bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug information resources at community pharmacies in Amman, Jordan
Authors: Wazaify Mayyada , Maani Mais , Ball Douglas
Published: October 2010

Objectives

The aim of this study was to investigate the drug information resources available in community pharmacies in Amman, Jordan.

Methods

A total of 156 private community (retail) pharmacies in different parts of Amman, the capital of Jordan, were recruited by personal contact. Pharmacists at the sample pharmacies completed a self-administered questionnaire that consisted of two sections. The first section elicited the drug information resources available in their pharmacies. The second section presented five mock medicines information scenarios and asked respondents to identify the most suitable information resource to be used from a given list. Answers then were coded and entered into SPSS for Windows for statistical analysis.

Key findings

All pharmacies had at least one reference book, but most were outdated. The Monthly Index of Medical Specialties (MIMS) was the most commonly found (n =101; 64.7%), and 40.4% (n = 63) had internet access. Only 19.2% (n = 30) of the respondents reported getting medicines information directly from pharmaceutical companies, usually through pharmaceutical representatives. Most pharmacists could identify appropriate information resources for drug dosing and side effects but did not fare well for medicine identification, drug interactions and primary research evidence.

Conclusions

The quality of drug information resources in private community pharmacies in Amman is far from optimal. This will affect the quality of information provided to patients and prescribers and have an adverse effect on the role that pharmacists can play in the health system in Jordan.
Clinical governance issues arising from the Mental Health and Learning Disabilities Pharmacy Workforce Survey (England) 2006
Authors: Taylor Denise A , Sutton Jane
Published: October 2010

Objectives

In the last 10 years changes in the Government's agenda for medicines management and improved patient safety have resulted in unprecedented calls for the provision of mental health pharmacy services. This has not been reflected in pharmacy workforce planning or budgets. We aim to ascertain pharmacy staffing levels in Mental Health Trusts and whether supply of medicines and delivery of clinical pharmacy services are at an appropriate level.

Methods

All Chief/Lead Pharmacists for Mental Health Trusts in England were sent a questionnaire. Follow-up was done twice by e-mail at 2-week intervals.

Key findings

The response rate was 48% (n = 38 usable questionnaires), and results showed that many Trusts were providing little more than a basic supply service. Pharmacy services equating with risk-management were often provided on an ad hoc basis. Staffing levels were reported as insufficient, with mainly part-time staff. A basic pharmacy ward visit was only offered by 60.8% (n = 14/23; not all participants answered all questions) of respondents, at the 100% level (i.e. a daily service). Six of 31 respondents receiving pharmaceutical services from external organisations reported no formal signed agreements with the external provider.

Conclusions

The increasing emphasis on community-based mental health teams, while still retaining on-site provision and Department of Health initiatives to improve patient safety via medicines management, has placed great strain on mental health pharmacy services. The resultant pharmaceutical input from external drivers is not reflected in appropriate pharmacy staffing levels. The results raise some serious governance issues.
Development of protocols for the provision of headache and back-pain treatments in Maltese community pharmacies
Authors: Vella Elaine , Azzopardi Lilian M , Zarb-Adami Maurice , Serracino-Inglott Anthony
Published: October 2010

Objective

The purpose of this study was to draw up two protocols designed to help Maltese pharmacists care for consumers seeking treatment for headache and back pain and to subsequently use the protocols to assess pharmacists' management of the named conditions.

Method

The setting was a sample of 10 of the 207 community pharmacies in Malta. Two flow-chart protocols for headache and back-pain management were developed from various reference sources. The protocols were first tested in a community pharmacy for practicality and applicability in a pilot study. In nine other pharmacies chosen at random the pharmacists' manner of addressing 10 headache and 10 back-pain cases in each pharmacy was compared with that recommended in the protocols. Consumers who visited the pharmacy to fill a prescription, to purchase a named product or for advice on how to deal with symptoms were included in the study.

Key findings

Of the 212 pharmacist interventions assessed, cases where pharmacists responded to symptoms were managed with the highest average compliance (57%) whereas cases in which the consumer asked for a product by name were managed with an average compliance with the protocols of 46%. Cases in which consumers presented at the pharmacy with a prescription were managed with an average compliance of 55%.

Conclusions

Protocols may be used as a means of measuring the impact of the intervention of community pharmacists in patient care. The findings suggest a lack of advice given to consumers presenting at the pharmacy to request a named product.
Community pharmacy contribution to weight management: identifying opportunities
Authors: Janet Krska , Lovelady Claire , Connolly Deborah , Parmar Shaun , Davies Michael J
Published: October 2010

Objectives

The aim of the study was to determine the public's views on weight-management services, including pharmacies as a potential venue, and the extent of current pharmacy involvement in weight management.

Methods

Two questionnaires were developed for face-to-face interview in one Primary Care Trust area: one for the general public and one for community pharmacists.

Key findings

Interviews were conducted with 177 members of the public, 75% of whom had tried to lose weight. More had used over-the-counter weight-loss products than prescribed medicines. There was greater awareness of commercial weight-management clinics than of NHS-led initiatives. Leisure centres were the preferred locations for weight-management clinics, with dieticians as the preferred staff. Pharmacies and pharmacists were not favoured as sources of advice on weight management. The questionnaire was completed by 49 community pharmacists (75%). All except one dispensed prescriptions for weight loss and 38 supplied over-the-counter weight-loss products. For both, estimated supply frequency increased with increasing deprivation of the pharmacy's location. Eight pharmacies provided a commercial weight-loss programme and more than half had weighing scales.

Conclusions

Opportunities exist for extending NHS-led weight-management services from community pharmacies, but further research is required into the public's expectations of services to support an increase in awareness and acceptance.
‘It's showed me the skills that he has’: pharmacists' and mentors' views on pharmacist supplementary prescribing
Authors: Lloyd Fran , Parsons Carole , Hughes Carmel M
Published: October 2010

Objectives

Supplementary prescribing has seen pharmacists assume greater responsibility for prescribing in collaboration with doctors. This study explored the context and experiences, in relation to the practice of supplementary prescribing, of pharmacists and physicians (who acted as their training mentors) at least 12 months after pharmacists had qualified as supplementary prescribers.

Methods

The setting was primary and secondary healthcare sectors in Northern Ireland. Pharmacists and mentors who had participated in a pre-training study were invited to take part. All pharmacists (n= 47) were invited to participate in focus groups, while mentors (n= 35) were asked to participate in face-to-face semi-structured interviews. The research took place between May 2005 and September 2007. All discussions and interviews were audiotaped, transcribed and analysed using constant comparison.

Key findings

Nine pharmacist focus groups were convened (number per group ranging from three to six; total n= 40) and 31 semi-structured interviews with mentors were conducted. The six main themes that emerged were optimal practice setting, professional progression for prescribing pharmacists, outcomes for prescribing pharmacists, mentors and patients, relationships, barriers to implementation and the future of pharmacist prescribing. Where practised, pharmacist prescribing had been accepted, worked best for chronic disease management, was perceived to have reduced doctors' workload and improved continuity of care for patients. However, three-quarters of pharmacists qualified to practise as supplementary prescribers were not actively prescribing, largely due to logistical and organisational barriers rather than inter-professional tensions. Independent prescribing was seen as contentious by mentors, particularly because of the diagnostic element.

Conclusions

Supplementary prescribing has been successful where it has been implemented but a number of barriers remain which are preventing the wider acceptance of this practice innovation.
Hybrid Cosmologies in Mesoamerica: A Reevaluation of theYax Cheel Cab, a Maya World Tree
Authors: Knowlton Timothy W. , Vail Gabrielle
Published: October 2010

During his visit to Nojpeten in 1696, Fray Andrés de Avendaño reported observing the Itzá Maya worshipping a stone column called yax cheel cab (the first tree of the world). Though claiming to recognize the yax cheel cab from depictions in pre-Hispanic Maya codices, Avendaño notes that the Itzá “want it to be understood that they give homage to it because this is the tree of whose fruit our first father Adam ate.” As no known pre-Hispanic source uses the term yax cheel cab, how are we to interpret Avendaño's report? Based on iconographic as well as primary textual sources from the Postclassic through Colonial periods written in Maya and Spanish, we document the transformation of pre-Hispanic Maya tree symbolism in response to contemporaneous European Christian myth and cosmology. We argue that, though having roots in pre-Hispanic iconography and practices millennia deep, the yax cheel cab known from the documentary record is a colonial amalgam, a world tree at the center of a hybrid cosmology emerging over the course of over a century and a half from processes of direct as well as indirect dialogue between Mayas and Europeans.
A mouse model for an erythropoietin-deficiency anemia
Authors: Zeigler Brandon M. , Vajdos Janis , Qin Wenning , Loverro Linda , Niss Knut
Published: October 2010

In mammals, the production of red blood cells is tightly regulated by the growth factor erythropoietin (EPO). Mice lacking a functional Epo gene are embryonic lethal, and studying erythropoiesis in EPO-deficient adult animals has therefore been limited. In order to obtain a preclinical model for an EPO-deficient anemia, we developed a mouse in which Epo can be silenced by Cre recombinase. After induction of Cre activity, EpoKO/flox mice experience a significant reduction of serum EPO levels and consequently develop a chronic, normocytic and normochromic anemia. Furthermore, compared with wild-type mice, Epo expression in EpoKO/flox mice is dramatically reduced in the kidney, and expression of a well-known target gene of EPO signaling, Bcl2l1, is reduced in the bone marrow. These observations are similar to the clinical display of anemia in patients with chronic kidney disease. In addition, during stress-induced erythropoiesis these mice display the same recovery rate as their heterozygous counterparts. Taken together, these results demonstrate that this model can serve as a valuable preclinical model for the anemia of EPO deficiency, as well as a tool for the study of stress-induced erythropoiesis during limiting conditions of EPO.
Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway
Authors: Blackiston Douglas , Adams Dany S. , Lemire Joan M. , Lobikin Maria , Levin Michael
Published: October 2010

Understanding the mechanisms that coordinate stem cell behavior within the host is a high priority for developmental biology, regenerative medicine and oncology. Endogenous ion currents and voltage gradients function alongside biochemical cues during pattern formation and tumor suppression, but it is not known whether bioelectrical signals are involved in the control of stem cell progeny in vivo. We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neural crest’s environment influences its function in vivo, we manipulated the activity of the native glycine receptor chloride channel (GlyCl). Molecular-genetic depolarization of a sparse, widely distributed set of GlyCl-expressing cells non-cell-autonomously induces a neoplastic-like phenotype in melanocytes: they overproliferate, acquire an arborized cell shape and migrate inappropriately, colonizing numerous tissues in a metalloprotease-dependent fashion. A similar effect was observed in human melanocytes in culture. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin (5-HT). These data reveal GlyCl as a molecular marker of a sparse and heretofore unknown cell population with the ability to specifically instruct neural crest derivatives, suggest transmembrane potential as a tractable signaling modality by which somatic cells can control stem cell behavior at considerable distance, identify a new biophysical aspect of the environment that confers a neoplastic-like phenotype upon stem cell progeny, reveal a pre-neural role for serotonin and its transporter, and suggest a novel strategy for manipulating stem cell behavior.
How moderate changes in Akt T-loop phosphorylation impact on tumorigenesis and insulin resistance
Authors: Wullschleger Stephan , Sakamoto Kei , Johnstone Lana , Duce Suzanne , Fleming Stewart , Alessi Dario R.
Published: October 2010

The Akt signalling pathway plays vital roles in controlling cellular responses to insulin as well as in proliferation and survival. Inhibition of Akt signalling leads to insulin resistance and type 2 diabetes, whereas hyperactivation of Akt promotes tumorigenesis. In this study, we investigate how modest changes in the activity of the Akt signalling pathway, to an extent that might be achieved by drug treatment, would impact on insulin resistance and tumorigenesis. Using insulin-resistant PDK1K465E/K465E PH domain knock-in mice, we found that introducing the PTEN+/− mutation to slightly stimulate Akt restored normal insulin sensitivity. Introducing the PDK1K465E/K465E PH domain knock-in mutation into cancer-prone PTEN+/− mice, lowered Akt activity only by about 50%, but led to a delay in tumour onset of ∼4 months in a broad range of tumours. This was also accompanied by slower growth of B cell follicular lymphomas, as monitored by magnetic resonance imaging. Our findings imply that signal transduction inhibitors that lead to a modest reduction in Akt activity would not only delay onset of tumours possessing elevated phosphoinositide 3-kinase pathway activity but would also reduce the growth rate of developed tumours.
Synthesis and Solution Properties of a Novel Thermosensitive Poly(benzyl ether) Dendron with Oligoethyleneoxy Chains at the Periphery
Authors: Xu Li , Shao Lidong , Chen Lin , Hu Minqi , Bi Yunmei
Published: October 2010

A novel thermosensitive second-generation poly(benzyl ether) dendron with oligoethyleneoxy chains at the periphery was synthesized. Its cloud point (CP) decreased with an increasing concentration over a range of concentrations from 9 to 60 wt %. Fluorescent spectroscopy and AFM studies revealed that the dendron self-assembled into the spherical micelles, about 50 nm in diameter, at concentration over its CMC in an aqueous solution. This dendron has a potential as smart thermosensitive materials.
Removal of Perchlorate and Tetrafluoroborate Anions from Aqueous Solutions by a Self-assembled Cu(II) Molecular Capsule System Using Water-insoluble Cu(II) Source
Authors: Yamaguchi Maiko , Hirakawa Takeshi , Nishina Naoko , Kondo Mitsuru , Aoki Hiromi , Okuda Emi , Zhang Liang
Published: October 2010

A self-assembled Cu–bitb molecular capsule system using basic copper(II) carbonate as a Cu2+ source removed perchlorate and tetrafluoroborate anions from aqueous solutions without contamination by Cu(II) ion.
Polystyrene-anchored Palladium(II) Complex as an Efficient and Reusable Catalyst for Suzuki Cross-coupling Reaction in Water Medium
Authors: Islam Manirul , Mondal Paramita , Tuhina Kazi , Hossain Dildar , Roy Anupam Singha
Published: October 2010

A new polystyrene-anchored palladium(II) catalyst has been prepared and characterized by conventional spectroscopic methods and elemental analyses. The catalyst was found to be highly effective for the Suzuki cross-coupling reactions of aryl halides with arylboronic acid in water medium under phosphine-free reaction conditions. The optimal reaction conditions of the coupling were determined. The present heterogeneous Pd(II) catalyst was reusable as well as air-stable to allow easy use.
Does Water Liquid Phase Intrude into Hydrophobic Nanospaces of Alkyl-grafted Mesoporous Silica Immersed in Water? Detection by 13C CP-MAS NMR
Authors: Inumaru Kei , Kakii Shintaro , Yoshida Hiroto , Yamanaka Shoji
Published: October 2010

In situ 13C CP-MAS NMR measurements enabled for the first time detection of the presence and absence of water liquid phase in nanospaces of alkyl-grafted mesoporous silicas through the signals of alkyl chains, when the materials were immersed in water. It was revealed that n-octyl-grafted mesoporous silica excluded liquid water from the hydrophobic nanospaces at least in an hour time scale while liquid water penetrated into n-pentyl-grafted material much faster. This is important for understanding the adsorbents in the working states in water.
Near-infrared Fluorescence Enhancement by Regularly Arranged Gold Nanoblocks
Authors: Ito Fuyuki , Ohta Ryuichi , Yokota Yukie , Ueno Kosei , Misawa Hiroaki , Nagamura Toshihiko
Published: October 2010

Fluorescence intensity of near infrared dyes immobilized in hydrophobic DNA thin film spin-coated on glass substrates with regularly arranged gold (Au) nanoblocks was about 2.5 times larger than that without Au nanoblocks, strongly suggesting the fluorescence intensity was enhanced by increased electric field intensity of excitation light due to local plasmon resonance of Au nanoblocks.
The telecardiology revolution: improving the management of cardiac disease in primary care
Authors: Backman Warren , Bendel Daniel , Rakhit Roby
Published: October 2010

Summary

Telecardiology allows for the remote specialist interpretation of electrocardiographic recordings via telephone transmission. It has the potential to change the way cardiac care is being delivered in the primary care setting. This review discusses the current status of cardiac care in the community, and highlights how telecardiology can help support general practitioners in the diagnosis and management of acute and chronic cardiac disease, as well as provide the potential for screening opportunities in particular patients at risk. Also reviewed is the success of recent trials of a telecardiology service in the north west of England. Thanks to developments in technology and ever decreasing costs, telecardiology has the potential to save time, money and lives. Telecardiology, it would seem, is set to revolutionize cardiac care in the community, making savings and bridging the gap between primary and secondary care.
Effects of Ovariectomy and Estrogen Replacement Therapy on Visceral Adipose Tissue and Serum Adiponectin Levels in Rats
Authors: Babaei Parvin , Mehdizadeh Rahimeh , Ansar Malek Moein , Damirchi Arsalan
Published: October 2010

Background.

Excess visceral adipose tissue accumulation after menopause is closely associated with decreased insulin sensitivity and adiponectin levels.

Objective.

The purpose of this study was to determine the effect of ovariectomy and estrogen replacement on visceral fat and serum adiponectin levels in ovariectomized (OVX) rats.

Method.

Forty 11-week-old female Wistar rats were divided into the four following groups ( n = 10 rats per group): sham-operated control (SHAM); sedentary OVX (OVX-SED); OVX with estrogen replacement (OVX-ER); and OVX with sesame oil treatment (OVX-C). Rats in OVX-ER and OVX-C groups received 17β-estradiol valerate (30 μg/kg, subcutaneously) and sesame oil as vehicle, five days a week, respectively. All animals were sacrificed after eight weeks of intervention.

Results

Ovariectomy after eight weeks increased body weight and visceral fat ( P < 0.05) in OVX-SED and OVX-C groups compared with SHAM rats with no change in plasma adiponectin levels. Estrogen replacement in OVX animals decreased body weight (13.4%, P < 0.05) and visceral fat (10.4%). Although they were not statistically significant, adiponectin, insulin sensitivity and lipid profile of OVX rats were ameliorated with estrogen treatment.

Conclusion.

We conclude that ovarian hormone withdrawal leads to higher body weight and visceral adipose tissue in rats, but surprisingly does not change adiponectin levels. Although a substantial decrease in body weight was achieved by estrogen replacement therapy in OVX animals, the beneficial metabolic effects of weight loss seems to be only mechanical, having a tendency to improve insulin sensitivity without elevating adiponectin production.
Vulval Disease in the Postmenopausal Patient: A Guide to Current Management
Authors: Kingston Abigail
Published: October 2010

In spite of overwhelming evidence that vulvovaginal symptoms plague up to 46% of menopausal and perimenopausal women, and that there persists a reluctance to seek help among patients, adequate vulval and sexual histories are still woefully rare in general gynaecology clinics. This review aims to present the key points of an effective vulval history and an overview of the accepted current management of vulval disease postmenopause, in order that our patients feel encouraged to present with their problems.
Effect of Delayed Formalin Fixation on Estrogen and Progesterone Receptors in Breast Cancer
Authors: Qiu Jingxin , Kulkarni Swati , Chandrasekhar Rameela , Rees Mark , Hyde Kathryn , Wilding Gregory , Tan Dongfeng , Khoury Thaer
Published: October 2010

We previously reported that delayed formalin fixation (DFF) has a negative effect on immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR), and HER2. The primary aim of the study was to determine if DFF affected commonly used clones of the ER and PR differentially. The specific clones evaluated were ER clones 1D5, 6F11, and SP1 and PR clones 16, 1E2, and PgR636. Ten breast cancer cases were dissected and fixed at different times (0, 10, and 30 minutes; 1, 2, 4, and 8 hours; and overnight) and were then stained with anti-ER and anti-PR antibodies. The mean Q score for ER started to decline at 2 to 4 hours for clones 1D5 and 6F11 and at 1 hour for SP1. SP1 was superior to 1D5 at the 8-hour mark (P = .03). The Q score for PR started to decline at 1 hour for clones PgR636 and 16 and 4 to 8 hours for 1E2 (P = .03). Based on our findings, it appears that regardless of the antibody clones evaluated, DFF has a negative effect on hormone receptors.
Induction of CYP3A4 by Vinblastine: Role of the Nuclear Receptor NR1I2
Authors: Smith Nicola F , Mani Sridhar , Schuetz Erin G , Yasuda Kazuto , Sissung Tristan M , Bates Susan E , Figg William D , Sparreboom Alex
Published: October 2010

Background:

Several microtubule targeting agents are capable of inducing CYP3A4 via activation of the pregnane X receptor (PXR; NR1I2).

Objective:

To evaluate the CYP3A4 induction potential of vinblastine both clinically and in vitro and determine the involvement of the nuclear receptors NR1I2 and the constitutive androstane receptor (NR1I3).

Methods:

Midazolam pharmacokinetics were evaluated in 6 patients who were enrolled in a Phase 1/2 study of infusional vinblastine given in combination with the ABCB1 (P-glycoprotein) antagonist valspodar (PSC 833) and received the CYP3A4 phenotyping probo midazolam on more than 1 occasion. Genotyping was conducted in CYP3A4, CYP3A5, and ABCB1 to rule out potential pharmacogenetic influences. Clinical data were followed-up by Western blotting and reporter assays in HepG2 and NIH3T3 cells treated with vinbfastine over a dose range of 150-4800 ng/mL for 48 hours.

Results:

In 6 patients with cancer, vinblastine increased the median (95% CI) clearance of the CYP3A4 phenotyping probe midazolam from 21.7 L/h (12.6 to 28.1) to 32.3 L/h (17.3 to 53.9) (p = 0.0156, Wilcoxon signed-rank test). No obvious effect of polymorphisms in CYP3A4, CYP3A5, and ABCB1 on midazolam clearance was observed. In vitro, vinblastine induced CYP3A4 protein. Furthermore, cell-based reporter gene assays using transiently transfected HepG2 and NIH3T3 cells indicated that vinblastine (150-4800 ng/mL) weakly activated human and mouse full-length NR1I2, but had no influence on NR1I3.

Conclusions:

Collectively, these findings suggest that vinblastine is able to induce CYP3A4, at least in part, via an NR1I2-dependent mechanism, and thus has the potential to facilitate its own elimination and cause interactions with other CYP3A4 substrates.
Standardizing plasma protein measurements worldwide: a challenging enterprise
Authors: Merlini Giampaolo , Blirup-Jensen Søren , Johnson A. Myron , Sheldon Joanna , Zegers Ingrid
Published: October 2010

The need for harmonizing laboratory results is particularly intense in the field of quantitative protein assays in consideration of the clinical impact of specific protein measurements and their relevance in monitoring disease. We report the efforts made by the Committee on Plasma Proteins of the IFCC Scientific Division to achieve worldwide comparability in plasma protein results. We focus on the production of reference materials and the methods applied throughout their production process. Particularly, the recent characterization of ERM-DA470k/IFCC and ERM-DA472/IFCC has demonstrated that it is possible to reproduce the earlier established procedures and thereby maintain standardization. Plasma protein reference materials have had a substantial impact in improving the harmonization of patient protein results that should translate into better patient care.

Clin Chem Lab Med 2010;48:1567–75.
Relationship of hepatic steatosis and alanine aminotransferase with coronary calcification
Authors: Jung Dong-Hyuk , Lee Yong-Jae , Ahn Hong-Yup , Shim Jae-Yong , Lee Hye-Ree
Published: October 2010

Background: It has been observed that hepatic steatosis is related to an increased risk of cardiovascular disease (CVD). Alanine aminotransferase (ALT), an indicator of the severity of hepatic steatosis is also associated with CVD. This study focused on the relationship between hepatic steatosis and ALT with coronary calcification.

Methods: We performed a cross-sectional study to examine the association between hepatic steatosis and serum ALT with coronary calcification in 1218 subjects (772 men, 446 women; ages 30–75 years). We evaluated hepatic steatosis and ALT as categorical variables, and constructed four groups (reference group; only with hepatic steatosis; only with ALT >30 U/L; with both hepatic steatosis and ALT >30 U/L), which did not overlap. Multi-detected row computed tomography (MDCT) was used to measure coronary calcium score.

Results: The adjusted ORs (95% CIs) for coronary calcification in the four groups were 1.00 (reference), 1.24 (0.68–2.26), 1.82 (0.78–4.23), and 2.12 (1.08–4.20) after adjusting for confounding variables. In addition, an increase in serum ALT activity of 10 U/L was associated with an increased risk of coronary atherosclerosis.

Conclusions: In summary, patients with both hepatic steatosis and increases in ALT are associated with coronary calcification as a marker of coronary atherosclerosis determined by MDCT. This finding suggested that subjects with both hepatic steatosis and increased ALT should be considered for further evaluation of coronary atherosclerosis.

Clin Chem Lab Med 2010;48:1829–34.
Investigation of the relationship between apolipoprotein E gene polymorphisms and hepatitis B virus infection in northern China
Authors: Yin Zhinong , Xiong Chenling , Wang Yongguang , Zhou Xin , Yan Sheng-Kai
Published: October 2010

Background: Certain genetic polymorphisms can lead to differences in immunity function, resulting in different clinical outcomes for hepatitis B virus (HBV) patients. The aim of this study was to investigate the association between apolipoprotein E (ApoE) gene polymorphisms and HBV infection status in northern Chinese individuals.

Methods: Genomic DNA was extracted using an improved sodium iodide (NaI) method from the peripheral blood of 270 patients with hepatitis B and 112 healthy controls. Multiplex Amplification Refractory Mutation System (Multi-ARMS) was performed to analyze ApoE gene poly-morphisms with three alleles (ɛ2, ɛ3, ɛ4) in patients and controls. A chemiluminescence assay was used to detect serological markers for hepatitis B infection status.

Results: An improved PCR system for the detection of ApoE gene polymorphisms was established successfully. The frequency of the ɛ2 allele in patients with HBV infection was higher than that of normal controls (p<0.05). The ɛ2 allele, compared with the ɛ3 and ɛ4 alleles, showed positive correlation with the different HBV infection models [odds ratio (OR)=1.735, 95% confidence interval (CI): 1.509–1.999, p<0.01; OR=1.768, 95% CI: 1.554–2.011, p<0.01]. The OR for the ApoE ɛ2 allele was 1.503 in a multivariate unconditional logistic regression model (OR=1.503, 95% CI: 1.212–1.754, p<0.01).

Conclusions: Our results indicated that the ApoE gene poly-morphism was associated with HBV infection, and the ɛ2 allele showed positive correlation with HBV infection in northern China.

Clin Chem Lab Med 2010;48:1803–7.
Harmonization of free thyroid hormone tests: a mission impossible?
Authors: Iervasi Giorgio , Clerico Aldo
Published: October 2010

The aim of in vitro testing of thyroid function is to accurately reflect the in vivo activity of key analytes, such as thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4). For these key laboratory parameters, it is highly desirable that assay results are interpretable in relation to consensus reference intervals, which should not vary depending on the choice of method used for measurement. The IFCC Working Group for Standardization of Thyroid Function Tests has recently published three reports on standardization of thyroid function tests in order to resolve the issues concerning method performance and quality specifications, as well as to meet clinical requirements. The aim of the present article is to discuss the relevant contribution of the IFCC Working Group study towards the standardization of free triiodothyronine (FT3) and free thyroxine (FT4) assays. The most important result obtained by this study is the establishment of a reliable candidate reference procedure and some commutable reference materials. These reference materials, including sera collected from blood donors, were measured by the gold standard method, and by several immunoassay methods and two equilibrium dialysis procedures in order to obtain a recalibration of test results. The recalibration on average eliminated assay-specific biases with respect to reference method values. However, sample-related effects remained among the immunoassay methods tested. Although these findings are clearly important, they should only be considered a start towards harmonization of patients test results. In conclusion, further studies are necessary to answer the question of whether standardization and harmonization of the FT3 and FT4 test is an impossible mission (or not).
Serum paraoxonase 1 (PON1) lactonase activity is lower in end-stage renal disease patients than in healthy control subjects and increases after hemodialysis
Authors: Gugliucci Alejandro , Kinugasa Eriko , Kotani Kazuhiko , Caccavello Russell , Kimura Satoshi
Published: October 2010

Background:The mechanism of paraoxonase 1 (PON1) atheroprotective remains elusive. The lactonizing/lactonase activity of PON1 is gaining favor as the most significant in physiology.

Methods:We studied 42 end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) and 49 control subjects. We measured PON1 lactonase, arylesterase and triesterase activities by kinetic methods.

Results:Serum lactonase activity was 11% lower in ESRD patients (p<0.0001) and did not correlate with high-density lipoprotein (HDL) cholesterol when controlling for confounders. Lactonase activity was significantly higher after dialysis. Using a repeated measure-ANOVA adjusted for the confounders (age, gender, total cholesterol, triglyceride and HDL cholesterol) we show that the changes in lactonase after dialysis were significant (p<0.0001). HD increases lactonase activity to levels indistinguishable from those of control subjects. In simple linear regression analyses we showed a significant inverse correlation between changes in lactonase and those of creatinine by dialysis (r=–0.339, p=0.028).

Conclusions:ESRD patients maybe more susceptible to lipid peroxidation and to protein homocysteinylation than healthy subjects due to the decreased activity of lactonase. A lower serum lactonase activity would be coupled with delayed catabolism of oxidized phospholipids in low-density lipoprotein and oxidized macrophages, and with greater protein homocysteinylation, accelerating atherogenesis. One mechanism for lower lactonase activity in ESRD patients may be inhibition by uremic toxins and oxidative stress. The pathophysiology of reduced lactonase activity in uremia and the beneficial effects of HD need further investigation.
Use of serum free light chain analysis and urine protein electrophoresis for detection of monoclonal gammopathies
Authors: Holding Stephen , Spradbery Dorothy , Hoole Robin , Wilmot Rachel , Shields Michael L. , Levoguer Alison M. , Doré Philip C.
Published: October 2010

Background: Serum free light chain (FLC) analysis is used in the prognostic assessment and monitoring of patients with monoclonal gammopathies (MG). Its use in detection of MG is less widespread despite good sensitivity for diseases poorly detected by serum protein electrophoresis (SPE), e.g., FLC disease and AL amyloidosis. FLC analysis may facilitate earlier diagnosis in these diseases. However, if replacing urine protein electrophoresis (UPE) in an initial screening algorithm, this must be balanced against any loss of detection of Bence Jones proteinuria (BJP).

Methods: We assessed the effect of replacing UPE with FLC. Sensitivity of FLC for BJP was assessed in 126 clinical cases where UPE and FLC analyses were performed. Impact on disease detection was assessed from 753 patient sera tested by SPE and FLC and 128 patients matched associated urine samples.

Results: Sensitivity of FLC for BJP was 98%. Use of FLC in routine testing increased the number of MG detected by 7%.

Conclusions: Using FLC alongside or in place of UPE can give clinical benefit through earlier diagnosis and hence treatment earlier in the patients' disease.
Testosterone is an independent determinant of bone mineral density in men with type 2 diabetes mellitus
Authors: Vasilkova Olga , Mokhort Tatiana , Sanec Igor , Sharshakova Tamara , Hayashida Naomi , Takamura Noboru
Published: October 2010

Background: Although many reports have elucidated pathophysiological characteristics of abnormal bone metabolism in patients with type 2 diabetes mellitus (DT2), determinants of bone mineral density (BMD) in patients with DT2 are still controversial.

Methods: We examined 168 Belarussian men 45–60 years of age. Plasma total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglycerides, hemoglobin A1c (HbA1c), immunoreactive insulin, and C-reactive protein concentrations were assessed. BMD was measured using dual energy X-ray densitometry of the lumbar spine (L1–L4). Total testosterone (TT) and sex hormone-binding globulin were measured, and free testosterone (FT) was calculated.

Results: Using univariate linear regression analysis, BMD of the lumbar spine was significantly correlated with FT (r=0.32, p<0.01) and TT (r=0.36, p<0.01). Using multiple linear regression analysis adjusted for confounding factors, BMD was significantly correlated with TT (β=0.23, p<0.001) and TC (β=–0.029, p=0.005). Age (β=0.005, p=0.071), body mass index (β=0.005, p=0.053), HbA1c (β=–0.002, p=0.72) and duration of diabetes (β=0.001, p=0.62) were not significantly correlated with BMD.

Conclusions: Our data indicate that androgens are independent determinants of BMD in male patients with DT2.
On regularization method for numerical inversion of the Laplace transforms computable at any point on the real axis
Authors: Kryzhniy V. V.
Published: October 2010

The regularized inversion of real-valued Laplace transforms computable at any point on the real axis is discussed from the point of view of practical calculations. New criterion for selection of free parameters is suggested. Selection of optimal values of free parameters allows to improve the numerical results significantly.

The effectiveness of the proposed criterion is demonstrated with examples. Method can be used in conjunction with other numerical methods for problems where the inverse Laplace transform is expected to tend to a monotonic function.
Decision Time, Slow Inhibition, and Theta Rhythm
Authors: Smerieri Anteo , Rolls Edmund T. , Feng Jianfeng
Published: October 2010

In this paper, we examine decision making in a spiking neuronal network and show that longer time constants for the inhibitory neurons can decrease the reaction times and produce theta rhythm. We analyze the mechanism and find that the spontaneous firing rate before the decision cues are applied can drift, and thereby influence the speed of the reaction time when the decision cues are applied. The drift of the firing rate in the population that will win the competition is larger if the time constant of the inhibitory interneurons is increased from 10 to 33 ms, and even larger if there are two populations of inhibitory neurons with time constants of 10 and 100 ms. Of considerable interest is that the decision that will be made can be influenced by the noise-influenced drift of the spontaneous firing rate over many seconds before the decision cues are applied. The theta rhythm associated with the longer time constant networks mirrors the greater integration in the firing rate drift produced by the recurrent connections over long time periods in the networks with slow inhibition. The mechanism for the effect of slow waves in the theta and delta range on decision times is suggested to be increased neuronal spiking produced by depolarization of the membrane potential on the positive part of the slow waves when the neuron's membrane potential is close to the firing threshold.
Human Immunodeficiency Virus-1 Tat Activates Calpain Proteases via the Ryanodine Receptor to Enhance Surface Dopamine Transporter Levels and Increase Transporter-Specific Uptake andVmax
Authors: Perry Seth W. , Barbieri Justin , Tong Ning , Polesskaya Oksana , Pudasaini Santosh , Stout Angela , Lu Rebecca , Kiebala Michelle , Maggirwar Sanjay B. , Gelbard Harris A.
Published: October 2010

Human immunodeficiency virus-associated neurological disease (HAND) still causes significant morbidity, despite success reducing viral loads with combination antiretroviral therapy. The dopamine (DA) system is particularly vulnerable in HAND. We hypothesize that early, “reversible” DAergic synaptic dysfunction occurs long before DAergic neuron loss. As such, aging human immunodeficiency virus (HIV)-infected individuals may be vulnerable to other age-related neurodegenerative diseases like Parkinson's disease (PD), underscoring the need to understand shared molecular targets in HAND and PD. Previously, we reported that the neurotoxic HIV-1 transactivating factor (Tat) acutely disrupts mitochondrial and endoplasmic reticulum calcium homeostasis via ryanodine receptor (RyR) activation. Here, we further report that Tat disrupts DA transporter (DAT) activity and function, resulting in increased plasma membrane (PM) DAT and increased DATVmax, without changes inKmor total DAT protein. Tat also increases calpain protease activity at the PM, demonstrated by total internal reflection fluorescence microscopy of a cleavable fluorescent calpain substrate. Tat-increased PM DAT and calpain activity are blocked by the RyR antagonists ryanodine and dantrolene, the calpain inhibitor calpastatin, and by a specific inhibitor of GSK-3β. We conclude that Tat activates RyRs via a calcium- and calpain-mediated mechanism that upregulates DAT trafficking to the PM, and is independent of DAT protein synthesis, reinforcing the feasibility of RyR and GSK-3β inhibition as clinical therapeutic approaches for HAND. Finally, we provide key translational relevance for these findings by highlighting published human data of increased DAT levels in striata of HAND patients and by demonstrating similar findings in Tat-expressing transgenic mice.
DrosophilaPQBP1 Regulates Learning Acquisition at Projection Neurons in Aversive Olfactory Conditioning
Authors: Tamura Takuya , Horiuchi Daisuke , Chen Yi-Chung , Sone Masaki , Miyashita Tomoyuki , Saitoe Minoru , Yoshimura Natsue , Chiang Ann-Shyn , Okazawa Hitoshi
Published: October 2010

Polyglutamine tract-binding protein-1 (PQBP1) is involved in the transcription-splicing coupling, and its mutations cause a group of human mental retardation syndromes. We generated a fly model in which theDrosophilahomolog of PQBP1 (dPQBP1) is repressed by insertion ofpiggyBac. In classical odor conditioning, learning acquisition was significantly impaired in homozygouspiggyBac-inserted flies, whereas the following memory retention was completely normal. Mushroom bodies (MBs) and antennal lobes were morphologically normal in dPQBP1-mutant flies. Projection neurons (PNs) were not reduced in number and their fiber connections were not changed, whereas gene expressions including NMDA receptor subunit 1 (NR1) were decreased in PNs. Targeted double-stranded RNA-mediated silencing ofdPQBP1in PNs, but not in MBs, similarly disrupted learning acquisition. NR1 overexpression in PNs rescued the learning disturbance of dPQBP1 mutants. HDAC (histone deacetylase) inhibitors, SAHA (suberoylanilide hydroxamic acid) and PBA (phenylbutyrate), that upregulated NR1 partially rescued the learning disturbance. Collectively, these findings identify dPQBP1 as a novel gene regulating learning acquisition at PNs.
The Contribution of Blood Lactate to Brain Energy Metabolism in Humans Measured by Dynamic13C Nuclear Magnetic Resonance Spectroscopy
Authors: Boumezbeur Fawzi , Petersen Kitt F. , Cline Gary W. , Mason Graeme F. , Behar Kevin L. , Shulman Gerald I. , Rothman Douglas L.
Published: October 2010

To determine whether plasma lactate can be a significant fuel for human brain energy metabolism, infusions of [3-13C]lactate and1H-13C polarization transfer spectroscopy were used to detect the entry and utilization of lactate. During the 2 h infusion study,13C incorporation in the amino acid pools of glutamate and glutamine were measured with a 5 min time resolution. With a plasma concentration ([Lac]P) being in the 0.8–2.8 mmol/L range, the tissue lactate concentration ([Lac]B) was assessed as well as the fractional contribution of lactate to brain energy metabolism (CMRlac). From the measured relationship between unidirectional lactate influx (Vin) and plasma and brain lactate concentrations, lactate transport constants were calculated using a reversible Michaelis–Menten model. The results show that (1) in the physiological range, plasma lactate unidirectional transport (Vin) and concentration in tissue increase close to linearly with the lactate concentration in plasma; (2) the maximum potential contribution of plasma lactate to brain metabolism is 10% under basal plasma lactate conditions of ∼1.0 mmol/L and as much as 60% at supraphysiological plasma lactate concentrations when the transporters are saturated; (3) the half-saturation constantKTis 5.1 ± 2.7 mmol/L andVMAXis 0.40 ± 0.13 μmol · g−1· min−1(68% confidence interval); and (4) the majority of plasma lactate is metabolized in neurons similar to glucose.
Endogenous Dopamine Regulates the Rhythm of Expression of the Clock Protein PER2 in the Rat Dorsal Striatum via Daily Activation of D2Dopamine Receptors
Authors: Hood Suzanne , Cassidy Pamela , Cossette Marie-Pierre , Weigl Yuval , Verwey Michael , Robinson Barry , Stewart Jane , Amir Shimon
Published: October 2010

A role for dopamine (DA) in the regulation of clock genes in the mammalian brain is suggested by evidence that manipulations of DA receptors can alter the expression of some clock genes outside the suprachiasmatic nucleus (SCN), the master circadian clock. The role of endogenous DA in the regulation of clock gene expression is unknown. Here, we demonstrate a direct relationship between extracellular DA levels and the rhythm of expression of the clock protein PERIOD2 (PER2) in the dorsal striatum of the male Wistar rat. Specifically, we show that the peak of the daily rhythm of extracellular DA in the dorsal striatum precedes the peak of PER2 by ∼6 h and that depletion of striatal DA by 6-hydroxydopamine or α-methyl-para-tyrosine or blockade of D2DA receptors by raclopride blunts the rhythm of striatal PER2. Furthermore, timed daily activation of D2DA receptors, but not D1DA receptors, restores and entrains the PER2 rhythm in the DA-depleted striatum. None of these manipulations had any effect on the PER2 rhythm in the SCN. Our findings are consistent with the idea that the rhythm of expression of PER2 in the dorsal striatum depends on daily dopaminergic activation of D2DA receptors. These observations may have implications for circadian abnormalities seen in Parkinson's disease.
Learning Alters the Tuning of Functional Magnetic Resonance Imaging Patterns for Visual Forms
Authors: Zhang Jiaxiang , Meeson Alan , Welchman Andrew E. , Kourtzi Zoe
Published: October 2010

Learning is thought to facilitate the recognition of objects by optimizing the tuning of visual neurons to behaviorally relevant features. However, the learning mechanisms that shape neural selectivity for visual forms in the human brain remain essentially unknown. Here, we combine behavioral and functional magnetic resonance imaging (fMRI) measurements to test the mechanisms that mediate enhanced behavioral sensitivity in the discrimination of visual forms after training. In particular, we used high-resolution fMRI and multivoxel pattern classification methods to investigate fine learning-dependent changes in neural preference for global forms. We measured the observers' choices when discriminating between concentric and radial patterns presented in noise before and after training. Similarly, we measured the choices of a pattern classifier when predicting each stimulus from fMRI activity. Comparing the performance of human observers and classifiers demonstrated that learning alters the observers' sensitivity to visual forms and the tuning of fMRI activation patterns in visual areas selective for task-relevant features. In particular, training on low-signal stimuli enhanced the amplitude but reduced the width of pattern-based tuning functions in higher dorsal and ventral visual areas. Thus, our findings suggest that learning of visual patterns is implemented by enhancing the response to the preferred stimulus category and reducing the response to nonpreferred stimuli in higher extrastriate visual cortex.