bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a new cosmetic active for safe skin brightening
Authors: Mangues M. , Carreño C. , Cebrián J. , Almiñana N.
Published: July 2010

IFSCC Magazine, 12 (4) 373–378 (2009)

Synopsis

In Asia, lighter skin is a desirable feature considered to be a symbol of beauty and femininity, and the use of skin brighteners is widespread due to traditional beliefs. In Western countries, skin brightening agents are applied for the treatment of irregular pigmentation such as age spots and to produce a more even skin tone. Most current skin brightening agents show numerous adverse effects such as high irritant and sensitizing potential, melanocyte cytotoxicity and instability in formulations. Moreover, their lightening activity appears to be quite limited when it is tested in vivo on human volunteers. Dimethylmethoxy chromanyl palmitate (INCI name) is a novel skin brightener that has been tested for efficacy and safety with satisfactory results. The new active does not have any of the side effects that are normally associated with depigmenting agents, presents good efficacy in vitro and in vivo and is unique in that, unlike all other skin brighteners, it has a photoprotective effect.
Suppression of the AvrBs1‐specific hypersensitive response by the YopJ effector homolog AvrBsT fromXanthomonasdepends on a SNF1‐related kinase
Authors: Szczesny Robert , Büttner Daniela , Escolar Lucia , Schulze Sebastian , Seiferth Anja , Bonas Ulla
Published: July 2010

Featured paper: See Editorial p877
The cell wall polysaccharide metabolism of the brown alga Ectocarpus siliculosus. Insights into the evolution of extracellular matrix polysaccharides in Eukaryotes
Authors: Michel Gurvan , Tonon Thierry , Scornet Delphine , Cock J. Mark , Kloareg Bernard
Published: July 2010

Featured paper: See Commentary p1
Altered microglial copper homeostasis in a mouse model of Alzheimer’s disease
Authors: Zheng Zhiqiang , White Carine , Lee Jaekwon , Peterson Troy S. , Bush Ashley I. , Sun Grace Y. , Weisman Gary A. , Petris Michael J.
Published: July 2010

J. Neurochem. (2010) 114, 1630–1638.

Alzheimer’s disease (AD) is characterized by progressive neurodegeneration associated with the aggregation and deposition of β‐amyloid (Aβ40 and Aβ42) peptide in senile plaques. Recent studies suggest that copper may play an important role in AD pathology. Copper concentrations are elevated in amyloid plaques and copper binds with high affinity to the Aβ peptide and promotes Aβ oligomerization and neurotoxicity. Despite this connection between copper and AD, it is unknown whether the expression of proteins involved in regulating copper homeostasis is altered in this disorder. In this study, we demonstrate that the copper transporting P‐type ATPase, ATP7A, is highly expressed in activated microglial cells that are specifically clustered around amyloid plaques in the TgCRND8 mouse model of AD. Using a cultured microglial cell line, ATP7A expression was found to be increased by the pro‐inflammatory cytokine interferon‐gamma, but not by TNF‐α or IL‐1β. Interferon‐gamma also elicited marked changes in copper homeostasis, including copper‐dependent trafficking of ATP7A from the Golgi to cytoplasmic vesicles, increased copper uptake and elevated expression of the CTR1 copper importer. These findings suggest that pro‐inflammatory conditions associated with AD cause marked changes in microglial copper trafficking, which may underlie the changes in copper homeostasis in AD. It is concluded that copper sequestration by microglia may provide a neuroprotective mechanism in AD.
Intravenous adrenaline infusion causes vasoconstriction close to an intramuscular microdialysis catheter in humans
Authors: Vedung Torbjörn , Jorfeldt Lennart , Henriksson Jan
Published: July 2010

Aim: To test if a small muscle injury influences the vascular reactivity to adrenaline in human skeletal muscle.

Methods: Blood flow was measured by133Xenon clearance in the gastrocnemius muscle of eight male subjects at basal and during i.v. infusion of adrenaline (0·1 nmol kg−1 min−1) or placebo. Measurements were done with (expts 2 and 3) or without (expt 1) the influence of a small muscle injury induced by inserting a microdialysis catheter.133Xenon was administered either (expt 1) conventionally into the muscle via a fine needle, or (expts 2 and 3) through a fine tube close to the inserted microdialysis catheter. Expt 3 (control expt) was identical to expt 2 except that placebo was infused instead of adrenaline. Mean ± SEM,n = 8.

Results: The blood flow tended to increase during the adrenaline infusion in expt 1 (1·17 ± 0·10 to 1·39 ± 0·15, N.S.), whereas it decreased during the adrenaline infusion in expt 2, from 1·39 ± 0·14 to 1·03 ± 0·14 ml min−1 100 g tissue−1(P<0·001). The blood flow change in response to adrenaline infusion was significantly different in expt 1 and expt 2 (P<0·05). Blood flow also decreased during the placebo infusion in expt 3 (1·15 ± 0·10 to 1·00 ± 0·09,P<0·01), but this decrease was significantly smaller than in response to the adrenaline infusion in expt 2,P<0·01.

Conclusion: The present results are consistent with the hypothesis that the small muscle injury caused by the inserted microdialysis catheter influences the vascular reactivity to adrenaline in a vasoconstrictive direction.
Evaluating Input Standards for Non‐Point Pollution Control under Firm Heterogeneity
Authors: Doole Graeme J.
Published: July 2010

The efficacy and cost of input standards for reducing nitrate pollution from New Zealand dairy production are evaluated. In contrast to previous studies, firm heterogeneity is explicitly considered through the novel integration of efficient techniques for the calibration and decomposition of large optimisation models. Nitrogen fertiliser application should not be targeted by policy given its minor role in determining emissions. In contrast, livestock intensity is an appropriate base for regulation given its strong correlation with pollutant load. Abatement cost increases as stocking rate declines, but this can be offset at low levels of regulation through utilising slack feed resources to improve per‐cow milk production. Both uniform and differentiated input standards based on livestock intensity achieve substantial decreases in pollutant load at moderate cost. However, because of disparity in the slopes of abatement cost curves across firms, a differentiated policy is more cost‐effective at the levels of regulation required to achieve key societal goals for improved water quality.
Rethinking Kashmir’s History from a Borderlands Perspective
Authors: Zutshi Chitralekha
Published: July 2010

Although borders haunt its historical and recent past as well as its contemporary political situation, Kashmir has rarely been theorized as a borderland. This article examines the perspective of borderlands as conceptualized in North American, Asian and African borderlands scholarship. It argues that the application of this perspective – in which borderlands are defined as middle grounds where imperial competition and negotiations among a variety of imperial and indigenous actors led to the production of distinct political cultures – to rethinking Kashmir’s history has the potential to liberate the region from the imperatives of national borders that misread its history, while also reinvigorating South Asian borderlands scholarship.
Equal Representation of Time and Space: Arno Peters’ Universal History
Authors: Müller Stefan
Published: July 2010

How is our world view constructed? Beside the formative ideologies of the 20th century, what is conditioning our view on social, political and economic lives? These questions were the lifelong focus of the West German historian Arno Peters (1916–2002). He crossed borders between West‐ and East‐Germany, academic disciplines (history, cartography, economy), and different fields when he published a historical atlas (Synchronoptical World History, 1952 ff.), drafted maps (Peters‐projection, 1974 ff.) and designed (but never realized) a so‐called ‘Synchronoptikum’ (mid‐1960s to mid‐1990s). Although he never wrote or published a classical historical work nor left an opus, his contemporaries called him a polyhistor. In brief, Peters’ aim was the equal representation of time and space in history and geography. He was vehement in his criticism of the Europe‐centred character and constant use of the Mercator‐projection. Peters was a critic of the historical focus on the last 500 years of world history as well as its concentration on western civilizations and on politics. Both maps and history books mislead readers to accept Europe and Western civilizations as the history’s core, thus leading to ignorance of 90% of world history and the majority of people living in the Southern hemisphere. Later he dealt with economics and developed a concept of a democratic economy, based on an equivalent exchange of goods. He identified modern societies with market economies as non‐equivalent economies. The concept of equal representation of goods came high on Peters’ agenda, after time and space. This article reviews the fields of Peters’ work, explicates his idea of world history and gives a biographical sketch. While the Peters‐projection has widely been discussed and criticized, the article focuses on the un‐translated Synchronoptical World History, which reminds us of the 18th century synchronistic tables. The design of a building (Synchronoptikum) resembling a panorama museum, characterized Peters as crossing the border between history as academic discipline and social intervention.
The Ties That Bind: Infanticide, Gender, and Society
Authors: Bechtold Brigitte H. , Graves Donna Cooper
Published: July 2010

Infanticide is seen to be a horrific act, and yet this article finds that a growing body of literature on the topic is proving that infanticide is tied to human history. It provides a synthesis of the literature and identifies new directions in the scholarship since William L. Langer. These new directions move beyond the infanticidal act itself to an understanding of the circumstances that prompt it. They make clear that women’s bodies tie them to their sexuality and the need to nurture children. Moreover, women must carry out these responsibilities while tied to hostile environments, cultural proscriptions, patriarchal law, and the violence of war. Infanticide scholarship, then, uncovers the numerous ties that bind women together as victims who are driven to infanticide and also as women who have exhibited agency in an attempt to move beyond victimhood and assert control over their own destiny.
The California School and Beyond: How to Study the Great Divergence?
Authors: Vries Peer
Published: July 2010

In this article the autor presents a description, analysis and evaluation of the fundamentally new interpretation of the economic history of the early modern world that is defended by authors who collectively have become known as the California School, the most important among them being Kenneth Pomeranz, Roy Bin Wong, Andre Gunder Frank and Jack Goldstone. He in particular analyses their claim that in the period from roughly 1400 to 1800 the most advanced economies of Eurasia formed a world of ‘surprising resemblances’ and that the Great Divergence between ‘the West’ and ‘the Rest’ only originated with industrialisation and must be interpretated as a fairly contingent and recent phenomenon, basically due to differences in the availability of resources. The author claims that the Californians have a tendency to exaggerate the resemblances between Western Europe and East Asia and should be more specific when it comes to time, place and the differing historical trajectories of various regions. Finally, he claims they should pay far more attention to political and military developments and to the role of culture and institutions.
Joachim of Fiore, Apocalyptic Conversion, and the ‘Persecuting Society’
Authors: Whalen Brett
Published: July 2010

In recent years, scholarship on the 12th‐century Christian apocalyptic thinker Joachim of Fiore has highlighted the place of the Jews in his scenarios for the end of the world. Responding in part to R. I. Moore’s 1987 workThe Formation of a Persecuting Society, historians argue that Joachim’s vision of a harmonious Jewish apocalyptic conversion stood in contrast with rise of a persecuting mentality among the Christian ruling elite of medieval Europe, who increasingly sought to identify, marginalize, and sometimes violently oppress non‐Christian and non‐orthodox communities. These scholarly discussions of apocalyptic conversion have extended to include the Western Christian belief that not just the Jews, but also pagans, Muslims, and even non‐Western Christians would convert during the earthly Sabbath age that would precede the apocalypse. The resulting field of inquiry into medieval apocalyptic thought promises further insights into the ways that Christian scenarios for the ‘end of days’ might complicate narratives of religious persecution, violence, and conversion.
Epitaxial quartz inclusions in corundum from a sapphirine–garnet boudin, Bamble Sector, SE Norway: SiO2–Al2O3 miscibility at high P–T dry granulite facies conditions
Authors: KIHLE J. , HARLOV D. E. , FRIGAARD Ø. , JAMTVEIT B.
Published: July 2010

An Al‐rich, SiO2‐deficient sapphirine–garnet‐bearing rock occurs as a metapelitic boudin within granulite facies Proterozoic charnockitic gneisses and migmatites on the island of Hisøy, Bamble Sector, SE Norway. The boudin is made up of peraluminous sapphirine, garnet, corundum, spinel, orthopyroxene, sillimanite, cordierite, staurolite and biotite in a variety of assemblages. Thermobarometric calculations based on coexisting sapphirine–spinel, garnet–corundum–spinel–sillimanite, sapphirine–orthopyroxene, and garnet–orthopyroxene indicate peak‐metamorphic conditions near to 930 °C at 10 kbar. Corundum occurs as single 200 to 3000 micron sized skeletal crystal intergrowths in cores of optically continuous pristine garnet porphyroblasts. Quartz occurs as 5–60 micron‐sized euhedral to lobate inclusions in the corundum where it is in direct contact with the corundum with no evidence of a reaction texture. Some crystal inclusions exhibit growth zoning, which indicates that textural equilibrium was achieved. Electron Back‐Scatter Diffraction (EBSD) studies reveal that the quartz inclusions share a common c‐axis with the host corundum crystal. The origin of the quartz inclusions in corundum is enigmatic as recent experimental studies have confirmed the instability of quartz–corundum over geologically realistic P–T ranges. The combined EBSD and textural observations suggest the presence of a former silica‐bearing proto‐corundum, which underwent exsolution during post‐peak‐metamorphic uplift and cooling. Exsolution of quartz in corundum is probably confined to fluid‐absent conditions where phase transitions by coupled dissolution–precipitation mechanisms are prevented.
Therapeutic strategies to avoid long‐term adverse outcomes of neonatal antiepileptic drug exposure
Authors: Forcelli Patrick A. , Janssen Megan J. , Stamps Lauren A. , Sweeney Cameron , Vicini Stefano , Gale Karen
Published: July 2010

Antiepileptic drugs (AEDs) such as phenobarbital, phenytoin, and valproic acid, when given in therapeutic doses to neonatal rats, cause pronounced neuronal apoptotic cell death. This effect is especially pronounced in the striatum and cortex during the second postnatal week, a period corresponding to the “brain growth spurt” (third trimester of gestation and early infancy) in humans. Of particular concern is the fact that phenobarbital is the most frequently used therapy for neonatal epilepsy. If AED‐induced neuronal cell death leads to long‐term functional impairment, then it becomes crucial to find therapies that avoid this neurotoxicity in the sensitive period. Herein we examine short‐ and long‐term functional effects following exposure of neonatal rat pups to phenobarbital; the functions tested include striatal γ‐aminobutyric acid (GABA)ergic synaptic responses and reflex development in pups, and fear conditioning, emotionality, and sensory‐motor gating in adults. In all cases, phenobarbital exposure during the second postnatal week was sufficient to cause significant impairment. In contrast, adult animals exposed as pups to lamotrigine (given in a dose that does not cause apoptotic neuronal death) were not impaired on the tasks we examined. Our data suggest that treatments devoid of proapoptotic actions may be promising therapies for avoiding adverse outcomes after neonatal exposure. In addition, our findings identify early exposure to certain AEDs as an important potential risk factor contributing to psychiatric and neurologic abnormalities later in life.
Seizures triggered by food intake in antimuscarinic‐treated fasted animals: Evaluation of the experimental findings in terms of similarities to eating‐triggered epilepsy
Authors: Enginar Nurhan , Nurten Asiye
Published: July 2010

Food intake triggers convulsions in fasted mice and rats treated with antimuscarinic drugs, scopolamine or atropine. Bearing some similarities in triggering factor and manifestations of the seizures in patients with eating‐evoked epilepsy, seizures in fasted animals may provide insight into the mechanism(s) of this rare and partially controlled form of reflex epilepsy.
Effects of direct brain stimulation depend on seizure dynamics
Authors: Jiruska Premysl , Powell Andrew D. , Deans Jacqueline K. , Jefferys John G.R.
Published: July 2010

Brain stimulation is currently used as an experimental treatment for patients with medically refractory epilepsy. However, the results of such stimulation are still less than optimal. A major factor is the lack of understanding of the mechanisms of applied stimuli. Herein we review evidence on the effects of stimulation in models of epileptic seizures. We show that the effects of stimulation during epileptic seizures can differ from those observed under normal conditions. Several studies suggest a potentially greater beneficial therapeutic effect of strong depolarizing and overactivating stimulations than hyperpolarizing ones in the treatment of seizures. The potential relevance of these results to other therapeutic stimulation protocols is discussed.
Outcome of vagus nerve stimulation for epilepsy in Budapest
Authors: Müller Katalin , Fabó Dániel , Entz László , Kelemen Anna , Halász Péter , Rásonyi György , Erőss Loránd
Published: July 2010

Vagus nerve stimulation (VNS) is a nonpharmacologic therapeutic option for patients with intractable epilepsy. Better clinical outcomes were recorded in nonfocal and Lennox‐Gastaut syndrome (LGS). We conducted a 2‐year, open label, prospective study to measure the seizure outcome of 26 VNS patients. The seizure numbers were assessed using clinician’s global impression scale (CGI) and patient diaries. The average seizure reduction was 23% at the first year and 22% at the second year. Seizure reduction was more pronounced among patients with nonfocal than with focal epilepsy. The response rate was 50% at first year and 30% at the second year. The best CGI record for clinically significant improvement was 15% in the LGS group. The only statistically significant result was the reduction of the generalized tonic–clonic seizures (GTCS). The side‐effect profile was good; however, the large number of mild and reversible effects influenced the stimulation parameters and thus probably the effectiveness of the therapy. We suggest that VNS is an optional treatment mostly in cases of therapy‐resistant Lennox‐Gastaut syndrome. Patients with GTCS may experience improvement such as reduction of seizure severity. We conclude that VNS is a safe neuromodulatory treatment, but future developments of neuromodulatory approaches are needed.
CB1 receptor antagonism impairs the induction of epileptiform activity by group I metabotropic glutamate receptor activation
Authors: Karr Linda , Pan Yu‐Zhen , Rutecki Paul A.
Published: July 2010

Exposure to the group I metabotropic glutamate receptor (mGluR) agonist dihydroxy phenylglycine (DHPG) induces epileptiform activity in the CA3 region of the hippocampus that persists following washout of DHPG. DHPG also can cause long‐term depression of synaptic transmission, and at some synapses this may be mediated by endocannabinoids. We evaluated whether the selective cannabinoid type 1 (CB1) receptor antagonists SR 141716 or AM 251 could modify induction of epileptiform activity produced by DHPG exposure. The induction of epileptiform activity by DHPG exposure was significantly reduced by CB1 receptor antagonists, SR 141716 or AM 251. Minimal effects on epileptiform activity were noted once the activity had been induced. In control slices, exposure to DHPG for 30 min produced long‐term depression (LTD) of synaptic transmission, on average about a 70% reduction in slope of the field excitatory postsynaptic potential (EPSP). When slices were exposed to both DHPG and SR 141716 (3 μm), LTD did not occur and the population EPSP remained at control values or greater. These results suggest that CB1 receptors mediate some of DHPG effects that result in persistent epileptiform activity, and antagonism of CB1 receptors has antiepileptogenic properties. Paradoxically DHPG also caused LTD of excitatory synaptic transmission in the CA3 region and CB1 receptor antagonism prevents the depression. We hypothesize that the ictal activity induced by DHPG requires depression of synaptic strength and CB1 receptor antagonism prevents this depression and the induction of ictal activity.
Effects and mechanisms of progestogens and androgens in ictal activity
Authors: Frye Cheryl A.
Published: July 2010

Steroid hormones, such as progestogens and androgens, influence seizures. Progestogens and androgens exert organizational and/or activational effects that may mitigate vulnerability to, and/or expression of, some seizure disorders. Progestogens, such as progesterone (P4) and its 5α‐reduced metabolite, 5α‐pregnan‐3α‐ol‐20‐one (3α,5α‐THP), which vary across the reproductive cycle and lifespan, may protect against seizures through actions at intracellular progestin receptors (PRs) and membrane receptors, such as γ‐aminobutyric acid (GABA)A receptors. Similarly, androgens, such as testosterone (T), which also vary across the reproductive cycle and the lifespan, can have antiseizure effects. Some of these effects of T may be due to aromatization to estrogen and/or 5α‐reduction to dihydrotestosterone (DHT), and its subsequent conversion through 3α‐hydroxysteroid dehydrogenase to 5α‐androstane‐3α,17α‐diol (3α‐diol). Sensitivity to steroids in some individuals may be mitigated by differences in stress, developmental phase, reproductive status, endocrine status, and treatments, such as antiepileptic drugs (AEDs), which alter levels of these ligands and/or function of their target sites. The evidence implicating sex steroids in differences associated with hormonal, reproductive, developmental, stress, seizure type, and/or therapeutics are discussed.
Comparative study of cellular and synaptic abnormalities in brain tissue samples from pediatric tuberous sclerosis complex and cortical dysplasia type II
Authors: Cepeda Carlos , André Véronique M. , Yamazaki Irene , Hauptman Jason S. , Chen Jane Y. , Vinters Harry V. , Mathern Gary W. , Levine Michael S.
Published: July 2010

Tuberous sclerosis complex (TSC) and severe cortical dysplasia (CD), or CD type II according to Palmini classification, share histopathologic similarities, specifically the presence of cytomegalic neurons and balloon cells. In this study we examined the morphologic and electrophysiologic properties of cells in cortical tissue samples from pediatric patients with TSC and CD type II who underwent surgery for pharmacoresistant epilepsy. Normal‐appearing pyramidal neurons from TSC and CD type II cases had similar passive membrane properties. However, the frequency of excitatory postsynaptic currents (EPSCs) was higher in neurons from TSC compared to severe CD cases, particularly the frequency of medium‐ and large‐amplitude synaptic events. In addition, EPSCs rise and decay times were slower in normal cells from TSC compared to severe CD cases. Balloon cells were found more frequently in TSC cases, whereas cytomegalic pyramidal neurons occurred more often in CD type II cases. Both cell types were similar morphologically and electrophysiologically in TSC and severe CD. These results suggest that even though the histopathology in TSC and severe CD is similar, there are subtle differences in spontaneous synaptic activity and topographic distribution of abnormal cells. These differences may contribute to variable mechanisms of epileptogenesis in patients with TSC compared with CD type II.
Interneurons, GABA currents, and subunit composition of the GABAA receptor in type I and type II cortical dysplasia
Authors: André Véronique M. , Cepeda Carlos , Vinters Harry V. , Huynh My , Mathern Gary W. , Levine Michael S.
Published: July 2010

Interneurons, γ‐aminobutyric acid (GABA)A receptor density, and subunit composition determine inhibitory function in pyramidal neurons and control excitability in cortex. Abnormalities in GABAergic cells or GABAA receptors could contribute to seizures in malformations of cortical development. Herein we review data obtained in resected cortex from pediatric epilepsy surgery patients with type I and type II cortical dysplasia (CD) and non‐CD pathologies. Our studies found fewer interneurons immunolabeled for glutamic acid decarboxylase (GAD) in type II CD, whereas there were no changes in tissue from type I CD. GAD‐labeled neurons had larger somata, and GABA transporter (VGAT and GAT1) staining showed a dense plexus surrounding cytomegalic neurons in type II CD. Functionally, neurons from type I CD tissue showed GABA currents with increased half maximal effective concentration compared to cells from the other groups. In type II CD, cytomegalic pyramidal neurons showed alterations in GABA currents, decreased sensitivity to zolpidem and zinc, and increased sensitivity to bretazenil. In addition, pyramidal neurons from type II CD displayed higher frequency of spontaneous inhibitory post synaptic currents. The GABAergic system is therefore, altered differently in cortex from type I and type II CD patients. Alterations in zolpidem, zinc, and bretazenil sensitivity and spontaneous inhibitory postsynaptic currents (IPSCs) suggest that type II CD neurons have altered GABAA receptor subunit composition and receive dense GABA inputs. These findings support the hypothesis that patients with type I and type II CD will respond differently to GABA receptor–mediated antiepileptic drugs and that cytomegalic neurons have features similar to immature neurons.
A human systems biology approach to discover new drug targets in epilepsy
Authors: Loeb Jeffery A.
Published: July 2010

One of the major challenges in developing novel therapeutics for human epileptic disorders comes from the wide range of brain abnormalities capable of producing epilepsy. In children and adults that undergo epilepsy surgery for treatment of refractory seizures, these abnormalities range from developmental defects to injuries, infections, tumors, and ischemia. Given the many molecular mechanisms likely involved in each of these, finding common therapeutic targets seems a futile task. However, patients undergoing surgery for neocortical seizures have surprisingly similar electrophysiologic abnormalities, which consist of the synchronous firing of large neuronal populations. Surgical removal of these regions is the only means at present time to permanently reduce or eliminate seizures. The precise locations of these hypersynchronous firing regions that produce seizures can be revealed using long‐term subdural electrical high‐density recordings. This therapeutic strategy not only can dramatically reduce seizures, but also offers the potential to generate molecular and cellular information that can be used to ask why certain regions of the cortex become and remain epileptic. We have taken advantage of these detailed clinical and electrophysiologic human studies by taking a “systems biology” approach to identify novel biomarkers and drug targets in neocortical human epilepsy. In this article, we describe our multidisciplinary systems approach that utilizes a relational database to interrelate clinical, quantitative electrophysiologic, pathologic, and gene expression profiling data together as a means to identify and validate new biomarkers and potential drug targets for human epilepsy.
Infantile spasms: A U.S. consensus report
Authors: Pellock John M. , Hrachovy Richard , Shinnar Shlomo , Baram Tallie Z. , Bettis David , Dlugos Dennis J. , Gaillard William D. , Gibson Patricia A. , Holmes Gregory L. , Nordli Douglas R. , O’Dell Christine , Shields W. Donald , Trevathan Edwin , Wheless James W.
Published: July 2010

The diagnosis, evaluation, and management of infantile spasms (IS) continue to pose significant challenges to the treating physician. Although an evidence‐based practice guideline with full literature review was published in 2004, diversity in IS evaluation and treatment remains and highlights the need for further consensus to optimize outcomes in IS. For this purpose, a working group committed to the diagnosis, treatment, and establishment of a continuum of care for patients with IS and their families—the Infantile Spasms Working Group (ISWG)—was convened. The ISWG participated in a workshop for which the key objectives were to review the state of our understanding of IS, assess the scientific evidence regarding efficacy of currently available therapeutic options, and arrive at a consensus on protocols for diagnostic workup and management of IS that can serve as a guide to help specialists and general pediatricians optimally manage infants with IS. The overall goal of the workshop was to improve IS outcomes by assisting treating physicians with early recognition and diagnosis of IS, initiation of short duration therapy with a first‐line treatment, timely electroencephalography (EEG) evaluation of treatment to evaluate effectiveness, and, if indicated, prompt treatment modification. Differences of opinion among ISWG members occurred in areas where data were lacking; however, this article represents a consensus of the U.S. approach to the diagnostic evaluation and treatment of IS.
Alcohol and Hepatitis C Virus–Interactions in Immune Dysfunctions and Liver Damage
Authors: Szabo Gyongyi , Wands Jack R. , Eken Ahmet , Osna Natalia A. , Weinman Steven A. , Machida Keigo , Joe Wang H.
Published: July 2010

Hepatitis C virus infection affects 170 million people worldwide, and the majority of individuals exposed to HCV develop chronic hepatitis leading to progressive liver damage, cirrhosis, and hepatocellular cancer. The natural history of HCV infection is influenced by genetic and environmental factors of which chronic alcohol use is an independent risk factor for cirrhosis in HCV‐infected individuals. Both the hepatitis C virus and alcohol damage the liver and result in immune alterations contributing to both decreased viral clearance and liver injury. This review will capture the major components of the interactions between alcohol and HCV infection to provide better understanding for the molecular basis of the dangerous combination of alcohol use and HCV infection. Common targets of HCV and alcohol involve innate immune recognition and dendritic cells, the critical cell type in antigen presentation and antiviral immunity. In addition, both alcohol and HCV affect intracellular processes critical for hepatocyte and immune cell functions including mitochondrial and proteasomal activation. Finally, both chronic alcohol use and hepatitis C virus infection increase the risk of hepatocellular cancer. The common molecular mechanisms underlying the pathological interactions between alcohol and HCV include the modulation of cytokine production, lipopolysaccharide (LPS)‐TLR4 signaling, and reactive oxygen species (ROS) production. LPS‐induced chronic inflammation is not only a major cause of progressive liver injury and fibrosis, but it can also contribute to modification of the tissue environment and stem cells to promote hepatocellular cancer development. Alteration of these processes by alcohol and HCV produces an environment of impaired antiviral immune response, greater hepatocellular injury, and activation of cell proliferation and dedifferentiation.
Opioid Utilization and Health‐Care Costs among Patients with Diabetic Peripheral Neuropathic Pain Treated with Duloxetine vs. Other Therapies
Authors: Wu Ning , Chen Shih‐Yin , Hallett Lindsay A. , Boulanger Luke , Fraser Kimberly A. , Patel Chintan K. , Zhao Yang
Published: July 2010

Objective: This retrospective cohort study assessed subsequent opioid utilization and health‐care costs among patients with diabetic peripheral neuropathic pain (DPNP) who initiated duloxetine vs. other standard of care (SOC) treatments.

Methods: Medical and pharmacy claims were analyzed for commercially‐insured individuals aged 18–64. Two study cohorts were constructed from DPNP patients who initiated duloxetine or SOC medications (tricyclic antidepressants, venlafaxine, gabapentin, pregabalin) between March 1, 2005 and December 31, 2005. Initiation was defined as a prior 90‐day period without access of the medication. The dispense date of the first initiation was denoted as the index date. Patients with opioids dispensed in the prior 90 days were excluded. Opioid utilization including total days, number of prescriptions filled, and morphine equivalent dosage was assessed for overall, long‐acting, and short‐acting opioids. Health‐care costs and opioid use in the 12‐month post‐index period were examined via multivariate regression analyses.

Results: Four hundred and ninety‐nine DPNP patients (272 duloxetine, 227 SOC) were identified. SOC patients had higher prevalence of comorbidities and pre‐index health‐care costs than duloxetine patients. Controlling for cross‐cohort differences, duloxetine patients were significantly less likely to use any opioids than SOC patients. Also, duloxetine patients had 20 fewer adjusted opioid supply days (largely due to the use of short‐acting opioids,P < 0.05) and significantly lower adjusted total costs ($8,088,P < 0.05) and diabetes‐related costs ($3,092,P < 0.05) in the 12‐month post‐index period, with most of the cost differences from lower outpatient costs.

Conclusions: DPNP patients who initiated duloxetine therapy were less likely to have subsequent opioid use and had lower health‐care costs than SOC patients.
Bipolar Radiofrequency Lesion Geometry: Implications for Palisade Treatment of Sacroiliac Joint Pain
Authors: Cosman, Jr. Eric R. , Gonzalez Christian D.
Published: July 2010

Ex vivo photographic temperature mapping of bipolar radiofrequency (RF) lesions in animal tissue is performed over a wide range of electrode tip spacings, tip lengths, tip diameters, tip temperatures, and lesion times. In vivo temperature measurements collected during clinical treatment of sacroiliac joint (SIJ) pain corroborate those collected ex vivo. Generation of a “strip lesion” connecting two separated bipolar electrode tips is demonstrated ex vivo for tip spacings as large as 20 mm. A rounded rectangular bipolar lesion with midline dimensions 12 mm × 15 mm × 8 mm (L × W × D) is demonstrated using 10 mm parallel tip spacing, 10 mm tip lengths, 20 gauge cannulae, 90°C tip temperature, and 3‐minute lesion time. Lesion length can be increased to 18 mm by using 15 mm tip lengths. Lesion width can be increased to 17 mm by using 12 mm tip spacing. The size of conventional bipolar lesions can exceed the size of lesions produced both by conventional monopolar RF (12 mm × 7 mm × 7 mm ellipsoidal) and by cooled monopolar RF as used in spinal pain management (10 mm × 10 mm × 10 mm spherical). SIJ pain is treated by placing 5 to 7 straight RF cannulae perpendicular to the dorsal sacrum and producing 4 to 6 overlapping bipolar RF lesions between the dorsal sacral foramina and the ipsilateral SIJ. This bipolar “palisade” (a defensive fence) creates a continuous lesion spanning the region through which multiple sacral lateral branch nerves travel along irregular, branching paths to reach the SIJ.
A Double‐blind, Randomized, Placebo‐controlled Study of the Efficacy and Safety of Duloxetine for the Treatment of Chronic Pain Due to Osteoarthritis of the Knee
Authors: Chappell Amy S. , Desaiah Durisala , Liu‐Seifert Hong , Zhang Shuyu , Skljarevski Vladimir , Belenkov Yuri , Brown Jacques P.
Published: July 2010

Objective:  To evaluate the efficacy and safety of duloxetine in the treatment of chronic pain due to osteoarthritis of the knee.

Methods:  This was a 13‐week, randomized, double‐blind, placebo‐controlled trial in patients meeting American College of Rheumatology clinical and radiographic criteria for osteoarthritis of the knee. At baseline, patients were required to have a ≥ 4 weekly mean of the 24‐hour average pain ratings. Patients were randomized to either duloxetine 60 mg once daily (QD) or placebo. At week 7, the duloxetine dosage was increased, in a blinded fashion, to 120‐mg QD in patients reporting < 30% pain reduction. The primary efficacy measure was Brief Pain Inventory (BPI) 24‐hour average pain. Secondary efficacy measures included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); Clinical Global Impressions of Severity (CGI‐S). Safety and tolerability was also assessed.

Results:  Of the total (n = 256) patients, 111 (86.7%) in placebo group and 93 (72.7%) in duloxetine group completed the study. Patients treated with duloxetine had significantly (P ≤ 0.001) greater improvement at all time points on BPI average pain and had significantly greater improvement on BPI pain severity ratings (P ≤ 0.05), WOMAC total (P = 0.044) and physical functioning scores (P = 0.016), and CGI‐S (P = 0.009) at the study endpoint. Frequency of treatment‐emergent nausea, constipation, and hyperhidrosis were significantly higher in the duloxetine group (P ≤ 0.05). Significantly more duloxetine‐treated patients discontinued the trial because of adverse events (P = 0.002).

Conclusions:  Treatment with duloxetine 60 mg to 120 mg QD was associated with significant pain reduction and improved function in patients with pain due to osteoarthritis of the knee.
Evidence for acoustic communication in the parasitoid wasp Glyptapanteles flavicoxis
Authors: Danci Adela , Takács Stephen , Schaefer Paul W. , Gries Gerhard
Published: July 2010

Females of the parasitoid wasp Glyptapanteles flavicoxis (Marsh) (Hymenoptera: Braconidae) deposit sex pheromone on substrate that elicits attraction and wing fanning in conspecific males. We tested the hypothesis that wing fanning sound induces a behavioral response from females which, in turn, affects the males’ orientation toward them. Females exposed to playback of the males’ wing fanning sound engaged in short flights, with sound characteristics different from those of the males’ wing fanning sound. In two‐choice bioassays, playback of the females’ flight sound attracted significantly more males than a silent control stimulus, and in combination with pheromone‐containing body extract of females it attracted more males than female body extract alone. Our data support the conclusion that the males’ wing fanning induces sound and visual reply signals from females that help males orient toward them.
Gingival overgrowth in subjects under immunosuppressive regimens based on cyclosporine, tacrolimus, or sirolimus
Authors: Cota Luís Otávio Miranda , Aquino Davi Romeiro , Franco Gilson César Nobre , Cortelli José Roberto , Cortelli Sheila Cavalca , Costa Fernando Oliveira
Published: July 2010

Cota LOM, Aquino DR, Franco GCN, Cortelli JR, Cortelli SC, Costa FO. Gingival overgrowth in subjects under immunosuppressive regimens based on cyclosporine, tacrolimus, or sirolimus. J Clin Periodontol 2010; 37: 894–902. doi: 10.1111/j.1600‐051X.2010.01601.x.

Aim:To assess the prevalence and variables associated with gingival overgrowth (GO) in renal transplant recipients medicated with cyclosporine (CsA), tacrolimus (Tcr), or sirolimus (Sir).

Materials and Methods:One hundred and thirty‐five eligible subjects were divided in CsA, Tcr, and Sir groups comprising 45 subjects each. GO was visually assessed and subjects were assigned as GO+ or GO− in apost hocdefinition. Saliva samples were collected and the presence of periodontal pathogens was assessed through polymerase chain reaction. Variables of interest were compared between GO+ and GO− subjects through univariate and multivariate analysis.

Results:Prevalence of GO was of 60.0% for CsA, 28.9% for Tcr, and 15.6% for Sir groups. Within the CsA group, GO was associated with papillary bleeding index (p=0.001); within the Tcr group, GO was associated with CsA previous use (p=0.013), and calcium channel blockers (CCB) use (p=0.003); within the Sir group, GO was associated with papillary bleeding index (p=0.018), and CCB use (p=0.020). A higher frequency ofTannerella forsythiawas observed among GO+ subjects medicated with Tcr.

Conclusion:Pharmacological and periodontal variables were associated with GO in different immunosuppressive regimens. Integration between the medical and the dental team may be an important approach in the post‐transplant maintenance routine.
Heterogeneity in phenotype and function of CD8+ and CD4/CD8 double‐negative Natural Killer T cell subsets in sooty mangabeys
Authors: Rout Namita , Else James G. , Yue Simon , Connole Michelle , Exley Mark A. , Kaur Amitinder
Published: July 2010

Background  We have recently reported the presence of CD8+ and CD4/8 double‐negative (DN) natural killer T (NKT) lymphocytes in sooty mangabeys. To investigate differences in the two NKT cell subsets, we compared the phenotype and function of sooty mangabey CD8+ and DN NKT cells.

Methods  Flow‐sorted NKT lymphocytes from one SIV‐negative sooty mangabey were subjected to limiting dilution cloning. Invariant NKT clones were characterized by flow cytometry and cytokine ELISA.

Results  The majority of NKT clones displayed an effector memory phenotype and expressed CXCR3 and NKG2D. While CD8+ NKT subsets expressed significantly higher levels of granzyme B and perforin and produced more IFN‐γ, the DN NKT subsets secreted significantly more IL‐4, IL‐13, and IL‐10.

Conclusions  The Th1 and Th2 cytokine bias of CD8+ and DN NKT cells, respectively, indicates the presence of functionally heterogeneous populations of NKT cells in sooty mangabeys.
Context dependency of litter‐mixing effects on decomposition and nutrient release across a long‐term chronosequence
Authors: Jonsson Micael , Wardle David A.
Published: July 2010

Litter decomposition is an important driver of terrestrial systems, and factors that determine decomposition rate for individual litter species have been widely studied. Fewer studies have explored the factors that regulate how mixing litters of multiple species affects litter decomposition and nutrient dynamics, and only a handful of studies have investigated how litter‐mixing effects may differ among different habitats or ecosystems, or how they respond to environmental gradients. We used a well‐established retrogressive chronosequence involving thirty lake islands in northern Sweden in which time since fire disturbance increases with decreasing island size; smaller islands therefore have reduced rates of aboveground and belowground ecosystem processes. On each of these islands we utilized plots with and without the long‐term experimental removal of shrubs. Litters from the six most common plant species on the islands were prepared in single‐, three‐ and six‐species litterbags, and placed on both the shrub‐removal and non‐removal plots on each island to decompose for one year. We found significant non‐additive effects of litter mixing on litter decomposition rates, on final litter N and P concentrations, and on litter N loss, but these non‐additive effects varied both in direction and magnitude with changed number of species, and even among litter mixtures with the same number of species. Further, the magnitude of non‐additive effects of litter mixing on both litter decomposition and nutrient dynamics was significantly influenced by both island size and the interaction between island size and shrub‐removal treatment. When shrubs were present, there was a U‐shaped relationship between these non‐additive effects and island size, while the relationship was positive when shrubs were removed. Hence, our results support previous findings that litter mixing may produce non‐additive effects on litter decomposition and nutrient dynamics, and that these effects tend to be idiosyncratic due to the importance of effects of individual species in the mixture. Most importantly, our results show that non‐additive litter‐mixing effects change greatly across environmental gradients, meaning that the biotic and abiotic characteristics of an ecosystem can be a powerful driver of the magnitude and even the direction of litter‐mixing effects on ecosystem processes.
Arterial oxygen saturation and diving response during dynamic apneas in breath‐hold divers
Authors: Andersson J. P. A. , Evaggelidis L.
Published: July 2010

Competitive breath‐hold divers try to achieve maximum times, depths, or distances underwater, thereby risking hypoxic syncope. In the present study, the cardiorespiratory responses to dynamic apnea (simultaneously initiated apneas and dynamic leg exercise) were investigated in 10 breath‐hold divers. The divers performed 60 s dynamic apneas with the face in air (A) or face immersed in cold water (AFI). During apneas, the arterial oxygen saturation was reduced (A: −10%), but to a lesser extent during AFI (−6%, P<0.01), reaching a nadir 10–15 s post‐apnea. Also, changes in end‐tidal O2 and CO2 pressures (PetO2/PetCO2) were smaller during AFI than A (ΔPetO2: 8.2 vs 8.7 kPa, P<0.01; ΔPetCO2: 3.1 vs 3.2 kPa, P<0.05). The heart rate was lower during AFI than A (66 vs 78 bpm, P<0.01), reflecting an augmented diving response during AFI. The maximum safe breath‐hold time under the conditions of the present study was calculated to be 101 and 106 s for A and AFI, respectively, consistent with the dynamic apnea times achieved by world‐class apnea divers. It is concluded that the augmented diving response during face immersion apneas is associated with a slower reduction of the pulmonary (and arterial) oxygen store, probably delaying the occurrence of a hypoxic syncope.
Maternal Immune Responses to Trophoblast: The Contribution of the Horse to Pregnancy Immunology
Authors: Noronha Leela E. , Antczak Douglas F.
Published: July 2010

Citation Noronha LE, Antczak DF. Maternal immune responses to trophoblast: the contribution of the horse to pregnancy immunology. Am J Reprod Immunol 2010

The horse has proven to be a distinctively informative species in the study of pregnancy immunology for several reasons. First, unique aspects of the anatomy and physiology of the equine conceptus facilitate approaches that are not possible in other model organisms, such as non‐surgical recovery of early stage embryos and conceptuses and isolation of pure trophoblast cell populations. Second, pregnant mares make strong cytotoxic antibody responses to paternal major histocompatibility complex class I antigens expressed by the chorionic girdle cells, permitting detailed evaluation of the antigenicity of these invasive trophoblasts and how they affect the maternal immune system. Third, there is abundant evidence for local maternal cellular immune responses to the invading trophoblasts in the pregnant mare. The survival of the equine fetus in the face of strong maternal immune responses highlights the complex immunoregulatory mechanisms that result in materno–fetal tolerance. Finally, the parallels between human and horse trophoblast cell types, their gene expression, and function make the study of equine pregnancy highly relevant to human health. Here, we review the most pertinent aspects of equine reproductive immunology and how studies of the pregnant mare have contributed to our understanding of maternal acceptance of the allogeneic fetus.