Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study.

HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white matter hyperintensities. METHODS: In the Leukoaraiosis And DISability in the elderly (LADIS) study, we investigated the relationships between DM, hypertension, blood pressure and MTA in 582 subjects, stratified by white matter hyperintensity severity, using multinomial logistic regression. MTA was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95% CI: 1.1-7.8) compared with an MTA score of 0 (no atrophy). The odds ratio for MTA score 2 was not significantly increased (OR 1.8; CI: 0.9-4). Systolic and diastolic blood pressure and a history of hypertension were not associated with MTA. There was no interaction between DM and hypertension. Stratification on white matter hyperintensities (WMH) did not alter the associations. CONCLUSION: Our study strengthens the observation that MTA is associated with DM, independently of the amount of small vessel disease as reflected by WMH.     

Intravenous fate of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes

The objective of this study was to assess the in vivo fate of poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA)-based polyplexes after intravenous administration into mice. Circulation kinetics and tissue distribution in terms of plasmid localization and transfection efficiency were assessed. To gain more insight into the observed biodistribution and gene expression profile, the interaction of pDMAEMA-based polyplexes with blood components (erythrocytes and albumin) was investigated in vitro. In the case of i.v. injection of positively charged polyplexes at a dose of 30 microg DNA most of the radioactivity was found in the lungs and the liver 60 min after injection. In the case of pDMAEMA/DNA polyplexes with a negative charge, uptake occurred mainly by the liver. Administration of positively charged complexes at a 30 microg DNA dose resulted in reporter gene expression primarily in the lungs. Injection of negatively charged complexes and naked plasmid did not result in luciferase expression in any of the organs examined. In vitro turbidity experiments showed the induction of a charge dependent aggregation process upon addition of albumin to the polyplexes pointing out to the involvement of aggregate formation in the dominant lung uptake of the positively charged polyplexes. Also, incubations of polyplexes after pre-incubation with a physiological concentration of albumin with washed erythrocytes confirmed that polyplexes induce the formation of extremely large structures. This paper underlines the need for the design of systems with reduced interaction with blood components to promote the delivery of DNA to target tissues outside the lungs.     

Iridium‐mediated β‐deuteration of enones

Exposure of captodative enone systems to deuterium in the presence of Crabtree's catalyst ( 1 ) results in deuteration at the vinylic site β‐ to the ketone carbonyl, as well as at any accessible ortho‐position. β‐exchange is also observed during the reduction of ethyl cinnamate ( 3 ) catalyzed by 1 . Copyright © 2003 John Wiley & Sons, Ltd.     

Causes and types of health effects during the use of crop protection chemicals: data from a survey of over 6,300 smallholder applicators in 24 different countries

Purpose  The present investigation looks in detail at the causes and types of health incidents reported by 6,300 mainly smallholder agrochemical users in 24 countries during 2005 and 2006. Methods  The investigation is based on a questionnaire survey of knowledge, attitude and practice that concentrated on the sequence of events from purchasing the pesticide to disposal. Information was also collected about health problems experienced while using agrochemicals. The survey targeted mainly smallholder knapsack spray operators who were expected to be at a highest risk of exposure. Results  In the 12 months prior to interview, 1.2% of users reported an agrochemical-related incident that required hospital treatment, 5.8% reported an incident requiring at least trained medical treatment but not hospitalisation and 19.8% reported only a minor sign or symptom. Users who had experienced an incident involving agricultural equipment were 3.38 (95% CI 2.29–4.99) times more likely to experience an agrochemical-related health incident, but confident users who felt that their use of personal protective equipment while spraying was best practice were 0.60 (95% CI 0.44–0.84) times less likely to experience such an incident. Over 80% of product-related incidents were caused by insecticides and the incidence rate per spraying time for incidents linked to insecticides was significantly higher than that for fungicides or herbicides. Headache/dizziness and nausea/vomiting, often smell related, were the most common symptoms reported by users who listed agrochemical products that had caused them health problems (52 and 38% of product mentions, respectively). Conclusions  In most countries, the incidence of serious health effects was low; however, there was a high incidence of minor signs and symptoms in a few countries, especially in Africa. A disproportionate number of incidents occurred during insecticide use relative to the time that they were sprayed. Failure to exercise caution as indicated by whether users had incidents involving agricultural equipment or livestock, and lack of confidence in their practices were the most important predictors of agrochemical-related incidents.     

瑞格列奈与迪沙片治疗新诊断2型糖尿病的疗效对比观察

比较对新诊断2型糖尿病患者应用瑞格列奈（11例）和迪沙片（10例）治疗4周后空腹血糖（FPG）、餐后2h血糖（2hPG）、晨3点血糖（3aPG）,空腹胰岛素（FIns）、餐后2h胰岛素（2hIns）,糖化白蛋白的值。结果显示,与迪沙片组相比,瑞格列奈组治疗后空腹血糖、餐后2h血糖的下降幅度更为明显,但低血糖的发生次数反而减少。     

TGF-β and IL-17 serum levels and specific immunotherapy

Two new T cell subsets may be involved in allergic rhinitis (AR) pathogenesis: Th17 and T regulatory cells, mainly producing IL-17 and TGF-β respectively. Successful Sublingual Immunotherapy (SLIT) induces relevant immunological changes, thus the aim of this study was to evaluate serum IL-17 and TGF-β levels in AR patients treated with SLIT for 2 years. Patients' blood samples were collected before initiating SLIT (baseline), three months after the end of the first pre-seasonal SLIT course, and at the end of the second pre-seasonal course. IL-17 was detectable only in the most severe allergic patients. SLIT significantly induced an increase in serum TGF-β levels. There was moreover a significant relationship between TGF-β and symptom severity and drug use at the end of the study. Therefore, this study provides clinically relevant evidence that two pre-seasonal SLIT courses may significantly affect serum TGF-β levels.     

Incidence of Type 2 diabetes in England and its association with baseline impaired fasting glucose: the Ely study 1990-2000.

AIM: To determine the incidence of Type 2 diabetes and to examine the effect of different cut-points for impaired fasting glucose (IFG) on diabetes incidence. METHODS: Population-based longitudinal study (1990-2000) with clinical, anthropometric and biochemical measurements, including an oral glucose tolerance test (OGTT), in 1040 non-diabetic adults aged 40-69 years at baseline. Baseline glucose status was defined as normoglycaemia < 5.6, IFG-lower 5.6-6.0 and IFG-original 6.1-6.9 mmol/l. The all-IFG group included fasting glucose values of 5.6-6.9 mmol/l. RESULTS: The 10-year cumulative incidence of diabetes was 7.3 per 1000 person-years. Diabetes incidence was 2.4 [95% confidence interval (CI) 1.2, 4.8], 6.2 (4.0, 9.8) and 17.5 (12.5, 24.5) per 1000 person-years in those with normoglycaemia, IFG-lower and IFG-original, respectively. Compared with normoglycaemia, the age/sex-adjusted risk [hazard ratio (HR) and 95% CI] for incident diabetes was greatest in the IFG-original category (HR 6.9; 3.1, 15.2) and increased to a lesser degree in the IFG-lower (HR 2.5; 1.1, 5.7) and all-IFG categories (HR 4.1; 1.9, 8.7). When adjusted for confounding factors, the magnitude and direction of associations persisted, with HR 1.9, 4.4 and 2.9, for the categories IFG-lower, IFG-original and all-IFG, respectively. CONCLUSIONS: Diabetes incidence is more strongly related to IFG defined as fasting glucose between 6.1 and 6.9 mmol/l than to the lower category of 5.6-6.0 mmol/l, or entire range of 5.6-6.9 mmol/l. Future studies should examine the association of IFG with cardiovascular outcomes, but for diabetes risk our study supports the use of the IFG cut-point at 6.1 mmol/l.     

The UK Diabetes Research Network--an opportunity and a challenge.

The Department of Health has funded a national diabetes network to support clinical research. The network will facilitate recruitment into clinical trials and has been widely welcomed by clinicians. However, if the network is to reach its full potential, all those involved will need to advocate a change in attitude towards clinical trials and research, encouraging participation and contribution of data. Clinicians need to be willing to take a proactive view about research studies, and to encourage patients to adopt a positive and altruistic attitude towards trial participation. The future of trials and other important clinical research in the UK may depend on it.     

Time and cost involved in the care of newly registered patients with diabetes mellitus and other lifestyle diseases at diabetes clinics in Japan (JDDM 4).

AIMS: To study the time and cost involved in the care of newly registered outpatients with Type 2 diabetes mellitus (DM), compared with patients with hypertension and/or hyperlipidaemia (HTL). METHODS: A total of 313 patients with DM and 58 patients with HTL without diabetes were registered on their first visits to 11 diabetes clinics across Japan. The time and cost involved in their care was recorded over the following 5 months. RESULTS: In the first 3 months, there was an extensive time commitment to both groups. The time spent by physicians was 1.5 times longer for DM than for HTL. The total care time spent by all the care providers for DM was twice that for HTL. The cost of DM care was twice that for HTL, with the cost of medicines excluded. However, half of the cost for DM was for laboratory tests. When these were excluded, and the remaining cost divided by the time spent, the amount for DM was half of that for HTL. Over the 5 months, mean glycated haemoglobin (HbA(1c)) in DM patients improved from 8.0% to 6.5%, and 72% of DM patients achieved the glycaemic target of HbA(1c) < or = 6.5%. CONCLUSIONS: DM care in a diabetes clinic requires a great deal more time and resources than HTL to achieve the best outcome. An educational system for self care, presently lacking in the primary care setting in Japan, would improve glycaemic control for DM patients in the community.     

Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.