bluuebunny/crossref_metadata_2025 huggingface dataset:
Ondansetron: A Selective 5‐HT3Receptor Antagonist and Its Applications in CNS‐Related Disorders
Authors: Ye Jiang‐Hong , Ponnudurai Rex , Schaefer Rebecca
Published: August 2010

Ondansetron is a selective 5‐hydroxytryptamine3 (5‐HT3) receptor antagonist that has been introduced to clinical practice as an antiemetic for cancer treatment‐induced and anesthesia‐related nausea and vomiting. Its use under these circumstances is both prophylactic and therapeutic. It has a superior efficacy, safety and pharmacoeconomic profile compared with other groups of antiemetics, namely antidopaminergics, antihistamines and anticholinergics. However, its place in the management of anticipatory and delayed vomiting in cancer treatment and as a rescue antiemetic in surgical patients needs to be further explored. Furthermore, recent animal and human research also reflects its possible novel application in the treatment of other disease states, such as alcoholism, cocaine addiction, opioid withdrawal syndrome, anxiety disorders, gastrointestinal motility disorders, Tourette's syndrome and pruritus. This review revisits the widespread physiological and pathological effects of 5‐HT and discusses both the basic science literature and the clinical developments responsible for the conventional and novel uses of ondansetron. In addition, new discoveries relating to the effects of ondansetron on other receptors/channels and their possible therapeutic applications are presented.
Adrogolide HCl (ABT‐431; DAS‐431), a Prodrug of the Dopamine D1Receptor Agonist, A‐86929: Preclinical Pharmacology and Clinical Data
Authors: Giardina William J. , Williams Michael
Published: August 2010

Adrogolide (ABT‐431; DAS‐431) is a chemically stable prodrug that is converted rapidly (<1 min) in plasma to A‐86929, a full agonist at dopamine D1receptors. Inin vitrofunctional assays, A‐86929 is over 400 times more selective for dopamine D1than D2receptors. In rats with a unilateral loss of striatal dopamine, A‐86929 produces contralateral rotations that are inhibited by dopamine D1but not by dopamine D2receptor antagonists. Adrogolide improves behavioral disability and locomotor activity scores in MPTP‐lesioned marmosets, a model of Parkinson's disease (PD), and shows no tolerance upon repeated dosing for 28 days.

In PD patients, intravenous (i.v.) adrogolide has antiparkinson efficacy equivalent to that of L‐DOPA with a tendency towards a reduced liability to induce dyskinesia. The adverse events associated with its use were of mild‐to‐moderate severity and included injection site reaction, asthenia, headache, nausea, vomiting, postural hypotension, vasodilitation, and dizziness.

Adrogolide can also attenuate the ability of cocaine to induce cocaine‐seeking behavior and does not itself induce cocaine‐seeking behavior in a rodent model of cocaine craving and relapse. In human cocaine abusers, i.v. adrogolide reduces cocaine craving and other cocaine‐induced subjective effects. The results of animal abuse liability studies indicate that adrogolide is unlikely to have abuse potential in man. Adrogolide has also been reported to reverse haloperidol‐induced cognitive deficits in monkeys, suggesting that it may be an effective treatment for the cognitive dysfunction associated with aging and disease.

Adrogolide undergoes a high hepatic “first‐pass” metabolism in man after oral dosing and, as a result, has a low oral bioavailability (±4%). This limitation may potentially be circumvented by oral inhalation formulations for intrapulmonary delivery that greatly increase the bioavailability of adrogolide. As the first full dopamine D1receptor agonist to show efficacy in PD patients and to reduce the craving and subjective effects of cocaine in cocaine abusers, adrogolide represents an important tool in understanding the pharmacotherapeutic potential of dopamine D1receptor agonists.
Eptastigmine: Ten Years of Pharmacology, Toxicology, Pharmacokinetic, and Clinical Studies
Authors: Braida Daniela , Sala Mariaelvina
Published: August 2010

Eptastigmine (heptyl‐physostigmine tartrate) is a carbamate derivative of physostigmine in which the carbamoylmethyl group in position 5 of the side chain has been substituted with a carbamoylheptyl group.In vitroandex vivoresults suggest that eptastigmine has a long‐lasting reversible brain cholinesterase (i.e., acetylcholinesterase and butyrylcholinesterase) inhibitory effect. When administeredin vivoto rodents by various routes, eptastigmine inhibits cerebral acetylcholinesterases (AChE) and increases acetylcholine (Ach) brain levels by 2500–3000%, depending on the dose. This effect leads to an improvement in the cerebral blood flow in the ischemic brain, excitatory and inhibitory effects on the gastrointestinal tract and to a protection from acute soman and diisopropylflu‐orophosphate intoxication.

Eptastigmine, by either acute or chronic administration, has been found to have memory enhancing effects in different species of normal, aged and lesioned animals. It also restored to normal the age‐related increase of EEG power without affecting spontaneous motor activity.

Clinical investigations on more than 1500 patients with Alzheimer's disease demonstrated that eptastigmine significantly improved cognitive performance (as assessed by the cognitive subscale of the Alzheimer's Disease Assessment Scale) as compared with placebo. This improvement was most evident in patients with more severe cognitive impairment at the baseline. The relationship between patient performance and average steady‐state AChE inhibition was described by an inverted U‐shaped dose‐response curve.

Pharmacokinetic studies have revealed that after oral administration eptastigmine is rapidly distributed to the tissues and readily enters the CNS, where it can be expected to inhibit AChE for a prolonged period.

Eptastigmine is generally well tolerated and the majority of adverse events (cholinergic) were mild to moderate in intensity. However, the adverse hematologic (granulocytopenia) effects reported in two studies have resulted in the suspension of further clinical trials.
Aniracetam: Its Novel Therapeutic Potential in Cerebral Dysfunctional Disorders Based on Recent Pharmacological Discoveries
Authors: Nakamura Kazuo
Published: August 2010

Aniracetam is a pyrrolidinone‐type cognition enhancer that has been clinically used in the treatment of behavioral and psychological symptoms of dementia following stroke and in Alzheimer's disease. New discoveries in the behavioral pharmacology, biochemistry and pharmacokinetics of aniracetam provided new indications for this drug in the treatment of various CNS disorders or disease states. This article reviews these new findings and describes the effects of aniracetam in various rodent models of mental function impairment or cerebral dysfunction. Also, several metabolites of aniracetam have been reported to affect learning and memory in animals. It is, therefore, conceivable that major metabolites of aniracetam contribute to its pharmacological effects. The animal models, used in pharmacological evaluation of aniracetam included models of hypo attention, hypovigilance‐arousal, impulsiveness, hyperactivity, fear and anxiety, depression, impaired rapid‐eye movement sleep, disturbed temporal regulation, behavioral performance, and bladder hyperactivity. These are models of clinical disorders or symptoms that may include personality disorders, anxiety, depression, posttraumatic stress disorder, attentiondeficit/hyperactivity disorder, autism, negative symptoms of schizophrenia, and sleep disorders. At present, there is no convincing evidence that promising effects of aniracetam in the animal models will guarantee its clinical efficacy. It is conceivable, however, that clinical trials will demonstrate beneficial effects of aniracetam in the above listed disease states. New findings regarding the mechanism of action of aniracetam, its central target sites, and its effects on signal transduction are also discussed in this review article.
Pharmacology of Flibanserin
Authors: Borsini Franco , Evans Kennett , Jason Kathryn , Rohde Frank , Alexander Barbara , Pollentier Stephan
Published: August 2010

Flibanserin has preferential affinity for serotonin 5‐HT1A, dopamine D4, and serotonin 5‐HT2Areceptors.In vitroand in microiontophoresis, flibanserin behaves as a 5‐HT1Aagonist, a very weak partial agonist on dopamine D4receptors, and a 5‐HT2Aantagonist.In vivoflibanserin binds equally to 5‐HT1Aand 5‐HT2Areceptors. However, under higher levels of brain 5‐HT (i.e., under stress), flibanserin may occupy 5‐HT2Areceptors in higher proportion than 5‐HT1Areceptors. The effects of flibanserin on adenylyl cyclase are different from those of buspirone and 8‐OH‐DPAT, two other purported 5‐HT1Areceptor agonists. Flibanserin reduces neuronal firing rate in cells of the dorsal raphe, hippocampus, and cortex with the CA1 region being the most sensitive in the brain. Flibanserin‐induced reduction in firing rate in the cortex seems to be mediated through stimulation of postsynaptic 5‐HT1Areceptors, whereas the reduction of the number of active cells seems to be mediated through dopamine D4receptor stimulation. Flibanserin quickly desensitizes somatic 5‐HT autoreceptors in the dorsal raphe and enhances tonic activation of postsynaptic 5‐HT1Areceptors in the CA3 region. Flibanserin preferentially reduces synthesis and extracellular levels of 5‐HT in the cortex, where it enhances extracellular levels of NE and DA. Flibanserin displays antidepressant‐like activity in most animal models sensitive to antidepressants. Such activity, however, seems qualitatively different from that exerted by other antidepressants. Flibanserin seems to act via direct or indirect stimulation of 5‐HT1A, DA, and opioid receptors in those animal models. Flibanserin does not display consistent effects in animal models of anxiety and seems to exert potential antipsychotic effects. Flibanserin may induce some sedation but does not induce observable toxic effects at pharmacologically relevant doses.
SL651498, a GABAAReceptor Agonist with Subtype‐Selective Efficacy, as a Potential Treatment for Generalized Anxiety Disorder and Muscle Spasms
Authors: Griebel Guy , Perrault Ghislaine , Simiand Jacques , Cohen Caroline , Granger Patrick , Depoortere Henri , Françon Dominique , Avenet Patrick , Schoemaker Hans , Evanno Yannick , Sevrin Mireille , George Pascal , Scatton Bernard
Published: August 2010

SL651498 (6‐fluoro‐9‐methyl‐2‐phenyl‐4‐(pyrrolidin‐1‐yl‐carbonyl)‐2, 9‐dihydro‐1H‐pyrido[3,4‐b]indol‐1‐one) was identified as a drug development candidate from a research program designed to discover subtype‐selective GABAAreceptor agonists for the treatment of generalized anxiety disorder and muscle spasms. The drug displays high affinity for rat native GABAAreceptors containing α1(Ki= 6.8 nM) and α2(Ki= 12.3 nM) subunits, and weaker affinity for α5‐containing GABAAreceptors (Ki= 117 nM). Studies on recombinant rat GABAAreceptors confirm these findings and indicate intermediate affinity for the α3β2γ2subtype. SL651498 behaves as a full agonist at recombinant rat GABAAreceptors containing α2and α3subunits, and as a partial agonist at recombinant GABAAreceptors expressing α1and α5subunits. SL651498 produced anxiolytic‐like and skeletal muscle relaxant effects qualitatively similar to those of benzodiazepines (BZs) [minimal effective dose (MED): 1 to 10 mg/kg, i.p. and 3 to 10 mg/kg, p.o.]. However, unlike these latter drugs, SL651498 induced muscle weakness, ataxia or sedation at doses much higher than those having anxiolytic‐like activity (MED: 30 to 100 mg /kg, i.p. or p.o.). Moreover, in contrast to BZs, SL651498 did not produce tolerance to its anticonvulsant activity or physical dependence. It was much less active than BZs in potentiating the depressant effects of ethanol or impairing cognitive processes in rodents. The differential profile of SL651498 as compared to BZs may be related to its selective efficacy at the α2and α3‐containing GABAAreceptors. This suggests that selectively targeting GABAAreceptor subtypes can lead to drugs with increased clinical specificity. SL651498 represents a promising alternative to agents currently used for the treatment of anxiety disorders and muscle spasms without the major side effects seen with classical BZs.
BP 897, a Selective Dopamine D3Receptor Ligand with Therapeutic Potential for the Treatment of Cocaine‐Addiction
Authors: Garcia‐Ladona F. J. , Cox B. F.
Published: August 2010

BP 897 is a potent (Ki= 0.92 nM) dopamine D3receptor compound developed for the treatment of cocaine abuse and craving. BP 897 has a high selectivity for the dopamine D3versus D2receptors (70‐fold) and a moderate affinity for 5‐HT1Areceptors, (Ki= 84 nM), adrenergic‐α1 (Ki= 60 nM) and ‐α2adrenoceptors (Ki= 83 nM). BP 897 displays significant intrinsic activity at the human dopamine D3receptor by decreasing forskolin‐stimulated cAMP levels and by stimulating mitogenesis of dopamine D3‐expressing NG108–15 cells. Although these findings suggest that BP 897 is a partial agonist, recent studies in Chinese Hamster Ovary (CHO) cells with expressed dopamine D3receptors demonstrated that BP 897 is devoid of any intrinsic activity but potently inhibits dopamine agonist effects (pIC50= 9.43 and 9.51) in agonist‐induced acidification rate or increase of GTPγS binding, respectively. In addition, BP 897 inhibitsin vivo(EC50= 1.1 mg/kg, i.v.) agonist‐induced decrease of firing rate of dopaminergic neurons in the substantia nigra.

It has been clearly shown that BP 897, 1 mg/kg, i.p., reduces cocaine‐seeking behavior in rats, without producing reinforcement on its own. In rhesus monkeys, BP 897 is not self‐administered (up to 30 μg/kg, i.v.) but reduces cocaine self‐administration. The potential usefulness of BP 897 in the treatment of drug‐seeking behavior is further supported by its effects in drug conditioning models. Although BP 897 reduces L‐DOPA‐induced dyskinesia in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated monkeys, it provokes a return of parkinsonian symptoms. At high doses BP 897 has been reported to produce catalepsy in rats. Pharmacokinetic and toxicological data have not yet been published. These interesting preclinical findings with BP 897 provide additional validation for dopamine D3receptor as a therapeutic target for the treatment of cocaine abuse and its associated central nervous system (CNS) disorders. BP 897 recently entered phase II clinical studies.
Pharmacology of Acamprosate: An Overview
Authors: Zornoza Teodoro , Cano María J. , Polache Ana , Granero Luis
Published: August 2010

In the last years important advances have been made in the development of drugs for the treatment of alcohol addiction. Acamprosate (calcium bis‐acetylhomotaurine) is one of the better established drugs in this field on the European market. This review focuses first on the pharmacokinetics of acamprosate. The published data and the recent advances in our knowledge on the mechanisms involved in the intestinal absorption and elimination of this drug are summarized. The importance of pharmacokinetics for the proper clinical use of acamprosate is highlighted. The anti‐relapse as well as the well‐known effects of acamprosate on ethanol intake are discussed. The recent experiments in animal models of conditioned withdrawal are reviewed. These experiments, explored for the first time the anticraving effect of the drug. Finally, the proposed hypotheses on the neuropharmacological mechanism of action of acamprosate are discussed. The discussion deals with the relative importance of various hypotheses as well as with the recent experiments that support them. It is pointed out that further research is necessary in order to clearly understand the mode of action of acamprosate as well as the neurobiological mechanisms involved in alcohol dependence.
The Neuropsychopharmacology and Toxicology of 3,4‐methylenedioxy‐N‐ethyl‐amphetamine (MDEA)
Authors: Freudenmann Roland W. , Spitzer Manfred
Published: August 2010

This paper reviews the pharmacology and toxicology of 3,4‐methylenedioxy‐N‐ethyl‐amphetamine (MDEA, “eve”). MDEA is a ring‐substituted amphetamine (RSA) like MDMA, its well known N‐methyl analog. Both have become very popular substances of abuse in the techno‐ and house‐music scene. They can evoke psychomotor stimulation, mild alterations of perception, sensations of closeness and a positive emotional state as well as sympathomimetic physical effects. At present, the name “ecstasy” is no longer used only for MDMA, but for the whole group of RSAs (MDA, MDMA, MDEA and MBDB) as they are chemically and pharmacologically nearly identical; moreover, many ecstasy pills contain mixtures of the RSAs. Hence, for a selective review on MDEA, it is crucial to strictly differentiate between: 1) street and chemical names, and 2) studies with or without chemically defined substances. In order to present MDEA‐specific information, the pharmacodynamics and kinetics are described on the basis of MDEA challenge studies in animals and humans. In the toxicology section, we present a collection of case reports on fatalities where MDEA was toxicologically confirmed. On the question of serotonergic neurotoxicity and possible long‐term consequences, however, MDEA‐specific information is available from animal studies only. The neurotoxic potential of MDEA in humans is difficult to estimate, as ecstasy users do not consume pure substances. For future research, challenge studies in animals using dosing regimens adapted to human consumption patterns are needed. Such challenge studies should directly compare individual RSAs. They will represent the most viable and fruitful approach to the resolution of the highly controversial issues of serotonergic neurotoxicity and its functional consequences.
Antinociceptive Properties of Fadolmidine (MPV‐2426), a Novel α2‐Adrenoceptor Agonist
Authors: Pertovaara Antti
Published: August 2010

Fadolmidine (MPV‐2426) is a novel α2‐adrenoceptor (α2‐AR) agonist developed for spinal analgesia. It is highly selective for α2‐ARs, but it lacks subtype selectivity. Due to its pharmacokinetic properties, it only poorly penetrates blood‐brain barrier or spreads from the site of injection within the central nervous system. By intrathecal (i.t.) administration to laboratory animals, fadolmidine produces dose‐dependent antinociception in healthy controls and in models of inflammatory, postoperative and neuropathic pain. Fadolmidine has been effective against various submodalities of pain such as heat pain, mechanical pain, and visceral pain. In general, the antinociceptive potency of fadolmidine, i.t., was equal to that of dexmedetomidine. At antinociceptive i.t. doses fadolmidine did not suppress motoneurons or responses to innocuous stimulation. It produced no hemody‐namic depression and considerably less sedation than dexmedetomidine. By peripheral administration fadolmidine had no or only a weak antinociceptive action, except following nerve injury, particularly that of the postganglionic sympathetic nerve fibers. Together these experimental animal studies indicate that i.t. administration of fadolmidine provides a segmentally restricted treatment of somatic and visceral pain, with only minor cardiovascular and sedative side effects. Additionally, peripheral administration of fadolmidine might provide a selective treatment for some hypersensitivity states that involve dysfunction of the sympathetic nervous system.
TC‐1734: An Orally Active Neuronal Nicotinic Acetylcholine Receptor Modulator with Antidepressant, Neuroprotective and Long‐Lasting Cognitive Effects
Authors: Gatto Gregory J. , Bohme G Andrees , Caldwell William S. , Letchworth Sharon R. , Traina Vincent M. , Obinu M. Carmen , Laville Michel , Reibaud Michel , Pradier Laurent , Dunbar Geoffrey , Bencherif Merouane
Published: August 2010

The development of selective ligands targeting neuronal nicotinic acetylcholine receptors to alleviate symptoms associated with neurodegenerative diseases presents the advantage of affecting multiple deficits that are the hallmarks of these pathologies. TC‐1734 is an orally active novel neuronal nicotinic agonist with high selectivity for neuronal nicotinic receptors. Microdialysis studies indicate that TC‐1734 enhances the release of acetylcholine from the cortex. TC‐1734, by either acute or repeated administration, exhibits memory enhancing properties in rats and mice and is neuroprotective following excitotoxic insult in fetal rat brain in cultures and against alterations of synaptic transmission induced by deprivation of glucose and oxygen in hippocampal slices. At submaximal doses, TC‐1734 produced additive cognitive effects when used in combination with tacrine or donepezil. Unlike (‐)‐nicotine, behavioral sensitization does not develop following repeated administration of TC‐1734. Its pharmacokinetic (PK) profile (half‐life of 2 h) contrasts with the long lasting improvement in working memory (18 h) demonstrating that cognitive improvement extends beyond the lifetime of the compound. The very low acute toxicity of TC‐1734 and its receptor activity profile provides additional mechanistic basis for its suggested potential as a clinical candidate. TC‐1734 was very well tolerated in acute and chronic oral toxicity studies in mice, rats and dogs. Phase I clinical trials demonstrated TC‐1734's favorable pharmacokinetic and safety profile by acute oral administration at doses ranging from 2 to 320 mg.

The bioavailability, pharmacological, pharmacokinetic, and safety profile of TC‐1734 provides an example of a safe, potent and efficacious neuronal nicotinic modulator that holds promise for the management of the hallmark symptomatologies observed in dementia.
ACEA 1021: Flip or Flop?
Authors: Petty Margaret A. , Weintraub Philip M. , Maynard Kenneth I.
Published: August 2010

Inasmuch as glutamate is the main excitatory neurotransmitter in the central nervous system, strategies aimed at counteracting glutamate excitotoxicity, which is at least partially involved in many acute neurologic, chronic neurodegenerative and psychiatric diseases, are challenging. Blockade of the NMDA receptor was identified as one way of achieving selective antagonism and overcoming glutamate neurotoxicity, yet not without liabilities. Glycine site antagonism of the NMDA receptor in 1987 offered a significant advance in blocking this receptor because such drugs were shown to lack most of the side effects, such as memory impairment, ataxia, lack of motor coordination and psychotomimetic effects, which accompanied competitive and non‐competitive NMDA receptor antagonists. To date, much has been done to improve the structure‐activity relationship (SAR) of compounds resulting in the synthesis of ACEA 1021. It is unclear, however, whether further chemical substitutions will lead to an improved compound. Many studies have been performed with ACEA 1021 and although there are muchin vitroandin vivodata to support its neuroprotective effects and improved safety profile, there is very little published information regarding its clinical pharmacology. In order to properly evaluate the true potential for ACEA 1021 in acute and chronic CNS disorders additional longer term safety and efficacy data in humans are needed.
Clinical Potential of GABABReceptor Modulators
Authors: Ong Jennifer , Kerr David I. B.
Published: August 2010

Metabotropic γ‐aminobutyric acidB(GABAB) receptors for the major inhibitory transmitter GABA, together with metabotropic glutamate (mGLuRs) receptors, the extracellular calcium‐sensing receptors (CaSRs), some V2R pheromone receptors and T1R taste receptors, belong to the family of 3 G‐protein‐coupled receptors (GPCRs). GABABreceptors are known to control neuronal excitability and modulate synaptic neurotransmission, playing a very important role in many physiological activities. These receptors are widely expressed and distributed in the nervous system and have been implicated in a variety of neurodegenerative and pathophysiological disorders including epilepsy, spasticity, chronic pain, depression, schizophrenia and drug addiction. To form a functional receptor entity, GABABreceptors must exist as a heterodimer consisting of GABAB1and GABAB2receptor subtypes with two 7‐transmembrane proteins, and these subunits arise from distinct genes. The GABAB1subunit binds the endogenous ligand within its extracellular N‐terminus, whilst the GABAB2subunit is not only essential for the correct trafficking of the GABAB1subunit to the cell surface, but is also responsible for the interaction of the receptor with its cognate G‐protein. Allosteric modulation has recently been recognized as an alternative pharmacological approach to gain selectivity in drug action. It is now generally accepted that modulators acting at the allosteric sites provide a novel perspective for the development of subtype‐selective agents acting at GPCRs. These agents interact with allosteric binding sites quite separate from the highly conserved agonist binding region. In this review, we present a new class of phenylalkylamines, based on the lead compound fendiline, that are potent positive potentiators of GABABreceptor‐mediated function and discuss their putative clinical applications. It is proposed that these new modulators may have therapeutic value in GABABreceptor pharmacology and are capable of selectively modifying GABABreceptor function. The allosteric modulators are offering an attractive and novel means to identify new leads, that are devoid of side effects associated with GABABreceptor agonists, and may, therefore, represent a major advance in the drug discovery process.
Differential diagnosis of keratoacanthomas and squamous cell carcinomas: diagnostic value of DNA image cytometry and p53 expression
Authors: Pilch H. , Weiss J. , Heubner C. , Heine M.
Published: August 2010

DNA‐cytometry and immunohistochemistry with the anti‐p53 antibody DO‐I was performed in 24 keratoacanthomas (KA) and 21 squamous cell carcinomas (SCC) (13 well‐differentiated, 8 moderately differentiated) to establish the possible value of these methods for the differential diagnosis of both epithelial tumors. Aneuploidy was detected in 1 (4%) KA and 12 (57%) SCC (p < 0.05). In the latter tumors, histologic grade was associated with an abnormal DNA‐content. Six (46%) well and 6 (75%) moderately differentiated SCC were shown to be aneuploid. Over‐expression of p53 protein was found in 16 (76%) SCC and 14(66%) KA (p>0.05; not significant). However, quantification of p53 expression by evaluating both the intensity of immunostaining and the number of cells with over‐expression by means of an immunoreactivity score (IRS) showed significant differences (p<0.05). There was no correlation of p53 over‐expression and aneuploidy in the tumors examined. The analysis of ploidy and immunostaining with anti‐p53 antibodies may give useful additional information regarding the differential diagnosis of SCC and KA, if only aneuploidy or a high IRS are considered.

Pilch H, Weiss J, Heubner C, Heine M. Differential diagnosis of keratoacanthomas and squamous cell carcinomas: diagnostic value of DNA image cytometry and p53 expression.
Upper dermal elastolysis: A comparative study with mid‐dermal elastolysis
Authors: Hashimoto Ken , Tye Mauray J.
Published: August 2010

We encountered a patient who complained of many small papules on the neck, shoulders, upper chest and upper back. Biopsy specimens showed complete loss of elastic fibers in the upper dermis including papillary dermis, whereas those of the mid dermis were intact. Electron microscopy revealed that assembly of component fibrils of elastic fibers was loose, and electron dense substance was aggregated in the spaces between these loosely bound subunit Fibrils or along the periphery of abnormal fibers. Dermal phagocytes engulfed abnormal as well as normal elastic fibers. Upper dermal elastolysis is a clinical and histopathological entity different from mid‐dermal elastolysis. Ultrastructural changes of the former are essentially similar to those of the latter but much more severe. It is suggested that activated elastophagocytosis of dermal phagocytes may play a role in this disease.

Hashimoto K, Tye MJ. Upper dermal elastolysis: A comparative study with mid‐dermal elastolysis.
Plasma medicine: possible applications in dermatology
Authors: Heinlin Julia , Morfill Gregor , Landthaler Michael , Stolz Wilhelm , Isbary Georg , Zimmermann Julia L. , Shimizu Tetsuji , Karrer Sigrid
Published: August 2010

As a result of both the better understanding of complex plasma phenomena and the development of new plasma sources in the past few years, plasma medicine has developed into an innovative field of research showing high potential. While thermal plasmas have long been used in various medical fields (for instance for cauterization and sterilization of medical instruments), current research mainly focuses on application of non‐thermal plasmas.

Experiments show that cold atmospheric plasmas (CAPs) allow efficient, contact‐free and painless disinfection, even in microscopic openings, without damaging healthy tissue. Plasmas influence biochemical processes and offer new possibilities for the selective application of individually designable medically active substances. In dermatology, new horizons are being opened for wound healing, tissue regeneration, therapy of skin infections, and probably many more diseases. First clinical trials show the efficacy and tolerability of plasma in treating infected chronic wounds. A major task will be the introduction of plasma into clinical medicine and, simultaneously, the further investigation of the mechanisms of action of plasma at the cellular level.
Meyerson‐Phenomenon hides a nevus flammeus
Authors: Simon Vera , Hartschuh Wolfgan , Flux Katharina
Published: August 2010

Facial eczema is a common disease in daily dermatological practice. The cause of facial eczema is often atopic dermatitis or allergic contact dermatitis. Usually, the eczema resolves with correct topical treatment and by avoiding allergic trigger factors. A 49‐year‐old woman presented with persistent eczema on her forehead which recurred over decades despite correct topical therapy. A skin biopsy revealed the astonishing diagnosis of a nevus flammeus with an overlying eczema known as the Meyerson phenomenon. The Meyerson phenomenon is often described in children with nevi flammei suffering from atopic dermatitis – in adults the phenomenon is rarely recognized as a reason for eczema. We show the interesting case of an adult woman with the Meyerson phenomenon on a nevus flammeus and discuss the possible pathomechanisms.
High diversity of polyketide synthase genes and the melanin biosynthesis gene cluster in Penicillium marneffei
Authors: Woo Patrick C. Y. , Tam Emily W. T. , Chong Ken T. K. , Cai James J. , Tung Edward T. K. , Ngan Antonio H. Y. , Lau Susanna K. P. , Yuen Kwok‐Yung
Published: August 2010

Despite the unique phenotypic properties and clinical importance of Penicillium marneffei, the polyketide synthase genes in its genome have never been characterized. Twenty‐three putative polyketide synthase genes and two putative polyketide synthase nonribosomal peptide‐synthase hybrid genes were identified in the P. marneffei genome, a diversity much higher than found in other pathogenic thermal dimorphic fungi, such as Histoplasma capsulatum (one polyketide synthase gene) and Coccidioides immitis (10 polyketide synthase genes). These genes were evenly distributed on the phylogenetic tree with polyketide synthase genes of Aspergillus and other fungi, indicating that the high diversity was not a result of lineage‐specific gene expansion through recent gene duplication. The melanin‐biosynthesis gene cluster had gene order and orientations identical to those in the Talaromyces stipitatus (a teleomorph of Penicillium emmonsii) genome. Phylogenetically, all six genes of the melanin‐biosynthesis gene cluster in P. marneffei were also most closely related to those in T. stipitatus, with high bootstrap supports. The polyketide synthase gene of the melanin‐biosynthesis gene cluster (alb1) in P. marneffei was knocked down, which was accompanied by loss of melanin pigment production and reduced ornamentation in conidia. The survival of mice challenged with the alb1 knockdown mutant was significantly better than those challenged with wild‐type P. marneffei (P < 0.005). The sterilizing doses of hydrogen peroxide, leading to a 50% reduction in survival of conidia, were 11 min for wild‐type P. marneffei and 6 min for the alb1 knockdown mutant of P. marneffei, implying that the melanin‐biosynthesis gene cluster contributed to virulence through decreased susceptibility to killing by hydrogen peroxide.
Mind the Gap! UNHCR, Humanitarian Assistance and the Development Process
Authors: Crisp Jeffrey
Published: August 2010

This article provides a historical critique of the initiatives taken by UNHCR to link its refugee and returnee assistance programs with longer-term development efforts in low-income countries. Such initiatives include the integrated zonal development approach of the 1960s; the refugee aid and development strategy of the 1970s and 1980s; the returnee aid and development strategy of the 1990s; and, most recently, the Brookings process. The article concludes that these initiatives have generally been flawed in their conceptualization and implementation and have consequently failed to meet their intended objectives.
All under One Roof: Mixed-Status Families in an Era of Reform
Authors: Fix Michael , Zimmermann Wendy
Published: August 2010

In this paper we document the prevalence of mixed immigration status families and discuss some of the immigration and citizenship policies that drive their formation. Using the 1998 Current Population Survey, we find that nearly one in ten families with children is a mixed status family: that is a family in which one or both parents is a noncitizen and one or more children is a citizen. We also find that 75 percent of children in immigrant families are citizens. We identify a number of the challenges that mixed status families pose for achieving the goals of recent welfare and illegal immigration reforms.
Race and Place in the Adaptation of Mariel Exiles
Authors: Skop Emily H.
Published: August 2010

The influx of lower class émigrés during the 1980 Mariel Boatlift complicates the “success story” image of previous waves of Cuban exiles to the United States. Examination of Mariel exiles in terms of racial variation in adaptation does not exist; nor is analysis of the geographic distribution and internal migration of Mariel Cubans within the United States represented. Mariel exiles maneuver along distinguishable paths of adaptation as evidenced by patterns of settlement and geographical mobility. I argue that place is a necessary ingredient in illuminating diverse adjustment experiences among immigrants and refugees in the United States.

Being a marielita specifically is different to being a Cuban in Miami. I feel first of all Cuban, not particularly marielita, but I can't deny that I left Cuba in 1980, and that sets me apart from other people that came here at the beginning of the revolution. Being a marielita is hard. A lot of people didn't understand us, didn't care for us, we were different. We were darker.
Temporary Migration Overseas and Household Labor Supply: Evidence from Urban Philippines
Authors: Rodriguez Edgard R. , Tiongson Erwin R.
Published: August 2010

The impact of international migration on the labor supply of workers' nonmigrant relatives has not been well documented in the literature. Using household survey data representing mostly overseas contract workers, i.e., temporary migrants, this paper shows that labor supplies of migrants and their nonmigrant relatives are inseparable. Migrants reduce the labor supply of nonmigrant relatives, which translates into lower earnings from local labor markets. Households substitute income for more leisure – a significant and previously little recognized benefit of emigration for Philippine households. This benefit varies by gender of nonmigrants and is generally higher for men.
Nativity and Self-Assessed Health among Pre-Retirement Age Hispanics and Non-Hispanic Whites
Authors: Angel Jacqueline L. , Buckley Cynthia J. , Finch Brian Karl
Published: August 2010

Economic, social and familial resources are known to influence subjective health assessments. We examine the salience of nativity in determining how these resources influence self-assessed health using a large, nationwide sample of Hispanic and non-Hispanic white adults. The results indicate that while education, accumulated assets and marital status benefit the physical and emotional health of the native and foreign-born, family resources and income are significant only for the native-born. English language proficiency is a significant protective factor for both groups and is especially protective for immigrants. These surprising findings call into question previous studies stressing the positive role of the family in maintaining immigrant health.
Under Two Flags: Dual Nationality in Latin America and Its Consequences for Naturalization in the United States
Authors: Jones-Correa Michael
Published: August 2010

This article surveys the practice of dual nationality in the Western Hemisphere, particularly as it impacts the naturalization rates of immigrants in the United States. The article begins by looking at the extent and spread of dual nationality provisions and the pathways for its implementation. Next, the article turns to a discussion of the multiple (and at times conflicting) interests – of immigrants, sending states and receiving states – in dual nationality. While immigrants and sending countries are in general agreement on the positive benefits of dual nationality, commentators in receiving countries like the United States continue to express deep unease at the spread of dual nationality and its consequences for American citizenship. Are these concerns justified? Not according to U.S. naturalization rates. Data from 1965 to 1997 indicate that immigrants from countries recognizing dual nationality average higher naturalization rates in the United States than countries that do not.
Return and Onwards Migration in Canada and Australia: Evidence from Fixed Interval Data
Authors: Newbold K. Bruce , Bell Martin
Published: August 2010

Analysis of return and onwards migration flows has typically relied upon lifetime migration definitions. Both Canada and Australia have collected data on usual place of residence both one and five years prior to the census, which provide a richer source of information on return and onwards moves. Utilizing data drawn from complementary sources, this article examines the incidence, composition and spatial patterning of return and onwards migration at the state and provincial level in Canada and Australia over the period of 1986–1990–1991. Results indicate a high degree of symmetry in these processes between the two countries. While many of the findings are consistent with those derived from analysis of lifetime data, we find that one quarter to one third of return moves were to the original (1986) dwelling, indicating a planned return rather than the failed migration as previous literature has often assumed.
Rehabilitating the Criminality of Immigrants under Section 19 of the Canadian Immigration Act
Authors: Yeager Matthew G.
Published: August 2010

Immigration has historically been associated with moral entrepreneur-ship and xenophobia. In periods of high unemployment and global dislocation, immigrants easily become the targets of political commentators who complain of their criminality, morals, demand on public services, and competition for scarce employment. In this exercise, looking at the recidivism of immigrants who come to Canada with a previous, foreign criminal history, quite a different picture emerges. Among this random sample (N=204), 97.5 percent of immigrants granted a rehabilitation waiver under the provisions of the Canadian Immigration Act were not re-arrested in Canada within a period of about 3.5 years after their landing was approved by the Minister. Of those who were arrested, most of the delinquency was manageable and, in fact, resulted in either an acquittal, diversion or lower-range sanctions. This is not the kind of imagery complained of by the tabloids or critics in the body politic. It behooves us, then, to exercise care in discussing crime and immigration, as it is a subject easily prone to the creation of ‘moral panics” and resulting repressive legislation against persons of color.
Female Labor Migrants to Shanghai: Temporary “Floaters” or Potential Settlers?
Authors: Roberts Kenneth
Published: August 2010

Using data on 54,373 migrants from the Fifth Sampling Survey of the Floating Population of Shanghai, this article isolates a group of 32,967 rural labor migrants who hold rural household registrations and whose previous occupations were in agriculture, and focuses on the women among them. The demographic and occupational characteristics of these 9,124 women are described, demonstrating that migration to Shanghai is a highly gendered process, with men and women working in different occupations and sectors. Moreover, important differences are found to exist between unmarried and married female rural labor migrants that indicate that the latter are probably accompanying and working with their migrant husbands. A significant proportion of female “social” migrants also exhibit characteristics that indicate that they are the spouses of male rural labor migrants, bringing to over one third the proportion of rural labor migrants to Shanghai who could be migrating as couples. These couples and their children may be the vanguard in a transition from temporary labor migration to settlement in China's large cities.
Migration and the “Second Wife” in South China: Toward Cross-Border Polygyny
Authors: Lang Graeme , Smart Josephine
Published: August 2010

Rapid industrialization in southern China has brought together two types of migrants: young women from towns and villages seeking work and upward mobility and affluent men from Hong Kong sojourning in the coastal provinces to supervise or service export-oriented industries. The result is that many married Hong Kong men who cross the border regularly on business have taken “second wives” or mistresses in China. We analyze this phenomenon using government statistics, selected court cases, and personal interviews. We show that the emergence of the “second wife” phenomenon among migrants in southern China is consistent with recent studies on the causes of polygyny, and we make some predictions about the likelihood of this type of polygyny among migrants.
The New Second Generation in the United States
Authors: Farley Reynolds , Alba Richard
Published: August 2010

Immigration to the United States accelerated in the late 1960s. Since many migrants are young people who form families shortly after arrival, there is now a large and rapidly growing second generation - many of them now young adults who recently completed school and started their careers. There is much speculation about whether this second generation will assimilate into the middle class rapidly or form a new urban underclass. The last census to ask parental birthplace questions was 1970, so an absence of data precluded testing hypotheses about the social and economic progress of the new second generation.

In 1994, the Census Bureau returned an inquiry about parental birthplace to the Current Population Survey so there is now an annual national sample of about 16,000 second-generation Americans. Data from the 1998 and 2000 surveys were pooled and analyzed. This investigation demonstrates that these comprehensive new data provide valuable descriptive information about today's second generation and permit the cautious testing of hypotheses concerning social and economic assimilation. They reveal a great diversity among the second generation depending upon country of origin but, in most comparisons, today's second generation exceed their first-generation parents in educational attainment, occupational achievement and economic status. In many comparisons, second-generation groups have educational attainments exceeding those of third- and higher-generation whites and African Americans. These data refute the hypothesis that today's second generation will languish in poverty. Nevertheless, intergenerational progress was less for persons of Puerto Rican and Mexican heritage than for those of Asian, European or South American heritage.
For Better, for Worse: Life Satisfaction Consequences of Migration
Authors: De Jong Gordon F. , Chamratrithirong Aphichat , Tran Quynh-Giang
Published: August 2010

This study explores the extension of microeconomic and migrant network theoretical frameworks for explaining perceived post-migration life satisfaction of repeat (temporary) and more permanent labor force internal migrants in Thailand. Data from the 1992 National Migration Survey were used in logistic regression models to predict increased versus decreased post-move satisfaction with employment situation, living environment, and community facilities. Contrary to the neoclassical migration theory assumption, results showed that migration was associated with decreased post-move satisfaction. Microeconomic theory indicators were related to increased employment satisfaction but decreased post-move satisfaction with living environment. For network theory indicators, the results showed the opposite pattern - related to improved living environment satisfaction but decreased employment post-move satisfaction. Repeat (temporary) migrants were disadvantaged in post-move employment satisfaction compared to more permanent single move labor force migrants.
Becoming American/Becoming New Yorkers: Immigrant Incorporation in a Majority Minority City
Authors: Kasinitz Philip , Mollenkopf John , Waters Mary C.
Published: August 2010

Many observers have noted that immigrants to the United States are highly concentrated in the largest metropolitan areas of a relatively few states. Though immigrants diffused into many places that had previously seen relatively few immigrants during the 1990s, as of the 2000 census, 77 percent of the nation's 31.1 million foreign born residents still lived in six states – California, New York, Texas, Florida, New Jersey, and Illinois. According to the 2000 census, the two largest metropolitan areas, Los Angeles and New York, accounted for one third of all immigrants ( http://www.census.gov/Press-Release/www/2002/demoprofiles.html ). While immigrants moved into many new areas during the 1990s, making the challenge of incorporating their children a national issue, their concentration in our largest cities remained pronounced.
Decolonization Immigrations and the Social Origins of the Second Generation: The Case of North Africans in France
Authors: Alba Richard , Silberman Roxane
Published: August 2010

Immigrations resulting from decolonization challenge the ability of researchers to track accurately the incorporation of the second generation through classifications based on country of origin. This article considers a classic example of such an immigration - from North Africa to France at the time of and after the independence of Algeria, Morocco, and Tunisia. This immigration was ethnically complex, composed - to take a rough cut - of the former colonists of European background (the pieds noirs) and low-wage laborers belonging to the indigenous population (the Maghrebins). A historical review indicates that the key to distinguishing these two groups lies in the exact citizenship status of the immigrants, for the former colonists were French by birth and the others generally were not. Analyzing micro-level data from the censuses of 1968, 1975, 1982, and 1990, we apply this distinction to the family origins of the second generation, born in France in the period 1958–1990. We show that the pied-noir population exhibits signs of rapid integration with the native French, while the Maghrebin population remains apart. A logistic regression analysis reveals that, based on a few characteristics of their parents, one can distinguish the Maghrebin from the pied-noir second generations with a high degree of accuracy. This finding demonstrates the sharp social distinction between the two groups and suggests a method for future research on their incorporation.