BackgroundObesity and type 2 diabetes (T2DM) are associated with increased circulating free fatty acids and triacylglycerols. However, very little is known about specific molecular lipid species associated with these diseases. In order to gain further insight into this, we performed plasma lipidomic analysis in a rodent model of obesity and insulin resistance as well as in lean, obese and obese individuals with T2DM.Methodology/Principal FindingsLipidomic analysis using liquid chromatography coupled to mass spectrometry revealed marked changes in the plasma of 12 week high fat fed mice. Although a number of triacylglycerol and diacylglycerol species were elevated along with of a number of sphingolipids, a particularly interesting finding was the high fat diet (HFD)-induced reduction in lysophosphatidylcholine (LPC) levels. As liver, skeletal muscle and adipose tissue play an important role in metabolism, we next determined whether the HFD altered LPCs in these tissues. In contrast to our findings in plasma, only very modest changes in tissue LPCs were noted. To determine when the change in plasma LPCs occurred in response to the HFD, mice were studied after 1, 3 and 6 weeks of HFD. The HFD caused rapid alterations in plasma LPCs with most changes occurring within the first week. Consistent with our rodent model, data from our small human cohort showed a reduction in a number of LPC species in obese and obese individuals with T2DM. Interestingly, no differences were found between the obese otherwise healthy individuals and the obese T2DM patients.ConclusionIrrespective of species, our lipidomic profiling revealed a generalized decrease in circulating LPC species in states of obesity. Moreover, our data indicate that diet and adiposity, rather than insulin resistance or diabetes per se, play an important role in altering the plasma LPC profile.

Abstract-In the present study, we investigated the role of the angiotensin type 2 (AT 2 ) receptor in the regulation of blood pressure in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We tested the hypothesis that AT 2 receptor activation may contribute to the antihypertensive effects of angiotensin type 1 (AT 1 ) receptor antagonists. Mean arterial pressure (MAP) and heart rate were measured over a 4-day protocol in various groups of rats that received the following drug combinations: the AT 1 receptor antagonist candesartan (0.01 or 0.1 mg/kg IV) alone, the AT 2 receptor agonist CGP42112 (1 g/kg per minute) alone, and candesartan plus CGP42112. In both SHR and WKY, 4-hour infusions of saline and CGP42112 alone did not alter MAP. In WKY, both doses of candesartan alone caused small decreases in MAP, which were similar when combined with CGP42112. In SHR, candesartan (0.1 mg/kg) caused an immediate, marked decrease in MAP, which was unaffected when combined with CGP42112. By contrast, in separate SHR, a 10-fold lower dose of candesartan (0.01 mg/kg) caused a slower-onset depressor response, which was enhanced when combined with CGP42112. The involvement of AT 2 receptors was confirmed in another group of SHR, since this facilitation of the antihypertensive effect of candesartan by CGP42112 was abolished by the coinfusion of the AT 2 receptor antagonist PD123319 (50 g/kg per minute) with the candesartan/CGP42112 combination. Collectively, these data suggest that in SHR, AT 2 receptor activation can facilitate the initial depressor response caused by an AT 1 receptor antagonist. (Hypertension. 1999;34:1112-1116.)

Objective. To determine cancer risk in a cohort of 459 rheumatoid arthritis (RA) patients treated with methotrexate in community practice. Methods. All RA patients who started methotrexate prior to June 1986 and were attending 1 of 6 rheumatologists were studied. Demographic data were matched to the State Cancer Registry to identify all malignancies (except nonmelanoma skin cancer) for 1983-1998, and to the National Death Index to identify all deaths to the end of 1999. Followup started on the date when methotrexate was started and ended either on the last confirmed date on which the patient was seen by the rheumatologist or at death. Standardized incidence ratios (SIRs) were calculated using state population cancer rates stratified by sex, age (in 5-year groups), and calendar year. Results. There were 4,145 person-years of followup (average 9.3 years). Eighty-seven malignancies were identified (14 before, 64 during, and 9 after the followup period). There was an estimated 50% excess risk of malignancy among methotrexate-exposed RA patients relative to the general population (SIR 1.5, 95% confidence interval [95% CI] 1.2-1.9), with a 3-fold increase in melanoma (SIR 3.0, 95% CI 1.2-6.2), a 5-fold increase in non-Hodgkin's lymphoma (SIR 5.1, 95% CI 2.2-10.0), and an almost 3-fold increase in lung cancer (SIR 2.9, 95% CI 1.6 -4.8). Conclusion. Compared with the general population, methotrexate-treated RA patients have an increased incidence of melanoma, non-Hodgkin's lymphoma, and lung cancer. There may be a role for regular skin cancer screening for all RA patients, particularly those receiving immunosuppressive therapy.

The objective of this paper is to measure health literacy in a representative sample of the Australian general population using three health literacy tools; to consider the congruency of results; and to determine whether these assessments were associated with socio-demographic characteristics. Face-to-face interviews were conducted in a stratified random sample of the adult Victorian population identified from the 2004 Australian Government Electoral Roll. Participants were invited to participate by mail and follow-up telephone call. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine (REALM), Test of Functional Health Literacy in Adults (TOFHLA) and Newest Vital Sign (NVS). Of 1680 people invited to participate, 89 (5.3%) were ineligible, 750 (44.6%) were not contactable by phone, 531 (32%) refused and 310 (response rate 310/1591, 19.5%) agreed to participate. Compared with the general population, participants were slightly older, better educated and had a higher annual income. The proportion of participants with less than adequate health literacy levels varied: 26.0% (80/308) for the NVS, 10.6% (51 33/310) for the REALM and 6.8% (21/309) for the TOFHLA. A varying but significant proportion of the general population was found to have limited health literacy. The health literacy measures we used, while moderately correlated, appear to measure different but related constructs and use different cut offs to indicate poor health literacy.

Objective-To improve the accuracy of genotype prediction and guide genetic testing in patients with muscle channelopathies we applied and refined specialised electrophysiological exercise test parameters.Methods-We studied 56 genetically confirmed patients and 65 controls using needle electromyography, the long exercise test, and short exercise tests at room temperature, after cooling, and rewarming.Results-Concordant amplitude-and-area decrements were more reliable than amplitude-only measurements when interpreting patterns of change during the short exercise tests. Concordant amplitude-and-area pattern I and pattern II decrements of >20% were 100% specific for PMC and MC respectively. When decrements at room temperature and after cooling were <20%, a repeat short exercise test after rewarming was useful in patients with myotonia congenita. Area measurements and rewarming distinguished true temperature sensitivity from amplitude reduction due to cold-induced slowing of muscle fibre conduction. In patients with negative short exercise tests, symptomatic eye closure myotonia predicted sodium channel myotonia over myotonia congenita. Distinctive 'tornado-shaped' neuromyotonia-like discharges may be seen in patients with paramyotonia congenita. In the long exercise test, area decrements from pre-exercise baseline were more sensitive than amplitude decrements-from-maximum-CMAP in patients with Andersen-Tawil syndrome. Possible ethnic differences in the normative data of the long exercise test argue for the use of appropriate ethnically-matched controls.Interpretation-Concordant CMAP amplitude-and-area decrements of >20% allow more reliable interpretation of the short exercise tests and aid accurate DNA-based diagnosis. In patients

No abstract

No abstract

In experiments manipulating temperature and food levels, rates of short-term otolith growth and somatic growth of juvenile King George whiting Sillaginodes punctata became decoupled. Food levels were starvation, 100 and 1000 g per fish per day and temperatures were 12 and 18 C. Short-term somatic growth was influenced predominantly by food, with negligible growth at starvation and low ration, and significant growth at high food ration at both temperatures. In contrast, short-term otolith growth was influenced predominantly by temperature, with significant otolith growth occurring for all food treatments, and elevated otolith growth occurring at the higher temperature across food treatments. The identification of such differential effects of food and temperature leading to decoupling is an important result that has significant implications for using otoliths to estimate short-term growth. 2001 The Fisheries Society of the British Isles