Truncation of Plasmodium berghei merozoite surface protein 8 does not affect in vivo blood-stage development

Merozoite surface protein 8 (MSP8) has shown promise as a vaccine candidate in the Plasmodium yoelii rodent malaria model and has a proposed role in merozoite invasion of erythrocytes. However, the temporal expression and localisation of MSP8 are unusual for a merozoite antigen. Moreover, in Plasmodium falciparum the MSP8 gene could be disrupted with no apparent effect on in vitro growth. To address the in vivo function of full-length MSP8, we truncated MSP8 in the rodent parasite Plasmodium berghei. PbΔMSP8 disruptant parasites displayed a normal blood-stage growth rate but no increase in reticulocyte preference, a phenomenon observed in P. yoelii MSP8 vaccinated mice. Expression levels of erythrocyte surface antigens were similar in P. berghei wild-type and PbΔMSP8-infected erythrocytes, suggesting that a parasitophorous vacuole function for MSP8 does not involve global trafficking of such antigens. These data demonstrate that a full-length membrane-associated form of PbMSP8 is not essential for blood-stage growth.

Like blood or brown water

Gaylene Perry records the paradox of being a vegetarian in a family of butchers.

Local nitric oxide synthase inhibition reduces skeletal muscle glucose uptake but not capillary blood flow during in situ muscle contraction in rats

OBJECTIVE: We have previously shown in humans that local infusion of a nitric oxide synthase (NOS) inhibitor into the femoral artery attenuates the increase in leg glucose uptake during exercise without influencing total leg blood flow. However, rodent studies examining the effect of NOS inhibition on contraction-stimulated skeletal muscle glucose uptake have yielded contradictory results. This study examined the effect of local infusion of an NOS inhibitor on skeletal muscle glucose uptake (2-deoxyglucose) and capillary blood flow (contrast-enhanced ultrasound) during in situ contractions in rats.

RESEARCH DESIGN AND METHODS: Male hooded Wistar rats were anesthetized and one hindleg electrically stimulated to contract (2 Hz, 0.1 ms) for 30 min while the other leg rested. After 10 min, the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (arterial concentration of 5 µmol/l) or saline was infused into the epigastric artery of the contracting leg.

RESULTS: Local NOS inhibition had no effect on blood pressure, heart rate, or muscle contraction force. Contractions increased (P < 0.05) skeletal muscle NOS activity, and this was prevented by L-NAME infusion. NOS inhibition caused a modest significant (P < 0.05) attenuation of the increase in femoral blood flow during contractions, but importantly there was no effect on capillary recruitment. NOS inhibition attenuated (P < 0.05) the increase in contraction-stimulated skeletal muscle glucose uptake by ~35%, without affecting AMP-activated protein kinase (AMPK) activation.

CONCLUSIONS: NOS inhibition attenuated increases in skeletal muscle glucose uptake during contraction without influencing capillary recruitment, suggesting that NO is critical for part of the normal increase in skeletal muscle fiber glucose uptake during contraction.

Stimulation of cytokine production in human peripheral blood mononuclear cells by an aqueous Chlorella extract

CPE is an aqueous extract of the edible micro alga Chlorella pyrenoidosa, which has been shown to have immunostimulatory effects in vivo. In the present study, CPE was evaluated for an ability to stimulate cytokine production by human peripheral blood mononuclear cells (PBMC). PBMC from healthy individuals were treated ex vivo for 24 hours with 1, 10 and 100 μg/mL CPE. This resulted in a marked increase in the level of IL-10, a regulatory cytokine, and strong stimulation of the T-helper-1 (Th1) cell cytokines, IFN-γ and TNF-α. In contrast, stimulation of representative T-helper-2 (Th2) cell cytokines, IL-4 and IL-13, was minor. CPE (1, 10 or 100 μg/mL) did not cause a proliferation of human PBMC suggesting that enhanced secretion of cytokines was not secondary to an increase in cell number. We conclude that CPE stimulation of human PBMC induces a Th1-patterned cytokine response and a strong anti-inflammatory regulatory cytokine response, observations that await confirmation in vivo.

Whole blood analysis of phagocytosis, apoptosis, cytokine production, and leukocyte subsets in healthy older men and women: the ZENITH study

Few studies to date have examined age-related changes in markers of immune status in healthy older individuals. The immune status of 93 healthy individuals aged 55–70 years was assessed by two- and three-color flow cytometry and biochemical analysis. There were significant age effects (p ≤.05) on monocyte phagocytic activity and cluster of differentiation (CD) 3/human leukocyte antigen-D-related (HLA-DR) late-activated T lymphocytes (% expression). There was a significant (p ≤ 0.1) Age x Sex interaction in absolute counts (x 10⁹/L) of CD3/CD8 total cytotoxic T lymphocytes (CTL), the CD4 T- helper to CD8 CTL ratio, the CD3/CD4/CD45RA naïve T helper to CD3/CD4/CD45RO memory T helper lymphocyte ratio, and interleukin (IL)-1ß (% expression) by activated monocytes. The study shows that alterations in markers of immune status occur between 55 and 70 years, and provides reference values for the lymphocyte measures in healthy men and postmenopausal women in this age group. The study further highlights the need for sex-specific reference ranges for such markers.

Long-term effect of calcium-vitamin D3 fortified milk on blood pressure and serum lipid concenstrations in healthy older men

Background/Objectives:
Some epidemiological and clinical studies have shown that increased dairy consumption or calcium and/or vitamin D supplementation can have a beneficial effect on blood pressure, and lipid and lipoprotein concentrations. The aim of this study was to assess the long-term effects of calcium-vitamin D3 fortified milk on blood pressure and lipid-lipoprotein concentrations in community-dwelling older men.

Subjects/Methods:
This is a substudy of a 2-year randomized controlled trial in which 167 men aged >50 years were assigned to receive either 400 ml per day of reduced fat (approx1%) milk fortified with approximately 1000 mg of calcium and 800 IU of vitamin D3 or to a control group receiving no additional fortified milk. Weight, blood pressure, lipid and lipoprotein concentrations were measured every 6 months. Participants on lipid-lowering (n=32) or antihypertensive medication (n=39) were included, but those who commenced, increased or decreased their medication throughout the intervention were excluded (n=27).

Results:
In the 140 men included in this study (milk, n=73; control, n=67), there were no significant effects of the calcium-vitamin D3 fortified milk on weight, systolic or diastolic blood pressure, total cholesterol, high-density lipoprotein or low-density lipoprotein cholesterol or triglyceride concentrations at any time throughout the intervention. Similar results were observed after excluding men taking antihypertensive or lipid-lowering medication or limiting the analysis to those with baseline calcium intakes <1000 mg per day and/or with hypovitaminosis D (25(OH)D <75 nmol/l).

Conclusions:
Supplementation with reduced-fat calcium-vitamin D3 fortified milk did not have a beneficial (nor detrimental) effect on blood pressure, lipid or lipoprotein concentrations in healthy community-dwelling older men.

Low-sodium dietary approaches to stop hypertension-type diet including lean red meat lowers blood pressure in postmenopausal women

Low-sodium Dietary Approaches to Stop Hypertension (DASH) diets are base producing but restrict red meat without clear justification. We hypothesized that a vitality diet (VD), a low-sodium DASH-type diet with a low dietary acid load containing 6 servings of 100 g cooked lean red meat per week, would be more effective in reducing blood pressure (BP) compared with a higher acid load reference healthy diet (RHD) based on general dietary guidelines to reduce fat intake and increase intake of breads and cereals. A randomized, parallel dietary intervention study was conducted to compare the BP-lowering effect of these 2 diets in postmenopausal women with high/normal BP. Women were randomly assigned to follow either VD or RHD for 14 weeks. Home BP was measured daily with an automated BP monitor under standard conditions. Of 111 women commencing the study, 95 completed (46 VD, 49 RHD). Systolic BP (SBP) throughout the intervention was lower in the VD group compared to the RHD group (repeated-measures analysis of variance time by diet, P = .04), such that at the end of the study, the VD had a fall of SBP by 5.6 ± 1.3 mm Hg (mean ± SEM) compared with a fall of 2.7 ± 1.0 mm Hg in the RHD (group difference, P = .08). When only those taking antihypertensive medications were assessed, the VD (n = 17) had a significant fall of 6.5 ± 2.5 mm Hg SBP (P = .02) and 4.6 ± 1.4 mm Hg diastolic BP (P = .005) after 14 weeks, and their BP was lower than that of the RHD group (n = 18) throughout the study (P < .05). We concluded that a low-sodium DASH diet with a low dietary acid load, which also included lean red meat on most days of the week, was effective in reducing BP in older women, particularly in those taking antihypertensive medications.

Development of a salmon protein hydrolysate that lowers blood pressure

A salmon protein hydrolysate (SPH) was developed containing several angiotensin I-converting enzyme (ACE) inhibitory tripeptides the most abundant of which were Val-Leu-Trp, Val-Phe-Tyr, and Leu-Ala-Phe. Simulated digestion experiments showed that active constituents of SPH would survive in the digestive tract and be available for absorption into the bloodstream. In fact, ACE inhibitory activity was improved following simulated digestion suggesting that there were larger peptides in SPH that might contribute to bioactivity in vivo. A single oral dose (1,500 mg/kg body mass) of SPH significantly lowered blood pressure in spontaneously hypertensive rats (SHR). The treatment of SHR with either SPH fraction (<3,000 Da) or SPH fraction (>3,000 Da) reduced blood pressure. We conclude that the ability of SPH to lower blood pressure is due to a combination of ACE inhibitory tripeptides as identified, as well as additional unknown, peptide species that are generated during digestion of SPH in the gastrointestinal tract.

Food patterns associated with blood lipids are predictive of coronary heart disease : the Whitehall II study

Analysis of the epidemiological effects of overall dietary patterns offers an alternative approach to the investigation of the role of diet in CHD. We analysed the role of blood lipid-related dietary patterns using a two-step method to confirm the prospective association of dietary pattern with incident CHD. Analysis is based on 7314 participants of the Whitehall II study. Dietary intake was measured using a 127-item FFQ. Reduced rank regression (RRR) was used to derive dietary pattern scores using baseline serum total and HDL-cholesterol, and TAG levels as dependent variables. Cox proportional hazard regression was used to confirm the association between dietary patterns and incident CHD (n 243) over 15 years of follow-up. Increased CHD risk (hazard ratio (HR) for top quartile: 2·01 (95 % CI 1·41, 2·85) adjusted for age, sex, ethnicity and energy misreporting) was observed with a diet characterised by high consumption of white bread, fried potatoes, sugar in tea and coffee, burgers and sausages, soft drinks, and low consumption of French dressing and vegetables. The diet-CHD relationship was attenuated after adjustment for employment grade and health behaviours (HR for top quartile: 1·81; 95 % CI 1·26, 2·62), and further adjustment for blood pressure and BMI (HR for top quartile: 1·57; 95 % CI 1·08, 2·27). Dietary patterns are associated with serum lipids and predict CHD risk after adjustment for confounders. RRR identifies dietary patterns using prior knowledge and focuses on the pathways through which diet may influence disease. The present study adds to the evidence that diet is an important risk factor for CHD.

Blood glucose meters : an independent head to head comparison

A new generation of blood glucose meters is now available for use by people with diabetes and health professionals, but little independent evaluation data is available. Previous models are prone to a variety of errors. We compared the accuracy, precision and features of the six latest meters available in Australia as of 1996. Meters studied were the Mini-Accutrend and Advantage (Boehringer Mannheim), Precision QID and Companion 2 (MediSense), Glucometer Elite (Bayer) and Lynx (National Diagnostic Products). We measured the blood glucose levels of 50 people with diabetes with these meters, and compared them to a reference method (YSI glucose analyser). Error grid analysis confirmed that accuracy of all meters was sufficient for their intended use as patient monitors. Precision was assessed using 25 samples from control solutions provided for each meter, and the coefficient of variation calculated. Improvements in strip and meter technology in some models have increased ease of use and reduced the likelihood of user error. This study, when considered with individual preferences for various features and price should assist patients in choosing a new blood glucose meter.

Beneficial associations of physical activity with 2-h, but not fasting, blood glucose in Australian adults

OBJECTIVE--We examined the associations of physical activity with fasting plasma glucose (FPG) and with 2-h postload plasma glucose (2-h PG) in men and women with low, moderate, and high waist circumference.

RESEARCH DESIGN AND METHODS--The Australian Diabetes, Obesity and Lifestyle (AusDiab) study provided data on a population-based cross-sectional sample of 4,108 men and 5,106 women aged [greater than or equal to] 25 years without known diabetes or health conditions that could affect physical activity. FPG and 2-h PG were obtained from an oral glucose tolerance test. Self-reported physical activity level was defined according to the current public health guidelines as active ([greater than or equal to] 150 min/week across five or more sessions) or inactive (<150 min/week and/or less than five sessions). Sex-specific quintiles of physical activity time were used to ascertain dose response.

RESULTS--Being physically active and total physical activity time were independently and negatively associated with 2-h PG. When physical activity level was considered within each waist circumference category, 2-h PG was significantly lower in active high-waist circumference women ([beta] -0.30 [95% CI -0.59 to -0.01], P = 0.044) and active low-waist circumference men ([beta] -0.25 [-0.49 to -0.02], P = 0.036) compared with their inactive counterparts. Considered across physical activity and waist circumference categories, 2-h PG levels were not significantly different between active moderate-waist circumference participants and active low-waist circumference participants. Associations between physical activity and FPG were nonsignificant.

CONCLUSIONS--There are important differences between 2-h PG and FPG related to physical activity. It appears that 2-h PG is more sensitive to the beneficial effects of physical activity, and these benefits occur across the waist circumference spectrum.