bluuebunny/crossref_metadata_2025 huggingface dataset:
An Integrated Strategy for Evaluation of Metabolic and Oxidative Defects in Neurodegenerative Illness Using Magnetic Resonance Techniques
Authors: JENKINS B. G. , CHEN Y. I. , KUESTERMANN E. , MAKRIS N. M. , NGUYEN T. V. , KRAFT E. , BROWNELL A. L. , ROSAS H. D. , KENNEDY D. N. , ROSEN B. R. , KOROSHETZ W. J. , BEAL M. F.
Published: February 2006

ABSTRACT: The number of physiologic and metabolic phenomena amenable to analysis using magnetic resonance (MR) techniques is increasing every year. MR techniques can now evalutate tissue parameters relevant to TCA cyclemetabolism, anerobic glycolysis, ATP levels, blood‐brain barrier permeability, macrophage infiltration, cytotoxic edema, spreading depression, cerebral blood flow and volume, and neurotransmitter function. The paramagnetic nature of certain oxidation states of iron leads to the ability to map out brain function using deoxyhemoglobin as an endogenous contrast agent, and also allows for mapping of local tissue iron concentrations. In addition to these metabolic parameters, the number of ways to generate anatomic contrast using MR is also expanding; and in addition to conventional anatomic scans, mapping of axonal fiber tracts can also be performed using the anisotropy of water diffusion. A strategy for integration of these multifarious parameters in a comprehensive neurofunctional exam in neurodegenerative illness is outlined in this paper. The goals of the integrated exam, as applied to a given neurodegenerative illness, can be subdivided into three categories: etiology, natural history, and therapeutic end points. The consequences of oxidative stress and/or mitochondrial dysfunction are explored in the context of the various parameters that can be measured using the integrated MR exam.
Vasoactive Intestinal Peptide: Link between Electrical Activity and Glia‐mediated Neurotrophism
Authors: BRENNEMAN DOUGLAS E. , HAUSER JANET , PHILLIPS TERRY M. , DAVIDSON ARIANE , BASSAN MERAV , GOZES ILLANA
Published: February 2006

Abstract:Vasoactive intestinal peptide has neurotrophic and neuroprotective properties that influence the survival of activity‐dependent neurons in the central nervous system. Investigations of the mechanism of this neurotrophic peptide indicated that these actions are contingent on interactions with astroglia. The complex mixture of neurotrophic mediators released from astroglia include cytokines, a protease inhibitor, and activity‐dependent neurotrophic factor, a protein with apparent structural similarities to hsp60. Investigations of ADNF resulted in the discovery of active peptides of extraordinary potency and broad neuroprotective properties. These studies indicate that a nine‐amino acid core peptide of ADNF had significantly greater neuroprotective properties in comparison to the parent growth factor and these advantages identify ADNF‐9 as an attractive lead compound for drug development.
Evolution of the Corticotropin‐releasing Hormone Signaling System and Its Role in Stress‐induced Phenotypic Plasticity
Authors: DENVER ROBERT J.
Published: February 2006

Abstract: Developing animals respond in variation in their habitats by altering their rules of development and/or their morphologies (i.e., they exhibit phenotypic plasticity). In vertebrates, one mechanism by which plasticity is expressed is through activation of the neuroendocrine system, which transduces environmental information into a physiological response. Recent findings of ours with amphibians and of others with mammals show that the primary vertebrate stress neuropeptide, corticotropin‐releasing hormone (CRH), is essential for adaptive developmental responses to environmental stress. For instance, CRH‐dependent mechanisms cause accelerated metamorphosis in response to pond‐drying in some amphibian species, and intrauterine fetal stress syndromes in humans precipitate preterm birth. CRH may be a phylogenetically ancient developmental signaling molecule that allows developing organisms to escape deleterious changes in their larval/fetal habitat. The response to CRH is mediated by at least two different receptor subtypes and may also be modulated by a secreted binding protein.
Corticotrophin‐releasing Hormone and CRH‐binding Protein: Differences between Patients at Risk for Preterm Birth and Hypertension
Authors: HOBEL CALVIN J. , ARORA CHANDER P. , KORST LISA M.
Published: February 2006

Abstract: Background: During pregnancy in the second and third trimester there is a progressive rise in plasma CRH thought to be secreted by the placenta. Plasma CRH‐BP inactivates CRH, which may prevent its peripheral action on the maternal pituitary and myometrium. In the last few weeks of pregnancy CRH‐BP decreases, thereby causing an increase in free CRH or a CRH/CRH‐BP complex available to play a role in the onset of parturition. Objective: We tested the hypothesis that differences in CRH, CRH‐BP, or a CRH/CRH‐BP complex in patients at risk for preterm birth (PTB) and hypertension (HYP) account for the differences in the timing of parturition. Methods: From a Behavior in Pregnancy Study database, we identified 18 patients who had spontaneous PTB and 23 patients who developed HYP. Both groups were case controlled and matched with patients who delivered at term (Normal). Maternal plasma samples had been appropriately collected from these patients at 18‐20, 28‐30, and 35‐36 weeks gestational age. CRH levels were measured by double antibody RIA kit and the CRH‐BP by a immunoradiometric technique. A CRH‐BP/CRH dimer complex index was calculated. Statistical analysis was done using Kruskal‐Wallis test for two cases. Results: Maternal CRH (pg/ml) in the PTB cases compared to the HYP cases was significantly elevated at all three time periods. Maternal CRH‐BP (pg/ml) in the PTB versus HYP cases was significantly lower at all three time periods in the PTB cases compared to the HYP cases. Maternal CRH‐BP/CRH dimer complex index was significantly lower in the PTB cases at all three time periods than either the controls or the HYP cases, suggesting excessive CRH. The mean GA at delivery for the PTB cases was significantly lower than the control or HYP cases. Conclusions: These results suggest that those patients at risk for PTB have significantly elevated CRH, lower CRH‐BP, and a reduced CRH‐BP/CRH dimer complex index at all three time periods of assessment.
Vasoactive Intestinal Peptide Regulates Embryonic Growth Through the Action of Activity‐dependent Neurotrophic Factor
Authors: HILL JOANNA M. , GLAZNER GORDON W. , LEE SUSAN J. , GOZES ILLANA , GRESSENS PIERRE , BRENNEMAN DOUGLAS E.
Published: February 2006

Abstract:Activity‐dependent neurotrophic factor is a potent, neuroprotective protein released from astroglia by VIP and accounts in part for the neuroprotective properties of this neuropeptide. The growth‐regulatory actions of VIP during embryogenesis may also occur indirectly through the release of activity‐dependent neurotrophic factor. Whole cultured day‐9 mouse embryos treated with activity‐dependent neurotrophic factor (10−13M) for 4 hr grew 3.1 somites, compared with 1.6 somites in control embryos. Treated embryos appeared morphologically normal and exhibited significant increases in cross‐sectional area, protein, and DNA content and bromodeoxyuridine incorporation. Anti‐activity‐dependent neurotrophic factor significantly inhibited growth. Co‐treatment of embryos with anti‐activity‐dependent neurotrophic factor inhibited VIP‐stimulated growth; however, anti‐VIP did not inhibit activity‐dependent neurotrophic factor‐induced growth. These data indicate that an activity‐dependent neurotrophic factor‐like substance is an endogenous embryonic growth factor and that VIP‐regulated growth occurs, at least in part, through activity‐dependent neurotrophic factor.
Regulation of Postimplantation Mouse Embryonic Growth by Maternal Vasoactive Intestinal Peptide
Authors: SPONG CATHERINE Y. , LEE SUSAN J. , McCUNE SUSAN K. , GIBNEY GRETCHEN , ABEBE DANIEL T. , BRENNEMAN DOUGLAS E. , HILL JOANNA M.
Published: February 2006

Vasoactive intestinal peptide (VIP) is an identified regulator of growth in the embryonic day (E) 9‐11 mouse. Mouse embryonic and extra‐embryonic tissues were studied to identify the source of VIP at this critical time. VIP mRNA was detected in the decidua/trophoblast at E8 and declined until E10, after which it was not detectable. VIP mRNA was not apparent in the embryo until E11‐E12. At E9, cells in decidua had VIP as well as lymphocyte marker (delta and CD3) immunoreactivity. VIP binding sites were dense in the decidua/trophoblast at E6, which gradually decreased until E10. VIP binding sites were detected in embryonic neuroepithelium by E9. The transient presence of VIP binding sites and mRNA in the decidua/trophoblast correlate with the identified period of VIP growth regulation, when VIP mRNA is absent in the embryo. Therefore, these findings suggest that maternal decidual lymphocytes are the source of VIP that regulate early postimplantation embryonic growth.
VIP Neuroprotection against Excitotoxic Lesions of the Developing Mouse Brain
Authors: GRESSENS PIERRE
Published: February 2006

Abstract:Intracerebral administration of the excitotoxin ibotenate to newborn mice induced white‐matter lesions mimicking the periventricular leukomalacia occurring in human premature babies. in this model, co‐injection of vasoactive intestinal peptide (VIP) prevented white‐matter lesions. VIP did not prevent the initial appearance of white‐matter lesion, but promoted a secondary repair with axonal regrowth. Co‐administration of ibotenate, VIP, and transduction inhibitors showed that protein kinase C (PKC) and mitogen‐associated protein kinase (MAPK) pathways were critical for neuroprotection. The combination ofin vitroandin vivostudies suggested the following model: VIP activates PKC in astrocytes, which release soluble factors; these released factors activate neuronal MAPK and PKC, which will permit axonal regrowth. Previous studies had shown that VIP‐treated cultured astrocytes release growth factors including activity‐dependent neurotrophic factor (ADNF) and that a 14‐amino‐acid peptide derived from ADNF protected the developing white matter against ibotenate. However, co‐treatment with ibotenate, VIP, and anti‐ADNF antibodies did not abolish VIP‐induced protection, suggesting that ADNF does not mediate VIP protective properties in the present model.
A Novel Signaling Molecule for Neuropeptide Action: Activity‐dependent Neuroprotective Protein
Authors: GOZES ILLANA , BASSAN MERAV , ZAMOSTIANO RACHEL , PINHASOV ALBERT , DAVIDSON ARIANE , GILADI ELIEZER , PERL ORLY , GLAZNER GORDON W. , BRENNEMAN DOUGLAS E.
Published: February 2006

Abstract:The complete coding sequence of a novel protein (828 amino acids, pI 5.99), a potential new mediator of vasoactive intestinal peptide (VIP) activity was recently revealed. The expression of this molecule, activity‐dependent neuroprotective protein (ADNP), was augmented in the presence of VIP, in cerebral cortical astrocytes. The mRNA transcripts encoding ADNP were enriched in the mouse hippocampus and cerebellum. The protein deduced sequence contained the following: (1) a unique peptide, NAPVSIPQ, sharing structural and immunological homologies with the previously reported, activity‐dependent neurotrophic factor (ADNF) and exhibiting neuroprotectionin vitroandin vivo; (2) a glutaredoxin active site; and (3) a classical zinc binding domain. Comparative studies suggested that the peptide, NAPVSIPQ (NAP), was more efficacious than peptides derived from ADNF. ADNP, a potential mediator of VIP‐associated neuronal survival, and the new peptide, a potential lead compound for drug design, are discussed below.
Endomorphins: Novel Endogenous μ‐Opiate Receptor Agonists in Regions of High μ‐Opiate Receptor Density
Authors: ZADINA JAMES E. , MARTIN‐SCHILD SHERYL , GERALL ARNOLD A. , KASTIN ABBA J. , HACKLER LASZLO , GE LIN‐JUN , ZHANG XING
Published: February 2006

Abstract: Endomorphin‐1 (Tyr‐Pro‐Trp‐Phe‐NH2, EM‐1) and endomorphin‐2 (Tyr‐Pro‐Phe‐Phe‐NH2, EM‐2) are peptides recently isolated from brain that show the highest affinity and selectivity for the m (morphine) opiate receptor of all the known endogenous opioids. The endomorphins have potent analgesic and gastrointestinal effects. At the cellular level, they activate G‐proteins (35S‐GTP γ‐S binding) and inhibit calcium currents. Support for their role as endogenous ligands for the μ‐opiate receptor includes their localization by radioimmunoassay and immunocytochemistry in central nervous system regions of high μ receptor density. Intense EM‐2 immunoreactivity is present in the terminal regions of primary afferent neurons in the dorsal horn of the spinal cord and in the medulla near high densities of μ receptors. Chemical (capsaicin) and surgical (rhizotomy) disruption of nociceptive primary afferent neurons depletes the immunoreactivity, implicating the primary afferents as the source of EM‐2. Thus, EM‐2 is well‐positioned to serve as an endogenous modulator of pain in its earliest stages of perception. In contrast to EM‐2, which is more prevalent in the spinal cord and lower brainstem, EM‐1 is more widely and densely distributed throughout the brain than EM‐2. The distribution is consistent with a role for the peptides in the modulation of diverse functions, including autonomic, neuroendocrine, and reward functions as well as modulation of responses to pain and stress.
Pain Inhibition by Endomorphins
Authors: PRZEWŁOCKI R. , ŁABUZ D. , MIKA J. , PRZEWŁOCKA B. , TOMBOLY Cs. , TOTH G.
Published: February 2006

Abstract:Spinal analgesic effects of endomorphin‐1 and endomorphin‐2 were studied during acute, inflammatory, and neuropathic pain in rats chronically implanted with intrathecal cannulas. Endomorphin‐1 and endomorphin‐2 (2.5‐10 μg i.t.), as well as their analogues, increased the tail‐flick and the paw pressure latencies. In a model of inflammatory pain, the formalin‐induced behavior was attenuated by endomorphins; however, the effect studied was not dose‐dependent and was less pronounced in comparison with that evoked by morphine. On the other hand, in rats with a sciatic nerve injury (crush), endomorphins antagonized allodynia in a dose‐dependent manner, whereas morphine was found to be ineffective in a similar dose range. Endomorphins also exhibited an antinociceptive potency in rats tolerant to morphine. In conclusion, our results show a powerful analgesic action of endomorphins at the spinal level. The most interesting finding is a strong effect of endomorphins in neuropathic pain, which opens up a possibility of using these compounds in pain therapy.
Vasodilator Responses to the Endomorphin Peptides, but Not Nociceptin/OFQ, Are Mediated by Nitric Oxide Release
Authors: CHAMPION H. C. , BIVALACQUA T. J. , ZADINA J. E. , KASTIN A. J. , KADOWITZ P. J.
Published: February 2006

Abstract: The endomorphin peptides, endogenous ligands for the μ‐opioid receptor, and nociceptin (orphanin FQ; OFQ), an endogenous ligand for the ORL1 receptor, have substantial vasodilator activity in the rat. The roles of nitric oxide, vasodilator prostaglandins, and the opening of K+ATP channels in mediating vasodilator responses to these novel agonists were investigated in the hindquarters vascular bed of the rat. Under constant‐flow conditions, injections of the μ‐selective agonists, endomorphin 1 and 2, PL017 ([N‐MePhe3, d‐Pro4]‐morphiceptin), and DAMGO, and the ORL1 receptor agonist, nociceptin/OFQ, produced dose‐dependent decreases in hindquarters perfusion pressure. Vasodilator responses to endomorphin 1, PL017, and DAMGO were attenuated by the nitric oxide synthase inhibitor l‐NAME at a time when vasodilator responses to nociceptin/OFQ were not altered. Responses to endomorphin 1 and 2, PL017, DAMGO, and nociceptin/OFQ were not altered by the cyclooxygenase inhibitor sodium meclofenamate or the K+ATP channel blocker U‐37883A. The results of these studies indicate that responses to endomorphin 1 and 2, PL017, and DAMGO are mediated in large part by the release of nitric oxide, while responses to nociceptin/OFQ are mediated by an l‐NAME‐insensitive mechanism. Moreover, these results demonstrate that responses to these peptides are not mediated by the release of vasodilator prostaglandins or K+ATP channel opening in the hindquarters vascular bed.
The Role of Brain‐Gut Peptides in the Control of Sodium Appetite
Authors: EDWARDS GAYLEN L. , POWER JOYCE D.
Published: February 2006

Abstract: Ingestion of food and fluid stimulates release of a number of peptides from the gastrointestinal system. These peptides are recognized to act as neurotransmitters/neuromodulators and act at both peripheral and central receptors. Many studies indicate that these peptides are important signals in terminating meals. Recent studies suggest that bombesin, a peptide related to gastrin‐releasing peptide, suppresses sodium appetite. We have investigated the role of cholecystokinin (CCK) in the control of sodium appetite. Our studies indicate that CCK is effective at reducing saline intake. We found that exogenous, intraperitoneal CCK octapeptide suppresses saline intake. Moreover, administration of trypsin inhibitor to stimulate endogenous CCK release resulted in suppression of saline intake. Finally, intraperitoneal administration of the CCK receptor antagonist lorglumide resulted in increased saline intake. These observations extend the potential role of gastrointestinal peptides in the modulation of ingestive behavior.
Actions of Nematode FMRFamide‐related Peptides on the Pharyngeal Muscle of the Parasitic Nematode, Ascaris suum
Authors: BROWNLEE D. J. A. , WALKER R. J.
Published: February 2006

Abstract: The endogenous nematode peptides known as FMRFamide‐related peptides (FaRPs) and various “classical” transmitters have a range of effects on nematodes that result in changes in behavior, particulary locomotion, including paralysis and inhibition of feeding. This study describes the application of an in vitro pharmacological approach to further delineate the action of a number of FaRP neurotransmitters on feeding behavior. Contraction of Ascaris suum pharyngeal muscle was monitored using a modified pressure transducer system that detects changes in intrapharyngeal pressure and therefore contraction of the radial muscle of the pharynx. The pharynx did not contract spontaneously. However, serotonin (5‐HT, 100 μM) stimulated rhythmic contractions and relaxations (pumping) at a frequency of 0.5 Hz. The native nematode peptide, KNEFIRFamide (AF1), inhibited the pumping elicited by 5‐HT. The duration of inhibition was concentration‐dependent (1‐1000 nM) with a threshold of 1 nM (n= 7). KSAYMRFamide (AF8/PF3) also inhibited pharyngeal pumping. There was no observable effect of any of the following nematode peptides on pharyngeal pumping behavior (1‐1000 nM; n= 8): AF2, AF3, AF4, AF6, AF16, PF1/CF1, PF2/CF2, or PF4. Thus, interruption of pharyngeal processes, such as feeding, regulation of hydrostatic pressure, and secretion, may provide a new site of anthelmintic action.
The Regulation of Juvenile Hormone Production in Arthropods: Functional and Evolutionary Perspectives
Authors: TOBE S. S. , BENDENA W. G.
Published: February 2006

Abstract:Although sesquiterpenoids are probably the ancestral regulators of reproduction and secondarily of metamorphosis in arthropods, our discussion suggests that the neuropeptides that regulate the biosynthesis of these compounds have arisen on several distinct occasions. These peptides probably occurred originally as regulators of other physiological processes and were subsequently co‐opted for the regulation of sesquiterpenoid biosynthesis, perhaps first in adult forms and thereafter in larval forms. The evolution of peptides to assume additional physiological functions probably occurred as a result of gene duplication, both at the peptide level and at the receptor level. There are likely to be numerous regulators of sesquiterpenoid biosynthesis in both Insecta and Crustacea, and investigations to date have only begun to reveal the host of peptide families involved in the regulation of juvenile hormone‐related biosynthesis across the arthropods.
Allatostatins: A Growing Family of Neuropeptides with Structural and Functional Diversity
Authors: BENDENA W. G. , DONLY B. C. , TOBE S. S.
Published: February 2006

Abstract: The high degree of conservation of the core sequence of the “cockroach‐types” of AST and their widespread distribution suggest that they should be considered a ubiquitous family of peptides within the invertebrates, regulating a range of important physiological processes. These functional processes, by either neural or humoral routes of action, include the inhibition of endocrine function, interneuronal functions, neuromodulatory roles, myotropic and myoendocrine roles, and direct action on biosynthetic pathways. The myomodulatory function appears to be conserved through evolutionary time, whereas the JH inhibitory activity appears to be confined to specific orders. This suggests that the myomodulatory role was the more ancestral of these two particular functions. Certainly, further purification and gene cloning as a means to precursor identification and functional analysis will be a prerequisite to understanding the diverse functions of this peptide family.
The Significance of Manduca sexta Allatostatin in the Tomato Moth Lacanobia oleracea
Authors: AUDSLEY NEIL , WEAVER ROBERT J. , EDWARDS JOHN P.
Published: February 2006

Abstract: The nature and regulation of juvenile hormone (JH) biosynthesis have been investigated in isolated corpora allata (CA) of adult males and females, and larvae of the tomato moth Lacanobia oleracea (Noctuidae). Larval CA (Vth day 1 to VIth day 1) appear to synthesize JH at very low rates (<0.5 fmol/pr/h). This synthesis was not affected by Manduca sexta allatostatin (Mas‐AS) nor Manduca sexta allatotropin. In contrast, adult female CA synthesize relatively high levels of JHI and JHII (>10 pmol/pr/h), each of which can be inhibited (approx. 60%) by Mas‐AS. CA from adult male L. oleracea do not produce detectable levels of JH but would appear to synthesize JH‐acids instead, which can also be inhibited (approx. 50%) by Mas‐AS. When assayed on adult female L. oleracea CA, brain extracts separated by liquid chromatography show inhibitory activity. The major biologically active fraction also has the greatest Mas‐AS‐like immunoreactivity and co‐elutes with synthetic Mas‐AS, indicating that most of the allatostatic activity in brain extracts is due to a Mas‐AS‐like peptide. In adult male brains, even though relatively high levels of immunoreactivity co‐elute with synthetic Mas‐AS, the majority of the Mas‐AS‐like immunoreactivity is more hydrophobic.
Insect Angiotensin‐converting Enzyme: A Processing Enzyme with Broad Substrate Specificity and a Role in Reproduction
Authors: ISAAC R. ELWYN , EKBOTE UMA , COATES DAVID , SHIRRAS ALAN D.
Published: February 2006

Abstract: Insect angiotensin‐converting enzyme (ACE) is a peptidyl dipeptidase that removes dipeptides and dipeptideamides from the C‐terminus of a broad range of in vitro oligopeptide substrates. In mammals, ACE has important roles in blood homeostasis and a recently recognized, but as yet undefined, role in the fertility of male mice. High levels of ACE are found in the male reproductive tissues of several insect species, and emerging data indicates an important role for the enzyme in insect reproduction. In this paper we review some of the recent findings about insect ACE, and we speculate as to the physiological role of this enzyme in insect reproduction.
Development of Amphiphylic Mimics of Insect Neuropeptides for Pest Control
Authors: TEAL PETER E. A. , MEREDITH JULIA A. , NACHMAN RONALD J.
Published: February 2006

Abstract: Insect neuropeptides regulate virtually all aspects of insect life and are excellent candidates for development of new methods for pest control. However, they do not penetrate insect cuticle and are degraded by enzymes both in the digestive system and hemolymph. We have designed mimics of model neuropeptides by attachment of various lipidic moieties to the amino terminus of the bioactive core of the neuropeptides. These mimics have amphiphylic characteristics that allowed them to penetrate the hydrophobic insect cuticle. The mimics also induced prolonged physiological responses (up to 20 hours) and were resistant to peptidase attack. This knowledge has been used to develop a novel, species‐specific approach to insect control.
Tachykinin‐like Peptides and Their Receptors: A Review
Authors: VANDEN BROECK JOZEF , TORFS HERBERT , POELS JEROEN , VAN POYER WENDY , SWINNEN ELFRIEDE , FERKET KATHELIJNE , DE LOOF ARNOLD
Published: February 2006

Abstract: Tachykinin‐like peptides have been identified in many vertebrate and invertebrate species. On the basis of the data reviewed in this paper, these peptides can be classified into two distinct subfamilies, which are recognized by their respective sequence characteristics. All known vertebrate tachykinins and a few invertebrate ones share a common C‐terminal sequence motif, ‐FXGLMa. The insect tachykinins, which have a common ‐GFX1GX2Ra C‐terminus, display about 30% of sequence homology with the first group.

Tachykinins are multifunctional brain/gut peptides. In mammals and insects, various isoforms play an important neuromodulatory role in the central nervous system. They are involved in the processing of sensory information and in the control of motor activities. In addition, members of both subfamilies elicit stimulatory responses on a variety of visceral muscles. The receptors for mammalian and insect tachykinins show a high degree of sequence conservation and their functional characteristics are very similar. In both mammals and insects, angiotensin‐converting enzyme (ACE) plays a prominent role in tachykinin peptide metabolism.
Survey of Electrical Burns in Philippine General Hospital
Authors: ACOSTA ASER S. , AZARCON‐LIM JEANE , RAMIREZ ALFREDO T.
Published: February 2006

ABSTRACT: A total of 211 patients were admitted at the UP‐PGH Burn Unit in 1995. Sixty‐eight (32.2%) patients suffered burn injuries secondary to electrical injury. In the period from July to December 1995, a total of 28 patients were admitted because of burns caused by electricity. Twenty‐six (92%) patients sustained injury secondary to high tension (>1000 V) electrical current and 2 (7.1%) secondary to low tension (<1000 V) electrical current, specifically 220 V, which were both self‐inflicted. Twenty‐seven (96%) patients were males. Injury was work‐related in 18 patients, nonwork‐related in 8, and self‐inflicted in 2. Sixteen (57%) patients suffered injuries on a rooftop, 11 (39%) patients on the ground, and 1 (3.5%) patient on top of an electric post. A total of 22 operations were performed on 28 patients, including 7 extremity amputations, which makes an amputation rate of 25%. There were 5 deaths secondary to overwhelming wound sepsis, making an overall mortality rate of 21.7% and an operative mortality rate of 22.7%. The average length of hospital stay was 17.2 days.
Thermoacoustic Energy Effects in Electrical Arcs
Authors: CAPELLI‐SCHELLPFEFFER M. , MILLER GREGORY H. , HUMILIER MICHEL
Published: February 2006

ABSTRACT:Electrical arcs commonly occur in electrical injury incidents. Historically, safe work distances from an energized surface along with personal barrier protection have been employee safety strategies used to minimize electrical arc hazard exposures. Here, the two‐dimensional computational simulation of an electrical arc explosion is reported using color graphics to depict the temperature and acoustic force propagation across the geometry of a hypothetical workroom during a time from 0 to 50 ms after the arc initiation. The theoretical results are compared to the experimental findings of staged tests involving a mannequin worker monitored for electrical current flow, temperature, and pressure, and reported data regarding neurologic injury thresholds. This report demonstrates a credible link between electrical explosions and the risk for pressure (acoustic) wave trauma. Our ultimate goal is to protect workers through the design and implementation of preventive strategies that properly account for all electrical arc‐induced hazards, including electrical, thermal, and acoustic effects.
A Clinical Analysis of 836 Cases with Electric Injury
Authors: YAN GENG‐RONG , LI MEI , WU YALI
Published: February 2006

ABSTRACT: Eight hundred thirty‐six patients with electric injury were admitted to Shanghai Power Hospital from 1972 to 1998. The majority of electric injury patients were young or middle‐aged industrial workers from both cities and rural areas. These patients were classified into three categories depending on the type of electric injury: (1) electric shock; (2) electric contact burn injury; (3) electric arc burn. In our study of wound management, we focused on three areas: first, the choice of operation time in electric burn injury; second, the methods of wound management on the injured extremities, especially the hands and upper limbs; third, functional site wounds that included some exposed blood vessels. Nerves and tendons were covered and repaired by various flaps. Through the analysis of 836 electric injury cases, we summarized our experience of treating electric injury with the purpose of increasing our knowledge in the area of electric injury prevention and treatment.
High Voltage Electrical Injury Leading to a Delayed Onset Tetraplegia, with Recovery
Authors: BREUGEM C. C. , VAN HERTUM W. , GROENEVELT F.
Published: February 2006

ABSTRACT: High voltage electrical injury can cause considerable damage to the central nervous system. Delayed spinal cord injury is uncommon, usually incomplete, and comprises predominantly motor fallout. The injury can be progressive, with only a few patients showing partial improvement. We present a case report of a 20‐year‐old male who had a delayed onset spinal cord injury after a high voltage electrical injury. The symptoms started several days postburn with an ascending paralysis, leading to tetraplegia. Gradual recovery became evident at 3 months after the accident, starting with his arms and later showing partial recovery of his lower limbs. The mechanisms of injury and pathophysiology to the spinal cord are poorly understood. Possible explanations for the delayed onset of neurologic complications are given. The exact reasons for the delayed, ascending paralysis and the mechanism of recovery still need further investigation.
Issues in Modeling Thermal Alterations in Tissues a
Authors: DILLER KENNETH R. , PEARCE JOHN A.
Published: February 2006

ABSTRACT: Thermal injury in living tissues is commonly modeled as a rate process in which cell death is interpreted to occur as a function of a single kinetic process. Experimental data indicate that multiple rate processes govern the manifestation of injury and that these processes may act over a broad spectrum of time domains. Injury is typically computed as a dimensionless function (Ω) of the temperature time history via an Arrhenius relationship to which numerical values are assigned based on defined threshold levels of damage. However, important issues central to calculation and interpretation of the Ω function remain to be defined. These issues include the following: how is temperature identified in time and space within a tissue exposed to thermal stress; what is the biophysical and physiological meaning of a quantitative value for Ω; how can Ω be quantified in an experimental system; how should Ω be scaled between graded levels of injury; and what are the differences in injury kinetics between unit volume‐ and unit surface area‐governed processes of energy deposition into tissue to cause thermal stress? This paper addresses these issues with the goal of defining a more rigorous and comprehensive standard for modeling thermal injury in tissues.
Changes in Skin Structure and Electrical Properties following High Voltage Exposure
Authors: GOWRISHANKAR T. R. , PLIQUETT UWE , WEAVER JAMES C.
Published: February 2006

ABSTRACT: Human skin experiences extensive alterations when exposed to a strong electric field. In high voltage electric shocks, tissues in the current path undergo large‐scale changes; the stratum corneum (SC), the outermost layer of the skin, loses its barrier function against ionic transport. The primary mechanism of electric field interaction with the skin is the creation of aqueous pathways, which increase the permeability of the skin to ions and macromolecules. Changes in skin structure and electrical properties were characterized by measuring the transport of fluorescent molecules in an in vitro preparation of human cadaver skin in a permeation chamber. Application of high voltage pulses (Uskin > 150 V,
τpulse= 1 ms

) decreased the skin resistance per unit area by three orders of magnitude from its initial value of 100 kΩ‐cm−2. The resistance reached a quasi‐steady state after about 20 pulses. After the cessation of pulsing, Rskin recovered immediately to about 4 kΩ‐cm−2 and remained low for 2 h thereafter. Transport of fluorescent molecules by high voltage pulses occurs in highly localized transport regions (LTRs), with diameters not exceeding 100 μm for short pulses (τpulse < 5 ms).
Dynamics of Membrane Sealing in Transient Electropermeabilization of Skeletal Muscle Membranes
Authors: GOWRISHANKAR T. R. , PLIQUETT UWE , LEE RAPHAEL C.
Published: February 2006

ABSTRACT: Large supraphysiologic transmembrane electrical potentials are known to alter the molecular organization of the bilayer lipid component of cell membranes, leading to ionic permeabilization or “electroporation”. Typically, membrane electroporation is followed by several orders of magnitude increases in electrical conductance and diffusive permeability to low‐molecular‐weight solutes. Electroporation may be transient or stable depending on whether the membrane eventually seals or remains permeabilized. Factors that control sealing have not been well characterized. This paper describes the kinetics of membrane sealing following electroporation by pulses over a range of supraphysiologic potentials. The increase in membrane conductance is highly nonlinear during a −440‐mV, 4‐ms pulse and reaches two orders of magnitude greater than baseline. Electroporation and relaxation sealing kinetics are quite different, reflecting a significant hysteresis effect. Thus, it appears that the magnitude and duration of the field pulse are important factors in sealing.
The Use of Collagen‐GAG Membranes in Reconstructive Surgery
Authors: ORGILL DENNIS P. , STRAUS FRANCIS H. , LEE RAPHAEL C.
Published: February 2006

ABSTRACT: Porous collagen‐glycosaminoglycan (PCG) membranes with a porous silicone elastomer coating have been useful as a scaffold for dermal replacement in burn victims. Critical physicochemical parameters of these membranes include pore size, cross‐link density, the percentage of glycosaminoglycan, and the degree of banding of the collagen. These factors govern the immunobiological response. Optimizing these parameters can reduce inflammation, scarring, and contraction of wounds grafted with PCG membranes. PCG membranes are currently commercially manufactured (Integra®, Integra Life Sciences, New Jersey) and available for clinical use.

Because clinical outcomes have improved using these membranes for burn wound coverage, other skin reconstruction problems including scar resurfacing, keloids, treatment of donor sites, and treatment of chronic wounds can be considered as potential applications. This manuscript illustrates our early experience using Integra® as a CG membrane for dermal replacement in reconstructive surgery. Our results indicate that CG membranes can lead to improved compliance and appearance compared to a meshed graft and may be sequentially placed in multiple layers to correct contour deformities. Also, in one case, we observed that, if placed on a wound bed with embedded skin epithelial cells, the PCG promotes epithelialization through the PCG matrix. The use of this material results in a supple integument with many similarities to normal skin.
Study on the Distribution Pattern of Skin Temperature in Normal Chinese and Detection of the Depth of Early Burn Wound by Infrared Thermography
Authors: ZHU WEI‐PING , XIN XIANG‐RONG
Published: February 2006

ABSTRACT: Objective Conduct basic research of the distribution pattern of skin temperature and estimate the wound depth in normal Chinese in the early stage of burn injury by using technical thermography.

Methods (1) Two hundred twenty‐three volunteers from the electrical power system were randomly chosen: 138 males and 85 females, mean age 42.5 ± 8.8, and mean weight 65.37 ± 9.7 kg. (2) Thermovisionr 470 Pro camera of AGEMA Corporation, Sweden, was used. (3) A total of 29,882 values of skin temperature from all over the body were classified, compared, and statistically analyzed.

Results The difference in temperature on the y‐axis of the body is relatively significant, from 0 to 9 °C. The difference in temperature on the x‐axis of the body is relatively invariable.

Conclusions The depth of early burn wound can be detected by using infrared thermography, which is an objective, fast, nontouching, and noninvasive method.
Using Engineering and Assistive Technologies for Rehabilitation after Electrical Traumaa
Authors: ROBINSON CHARLES J.
Published: February 2006

ABSTRACT: A framework is presented for judging when, how, and why rehabilitation engineering and its related assistive technologies are appropriate interventions following electrically induced trauma or burns. Instead of relying on the World Health Organization's medically based classification scheme of “Impairment, Disability, and Handicap,” this newer framework is built on a rational demarcation proposed by the National Center for Medical Rehabilitation and Research at the U.S. National Institutes of Health. This latter client‐centered framework encompasses pathophysiology, impairment, functional limitations, “disability”, and societal limitations. This framework is well suited to handle the varied sequelae of electrical trauma and burn injuries and provides guidance towards the most effective use of traditional rehabilitation interventions and of assistive technologies. For electrical injuries, rehabilitative technologies can be classified as those promoting job accommodations (i.e., that help an individual return to active employment, albeit possibly in a different role) or as aids to the other activities of daily living (ADLs) that provide an enhanced quality of life to the individual with disability. While the traditional rehabilitative focus has been on return‐to‐work, especially among professional tradesmen, a more productive rehabilitative effort in some cases may occur through psychosocial adjustments achieved via effective technological interventions that enhance ADLs.
Management and Coordination of Postacute Medical Care for Electrical Trauma Survivors
Authors: CHICO MARIA S. , CAPELLI‐SCHELLPFEFFER M. , KELLEY KATHLEEN M. , LEE RAPHAEL C.
Published: February 2006

ABSTRACT:The clinical spectrum of electrical injury ranges from the absence of any external physical signs to severe multiple trauma. Reported neuropsychiatric sequelae can vary from vague complaints, which may seem unrelated to the injury in their occurrence over time or by their apparent severity, to sequelae consistent with brain injury accompanying an electrical trauma. In this report, a case study and discussion are presented on the management and coordination of postacute care of an electrical trauma survivor. Expertise and a multi‐disciplinary team are essential to cohesive patient care. Patient monitoring for progressive changes and prompt intervention are needed to address the potential difficulties experienced by trauma survivors as they rehabilitate to return to their work and their activities of daily living.
The Pivotal Role of Iron in NF‐κB Activation and Nigrostriatal Dopaminergic Neurodegeneration: Prospects for Neuroprotection in Parkinson's Disease with Iron Chelators
Authors: YOUDIM M.B. H. , GRÜNBLATT E. , MANDEL S.
Published: February 2006

ABSTRACT: R‐Apomorphine (APO) the catechol‐derived dopamine D1‐D2 receptor agonist has been shown to be highly potent iron chelator and radical scavenger and inhibitor of membrane lipid peroxidation in vitro, in vivo and in cell culture employing PC12 cells. Its potency has been compared to the prototype iron chelator desferrioxamine (desferal), dopamine, nifedipine and dopamine D2 receptor agonists, bromocriptine, lisuride, pergolide and pramipexole. APO also inhibits brain and mitochondrial protein oxidation. In vivo APO protects against MPTP (N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine)‐induced striatal dopaminergic neurodegeneration in C57 black mice with as low as 5 mg/kg. APO is a reversible competitive inhibitor of monoamine oxidase (MAO) A and B with IC50 values of 93 and 214 uM, respectively. The iron chelating and radical scavenging actions of desferal and APO explains their ability to inhibit iron and 6‐hydroxydopamine (6‐OHDA)‐induced neurodegeneration and activation of redox‐sensitive transcription factor NF‐κB and the subsequent transactivation of promoters of genes involved in inflammatory cytokines. Iron is thought to play a pivotal role in neurodegeneration, and APO may be an ideal drug to investigate neuroprotection in Parkinson's disease where iron and oxidative stress have been implicated in the pathogenesis of nigrostriatal dopamine neuron degeneration.
Hypothermia‐Induced Ischemic Tolerance
Authors: NISHIO SHINSAKU , CHEN ZONG‐FU , YUNOKI MASATOSHI , TOYODA TOMIKATSU , ANZIVINO MATTHEW , LEE KEVIN S.
Published: February 2006

ABSTRACT:Delayed resistance to ischemic injury can be induced by a variety of conditioning stimuli. This phenomenon, known as delayed ischemic tolerance, is initiated over several hours or a day, and can persist for up to a week or more. The present paper describes recent experiments in which transient hypothermia was used as a conditioning stimulus to induce ischemic tolerance. A brief period of hypothermia administered 6 to 48 hours prior to focal ischemia reduces subsequent cerebral infarction. Hypothermia‐induced ischemic tolerance is reversed by 7 days postconditioning, and is blocked by the protein synthesis inhibitor anisomycin. Electrophysiological studies utilizingin vitrobrain slices demonstrate that hypoxic damage to synaptic responses is reduced in slices prepared from hypothermia‐preconditioned animals. Taken together, these findings indicate that transient hypothermia induces tolerance in the brain parenchyma, and that increased expression of one or more gene products contributes to this phenomenon. Inasmuch as hypothermia is already an approved clinical procedure for intraischemic and postischemic therapy, it is possible that hypothermia could provide a clinically useful conditioning stimulus for limiting injury elicited by anticipated periods of ischemia.
A Double‐Blind, Placebo‐Controlled Study of the Safety, Tolerability and Pharmacokinetics of CP‐101,606 in Patients with a Mild or Moderate Traumatic Brain Injury
Authors: MERCHANT RANDALL E. , BULLOCK M. ROSS , CARMACK CYNTHIA A. , SHAH AJIT K. , WILNER KEITH D. , KO GRANT , WILLIAMS STEPHEN A.
Published: February 2006

ABSTRACT:CP‐101,606 is a postsynaptic antagonist of the glutamate‐mediated NR2B subunit of theN‐methyl‐d‐aspartate (NMDA) receptor. When administered intravenously (i.v.) at the time of injury, CP‐101,606 is neuroprotective in animal models of traumatic brain injury (TBI) and ischemia. Minimal adverse effects have been observed in normal human volunteers given i.v. doses of up to 3 mg/kg/hr for 72 hours. The objective of the present clinical trial was to assess the safety, pharmacokinetics, and tolerability of CP‐101,606 infused for various times in patients who had suffered either an acute moderate or mild TBI (Glasgow Coma Score 9‐14) or hemorrhagic stroke. Patients began receiving treatment within 12 hours of brain injury. A total of 53 subjects (45 with TBI and 8 with stroke) were randomized in a double‐blind fashion to receive CP‐101,606 or placebo (4 drug:1 placebo). Drug/placebo was administered by i.v. infusion (0.75 mg/kg/hr) for 2 hours and then stopped (n= 25) or continued for 22 hours (n= 4) or 70 hours (n= 24) at a rate of 0.37 mg/kg/hr. Mean plasma drug concentrations were well above the predicted therapeutic concentration of 200 ng/ml within two hours of initiating treatment and were sustained as long as drug was infused. All the patients tolerated their drug/placebo treatment, and there were no clinically significant cardiovascular or hematological abnormalities in either group. A Neurobehavioral Rating Scale, used to detect personality changes and behavioral disturbances, indicated that all subjects showed an improvement from their postinjury, predosing baseline but did not significantly differ from each other with respect to type of head injury and/or treatment with drug or placebo. Modified Kurtzke Scoring also showed a similar pattern of improvement irrespective of type of head injury or drug/placebo treatment. This study suggests that CP‐101,606, infused for up to 72 hours has no psychotropic effects and is well‐tolerated in patients who have sustained a mild or moderate TBI or hemorrhagic stroke.
Estrogens: Neuroprotective or Neurotoxic?
Authors: SCALLET ANDREW C.
Published: February 2006

ABSTRACT: The present paper reviews the major modes of action of estrogen on the molecular, cellular, tissue, and neurobehavioral levels of mammalian physiology, with an emphasis on the brain as an estrogen target tissue. We draw a distinction between receptor‐ and nonreceptor‐mediated actions, as well as delineate the range of different signal transduction pathways that might be available within a given tissue to mediate estrogenic effects. We consider species differences relevant to understanding the predictability of effects in humans from data obtained in rats or monkeys. Finally, we emphasize the importance of developmental stage in determining whether estrogenic effects are beneficial or harmful; “neuroprotective” or “neurotoxic.”
Intraneuronal Ion Distribution during Experimental Oxygen/Glucose Deprivation: Routes of Ion Flux as Targets of Neuroprotective Strategies
Authors: LOPACHIN RICHARD M.
Published: February 2006

ABSTRACT:Ischemic neuronal injury appears to be mediated by disruption of subcellular ion distribution and, therefore, prevention of ion relocation might be neuroprotective. X‐ray microanalysis was used to measure concentrations of Na, K, Ca and other elements in subcellular compartments (e.g., mitochondria) of CA1 neurons from oxygen/glucose‐deprived (OGD) hippocampal slices. Results showed that OGD produced progressive loss of ion regulation in CA1 cells. Post‐OGD reperfusion with normal media exacerbated the initial ion deregulation. To study neuroprotective mechanisms, we determined the ability of hypothermia (31°C) or ion channel blockade to retard intraneuronal ion disruption induced by OGD/reperfusion. Whereas Ca2+channel blockade (ω‐conotoxin MVIIC, 3 μM) was ineffective, hypothermia and Na+channel blockers (tetrodotoxin, TTX, 1 μM; lidocaine, 200 μM) reduced ion deregulation in subneuronal compartments. Blockade of glutamate receptors (AMPA, 10 μM; the non‐NMDA receptor antagonist CNQX, 10 μM/100 μM glycine; the NMDA receptor antagonist CCP, 100 μM) during OGD/reperfusion provided nearly complete protection. These findings provide a foundation for identifying potential pharmacotherapeutic approaches and for discerning corresponding mechanisms of neuroprotection