bluuebunny/crossref_metadata_2025 huggingface dataset:
One-step Preparation of ZnSe Nanorod Aggregates
Authors: Zhao Qingchun , Xu Wenzong
Published: September 2006

ZnSe semiconductor aggregations were prepared via γ-ray irradiation method. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images of the products clearly show that ZnSe possesses an aggregation structure, and these aggregations were found to form through the aggregation of ZnSe nanorods. The length and the diameter of the ZnSe nanorods are about 500–1000 and 30–60 nm, respectively. Electron diffraction patterns of an individual ZnSe nanorod and X-ray diffraction (XRD) analysis were used to examine the crystal structure of the products. The obtained product is pure-phase hexagonal system ZnSe. The composition of the products was analyzed by X-ray photoelectron spectroscopy (XPS). Effect of the pH value on product morphology was investigated.
Light-induced Electron Transfer on the Single Wall Carbon Nanotube Surrounded in Anthracene Dendron in Aqueous Solution
Authors: Sandanayaka Atula S D , Takaguchi Yutaka , Uchida Tetsuya , Sako Yuuki , Morimoto Yu , Araki Yasuyuki , Ito Osamu
Published: September 2006

Light illumination of single-wall carbon nanotubes (SWCNTs) dispersed with anthracene (An) dendrons afforded the accumulation of the reduced form of methyl viologen in the presence of a hole shifter. With the helps of the fluorescence lifetime and transient absorption measurements, the charge-separation process from the excited state of the hybrides of An dendrimer to SWCNT was confirmed.
Interpretation of the short Synacthen test in the presence of low cortisol-binding globulin: two case reports
Authors: Moisey Robert , Wright Dianne , Aye Mo , Murphy Elaine , Peacey Steven R
Published: September 2006

Context: Ten percent of serum total cortisol (TC) is unbound; the remainder is bound to cortisol-binding globulin (CBG) and, to a lesser extent, albumin. CBG concentrations can drop significantly, particularly in critical illness, resulting in a low TC although the free, active, cortisol may be normal or increased. In the context of a low CBG, the diagnosis of pituitary-adrenal insufficiency with measurements of TC is difficult.

Objective: To remind clinicians of the difficulty in interpreting TC when the CBG is low, the circumstances when CBG concentrations may decrease and that measurement of CBG and calculation of the free cortisol index can help in the assessment of pituitary-adrenal reserve.

Case: We present two patients at risk of primary and secondary adrenal insufficiency with a poor response to 250 μg Synacthen. In both cases we confirmed low CBG concentrations but a normal free cortisol index (FCI), confirming normal pituitary-adrenal reserve.

Intervention: In case one, we have been able to avoid long-term steroid replacement therapy. We continue to reduce the steroid dose in case 2 but have been limited by the need for high-dose steroid treatment for exacerbations of the patient's airways disease.

Conclusion: The use of TC in the assessment of the hypothalamic-pituitary-adrenal (HPA) axis may give rise to misleading results if the CBG concentration is low. The FCI may be a better marker of pituitary-adrenal reserve in these subjects. Clinicians should be cautious when interpreting abnormal cortisol results and we emphasize the importance of good clinical assessment.
Whole-blood thiopurine S-methyltransferase activity with genotype concordance: a new, simplified phenotyping assay
Authors: Ford Loretta , Graham Valerie , Berg Jonathan
Published: September 2006

Background: We have developed a new thiopurine S-methyltransferase (TPMT) phenotyping method that measures TPMT activity in whole blood. To evaluate this assay, we compared it with conventional TPMT phenotyping, which uses a red blood cell (RBC) lysate and genotyping for analysis of common TPMT mutations.

Methods: Whole-blood and RBC lysates were prepared from 402 patients' samples received for routine analysis. The TPMT activity of lysates was determined using 6-thioguanine as substrate with high-performance liquid chromatographic (HPLC) analysis and fluorimetric detection. DNA was extracted from buffy coats using phenol-chloroform extraction. A multiplex amplification refractory mutation system (ARMS) strategy was used to screen for the common TPMT mutations TPMT*2 and TPMT*3 (TPMT*3A, TPMT*3C and TPMT*3D).

Results: TPMT activities were higher in the whole-blood (mean TPMT activity 51 nmol 6-MTG/gHb/h) compared with the RBC lysate (37 nmol 6-MTG/gHb/h). Overall, concordance with TPMT genotypic analysis was 97% for both the new whole-blood and standard RBC lysate methods. Between low TPMT activity and heterozygotes, both phenotypic methods gave a concordance of 79%.

Conclusion: Using multiplex ARMS testing for TPMT*2 and 3*C mutations to define the cut-off between low and normal TPMT activity, we have demonstrated that the new whole-blood TPMT phenotyping method performs as well as the conventional RBC lysate assay. This new method overcomes the need to prepare a RBC lysate, a process which is time consuming and increases analytical variation. The resulting assay is better suited to a regional or national TPMT phenotyping service.
Reflective testing: what do patients think?
Authors: Paterson Sarah G , Robson Jean E , McMahon Michael J , Baxter Gwen , Murphy Michael J , Paterson John R
Published: September 2006

Introduction: Reflective testing refers to the practice of adding on tests by laboratory staff. Little is known about what patients think of this practice.

Methods: We surveyed patients attending a general practice surgery and patients attending hospital outpatient clinics. We sought their views about the practice of adding on tests and about the information they received from requesting clinicians about their investigations.

Results: In both groups of patients, large majorities favoured an approach in which relevant additional tests are performed without consulting the requesting clinician or patient first. Most patients also felt that the requesting clinicians had provided a satisfactory explanation about what tests were to be performed and why.

Conclusion: Most patients are content to let NHS professionals add on relevant tests if this is felt to be in their interest.
Outcomes of discretionary laboratory requesting of serum protein electrophoresis
Authors: Hughes Marie , Davidson D Fraser , McColl Mark
Published: September 2006

Background: Discretionary laboratory requesting of serum protein electrophoresis (SPE) is widespread throughout the UK despite limited evidence to support clinical usefulness. We aimed to examine the clinical usefulness of discretionary SPE requesting on serum samples with globulins > 45 g/L by documenting the number of discretionary tests performed and the number of paraproteins identified in an audit period, by determining if such findings led to further investigation/specialty referral, and by identifying the final diagnosis and subsequent management of these patients.

Methods: A retrospective one-year audit from July 2002 to June 2003 was carried out using information from biochemistry databases and review of medical records.

Results: Of 1332 discretionary SPEs performed in one year, 72 paraproteins were identified (5.4%). Further clinical information could be obtained in 66 cases. Appropriate follow-up occurred in 84% of cases. The most common diagnosis was monoclonal gammopathy of undetermined significance (56%). Eighteen percent of patients with an identified paraprotein were diagnosed with B-cell malignancies that warranted treatment. A further 6% progressed to requiring treatment during follow-up.

Conclusion: Using screening criteria of serum globulins > 45 g/L, one in 20 discretionary laboratory requests resulted in a clinically relevant finding. These results suggest such requesting is worthwhile and should aid future debate on the appropriateness of this practice.
Human circadian rhythms: physiological and therapeutic relevance of light and melatonin
Authors: Skene Debra J , Arendt Josephine
Published: September 2006

Ocular light plays a key role in human physiology by transmitting time of day information. The production of the pineal gland hormone melatonin is under the control of the light-dark cycle. Its profile of secretion defines biological night and it has been called the 'darkness hormone'. Light mediates a number of non-visual responses, such as phase shifting the internal circadian clock, increasing alertness, heart rate and pupil constriction. Both exogenous melatonin and light, if appropriately timed, can phase shift the human circadian system. These 'chronobiotic' effects of light and melatonin have been used successfully to alleviate and correct circadian rhythm disorders, such as those experienced following travel across time zones, in night shift work and in circadian sleep disorders. The effectiveness of melatonin and light are currently being optimized in terms of time of administration, light intensity, duration and wavelength, and melatonin dose and formulation. The aim of this review is not to replicate information that has been reported in a number of reviews of the human circadian timing system and the role of melatonin and light, but rather to extract findings relevant to the field of clinical biochemistry.
Cardiovascular disease prevention: the new Joint British Societies' guidelines
Authors: Laker Michael F
Published: September 2006

The Joint British Societies' recommendations for coronary heart disease (CHD) prevention have been updated in the light of recent developments. Key features of the new guidelines include focusing on cardiovascular disease (CVD) prevention rather than CHD and adopting strategies that target high-risk groups, with equal priority being given to all those with established CVD or diabetes mellitus. Subjects without CVD but with a risk factor profile resulting in an absolute risk of developing CVD -20% over 10 years should be included in these strategies and CVD prevention should also be applied to subjects with particularly unfavourable single risk factors including familial dyslipidaemias, such as familial hypercholesterolaemia, hypercholesterolaemia when the total cholesterol:HDL cholesterol ratio is -7.0, hypertension when the blood pressure (BP) -160 mmHg systolic or -100 mmHg diastolic or lesser degrees of hypertension when there is end-organ damage. The optimal target for total cholesterol is <4.0 mmol/L and for LDL cholesterol <2.0 mmol/L, or a reduction of 25% in total cholesterol and a 30% reduction in LDL cholesterol, whichever achieves the lower absolute level. The optimal BP target is <140 mmHg systolic and <85 mmHg diastolic pressure with lower targets in subjects with CVD, diabetes or chronic renal failure. If these conditions are present, treatment should aim to achieve <130 mmHg systolic and <80 mmHg diastolic pressures.
Minnesota academy of ophthalmology and OTO‐laryngology: Section of OTO‐laryngology
Authors: Wood Douglas
Published: September 2006

Radical Sinus Exenteration in Pansinusitis, With an Analysis of Fifty Cases as to Results Obtained. Dr. E. L. Armstrong.
The management of cancer of the nasal sinuses
Authors: Myerson Mervin C.
Published: September 2006

Cancer of the paranasal sinuses is not frequently encountered in otolaryngological practice. These tumors constitute less than 1 per cent of the cases seen at the Brooklyn Cancer Institute. During 1937, there were five malignant tumors of the sinuses among 737 admissions. Most of these cases are seen when the disease is far advanced and therefore present special problems. Fear, ignorance and the unfortunate circumstance of the absence of symptoms are factors in the late appearance of these patients for treatment. Fortunately, in many cases, a late diagnosis does not mean a hopeless prognosis. These neoplasms are usually out of sight and are frequently painless. When pain occurs it may be referred to the alveolar process, suggesting a dental condition, or it may be referred to the cheek, suggesting an antrum suppuration. Irrigation of the antrum may be negative or may reveal the presence of pus. When blood or sanguineous material are returned with the irrigation, the diagnosis is fairly certain. If a malignancy of the antrum is suspected because of the symptoms or because of the Roentgen findings, the interior of the sinus should be examined by means of an exploratory opening.
Chronic frontal sinusitis. A new endonasal surgical approach
Authors: Stone Frederick E. , Berger M.
Published: September 2006

The multiplicity of surgical procedures for the attempted relief of persistent frontal sinusitis in itself suggests their inadequacy. Every rhinologist is almost constantly haunted by the spectre of unrelieved patients who have left the operating table with adequate surgical endonasal ostia only to return six months later with bony or fibrous stenosis and recurrent symptoms. Further surgery serves only to create new additions to the already impressive group of surgical nihilists among the general medical advisers, as well as the discouraged laity. This seems to be the only too frequent experience after the extensive external operation, as well as the various ingenious intranasal manipulations. The only outstanding exception to this situation appears to be the obliterating collapse operation, which, unfortunately, is so deforming in the large sinus usually present in serious frontal disease that both patient and surgeon rightfully hesitate until everything else possible has been tried.
Primary carcinoma of the external auditory canal and meatus. Review of the literature and report of a case
Authors: Risch Otto C. , Lisa James R.
Published: September 2006

Malignant disease originating in the external auditory canal and meatus is one of the most uncommon lesions seen in otolaryngological practice. Many of the textbooks do not even mention the condition, although Politzer1has accurately described it. Even in the larger clinics it is seldom seen. Robinson2states that among 212,000 cases at the Manhattan Eye and Ear Hospital, New York between 1904 and 1924, only 19 cases were seen of carcinoma of the external ear and canal. Story3reports that no case was seen in the largest aural hospital in Ireland in 17 years. Fraser4says that only three cases of malignancy of the external auditory canal were seen by him in private practice among 646 patients between 1906 to 1929, inclusive. In the Department of Otology, Royal Infirmary, Edinburgh,5of 6,605 cases of disease of the external ear and meatus, 13 were malignant. Connal6mentions four carcinomas and two sarcomas among 15,000 cases in the General Ear Hospital, of Glasgow. Pritchard7stated that he had not seen a dozen cases of epithelioma beginning in the skin of the meatus in over 25 years' practice. McBride8had seen only three cases in 20 years at the Edinburgh Infirmary and in private practice. Bezold9found only four among 20,000 as cases. Broders10reports by far the highest incidence, 14.28 per cent of involvement of the external auditory canal among 63 cases of carcinoma of the ear. The experience of West11alikewise is unusual. In two years, seven cases were seen by him in St. Bartholomew's Hospital, London, six at least presenting good evidence of origin in the meatus. Bonner12aclaimed that they were fairly common and often overlooked. He had seen five or six in a period of a few years.
Will performance league tables change the way surgeons select and operate on patients?
Authors: Nixon MF , Johari Y , Taylor GJS
Published: September 2006

The Freedom of Information Act became law in January 2005 and means that any information held by a public authority is eligible for release upon demand. It was designed to make government authorities more transparent and each authority is required to document what information it holds and how that information can be obtained.
The effect of independent treatment centres on patient case mix within orthopaedic waiting lists
Authors: Bolland BJ , Corbin C , Bissell IJ , Latham JM
Published: September 2006

There is concern that the current drive to reduce waiting lists and promote alternative providers, such as independent sector treatment centres (ISTCs), will lead to a change in the case mix of patients remaining on the waiting lists of local hospitals. The reallocation of routine procedures on medically fit patients to alternative providers will result in an increase in the proportion of complex or medically unwell patients remaining on a Trust's waiting list. Overall waiting times for routine surgery will be reduced but there are concerns about the uncertain effects on patient outcome, general hospital resources and the experience of orthopaedic trainees.
The Human Tissue Act 2004: implications for anatomical work at the College
Authors: Mahadevan Vishy
Published: September 2006

The Human Tissue Act 2004 is a new, important, comprehensive and, above all, timely legislation that is due to come into force on 1 September 2006. The act has considerable implications for the practice of anatomy at the College. The significance of these implications cannot be overemphasised, given the imminence of the many and far-reaching changes that are to take place in the nature of postgraduate surgical training in the UK and the fresh demands that the new training schemes will impose on the delivery of effective postgraduate surgical education (in particular, surgical anatomy).
'All changed, changed utterly'
Authors: Ribeiro Bernard
Published: September 2006

'All changed, changed utterly' – these words, written by WB Yeats (1865–1939) 90 years ago this September to describe the Irish uprising, were used by Richard Smith, editor of the British Medical Journal, in 1998 to describe the seismic change that would affect surgical practice after the Bristol Royal Infirmary inquiry.
The Chronic Pain Policy Coalition
Authors: Fountain Yvonne
Published: September 2006

The Chronic Pain Policy Coalition (CPPC) parliamentary launch took place on 14 June 2006 at Portcullis House, Westminster. Pain is an unpleasant experience with both sensory and emotional aspects; there can be pain whether or not there is tissue damage. Acute pain has a short and relatively severe course whereas chronic pain is pain that persists for longer than three months or in diseases where pain is always present.
Delivering high-quality surgical services for the future
Authors: O'Riordan Dermot , Cripps Jo
Published: September 2006

In March 2006 the reconfiguration working party published its initial report Delivering High-quality Surgical Services for the Future. This consultation document looked at the key reform dilemmas in the 'new NHS' and set out some potential future areas of work for the College. It was disseminated widely to surgeons, service planners, Trust, strategic health authority and Primary Care Trust chief executives and patient groups. The consultation closed on 30 June 2006 and the responses are being considered by the working party. This article examines the key features of the consultation responses and looks to the future, at how the College will take the reform agenda forward.
Efficacy and Safety of Rosuvastatin Every Other Day Compared with Once Daily in Patients with Hypercholesterolemia
Authors: Wongwiwatthananukit Supakit , Sansanayudh Nakarin , Dhummauppakorn Rawadee , Kitiyadisai Chutiporn
Published: September 2006

Background:

Although most patients with hypercholesterolemia require life-long therapy with statins, these drugs are underused due to high costs. Every-other-day therapy could be one strategy to resolve this problem.

Objective:

To compare the efficacy and safety of rosuvastatin 10 mg administered every other day versus once daily.

Methods:

An 8 week, randomized, open-label, parallel trial was conducted at the outpatient department of Phramongkutklao Hospital in Bangkok, Thailand. Eighty patients with primary hypercholesterolemia were equally randomized to receive rosuvastatin 10 mg once daily or every other day; 76 patients completed the study. Laboratory data were assessed at baseline and at the end of the study.

Results:

Low-density lipoprotein cholesterol (LDL-C) levels were reduced by 48% and 39% in the once-daily and every-other-day groups, respectively (p = 0.011). The percentage of patients who achieved LDL-C goals according to National Cholesterol Education Program-Adult Treatment Panel III guidelines was not significantly different between the once-daily (85%) and every-other-day (70%) groups (p = 0.180). In addition, both regimens were well tolerated, with no patient developing an elevation of more than 3 times baseline levels of aspartate aminotransferase or alanine aminotransferase or 10 times that of creatine kinase. As expected, the monthly cost per percent LDL-C reduction of the once-daily ($0.72) regimen was about 38% higher than that of the every-other-day ($0.44) regimen.

Conclusions:

Every-other-day dosing of rosuvastatin may be an alternative regimen for cost savings, without a major decrease in therapeutic benefit or increase in adverse events, in patients with hypercholesterolemia. The number of patients achieving their LDL-C goal using the every-other-day regimen is comparable with the number using the once-daily regimen, especially in the low-risk patient category.
Renin—Angiotensin System Mediators and Raynaud's Phenomenon
Authors: Wood Heidi M , Ernst Michael E
Published: September 2006

Objective:

To review the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in the treatment of Raynaud's phenomenon (RP).

Data Sources:

Biomedical literature was accessed through July 2006 via PubMed, the Iowa Drug Information System (OS), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus. PubMed database terms included Raynaud's disease, angiotensin-converting enzyme inhibitors, and angiotensin II type 1 receptor blockers [pharmacological action]; IDIS terms included hypotensive agents-ace inhib 24080200, raynaud's syndrome 443.0, and hypotensive agents-angioten II 24080400; and CINAHL Plus terms included Raynaud's disease, angiotensin-converting enzyme inhibitors, losartan, and irbesartan.

Study Selection and Data Extraction:

All clinical trials published in English that reported both subjective and objective outcomes of efficacy were reviewed.

Data Synthesis:

Several small, short-term studies have evaluated captopril, enalapril, and losartan in the treatment of RP. The studies of ACE inhibitors have found conflicting results in their ability to improve digit blood flow and reduce both frequency and severity of RP attacks. Two studies have focused on the use of losartan for RP treatment, with both finding a statistically significant reduction in attacks and one showing improvement in symptoms of RP in comparison with the commonly utilized calcium-channel blocker, nifedipine. Most of the studies were short term (≤2 wk) and included a limited number of patients (CONCLUSIONS: ACE inhibitors and ARBs may provide some minor benefits in the relief of RP, although no definite evidence exists to suggest that they are superior to traditionally used treatments such as calcium-channel blockers. Larger, randomized controlled trials of longer duration are needed to compare the effectiveness of ACE inhibitors and ARBs with conventional treatment.
Relief of Acute Pain in Chronic Idiopathic Gastroparesis with Intravenous Phentolamine
Authors: Phillips William J , Tollefson Brian , Johnson Alisa , Abell Thomas , Lerant Anna
Published: September 2006

Objective:

To report a case in which complete relief of pain associated with gastroparesis, with promotion of gastric emptying, was achieved with administration of phentolamine.

Case Summary:

A 37-year-old opiate-tolerant female with a history of recurrent abdominal pain, gastroparesis, cyclic vomiting syndrome, and migraine headaches was admitted to the emergency department (ED) with severe acute abdominal pain, nausea, and vomiting. The patient had been previously implanted with a permanent gastric electrical stimulator and she was adherent to her prokinetic, antiemetic, analgesic, and migraine prophylactic medications. Pain relief was achieved rapidly and completely in the ED with sympatholysis by administration of intravenous phentolamine 0.5 mg/kg over 60 minutes, with continuous cardiac monitoring. At a 2 month follow-up visit, the patient reported chronic pain relief, and a decrease in opiate doses was maintained by oral administration of clonidine 0.1 mg twice daily.

Discussion:

Gastroparesis represents a difficult treatment challenge because management of gastric dysmotility and the accompanying severe abdominal pain is often mutually exacerbating and ineffective. Sympatholysis by intravenous phentolamine provided profound and immediate relief of acute gastroparesis-related abdominal pain in our patient. The mechanism of phentolamine is believed to be receptor blockade at ά-adrenergic receptors and, therefore, inhibition of the peripheral sensitizing effects of circulating norepinephrine. Although action at a peripheral nerve level is presumed, modulation of ά-adrenoreceptors receptors is also possible at the dorsal root ganglion or at other central nervous system sites.

Conclusions:

The dramatic relief of acute pain in gastroparesis by phentolamine observed in this case would warrant investigation of a larger, controlled case series. Patients who respond to intravenous sympatholysis may likewise be candidates for longer term sympathetic modulation with oral sympatholytics.
The performance evaluation of novices: The importance of competence in specific work activity clusters
Authors: Molleman Eric , Van der Vegt Gerben S.
Published: September 2006

In this study, we examine the relationships between newcomers' competence in specific work activity clusters and the evaluation of their performance. Longitudinal data were gathered on 92 novice nurses from themselves and from the senior staff at three stages: before entering the job, 6 weeks after entry and 18 months after entry. Results showed that, after entry, a newcomer's competence in the cluster of care activities contributed more to a positive performance evaluation than competence in the cluster of non‐care activities. Competence in the non‐care cluster was only found to contribute to a positive performance evaluation, if the newcomer also showed competence in the care cluster. Moreover, novices showed a greater improvement in their care competence than their non‐care competence during the first 18 months of socialization. Finally, we found that after 18 months competence in the non‐care cluster contributes more to a positive performance evaluation than competence in the care cluster.
Advancing conjugated polymers into nanometer-scale devices
Authors: Hu Wenping , Nakashima Hiroshi , Wang Erjing , Furukawa Kazuaki , Li Hongxiang , Luo Yi , Shuai Zhigang , Kashimura Yoshiaki , Liu Yunqi , Torimitsu Keiichi
Published: September 2006

In this article, we review the possibility of combining conjugated polymers with nanometer-scale devices (nanodevices), in order to introduce the properties associated with conjugated polymers into such nanodevices. This approach envisages combining the highly topical disciplines of polymer electronics and nanoelectronics to engender a new subdirection of polymer nanoelectronics, which can serve as a tool to probe the behavior of polymer molecules at the nanometer/molecular level, and contribute to clarifying transport mechanisms in conjugated polymers. In this study, we exemplify this combination, using a family of linear and conjugated polymers, poly(p-phenylene-ethynylene)s (PPEs) with thiolacetate-functionalized end groups.
Materials of cellulose derivatives and fiber-reinforced cellulose-polypropylene composites: Characterization and application
Authors: Zugenmaier Peter
Published: September 2006

Cellulose is a biodegradable polymer produced sustainably in large quantities by nature. It has been used by mankind for centuries because of its favorable properties, but suffers disadvantages such as the high cost of production and limited processibility. For example, it cannot be melted and is only soluble in less common solvents. The latter limitation can be overcome through appropriate derivatization of cellulose, which increases the solubility range and may generate thermoplastic materials. This paper will review three new developments leading to enhanced utilization of cellulosics.

Firstly, an overview is given of the progress in the formulation of fiber-reinforced thermoplastic cellulose composites to facilitate extrusion processing. Cellulose-polypropylene composites show enhanced properties in comparison with neat polypropylene, and offer scope for replacing composites containing glass fibers, owing to resultant advantages in weight, recyclability, and ease of disposal. Progress is also reported in improving the predictability of essential physical quantities and melt flow in cellulose esters. Finally, an account is given of the successful development of microcrystalline cellulose (CFM) derivatives, synthesized in a heterogeneous manner, as chiral recognition agents in liquid chromatography. The structural features of these materials are decisive for their use. A model is proposed for the morphology of the cellulosic fibrils.
Synthesis of fine chemicals by the conjugate addition of nitroalkanes to electrophilic alkenes
Authors: Ballini R. , Barboni L. , Bosica G. , Fiorini D. , Palmieri A.
Published: September 2006

Several aliphatic nitro compounds have been employed as stabilized carbanions in the conjugate addition to a variety of electron-poor alkenes (Michael reaction). Depending on the nature of the alkene, new carbon-carbon single or double bonds can be generated. However, all the Michael adducts can be efficiently utilized as key building blocks for the synthesis of a huge array of fine chemicals, including homo- and heterocyclic structures.
Graphical representation of stereochemical configuration (IUPAC Recommendations 2006)
Authors: Brecher Jonathan
Published: September 2006

Stereochemical configuration is determined by the relationship of atoms in three-dimensional space, yet remains most commonly represented in two-dimensional media such as printed publications or computer screens. Recommendations are provided for the display of three-dimensional stereochemical information in two-dimensional diagrams in ways that avoid ambiguity and are likely to be understood correctly by all viewers. Examples are provided for all types of stereochemical configuration, with explanation of which styles are preferred and which should be avoided. Principal recommendations include:

Know your audience: Diagrams that have a wide audience should be drawn as simply as possible.

Avoid ambiguous drawing styles.

Avoid the use of perspective diagrams and class-specific drawing styles (Fischer projections, Haworth projections, etc.) when structures are to be interpreted by computers.

Use solid wedges to indicate bonds that project above the plane of the paper and hashed wedges to indicate bonds that project below the plane of the paper; in both cases, the bonds must be oriented with the narrow end at the stereogenic center.

Avoid connecting stereogenic centers with a stereobond.
Comprehensive Wave Propagation Model to Improve TDR Interpretations for Geotechnical Applications
Authors: Lin C-P , Tang S-H
Published: September 2006

Time domain reflectometry (TDR) is becoming an important monitoring technique for various geotechnical problems. Better data interpretation and new developments rely on the ability to accurately model the TDR waveform, especially when long cables are used. This study developed an efficient, complete, and general-purpose TDR model that accounts for all wave phenomena including multiple reflection, dielectric dispersion, and cable resistance all together. Inverse analysis based on the TDR wave propagation model is proposed to calibrate the TDR system parameters and determine the TDR parameter that changes with the physical parameter to be monitored. Calibration of TDR cable and data interpretations for various geotechnical applications were demonstrated with laboratory experiments. The excellent match between the simulated and measured waveforms validates the TDR wave propagation model. The results show that the proposed numerical procedure is a relatively simple, efficient and high-resolution tool for probe design, parametric studies, data interpretation, and inverse analyses. This study should provide a sound theoretical foundation for further TDR developments in geotechnical monitoring.
Local Interneurons Regulate Synaptic Strength by Retrograde Release of Endocannabinoids
Authors: Beierlein Michael , Regehr Wade G.
Published: September 2006

Neurons release endocannabinoids from their dendrites to trigger changes in the probability of transmitter release. Although such retrograde signaling has been described for principal neurons, such as hippocampal pyramidal cells and cerebellar Purkinje cells (PCs), it has not been demonstrated for local interneurons. Here we tested whether inhibitory interneurons in the cerebellum, stellate cells (SCs) and basket cells, regulate the strength of parallel fiber (PF) synapses by releasing endocannabinoids. We found that depolarization-induced suppression of excitation (DSE) is present in both SCs and basket cells. The properties of retrograde inhibition were examined more thoroughly for SCs. Both DSE and synaptically evoked suppression of excitation (SSE) triggered with brief PF bursts require elevations of postsynaptic calcium, are blocked by a type 1 cannabinoid receptor (CB1R) antagonist, and are absent in mice lacking the CB1R. SSE for SCs is similar to that described previously for PCs in that it is prevented by BAPTA and DAG lipase inhibitors in the recording pipette; however, unlike in PCs, NMDA receptors (NMDARs) play an important role in SSE for SCs. Although SCs express CB1Rs postsynaptically, neither high-frequency firing of SCs nor PF bursts lead to autocrine suppression of subsequent SC activity. Instead, PF bursts decrease the amplitude of disynaptic inhibition in PCs by evoking endocannabinoid release that transiently reduces the ability of PF synapses to trigger spikes in SCs. Thus, local interneurons within the cerebellum can release endocannabinoids through metabotropic glutamate receptor- and NMDAR-dependent mechanisms and contribute to use-dependent modulation of circuit properties.
Synaptic Currents in Anatomically Identified CA3 Neurons during Hippocampal Gamma OscillationsIn Vitro
Authors: Oren Iris , Mann Edward O. , Paulsen Ole , Hájos Norbert
Published: September 2006

Gamma-frequency oscillations are prominent during active network states in the hippocampus. An intrahippocampal gamma generator has been identified in the CA3 region. To better understand the synaptic mechanisms involved in gamma oscillogenesis, we recorded action potentials and synaptic currents in distinct types of anatomically identified CA3 neurons during carbachol-induced (20–25 μm) gamma oscillations in rat hippocampal slices. We wanted to compare and contrast the relationship between excitatory and inhibitory postsynaptic currents in pyramidal cells and perisomatic-targeting interneurons, cell types implicated in gamma oscillogenesis, as well as in other interneuron subtypes, and to relate synaptic currents to the firing properties of the cells. We found that phasic synaptic input differed between cell classes. Most strikingly, the dominant phasic input to pyramidal neurons was inhibitory, whereas phase-coupled perisomatic-targeting interneurons often received a strong phasic excitatory input. Differences in synaptic input could account for some of the differences in firing rate, action potential phase precision, and mean action potential phase angle, both between individual cells and between cell types. There was a strong positive correlation between the ratio of phasic synaptic excitation to inhibition and firing rate over all neurons and between the phase precision of excitation and action potentials in interneurons. Moreover, mean action potential phase angle correlated with the phase of the peak of the net-estimated synaptic reversal potential in all phase-coupled neurons. The data support a recurrent mechanism of gamma oscillations, whereby spike timing is controlled primarily by inhibition in pyramidal cells and by excitation in interneurons.
Bidirectional Dopaminergic Modulation of Excitatory Synaptic Transmission in Orexin Neurons
Authors: Alberto Christian O. , Trask Robert B. , Quinlan Michelle E. , Hirasawa Michiru
Published: September 2006

Orexin neurons in the lateral hypothalamus (LH)/perifornical area (PFA) are known to promote food intake as well as provide excitatory influence on the dopaminergic reward pathway. Dopamine (DA), in turn, inhibits the reward pathway and food intake through its action in the LH/PFA. However, the cellular mechanism by which DA modulates orexin neurons remains largely unknown. Therefore, we examined the effect of DA on the excitatory neurotransmission to orexin neurons. Whole-cell patch-clamp recordings were performed using acute rat hypothalamic slices, and orexin neurons were identified by their electrophysiological and immunohistochemical characteristics. Pharmacologically isolated action potential-independent miniatures EPSCs (mEPSCs) were monitored. Bath application of DA induced a bidirectional effect on the excitatory synaptic transmission dose dependently. A low dose of DA (1 μm) increased mEPSC frequency, which was blocked by the D1-like receptor antagonist SCH 23390, and mimicked by the D1-like receptor agonist SKF 81297. In contrast, higher doses of DA (10–100 μm) decreased mEPSC frequency, which could be blocked with the D2-like receptor antagonist, sulpiride. Quinpirole, the D2-like receptor agonist, also reduced mEPSC frequency. None of these compounds affected the mEPSCs amplitude, suggesting the locus of action was presynaptic. Furthermore, DA (1 μm) induced an increase in the action potential firing, whereas DA (100 μm) hyperpolarized and ceased the firing of orexin neurons, indicating the effect of DA on excitatory synaptic transmission may influence the activity of the postsynaptic cell. In conclusion, our results suggest that D1- and D2-like receptors have opposing effects on the excitatory presynaptic terminals impinging onto orexin neurons.
Matrix Metalloproteinase-2 Facilitates Wound Healing Events That Promote Functional Recovery after Spinal Cord Injury
Authors: Hsu Jung-Yu C. , McKeon Robert , Goussev Staci , Werb Zena , Lee Jung-Uek , Trivedi Alpa , Noble-Haeusslein Linda J.
Published: September 2006

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in both injury and repair mechanisms in the CNS. Pharmacological blockade of MMPs, limited to the first several days after spinal cord injury, improves locomotor recovery. This beneficial response is, however, lost when treatment is extended beyond the acutely injured cord to include wound healing and tissue remodeling. This suggests that some MMPs play a beneficial role in wound healing. To test this hypothesis, we investigated the role of MMP-2, which is actively expressed during wound healing, in white matter sparing and axonal plasticity, the formation of a glial scar, and locomotor recovery after spinal cord injury. MMP-2 increased between 7 and 14 d after injury, where it was immunolocalized in reactive astrocytes bordering the lesion epicenter. There was reduced white matter sparing and fewer serotonergic fibers, caudal to the lesion in injured MMP-2 null animals. MMP-2 deficiency also resulted in increased immunoreactivity to chondroitin sulfate proteoglycans and a more extensive astrocytic scar. Most importantly, locomotion in an open field, performance on a rotarod, and grid walking were significantly impaired in injured MMP-2 null mice. Our findings suggest that MMP-2 promotes functional recovery after injury by regulating the formation of a glial scar and white matter sparing and/or axonal plasticity. Thus, strategies exploiting MMPs as therapeutic targets must balance these beneficial effects during wound healing with their adverse interactions in the acutely injured spinal cord.
GGA1 Acts as a Spatial Switch Altering Amyloid Precursor Protein Trafficking and Processing
Authors: von Arnim Christine A. F. , Spoelgen Robert , Peltan Ithan D. , Deng Meihua , Courchesne Stephanie , Koker Mirjam , Matsui Toshifumi , Kowa Hisatomo , Lichtenthaler Stefan F. , Irizarry Michael C. , Hyman Bradley T.
Published: September 2006

The β-amyloid (Aβ) precursor protein (APP) is cleaved sequentially by β-site of APP-cleaving enzyme (BACE) and γ-secretase to release the Aβ peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized γ-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from β-cleavage but surprisingly reduced Aβ. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP β-cleavage products from becoming substrates for γ-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP–GGA1 interactions may have pathophysiological relevance in AD.
Reconsolidation and Extinction of Conditioned Fear: Inhibition and Potentiation
Authors: Lee Jonathan L. C. , Milton Amy L. , Everitt Barry J.
Published: September 2006

NMDA receptors are important for the acquisition, reconsolidation, and extinction of memories. NMDA receptor antagonists impair these memory processes, whereas the partial agonistd-cycloserine (DCS) potentiates both learning and extinction. Here, we used DCS and the noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-SH-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) to investigate the effects of enhancing and blocking NMDA receptor-mediated glutamatergic transmission on the reconsolidation and extinction of a conditioned fear memory. Either long extinction training or short memory reactivation sessions were used to preferentially engage extinction and reconsolidation processes, respectively. MK-801 blocked extinction to maintain high levels of conditioned freezing, and DCS potentiated extinction to reduce freezing, when they were administered before a long extinction training session. However, the opposite behavioral outcome was observed when the brief memory reactivation session was used: MK-801 administration impaired, whereas DCS increased, freezing, likely reflecting impairment and enhancement of reconsolidation, respectively. Finally, by using localized intracerebral infusions, we showed that the basolateral amygdala is a primary locus of action of systemically administered DCS. Thus, intrabasolateral amygdala DCS potentiated both the extinction and the reconsolidation of fear conditioning, depending on the length of the extinction/memory reactivation session. Therefore, memory reconsolidation can be both disrupted and enhanced, and extinction can be both potentiated and impaired, either to reduce or increase conditioned fear. These results have important implications for the use of reconsolidation blockade and potentiation of extinction as treatment strategies for maladaptive memory disorders.
Targeted Deletion of a SingleSca8Ataxia Locus Allele in Mice Causes Abnormal Gait, Progressive Loss of Motor Coordination, and Purkinje Cell Dendritic Deficits
Authors: He Yungui , Zu Tao , Benzow Kellie A. , Orr Harry T. , Clark H. Brent , Koob Michael D.
Published: September 2006

Spinocerebellar ataxia type 8 (SCA8) patients typically have a slowly progressive, adult-onset ataxia. SCA8 is dominantly inherited and is caused by large CTG repeat expansions in the untranslated antisense RNA of theKelch-like 1 gene(KLHL1), but the molecular mechanism through which this expansion leads to disease is still unknown. To more fully characterize the underlying molecular mechanisms involved in SCA8, we developed a mouse model in whichKlhl1is deleted in either all tissues or is deleted specifically in Purkinje cells only. We found that mice that are either homozygous or heterozygous for theKlhl1deletion have significant gait abnormalities at an early age and develop a significant loss of motor coordination by 24 weeks of age. This loss progresses more rapidly in homozygous knock-outs. Mice withKlhl1specifically deleted in only Purkinje cells had a loss of motor coordination that was almost identical to the total-tissue deletion mice. Finally, we found significant Purkinje cell dendritic deficits, as measured by the thickness of the molecular layer, in all mice in whichKlhl1was deleted (both total and Purkinje cell-specific deletions) and an intermediate reduction in molecular layer thickness in mice with reduced levels of Klhl1 expression (heterozygous deletions). The results from this mouse model show that even a partial loss of Klhl1 function leads to degeneration of Purkinje cell function and indicates that loss of KLHL1 activity is likely to play a significant part in the underlying pathophysiology of SCA8.
Modulation of Gq-Protein-Coupled Inositol Trisphosphate and Ca2+Signaling by the Membrane Potential
Authors: Billups Daniela , Billups Brian , Challiss R. A. John , Nahorski Stefan R.
Published: September 2006

Gq-protein-coupled receptors (GqPCRs) are widely distributed in the CNS and play fundamental roles in a variety of neuronal processes. Their activation results in phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis and Ca2+release from intracellular stores via the phospholipase C (PLC)–inositol 1,4,5-trisphosphate (IP3) signaling pathway. Because early GqPCR signaling events occur at the plasma membrane of neurons, they might be influenced by changes in membrane potential. In this study, we use combined patch-clamp and imaging methods to investigate whether membrane potential changes can modulate GqPCR signaling in neurons. Our results demonstrate that GqPCR signaling in the human neuronal cell line SH-SY5Y and in rat cerebellar granule neurons is directly sensitive to changes in membrane potential, even in the absence of extracellular Ca2+. Depolarization has a bidirectional effect on GqPCR signaling, potentiating thapsigargin-sensitive Ca2+responses to muscarinic receptor activation but attenuating those mediated by bradykinin receptors. The depolarization-evoked potentiation of the muscarinic signaling is graded, bipolar, non-inactivating, and with no apparent upper limit, ruling out traditional voltage-gated ion channels as the primary voltage sensors. Flash photolysis of caged IP3/GPIP2(glycerophosphoryl-myo-inositol 4,5-bisphosphate) places the voltage sensor before the level of the Ca2+store, and measurements using the fluorescent bioprobe eGFP–PHPLCδ(enhanced green fluorescent protein–pleckstrin homology domain–PLCδ) directly demonstrate that voltage affects muscarinic signaling at the level of the IP3production pathway. The sensitivity of GqPCR IP3signaling in neurons to voltage itself may represent a fundamental mechanism by which ionotropic signals can shape metabotropic receptor activity in neurons and influence processes such as synaptic plasticity in which the detection of coincident signals is crucial.