Approximately 2-3% of young children develop allergy or intolerance to cows' milk. The only available treatment is elimination of milk from the diet. However, as milk is an important source of ...nutrients in childhood, a milk-free diet may not adequately meet the child's nutritional needs. A dietary survey was conducted to assess the nutrient intake of children on cows' milk-restricted diets. A population-based sample of families with young children (31-37 mo) with adverse reaction to cows' milk and/or eggs was contacted, of which 75% agreed to complete a dietary intake assessment. Dietary intake was assessed using a 4-d weighed recording. The nutrient intake in a group of children on cows' milk protein-free (n = 16) and cows' milk reduced (n = 8) diets were compared to a group of cows' milk consumers (n = 10). There were significant differences in nutrient intake of children on milk-free diets and children consuming milk. Children on milk-free diets had significantly lower intake of energy, fat, protein, calcium, riboflavin and niacin. Use of milk substitutes improved the nutritional content of the cows' milk-free diets; however, the recommendations for riboflavin and calcium were still not met.
The results reveal a risk for malnutrition in children on cows' milk-free diets, unless precautions are taken to replace the valuable nutrients from milk in the diet. Parents of children on milk-free diets need advice about food choices in order to reduce the risk of low intake of energy, fat and protein. Supplements with calcium, vitamin D and riboflavin are indicated.
Progressive multiple sclerosis (MS) will be a major area of research interest for years to come. No treatments exist and success in the field will generalise to other neurological conditions where ...neurodegeneration coexists with neuroinflammation. The issue is complex, and interdisciplinary approaches – uniting scientists with different competences (neurobiology, immunogenetics, etc.) and ‘mindsets’ (academia and industry) – will be decisive. The International Progressive MS Alliance is catalysing this process through various initiatives, the most recent of which was a meeting where scientists from academia (also outside the MS field) and from industry reviewed data and strategies to determine the next steps towards the translation of current knowledge into effective therapies.
Key findings are:
(i). Concerted efforts are essential to prioritise pathogenetic mechanisms according to impact on the disease and druggability.
(ii). Combination therapies will probably be needed, possibly early in the disease, along with new trial designs and treatment schedules.
(iii). Drug screenings are a pragmatic approach hopefully enriched by the use of neural and oligodendrocyte progenitors differentiated from induced pluripotent stem cells (iPSCs).
(iv). The field of network biology will increase our ability to predict therapeutic targets.
(v). Genome-wide association studies (GWAS) must try to identify variants associated with disease progression.
Osteoclasts prefer aged bone HENRIKSEN, K; LEEMING, D. J; BYRJALSEN, I ...
Osteoporosis international,
06/2007, Letnik:
18, Številka:
6
Journal Article
Recenzirano
We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged ...bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of aged bones.
Osteoclasts resorb aging bone in order to repair damage and maintain the quality of bone. The mechanism behind the targeting of aged bone for remodeling is not clear. We investigated whether bones endogenously possess the ability to control osteoclastic resorption.
To biochemically distinguish aged and young bones; we measured the ratio between the age-isomerized betaCTX fragment and the non-isomerized alphaCTX fragment. By measurement of TRACP activity, CTX release, number of TRACP positive cells and pit area/pit number, we evaluated osteoclastogenesis as well as osteoclast resorption on aged and young bones.
We found that the alphaCTX/betaCTX ratio is 3:1 in young compared to aged bones, and we found that both alpha and betaCTX are released by osteoclasts during resorption. Osteoclastogenesis was augmented on aged compared to young bones, and the difference was enhanced under low serum conditions. We found that mature osteoclasts resorb more on aged than on young bone, despite unchanged adhesion and morphology.
These data indicate that the age of the bone plays an important role in controlling osteoclast-mediated resorption, with significantly higher levels of osteoclast differentiation and resorption on aged bones when compared to young bones.
Background: The aim of the present study was to investigate whether a combination of rofecoxib and gabapentin could improve pain relief and reduce opioid requirements, compared with rofecoxib alone, ...during the first 5 days after tonsillectomy.
Methods: In a randomized, double‐blind, placebo‐controlled study, 49 patients received gabapentin 1200 mg pre‐operatively, followed by gabapentin 2 × 600 mg on the day of operation and gabapentin 3 × 600 mg for the next 5 days, or placebo. Both groups were given rofecoxib 50 mg daily. In the post‐operative care unit, intravenous morphine was administered in doses of 2.5 mg on request. From 4 h to 5 days post‐operatively, ketobemidone was offered as escape drug. Pain at rest and during swallowing, and side‐effects, were assessed using a four‐point verbal rating scale.
Results: As a result of the global withdrawal of rofecoxib, the study had to be terminated prematurely. This report comprises the results from 22 patients in the gabapentin group and 27 patients in the placebo group. Gabapentin reduced ketobemidone requirements during the first 24 h post‐operatively 4.5 mg (standard deviation, 3.0 mg) in the placebo group vs. 2.0 mg (standard deviation, 2.0 mg) in the gabapentin group; P < 0.003. Gabapentin induced more dizziness (P < 0.002), gait disturbance (P < 0.02) and vomiting (P < 0.05) during days 0–5 than placebo. No other statistically significant differences were observed.
Conclusion: Gabapentin reduced opioid requirements in the first 24 h after tonsillectomy. The benefits of the reduced opioid intake may be overshadowed by the drawbacks of side‐effects.
Many international clinical guidelines recommend therapeutic exercise as a core treatment for knee and hip osteoarthritis. We aimed to identify individual patient-level moderators of the effect of ...therapeutic exercise for reducing pain and improving physical function in people with knee osteoarthritis, hip osteoarthritis, or both.
We did a systematic review and individual participant data (IPD) meta-analysis of randomised controlled trials comparing therapeutic exercise with non-exercise controls in people with knee osteoathritis, hip osteoarthritis, or both. We searched ten databases from March 1, 2012, to Feb 25, 2019, for randomised controlled trials comparing the effects of exercise with non-exercise or other exercise controls on pain and physical function outcomes among people with knee osteoarthritis, hip osteoarthritis, or both. IPD were requested from leads of all eligible randomised controlled trials. 12 potential moderators of interest were explored to ascertain whether they were associated with short-term (12 weeks), medium-term (6 months), and long-term (12 months) effects of exercise on self-reported pain and physical function, in comparison with non-exercise controls. Overall intervention effects were also summarised. This study is prospectively registered on PROSPERO (CRD42017054049).
Of 91 eligible randomised controlled trials that compared exercise with non-exercise controls, IPD from 31 randomised controlled trials (n=4241 participants) were included in the meta-analysis. Randomised controlled trials included participants with knee osteoarthritis (18 58% of 31 trials), hip osteoarthritis (six 19%), or both (seven 23%) and tested heterogeneous exercise interventions versus heterogeneous non-exercise controls, with variable risk of bias. Summary meta-analysis results showed that, on average, compared with non-exercise controls, therapeutic exercise reduced pain on a standardised 0–100 scale (with 100 corresponding to worst pain), with a difference of –6·36 points (95% CI –8·45 to –4·27, borrowing of strength BoS 10·3%, between-study variance τ2 21·6) in the short term, –3·77 points (–5·97 to –1·57, BoS 30·0%, τ2 14·4) in the medium term, and –3·43 points (–5·18 to –1·69, BoS 31·7%, τ2 4·5) in the long term. Therapeutic exercise also improved physical function on a standardised 0–100 scale (with 100 corresponding to worst physical function), with a difference of –4·46 points in the short term (95% CI –5·95 to –2·98, BoS 10·5%, τ2 10·1), –2·71 points in the medium term (–4·63 to –0·78, BoS 33·6%, τ2 11·9), and –3·39 points in the long term (–4·97 to –1·81, BoS 34·1%, τ2 6·4). Baseline pain and physical function moderated the effect of exercise on pain and physical function outcomes. Those with higher self-reported pain and physical function scores at baseline (ie, poorer physical function) generally benefited more than those with lower self-reported pain and physical function scores at baseline, with the evidence most certain in the short term (12 weeks).
There was evidence of a small, positive overall effect of therapeutic exercise on pain and physical function compared with non-exercise controls. However, this effect is of questionable clinical importance, particularly in the medium and long term. As individuals with higher pain severity and poorer physical function at baseline benefited more than those with lower pain severity and better physical function at baseline, targeting individuals with higher levels of osteoarthritis-related pain and disability for therapeutic exercise might be of merit.
Chartered Society of Physiotherapy Charitable Trust and the National Institute for Health and Care Research.
Osteoclasts possess a large amount of ion transporters, which participate in bone resorption; of these, the vacuolar-adenosine trisphosphatase (V-ATPase) and the chloride-proton antiporter ClC-7 ...acidify the resorption lacuna. However, whether other ion transporters participate in this process is currently not well understood. We used a battery of ion channel inhibitors, human osteoclasts, and their subcellular compartments to perform an unbiased analysis of the importance of the different ion transporters for acidification of the resorption lacuna in osteoclasts. CD14
+
monocytes from human peripheral blood were isolated, and mature osteoclasts were generated using RANKL and M-CSF. The human osteoclasts were (1) used for acridine orange assays for evaluation of lysosomal acidification, (2) used for bone resorption assays, (3) used for generation of osteoclasts membranes for acid influx experiments, or (4) lysed in trizol for mRNA isolation for Affymetrix array analysis. Inhibitors targeted toward most of the ion transporters showed low potency in the acidification-based assays, although some inhibitors, such as carbonic anhydrase II and the sodium–hydrogen exchanger (NHE) inhibitors, reduced resorption potently. In contrast, inhibitors targeted at V-ATPase and ClC-7 potently inhibited both acidification and resorption, as expected. We here show evidence that acidification of the resorption lacuna is mainly mediated by V-ATPase and ClC-7. Furthermore, a group of other ion transporters, including carbonic anhydrase II, the NHEs, and potassium–chloride cotransporters, are all involved in resorption but do not seem to directly be involved in acidification of the lysosomes.
Sensitive and selective gas measurements are crucial for a large variety of applications. This paper describes the manufacturing and characterization of a photoacoustic gas sensor system. The system ...is based on a pressure sensor element with a sensitivity of 10 muV/V/Pa. To demonstrate and evaluate the concept, 12 prototypes for measuring CO 2 have been manufactured and characterized. Detection limits ranging from 92 ppm to below 6 ppm CO 2 were obtained with a path length of 10 cm, depending on the measurement time and photoacoustic cell design. Measurements showed no cross-sensitivity towards CO, CH 4 , or humidity in any of the sensors. The temperature drift of the uncompensated raw signal of two sensor designs was below 117 ppm CO 2 in the range from 25degC to 50degC.
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