnatal ages received subpial ethylene vinyl acetate 40W implants to deliver an MMP inhibitor or vehicle to the superior colliculus. Animals received intraocular injections of horseradish peroxidase for anterograde tracing of ipsilateral projections. For immunoblotting and zymography, colliculi were removed without fixation. Results: We observed the highest MMP activity in the first postnatal week, with decreasing activity thereafter. Monocular enucleation at postnatal day 10 yielded a rapid increase in MMP activity, 24 h following denervation of the contralateral colliculus. Importantly, inhibition of MMP activity in vivo induced a marked delay of axonal clustering along the medial aspect of colliculus. Conclusions: Our data indicate that MMPs are crucial in retinotectal development concurring to the fine tuning of topographical order and synaptic specificity of these connections.
Central Blockade of IL-1 Does Not Impair Taste-LPS Associative Learning
Authors: Pacheco-López Gustavo , Niemi Maj-Britt , Kou Wei , Baum Sven , Hoffman Marcus , Altenburger Pia , del Rey Adriana , Besedovsky Hugo O. , Schedlowski Manfred
Published: December 2007

After saccharin intake is associated with the consequences of peripheral lipopolysaccharide (LPS) administration, rats develop a strong conditioned avoidance behavior against this gustatory stimulus. To investigate the role of central interleukin-1 (IL-1) as a key signal during taste-LPS engram formation, rats were chronically infused with IL-1 receptor antagonist into the lateral ventricle of the brain before, during and after a single association trial. The results indicate that a stable taste-LPS engram can be formed even under the chronic blockade of central IL-1 signaling during engram formation and consolidation. More importantly, our data show that animals which did not experience a fever response during association phase (due to the LPS encounter) were unable to elicit hyperthermia as part of the conditioned response. These data indicate that pairing a relevant taste stimulus with an immune challenge, such as LPS, might result in the formation of multiple engrams, specifically codifying independent information.
Similar Biological Medicinal Products Containing Recombinant Human Growth Hormone: European Regulation
Authors: Pavlovic Mira , Girardin Elizabeth , Kapetanovic Liliana , Ho Kowid , Trouvin Jean-Hugues
Published: December 2007

The concept of similar biological medicinal products (‘biosimilar’ medicinal products) allows pharmaceutical companies to develop products based on an abridged dossier once the marketing protection of the ‘reference’ biological medicinal product has expired. A biosimilar medicinal product can be granted a marketing authorization provided that its similarity to a reference product is established in terms of quality, safety and efficacy (step-wise comparability exercise). A decision to launch a biosimilar medicinal product on the market is taken if it has a similar efficacy and comparable or better (less) immunogenicity than the chosen reference biological medicinal product. However, this decision is based on limited data and the comparability program may detect substantial differences in immunogenicity profiles but is likely incapable of detecting rare events. This is why clinical experience, through clinical trials and extensive pharmacovigilance programs, remains the most reliable way to assess the immunogenicity and tolerance profile of recombinant therapeutic proteins. Substitution of one biological medicinal product by a biosimilar medicinal product is not currently recommended before long-term clinical efficacy and safety have been acquired in all relevant populations. Here we review recent regulatory guidelines provided by EMEA and comment on the marketing authorizations and risk management plans of two recently approved biosimilar somatropins.
Fetal Adiponectin and Resistin in Correlation with Birth Weight Difference in Monozygotic Twins with Discordant Growth
Authors: Gohlke Bettina C. , Bartmann Peter , Fimmers Rolf , Huber Agnes , Hecher Kurt , Roth Christian L.
Published: December 2007

Background: Various studies have demonstrated an increased risk for adult diseases in newborns born small-for-gestational-age (SGA). Adiponectin and resistin can be detected in cord blood and are suggested to affect insulin resistance (IR). This might represent a link between metabolic syndrome and SGA birth. Study Design: We investigated the relationship between the adipocytokines and inter-twin birth weight (BW) difference of 31 monozygotic twins with twin-twin transfusion syndrome; in 14 twin pairs BW difference was >15% (1 SGA twin, 1 appropriate-for-gestational-age, AGA, twin). Results: BW and length of all patients were positively related to adiponectin (r = 0.57; p < 0.0001; r = 0.47; p < 0.0001) and to resistin (r = 0.31; p < 0.01; r = 0.35; p < 0.01). In 71% (10/14), the SGA twins showed lower adiponectin concentrations than their AGA co-twins (only 6/14 for resistin). To correct for gestational age we calculated the relationship between the intrapair differences (Δ) of BW and Δ of the hormones. We found ΔBW positively correlated with adiponectin (r = 0.55; p < 0.001) but not with resistin (r = 0.22; p = 0.2). Δadiponectin was positively correlated with Δresistin (r = 0.45; p < 0.01). Conclusion: These data demonstrate that adiponectin and resistin levels are associated with BW with only adiponectin levels being reduced in SGA children independently of gestational age. Prenatally different metabolic status between the twins might predispose the SGA twin to develop IR later in life.
A Novel Germline Mutation, IVS4+1G>A, of the POU1F1 Gene Underlying Combined Pituitary Hormone Deficiency
Authors: Snabboon Thiti , Plengpanich Wanee , Buranasupkajorn Patinat , Khwanjaipanich Ratchada , Vasinanukorn Padiporn , Suwanwalaikorn Sompongse , Khovidhunkit Weerapan , Shotelersuk Vorasuk
Published: December 2007

Background: POU1F1 is a pituitary transcription factor that plays a pivotal role in pituitary development and expression of the GH, PRL and TSHβ genes. Therefore, abnormalities of the POU1F1 gene are known to be responsible for a phenotype causing combined pituitary hormone deficiency (CPHD) involving growth hormone, prolactin and thyrotropin. Methods: We described an 18-year-old Thai man, from a consanguineous family, who presented with short stature and cognitive deficit. He underwent endocrinological and molecular investigations. Results: Hormonal studies showed that the patient had GH deficiency and secondary hypothyroidism, consistent with CPHD. Direct DNA sequencing revealed a novel homozygous mutation at the splice site of exon 4, IVS4+1G>A. It is the first splice site mutation in the POU1F1 gene described to date. Of the 7 other family members studied for this mutation by restriction enzyme digestions, 5 were heterozygous. They were all unaffected, suggesting a recessive pattern of inheritance. Conclusions: We described a novel POU1F1 splice site mutation, IVS4+1G>A, the first of its kind, in a Thai patient with CPHD. Recessive inheritance is suggested. We also noted preventable morbidities which resulted from delay in diagnosis of concomitant pituitary hormone defects in newborns suspected of CPHD.
Endocrine Late Effects of Childhood Cancer Therapy: A Report from the Children’s Oncology Group
Authors: Nandagopal Radha , Laverdière Caroline , Mulrooney Daniel , Hudson Melissa M. , Meacham Lillian
Published: December 2007

Pediatric oncologists are curing increasing numbers of patients with childhood cancer, and most children diagnosed with a malignancy may now be expected to become long-term survivors. As the number of childhood cancer survivors grows, so too does the need for evidence-based surveillance of the long-term effects of cancer therapy. Long-term effects involving the endocrine system represent a frequent complication of therapy. The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers(COG LTFUG), most recently updated in 2006, provide a summary of the known endocrine late effects of surgery, radiation, chemotherapy, and stem cell transplant. This paper summarizes the scope and nature of the endocrine late effects of childhood cancer therapy based upon a review of the pertinent medical literature, and demonstrates how pediatric oncologists can use these guidelines in clinical practice.
Subclassification of Small for Gestational Age Children with Persistent Short Stature: Growth Patterns and Response to GH Treatment
Authors: Ester Wietske , Bannink Ellen , van Dijk Marije , Willemsen Ruben , van der Kaay Danielle , de Ridder Maria , Hokken-Koelega Anita
Published: December 2007

Aim: We determined whether subclassification of short small for gestational age (SGA) children according to birth anthropometrics could delineate different patterns in gestation, delivery, postnatal growth, response to growth hormone (GH) treatment and parental height. Methods: 201 short SGA children were divided into three groups, SGAL, SGAL+W and SGAL+W+HC, according to birth length (L), weight (W) and head circumference (HC) ≤–2.00 standard deviation score (SDS). Results: SGAL+W+HC children were born after the shortest gestational age and more often by caesarean section than SGAL children (36.3 vs. 38.1 weeks, 68.4 vs. 24.4%). SGAL+W children had an intermediate pattern and experienced most gestational hypertension (p = 0.01). At birth, SGAL+W+HC children were shorter than SGAL or SGAL+W (–4.12 vs. –2.67 and –3.72 SDS, p ≤ 0.001). During the first 3 years of life, SGAL+W+HC children exhibited an increased growth in height (0.98 SDS) and HC (1.28 SDS) than SGAL (height, –0.06 SDS; HC, –0.30 SDS) and SGAL+W (height, 0.62 SDS; HC, –0.31 SDS). However, HC SDS remained smaller for SGAL+W+HC than the other groups at age 3. The groups did not differ in growth response during GH treatment. SGAL children tended to have shorter parents and target height than SGAL+W+HC children. Conclusions: Our study shows that subclassification of short SGA children might be a useful method for investigating SGA children as the subgroups revealed a different gestation, delivery and postnatal growth pattern. Response to GH treatment was not different between the groups.
Longitudinal Study of the Maternal Insulin-Like Growth Factor System before, during and after Pregnancy in Relation to Fetal and Infant Weight
Authors: Olausson H. , Lof M. , Brismar K. , Lewitt M. , Forsum E. , Sohlstrom A.
Published: December 2007

Background: The maternal insulin-like growth factor (IGF) system is considered to be involved in fetal growth regulation. However, available data linking this system to fetal growth are contradictory and incomplete. Aims: To measure components of the IGF system before, during and after pregnancy in healthy women and to relate these results, and their changes during pregnancy, to fetal weight (gestational week 31) and birth weight. Methods: Serum concentrations of IGF-I, IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-3 and IGFBP-3 protease activity were assessed in 23 women before conception, at weeks 8, 14, 20, 32 and 35 of pregnancy and 2 weeks postpartum. The data were analyzed using simple and multiple linear regression. Results: One third of the variability in fetal weight was explained by IGF-I in combination with IGFBP-3 protease activity, both assessed at gestational week 32 (p = 0.013). Birth weight was negatively correlated (r = –0.43 to –0.59) with IGFBP-1 at gestational week 20 (p = 0.041), 32 (p = 0.012) and 35 (p = 0.003). Conclusion: We propose there is a finely tuned balance among the components of the IGF system, providing a means for fetal growth regulation.
Type 2 Diabetes in Children and Adolescents in a 2-Year Follow-Up: Insufficient Adherence to Diabetes Centers
Authors: Reinehr Thomas , Schober Edith , Roth Christian L. , Wiegand Susanna , Holl Reinhard
Published: December 2007

Background/Aims: To study the 2-year course of children and adolescents with type 2 diabetes mellitus (T2DM) in general practice to present (1) the treatment modalities, (2) patient adherence, and (3) the occurrence of comorbidities. Methods: HBA1c, lipids, blood pressure, treatment modalities, occurrence of retinopathy and nephropathy were analyzed in 129 children and adolescents with T2DM (median age 13.4 years, 75% female) in specialized diabetes centers in Germany. Results: Seventy-eight (60%) children dropped out of care after a mean of 7.1 months. Drug treatment was not stopped in any of the 64 children initially treated with antidiabetic drugs. Sixteen (12%) children were treated solely by lifestyle intervention over the 2-year course. In the 51 children with complete follow-up, median HbA1c was 7.7% at diagnosis and 6.3% after 2 years. Less than 5% of all children were treated with antihypertensive or lipid-lowering drugs, while 65% suffered from hypertension and 44% from dyslipidemia. Over the course of the disease, retinopathy was not observed, while microalbuminuria occurred in 25%. Conclusions: In general practice, many children and adolescents with T2DM were lost of follow-up. Lifestyle intervention as sole treatment was not often useful for long-term metabolic control. Dyslipidemia and hypertension were seldom treated as recommended.
Gene Expression Profiling of Hypothalamic Hamartomas: A Search for Genes Associated with Central Precocious Puberty
Authors: Parent Anne-Simone , Matagne Valerie , Westphal Manfred , Heger Sabine , Ojeda Sergio , Jung Heike
Published: December 2007

Background: Hypothalamic hamartomas (HHs) are congenital lesions composed of neurons and astroglia. Frequently, HHs cause central precocious puberty (CPP) and/or gelastic seizures. Because HHs might express genes similar to those required for the initiation of normal puberty, we used cDNA arrays to compare the gene expression profile of an HH associated with CPP with three HHs not accompanied by sexual precocity. Methods: Global changes in gene expression were detected using Affymetrix arrays. The results were confirmed by semiquantitative PCR, which also served to examine the expression of selected genes in the hypothalamus of female monkeys undergoing puberty. Results: All HHs were associated with seizures. Ten genes whose expression was increased in the HH with CPP were identified. They encode proteins involved in three key cellular processes: transcriptional regulation, cell-cell signaling, and cell adhesiveness. They include IA-1 and MEF2A, two transcription factors required for neuronal development; mGluR1 and VILIP-1, which encode proteins involved in neuronal communication, and TSG-6 that encodes a protein involved in cell adhesiveness. Of these, expression of mGluR1 also increases in the female monkey hypothalamus at puberty. Conclusions: Increased expression of these genes in HHs may be relevant to the ability of some HHs to induce sexual precocity.
Impaired Exercise Capacity in Diabetic Patients after Coronary Bypass Surgery: Effects of Diastolic and Endothelial Function
Authors: Wu Yen-Wen , Hsu Ching-Ling , Wang Shoei-Shen , Tsai Mei-Wun , Chu Shu-Hsiun , Chen Yih-Sharng , Yang Wei-Shiung , Wu Ying-Tai
Published: December 2007

Objectives: The aims of this study were to clarify the influence of cardiac diastolic and peripheral vascular function on the exercise capacity of patients with coronary bypass surgery (CABG) and diabetes mellitus (DM) by tissue Doppler imaging (TDI) and flow-mediated vasodilatation (FMD), and to investigate interrelations between exercise capacity and LV diastolic function, endothelial function and biochemical parameters. Methods: We analyzed the exercise capacity, TDI at the mitral annulus and FMD in 51 uncomplicated first-time CABG survivors (23 DM) at an average interval of 21.6 ± 12.2 months after surgery. Results: Diabetics had lower E’, A’, VO2peak, (a-v)O2 difference, and higher E/E’ ratios (p < 0.05) than non-DM patients, but not FMD (p = 0.17). The A and E/E’ ratios correlated negatively with VO2peak after age adjustment (r = –0.336, p = 0.024). In addition, HbA1c, and triglyceride also correlated negatively with VO2peak (r = –0.377, –0.307, respectively, p < 0.05). Conclusions: Diabetics after CABG had more advanced diastolic dysfunction and oxygen extraction impairment than non-DM. It suggests these factors could contribute to lower exercise capacity, risk of developing heart failure despite preserved systolic function and poorer long-term survival of diabetic patients after CABG.
Preoperative Maneuvers to Avert Postoperative Respiratory Failure in Elderly Patients
Authors: Gore Dennis C.
Published: December 2007

Background: The elderly appear particularly vulnerable to pulmonary complications following surgical procedures. Objective: The purpose of this study was to identify and assess the merit of various maneuvers employed to mitigate respiratory difficulties in elderly patients undergoing surgery. Results: The literature revealed evidence that diminishing sputum production with selective antibiotics and augmentation of sputum clearance with assisted coughing, postural drainage, and bronchodilators were deemed important. Futhermore, efforts to optimize nutritional status and eliminate tobacco and alcohol consumption are also felt to be of value in improving postsurgical outcome. Conclusion: One significant aspect of this review was the apparent posity of recent work on this subject despite the profound magnitude of the demise related to postsurgical respiratory complications in elderly patients.
Sporadic Culture-Negative Peritonitis in Peritoneal Dialysis Patients – Absence of Endotoxin in Dialysate
Authors: Hausmann Michael J. , Yulzari Robert , Vorobiov Marina , Douvdevani Amos , Zlotnik Moshe
Published: December 2007

Background: Indiscriminate use of broad-spectrum antibiotics in peritonitis may have either unwanted side effects or contribute to the development of antibiotic resistance. It is tempting to use broad-spectrum antibiotics in cases of culture-negative peritonitis. This study examines whether Gram-negative agents have to be considered in the management of culture-negative peritonitis. Gram-negative agents are manifested by endotoxin easily detected by the Limulus amebocyte lysate (LAL) test. Methods: 138 episodes of Gram-negative and culture-negative peritonitis have been retrospectively analyzed; episodes of Gram-negative peritonitis were controls. Correlation between LAL and culture results was compared between the two groups. The LAL test was performed using a commercial kit by incubating a mixture of dialysate effluent and LAL reagent at 37°C. Development of a stable solid clot was considered positive. Results: In controls, 80 out of 117 Gram-negative peritonitis were LAL positive (68%). None of the 21 culture-negative episodes was LAL positive. In 7 recurrences of Gram-negative peritonitis, the LAL test turned from negative to positive but in none of the recurrences of culture-negative peritonitis. The difference in correlation was highly significant. Conclusions: Gram-negative organisms do not seem to be involved in sporadic culture-negative peritonitis. In episodes of peritonitis in which bacteriologic cultures stay negative for 48 h, initial coverage of Gram-negative organisms may be dropped.
Emerging Role of MicroRNAs in Cardiovascular Biology
Authors: Latronico Michael V.G. , Catalucci Daniele , Condorelli Gianluigi
Published: December 2007

The heart is among the most conserved organs of the body and is susceptible to defects more than any other organ. Heart malformations, in fact, occur in roughly 1% of newborns. Moreover, cardiovascular disease arising during adult life is among the main causes of morbidity and mortality in developed countries. It is not surprising, therefore, that much effort is being channeled into understanding the development, physiology, and pathology of the cardiovascular system. MicroRNAs, a newly discovered class of small ribonucleotide-based regulators of gene expression, are being implicated in an increasing number of biological processes, and the study of their role in cardiovascular biology is just beginning. Here, we briefly overview microRNAs in general and report on the recent findings regarding their importance for the heart and vasculature, in particular. The new insights that are being gained will permit not only a greater understanding of cardiovascular pathologies but also, hopefully, the development of novel therapeutic strategies.
An Analysis of Deaths in Portable Cribs and Playpens: What Can Be Learned?
Authors: Jackson Allison , Moon Rachel Y.
Published: December 2007

To assess the risk of using portable cribs and playpens as sleep surfaces for infants, data from playpen/portable crib deaths occurring between January 1, 1999, and February 4, 2004, that were reported to the Consumer Product Safety Commission were retrospectively reviewed. Twenty-one playpen/portable crib deaths were identified. Two-thirds of the deaths were in infants. Asphyxia, positional asphyxia, and suffocation were the leading causes of death. Several deaths were the consequence of risks unique to playpens and portable cribs: playpen collapse, modifications to the playpen, and improper assembly. The data demonstrate some unique risks posed by playpens/portable cribs, including risks from improper assembly and setup. Programs recommending and using playpens/portable cribs as routine infant sleep surfaces must be aware of the need for additional guidance regarding use of playpens/portable cribs.
Prevention of pulmonary complications after upper abdominal surgery by preoperative intensive inspiratory muscle training: a randomized controlled pilot study
Authors: Dronkers Jaap , Veldman André , Hoberg Ellen , van der Waal Cees , van Meeteren Nico
Published: December 2007

Objective: To investigate the feasibility and effects of preoperative inspiratory muscle training on the incidence of atelectasis in patients at high risk of postoperative pulmonary complications scheduled for elective abdominal aortic aneurysm surgery.

Design: Single-blind randomized controlled pilot study.

Setting: Gelderse Vallei Hospital Ede, the Netherlands.

Subjects: Twenty high-risk patients undergoing elective abdominal aortic aneurysm surgery were randomly assigned to receive preoperative inspiratory muscle training or usual care.

Main measures: Effectiveness outcome variables were atelectasis, inspiratory muscle strength and vital capacity, and feasibility outcome variables were adverse effects and patient satisfaction with inspiratory muscle training.

Results: Despite randomization, patients in the intervention group were significantly older than the patients in the control group (70 ± 6 years versus 59 ± 6 years, respectively; P = 0.001). Eight patients in the control group and three in the intervention group developed atelectasis (P = 0.07). The median duration of atelectasis was 0 days in the intervention group and 1.5 days in the control group (P = 0.07). No adverse effects of preoperative inspiratory muscle training were observed and patients considered that inspiratory muscle training was a good preparation for surgery. Mean postoperative inspiratory pressure was 10% higher in the intervention group.

Conclusion: Preoperative inspiratory muscle training is well tolerated and appreciated and seems to reduce the incidence of atelectasis in patients scheduled for elective abdominal aortic aneurysm surgery.
Treadmill training for ataxic patients: a single-subject experimental design
Authors: Vaz Daniela Virgínia , Schettino Renata de Carvalho , Rolla de Castro Teresa Regina , Teixeira Valéria Reis , Cavalcanti Furtado Sheyla Rossana , de Mello Figueiredo Elyonara
Published: December 2007

Objective: To investigate changes in gait quality, balance and mobility associated with treadmill training for ataxic individuals.

Design: Single-subject ABA design. Baseline phases (A) lasted three weeks and intervention (B) lasted four weeks.

Setting: University rehabilitation clinic.

Subjects: A woman (25 years) and a man (53 years) with chronic ataxia due to head trauma.

Intervention: Three 20-minute treadmill training sessions each week with progression in velocity and step length.

Main measures: Rivermead Visual Gait Assessment, Timed Up and Go, time to complete a balance task, walking speed, cadence, and stride length assessments three times a week during the 10 weeks. Data were analysed with the celeration line technique and two standard deviation band.

Results: Both individuals demonstrated gains in all parameters over initial baseline and subsequent phases, with performance increases ranging from 26% to 233% when first and last assessments were compared. Significantly superior effects of treadmill training over baseline conditions on cadence were detected (P<0.05). Gains in walking speed were not significantly better during intervention, but intervention withdrawal produced deceleration of performance gains. Gains in Timed Up and Go, step length and balance were not consistent and were possibly caused by a learning effect of the association between repeated testing and treadmill training. Rivermead Visual Gait Assessment gains reached significance only for subject 2 (P<0.05), probably because of increased variability of performance of subject 1. Results suggest that the association between repeated testing and treadmill training might have been responsible for the observed gains in the two ataxic patients.
A dyskerin motif reactivates telomerase activity in X-linked dyskeratosis congenita and in telomerase-deficient human cells
Authors: Machado-Pinilla Rosario , Sánchez-Pérez Isabel , Ramón Murguía José , Sastre Leandro , Perona Rosario
Published: December 2007

Dyskerin gene is mutated in patients with X-linked dyskeratosis congenita (X-DC), which results in greatly reduced levels of telomerase activity. A genetic suppressor element (GSE) termed GSE24-2 has been isolated in a screening for cisplatin resistance. GSE24-2–expressing cells presented impaired telomerase inhibition following in vitro exposure to chemotherapies, such as cisplatin, or telomerase inhibitors. The promoter of the telomerase component hTERT was constitutively activated in GSE24-2 cells in a c-myc expression–dependent manner. Deletion analyses and mutagenesis of the human c-myc promoter demonstrated that the target sequence for activation was the nuclease hypersensitive element-III (NHEIII) site located upstream to the P1 region of the promoter. Further, expression of GSE24-2 in cell lines derived from patients with X-DC and in VA13 cells induced increased hTERT RNA and hTR levels and recovery of telomerase activity. Finally, expression of GSE24-2 was able to rescue X-DC fibroblasts from premature senescence. These data demonstrate that this domain of dyskerin plays an important role in telomerase maintenance following cell insults such as cisplatin treatment, and in telomerase-defective cells in patients with X-DC. The expression of this dyskerin fragment has a dominant function in X-DC cells and could provide the basis for a therapeutic approach to this disease.
Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with or without chronic rejection
Authors: Blondeau K. , Mertens V. , Vanaudenaerde B. A. , Verleden G. M. , Van Raemdonck D. E. , Sifrim D. , Dupont L. J.
Published: December 2007

Acid gastro-oesophageal reflux (GOR) and gastric aspiration have been labelled as risk factors for chronic rejection bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). The present study aimed to further characterise GOR (both acid and nonacid) and the degree of gastric aspiration in LTx recipients both with and without BOS.

Impedance-pH recordings were used for GOR detection. Pepsin and bile acid levels were measured in bronchoalveolar lavage fluid (BALF).

A total of 48% of patients had increased GOR, of which 27% had exclusively increased nonacid reflux. Cystic fibrosis patients had the highest prevalence of GOR. Pepsin was found in BALF of all patients and bile acids in BALF of 50% of the patients. Patients with BOS had neither increased GOR nor elevated pepsin in BALF. However, 70% of the patients with BOS had bile in BALF compared with 31% of stable patients. Proton pump inhibitor (PPI) treatment reduced acid reflux but did not affect nonacid reflux. Moreover, pepsin and bile levels in BALF were not reduced by PPI.

One-half of the lung transplant patients had increased reflux, and nonacid reflux was common. Gastric aspiration occurred in most lung transplant patients. Pepsin was a more general marker and bile acids a more specific marker that might be associated with bronchiolitis obliterans syndrome. Proton pump inhibitor treatment did not prevent nonacid reflux and gastric aspiration.