The effects of a combination of ion channel inhibitors in female rats following repeated mild traumatic brain injury

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Following mild traumatic brain injury (mTBI), the ionic homeostasis of the central nervous system (CNS) becomes imbalanced. Excess Ca2+ influx into cells triggers molecular cascades, which result in detrimental effects. The authors assessed the effects of a combination of ion channel inhibitors (ICI) following repeated mTBI (rmTBI). Adult female rats were subjected to two rmTBI weight-drop injuries 24 h apart, sham procedures (sham), or no procedures (normal). Lomerizine, which inhibits voltage-gated calcium channels, was administered orally twice daily, whereas YM872 and Brilliant Blue G, inhibiting a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and P2X7 receptors, respectively, were delivered intraperitoneally every 48 h post-injury. Vehicle treatment controls were included for rmTBI, sham, and normal groups. At 11 days following rmTBI, there was a significant increase in the time taken to cross the 3 cm beam, as a sub-analysis of neurological severity score (NSS) assessments, compared with the normal control (p < 0.05), and a significant decrease in learning-associated improvement in rmTBI in Morris water maze (MWM) trials relative to the sham (p < 0.05). ICI-treated rmTBI animals were not different to sham, normal controls, or rmTBI treated with vehicle in all neurological severity score and Morris water maze assessments (p > 0.05). rmTBI resulted in increases in microglial cell density, antioxidant responses (manganese-dependent superoxide dismutase (MnSOD) immunoreactivity), and alterations to node of Ranvier structure. ICI treatment decreased microglial density, MnSOD immunoreactivity, and abnormalities of the node of Ranvier compared with vehicle controls (p < 0.01). The authors’ findings demonstrate the beneficial effects of the combinatorial ICI treatment on day 11 post-rmTBI, suggesting an attractive therapeutic strategy against the damage induced by excess Ca2+ following rmTBI

West Nile virus: the Italian national transplant network reaction to an alert in the north-eastern region, Italy 2011

We report four cases of West Nile virus (WNV) transmission following a single multiorgan donation in north-eastern Italy. The transmissions were promptly detected by local transplant centres. The donor had been tested for WNV by nucleic acid amplification test (NAT) prior to transplantation and was negative. There were no detected errors in the nationally implemented WNV safety protocols

West Nile virus: the Italian national transplant network reaction to an alert in the north-eastern region, Italy 2011.

We report four cases of West Nile virus (WNV) transmission following a single multiorgan donation in north-eastern Italy. The transmissions were promptly detected by local transplant centres. The donor had been tested for WNV by nucleic acid amplification test (NAT) prior to transplantation and was negative. There were no detected errors in the nationally implemented WNV safety protocols

Lower cardiorespiratory fitness contributes to increased insulin resistance and fasting glycaemia in middle-aged South Asian compared with European men living in the UK

AIMS/HYPOTHESIS: This study aimed to determine the extent to which increased insulin resistance and fasting glycaemia in South Asian men, compared with white European men, living in the UK, was due to lower cardiorespiratory fitness (maximal oxygen uptake [[Formula: see text]]) and physical activity. METHODS: One hundred South Asian and 100 age- and BMI-matched European men without diagnosed diabetes, aged 40–70 years, had fasted blood taken for measurement of glucose concentration, HOMA-estimated insulin resistance (HOMA(IR)), plus other risk factors, and underwent assessment of physical activity (using accelerometry), [Formula: see text], body size and composition, and demographic and other lifestyle factors. For 13 South Asian and one European man, HbA(1c) levels were >6.5% (>48 mmol/mol), indicating potential undiagnosed diabetes; these men were excluded from the analyses. Linear regression models were used to determine the extent to which body size and composition, fitness and physical activity variables explained differences in HOMA(IR) and fasting glucose between South Asian and European men. RESULTS: HOMA(IR) and fasting glucose were 67% (p < 0.001) and 3% (p < 0.018) higher, respectively, in South Asians than Europeans. Lower [Formula: see text], lower physical activity and greater total adiposity in South Asians individually explained 68% (95% CI 45%, 91%), 29% (11%, 46%) and 52% (30%, 80%), respectively, and together explained 83% (50%, 119%) (all p < 0.001) of the ethnic difference in HOMA(IR). Lower [Formula: see text] and greater total adiposity, respectively, explained 61% (9%, 111%) and 39% (9%, 76%) (combined effect 63% [8%, 115%]; all p < 0.05) of the ethnic difference in fasting glucose. CONCLUSIONS/INTERPRETATION: Lower cardiorespiratory fitness is a key factor associated with the excess insulin resistance and fasting glycaemia in middle-aged South Asian, compared with European, men living in the UK. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-013-2969-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Levels of omega-3 fatty acid in serum phospholipids and depression in patients with lung cancer

Previous studies suggested that omega-3 fatty acids (FAs) have therapeutic effects against depression, but there is no evidence in the oncological setting. Our preliminary study reported the association between lower omega-3 FA intake and occurrence of depression in lung cancer patients. To explore the association further, the present study examined whether depression was associated with lower levels of omega-3 FAs in serum phospholipids. A total of 717 subjects in the Lung Cancer Database Project were divided into three groups by two cutoff points of the Hospital Anxiety and Depression Scale depression subscale (HADS-D). In all, 81 subjects of the nondepression and minor depression groups (HADS-D<5 and 5⩽HADS-D⩽10, respectively) were selected to match with 81 subjects of the major depression group (HADS-D>10) for age, gender, clinical stage, and performance status. Fatty acids were assayed by gas chromatography and compared among the three matched groups. There were no differences between the major depression group and nondepression group in any FAs. The minor depression group had higher mean levels of docosahexaenoic acid (mean±s.d. (%), nondepression: 7.40±1.54; minor depression: 7.90±1.40; major depression: 7.25±1.52, P=0.017). These results suggested that serum FAs are associated with minor, but not major, depression in lung cancer patients

Saturated Fatty Acids and Risk of Coronary Heart Disease: Modulation by Replacement Nutrients

Despite the well-established observation that substitution of saturated fats for carbohydrates or unsaturated fats increases low-density lipoprotein (LDL) cholesterol in humans and animal models, the relationship of saturated fat intake to risk for atherosclerotic cardiovascular disease in humans remains controversial. A critical question is what macronutrient should be used to replace saturated fat. Substituting polyunsaturated fat for saturated fat reduces LDL cholesterol and the total cholesterol to high-density lipoprotein cholesterol ratio. However, replacement of saturated fat by carbohydrates, particularly refined carbohydrates and added sugars, increases levels of triglyceride and small LDL particles and reduces high-density lipoprotein cholesterol, effects that are of particular concern in the context of the increased prevalence of obesity and insulin resistance. Epidemiologic studies and randomized clinical trials have provided consistent evidence that replacing saturated fat with polyunsaturated fat, but not carbohydrates, is beneficial for coronary heart disease. Therefore, dietary recommendations should emphasize substitution of polyunsaturated fat and minimally processed grains for saturated fat

Fat Oxidation, Fitness and Skeletal Muscle Expression of Oxidative/Lipid Metabolism Genes in South Asians: Implications for Insulin Resistance?

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; South Asians are more insulin resistant than Europeans, which cannot be fully explained by differences in adiposity. We investigated whether differences in oxidative capacity and capacity for fatty acid utilisation in South Asians might contribute, using a range of whole-body and skeletal muscle measures.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology/Principal Findings:&lt;/b&gt; Twenty men of South Asian ethnic origin and 20 age and BMI-matched men of white European descent underwent exercise and metabolic testing and provided a muscle biopsy to determine expression of oxidative and lipid metabolism genes and of insulin signalling proteins. In analyses adjusted for age, BMI, fat mass and physical activity, South Asians, compared to Europeans, exhibited; reduced insulin sensitivity by 26% (p = 0.010); lower VO2max (40.6±6.6 vs 52.4&#177;5.7 ml.kg−1.min−1, p = 0.001); and reduced fat oxidation during submaximal exercise at the same relative (3.77&#177;2.02 vs 6.55&#177;2.60 mg.kg−1.min−1 at 55% VO2max, p = 0.013), and absolute (3.46&#177;2.20 vs 6.00&#177;1.93 mg.kg−1.min−1 at 25 ml O2.kg−1.min−1, p = 0.021), exercise intensities. South Asians exhibited significantly higher skeletal muscle gene expression of CPT1A and FASN and significantly lower skeletal muscle protein expression of PI3K and PKB Ser473 phosphorylation. Fat oxidation during submaximal exercise and VO2max both correlated significantly with insulin sensitivity index and PKB Ser473 phosphorylation, with VO2max or fat oxidation during exercise explaining 10–13% of the variance in insulin sensitivity index, independent of age, body composition and physical activity.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; These data indicate that reduced oxidative capacity and capacity for fatty acid utilisation at the whole body level are key features of the insulin resistant phenotype observed in South Asians, but that this is not the consequence of reduced skeletal muscle expression of oxidative and lipid metabolism genes.&lt;/p&gt

Erythrocyte Transketolase Activity, Markers of Cardiac Dysfunction and the Diagnosis of Infantile Beriberi

Infantile beriberi, or clinical thiamin (vitamin B1) deficiency in infants, is a forgotten disease in Asia, where ∼100 years ago it was a major public health problem. Children aged ∼2–3 months present in cardiac failure but usually rapidly improve if given thiamin injections. It remains relatively common in Vientiane, Lao PDR (Laos) probably because of prolonged intra- and post-partum maternal food avoidance behaviours. There has been very little recent research on the best diagnostic techniques. We conducted a case control study of 47 infants with beriberi and age-matched afebrile and febrile controls in Vientiane. The conventional measures of thiamin deficiency, basal and activated erythrocyte transketolase activities (ETK) and activation (α) coefficients, were assayed along with three markers of cardiac dysfunction - plasma brain natriuretic peptide, N-terminal pro-brain natriuretic peptide, and troponin T. Basal ETK was a better biochemical marker of infantile beriberi than the activation coefficient. Raised plasma troponin T may be a useful indicator of infantile beriberi in babies at risk and in the absence of other evident causes

Diet, lung function, and lung function decline in a cohort of 2512 middle aged men

BACKGROUND—A prospective cohort study of 2512 Welshmen aged 45-59 living in Caerphilly in 1979-1983 was used to investigate associations between diet and lung function.
METHODS—At baseline (phase I) and at five year follow up (phase II), forced expiratory volume in one second (FEV(1)) was measured using a McDermott spirometer and dietary data were obtained using a semi-quantitative food frequency questionnaire.
RESULTS—Good lung function, indicated by high maximum FEV(1) given age and height, was associated with high intakes of vitamin C, vitamin E, β-carotene, citrus fruit, apples, and the frequent consumption of fruit juices/squashes. Lung function was inversely associated with magnesium intake but there was no evidence of an association with fatty fish. Following adjustment for confounders including body mass index, smoking history, social class, exercise, and total energy intake, only the associations with vitamin E and apples persisted, with lung function estimated to be 39 ml (95% confidence interval (CI) 9 to 69) higher for vitamin E intakes one standard deviation (SD) apart and 138 ml higher (95% CI 58to 218) for those eating five or more apples per week compared with non-consumers. Decline in lung function between phases was not significantly associated with the changing intakes of apples or vitamin E. An association between high average apple consumption and slow decline in lung function lost significance after adjustment for confounders.
CONCLUSIONS—A strong positive association is seen between lung function and the number of apples eaten per week cross sectionally, consistent with a protective effect of hard fruit rather than soft/citrus fruit. The recent suggestion that such effects are reversible was not supported by our longitudinal analysis.


A randomised controlled trial to investigate the effect of a high fibre diet on blood pressure and plasma fibrinogen

Two hundred and one subjects (147 men and 54 women) were randomly allocated to either a high cereal fibre diet or a low cereal fibre diet for four weeks. Each group then followed the alternative diet for a further four weeks. Cereal fibre intakes were 19g/d (31 g/d 21 g/d total fibre) and 6g/d (19g/d total fibre) on the high and low fibre diets respectively (p less than 0.001). Energy, protein, fat, carbohydrate, and alcohol intakes calculated from weighed intake records did not differ between the two diets, although there was a slight difference in body weight, the mean being 0.3 kg heavier at the end of the high fibre period. The high cereal fibre diet had no detectable effect on blood pressure or plasma fibrinogen