A natural mineral supplement provides relief from knee osteoarthritis symptoms: a randomized controlled pilot trial

<p>Abstract</p> <p>Background</p> <p>This small, pilot study evaluated the impact of treatment with a natural multi-mineral supplement from seaweed (Aquamin) on walking distance, pain and joint mobility in subjects with moderate to severe osteoarthritis of the knee.</p> <p>Methods</p> <p>Subjects (n = 70) with moderate to severe osteoarthritis of the knee were randomized to four double-blinded treatments for 12 weeks: (a) Glucosamine sulfate (1500 mg/d); (b) Aquamin (2400 mg/d); (c) Combined treatment composed of Glucosamine sulfate (1500 mg/d) plus Aquamin (2400 mg/d) and (d) Placebo. Primary outcome measures were WOMAC scores and 6 Minute Walking Distances (6 MWD). Laboratory based blood tests were used as safety measures.</p> <p>Results</p> <p>Fifty subjects completed the study and analysis of the data showed significant differences between the groups for changes in WOMAC pain scores over time (p = 0.009 ANCOVA); however, these data must be reviewed with caution since significant differences were found between the groups at baseline for WOMAC pain and stiffness scores (p = 0.0039 and p = 0.013, respectively, ANOVA). Only the Aquamin and Glucosamine groups demonstrated significant improvements in symptoms over the course of the study. The combination group (like the placebo group) did not show any significant improvements in OA symptoms in this trial. Within group analysis demonstrated significant improvements over time on treatment for the WOMAC pain, activity, composite and stiffness (Aquamin only) scores as well as the 6 minute walking distances for subjects in the Aquamin and Glucosamine treatment groups. The Aquamin and Glucosamine groups walked 101 feet (+7%) and 56 feet (+3.5%) extra respectively. All treatments were well tolerated and the adverse events profiles were not significantly different between the groups.</p> <p>Conclusion</p> <p>This small preliminary study suggested that a multi mineral supplement (Aquamin) may reduce the pain and stiffness of osteoarthritis of the knee over 12 weeks of treatment and warrants further study.</p> <p>Trial registration</p> <p>ClinicalTrials.gov number: NCT00452101.</p

A natural mineral supplement provides relief from knee osteoarthritis symptoms: a randomized controlled pilot trial

<p>Abstract</p> <p>Background</p> <p>This small, pilot study evaluated the impact of treatment with a natural multi-mineral supplement from seaweed (Aquamin) on walking distance, pain and joint mobility in subjects with moderate to severe osteoarthritis of the knee.</p> <p>Methods</p> <p>Subjects (n = 70) with moderate to severe osteoarthritis of the knee were randomized to four double-blinded treatments for 12 weeks: (a) Glucosamine sulfate (1500 mg/d); (b) Aquamin (2400 mg/d); (c) Combined treatment composed of Glucosamine sulfate (1500 mg/d) plus Aquamin (2400 mg/d) and (d) Placebo. Primary outcome measures were WOMAC scores and 6 Minute Walking Distances (6 MWD). Laboratory based blood tests were used as safety measures.</p> <p>Results</p> <p>Fifty subjects completed the study and analysis of the data showed significant differences between the groups for changes in WOMAC pain scores over time (p = 0.009 ANCOVA); however, these data must be reviewed with caution since significant differences were found between the groups at baseline for WOMAC pain and stiffness scores (p = 0.0039 and p = 0.013, respectively, ANOVA). Only the Aquamin and Glucosamine groups demonstrated significant improvements in symptoms over the course of the study. The combination group (like the placebo group) did not show any significant improvements in OA symptoms in this trial. Within group analysis demonstrated significant improvements over time on treatment for the WOMAC pain, activity, composite and stiffness (Aquamin only) scores as well as the 6 minute walking distances for subjects in the Aquamin and Glucosamine treatment groups. The Aquamin and Glucosamine groups walked 101 feet (+7%) and 56 feet (+3.5%) extra respectively. All treatments were well tolerated and the adverse events profiles were not significantly different between the groups.</p> <p>Conclusion</p> <p>This small preliminary study suggested that a multi mineral supplement (Aquamin) may reduce the pain and stiffness of osteoarthritis of the knee over 12 weeks of treatment and warrants further study.</p> <p>Trial registration</p> <p>ClinicalTrials.gov number: NCT00452101.</p

Transcriptional regulation of the IGF signaling pathway by amino acids and insulin-like growth factors during myogenesis in Atlantic salmon

The insulin-like growth factor signalling pathway is an important regulator of skeletal muscle growth. We examined the mRNA expression of components of the insulin-like growth factor (IGF) signalling pathway as well as Fibroblast Growth Factor 2 (FGF2) during maturation of myotubes in primary cell cultures isolated from fast myotomal muscle of Atlantic salmon (Salmo salar). The transcriptional regulation of IGFs and IGFBP expression by amino acids and insulin-like growth factors was also investigated. Proliferation of cells was 15% d(-1) at days 2 and 3 of the culture, increasing to 66% d(-1) at day 6. Three clusters of elevated gene expression were observed during the maturation of the culture associated with mono-nucleic cells (IGFBP5.1 and 5.2, IGFBP-6, IGFBP-rP1, IGFBP-2.2 and IGF-II), the initial proliferation phase (IGF-I, IGFBP-4, FGF2 and IGF-IRb) and terminal differentiation and myotube production (IGF2R, IGF-IRa). In cells starved of amino acids and serum for 72 h, IGF-I mRNA decreased 10-fold which was reversed by amino acid replacement. Addition of IGF-I and amino acids to starved cells resulted in an 18-fold increase in IGF-I mRNA indicating synergistic effects and the activation of additional pathway(s) leading to IGF-I production via a positive feedback mechanism. IGF-II, IGFBP-5.1 and IGFBP-5.2 expression was unchanged in starved cells, but increased with amino acid replacement. Synergistic increases in expression of IGFBP5.2 and IGFBP-4, but not IGFBP5.1 were observed with addition of IGF-I, IGF-II or insulin and amino acids to the medium. IGF-I and IGF-II directly stimulated IGFBP-6 expression, but not when amino acids were present. These findings indicate that amino acids alone are sufficient to stimulate myogenesis in myoblasts and that IGF-I production is controlled by both endocrine and paracrine pathways. A model depicting the transcriptional regulation of the IGF pathway in Atlantic salmon muscle following feeding is proposed.Publisher PDFPeer reviewe

Cell-Type Specific Expression of a Dominant Negative PKA Mutation in Mice

We employed the Cre recombinase/loxP system to create a mouse line in which PKA activity can be inhibited in any cell-type that expresses Cre recombinase. The mouse line carries a mutant Prkar1a allele encoding a glycine to aspartate substitution at position 324 in the carboxy-terminal cAMP-binding domain (site B). This mutation produces a dominant negative RIα regulatory subunit (RIαB) and leads to inhibition of PKA activity. Insertion of a loxP-flanked neomycin cassette in the intron preceding the site B mutation prevents expression of the mutant RIαB allele until Cre-mediated excision of the cassette occurs. Embryonic stem cells expressing RIαB demonstrated a reduction in PKA activity and inhibition of cAMP-responsive gene expression. Mice expressing RIαB in hepatocytes exhibited reduced PKA activity, normal fasting induced gene expression, and enhanced glucose disposal. Activation of the RIαB allele in vivo provides a novel system for the analysis of PKA function in physiology

Malnutrition Has No Effect on the Timing of Human Tooth Formation

The effect of nutrition on the timing of human tooth formation is poorly understood. Delays and advancements in dental maturation have all been reported as well as no effect. We investigated the effect of severe malnutrition on the timing of human tooth formation in a large representative sample of North Sudanese children. The sample (1102 males, 1013 females) consisted of stratified randomly selected healthy individuals in Khartoum, Sudan, aged 2-22 years using a cross-sectional design following the STROBE statement. Nutritional status was defined using WHO criteria of height and weight. Body mass index Z-scores and height for age Z-scores of ≤-2 (cut-off) were used to identify the malnourished group (N = 474) while the normal was defined by Z-scores of ≥0 (N = 799). Clinical and radiographic examination of individuals, with known ages of birth was performed including height and weight measurements. Mandibular left permanent teeth were assessed using eight crown and seven root established tooth formation stages. Mean age at entry and mean age within tooth stages were calculated for each available tooth stage in each group and compared using a t-test. Results show the mean age at entry and mean age within tooth stages were not significantly different between groups affected by severe malnutrition and normal children (p>0.05). This remarkable finding was evident across the span of dental development. We demonstrate that there is little measurable effect of sustained malnutrition on the average timing of tooth formation. This noteworthy finding supports the notion that teeth have substantial biological stability and are insulated from extreme nutritional conditions compared to other maturing body systems

The Role of Zinc in the Modulation of Neuronal Proliferation and Apoptosis

Although a requirement of zinc (Zn) for normal brain development is well documented, the extent to which Zn can modulate neuronal proliferation and apoptosis is not clear. Thus, we investigated the role of Zn in the regulation of these two critical events. A low Zn availability leads to decreased cell viability in human neuroblastoma IMR-32 cells and primary cultures of rat cortical neurons. This occurs in part as a consequence of decreased cell proliferation and increased apoptotic cell death. In IMR-32 cells, Zn deficiency led to the inhibition of cell proliferation through the arrest of the cell cycle at the G0/G1 phase. Zn deficiency induced apoptosis in both proliferating and quiescent neuronal cells via the intrinsic apoptotic pathway. Reductions in cellular Zn triggered a translocation of the pro-apoptotic protein Bad to the mitochondria, cytochrome c release, and caspase-3 activation. Apoptosis is the resultant of the inhibition of the prosurvival extracellular-signal-regulated kinase, the inhibition of nuclear factor-kappa B, and associated decreased expression of antiapoptotic proteins, and to a direct activation of caspase-3. A deficit of Zn during critical developmental periods can have persistent effects on brain function secondary to a deregulation of neuronal proliferation and apoptosis

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing

Background: Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor event, which increases the risk of adverse outcomes including falls, disability and death. The underlying pathophysiological pathways of frailty are not known but the hypothalamic–pituitary–adrenal axis and heightened chronic systemic inflammation appear to be major contributors. Methods: We used the English Longitudinal Study of Ageing dataset of 3160 individuals over the age of 50 and assessed their frailty status according to the Fried-criteria. We selected single nucleotide polymorphisms in genes involved in the steroid hormone or inflammatory pathways and performed linear association analysis using age and sex as covariates. To support the biological plausibility of any genetic associations, we selected biomarker levels for further analyses to act as potential endophenotypes of our chosen genetic loci. Results: The strongest association with frailty was observed in the Tumor Necrosis Factor (TNF) (rs1800629, P = 0.001198, β = 0.0894) and the Protein Tyrosine Phosphatase, Receptor type, J (PTPRJ) (rs1566729, P = 0.001372, β = 0.09397) genes. Rs1800629 was significantly associated with decreased levels of high-density lipoprotein (HDL) (P = 0.00949) and cholesterol levels (P = 0.00315), whereas rs1566729 was associated with increased levels of HDL (P = 0.01943). After correcting for multiple testing none of the associations remained significant. Conclusions: We provide potential evidence for the involvement of a multifunctional proinflammatory cytokine gene (TNF) in the frailty phenotype. The implication of this gene is further supported by association with the endophenotype biomarker results

Prevalence and correlates of frailty in an older rural African population:findings from the HAALSI cohort study

Background: Frailty is a key predictor of death and dependency, yet little is known about frailty in sub-Saharan Africa despite rapid population ageing. We describe the prevalence and correlates of phenotypic frailty using data from the Health and Aging in Africa: Longitudinal Studies of an INDEPTH Community cohort. Methods: We analysed data from rural South Africans aged 40 and over. We used low grip strength, slow gait speed, low body mass index, and combinations of self-reported exhaustion, decline in health, low physical activity and high self-reported sedentariness to derive nine variants of a phenotypic frailty score. Each frailty category was compared with self-reported health, subjective wellbeing, impairment in activities of daily living and the presence of multimorbidity. Cox regression analyses were used to compare subsequent all-cause mortality for non-frail (score 0), pre-frail (score 1–2) and frail participants (score 3+). Results: Five thousand fifty nine individuals (mean age 61.7 years, 2714 female) were included in the analyses. The nine frailty score variants yielded a range of frailty prevalences (5.4% to 13.2%). For all variants, rates were higher in women than in men, and rose steeply with age. Frailty was associated with worse subjective wellbeing, and worse self-reported health. Both prefrailty and frailty were associated with a higher risk of death during a mean 17 month follow up for all score variants (hazard ratios 1.29 to 2.41 for pre-frail vs non-frail; hazard ratios 2.65 to 8.91 for frail vs non-frail). Conclusions: Phenotypic frailty could be measured in this older South African population, and was associated with worse health, wellbeing and earlier death

Piloting online self-audit of methadone treatment in Irish general practice: results, reflections and educational outcomes

Background: Work based learning underpins the training and CPD of medical practitioners. Medical audit operates on two levels; individual self-assessment and professional/practice development. In Ireland, annual practice improvement audit is an essential requirement for the successful completion of continuous professional development (CPD) as determined by the regulatory body, the Irish Medical Council. All general practice (GP) doctors providing methadone maintenance treatment (MMT) in Ireland have a contractual obligation to partake in a yearly methadone practice audit. The Irish College of General Practitioners (ICGP) as national training provider is tasked to facilitate this annual audit process. The purpose of this audit is to assess the quality of care provided to patients against an agreed set of national standards, enhance learning, and promote practice improvement and reflective practice. The aim was to present an online MTP self-audit and evaluate results from a 12-month pilot among GPs providing MMT in Ireland. Method A mixed method study describing three phases (design and development, pilot/implementation and evaluation) of a new online self –audit tool was conducted. Descriptive and thematic analysis of audit and evaluation data was conducted. Results: Survey Monkey is a suitable software package for the development and hosting of an easy to use online audit for MMT providing doctors. Analysis of the audit results found that the majority of GPs scored 80% or over for the 25 identified essential criteria for MMT provision. The evaluation of the GP audit experience underscores the positive outcomes of the online self-audit in terms of improving practice systems, encouraging reflective practice, enhanced patient care and doctor commitment to continued provision of MMT in addiction clinics and in primary care. Conclusions: Results from this audit demonstrate a high level of compliance with best practise MMT guidelines by Irish GPs providing MMT. The online self-audit process was well received and encouraged reflective practice. The audit process hinged on the individual GP’s ability to review and critically analyse their professional practice, and manage change. This model of audit could be adapted and used to monitor the management of other chronic illnesses in general practice

Lrp Acts as Both a Positive and Negative Regulator for Type 1 Fimbriae Production in Salmonella enterica Serovar Typhimurium

Leucine-responsive regulatory protein (Lrp) is known to be an indirect activator of type 1 fimbriae synthesis in Salmonella enterica serovar Typhimurium via direct regulation of FimZ, a direct positive regulator for type 1 fimbriae production. Using RT-PCR, we have shown previously that fimA transcription is dramatically impaired in both lrp-deletion (Δlrp) and constitutive-lrp expression (lrpC) mutant strains. In this work, we used chromosomal PfimA-lacZ fusions and yeast agglutination assays to confirm and extend our previous results. Direct binding of Lrp to PfimA was shown by an electrophoretic mobility shift assay (EMSA) and DNA footprinting assay. Site-directed mutagenesis revealed that the Lrp-binding motifs in PfimA play a role in both activation and repression of type 1 fimbriae production. Overproduction of Lrp also abrogates fimZ expression. EMSA data showed that Lrp and FimZ proteins independently bind to PfimA without competitive exclusion. In addition, both Lrp and FimZ binding to PfimA caused a hyper retardation (supershift) of the DNA-protein complex compared to the shift when each protein was present alone. Nutrition-dependent cellular Lrp levels closely correlated with the amount of type 1 fimbriae production. These observations suggest that Lrp plays important roles in type 1 fimbriation by acting as both a positive and negative regulator and its effect depends, at least in part, on the cellular concentration of Lrp in response to the nutritional environment