bluuebunny/crossref_metadata_2025 huggingface dataset:
GV150526: A Neuroprotective Agent
Authors: Bordi Fabio , Mugnaini Manolo , Terron Andrea , Barnaby Robert , Reggiani Angelo
Published: August 2010

Thromboembolic stroke is a severe, disabling disease characterized by an abrupt reduction of cerebral blood flow, which leads to deprivation of oxygen and nutrients to neuronal tissue, followed by permanent brain damage. Evidence has been accumulated to implicate excitotoxicity in the pathogenesis of ischemic brain injury. Overstimulation of excitatory amino acid receptors becomes deleterious for neuronal cell survival. Glutamate antagonists can ameliorate the ischemic injury by any of several mechanisms. Because blockade of the glycine site of theN‐methyl‐D‐aspartate (NMDA) receptor seems to offer a better side‐effect profile, glycine antagonists are attractive targets for blocking excitotoxicity following stroke.

GV150526 is a selective and potent glycine antagonist at the NMDA receptor complex. It binds to the glycine site with both high affinity and high selectivity inin vitrobinding studies.In vivostudies have shown that GV150526 significantly reduces infarct volume in the middle cerebral artery occlusion model of stroke. This effect remained statistically significant, even if treatment was delayed for as long as 6 h post‐occlusion. GV150526 showed no evidence of adverse effects usually associated with NMDA receptor blockers, such as neuronal vacuolization in standard assays or cognitive impairment in behavioral tests. GV150526 had no significant treatment‐related respiratory or cardiovascular effects or effects on behavior, body temperature, or blood pressure in mice or rats. Pharmacokinetic studies indicated that GV150526 has low clearance and volume of distribution in both the rat and the dog. Preclinical toxicology studies have shown that the compound is well tolerated in both species. Phase I/II studies were undertaken to assess the safety, tolerability, and pharmacokinetics of GV150526 in healthy volunteers and acute stroke patients, and from these a dose was selected to be studied in Phase III clinical trials. These efficacy studies have now completed recruitment and data reconciliation is ongoing. GV150526 has the potential to be an effective therapy for acute ischemic stroke.
Paroxetine: A Review
Authors: Bourin Michel , Chue Pierre , Guillon Yannick
Published: August 2010

Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive‐compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache.

Paroxetine, a phenylpiperidine derivative, is the most potent inhibitor of the reuptake of serotonin (5‐hydroxytryptamine, 5‐HT) of all the currently available antidepressants including the class of SSRIs. It is a very weak inhibitor of norepinephrine (NE) uptake but it is still more potent at this site than the other SSRIs. The selectivity of paroxetine, i.e., the ratio of inhibition of uptake of norepinephrine to serotonin (NE/5‐HT) is amongst the highest of the SSRIs. Paroxetine has little affinity for catecholaminergic, dopaminergic or histaminergic systems and by comparison with tricyclic antidepressants (TCAs) has, therefore, has a reduced propensity to cause central and autonomic side effects. Paroxetine exhibits some affinity for the muscarinic cholinergic receptor but much less than the TCAs. In addition, the adaptive changes of somatodendritic (5‐HT1A) and terminal (5‐HT1B/1D) autoreceptors observed with paroxetine are different to those observed with TCAs; it also inhibits nitric oxide synthase. It is both a substrate and an inhibitor of cytochrome isoenzyme P450 2D6. Paroxetine is well absorbed orally and undergoes extensive first pass metabolism that is partially saturable. Its metabolites are pharmacologically inactivein vivo.Steady state levels are achieved after 4–14 days and an elimination half‐life of 21 h is consistent with once‐daily dosing. There is wide inter‐individual variation in the pharmacokinetics of paroxetine in adults as well as in the young and the elderly with higher plasma concentrations and slower elimination noted in the latter. Elimination is also reduced in severe renal and hepatic impairment. Serious adverse events are, however, extremely rare even in overdose.

In summary, paroxetine is well tolerated and effective in the treatment of both depressive and anxiety disorders across the age range.
HU 210: A Potent Tool for Investigations of the Cannabinoid System
Authors: Ottani Alessandra , Giuliani Daniela
Published: August 2010

The synthetic compound HU 210 displays a multiplicity of biochemical, pharmacological, and behavioral effects, most of which have been demonstrated to be dependent on a selective agonistic activity at CB1and CB2cannabinoid receptors and to involve the main neurotransmitter systems. Results obtained in various studies suggest a potential clinical application of this highly potent drug (e.g., as antipyretic, antiinflammatory, analgesic, antiemetic, and antipsychotic agent) as well as its usefulness in research aimed to develop a better understanding of the involvement of the endogenous cannabinoid system in a number of physiopathological functions.
Donepezil for Alzheimer's Disease: Pharmacodynamic, Pharmacokinetic, and Clinical Profiles
Authors: Shigeta Masahiro , Homma Akira
Published: August 2010

Donepezil was developed in order to overcome the disadvantages of physostigmine and tacrine. Its use is based on the cholinergic hypothesis. Donepezil is a piperidine‐based, reversible acetylcholinesterase inhibitor, that is chemically unrelated to other cholinesterase inhibitors. It was developed for the symptomatic treatment of Alzheimer's disease (AD). Donepezil is highly selective for acetylcholinesterase with a significantly lower affinity for butyrylcholinesterase, which is present predominantly in the periphery. Phase I and II clinical trials demonstrated donepezil's favorable Pharmacokinetic, pharmacodynamic and safety profile. There is no need to modify the dose of donepezil in the elderly or in patients with renal and hepatic failure. Pivotal phase‐III trials in the US, European countries, and Japan showed that donepezil significantly improved cognition and global function in patients with mild to moderate AD. In long‐term trials, donepezil maintained cognitive and global function for up to 1 year prior to the resumption of gradual deterioration. Donepezil is generally well tolerated; most of its adverse events are mild, transient and cholinergic in nature. Donepezil produces no clinically significant changes in laboratory parameters, including liver function.

The drug is approved for the treatment of mild to moderate Alzheimer's disease, but donepezil therapy does not have to be discontinued if a patient continues to deteriorate. Possible new indications for donepezil in psychiatric and neurologic diseases, other than AD, include dementia with Lewy bodies, brain injury, attention deficit hyperactivity, multiple sclerosis, Down's syndrome, delirium, mood disorders, Huntington's disease and sleep disorders.
CHF2819: Pharmacological Profile of a Novel Acetylcholinesterase Inhibitor
Authors: Trabace Luigia , Cassano Tommaso , Loverre Antonia , Steardo Luca , Cuomo Vincenzo
Published: August 2010

CHF2819 is a novel orally active acetylcholinesterase inhibitor (AChEI) developed for the treatment of Alzheimer's disease (AD). CHF2819 is a selective inhibitor of AChE, it is 115 times more potent against this enzyme than against butyrylcholinesterase (BuChE). Moreover, CHF2819 is more selective for inhibition of central (brain) AChE than peripheral (heart) AChE.In vivoCHF2819, 0.5, 1.5, and 4.5 mg/kg p.o., significantly and in dose‐dependent manner increased acetylcholine (ACh) levels in hippocampus of young adult rats. Moreover, aging animals, with lower basal ACh levels than young adult rats, also exhibit a marked increase in hippocampal levels of this neurotransmitter after administration of CHF2819. At 1.5 mg/kg p.o. CHF2819 attenuated scopolamine‐induced amnesia in a passive avoidance task. Furthermore, it decreased dopamine (DA) levels and increased extracellular levels of 5‐hydroxytryptamine (5‐HT) in the hippocampus, without modifying norepinephrine (NE) levels. By oral administration to young adult rats CHF2819 did not affect extracellular hippocampal levels of glutamate (Glu), aspartate (Asp), γ‐aminobutyric acid (GABA), taurine (Tau), arginine (Arg) or citrulline (Cit).

Functional observational battery (FOB) screening demonstrated that CHF2819 (1.5 and 4.5 mg/kg p.o.) does not affect activity, excitability, autonomic, neuromuscular, and sensorimotor domains, as well as physiological endpoints (body weight and temperature). CHF2819 induced, however, involuntary motor movements (ranging from mild tremors to myoclonic jerks) in a dose‐dependent manner.

The neurochemical and behavioral profiles of CHF2819 suggest that this orally active novel AChEI could be of clinical interest for the treatment of Alzheimer‐type dementia associated with multiple neurotransmitter abnormalities in the brain. In particular, CHF2819 might be a useful therapeutic drug for AD patients with cognitive impairment accompanied by depression.
Duloxetine Pharmacology: Profile of a Dual Monoamine Modulator
Authors: Karpa Kelly D. , Cavanaugh Jane E. , Lakoski Joan M.
Published: August 2010

Dysregulation within central monoaminergic systems is believed to underlie the pathology of depression. Drugs that selectively inhibit the reuptake of central monoamines have been used clinically to alleviate symptoms of depressive illnesses. Duloxetine, a novel compound currently under investigation for the treatment of depression, binds selectively with high affinity to both norepinephrine (NE) and serotonin (5‐HT) transporters and lacks affinity for monoamine receptors within the central nervous system. It has been suggested that dual inhibition of monoamine reuptake processes may offer advantages over other antidepressants currently in use.

In preclinical studies, duloxetine mimics many physiologic effects of antidepressants. Consistent with other antidepressants, duloxetine, by acute administration, elevates extracellular monoamine levels, while by chronic administration it does not alter basal monoamine levels. Like the selective serotonin reuptake inhibitor, fluoxetine, by microiontophoretic application, duloxetine inhibits neuronal cell firing. However, in comparison with fluoxetine, duloxetine is a more potent serotonin reuptake inhibitor. Furthermore, in behavioral experiments, duloxetine attenuates immobility in forced swim tests in animal models of depression to a greater extent than several other commonly used antidepressants.

In a six‐week open label uncontrolled study, duloxetine was evaluated in patients with a history of depression. Duloxetine was effective in treating depression as determined by marked reduction in Hamilton Depression Rating scores. Adverse effects reported during duloxetine treatment were minor and similar to those of other antidepressants. In an eight‐week multicenter, double‐blind, placebo‐controlled study in patients with a major depressive disorder, duloxetine was effective as an antidepressant, particularly in patients with greater symptom severity. Only limited data are available regarding the pharmacokinetic profile of duloxetine in humans, although a half‐life of 10 to 15 h has been reported. Studies conducted in healthy human subjects confirm the preclinical profile of duloxetine as an inhibitor of 5‐HT and NE reuptake. Taken together, existing data suggest that duloxetine is a novel and effective antidepressant.
Xanomeline and the Antipsychotic Potential of Muscarinic Receptor Subtype Selective Agonists
Authors: Mirza Naheed R. , Peters Dan , Sparks Robin G.
Published: August 2010

Binding studies initially suggested that the muscarinic agonist, xanomeline, was a subtype selective muscarinicM1receptor agonist, and a potential new treatment for Alzheimer's disease. However, laterin vitroandin vivofunctional studies suggest that this compound is probably better described as a subtype selective M1/M4muscarinic receptor agonist. This subtype selectivity profile has been claimed to explain the limited classical cholinomimetic side effects, particularly gastrointestinal, seen with xanomeline in animals. However, in both healthy volunteers and Alzheimer's patients many of these side effects have been reported for xanomeline and in the patient population this led to a>50% discontinuation rate. Clearly, the preclinical studies have not been able to predict this adverse profile of xanomeline, and this suggests that either xanomeline is not as subtype selective as predicted from preclinical research or that there are differences between humans and animals with regard to muscarinic receptors. Nevertheless, in Alzheimer's patients xanomeline dose‐dependently improves aspects of behavioral disturbance and social behavior including a reduction in hallucinations, agitation, delusions, vocal outbursts and suspiciousness. The effects on cognition are not as robust and mainly seen at the highest doses tested. These effects in Alzheimer's patients have given impetus to the suggestion that muscarinic agonists have potential antipsychotic effects. The current review assesses the antipsychotic profile of xanomeline within the framework of the limited clinical studies with cholinergic agents in man, and the preclinical research on xanomeline using various models commonly used for the assessment of new antipsychotic drugs. In general, xanomeline has an antipsychotic‐like profile in various dopamine models of psychosis and this agrees with the known interactions between the cholinergic and dopaminergic systems in the brain. Moreover, current data suggests that the actions of xanomeline at the M4muscarinic receptor subtype might mediate its antidopaminergic effects. Particularly intriguing are studies showing that xanomeline, even after acute administration, selectively inhibits the firing of mesolimbic dopamine cells relative to dopamine cell bodies projecting to the striatum. This data suggest that xanomeline would have a faster onset of action compared to current antipsychotics and would not induce extrapyramidal side effects. The preclinical data on the whole are promising for an antipsychotic‐like profile. If in a new formulation (i.e., transdermal) xanomeline has less adverse effects, this drug may be valuable in the treatment of patients with psychosis.
The Cellular Biochemistry of Cholesterol and Statins: Insights into the Pathophysiology and Therapy of Alzheimer's Disease
Authors: Wolozin Benjamin , III James Brown , Theisler Catherine , Silberman Simone
Published: August 2010

The causes of late onset Alzheimer disease (AD) are poorly understood. Although β‐amyloid (Aβ) is thought to play a critical role in the pathophysiology of AD, no genetic evidence directly ties Aβ to late onset AD. This suggests that the accumulation of Aβ and neurodegeneration associated with AD might result from an abnormality that indirectly affects Aβ production or accumulation. Increasing evidence suggests that abnormalities in the metabolism of cholesterol and related molecules, such as cholseterol esters and 24(S) hydroxycholesterol might contribute to the pathophysiology of late onset AD by increasing production of Aβ. 24(S) Hydroxycholesterol is a member of a family of oxidized cholesterol catabolites, termed oxysterols, which function to regulate export of cholesterol from the cell and transcription of genes related to cholesterol metabolism. Cholesterol esters are cholesterol derivatives used for cholesterol storage. Levels of 24(S) hydroxycholesterol increase with AD. Polymorphisms in several different genes important for cholesterol physiology are associated with an increased load or level of Aβ in AD. These genes include apolipoprotein E, cholesterol 24 hydroxylase (Cyp46), acyl‐CoA:choles‐terol acetyltransferase (ACAT), and the cholesterol transporter ABCA1. Other studies show that levels of cholesterol, or its precursors, are elevated in subjects early in the course of AD. Finally, studies of the processing of amyloid precursor protein show that cholesterol and its catabolites modulate amyloid precursor protein processing and Aβ production. These lines of evidence raise the possibility that genetic abnormalities in cholesterol metabolism might contribute to the pathophysiology of AD.
ABT‐089: Pharmacological Properties of a Neuronal Nicotinic Acetylcholine Receptor Agonist for the Potential Treatment of Cognitive Disorders
Authors: Rueter Lynne E. , Anderson David J. , Briggs Clark A. , Donnelly‐Roberts Diana L. , Gintant Gary A. , Gopalakrishnan Murali , Lin Nan‐Horng , Osinski Mark A. , Reinhart Glenn A. , Buckley Michael J. , Martin Ruth L. , McDermott Jeffrey S. , Preusser Lee C. , Seifert Terese R. , Su Zhi , Cox Bryan F. , Decker Michael W. , Sullivan James P.
Published: August 2010

ABT‐089 [2‐methyl‐3‐(2‐(S)‐pyrrolidinylmethoxy)pyridine dihydrochloride salt] is a selective neuronal nicotinic receptor (NNR) modulator with cognitive enhancing properties in animal models of cognitive functioning. Amongst NNR subtypes, ABT‐089 shows selectivity for the cytisine binding site on the α4β2receptor subtype as compared to the α‐bungarotoxin (α‐BgT) binding sites on the α7and α1β1δγ receptor subtypes. In functionalin vitroelectrophysiological and cation flux assays, ABT‐089 displays differential activity including agonism, partial agonism and antagonism depending upon the NNR subtype and assay. ABT‐089 is as potent and efficacious as (–)‐nicotine at evoking acetylcholine (ACh) release from hippocampal synaptosomes. Furthermore, ABT‐089 is neuroprotective against excitotoxic glutamate insults, with even greater potency seen after chronic treatment. Similarly, ABT‐089 is effective in models of cognitive functioning, including enhancement of baseline functioning as well as improvement of impaired cognitive functioning seen following septal lesioning and natural aging. In neuroprotective assays the compound is most potent by chronic administration. In stark contrast to the positive effects in the cognitive models, ABT‐089 shows little propensity to induce adverse
Aripiprazole: A Novel Atypical Antipsychotic Drug With a Uniquely Robust Pharmacology
Authors: Davies Marilyn A , Sheffler Douglas J. , Roth Bryan L.
Published: August 2010

Aripiprazole (Abilify®) is an atypical antipsychotic drug that has been recently introduced for clinical use in the treatment of schizophrenia. Aripiprazole has a unique pharmacologic profile that includes partial agonism at several G‐protein coupled receptors (GPCRs) [especially dopamine (D2) and 5‐HT1A] and antagonistic action at others (especially 5‐HT2A). Clinical trials indicate that aripiprazole is effective in treating the positive and negative symptoms of schizophrenia. In short‐term studies rapid onset of action (within one week) has been demonstrated. Preliminary data indicate that aripiprazole may also be effective in the treatment of manic symptoms of bipolar disorder. At recommended doses, aripiprazole appears to be safe and well tolerated in most adult patients with schizophrenia and Schizoaffective disorder. There is only limited information available on the use of aripiprazole in children and adolescents, and pilot data suggest that a revised dosing strategy, based on weight, is indicated in this population. In the long‐term studies, the use of aripiprazole was associated with continued efficacy, good compliance and increased time‐to‐relapse.

Aripiprazole represents the first functionally selective atypical antipsychotic drug.
Cortagine: Behavioral and Autonomic Function of the Selective CRF Receptor Subtype 1 Agonist
Authors: Farrokhi Catherine Borna , Tovote Philip , Blanchard Robert J. , Blanchard D. Caroline , Litvin Yoav , Spiess Joachim
Published: August 2010

Corticotropin‐releasing factor (CRF) is a neuropeptide and mediating component of neuroendocrine, autonomic, and behavioral processes associated with the stress response. The two receptor subtypes identified in the mammalian brain, CRF receptor subtype 1 (CRF1) and CRF2, are suggested to differentially modulate these processes. Manipulation of these receptors with selective CRF compounds and transgenic models has revealed, in most studies, a clear potentiation of the stress response through central activation of CRF1. However, pharmacological activation of CRF restricted to CRF1 has been limited by the availability of selective peptidic compounds. Recently, a highly selective CRF1 agonist, cortagine, has been developed. It was synthesized from chimeric intermediate sequences of ovine CRF, sauvagine, and human/rat CRF into a highly soluble peptide with strong affinity for CRF1 (IC50< 5 nM) and a very low binding preference for CRF2 (IC50> 500 nM). Affinity for the CRF binding protein (IC50> 1,000nM) can be abolished by the addition of a glutamate residue on position 21 of the cortagine peptide sequence. Cortagine has recently been tested in a variety of preclinical models of behavior including the elevated‐plus‐maze (EPM), forced swim test (FST), homecage, and rat exposure test (RET). Preliminary characterization in the EPM and FST suggested that this compound elicits anxiogenic and antidepressant‐like effects, respectively. Additional testing in the homecage and RET, which targets various elements of behavior, directs to a more potent anxiogenic profile of cortagine. In this review, we discuss the behavioral findings and the tests used to measure these effects. Finally, we also discuss preliminary findings of autonomic activation obtained by central injection of cortagine that support CRF1 involvement in the modulation of heart rate and heart rate variability.
The Soviet Sausage Renaissance
Authors: Klumbytė Neringa
Published: August 2010

ABSTRACT In Lithuania, the first country to secede from the Soviet Union, the termSoviethas been used in public space to refer to the vanished Soviet empire and to experiences of colonization and resistance. However, in 1998, the “Soviet” symbol was successfully revived in the Lithuanian consumer food market as a brand name for meat products—primarily sausages. In this article, I argue that the market is a political arena in which values, ideologies, identities, and history are being shaped. The marketing and consumption of “Soviet” sausages is a form of political engagement that negotiates current power relations and inequalities. The meanings and practices surrounding “Soviet” sausages tell an intriguing story about broader processes of change. The “Soviet” sausage renaissance in Lithuania implies a critique of the postsocialist neoliberal state and constitutes an attempt to create an alternative modernity that is both post‐Soviet and European.
Making and Remaking “Good Government” in Brazil: Subnational Industrial Policy in Minas Gerais
Authors: Montero Alfred P.
Published: August 2010

Comparative examples of “good government” at the subnational level may underanalyze the “public goods” problem facing politicians. Delegating authority and resources to policymaking agencies is possible when political conflict is low. The benefits can be maintained only if public agencies establish ties of “horizontal embeddedness” with industrial clients. This case study of innovative industrial policymaking in Minas Gerais, which is compared with one from Rio de Janeiro, finds that horizontal, interagency ties were critical to policy success. The contrast leads to an examination of themineirosystem's efficacy in promoting externalities, attracting foreign investment, and planning infrastructure in the state's automotive industry.
“We Have a Consensus”: Explaining Political Support for Market Reforms in Latin America
Authors: Armijo Leslie Elliott , Faucher Philippe
Published: August 2010

By the 1990s, to the astonishment of many observers, most Latin American countries had reformed their systems of national economic governance along market lines. Many analysts of this shift have assumed that it circumvented normal political processes, presuming that such reforms could not be popular. Explanations emphasizing economic crisis, external assistance, and politically insulated executives illustrate this approach. Through a qualitative investigation of the reform process in the region's four most industrialized countries, Argentina, Brazil, Chile, and Mexico, this study argues, to the contrary, that reforming governments found or created both elite and mass political support for their policies.
Clerics, Exiles, and Academics: Opposition to the Brazilian Military Dictatorship in the United States, 1969–1974
Authors: Green James N.
Published: August 2010

Virtually no one in the United States raised objections to the 1964 military takeover of the Brazilian civilian government. In the early 1970s, however, the Brazilian regime had become associated with torture and the arbitrary rule of law. By the end of that decade, compliance with human rights standards had developed into a yardstick for measuring U.S. foreign policy initiatives in Latin America. This paper argues that between 1969 and 1974, a small group of dedicated church activists, exiled Brazilians, and academics introduced the issue of human rights in Latin America into the U.S. national body politic. A network of concerned activists fashioned a systematic campaign to educate journalists, government officials, and the public about the abuses taking place under the generals' rule. Their activities helped isolate the military regime and laid the groundwork for a broader solidarity movement with Latin American popular struggles in the late 1970s and 1980s.
The Renovation of Old Institutions: State Governors and the Political Transition in Mexico
Authors: Hernández-Rodríguez Rogelio
Published: August 2010

The process of political transition in Mexico has fostered several institutional transformations in the political system. Such changes do not modify the system's design, but they do reactivate some basic institutions and forgotten powers that affect the operation of the political system as a whole. The state governors have undergone one of the most relevant transformations: they have gained more autonomy and have forged a new relationship with the federal executive. This essay analyzes the different actions governors have taken depending on their partisan origin. While the PAN governors focus on administrative and financial issues, the PRI governors have developed the most important political challenges to the president's authority.
“For a Few Senators More”? Negotiating Constitutional Changes During Chile's Transition To Democracy
Authors: Uggla Fredrik
Published: August 2010

Chile's 1980 Constitution embodied the political aspirations of the nation's military regime. Before democratization, the constitution underwent a process of reform that did away with some of its most blatantly authoritarian provisions but preserved a set of institutions that would characterize and constrain the regained Chilean democracy. This article presents an account of that process. It juxtaposes two theoretical perspectives: one that sees the results as determined primarily by the power relationship of the participants, and one that stresses contextual factors, such as institutional traditions. This study argues that while the Chilean case largely confirms the importance of the existing constitution for the outcome, the final outcome depended nonetheless on the participants' assessment of the relations of power, and therefore might have been open to different results.
Defining Rights in Democratization: The Argentine Government and Human Rights Organizations, 1983–2003
Authors: Bonner Michelle D.
Published: August 2010

Defining the rights that must be protected in a democracy is an integral component of the process of democratization. In the case of Argentina, the definition of these rights results partly from important debates between human rights organizations (HROs) and the state. Argentine HROs have framed their demands for state protection of human rights in terms of the need to protect the family. Yet HROs' successes in using international courts as arbiters may be reducing their need to present their demands in this framework.
Toward a Critique of Latin American Neostructuralism
Authors: Leiva Fernando Ignacio
Published: August 2010

This article offers a critical assessment of the first postneoliberalism development framework that emerged in Latin America after 1990. The ability of neostructuralism to present an attractive narrative about a twenty-first-century “modernity with solidarity” is based on abandoning key tenets of ECLAC's structuralism and the thinking of Raúl Prebisch and Celso Furtado; namely, a focus on the distribution and appropriation of economic surplus and a framing of Latin American development problems in a world capitalist system. This article argues that Latin American neostructuralism's discursive strengths, as well as its analytical weaknesses, stem from the marginalization of power relations from key dimensions of the region's political economy. Since 2000, neostructuralism has exacerbated its descriptive, short-term perspective, further dulling its analytical edge, by focusing on policies that promote social cohesion and state intervention in the cultural and the socioemotional realm.
Despite Insurgency: Reducing Military Prerogatives in Colombia and Peru
Authors: Avilés William
Published: August 2010

Colombia and Peru made significant progress in reducing the institutional prerogatives of their respective militaries in the 1990s and 2000s while reforming their economies in a neoliberal direction. They accomplished this despite internal armed threats to state authority and stability. The end of the Cold War, U.S. promotion of “market democracies,” and the international centrality of free markets and formal democratic governance coincided with the rise to power in Peru and Colombia of “neoliberal policy coalitions.” The internal insurgency mitigated the emergence of antiglobalization or antidemocratic reform factions in the military and civil society. The armed forces unified behind their counterinsurgency mission, and opposition in civil society was weakened, creating greater space for neoliberal elites to reform their economies and reduce military prerogatives.
p53 and p21WAF1/CIP1overexpression at the invasive front of lower lip squamous cell carcinoma
Authors: Horta Martinho Campolina Rebello , De Assis Luis Alpino Prandini , De Souza Antonio Francisco , De Araújo Vera Cavalcanti , Gomez Ricardo Santiago , Aguiar Maria Cássia Ferreira
Published: August 2010

Background: Lower lip squamous cell carcinoma (LLSCC) is an oral cancer that has distinct epidemiology and etiopathogenesis. Although risk factors for this neoplasia are acknowledged, few studies have investigated the molecular basis of its development and behavior.

Methods: Expression of p53 and p21WAF1/CIP1was examined by immunohistochemistry of archived tissue from 21 specimens of LLSCC. Differences in this expression between the whole tumor (WT) and the invasive front (IF) as well as correlation between p53 and p21WAF1/CIP1expression were analyzed.

Results: p53 and p21WAF1/CIP1were overexpressed at the IF of LLSCC. The expression of both proteins was higher at IF than at WT. No correlation was observed between p53 and p21WAF1/CIP1expression.

Conclusions: Our results indicate that p53 and p21WAF1/CIP1overexpression is important in LLSCC pathogenesis, reinforce that IF is the most important area for tumor behavior, and support that p53‐independent mechanisms should be involved in the expression of p21WAF1/CIP1.
Experimental Graft versus Host Disease in the (BNxLEW)FI rat hybrid: an immunohistochemical study of early disease in oral mucosa
Authors: Peszkowski MJ , Fujiwara K , Warfvinge G , Larsson Å
Published: August 2010

OBJECTIVE: To study the initial cellular events in oral mucosa (tongue) of experimental hyperplastic GVHD. in order to increase our understanding of the possible pathogenic mechanisms that may be shared with eg mercury (and other drug)‐induced immunological reactions.

MATERIALS AND METHODS: GVHD was induced by one iv. injection of 0.5–1 times 108 BN spleen cells into (BNxLEW)F I hybrid rats. The pre‐onset stages of the developing semiallogeneic GVHD were investigated in tongue mucosa by immunohistochemistry and monoclonal antibodies.

RESULTS: No detectable tissue infiltrates were found 24 h post induction. The pioneer cells appeared at day 3 and were RTIB+ICD2+ and RTIB1–/CD45 (240 kD)‐/ ED I‐/CD45RC‐. At day 3, there was also a visible increase in spleen and lymph node size. Between day 3 and 7, there was a statistically significant increase of CD2+, RTIB+, TCR‐αβ+, CD4+ and CD8+ cells, but no increase of NKR‐PI+ cells. At day 10 there were focal accumulations of CD8+ and NKR‐PI+ cells in subepithelial c.t. and in the basal parts of the adjacent epithelium. Animals not sacrificed earlier, showed signs of disease onset at day 11–14.

CONCLUSIONS: The early inflammatory infiltrate in this GVHD model consists of activated T cells of donor origin. We suggest, that these originally ‘naive’ cells migrate initially into lymphoid tissue and following an activation (day 3) enter host's peripheral tissue. Here, (allo‐) antigen in constitutively RTIB1 (and EDI) expressing connective tissue dendritic cells may be immune targets of the primed T cells. Such interaction may lead to focal inflammation (increase of CD2+, RTIB+, TCR‐αβ+, CD4+ and CD8+ cells) and to secondary epithelial damage executed by CD8+ and NKR‐PI + lymphocytes.
CYTOGENETICAL FINDINGS IN CHILDREN BORN TO CARRIERS OF HEPATITIS‐ASSOCIATED ANTIGEN
Authors: Mikkelsen Margareta , Skinhøj Peter , Olesen Henrik
Published: August 2010

The chromosomes of 50 newborn infants, born to healthy HAA carriers were examined. No chromosomal syndrome was observed. As compared with a control group, the number of amodal cells was found to be significantly higher and the relative proportion of stable aberrations was also higher in the HAA group. Furthermore, cells with rings and dicentrics were found and the number of culture failures was significantly higher. These findings suggest that infection with the HAA agent has occurred early in pregnancy even though HAA could not be detected in cord blood.
ESCHERICHIA COLI SEROGROUPS IN BREAST‐FED AND BOTTLE‐FED INFANTS
Authors: ØRSKOV F. , SøRENSEN K. BIERING
Published: August 2010

1) Eighty‐seven breast‐fed and 95 bottle‐fed infants were examined for differences in Escherichia coli serogroup pattern. 2) The serogroup composition was less complex in breast‐fed infants. Fewer serogroups were found in the individual breast‐fed child. However, with few exceptions, the same O groups were found in the two groups of infants. The prevalent O groups were among those also found most frequently in faeces from adults. 06 strains were more common in the breast‐fed group, while 07 and 016 were not at all found in that group. 3) A special search for E. coli strains with K1 antigen showed that this antigen predominated in the bottle‐fed infants. 4) Klebsiella and other Enterobacteriaceae were more frequently found among bottle‐fed infants. 5) It is concluded that the intestinal milieu exerts a selective pressure which may result in a selection of different serotypes in two different intestinal milieus such as those examined.
INFLUENCE OF METHYLPREDNISOLONE ON COMPLEMENT ACTIVITY IN GERMFREE RATS AND ON ANTIBODY ACTIVITY TO ESCHERICHIA COLI IN MONOCONTAMINATED RATS
Authors: BAARDSEN A. , MIDTVEDT T. , TRIPPESTAD A.
Published: August 2010

By means of radio‐isotope technique, the influence of methylprednisolone treatment on opsonic and bactericidal serum activities against E. coli was studied on germfree and monocontaminated rats. Based on the present results it seems unlikely that methylprednisolone impairs the production of complement components. A slight suppression of antibody activity was only found in markedly wasted monocontaminated rats treated with very high doses of methylprednisolone from the day before contamination.
PREPARATION OF TYPE SPECIFIC HERPES SIMPLEX ANTISERA BY AN IMMUNOSORBENT METHOD
Authors: JEANSSON STIG
Published: August 2010

Herpes simplex virus (HSV) type 1 and type 2 specific immune sera have been produced by adsorption with glutaraldehyde‐polymerized heterologous virus antigen. The adsorbed sera showed high specificity in complement fixation, immunoelectroosmophoresis and neutralization tests. The precipitin patterns in IEOP indicate the presence of at least five HSV type 1 and three HSV type 2 specific antigens.
STUDIES ON THE GROWTH OF FELINE PANLEUKOPAENIA VIRUS IN CELL CULTURES
Authors: FLAGSTAD A.
Published: August 2010

The growth of feline panleukopaenia virus was examined in relation to various cell growth curves of secondary feline kidney cells. In cell cultures with a high mitotic index, the manifestation of virus infection, expressed as percentage number of cells with inclusion bodies, was correspondingly high. In cultures with low mitotic index, the percentage number of cells with inclusion bodies was low. A cytopathic effect was seen by inoculation of virus with a titre of 103.5TCID50/ml. This effect was most pronounced using cell cultures seeded in a quantity of 1 million cells per ml to 500,000 cells per ml with inoculation made during the first 24 hours after seeding when the mitotic index was high. Both the cytopathic effect and the occurrence of inclusion bodies were of transient nature. The peak of infection, both with regard to the cytopathic effect and the percentage number of cells with inclusion bodies, was seen three days after inoculation.
LOCALIZATION OF ANTIGENS IN THIN SECTIONS OF BACTERIA BY THE IMMUNO‐PEROXIDASE TECHNIQUE
Authors: HAUGEN A. , HELGELAND S. , GROV A.
Published: August 2010

The immunoperoxidase technique together with electron microscopy has been examined for the ultrastructural localization of staphylococcal protein A, the immunoferritin method being included for comparison. The results show that protein A is uniformly distributed in the whole cell wall. Both the direct and indirect methods, Fab‐ as well as Fc‐reactions, showed identical results. The immunoperoxidase method was superior to the immunoferritin method, especially when applied to thin sections of the bacteria, and the clear specificity demonstrated indicates a useful method for localization of cellular antigens.
INFLUENCE OF OSMOTIC PRESSURE ON TRANSFORMABLE AND NON TRANSFORMABLE VARIANTS OF NEISSERIA MENINGITIDIS
Authors: JYSSUM KAARE
Published: August 2010

The Neisseria meningitidis Strain M1 could grow in media made hypertonic with 0.7 M sucrose, but the growth rate was much reduced. The reduction was more pronounced in the competent (cp+) variant than in the incompetent (cp‐) one. After exposure to increased osmotic pressure, growth was resumed after a pronounced lag which was regularly longer in the cp+ variant. Cellular lysis took place during the lag. The lag could be shortened by the addition of MgCl2. N. meningitidis cells lysed slowly when suspended in various isotonic solutes, but rapid lysis was activated in exponential phase cells by exposure to hypotonic as well as to hypertonic conditions. This activation was more pronounced in the cp‐ variant than in the cp+ variant. In stationary phase cells there was very little activation of autolysis. The rate of autolysis was inhibited by MgCl2, and CaCl2 in low concentration. Osmotic fragility developed during autolysis in the presence of high concentrations of acetate or sucrose but not in the presence of high concentrations of NaCl or phosphate. MgCl2, increased the osmotic stabilization caused by acetate or sucrose, whereas CaCl2, in low concentration abolished the stabilizing effect of these solutes.
LIPOLYTIC ACTIVITY OF STAPHYLOCOCCUS AUREUS STRAINS FROM CASES OF HUMAN CHRONIC OSTEOMYELITIS AND OTHER INFECTIONS
Authors: HEDSTRÖM SVEN ÅKE
Published: August 2010

The fatty acid accumulation in a lipid emulsion broth was examined after growth of S. aureus strains incubated for 18 hours at 37° C. Among 40 strains from acute infections and from nasal carriers, Tween 80‐positive staphylococci in phage group III caused accumulation of significantly larger amounts of fatty acids than did Tween 80‐positive strains in phage group I and Tween 80‐negative strains in phage groups I and III. Eight out of 17 S. aureus strains isolated from chronic osteomyelitis gave rise to a low amount of, or total lack of, fatty acids in the lipid broth. Seven of these 8 strains were isolated from cases showing relapse after intensive and prolonged antibiotic treatment. The lipid metabolism of 4 strains showing fatty acid accumulation in lipid broth, ranging from zero to the highest value found in the investigation, was further studied. Results of examination of lipolytic action on trioleinphospholipid and incorporation of 14C‐labelled oleic acid suggest that the degree of accumulation of fatty acids in lipid broth depends on variations in the lipolytic activity of the strains rather than on differences in incorporation of the produced fatty acids. The significance of fatty acid accumulation is discussed in relation to the prognosis of chronic staphylococcal osteomyelitis.
BORIC ACID TOLERANT VIBRIO CHOLERAE: BIOLOGICAL AND PHYSICAL PROPERTIES
Authors: Ojo M. O.
Published: August 2010

Two boric acid tolerant variants were developed by passage in boric acid containing media from a mouse virulent parent Vibrio cholerae strain. The variants were stable, exhibited increased acid resistance, were less virulent to mice, but protected mice against challenge with the mouse virulent parent strain.
THE SEROLOGY OF PSEUDOMONAS AERUGINOSA ANALYSED BY MEANS OF QUANTITATIVE IMMUNOELECTROPHORETIC METHODS
Authors: HØIBY NIELS
Published: August 2010

The occurrence of antibodies against antigens prepared from strains representing 13 O groups of Pseudomonas aeruginosa and against a polyvalent Ps. aeruginosa antigen (St‐Ag) has been investigated in sera from 100 patients. By means of fused rocket immunoelectrophoresis with intermediate gel it was found that the humoral immune response against Ps. aeruginosa resulting in precipitating antibodies will be detected by St‐Ag as well as by any other of the antigen samples investigated. Six of the sera contained group‐specific antibodies which were revealed by only one of the antigen samples used and not by St‐Ag. These six sera were further studied by means of various quantitative immunoelectrophoretic methods using St‐Ag as well as antigens prepared from the infecting Ps. aeruginosa strain in the patient concerned. In all six sera, only one extra precipitin could be detected using antigens prepared from the homologous strain instead of St‐Ag. This extra precipitin corresponded presumably to group‐specific O‐antigens not included in St‐Ag. In sera from patients, these group‐specific antibodies were always accompanied by antibodies against antigens common to all strains of Ps. aeruginosa.
THE USE OF PROTEIN A‐CONTAINING STAPHYLOCOCCI SENSITIZED WITH ANTI‐MENINGOCOCCAL ANTIBODIES FOR GROUPING NEISSERIA MENINGITIDIS AND DEMONSTRATION OF MENINGOCOCCAL ANTIGEN IN CEREBROSPINAL FLUID
Authors: OLCÉN PER , DANIELSSON DAN , KJELLANDER JAN
Published: August 2010

The co‐agglutination technique, utilizing antibody coated protein A‐containing staphylococci, was successfully adapted to grouping N. meningitidis strains. It was found to give more clear‐cut results than the standard slide test, especially in the case of strains isolated from throat specimens. The co‐agglutination technique has also other advantages over the standard slide test in the grouping of meningococci: minor influence by auto‐agglutination, higher specificity, easy performance and low consumption of specific antisera. Preliminary results also showed that the co‐agglutination technique could be applied for the rapid detection of meningococcal antigen in cerebrospinal fluid.
THE SEROLOGY OF PSEUDOMONAS AERUGINOSA ANALYSED BY MEANS OF QUANTITATIVE IMMUNOELECTROPHORETIC METHODS
Authors: HØIBY NIELS
Published: August 2010

The reproducibility of a polyvalent Pseudomonas aeruginosa antigen (St‐Ag) composed of a mixture of antigens from 4 O groups of this bacterium has been studied. Ten batches of St‐Ag were produced, and each of these and each of the 10 batches of antigens from the 4 strains of P. aeruginosa were compared with St‐Ag batch 1 by means of quantitative immunoelectrophoretic methods and a polyvalent antiserum (St‐Ab) raised against St‐Ag. Fifty‐three of the 55 antigens of St‐Ag were stable and could be reproduced with reasonable precision in all 10 batches, and 3 of the 4 strains of P. aeruginosa were stable in antigen composition in all batches. One of the strains (0‐5A) had lost 2 antigens in the last 5 batches, and the concentrations of 7 other antigens were simultaneously changed, reflecting a smooth‐rough dissociation. The disappearance of the 2 antigens in the latest 5 batches of 0‐5A was also reflected in similar changes in the antigen composition of the latest 5 batches of St‐Ag.
IMMUNOCHEMISTRY OF A CELL WALL POLYSACCHARIDE ISOLATED FROM EUBACTERIUM SABURREUM, STRAIN L49
Authors: HOFSTAD TOR
Published: August 2010

A polymer isolated from E. saburreum strain L49 contained O‐acetylated glycero‐galacto‐heptose as the main constituent, and in addition an unknown aldose. The polymer was located at the outer part of the bacterial cell wall. The polymer reacted with antiserum to L49 microorganisms by precipitation and complement fixation. Two antigenic specificities were detected, one of which was destroyed by de‐acetylation. The rabbit antibodies to both specificities were low‐molecular‐weight antibodies.
O‐ANTIGENIC SPECIFICITY OF LIPOPOLYSACCHARIDES FROM BACTEROIDES FRAGILIS SS. FRAGILIS
Authors: HOFSTAD TOR
Published: August 2010

Lipopolysaccharides (LPS) isolated from three strains of Bacteroides fragilis ss. fragilis were examined by indirect haemagglutination and inhibition of haemagglutination in unabsorbed and absorbed rabbit antisera. Six different antigenic specificities were detected. All serological activity was destroyed by oxidation of LPS with periodate.
QUANTITATION OF THE INHIBITORY EFFECT OF ERIOCHROME BLACK AND SODIUM NITRITE ON NON‐SPECIFIC IMMUNOFLUORESCENT STAINING
Authors: KARLSSON KARL‐AXEL , NILSSON GUSTAF , THORE ANDERS , MOREIN BROR
Published: August 2010

To evaluate non‐specific staining (NSS) of animal tissues by FITC‐labelled immunoglobulins a model system was developed. HeLa cells were treated with labelled antisalmonella globulins and the fluorescence intensity of the cells was determined quantitatively by means of a fibre optic probe system. This system was used to determine the optimal treatment conditions (adequate concentrations, duration of treatment) using the two NSS‐reducing agents eriochrome black and sodium nitrite. Approximatively the same inhibitory effects (40–50 per cent using nitrite; about 85 per cent using eriochrome black) were obtained by conjugates of different F/P ratio values. The fibre optic probe system was also used to determine the effects of the above‐mentioned agents on the NSS of liver sections. In this system, the NSS was strongly reduced by eriochrome black whereas nitrite treatment did not induce any inhibitory effect. The applicability of nitrite and eriochrome black as NSS‐reducing agents was further demonstrated by the fact that they had no influence on the specific fluorescence intensity of salmonella bacteria. The effect of eriochrome black was also studied in clinical specimens infected with salmonella or tularemia bacteria.