bluuebunny/crossref_metadata_2025_split huggingface dataset:
Premature expression of KCC2 in embryonic mice perturbs neural development by an ion transport‐independent mechanism
Authors: Horn Zachi , Ringstedt Thomas , Blaesse Peter , Kaila Kai , Herlenius Eric 
Published: June 2010

AbstractDuring neuronal maturation, the neuron‐specific K–Cl co‐transporter KCC2 lowers the intracellular chloride and thereby renders GABAergic transmission hyperpolarizing. Independently of its role as a co‐transporter, KCC2 plays a crucial role in the maturation of dendritic spines, most probably via an interaction with the cytoskeleton‐associated protein 4.1N. In this study, we show that neural‐specific overexpression of KCC2 impairs the development of the neural tube‐ and neural crest‐related structures in mouse embryos. At early stages (E9.5–11.5), the transgenic embryos had a thinner neural tube and abnormal body curvature. They displayed a reduced neuronal differentiation and altered neural crest cell pattern. At later stages (E11.5–15.5), the transgenic embryos had smaller brain structures and a distinctive cleft palate. Similar results were obtained using overexpression of a transport‐inactive N‐terminal‐deleted variant of KCC2, implying that the effects were not dependent on KCC2′s role as a K–Cl co‐transporter. Interestingly, the neural tube of transgenic embryos had an aberrant cytoplasmic distribution of 4.1N and actin. This was corroborated in a neural stem cell line with ectopic expression of KCC2. Embryo phenotype and cell morphology were unaffected by a mutated variant of KCC2 which is unable to bind 4.1N. These results point to a role of KCC2 in neuronal differentiation and migration during early development mediated by its direct structural interactions with the neuronal cytoskeleton.
Early and late urodynamic assessment of simplified Indiana pouch with multiple taeniamyotomies
Authors: Ferriero Mariaconsiglia , Simone Giuseppe , Papalia Rocco , Guaglianone Salvatore , Forastiere Ester , Gallucci Michele 
Published: June 2010

Study Type – Therapy (outcomes research) Level of Evidence 2c What’s known on the subject? and What does the study add? Continent urinary diversion represents a valid alternative to orthotopic reconstruction when this is unsuitable. Inclusion criteria for continent cutaneous diversion are strict and patients must be carefully selected. To date, several continent urinary diversions have been used such as Mainz, Indiana and Miami pouches.Simplified Indiana Pouch with multiple taeniamyotomies (SIPMT) represents a valid continent cutaneous urinary diversion with stable urodynamic features along 4 years. Appendicostomies guarantees better continence than ileostomies. In our series the EORTC QLQ‐C30 and QLQ‐BLM30 questionnaires showed a good health related quality of life.OBJECTIVETo compare the early and late urodynamic assessment of simplified Indiana pouch with multiple taeniamyotomies (SIPMT).PATIENTS AND METHODSBetween April 1999 and May 2005, 62 consecutive patients underwent radical cystectomy (RC) and SIMPT. Cystometry and efferent tract pressure profilometry were performed at 12 (early) and 48 (late) months after RC in 32 patients. The efferent tract of the reservoir was the appendix in 62.5% of patients and an ileum invagination nipple in 37.5%. All patients were asked to complete questionnaires on HRQL: the European Organization for Cancer Research and Treatment of Cancer Quality of life Questionnaire version 3.0 (EORTC QLQ‐C30) and the bladder cancer‐specific module (EORTC QLQ‐BLM30).RESULTSThere was no significant change in cystometric capacity (median 627.5 vs 607.5 mL, P= 0.79), while end‐filling pressure (median 28 vs 18 cmH2O) and amplitude of involuntary contractions (median 38 vs 32 cmH2O; both P < 0.001) decreased. Efferent tract‐closing pressure increased in the appendicostomies (median 74.5 vs 91.0 cmH2O, P= 0.029) and decreased in the ileostomies (median 72.5 vs 63 cmH2O, P= 0.015), also the leakage rates during the pressure peaks decreased from 15% to 5% in appendicostomies, while there was no change in those with ileostomies (15%). At late evaluation, daytime and night‐time continence rates were 94% and 88%, respectively, in patients with appendicostomies, and 90% and 85%, respectively, in those with ileostomies. A good HRQL was determined by the EORTC QLQ‐C30 and QLQ‐BLM30 questionnaires.CONCLUSIONSAt 48 months after surgery SIPMT maintained an adequate capacity with low internal pressure, good continence rates and HRQL. When feasible, appendicostomy should be performed, as it was associated with better continence.
Aversive picture processing: Effects of a concurrent task on sustained defensive system engagement
Authors: Wangelin Bethany C. , Löw Andreas , McTeague Lisa M. , Bradley Margaret M. , Lang Peter J. 
Published: June 2010

AbstractViewing a series of aversive pictures prompts emotional reactivity reflecting sustained defensive engagement. The present study examined the effects of a concurrent visual task on autonomic, somatic, electrocortical, and facial components of this defensive state. Results indicated that emotional activation was largely preserved despite continuous visual distraction, although evidence of attenuation was observed in startle reflex and electrocortical measures. Concurrent task‐specific reactivity was also apparent, suggesting that motivational circuits can be simultaneously activated by stimuli with intrinsic survival significance and instructed task significance and that these processes interact differently across the separate components of defensive engagement.
Distinct biochemical signatures characterize peripherin isoform expression in both traumatic neuronal injury and motor neuron disease
Authors: McLean Jesse , Liu Hsueh‐Ning , Miletic Denise , Weng Yuan Cheng , Rogaeva Ekaterina , Zinman Lorne , Kriz Jasna , Robertson Janice 
Published: June 2010

J. Neurochem. (2010) 114, 1177–1192.AbstractPeripherin is a type III intermediate filament protein that is up‐regulated during neuronal injury and is a major component of pathological inclusions found within degenerating motor neurons of patients with amyotrophic lateral sclerosis (ALS). The relationship between these inclusions and their protein constituents remains largely unknown. We have previously shown that peripherin expression is characterized by tissue‐specific, intra‐isoform associations that contribute to filament structure; changes to the normal isoform expression pattern is associated with malformed filaments and intracellular inclusions. Here, we profile peripherin isoform expression and ratio changes in traumatic neuronal injury, transgenic mouse models of motor neuron disease, and ALS. Extensive western blot analyses of Triton X‐100 soluble and insoluble fractions of neuronal tissue from these conditions revealed significant changes in peripherin isoform content which could be differentiated by electrophoretic banding patterns to produce distinct peripherin biochemical signatures. Significantly, we found that the pattern of peripherin expression in ALS most closely approximates that of peripherin over‐expressing mice, but differs with regard to inter‐individual variations in isoform‐specific expression. Overall, these results provide important insights into complex post‐transcriptional processes that may underlie a continuum between peripherin‐mediated neuronal repair and its role in the pathogenesis of motor neuron disease.
Role of cysteinyl leukotrienes in antigen‐induced immune response in the airway: from bronchus to the nose
Authors: Dohi M. 
Published: June 2010

SummaryThere are similarities between allergic rhinitis (AR) and atopic bronchial asthma in their pathophysiology, although some differences also exist. For example, some AR patients without asthma demonstrate airway hyperresponsiveness (AHR) of the lower respiratory tract. Similar findings have been noted in patients with atopic dermatitis. This indicates that a systemic sensitization to antigen itself plays a pivotal role in the induction of AHR in sensitized individuals independently of eosinophilic inflammation in the lower airway. To clarify the mechanism, we studied a mouse model and found that transfer of antigen‐induced memory/effector cells can induce AHR in normal mice without airway inflammation. Dendritic cells (DCs) play a critical role in antigen‐induced immune response. We investigated the role of cysteinyl leukotrienes (cysLTs) in DC functions. BALB/c mice were sensitized with ovalbumin (OVA) and aluminium hydroxide (alum) twice, and subjected to OVA inhalation to induce airway inflammation. Systemic OVA sensitization alone up‐regulated cysLTs in the lung and stimulated T‐helper type 2 (Th2) cytokines production, whereas leukotriene receptor antagonist (LTRA) suppressed these productions. OVA sensitization enhanced DC functions such as antigen‐presenting capacity and cytokine production, and LTRA also attenuated them. Finally, we treated mice with LTRA during systemic sensitization and examined the effect on subsequent airway inflammation induced by OVA inhalation. LTRA suppressed all indicators of inflammation such as airway eosinophilia, Th2‐type cytokine production, and AHR along with decreased DC functions of the lung. These results indicate that modulating the antigen‐induced up‐regulation of DC functions in the early phase could attenuate further development of eosinophilic inflammation in the lower airway. Taking the similarities of lower and nasal airway into account, cysLTs may also play a critical role in the pathogenesis of AR; therefore, LTRA could be effective against AR from the initial presentation to the inflammation phase.
Japanese cedar/Japanese cypress pollen‐dispersion information and the initial therapy
Authors: Endo T. 
Published: June 2010

SummaryThe original initial therapy against pollinosis was introduced to the clinical setting in Japan in the 1980s, led by the launch of anti‐allergic drugs that were expected to exert prophylactic effects. The purpose of the therapy was to control the typical pollinosis seen in Japan: that occurs due to Japanese cedar/Japanese cypress pollens. The original therapy included prophylactic use of anti‐allergic drugs administered from before the start of the pollen season. Thanks to the launch of epinastine hydrochloride – which allows long‐term use, exerts adequate effects by once‐daily dosing, and seldom causes drowsiness as an adverse reaction – the initial therapy became safer and more defined. Meanwhile, precision of pollen‐dispersion forecast improved, automatic counting of dispersed pollen grains became available, and real‐time access to pollen‐dispersion information was facilitated due to widespread Internet use. Today, the initial therapy has improved to be a scheduled, comprehensive regimen that adopts hyposensitization as a fundamental procedure and incorporates measures against aggravation factors before the pollen season and complications likely to occur after the pollen season. Every day, we are practising this therapy and achieving great results; we believe that this regimen will benefit many people who suffer from pollinosis.
Melasma: Treatment with 10% tretinoin peeling mask
Authors: Ghersetich Ilaria , Troiano Michela , Brazzini Benedetta , Arunachalam Meena , Lotti Torello 
Published: June 2010

SummaryBackground  Melasma is one of the most frequently acquired hyperpigmentation disorders clinically characterized by symmetrical brown patches on sun exposed areas. The first approach is an avoidance of sun exposure and inflammation combined with a use of photoprotection. Patient treatment is particularly difficult and challenging, and necessitates consideration of many therapies, including tretinoin to obtain an amelioration of this important skin condition.Aims  To evaluate the efficacy of a 10% tretinoin peeling mask before and after treatment using standardized digital photos, mexameter measures, and melasma area and severity index (MASI) evaluation.Patients/Methods  The present study was carried out on 20 female patients.Results  Physician global evaluation showed moderate or marked improvement of melasma in all patients using three parameters of assessment: digital photography, mexameter measurement, and the MASI.Conclusions  Tretinoin peeling mask can be considered an alternative treatment modality in treating melasma. We noted a particular high tolerability and efficacy without adverse events.
Medication adherence among acne patients: a review
Authors: Lott Robert , Taylor Sarah L , O’Neill Jenna L , Krowchuk Daniel P , Feldman Steven R 
Published: June 2010

SummaryBackground  Acne is a chronic disease often requiring the use of medications for extended periods of time. In general, adherence decreases over time in patients with chronic diseases, and adherence to topical medications is poor compared to adherence to oral medications, placing individuals using topical medications at increased risk for nonadherence and treatment failure. Poor adherence may also be a common cause of treatment failure in teens with acne.Purpose  We reviewed the current literature on medication adherence in teenagers with acne to assess adherence levels and predictors of adherence. We hope to provide a foundation for further research into medication adherence in acne patients.Methods  A Medline search was conducted using the key words “acne” and “adherence” or “compliance.” Studies reporting adherence were included in the analysis.Results  A positive correlation was found between quality of life of patients with acne and medication adherence. Weaker predictors of adherence include increased age, female gender, and employment. The most commonly reported reason for nonadherence was inadequate time to use the treatment medication. Patients taking medications requiring less frequent dosing had better adherence, and medication adherence correlated with better health status among acne patients. A longer duration between office visits may be associated with decreased compliance.Limitations  Few studies investigating the prevalence and causes of nonadherence in acne patients were identified.Conclusions  Adherence to medications is difficult to measure and rates reported by patients often overestimate actual adherence. Patients cite lack of time as a common reason for nonadherence to topical medications.
A comparison of transcutaneous electrical nerve stimulation (TENS) at 3 and 80 pulses per second on cold‐pressor pain in healthy human participants
Authors: Chen Chih‐Chung , Johnson Mark I 
Published: June 2010

SummaryElectrophysiological studies suggest that there are differential frequency effects during TENS. The aim of this experimental study was to assess the effects of strong non‐painful TENS administered at 3 pulses per second (pps) and 80 pps on cold‐pressor pain in healthy human participants. A repeated measure design was used with participants receiving TENS at 3 pps and 80 pps in the same experiment. There were six cold‐pressor pain tests conducted on the hand with each type of TENS delivered via four electrodes on the ipsilateral forearm for 20 min. Outcomes were differences in pain threshold (s) and intensity (VAS) after 5 and 15 min of TENS. A 2 × 3 factorial repeated measure ANOVA was performed on data. Thirty‐five participants completed the experiment. Statistically significant effects were detected for condition, time and interactions between time × condition for both threshold and intensity. There were statistically higher pain thresholds and lower pain intensities for 3 pps when compared to 80 pps after 5 and 15 min of TENS. The differences after 15 min of TENS were 1·70 s to 3·70 s (95% CI) for threshold and 6·63–15·5 mm (95% CI) for pain intensity. In conclusion, strong non‐painful TENS at 3 pps was superior to 80 pps at reducing experimentally induced cold‐pressor pain. The implications of these findings are discussed.
Spinal long‐term potentiation is associated with reduced opioid neurotransmission in the rat brain
Authors: Hjornevik Trine , Schoultz Bent W. , Marton János , Gjerstad Johannes , Drzezga Alexander , Henriksen Gjermund , Willoch Frode 
Published: June 2010

SummaryIntroduction:  Neuronal events leading to development of long‐term potentiation (LTP) in the nociceptive pathways may be a cellular mechanism underlying hyperalgesia. In the present study, we examine if induction of spinal LTP may be associated with functional changes in the supraspinal opioidergic system. The opioid receptors (ORs) play a key role in nociceptive processing and controlling the descending modulatory system to the spinal cord.Methods:  Spinal LTP was induced by electrical high‐frequency stimulation (HFS) conditioning applied to the sciatic nerve, and the excitability at spinal level was verified by spinal field potential recordings. To study supraspinal changes in opioid neurotransmission following the same HFS conditioning, we used small animal positron emission tomography (PET) and [11C]Phenethyl‐Orvinol ([11C]PEO). All rats included in the PET study were scanned at baseline and 150 min after HFS, and specific binding was calculated with a reference tissue model.Results:  A clear C‐fibre LTP, i.e. increased C‐fibre response and reduced C‐fibre threshold, was observed 150 min after HFS conditioning (t‐test, P<0·05, n = 6). Moreover, increased OR binding, relative to baseline, was observed after the same type of HFS conditioning ipsilaterally in the amygdala, hippocampus, somatosensory cortex and superior colliculus, and bilaterally in the nucleus accumbens, caudate putamen and hypothalamus (paired t‐test, HFS>baseline, P<0·05, n = 8).Conclusions:  HFS conditioning of the sciatic nerve resulted in both spinal LTP and functional changes in supraspinal opioidergic signalling. Our findings suggest that induction of spinal LTP may be associated with reduced opioid neurotransmission in brain regions involved in pain modulation and affective‐emotional responses.
Neuroprotective effects of andrographolide in a rat model of permanent cerebral ischaemia
Authors: Chan Su Jing , Wong WS Fred , Wong Peter TH , Bian Jin‐Song 
Published: June 2010

BACKGROUND AND PURPOSE Andrographolide is a diterpenoid lactone isolated from a traditional medicinal herb, Andrographis paniculata. It possesses potent anti‐inflammatory activity. The present study examined potential therapeutic effects of andrographolide on cerebral ischaemia using a rat model with permanent middle cerebral artery occlusion (pMCAO).EXPERIMENTAL APPROACH The MCA in rats was permanently occluded (by cautery), and 24 h later neurological effects were assessed with behavioural scores. Infarct volume and microglial activation were determined histologically. The p65 form of the transcription factor, nuclear factor‐κB (NF‐κB), was measured by Western blot, and cytokines by immunoassay of brain extracts.KEY RESULTS Andrographolide, given i.p. 1 h after pMCAO, reduced infarct volume with a maximum reduction of approximately 50% obtained at 0.1 mg·kg−1. Neurological deficits were also reduced by andrographolide, reflecting a correlation between infarct volume and neurological deficits. pMCAO was found to induce activation of microglia and elevate tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β and prostaglandin (PG)E2 in the ischaemic brain areas. Andrographolide (0.1 mg·kg−1) significantly attenuated or abolished these effects. In addition, andrographolide suppressed the translocation of p65 from cytosol to nucleus, indicating reduced NF‐κB activation.CONCLUSIONS AND IMPLICATIONS Andrographolide exhibited neuroprotective effects, with accompanying suppression of NF‐κB and microglial activation, and reduction in the production of cytokines including TNF‐α and IL‐1β, and pro‐inflammatory factors such as PGE2. Our findings suggest that andrographolide may have therapeutic value in the treatment of stroke.
A novel peripherally restricted cannabinoid receptor antagonist, AM6545, reduces food intake and body weight, but does not cause malaise, in rodents
Authors: Cluny NL , Vemuri VK , Chambers AP , Limebeer CL , Bedard H , Wood JT , Lutz B , Zimmer A , Parker LA , Makriyannis A , Sharkey KA 
Published: June 2010

BACKGROUND AND PURPOSE Cannabinoid CB1 receptor antagonists reduce food intake and body weight, but clinical use in humans is limited by effects on the CNS. We have evaluated a novel cannabinoid antagonist (AM6545) designed to have limited CNS penetration, to see if it would inhibit food intake in rodents, without aversive effects.EXPERIMENTAL APPROACH Cannabinoid receptor binding studies, cAMP assays, brain penetration studies and gastrointestinal motility studies were carried out to assess the activity profile of AM6545. The potential for AM6545 to induce malaise in rats and the actions of AM6545 on food intake and body weight were also investigated.KEY RESULTS AM6545 binds to CB1 receptors with a Ki of 1.7 nM and CB2 receptors with a Ki of 523 nM. AM6545 is a neutral antagonist, having no effect on cAMP levels in transfected cells and was less centrally penetrant than AM4113, a comparable CB1 receptor antagonist. AM6545 reversed the effects of WIN55212‐2 in an assay of colonic motility. In contrast to AM251, AM6545 did not produce conditioned gaping or conditioned taste avoidance in rats. In rats and mice, AM6545 dose‐dependently reduced food intake and induced a sustained reduction in body weight. The effect on food intake was maintained in rats with a complete subdiaphragmatic vagotomy. AM6545 inhibited food intake in CB1 receptor gene‐deficient mice, but not in CB1/CB2 receptor double knockout mice.CONCLUSIONS AND IMPLICATIONS Peripherally active, cannabinoid receptor antagonists with limited brain penetration may be useful agents for the treatment of obesity and its complications.
Dual effect of nitric oxide on uterine prostaglandin synthesis in a murine model of preterm labour
Authors: Cella M , Farina MG , Dominguez Rubio AP , Di Girolamo G , Ribeiro ML , Franchi AM 
Published: June 2010

BACKGROUND AND PURPOSE Maternal infections are one of the main causes of adverse developmental outcomes including embryonic resorption and preterm labour. In this study a mouse model of inflammation‐associated preterm delivery was developed, and used to study the relationship between nitric oxide (NO) and prostaglandins (PGs).EXPERIMENTAL APPROACH The murine model of preterm labour was achieved by assaying different doses of bacterial lipopolysaccharides (LPS). Once established, it was used to analyse uterine levels of prostaglandins E2 and F2α (by radioimmunoassay), cyclooxygenases (COX) and NOS proteins (by Western blot) and NO synthase (NOS) activity. Effects of inhibitors of COX and NOS on LPS‐induced preterm labour were also studied. In vitro assays with a nitric oxide donor (SNAP) were performed to analyse the modulation of prostaglandin production by NO.KEY RESULTS Lipopolysaccharide increased uterine NO and PG synthesis and induced preterm delivery. Co‐administration of meloxicam, a cyclooxygenase‐2 inhibitor, or aminoguanidine, an inducible NOS inhibitor, prevented LPS‐induced preterm delivery and blocked the increase in PGs and NO. Notably, the levels of NO were found to determine its effect on PG synthesis; low concentrations of NO reduced PG synthesis whereas high concentrations augmented them.CONCLUSIONS AND IMPLICATIONS An infection‐associated model of preterm labour showed that preterm delivery can be prevented by decreasing PG or NO production. NO was found to have a dual effect on PG synthesis depending on its concentration. These data contribute to the understanding of the interaction between NO and PGs in pregnancy and parturition, and could help to improve neonatal outcomes.