bluuebunny/crossref_metadata_2025 huggingface dataset:
The management of uncomplicated adult gonococcal infection: should test of cure still be routine in patients attending genitourinary medicine clinics?
Authors: Harry C
Published: May 2006

In this retrospective study of the outcome of treatment of 245 patients (87 females and 158 males) with a diagnosis of Neisseria gonorrhoeae infection seen between 1996 and 2002, 81% (95% confidence interval (CI) 74%–86.8%) of the males and 88.5% (95% CI 79.9%–94.3%) of the females attended for a test of cure. At initial presentation, 93% (95% CI 87.9%–96.5%) and 94.3% (95% CI 89.5%–97.4%) of males respectively, had symptoms and signs of gonococcal infection compared with 48.3% (95% CI 37.4%–59.2%) and 44.8% (95% CI 34.1%–55.9%) of females, and this difference was statistically significant ( P = 0.005). Initial diagnosis at first visit was made by Gram-stained smear in 88.6% (95% CI 82.6%–93.1%) of males and 32.2% (95% CI 22.6%–43.1%) of females, a statistically significant difference P = 0.001. There were 12 (4.9%) cases of reinfection that rebooked to attend after failing to attend for their test of cure in two females and 10 males. There were two (0.8%) treatment failures amongst the 245 episodes in two males who still had symptoms when they returned for their test of cure. One male had a ciprofloxacin-resistant strain (CRNG) acquired locally and the other one had a betalactamase-producing CRNG/penicillinase-producing N. gonorrhoeae (PPNG) isolate acquired abroad in South America. These patients would have sought to return, as they still had signs and symptoms of gonococcal infection, and they would have been recalled following receipt of the antimicrobial susceptibility report. Post-gonococcal urethritis occurred in 36.3% (95% CI 27.8%–45.4%) of the males who attended for their test of cure, 74.8% (95% CI 67.2%–81.5%) received anti-chlamydial therapy with their standard treatment. In men who received anti-chlamydial therapy the odds ratio of having post-gonococcal urethritis was 0.42 (95% CI 0.17–1.06), P = 0.04. Co-infection with Chlamydia trachomatis was more likely to occur amongst females (43.9%), odds ratio 3.97 (95% CI 2.07–7.67), P < 0.001 than males (16.5%). We have now discontinued routine attendance for a test of cure and encourage our patients to telephone for their results with recall only of patients whose antimicrobial susceptibility indicate inappropriate first line therapy or who are still symptomatic.
HIV prevalence and risk factors among fishermen in Sihanouk Ville, Cambodia
Authors: Samnang Po , Leng Hor Bun , Kim Andrea , Canchola Alison , Moss Andrew , Mandel Jeffrey S , Page-Shafer Kimberly
Published: May 2006

We assessed HIV antibody and risk exposures in a cross-sectional sample of 446 fishermen in Sihanouk Ville, a port and fishing area in Cambodia, where high HIV prevalence has been found in sentinel surveillance studies. HIV prevalence was 16.1%, and was highest among unmarried men (17.3%) compared with married (14.6%). Men who stayed in port over one day had a significantly higher prevalence of HIV (31.7%) than those in port for ≤ day (14.6%). Men who had sex exclusively with their wife or girlfriend in the previous three months were significantly less likely to be HIV-infected than those who reported no sexual relations during the same time period (11% vs 23.7%, respectively). HIV infection in Cambodian fishermen was more than double that estimated in the general Khmer population. Although a large-scale condom promotion programme has been implemented in Sihanouk Ville, additional prevention programmes are needed to prevent further spread of HIV.
Declining HIV rates in Uganda: due to cleaner needles, not abstinence or condoms
Authors: Brody Stuart
Published: May 2006

Public health and political authorities have ascribed the apparent decline in Ugandan HIV or AIDS rates to increased rates of sexual abstinence or condom use. However, what appears to be special about Uganda is that in the middle to late 1980s there was a growing public awareness of health care risks. Given the lack of evidence for transmission of HIV to healthy persons by penile–vaginal intercourse, the improvement in injection safety is the best candidate for declining HIV and AIDS rates.
Opportunistic infections in hospitalized HIV-infected adults in Ho Chi Minh City, Vietnam: a cross-sectional study
Authors: Louie Janice K , Chi Nguyen Huu , Thao Le Thi Thu , Quang Vo Minh , Campbell James , Chau Nguyen Van Vinh , Rutherford George W , Farrar Jeremy J , Parry Christopher M
Published: May 2006

The HIV epidemic is emerging rapidly in Vietnam. We studied the prevalence of opportunistic infections by performing clinical and microbiological investigations in 100 hospitalized HIV-infected adults in Ho Cho Minh City, Vietnam. The median CD4 count was 20 cells/mm3 and in-hospital mortality was 28%. The most frequent diagnoses were oral candidiasis (54), tuberculosis (37), wasting syndrome (34), lower respiratory tract infection (13), cryptococcosis (9), and penicilliosis (7). Bacterial (other than tuberculosis) and parasitic infections were uncommon. Regional differences should be considered when deciding which diagnostic procedures and prophylactic measures to implement. In Vietnam, routine mycobacterial blood cultures do not provide greater yield than chest radiography and sputum and lymph node aspirate smears. Prophylactic trimethoprim/sulphamethoxazole against Pneumocystis jiroveci pneumonia may confer little benefit, and high rates of isoniazid resistance may affect the efficacy and feasibility of tuberculosis chemoprophylaxis. However, the usefulness of itraconazole prophylaxis for cryptococcosis and penicilliosis merits further consideration.
Changing pattern of HIV infection in a tertiary care hospital in New Delhi, India
Authors: Ray Krishna
Published: May 2006

HIV seroprevalence was carried out in 42,738 individuals attending the STD Centre of a New Delhi hospital from September 1990 to December 2001. The different epidemiological parameters of the patients in Group 1 (asymptomatic HIV-seropositive individuals) and Group 2 (AIDS cases), were compared in four spans A, B, C, D. Significant rise in seroprevalence from 0.4% to 4.4% was observed with time.

The patients in Group 1 were mainly 15–19 years followed by 30–44 years age group. Overall, the Male:Female ratio in Groups 1 and 2 were 3:1 and 6:1, respectively. The transmission was predominantly heterosexual in both the groups.

The patients with sexually transmitted infections (STIs) emerged as the most prominent category in Group 1, showing a steady rising trend till 1999 and stabilizing thereafter. Ulcerative STIs, mainly syphilis, showed maximum association. In most of the cases, the infection was acquired by promiscuous males from female commercial sex workers or casual acquaintances and further transmitted to their spouses.

Tuberculosis was the most common opportunistic infection. However, patients presented with fever, loss of weight and diarrhoea in increasing number during time D.

The present study reiterates the importance of early management of STI patients and counselling of high risk groups, early partner notification and routine antenatal HIV check-up in the prevention and control of HIV/AIDS infection in third world countries like India.
Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy
Authors: Reid S E , Reid C A , Vermund S H
Published: May 2006

Declining drug costs and increases in international donor interest are leading to greater availability of antiretroviral treatment programmes for persons living with the human immunodeficiency virus in parts of sub-Saharan Africa. Ensuring adequate adherence to antiretroviral drug therapy is one of the principal challenges facing successful implementation in Africa, where 70% of the world's infected persons live. Tuberculosis and leprosy are two diseases of global importance whose control programmes can provide important lessons for developing antiretroviral drug adherence strategies. This paper examines various approaches used in tuberculosis and leprosy control which could help enhance adherence to antiretroviral therapy in resource-limited settings.
Re-infection of Chlamydia trachomatis in patients presenting to the genitourinary medicine clinic in Portsmouth: the chlamydia screening pilot study — three years on
Authors: Lee V F , Tobin J M , Harindra V
Published: May 2006

Chlamydia trachomatis is the most common bacterial sexually transmitted infection (STI) in the UK. The Department of Health set up an opportunistic screening programme for genital chlamydia infection, focusing on sexually active 16–24-year-old women and some men. This study identified those patients re-attending the genitourinary medicine (GUM) clinic and followed them up until September 2002. We examined the reasons for attendance and re-infection with chlamydia. Two hundred and eighty-five patients re-attended the clinic. Two-thirds of these had changed their sexual partners in the follow-up period. Fifty-six patients were diagnosed with genital chlamydia infection in subsequent clinic visits. The majority of them had changed their sexual partners, suggesting new acquisition of infection. This suggests that in this age group re-screening should be offered at a year interval. Patients diagnosed with genital chlamydia infection should be referred to the GUM clinic for further STI screening and partner notification.
Management of HIV-related lymphoma in HIV treatment centres in North Thames Region
Authors: Brook M G , Jones K , Bower M , Miller R F
Published: May 2006

We describe an audit of lymphoma care in HIV-positive patients. In the smaller units (< 500 patients) areas of potentially sub-optimal care were identified.
Seeking and engaging in internet sex: a survey of patients attending genitourinary medicine clinics in Plymouth and in London
Authors: Malu M K , Challenor R , Theobald N , Barton S E
Published: May 2006

We conducted a survey of patients attending two GUM clinics to evaluate the use of the internet for seeking sexual partners and for seeking on-line sexual health information. Prevalence of internet sex-seeking (ISS) was 11% (57/500) in Plymouth and 21% (50/237) in London. ISS was more common among men who have sex with men (MSM) (43/92 = 47%) than men who have sex with women (MSW) (38/280 = 14%, P < 0.0001) and more common amongst MSW than women who have sex with men (WSM) (25/350 = 7%, P = 0.007). In both samples, accessing sexual health information online was associated with ISS (Plymouth, P = 0.05 and London, P = 0.001), as was reporting more than 10 sexual partners per year (Plymouth and London, P < 0.001). It remains to be seen whether the potential sexual health promotion benefits of the internet could balance potential risks of STI acquisition.
Post-HIV test counselling of clients of a mobile STD/HIV clinic
Authors: Ellen Jonathan M , Liang Thomas S , Jacob Claude A , Erbelding Emily , Christmyer Carol
Published: May 2006

The objective of the study was to determine the post-test counselling (PTC) rates for HIV-infected and uninfected individuals receiving HIV counselling and testing on a mobile STD/HIV screening clinic and to determine whether individuals at highest risk for transmitting their infection were less likely to receive PTC than those at lower risk for transmitting. Clients presenting for HIV counselling and testing were asked about their demographic characteristics, clinical history, personal risk behaviours, and partner risk factors and told to return after 14 days for results. Disease intervention specialists (DIS) attempted to locate and counsel positive clients. The PTC rate among infected and uninfected clients was 66% and 46%, respectively. There were significant differences in demographics and risk factors for those who were post-test counselled versus those who were not. Among HIV-uninfected clients, there was a positive association between PTC and drug treatment in the past three months and having engaged in sex work within the last three months. Being female was negatively associated with PTC. Among HIV-infected clients, there was a positive association between PTC and current enrolment in drug treatment. These data suggest that mobile STD/HIV screening clinics may be limited in their effectiveness by low rates of PTC.
Managing genital chlamydial infection: the effects of ethnic origin and method of follow-up
Authors: Apoola Ade , Boothby Meg , Radcliffe Keith
Published: May 2006

We assessed if ethnicity and method of follow-up were associated with differences in the number of patients and the number of partners successfully treated for genital chlamydial infection. This was done by retrospectively reviewing the first 400 cases of genital chlamydia diagnosed between February and June 2001 who had a traditional clinic follow-up and the first 400 cases from the same period in 2002 when the telephone follow-up was used. The telephone follow-up appointment system, when compared to a traditional clinic follow-up appointment system, eliminated differences between Black and White ethnic groups in the numbers of patients and partners satisfactorily treated.
Accelerating the audit cycle: data gathering, analysis and dissemination of results by electronic methods. The third Yorkshire audit of genital chlamydial management
Authors: McClean Hugo , Haworth Pat , Clarke Janette ,   Yorkshire Multi-District Genitourinary Medicine Clinical Audit Group
Published: May 2006

An electronic database was used as an audit tool by a peripatetic auditor to collect data on the management of genital chlamydial infection from genitourinary medicine clinics. A paper proforma was used to obtain data on clinic facilities. The database generated pre-specified quantitative reports for comparison to national standards and guidelines, as well as comparison of performance between clinics and to a previous regional audit. Feedback and discussion took place to identify interventions intended to improve practice. This methodology allowed for rapid dissemination of the audit findings to clinics.
Is telephone follow-up as good as traditional clinic follow-up in achieving the proposed national outcome standards for chlamydia management?
Authors: Apoola A , Boothby M , Radcliffe K
Published: May 2006

A retrospective review of 400 cases of genital chlamydia managed with a traditional clinic follow-up was compared to 400 cases with a telephone follow-up appointment. We satisfactorily treated more patients with the telephone follow-up appointment than with a traditional clinic follow-up (204 [51%] vs 121 [30%]; P <0.0001). We also satisfactorily treated more partners with the telephone follow-up system than a traditional clinic appointment system (0.57 vs 0.45 contacts per case; P =0.0006). The introduction of the telephone follow-up appointment system in the clinic increased the number of patients and contacts of patients successfully managed for genital chlamydial infection. Our findings should lead to increased research and adoption of different methods of follow-up and help develop proper outcome standards.
Genotypic resistance testing in HIV-infected pregnant women in an urban setting
Authors: Shah S S , Crane M , Monaghan K , McGowan J P
Published: May 2006

This study examines the utility of HIV genotypic resistance testing (GT) in pregnant women at their initial pregnancy evaluation. A retrospective medical record review of 50 consecutive HIV-infected pregnant women in whom GT was obtained in the Bronx, New York was conducted. Twenty-eight (56%) were antiretroviral experienced, including 12 on antiretroviral therapy (ART) at time of GT. Major mutations were found in 11 (24%) of 45 amplifiable GTs. Major resistance mutations were identified against nucleoside reverse transcriptase inhibitors (NRTIs) in six (13%) patients; against non-nucleoside reverse transcriptase inhibitors (NNRTIs) in eight (18%) patients, and against protease inhibitors in two (4%) patients. Duration of ART exposure was significantly associated with identification of resistance mutations by GT for NRTIs and NNRTIs ( P ≥0.05). Results of this study indicate that GT at presentation may have implications on the initial choice of ART in up to one-quarter of HIV-infected pregnant women, especially with current or prior antiretroviral use.
Epidemiology of HIV infection in urban Burkina Faso
Authors: Lagarde Emmanuel , Congo Zakari , Meda Nicolas , Baya Banza , Yaro Seydou , Sangli Gabriel , Traoré Yves , Van Renthergem Henk , Caraël Michel ,   for the Study Group on HIV Dynamic Among Young Adults In Burkina Faso
Published: May 2006

We conducted a cross-sectional study of sexually transmitted disease and HIV infections among a random sample of the 2364 adult population in 2000 in Bobo-Dioulasso, the second largest town in Burkina Faso. The prevalence of HIV infection was 5.2%. Risk factor analysis was conducted among sexually active men 20 to 34 years old and women 15 to 24 years old. Factors independently associated with HIV infection among men were having been married (adjusted odds ratio (aOR)=8.19 [1.70-39]), reporting more than two non-marital partners in the last 12 months (aOR=6.07 [1.14-32.4]), reporting a past urban residence other than Bobo-Dioulasso (aOR =6.37 [1.96-20.7] and having a positive serology for HSV-2 infection (aOR=12.0 [3.49-40.9]). Among women the factors were being Christian (aOR=3.73 [1.20-11.6]), having had a first sexual partner more than 24 years old (aOR =4.30 [1.35-13.6]) and having a positive serology for HSV-2 infection (aOR =4.40 [1.32-14.6]). HIV infection in Bobo-Dioulasso therefore depends on both exposure factors (sexual behaviours) and transmissibility cofactors (HSV-2).
Prevalence and risk factors of asymptomatic chlamydial infection among students in Japan
Authors: Imai Hirohisa , Shinohara Hisae , Nakao Hiroyuki , Tsukino Hiromasa , Hamasuna Ryoichi , Katoh Takahiko
Published: May 2006

The objective was to determine the prevalence of asymptomatic Chlamydia trachomatis infection (CTI) among students in Japan, and to examine risk factors and methods of prevention. A total of 1004 students were analysed. Urine samples were checked for chlamydial DNA using polymerase chain reaction techniques. Prevalence of CTI was 8.3%. Risk factors were age and a history of four or more sexual partners for females, and history of CTI and contact with new sexual partners for males. Age did not represent a risk factor for male students. A correlation was identified between history of genital infection and experience with commercial sex workers for male students. Sex education programmes should be implemented encouraging use of condoms not only by students over 18 years, but also by senior high school students. Development of efficient and practical screening systems tailored to the current status of school health management in Japan is also needed.
Partner notification: preferences of Melbourne clients and the estimated proportion of sexual partners they can contact
Authors: Tomnay J E , Pitts M K , Fairley C K
Published: May 2006

This study was conducted to determine the estimated proportion of contactable sexual partners, the most common types of contact information available and the most acceptable contact tracing strategies for our clients. Five hundred 'walk in' clients completed a questionnaire about their total number of sexual partners, the proportion of contactable partners and available contact information.

Women had the highest estimated number of contactable partners (89-94%), men who have sex with men had the lowest (51-73%). The preferred contact tracing strategy was to give partners a website address (76%) and the least preferred was provider referral (33%). There was a difference in the type of information available for contacting sexual partners ( P <0.001); most commonly clients reported partners contactable by phone or face to face and least commonly through a third person.

The currently used method (doctor's letter) is not the preferred choice of these clients and more innovative methods using recent technology may prove more effective.
HIV-1 cord-blood seroprevalence of parturient women in Sihanoukville, Cambodia
Authors: Theng T , Sok P , Pugatch D , Harwell J I , Rufner K M , Chhi Mean V , Mayer K H , Cu-Uvin S
Published: May 2006

Facing a 1.2% HIV-1 seroprevalence amongst its adult female population, Cambodia recently established national guidelines for the expansion of services to prevent mother-to-child transmission. Anticipating this expansion, Sihanoukville Hospital performed an anonymous HIV-1 cord-blood serosurvey of 600 consecutive deliveries from May 2001 through June 2002. Laboratory analysis utilizing ELISA and Western blot techniques yielded a 4.2% seroprevalence; a value resembling previous reports from other Sihanoukville antenatal clinics (3.9%) but exceeding the national ANC clinic average of 2.3%. Demographic information was confidentially collected and analysed for co-variation to HIV-1 status. One hundred percent of HIV positive mothers ( P =0.013) self-reported the occupation of housewife, consistent with previous documentations suggesting the shift in infection burden from high-risk groups into the general female population. A substantial proportion received no prenatal care, suggesting that interventions addressing mother-to-child transmission will need to prepare for the management of pregnant women presenting at or near the time of delivery.
Does medical culture limit doctors' adoption of quality improvement? Lessons from Camelot
Authors: Jorm Christine , Kam Peter
Published: May 2006

This paper analyses aspects of medical culture, explains why this culture is antagonistic to quality improvement, and provides solutions to help medical colleges meet the challenge of clinical governance. Like the knights of Camelot, doctors have their own all-pervading culture, occupationally centred, exclusive to the initiated and tending to the traditional, either overtly or through assumed values. The Camelot metaphor is supported by analysis of empirical evidence, especially the documents produced by medical colleges. Suggested initiatives to overcome these organisational barriers include improvements in continuing medical education, accreditation, guideline production and responsibility for the performance of doctors. Central to these improvements should be the involvement of every doctor, via the Delphi process, and substantial contributions to college processes from other health care professions and patients.
Integer Polynomial Optimization in Fixed Dimension
Authors: De Loera Jesús A. , Hemmecke Raymond , Köppe Matthias , Weismantel Robert
Published: May 2006

We classify, according to their computational complexity, integer optimization problems whose constraints and objective functions are polynomials with integer coefficients, and the number of variables is fixed. For the optimization of an integer polynomial over the lattice points of a convex polytope, we show an algorithm to compute lower and upper bounds for the optimal value. For polynomials that are nonnegative over the polytope, these sequences of bounds lead to a fully polynomial-time approximation scheme for the optimization problem.
Rash with Both Clopidogrel and Ticlopidine in Two Patients Following Percutaneous Coronary Intervention with Drug-Eluting Stents
Authors: Makkar Kathy , Wilensky Robert L , Julien Maureen Burke , Herrmann Howard C , Spinler Sarah A
Published: May 2006

Objective:

To describe 2 cases of rash that occurred following oral administration of both clopidogrel and ticlopidine and to review previously published case reports.

Case Summary:

Two patients developed maculopapular pruritic rashes that began on the abdomen and spread to the back, neck, and face following clopidogrel administration after placement of a drug-eluting intracoronary stent. Following recurrence of the rash after ticlopidine was initiated, thienopyridines were discontinued, and the patients were treated for 3–6 months with aspirin, cilostazol, and enoxaparin or warfarin for prevention of stent thrombosis and reinfarction. One patient self-discontinued cilostazol, reinitiated clopidogrel, and redeveloped a rash.

Discussion:

While there have been several published cases of thienopyridine-associated rash, there have been only 2 reported cases of cross-sensitivity between orally administered clopidogrel and ticlopidine. Preliminary reports suggest that clopidogrel desensitization may be accomplished in selected patients several months to years following thienopyridine rash using an allergy desensitization protocol, with close monitoring for anaphylaxis. An objective causality assessment using the Naranjo probability scale indicated that both ticlopidine and clopidogrel were probable causes of the rash in the first patient; in the second patient, clopidogrel was judged a definite cause and ticlopidine was a probable cause of the rash.

Conclusions:

In a patient who develops a rash following clopidogrel treatment after intracoronary stent placement, ticlopidine therapy should be attempted, provided the initial reaction did not include life-threatening symptoms. In a patient who experiences rash with both clopidogrel and ticlopidine and does not have a contraindication to cilostazol or anticoagulation, therapy with aspirin, cilostazol, and either enoxaparin or warfarin may be administered for 2–6 months following placement of a drug-eluting stent.
Developmental Links between Cruelty to Animals and Human Violence
Authors: Dadds Mark R. , Turner Cynthia M , McAloon John
Published: May 2006

Reviews evidence for the significance of childhood cruelty to animals as a predictor of later violence toward humans. Moves are underway in the United States (US) and Britain to encourage communication and cross-fertilisation between animal welfare and child protection and crime prevention services. Literature on healthy versus deviant child-pet interactions is reviewed, with particular regard to the prediction of later violence. Assessment and definitional issues are addressed. The discussion culminates with a summary of substantive findings and the identification of several research designs that are needed to clarify the potential of early identification and remediation of child cruelty to animals as a mental health promotion and violence prevention strategy.
Individual Differences in Reward Drive Predict Neural Responses to Images of Food
Authors: Beaver John D. , Lawrence Andrew D. , van Ditzhuijzen Jenneke , Davis Matt H. , Woods Andrew , Calder Andrew J.
Published: May 2006

A network of interconnected brain regions, including orbitofrontal, ventral striatal, amygdala, and midbrain areas, has been widely implicated in a number of aspects of food reward. However, in humans, sensitivity to reward can vary significantly from one person to the next. Individuals high in this trait experience more frequent and intense food cravings and are more likely to be overweight or develop eating disorders associated with excessive food intake. Using functional magnetic resonance imaging, we report that individual variation in trait reward sensitivity (as measured by the Behavioral Activation Scale) is highly correlated with activation to images of appetizing foods (e.g., chocolate cake, pizza) in a fronto–striatal–amygdala–midbrain network. Our findings demonstrate that there is considerable personality-linked variability in the neural response to food cues in healthy participants and provide important insight into the neurobiological factors underlying vulnerability to certain eating problems (e.g., hyperphagic obesity).
Systems Consolidation Requires Postlearning Activation of NMDA Receptors in the Medial Prefrontal Cortex in Trace Eyeblink Conditioning
Authors: Takehara-Nishiuchi Kaori , Nakao Kazuhito , Kawahara Shigenori , Matsuki Norio , Kirino Yutaka
Published: May 2006

The importance of the hippocampus in declarative memory is limited to recently acquired memory, and remotely acquired memory is believed to be stored somewhere in the neocortex. However, it remains unknown how the memory network is reorganized from a hippocampus-dependent form into a neocortex-dependent one. We reported previously that the medial prefrontal cortex (mPFC) is important for this neocortex-dependent remote memory in rat trace eyeblink conditioning. Here, we investigate the involvement of NMDA receptors in the mPFC in this reorganization and determine the time window of their contribution using chronic infusion of an antagonist into the mPFC, specifically during the postlearning consolidation period. The rats with blockade of the mPFC NMDA receptors during the first 1 or 2 weeks after learning showed a marked impairment in memory retention measured 6 weeks after learning, but relearned normally with subsequent conditioning. In contrast, the same treatment had no effect if it was performed during the third to fourth weeks or during the first day just after learning. The specificity of NMDA receptor blockade was confirmed by the reduced long-term potentiation in the hippocampal-prefrontal pathway in these rats. These results suggest that successful establishment of remotely acquired memory requires activation of NMDA receptors in the mPFC during at least the initial week of the postlearning period. Such NMDA receptor-dependent processes may mediate the maturation of neocortical networks that underlies permanent memory storage and serve as a way to reorganize memory circuitry to the neocortex-dependent form.
Two mRNA-Binding Proteins Regulate the Distribution of Syntaxin mRNA inAplysiaSensory Neurons
Authors: Liu Jinming , Hu Jiang-Yuan , Wu Fang , Schwartz James H. , Schacher Samuel
Published: May 2006

Targeting mRNAs to different functional domains within neurons is crucial to memory storage. InAplysiasensory neurons, syntaxin mRNA accumulates at the axon hillock during long-term facilitation of sensory-motor neuron synapses produced by serotonin (5-HT). We find that the 3′ untranslated region ofAplysiasyntaxin mRNA has two targeting elements, the cytosolic polyadenylation element (CPE) and stem-loop double-stranded structures that appear to interact with mRNA-binding proteins CPEB and Staufen. Blocking the interaction between these targeting elements and their RNA-binding proteins abolished both accumulation at the axon hillock and long-term facilitation. CPEB, which we previously have shown to be upregulated after stimulation with 5-HT, is required for the relocalization of syntaxin mRNA to the axon hillock from the opposite pole in the cell body of the sensory neuron during long-term facilitation, whereas Staufen is required for maintaining the accumulation of the mRNA both at the axon hillock after the treatment with 5-HT and at the opposite pole in stable, unstimulated sensory neurons. Thus, the cooperative actions of the two mRNA-binding proteins serve to direct the distribution of an mRNA encoding a key synaptic protein.
Corn, Cucurbits, Cordage, and Colonization: An Absolute Chronology for the Appearance of Mesoamerican Domesticates and Perishables in the Jornada Basin, New Mexico
Authors: Hyland D. C. , Adovasio J. M. , Taylor R. Ervin
Published: May 2006

Detailed attribute analysis of basketry and cordage remains from Pendejo Cave and the region encompassed by the Jornada Basin in south-central New Mexico has suggested that the introduction of non-local cultigens in the study area is signaled by the simultaneous and not unrelated appearance of bundle foundation coiling, twill plaiting, and final S twist cordage of north Mexican origin or affiliation. Accelerator mass spectrometry (AMS) radiocarbon dates of selected allochthonous perishable fiber artifacts from Pendejo Cave are presented and evaluated in terms of the local chronology of coiling, plaiting, and cordage types, their association with the adoption of cultigens, as evidence of material culture change via migration and hybridization, as well as their role in the onset of the Formative in the Jornada Basin.
Design of a Fuel Cell Power System for Automotive Applications
Authors: Kolavennu Panini K. , Telotte John C. , Palanki Srinivas
Published: May 2006

In this paper, the primary components of a PEM fuel cell for automotive applications, using methane as a fuel, are analyzed. Basic chemical engineering principles are utilized to assess the role of thermodynamics, heat transport, and reaction kinetics. The amount of methane required is calculated as function of hydrogen produced as well as the power produced. The heat duty for thermal control of the system is analyzed.
Simulation of a Two-Stage Micro Trickle-Bed Hydrotreating Reactor using Athabasca Bitumen-Derived Heavy Gas Oil over Commercial NiMo/Al2O3 Catalyst: Effect of H2S on Hydrodesulfurization and Hydrodenitrogenation
Authors: Botchwey Christian , Dalai Ajay K , Adjaye John
Published: May 2006

A two-stage, micro trickle-bed reactor (for studies of the effects of hydrogen sulfide on hydrodesulfurization (HDS) and hydrodenitrogenation (HDN) of Athabasca bitumen-derived heavy gas oil over commercial NiMo/Al2O3 catalyst) has been simulated. One dimensional homogeneous mass transfer and a two dimensional heat transfer models were developed. The essence of the simulation was to enhance the understanding of the effects of hydrogen sulfide in the hydrotreating catalyst bed in a two-stage mode and also to predict the catalyst requirements for deep HDS and HDN processes. The kinetic model used in the simulation was based on the Langmuir-Hingshelwood method of rate determination. Adsorption constants were estimated by non-linear least squares method. The kinetic models were tested on independent set of data and found to predict the experimental data satisfactorily. The mass transfer simulation considered the effects of variables such as temperature and catalyst loading or liquid hourly space velocity (LHSV) on the trends of hydrogen sulfide generation and, sulfur and nitrogen conversions along the catalyst bed. The model was numerically solved using a fourth-order Runge-Kutta technique. The 1:3 wt/wt catalyst loading with inter-stage hydrogen sulfide removal was found to give the best HDN and HDS activities. Simulated results showed that doubling the present catalyst mass and operating at 653 °C with inter-stage hydrogen sulfide removal would give 6 and 179 ppm product sulfur and nitrogen, respectively. On the other hand, without hydrogen sulfide removal, only 49 and 302 ppm product sulfur and nitrogen could be attained, respectively. The heat transfer simulation compared temperature profiles in the two-stage process to a single stage process for the 1:3 wt/wt catalyst loading at 653 K. The temperature regime in Stage II was found to be more uniform unlike Stage I and the single stage. Crank Nicholson algorithm was used to solve the 2-D partial differential equations.
Intestinal Insulin Resistance and Aberrant Production of Apolipoprotein B48 Lipoproteins in an Animal Model of Insulin Resistance and Metabolic Dyslipidemia
Authors: Federico Lisa M. , Naples Mark , Taylor Denise , Adeli Khosrow
Published: May 2006

Postprandial dyslipidemia is recognized as an important complication of insulin-resistant states, and recent evidence implicates intestinal lipoprotein overproduction as a causative factor. The mechanisms linking intestinal lipoprotein overproduction and aberrant insulin signaling in intestinal enterocytes are currently unknown. Intestinal insulin sensitivity and lipid metabolism were studied in a fructose-fed hamster model of insulin resistance and metabolic dyslipidemia. Intestinal lipoprotein production in chow-fed hamsters was responsive to the inhibitory effects of insulin, and a decrease in circulating levels of triglyceride-rich apolipoprotein (apo)B48-containing lipoproteins occurred 60 min after insulin administration. However, fructose-fed hamster intestine was not responsive to the insulin-induced downregulation of apoB48-lipoprotein production, suggesting insulin insensitivity at the level of the intestine. Enterocytes from the fructose-fed hamster exhibited normal activity of the insulin receptor but reduced levels of insulin receptor substrate-1 phosphorylation and mass and Akt protein mass. Conversely, the protein mass of the p110 subunit of phosphatidylinositol 3-kinase, protein tyrosine phosphatase-1B, and basal levels of phosphorylated extracellular signal–related kinase (ERK) were significantly increased in the fructose-fed hamster intestine. Modulating the ERK pathway through in vivo inhibition of mitogen-activated protein/ERK kinase 1/2, the upstream activator of ERK1/2, we observed a significant decrease in intestinal apoB48 synthesis and secretion. Interestingly, enhanced basal ERK activity in the fructose-fed hamster intestine was accompanied by an increased activation of sterol regulatory element–binding protein. In summary, these data suggest that insulin insensitivity at the level of the intestine and aberrant insulin signaling are important underlying factors in intestinal overproduction of highly atherogenic apoB48-containing lipoproteins in the insulin-resistant state. Basal activation of the ERK pathway may be an important contributor to the aberrant insulin signaling and lipoprotein overproduction in this model.
Impact of Mitochondrial Reactive Oxygen Species and Apoptosis Signal–Regulating Kinase 1 on Insulin Signaling
Authors: Imoto Koujiro , Kukidome Daisuke , Nishikawa Takeshi , Matsuhisa Takako , Sonoda Kazuhiro , Fujisawa Kazuo , Yano Miyuki , Motoshima Hiroyuki , Taguchi Tetsuya , Tsuruzoe Kaku , Matsumura Takeshi , Ichijo Hidenori , Araki Eiichi
Published: May 2006

Tumor necrosis factor (TNF)-α inhibits insulin action; however, the precise mechanisms are unknown. It was reported that TNF-α could increase mitochondrial reactive oxygen species (ROS) production, and apoptosis signal–regulating kinase 1 (ASK1) was reported to be required for TNF-α–induced apoptosis. Here, we examined roles of mitochondrial ROS and ASK1 in TNF-α–induced impaired insulin signaling in cultured human hepatoma (Huh7) cells. Using reduced MitoTracker Red probe, we confirmed that TNF-α increased mitochondrial ROS production, which was suppressed by overexpression of either uncoupling protein-1 (UCP)-1 or manganese superoxide dismutase (MnSOD). TNF-α significantly activated ASK1, increased serine phosphorylation of insulin receptor substrate (IRS)-1, and decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt, and all of these effects were inhibited by overexpression of either UCP-1 or MnSOD. Similar to TNF-α, overexpression of wild-type ASK1 increased serine phosphorylation of IRS-1 and decreased insulin-stimulated tyrosine phosphorylation of IRS-1, whereas overexpression of dominant-negative ASK1 ameliorated these TNF-α–induced events. In addition, TNF-α activated c-jun NH2-terminal kinases (JNKs), and this observation was partially inhibited by overexpression of UCP-1, MnSOD, or dominant-negative ASK1. These results suggest that TNF-α increases mitochondrial ROS and activates ASK1 in Huh7 cells and that these TNF-α–induced phenomena contribute, at least in part, to impaired insulin signaling.
Dexamethasone Induces Cell Death in Insulin-Secreting Cells, an Effect Reversed by Exendin-4
Authors: Ranta Felicia , Avram Diana , Berchtold Susanne , Düfer Martina , Drews Gisela , Lang Florian , Ullrich Susanne
Published: May 2006

Glucocorticoid excess induces hyperglycemia, which may result in diabetes. The present experiments explored whether glucocorticoids trigger apoptosis in insulin-secreting cells. Treatment of mouse β-cells or INS-1 cells with the glucocorticoid dexamethasone (0.1 μmol/l) over 4 days in cell culture increased the number of fractionated nuclei from 2 to 7 and 14%, respectively, an effect that was reversed by the glucocorticoid receptor antagonist RU486 (1 μmol/l). In INS-1 cells, dexamethasone increased the number of transferase-mediated dUTP nick-end labeling–staining positive cells, caspase-3 activity, and poly-(ADP-) ribose polymerase protein cleavage; decreased Bcl-2 transcript and protein abundance; dephosphorylated the proapoptotic protein of the Bcl-2 family (BAD) at serine155; and depolarized mitochondria. Dexamethasone increased PP-2B (calcineurin) activity, an effect abrogated by FK506. FK506 (0.1 μmol/l) and another calcineurin inhibitor, deltamethrin (1 μmol/l), attenuated dexamethasone-induced cell death. The stable glucagon-like peptide 1 analog, exendin-4 (10 nmol/l), inhibited dexamethasone-induced apoptosis in mouse β-cells and INS-1 cells. The protective effect of exendin-4 was mimicked by forskolin (10 μmol/l) but not mimicked by guanine nucleotide exchange factor with the specific agonist 8CPT-Me-cAMP (50 μmol/l). Exendin-4 did not protect against cell death in the presence of cAMP-dependent protein kinase (PKA) inhibition by H89 (10 μmol/l) or KT5720 (5 μmol/l). In conclusion, glucocorticoid-induced apoptosis in insulin-secreting cells is accompanied by a downregulation of Bcl-2, activation of calcineurin with subsequent dephosphorylation of BAD, and mitochondrial depolarization. Exendin-4 protects against glucocorticoid-induced apoptosis, an effect mimicked by forskolin and reversed by PKA inhibitors.
Elevated Activity of Transcription Factor Nuclear Factor of Activated T-Cells 5 (NFAT5) and Diabetic Nephropathy
Authors: Yang Bingmei , Hodgkinson Andrea D. , Oates Peter J. , Kwon Hyug Moo , Millward Beverley A. , Demaine Andrew G.
Published: May 2006

The expression of aldose reductase is tightly regulated by the transcription factor tonicity response element binding protein (TonEBP/NFAT5) binding to three osmotic response elements (OREs; OREA, OREB, and OREC) in the gene. The aim was to investigate the contribution of NFAT5 to the pathogenesis of diabetic nephropathy. Peripheral blood mononuclear cells (PBMCs) were isolated from the following subjects: 44 Caucasoid patients with type 1 diabetes, of whom 26 had nephropathy and 18 had no nephropathy after a diabetes duration of 20 years, and 13 normal healthy control subjects. In addition, human mesangial cells (HMCs) were isolated from the normal lobe of 10 kidneys following radical nephrectomy for renal cell carcinoma. Nuclear and cytoplasmic proteins were extracted from PBMCs and HMCs and cultured in either normal or high-glucose (31 mmol/l d-glucose) conditions for 5 days. NFAT5 binding activity was quantitated using electrophoretic mobility shift assays for each of the OREs. Western blotting was used to measure aldose reductase and sorbitol dehydrogenase protein levels. There were significant fold increases in DNA binding activities of NFAT5 to OREB (2.06 ± 0.03 vs. 1.33 ± 0.18, P = 0.033) and OREC (1.94 ± 0.21 vs. 1.39 ± 0.11, P = 0.024) in PBMCs from patients with diabetic nephropathy compared with diabetic control subjects cultured under high glucose. Aldose reductase and sorbitol dehydrogenase protein levels in the patients with diabetic nephropathy were significantly increased in PBMCs cultured in high-glucose conditions. In HMCs cultured under high glucose, there were significant increases in NFAT5 binding activities to OREA, OREB, and OREC by 1.38 ± 0.22-, 1.84 ± 0.44-, and 2.38 ± 1.15-fold, respectively. Similar results were found in HMCs exposed to high glucose (aldose reductase 1.30 ± 0.06-fold and sorbitol dehydrogenease 1.54 ± 0.24-fold increases). Finally, the silencing of the NFAT5 gene in vitro reduced the expression of the aldose reductase gene. In conclusion, these results show that aldose reductase is upregulated by the transcriptional factor NFAT5 under high-glucose conditions in both PBMCs and HMCs.
Mature-Onset Obesity in Interleukin-1 Receptor I Knockout Mice
Authors: García Maria C. , Wernstedt Ingrid , Berndtsson Anna , Enge Maria , Bell Michal , Hultgren Olof , Horn Michael , Ahrén Bo , Enerback Sven , Ohlsson Claes , Wallenius Ville , Jansson John-Olov
Published: May 2006

Interleukin-1 (IL-1) is a major mediator of inflammation that exerts its biological activities through the IL-1 type I receptor (IL-1RI). The body weights of IL-1RI−/− mice of both sexes started to deviate from those of wild-type mice at 5–6 months of age and were 20% higher at 9 months of age. Visceral and subcutaneous fat mass, measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, was markedly (1.5- to 2.5-fold) increased. Lean body mass and crown-rump length were also slightly (11 and 5%, respectively) increased, as was serum IGF-I. Obese IL-1RI−/− mice were insulin resistant, as evidenced by hyperinsulinemia, decreased glucose tolerance, and insulin sensitivity. To elucidate the mechanisms for the development of obesity, young preobese IL-1RI−/− mice were investigated. They showed decreased suppression of body weight and food intake in response to systemic leptin treatment. The decreased leptin responsiveness was even more pronounced in older obese animals. Moreover, spontaneous locomotor activity and fat utilization, as measured by respiratory quotient, were decreased in preobese IL-1RI−/− mice. In conclusion, lack of IL-1RI–mediated biological activity causes mature-onset obesity. This obese phenotype is preceded by decreased leptin sensitivity, fat utilization, and locomotor activity.
Blockade of β1 Integrin–Laminin-5 Interaction Affects Spreading and Insulin Secretion of Rat β-Cells Attached on Extracellular Matrix
Authors: Parnaud Geraldine , Hammar Eva , Rouiller Dominique G. , Armanet Mathieu , Halban Philippe A. , Bosco Domenico
Published: May 2006

When attached on a matrix produced by a rat bladder carcinoma cell line (804G matrix), rat pancreatic β-cells spread in response to glucose and secrete more insulin compared with cells attached on poly-l-lysine. The aim of this study was to determine whether laminin-5 and its corresponding cell receptor β1 integrin are implicated in these phenomena. By using specific blocking antibodies, we demonstrated that laminin-5 is the component present in 804G matrix responsible for the effect of 804G matrix on β-cell function and spreading. When expression of two well-known laminin-5 ligands, β1 and β4 integrin, was assessed by Western blot and RT-PCR, only the β1 integrin was detected in β-cells. Anti–β1 integrin antibody reduced the spreading of β-cells on 804G matrix. Blockade of the interaction between β1 integrins and laminin-5 resulted in a reduction in glucose-stimulated insulin secretion. Blocking anti–β1 integrin antibody also inhibited focal adhesion kinase phosphorylation induced by 804G matrix. In conclusion, anti–β1 integrin and –laminin-5 antibodies interfere with spreading of β-cells, resulting in decreased insulin secretion in response to glucose. Our findings indicate that outside-in signaling via engagement of β1 integrins by laminin-5 is an important component of normal β-cell function.