Excitatory amino acid transporter 5 is widely expressed in peripheral tissues.

It is routinely stated in the literature that Excitatory Amino Acid Transporter 5 (EAAT5) is a retina-specific glutamate transporter. EAAT5 is expressed by retinal photoreceptors and bipolar cells, where it serves as a slow transporter and as an inhibitory glutamate receptor, the latter role is due to the gating of a large chloride conductance. The dogma of an exclusively retinal distribution has arisen because Northern blot analyses have previously shown only modest hybridisation in non-retinal tissues. Others have re-interpreted this as indicating that EAAT5 was only present in retinal tissues. However, this view appears to be erroneous; recent evidence demonstrating abundant expression of EAAT5 in rat testis prompted us to re-examine this dogma. A new antibody was developed to an intracellular loop region of rat EAAT5. This new tool, in concert with RT-PCR and sequencing, demonstrated that EAAT5 is widely distributed at the mRNA and protein levels in many non-nervous tissues including liver, kidney, intestine, heart, lung, and skeletal muscle. We conclude that EAAT5 is a widely distributed protein. Whether it functions in all locations as a glutamate transporter, or mainly as a glutamate-gated chloride conductance, remains to be determined.

The concentration of oleocanthal in olive oil waste.

The aim of this study was to determine the concentration of oleocanthal in olive pomace waste and compare this to its concentration in extra-virgin olive oil (EVOO). The concentration of oleocanthal in freshly pressed EVOO and its subsequent waste was analysed at early, mid and late season harvests. Oleocanthal concentrations were quantified using high-performance liquid chromatography-mass spectrometry. In oil, oleocanthal concentration was as follows: 123.24 ± 6.48 mg kg(-1) in early harvest, 114.20 ± 17.42 mg kg(-1) in mid harvest and 152.22 ± 10.54 mg kg(-1) in late harvest. Its concentration in waste was determined to be: 128.25 ± 11.33 mg kg(-1) in early harvest, 112.15 ± 1.51 mg kg(-1) in mid harvest and 62.35 ± 8.00 mg kg(-1) in late harvest. Overall, olive pomace waste is a valuable source of oleocanthal.

Partial least squares and principal components analysis of wine vintage by high performance liquid chromatography with chemiluminescence detection.

HPLC with acidic potassium permanganate chemiluminescence detection was employed to analyse 17 Cabernet Sauvignon wines across a range of vintages (1971-2003). Partial least squares regression analysis and principal components analysis was used in order to investigate the relationship between wine composition and vintage. Tartaric acid, vanillic acid, catechin, sinapic acid, ethyl gallate, myricetin, procyanadin B and resveratrol were found to be important components in terms of differences between the vintages.

The pattern and course of cognitive impairment in late-life depression.

BACKGROUND: Cognitive deficits persist despite clinical recovery in subjects with late-life depression, but more needs to be known about their longer-term outcome and factors affecting their course. To investigate this, we followed the pattern of cognitive impairments over time and examined the effects of current mood, remission status, age of depression onset and antidepressant (AD) treatment on these deficits. METHOD: Sixty-seven subjects aged > or = 60 years with DSM-IV major depressive disorder and 36 healthy comparison subjects underwent tests of global cognition, memory, executive functioning and processing speed at baseline, 6 and 18 months, with some subjects tested again after 4 years. z scores were compared between groups, with analyses of clinical factors that may have influenced cognitive performance in depressed subjects. RESULTS: Half of the patients exhibited a generalized cognitive impairment (GCI) that persisted after 18 months. Patients performed worse across all cognitive domains at all time points, without substantial variability due to current mood, remission status or AD treatment. Late age of onset was associated significantly with decline in memory and executive functioning. Impaired processing speed may be a partial mediator of some deficits, but was insufficient to explain differences between patients and controls. Four-year follow-up data suggest impairments persist, but do not further decline. CONCLUSIONS: Cognitive deficits in late-life depression persist up to 4 years, affect multiple domains and are related to trait rather than state effects. Differences in severity and course between early and late onset depression suggest different pathogenic processes.

Geographical classification of some Australian wines by discriminant analysis using HPLC with UV and chemiluminescence detection.

HPLC with UV and acidified potassium permanganate chemiluminescence detection, combined with multivariate data analysis techniques, were used for the geographical classification of some Australian red (Cabernet Sauvignon) and white (Chardonnay) wines from two regions (Coonawarra and Geelong). Identification of the wine constituents prominent in the chromatography was performed by mass spectrometry. Principal components analysis and linear discriminant analysis were used to classify the wines according to region of production. Separation between regions was achieved with both detection systems and key components leading to discrimination of the wines were identified. Using two principal components, linear discriminant analysis with UV detection correctly classified 100% of the Chardonnay wines and, overall 91% of the Cabernet Sauvignon wines. With acidified potassium permanganate chemiluminescence detection, 75% of the Chardonnay wines and 94% of the Cabernet Sauvignon wines were correctly classified using two factors.

Selective inner retinal dysfunction precedes ganglion cell loss in a mouse glaucoma model.

BACKGROUND/AIMS: To correlate ganglion cell function with defined parameters of the elevated intraocular pressure profile (IOP) in a mouse glaucoma model and to determine the temporal relationship of these functional changes with ganglion cell death. METHODS: Unilateral chronic ocular hypertension was induced in C57BL6/J mice by laser ablation of the limbal episcleral veins. Scotopic flash electroretinograms were recorded after 5, 10, 20, and 40 days to isolate specific outer and inner retinal responses. Inner retinal function was correlated with the pressure differential between treated and non-treated eyes at the time of electroretinographic recording, and with the cumulative IOP insult (the integral of the IOP.time profile). Peripheral and central ganglion cell densities were quantified by Brn-3 immunohistochemistry. RESULTS: Elevated IOP induced a preferential deficit in inner retinal function. The positive scotopic threshold response (pSTR) was suppressed by 68% on day 5, by 50% on day 10, by 54% on day 20 and by 46% on day 40 after laser treatment. Inhibition of the STR correlated with the pressure differential between treated and non-treated eyes but not with the IOP.time integral. Inner retinal dysfunction preceded the progressive death of ganglion cells. Ganglion cell loss occurred preferentially in peripheral retina and correlated with the cumulative IOP insult. CONCLUSION: We have demonstrated specific inner retinal dysfunction in an inducible mouse glaucoma model. STRs are sensitive to elevated IOP per se, and their early suppression reflects ganglion cell dysfunction rather than cell death. The correlation between IOP elevation and suppression of inner retinal function, in the context of the temporal progression of ganglion cell death, suggests that a portion of the IOP-mediated ganglion cell dysfunction may be reversible.

Validation of the Marijuana Effect Expectancy Questionnaire-Brief.

The purpose of this study was to evaluate a brief version of the Marijuana Effect Expectancy Questionnaire (MEEQ; Schafer & Brown, 1991). The original MEEQ was reduced to 6 items (MEEQ-B). Principal component analysis (PCA) was performed and two factors were identified (positive effects and negative effects) accounting for 52.3% of the variance. Internal consistencies (0.42 to 0.60) were slightly lower than those of the original MEEQ. The negative effect expectancy scale correlated with criterion variables that assess marijuana use (p ≤ .05). This measure is a helpful tool for clinicians to use when assessing youth expectancies. Replication across different samples of adjudicated youth is recommended.

Investigation into the temporal stability of aqueous standard solutions of psilocin and psilocybin using high performance liquid chromatography.

This paper reports an investigation into the temporal stability of aqueous solutions of psilocin and psilocybin reference drug standards over a period of fourteen days. This study was performed using high performance liquid chromatography utilising a (95:5% v/v) methanol: 10 mM ammonium formate, pH 3.5 mobile phase and absorption detection at 269 nm. It was found that the exclusion of light significantly prolonged the useful life of standards, with aqueous solutions of both psilocin and psilocybin being stable over a period of seven days.

A questionnaire study for 128 patients with Gaucher disease.

Gaucher disease is an uncommon autosomal recessive disorder characterized by lysosomal storage of glucosyl ceramide, a material released during cell degradation. Patients with Gaucher disease often have significant hematologic, bone structural, and visceral problems which sometimes greatly affect their health and life style. Based on some extraordinary scientific discoveries over the past 45 years, a treatment system has evolved which consists of administration of an enzyme, which destroys the lysosome-stored material and to some extent restores the patients to good health. There are still some problems for these patients; however, and the purpose of the study is to define some of the clinical, sociologic, and psychologic problems with a specially designed questionnaire. Questionnaire data was collected for 128 patients from two institutions with complete anonymity, and the information compared against data from a National Health Interview Survey. The results show that many of the patients still have fairly extensive problems, which could possibly be helped by some alterations in treatment protocols.

Improving medication management for patients: the effect of a pharmacist on post-admission ward rounds.

PROBLEM: Medication management in the NHS has been highlighted by the UK Department of Health as an area for improvement. Pharmacist participation on post-take (post-admission) ward rounds was shown to reduce medication errors and reduced prescribing costs in the USA and in UK teaching hospitals, which can contribute to improved medication management. We sought to demonstrate the problem in our hospital by collecting data on prescribing practice from three consecutive general medical post-take ward rounds. SETTING: Northwick Park Hospital, a district general hospital in north-west London, which provides acute medical services to a population of 300,000. STRATEGY FOR CHANGE: A pharmacist was invited to become a member of the post-take ward round team that reviewed medical patients admitted within the preceding 24 hours. Patients also continued to receive care from a ward based pharmacist. Patient notes were analysed for cost of drugs on admission and discharge, discrepancies between admission drug history and pharmacist history, number of admission drugs stopped before discharge, and pharmacist recommendations. Pharmacist recommendations and actions were classified using a National Patient Safety Agency risk matrix. EFFECTS OF CHANGE: Discrepancies between the admission and the pharmacist derived drug history were noted in 26 of 50 in the pre-intervention group and 52 of 53 in the intervention group. The annual drug cost per patient following discharge increased by pounds 181 in the pre-intervention group and by pounds 122 in the intervention group. Five pre-admission drugs were stopped in three pre-intervention patients saving pounds 276 per annum, while the 42 drugs stopped in 19 intervention patients saved pounds 4699 per annum. No ward based pharmacist recommendations were recorded in the pre-intervention group. Recommendations regarding drug choice, dose, and need for drug treatment were most common; 58 minor, 48 moderate and four major risks to patients were potentially avoided. LESSONS LEARNT: The presence of a pharmacist on a post-take ward round improved the accuracy of drug history documentation, reduced prescribing costs, and decreased the potential risk to patients in our hospital. As a result of this work a full time pharmacist has now been funded to attend daily post-take ward rounds on a permanent basis.

Adolescent alcohol use and injury. A summary and critical review of the literature.

BACKGROUND: Survey research indicates that alcohol use and misuse by adolescents is prevalent worldwide and has been associated with multiple negative health, social, and economic consequences. Physical injury is one of the negative consequences of alcohol use that appears to be on the rise among adolescents. METHODS: A retrospective review was conducted of published data currently available regarding alcohol use and injury among adolescents. Studies were reviewed if 1) the sample included adolescents between the ages of 13 and 19 years, 2) the study site was a medical setting, and 3) data were collected regarding alcohol ingestion. RESULTS: Data indicate that rates of adolescent alcohol use range from 5% among general emergency department (ED) admissions to nearly 50% among trauma admissions. Alcohol-positive adolescents are more likely than alcohol-negative adolescents to be injured, have a prior history of injury, require trauma service care, and have injury complications. One-third to one-half of alcohol-positive adolescents are referred for or receive intervention related to their alcohol use. CONCLUSIONS: Alcohol use by adolescents is associated with increases in severity of injury and cost of medical treatment. Screening of adolescent trauma unit admissions for alcohol use might be justified based on the literature. Optimal methods of screening, identification, and brief intervention for alcohol abusing adolescents within the medical setting are discussed.

A neurological symptom survey of patients with type I Gaucher disease.

Gaucher disease is an inborn error of glycosphingolipid metabolism resulting from deficiency of the lysosomal enzyme glucocerebrosidase. The majority of the patients (with type I disease) do not have primary central nervous system involvement. However, several studies have noted that secondary neurological complications may develop as a consequence of nerve root or spinal cord compression following vertebral body collapse or, for those with coagulation disorders, bleeding within confined compartments. An epidemiological survey was conducted to ascertain the incidence of neurological symptoms in patients with Gaucher disease type I (GD I). The survey included a review of the patients' medical history, an estimate of Gaucher disease severity according to a modified Symptom Severity Index (SSI), and completion of a questionnaire regarding their neurological status and Quality of Life (QoL) according to the SF-36 Health Survey. Seventy-three per cent of respondents were found to have experienced at least one neurological complaint in the preceding 3 months. Adult patients with Gaucher disease often have other medical problems unrelated to their primary diagnosis. Thus, the high incidence of neurological complaints in these patients may be attributable to concurrent medical problems and/or side-effects from concomitant medications. These issues may influence patients' assessment of their disease severity and/or response to treatment.

Risks associated with alcohol-positive status among adolescents in the emergency department: a matched case-control study.

OBJECTIVE: The purpose of this study was to examine alcohol use, alcohol-related problems, other risk-taking behaviors, and parental monitoring in adolescents who tested positive for alcohol in an emergency department. STUDY DESIGN: A matched case-control design was implemented for adolescents presenting to a pediatric emergency department who were screened for alcohol use. An alcohol-positive sample (N = 150) was compared with a matched alcohol-negative sample (N = 150) for alcohol use, alcohol problems, depression, smoking, risk-taking behavior, and parental monitoring. RESULTS: The alcohol-positive group reported significantly higher drinking frequency, drinking problems, prior alcohol-related injuries, and episodes of driving after drinking and riding with a drinking driver than the alcohol-negative adolescents. The same pattern was true for depressed mood, reckless behaviors, poor grades in school, and daily smoking. The parents of alcohol-positive teens reported their teens had come home intoxicated more often than parents of alcohol-negative teens. There were no differences between parent groups in monitoring of teens. CONCLUSION: Adolescents who test positive for alcohol in an emergency department are a high-risk group who meet the criteria for indicated prevention. Screening for alcohol abuse is recommended.

Australia's university courses: are they meeting the educational expectations of the National Environmental Health Strategy?

Australia has developed a national strategy to encourage an intersectoral approach to environmental health and the creation of an environment that promotes good health and prevents problems. This strategy has implications for the education and training of the workforce. Therefore, the authors conducted a survey of courses in environmental health and other courses highly relevant to the environment offered by Australian universities in 2000. The purpose was to determine the extent to which those courses meet the educational expectations of the National Environmental Health Strategy. Results of the survey showed that Australia's universities are not meeting all the educational expectations of the national strategy. These findings might prompt other countries that agree with the thrust of the strategy to review their own educational offerings.

Differential perturbation of neuronal and glial glutamate transport systems in retinal ischaemia.

Glutamate is the major excitatory neurotransmitter in the retina and is removed from the extracellular space by an energy-dependent process involving neuronal and glial cell transporters. The radial glial Müller cells express the glutamate transporter, GLAST, and preferentially accumulate glutamate. However, during an ischaemic episode, extracellular glutamate concentrations may rise to excitotoxic levels. Is this catastrophic rise in extracellular glutamate due to a failure of GLAST? Using immunocytochemistry, we monitored the transport of the glutamate transporter substrate, D-aspartate, in the retina under normal and ischaemic conditions. Two models of compromised retinal perfusion were compared: (1) Anaesthetised rats had their carotid arteries occluded for 7 days to produce a chronic reduction in retinal blood flow. Retinal function was assessed by electroretinography. D-aspartate was injected into the eye for 45 min. Following euthanasia, the retina was processed for D-aspartate, GLAST and glutamate immunocytochemistry. Although reduced retinal perfusion suppresses the electroretinogram b-wave, neither retinal histology, GLAST expression, nor the ability of Müller cells to uptake D-aspartate is affected. As this insult does not appear to cause excitotoxic neuronal damage, these data suggest that GLAST function and glutamate clearance are maintained during periods of reduced retinal perfusion. (2) Occlusion of the central retinal artery for 60 min abolishes retinal perfusion, inducing histological damage and electroretinogram suppression. Although GLAST expression appears to be normal, its ability to transport D-aspartate into Müller cells is greatly reduced. Interestingly, D-aspartate is transported into neuronal cells, i.e. photoreceptors, bipolar and ganglion cells. This suggests that while GLAST is vitally important for the clearance of excess extracellular glutamate, its capability to sustain inward transport is particularly susceptible to an acute ischaemic attack. Manipulation of GLAST function could alleviate the degeneration and blindness that result from ischaemic retinal disease.

Critical review of epidemiological studies of the association between smoking and non-Hodgkin's lymphoma.

Smoking has been suggested to increase the risk of non-Hodgkin's lymphoma (NHL) but the results of epidemiological studies have been inconsistent. The aim of this work was to assess whether the findings of individual studies might have arisen by chance, bias or confounding and whether any associations found between smoking and NHL represent cause-and-effect. Reports of the association between smoking and NHL were identified from Medline. Confidence intervals on relative risks and odds ratios, use of multiple comparisons, and information on source, direction, actual existence and size of potential biases and confounding and features of any associations were abstracted. Four out of five cohort studies found no association between current smoking and NHL but three may have been biased against doing so. One found an association with follicular lymphoma but without a convincing exposure-risk gradient. The fifth found a strong association and an exposure-response gradient with ever smoking but excluded living cases from the end-point. Only one study found an association with past smoking which lacked features of causality. Eight out of 14 case-control studies found no association between current and/or past smoking and NHL but five may have been biased against doing so. Of six positive studies, three involved multiple comparisons, the association of one became non-significant after eliminating bias, four did not explore features of causality and one found an association only in heavy smokers, particularly under 45 years old. There are no grounds to reject the null hypothesis but associations should continue to be sought particularly in subgroups of smokers and with NHL subtypes.

Combined effect of cyclosporine and sirolimus on improving the longevity of recombinant adenovirus-mediated transgene expression in the retina.

OBJECTIVES: To reevaluate the longevity and intraocular safety of recombinant adenovirus (rAd)-mediated gene delivery after subretinal injection, and to prolong transgene expression through the combination of 2 synergistic immunosuppressants. METHODS: An rAd vector carrying green fluorescent protein (GFP) gene was delivered subretinally in the rat eye. The GFP expression was monitored in real time by fundus fluorescent photography. Intraocular safety was examined by observation of changes of retinal pigmentation, cell infiltration in virus-contacted area, immunophenotyping for CD4(+) and CD8(+) cytotoxic T lymphocytes, and CD68(+) macrophages, histologic findings, and dark-adapted electroretinography. Two synergistic immunosuppressants, cyclosporine and sirolimus, were used alone or in combination to prolong transgene expression by temporary immunosuppression. RESULTS: The GFP expression peaked on day 4, dramatically decreased on day 10, and was not detectable on day 14. The decreased GFP expression was coincident with cell infiltration in virus-contacted area. Immunostaining showed that the infiltrating cells were CD4(+) and CD8(+) cytotoxic T lymphocytes and CD68(+) macrophages. Clumped retinal pigmentation and decreased b wave of dark-adapted electroretinogram were observed at 3 to 4 weeks after injection. Histologic examination confirmed rAd-induced retinal degeneration. Transient immunosuppression by cyclosporine and sirolimus, either alone or in combination, improved transgene expression, with the combination being the most efficient. The combined immunosuppression attenuated but did not retard the rAd-induced retinal damage. CONCLUSIONS: Transgene expression mediated by rAd after subretinal delivery is short-term and toxic to the retina. Combination of cyclosporine and sirolimus may act as an immunosuppressive adjunct to prolong rAd-mediated gene transfer. CLINICAL RELEVANCE: The intraocular safety of rAd should be carefully considered before clinical trials are performed.

Helicobacter pylori infection and fasting plasma glucose concentration.

BACKGROUND: Helicobacter pylori infection raises basal and meal stimulated serum gastrin concentrations and lowers iron stores, which may in turn reduce fasting plasma glucose concentrations in the population. AIM: To determine whether H pylori infection leads to lower fasting plasma glucose concentrations in the population. METHODS: One hundred and seventy three women and 165 men, randomly selected from the electoral rolls of an Australian city, participated in a cardiovascular risk factor survey. Plasma glucose concentrations and H pylori IgG antibody titres were measured. Non-fasting subjects and pregnant women were excluded, as were known diabetics, whose plasma glucose concentrations would be affected by diet and/or medications. Fasting plasma glucose concentrations were logarithmically transformed and the relation with H pylori infection, adjusting for age and other confounding factors, was determined for men and women separately by analyses of variance. RESULTS: Helicobacter pylori infection was significantly associated with fasting plasma glucose concentration among women. Infected women had a lower mean fasting plasma glucose concentration (5.2 mmol/litre; range, 3.9-8.2) than did non-infected women (5.4 mmol/litre; range, 3.9-11.1). CONCLUSIONS: Helicobacter pylori infection may lead to lower fasting plasma glucose concentrations among women and should be considered when interpreting concentrations bordering on diabetes.