Immediate response of 5-methoxytryptophol in the circulation to hypoglycaemic stress induced by insulin.

Pineal indoles have been shown to affect the release of anterior pituitary hormones but details of the interrelationships are lacking. Using a new gas chromatography-mass spectrometry (g.c.-m.s.) assay the concentration of 5-methoxytryptophol (ML) was measured in plasma samples obtained from 16 children undergoing investigation of pituitary function for delayed growth. All the children received an insulin tolerance test (ITT) to study their endocrine response to stress. Some children received luteinizing hormone releasing hormone (LH-RH) and/or thyrotrophin releasing hormone (TRH). The change in concentration of ML during an ITT was similar to the change in concentration of blood sugar; a drop at 20 min followed by a rise at 30 min. This was not significantly altered by the administration of LH-RH or TRH, nor was there a different pattern of response in children who were deficient in growth hormone as opposed to those with idiopathic delayed growth. The fall in concentration of ML with stress may mediate the increased secretion of pituitary hormones. Alternatively, the pineal gland may respond directly to insulin.     

A new configuration for right ventricular assist with skeletal muscle ventricle. Short-term studies

BACKGROUND. Previous attempts to provide right heart assistance with skeletal muscle ventricles (SMVs) have been frustrated by the low preload supplied by the systemic venous blood pressure. In the present study, right ventricular pressure was exploited to provide more optimal preload, the SMV being connected by valved conduits between right ventricular free wall and the main pulmonary artery. METHODS AND RESULTS. SMVs were constructed from the right latissimus dorsi muscle in seven mongrel dogs. Following a delay period of 4 weeks, SMVs were preconditioned with 2-Hz continuous stimulation for 5-6 weeks. The SMV was then connected to the right ventricle using a porcine valved Dacron conduit. A similar valved conduit connected the SMV to the main pulmonary artery that had been ligated proximally. SMVs were stimulated with 33-Hz burst frequency to contract synchronously with ventricular diastole in a 1:2 mode. The stimulator was intermittently turned off to permit comparison of assisted and nonassisted circulation. Cardiac output increased by 27% at 1 hour (1,437 +/- 54 versus 1,140 +/- 64 ml/min, p less than 0.005) and by 30% at 4 hours (1,403 +/- 161 versus 1,074 +/- 99 ml/min, p less than 0.005), systemic arterial systolic pressure increased at 1 hour by 12% (87.1 +/- 4.9 versus 78.0 +/- 4.9 mm Hg, p less than 0.05) and by 13% at 4 hours (81.4 +/- 2.8 versus 72.3 +/- 3.4 mm Hg, p less than 0.005), and peak pulmonary arterial pressure increased at 1 hour by 35% (28.0 +/- 2.1 versus 20.9 +/- 1.8 mm Hg, p less than 0.01) and by 37% at 4 hours (31.5 +/- 2.6 versus 23.0 +/- 0.4 mm Hg, p less than 0.05). Peak SMV pressure was 52.8 +/- 2.0 mm Hg at 1 hour and 49.9 +/- 3.3 mm Hg at 4 hours (p = NS). CONCLUSIONS. The improved preload supplied by this configuration of right ventricular assist enabled an SMV to provide stable and effective circulatory support throughout the 4-hour duration of the experiment.     

The contribution of yogurt to nutrient intakes across the life course

Yogurt is a nutrient‐dense food within the milk and dairy products food group. The nutritional content of yogurt varies depending on the processing method and ingredients used. Like milk, it is a good source of protein and calcium, and can be a source of iodine, potassium, phosphorus and the B vitamins – riboflavin (B₂) and vitamin B₁₂ (depending on type). Some yogurt products are also fortified with vitamin D. The nutritional value of dairy products (milk, cheese and yogurt) and the importance of the nutrients they provide for bone health are well recognised. These foods are collected together as one of the four main food groups within the UK's eatwell plate model that illustrates a healthy, balanced diet. Studies exploring the nutritional and health attributes of yogurt are limited but some research has suggested benefits in relation to bone mineral content, weight management, type 2 diabetes and metabolic profile. Yogurt consumption has also been associated with diet quality. The aim of this paper is to use national survey data to examine yogurt consumption in the UK and consider its contribution to nutrient intakes at different life stages within the context of nutritional challenges in each age group. The contribution of yogurt to energy and nutrient intakes across the life course was calculated via secondary analysis of data from the Diet and Nutrition Survey of Infants and Young Children (2011) and the National Diet and Nutrition Survey (2008/2009–2010/2011). The products categorised within the ‘yogurt group’ included all yogurt, fromage frais and dairy desserts, and fortified products. Comparisons were also made between specific sub‐categories of yogurt, namely ‘yogurt’, ‘fromage frais’ and ‘dairy desserts’. Nutrients included in the analyses were energy; the macronutrients; micronutrients that yogurt can be defined as a ‘source of’; micronutrients that may be of concern in the UK population; and vitamin D for fortified products. A simple dietary modelling exercise was also undertaken to investigate the potential impact of including an additional pot of yogurt per day on the nutrient intakes of adolescents. Children aged 3 years and under had the highest intakes of yogurt [mean intake 43.8 g/day (SD 39.7 g) in 4–18 month‐olds; 46.7 g/day (SD 39.1 g) in 1.5–3 year‐olds], and adolescents (11–18 years) consumed the least [21 g/day (SD 38.0 g)]. In adults, highest mean consumption [35.7 g/day (SD 55.0 g)] was during middle age (50–64 years), equivalent to less than a third of a standard 125 g pot. Around 80% of young children (aged 3 years and under) but only a third of teenagers and young adults had consumed any yogurt product during the survey period of 4 days. Average yogurt consumption was twice as high in women as men among older adults (65 years and over), while gender differences in consumption were less apparent in children. Fromage frais and fortified yogurt products were most commonly consumed by younger children, as were dairy desserts in those aged 4–18 years. Among adults, yogurt per se was most commonly consumed. Children aged 4–10 years exhibited the most variety in the types of yogurt consumed. Low‐fat yogurt (including those with added fruit, nuts and cereals) was the most commonly consumed yogurt type when all ages were combined. More than a third of all yogurt products consumed by children aged 3 years and under were fortified, compared with 18% in those aged 4–10 years. During adulthood, the consumption of fortified products was negligible. The yogurt group made a useful contribution to micronutrient intakes in children aged 4 months to 10 years, particularly vitamin B₁₂ (4–18 months: 7.6%; 1.5–3 years: 5.3%; 4–10 years: 3.8%), riboflavin (7.8%, 6.9%, and 5.7%, respectively), calcium (9.5%, 8.2%, and 5.9%, respectively), iodine (7.2%, 7.6%, and 7%, respectively) and phosphorus (8.1%, 6.3%, and 4.3%, respectively). It also provided 3.9% of the total intake of vitamin D in those aged 4–18 months and 10.5% in those aged 1.5–3 years. Although the contribution to total dietary energy intake was low (4.9% at 4–18 months and 4.2% at 1.5–3 years), yogurt contributed a high proportion of non‐milk extrinsic sugars (NMES) to the diets of young children (22.7% and 11.1% in 4–18 months and 1.5–3 years, respectively). However, the total NMES intake was comparatively low in children aged 4–18 months (6.7% total energy), and 11.6% in 1.5–3 year‐olds (compared to 15.3% total energy in children aged 11–18 years in this survey). As children aged, the contribution of yogurt (all categories combined) to micronutrient intake, as well as to NMES, decreased, reflecting the increasing amounts and variety of foods in the diet. Yogurt made a small contribution to energy and macronutrient intakes during adulthood, with the greatest proportions mostly in the older age group (65 years and over) (energy: 1.7%; fat: 1.3%; saturated fatty acids: 2.1%; NMES: 4%). As intake was higher among women, yogurt made a greater contribution to their micronutrient intakes compared with men, providing >5% of the reference nutrient intakes (RNIs) for phosphorus, iodine, calcium, vitamin B₁₂ and riboflavin. Simple dietary modelling was carried out to investigate the hypothetical change in mean nutrient intakes among adolescents aged 11–14 and 15–18 years, if they were all to add an extra 125 g pot of low‐fat fruit yogurt to their current diet. This showed an increase in average intake, as a percentage of the RNI, for several micronutrients for which there is some evidence of low intakes in this age group, notably calcium in boys and girls (11–18 years) and iodine in girls (11–18 years). Although some benefits for micronutrient intakes were noted, such advice would impact on energy and macronutrient intakes (including NMES), and would need to be given in the context of the wider diet (e.g. as ‘swaps’ for less nutrient‐dense foods). In conclusion, yogurt makes a small but valuable contribution to nutrient intakes in the UK, particularly in young children. Among adolescents, the addition of a low‐fat yogurt would help meet recommended intakes for several micronutrients, particularly calcium and iodine, which are of concern in some teenage diets. Advice to replace some types of snacks and desserts, particularly those high in fat and sugars and low in micronutrients, with a pot of yogurt or similar dairy product may improve the nutrient density of their diet.     

Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review

We conducted a systematic review of genetic association studies for osteoarthritis of the peripheral joints (OA) and spinal degenerative disease (SDD). Electronic searches were carried out for any English language article reporting on a gene association study for either OA or SDD published up until the end of 2006. A team of seven reviewers used a standardised template to extract data in duplicate. In all, 90 studies fulfilled our inclusion criteria, reporting a total of 94 significant associations from 83 different genes. We found relatively few instances in which a specific gene-disease association had been analysed by more than one study, and there were 14 cases in which significant associations were replicated in independent studies (at joints associated with the AGC1, ASPN, COL9A2, COL9A3, COL11A2, ESR1, FZRB, HFE, IL1A, IL1RN, PTGS2 and VDR genes). METHOD: logical and reporting problems were widespread, including failure to report full results, missing population details, multiple testing, and over-reliance on subgroup analysis. In summary, the complex phenotypes of OA and SDD may have made it difficult for researchers to focus their efforts. The field is dominated by isolated analyses of disparate potential associations, a problem that is amplified by the frequent analysis of different polymorphisms within individual genes. Flaws in study methodology and interpretation undoubtedly increase the risk of publication bias. Closer adherence to published recommendations (in particular those produced by HuGENet) will help to ensure that future studies are well-designed and build on current understanding, rather than simply adding to the growing bank of potential associations.     

The Immediate Effects of Foam Rolling and Stretching on Iliotibial Band Stiffness: A Randomized Controlled Trial

BackgroundIliotibial Band Syndrome (ITBS) is a common clinical condition likely caused by abnormal compressive forces to the iliotibial band (ITB). Stretching interventions are common in ITBS treatment and may predominantly affect tensor fascia latae (TFL). Another ITBS treatment is foam rolling, which may more directly affect the ITB. Shear wave ultrasound elastography (SWUE) measures real-time soft tissue stiffness, allowing tissue changes to be measured and compared.PurposeTo examine effects of foam rolling and iliotibial complex stretching on ITB stiffness at 0˚ and 10˚ of hip adduction and hip adduction passive range of motion (PROM).Study DesignRandomized controlled trial.MethodsData from 11 males (age = 30.5 ± 9.0 years, Body Mass Index (BMI) = 27.8 ± 4.0) and 19 females (age = 23.5 ± 4.9, BMI = 23.2 ± 2.1) were analyzed for this study. Subjects were randomly assigned to one of three groups: control, stretching, and foam rolling. Shear wave ultrasound elastography measurements included ITB Young’s modulus at the mid-thigh, the distal femur and the TFL muscle belly. ITB-to-femur depth was measured at mid-thigh level. Hip adduction PROM was measured from digital images taken during the movement.ResultsNo significant interactions or main effects were found for group or time differences in ITB Young’s modulus at the three measured locations. The ITB stiffness at the mid-thigh and distal femur increased with 10° adduction, but TFL stiffness did not increase. A main effect for adduction PROM was observed, where PROM increased 0.8˚ post-treatment (p = 0.02).ConclusionA single episode of stretching and foam rolling does not affect short-term ITB stiffness. The lack of ITB stiffness changes may be from an inadequate intervention stimulus or indicate that the interventions have no impact on ITB stiffness.Levels of Evidence1b     

Achilles tendon loading patterns during barefoot walking and slow running on a treadmill: An ultrasonic propagation study

Measurement of tendon loading patterns during gait is important for understanding the pathogenesis of tendon “overuse” injury. Given that the speed of propagation of ultrasound in tendon is proportional to the applied load, this study used a noninvasive ultrasonic transmission technique to measure axial ultrasonic velocity in the right Achilles tendon of 27 healthy adults (11 females and 16 males; age, 26 ± 9 years; height, 1.73 ± 0.07 m; weight, 70.6 ± 21.2 kg), walking at self‐selected speed (1.1 ± 0.1 m/s), and running at fixed slow speed (2 m/s) on a treadmill. Synchronous measures of ankle kinematics, spatiotemporal gait parameters, and vertical ground reaction forces were simultaneously measured. Slow running was associated with significantly higher cadence, shorter step length, but greater range of ankle movement, higher magnitude and rate of vertical ground reaction force, and higher ultrasonic velocity in the tendon than walking (P < 0.05). Ultrasonic velocity in the Achilles tendon was highly reproducible during walking and slow running (mean within‐subject coefficient of variation < 2%). Ultrasonic maxima (P1, P2) and minima (M1, M2) were significantly higher and occurred earlier in the gait cycle (P1, M1, and M2) during running than walking (P < 0.05). Slow running was associated with higher and earlier peaks in loading of the Achilles tendon than walking.     

Interactions between QnrB,QnrB Mutants,and DNA Gyrase

Plasmid-encoded protein QnrB1 protects DNA gyrase from ciprofloxacin inhibition. Using a bacterial two-hybrid system, we evaluated the physical interactions between wild-type and mutant QnrB1, the GyrA and GyrB gyrase subunits, and a GyrBA fusion protein. The interaction of QnrB1 with GyrB and GyrBA was approximately 10-fold higher than that with GyrA, suggesting that domains of GyrB are important for stabilizing QnrB1 interaction with the holoenzyme. Sub-MICs of ciprofloxacin or nalidixic acid reduced the interactions between QnrB1 and GyrA or GyrBA but produced no reduction in the interaction with GyrB or a quinolone-resistant GyrA:S83L (GyrA with S83L substitution) mutant, suggesting that quinolones and QnrB1 compete for binding to gyrase. Of QnrB1 mutants that reduced quinolone resistance, deletions in the C or N terminus of QnrB1 resulted in a marked decrease in interactions with GyrA but limited or no effect on interactions with GyrB and an intermediate effect on interactions with GyrBA. While deletion of loop B and both loops moderately reduced the interaction signal with GyrA, deletion of loop A resulted in only a small reduction in the interaction with GyrB. The loop A deletion also caused a substantial reduction in interaction with GyrBA, with little effect of loop B and dual-loop deletions. Single-amino-acid loop mutations had little effect on physical interactions except for a Δ105I mutant. Therefore, loops A and B may play key roles in the proper positioning of QnrB1 rather than as determinants of the physical interaction of QnrB1 with gyrase.     

The neuropeptide vasoactive intestinal peptide: direct effects on immune cells and involvement in inflammatory and autoimmune diseases

Neuropeptides represent an important category of endogenous contributors to the establishment and maintenance of immune deviation in the immune‐privileged organs such as the CNS and in the control of acute inflammation in the peripheral immune organs. Vasoactive intestinal peptide (VIP) is a major immunoregulatory neuropeptide widely distributed in the central and peripheral nervous system. In addition to neurones, VIP is synthesized by immune cells which also express VIP receptors. Here, we review the current information on VIP production and VIP‐receptor‐mediated effects in the immune system, the role of endogenous and exogenous VIP in inflammatory and autoimmune disorders and the present and future VIP therapeutic approaches.