The relationship between patient blood pathology values and patient falls in an acute-care setting : a retrospective analysis

Few studies have investigated the relationship between patient falls and patient blood pathology values, which can reveal objective information about the health and nutritional status of a patient. It could be that some abnormal values are associated with patients that fall. The objectives of the current study were to determine whether blood pathology values were different in patients who fell compared to patients who did not fall, and whether there was a difference in the type and number of currently documented risk factors for falls found for patients who fell compared to patients who did not fall. A retrospective audit of patient incident reports and medical records was conducted in an acute-care hospital for 220 patients who fell and who did not fall. Faller and non-faller patients were matched by casemix type and length of stay. Findings revealed a significant relationship between patients who fell and the variables of age, confusion status and alkaline phosphatase blood values.

Cytochemical characterisation of the leucocytes and thrombocytes from murray cod (Maccullochella peelii peelii, Mitchell)

Cytochemistry has proven effective in differentiating specific cell lineages and elucidating their functional properties. This study utilised a range of cytochemical techniques to further investigate the leucocyte populations from Murray cod, an iconic Australian teleost fish species. This analysis provided clear insight into the structure and function of the leucocytes from this fish, which were found to be broadly similar to those of other fish species. However, some important differences were identified in Murray cod, such as the presence of naphthol AS chloroacetate esterase activity in the heterophil population, positive staining for periodic acid Schiff's, alkaline phosphatase and Sudan black B in the lymphocyte population, and a prevalent population of myeloid precursor cells.

Three-month bilateral hopping intervention is ineffective in initiating bone biomarker response in healthy elderly men.

In animal studies, bone adaptation has been initiated successfully without the transient force spike associated with high impact exercises. Consequently, a 12-week bilateral hopping on the balls of the feet intervention was conducted. 25 elderly men (age 72(SD4) years, height 171(6) cm, weight 75(9) kg) were randomly assigned into exercise and control groups. Ten subjects in each group completed the study. Carboxyterminal propeptide of type I collagen (CICP), bone-specific alkaline phosphatase (bALP) and carboxyterminal telopeptide of type I collagen (CTx) were measured from venous blood samples at baseline, at 2 weeks and at the end of the intervention. Maximal ground reaction force (GRF), osteogenic index (OI) and jump height (JH) were determined from bilateral hopping test and balance was assessed with velocity of center of pressure (COPvelocity) while standing on the preferred leg with eyes open. The intervention consisted of 5–7 sets of 10 s timed bilateral hopping exercise at 75–90% intensity three times/week. There was no significant group 9 time interaction for GRF, OI and JH (P = 0.065). GRF (11% change from baseline vs. 4%), OI (15 vs. 6%) and COPvelocity (-10 vs. -1%) were not influenced by the intervention (P[0.170), while the control group improved JH (P = 0.031) (2 vs. 18%). For the biomarkers, no effect was observed in MANOVA (P = 0.536) or in univariate analyses (P = 0.082 to P = 0.820) (CICP -2 vs. -3%, CTx 8 vs. -12%, bALP 0 vs. -3.7%). Allowing transient impact force spikes may be necessary to initiate a bone response in elderly men as the intervention was ineffective.

Long-distance delivery of bacterial virulence factors by Pseudomonas aeruginosa outer membrane vesicles

Bacteria use a variety of secreted virulence factors to manipulate host cells, thereby causing significant morbidity and mortality. We report a mechanism for the long-distance delivery of multiple bacterial virulence factors, simultaneously and directly into the host cell cytoplasm, thus obviating the need for direct interaction of the pathogen with the host cell to cause cytotoxicity. We show that outer membrane–derived vesicles (OMV) secreted by the opportunistic human pathogen Pseudomonas aeruginosa deliver multiple virulence factors, including b-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif, directly into the host cytoplasm via fusion of OMV with lipid rafts in the host plasma membrane. These virulence factors enter the cytoplasm of the host cell via N-WASP–mediated actin trafficking, where they rapidly distribute to specific subcellular locations to affect host cell biology. We propose that secreted virulence factors are not released individually as naked proteins into the surrounding milieu where they may randomly contact the surface of the host cell, but instead bacterial derived OMV deliver multiple virulence factors simultaneously and directly into the host cell cytoplasm in a coordinated manner.

β-blockers reduce bone resorption marker in early postmenopausal women

Background: There is evidence to suggest that β-blockers used in the management of cardiovascular disease may also modulate bone metabolism and reduce bone fragility.

Aim: The study aimed to determine the association between β-blocker use, serum markers of bone turnover and bone loss in early postmenopausal women.

Subjects and methods: In this observational study, we evaluated β-blocker exposure in association with serum levels of C-telopeptide and bone-specific alkaline phosphatase, and rates of bone loss. β-blocker use, concomitant therapy and lifestyle were documented for 197 women (50–59 years), 175 of whom had changes in whole body bone mineral density monitored over a 2–year period.

Results: Twenty-four β-blocker users were identified at baseline. After controlling for concomitant use of hormone therapy, C-telopeptide levels were 6.7% lower among β-blocker users (p = 0.02). No association was detected between bone-specific alkaline phosphatase and β-blocker use. Analysis of 15 β-blocker users and 152 non-users identified 2 years post-baseline showed that levels of C-telopeptide but not bone-specific alkaline phosphatase were predictors of adjusted rates of bone loss (p = 0.008 and p>0.05, respectively). Adjusted rates of bone loss were −0.001 ± 0.026 g cm−2 over 2 years for the users and −0.004 ± 0.025 g cm−2 over 2 years for non-users, but this difference was not significant.

Conclusion: β-blockers might suppress bone resorption with relative preservation of bone formation. A study with greater power is required to determine whether β-blocker use is associated with lower rates of bone loss.

Antioxidant vitamin supplements and markers of bone turnover in a community sample of nonsmoking women

Background: Whereas several epidemiological studies suggest that low dietary intake of vitamins C and E is linked to increased hip fracture in smokers and antioxidants (dietary and endogenous) are reduced in elderly osteoporotic women, none has demonstrated an effect of supplemental antioxidants on bone turnover.

Methods: In an observational study of 533 randomly selected women, we investigated the associations among the use of antioxidant supplements, vitamins C and E, serum levels of biochemical markers of bone turnover (C-telopeptide [CTx] and bone-specific alkaline phosphatase [BSAP]), and whole body bone mineral density (BMD).

Results: Twenty-two women were identified as current users of supplemental vitamin C or E. Duration of antioxidant supplement use was negatively associated with age-adjusted and weight-adjusted serum CTx, such that mean CTx levels (natural log transformed) were 0.022 units lower for each year of exposure. No significant differences were detected for adjusted serum BSAP or whole body BMD.

Conclusions: Our results suggest that antioxidant vitamin E or C supplements may suppress bone resorption in nonsmoking postmenopausal women. Coupling of bone formation and resorption may explain the absence of an effect on bone formation markers, given evidence of enhanced effects of antioxidants on osteoblast differentiation; this warrants further investigation. This work adds to the growing body of evidence that antioxidants may play a role in preventing osteoporosis.

Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial)

We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units. As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers, the proximal tubular brush border enzymes γ-glutamyl transpeptidase and alkaline phosphatase. Randomization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3, with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days. Of 529 patients, 162 were randomized within an average of 3.5 h of a positive sample. There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups. The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury, dialysis, or death; however, the marker elevations were transient. Early intervention with high-dose erythropoietin was safe but did not alter the outcome. Although these two urine biomarkers facilitated our early intervention, their transient increase compromised effective triaging. Further, our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury.

Layer-by-layer assembly of silica nanoparticles on 3D fibrous scaffolds : enhancement of osteoblast cell adhesion, proliferation, and differentiation

Silica nanoparticles were applied onto the fiber surface of an interbonded three-dimensional polycaprolactone fibrous tissue scaffold by an electrostatic layer-by-layer self-assembly technique. The nanoparticle layer was found to improve the fiber wettability and surface roughness. Osteoblast cells were cultured on the fibrous scaffolds to evaluate the biological compatibility. The silica nanoparticle coated scaffold showed enhanced cell attachment, proliferation, and alkaline phosphatase activities. The overall results suggested that interbonded fibrous scaffold with silica nanoparticulate coating could be a promising scaffolding candidate for various applications in bone repair and regeneration.

Ti-SrO metal matrix composites for bone implant materials

Titanium-strontia (Ti-SrO) metal matrix composites (MMCs) with 0, 1, 3 and 5% (weight ratio) of SrO have been fabricated through the powder metallurgy method. Increasing the weight ratio of SrO from 0 to 5%, the compressive strength of Ti-SrO MMCs increased from 982 MPa to 1753 MPa, while the ultimate strain decreased from 0.28 to 0.05. The elastic moduli of Ti-3SrO and Ti-5SrO MMCs were higher than those of Ti and Ti-1SrO MMC samples. Additionally, the micro hardness of Ti-SrO MMCs was enhanced from 59% to 190% with the addition of SrO. The enhanced compression strength and micro hardness of Ti-SrO MMCs were attributed to the Hall-Petch effect and the SrO dispersion strengthening in the Ti matrix. MTS assay results demonstrated that Ti-SrO MMCs with 3% SrO exhibited enhanced proliferation of osteoblast-like cells. Alkaline phosphatase activity of cells was not influenced significantly on the surface of Ti-SrO MMCs compared with pure Ti in a term longer than 10 days. The cell morphology on the Ti-SrO MMCs was observed using confocal microscopy and scanning electron microscopy, which confirmed that the Ti-3%SrO MMCs showed optimal in vitro biocompatibility. This journal is © the Partner Organisations 2014.

Cissus quadrangularis inhibits IL-1β induced inflammatory responses on chondrocytes and alleviates bone deterioration in osteotomized rats via p38 MAPK signaling

INTRODUCTION: Inflammatory mediators are key players in the pathogenesis of osteoarthritis (OA) and bone destruction. Conventional drugs suppress symptomatic activity and have no therapeutic influence on disease. Cissus quadrangularis and Withania somnifera are widely used for the treatment of bone fractures and wounds; however, the cellular and molecular mechanisms regulated by these herbals are still unclear. METHODS: We established an in vitro OA culture model by exposing human chondrocytes to proinflammatory cytokine and interleukin (IL)-1β for 36 hours prior to treatment with the herbals: C. quadrangularis, W. somnifera, and the combination of the two herbals. Cell viability, toxicity, and gene expression of OA modifying agents were examined. In addition, expression of survivin, which is crucial for cell growth, was analyzed. In vivo work on osteotomized rats studied the bone and cartilage regenerative effects of C. quadrangularis, W. somnifera, and the combination therapy. RESULTS: Exposure of chondrocytes to IL-1β induced significant toxicity and cell death. However, herbal treatment alleviated IL-1β induced cell toxicity and upregulated cell growth and proliferation. C. quadrangularis inhibited gene expression of cytokines and matrix metalloproteinases, known to aggravate cartilage and bone destruction, and augmented expression of survivin by inhibiting p38 MAPK. Interestingly, osteotomized rats treated with C. quadrangularis drastically enhanced alkaline phosphatase and cartilage tissue formation as compared to untreated, W. somnifera only, or the combination of both herbals. CONCLUSION: Our findings demonstrate for the first time the signaling mechanisms regulated by C. quadrangularis and W. somnifera in OA and osteogenesis. We suggest that the chondroprotective effects and regenerative ability of these herbals are via the upregulation of survivin that exerts inhibitory effects on the p38 MAPK signaling pathway. These findings thus validate C. quadrangularis as a potential therapeutic for rheumatic disorders.

Identification and characterization of a novel IL-4 receptor α chain (IL-4Rα) antagonist to inhibit IL-4 signalling

BACKGROUND/AIMS: In recent times, allergy has become a financial, physical and psychological burden to the society as a whole. In allergic cascades, cytokine IL-4 binds to IL-4 receptor (IL-4R), consequently producing allergen-specific IgE antibodies by B cells. In addition, among other functions, IL-4 is also responsible for B and T cell proliferation and differentiation. Hence, characterization of novel antagonists that inhibit IL-4 signalling forms the overall aim of this study. METHODS: Phage display was used to screen a random 12-mer synthetic peptide library with a human IL-4Rα to identify peptide candidates. Once identified, the peptides were commercially synthesized and used for in vitro immunoassays. RESULTS: We have successfully used phage display to identify M13 phage clones that demonstrated specific binding to IL-4Rα. The peptide N1 was synthesized for use in ELISA, demonstrating significant binding to IL-4Rα and inhibiting interaction with cytokine IL-4. Furthermore, the peptide was tested in a transfected HEK-Blue IL-4 reporter cell line model, which produces alkaline phosphatase (AP). QUANTI-Blue, a substrate, breaks down in the presence of AP producing a blue coloration. Using this colorimetric analysis, >50% inhibition of IL-4 signalling was achieved. CONCLUSION: We have successfully identified and characterised a synthetic peptide antagonist against IL-4Rα, which effectively inhibits IL-4 interaction with the IL-4Rα in vitro. Since IL-4 interaction with IL-4Rα is a common pathway for many allergies, a prophylactic treatment can be devised by inhibiting this interaction for future treatment of allergies.

Exploring the effects of omega-3 and omega-6 fatty Acids on allergy using a HEK-blue cell line.

BACKGROUND: Allergic reactions can result in life-threatening situations resulting in high economic costs and morbidity. Therefore, more effective reagents are needed for allergy treatment. A causal relationship has been suggested to exist between the intake of omega-3/6 fatty acids, such as docosahexanoic acid (DHA), eicosapentanoic acid (EPA), docosapentanoic acid (DPA) and arachidonic acid (AA), and atopic individuals suffering from allergies. In allergic cascades, the hallmark cytokine IL-4 bind to IL-4 receptor (IL-4R) and IL-13 binds to IL-13 receptor (IL-13R), this activates the STAT6 phosphorylation pathway leading to gene activation of allergen-specific IgE antibody production by B cells. The overall aim of this study was to characterize omega-3/6 fatty acids and their effects on STAT6 signaling pathway that results in IgE production in allergic individuals. METHODS: The fatty acids were tested in vitro with a HEK-Blue IL-4/IL-13 reporter cell line model, transfected with a reporter gene that produces an enzyme, secreted embryonic alkaline phosphatase (SEAP). SEAP acts as a substitute to IgE when cells are stimulated with bioactive cytokines IL-4 and/or IL-13. RESULTS: We have successfully used DHA, EPA and DPA in our studies that demonstrated a decrease in SEAP secretion, as opposed to an increase in SEAP secretion with AA treatment. A statistical Student's t-test revealed the significance of the results, confirming our initial hypothesis. CONCLUSION: We have successfully identified and characterised DHA, EPA, DPA and AA in our allergy model. While AA was a potent stimulator, DHA, EPA and DPA were potential inhibitors of IL-4R/IL-13R signalling, which regulates the STAT6 induced pathway in allergic cascades. Such findings are significant in the future design of dietary therapeutics for the treatment of allergies.

The isolation and characterisation of humic acids using a variety of alkaline extractants

The investigation into humic acid; chemistry examined the effect the extraction technique used to isolate humic material from the sediment had on the chemical/structural composition and yield of the acid; compared the various isolation techniques used in the literature and developed an extraction technique which minimises the solubilisation of the heavy metals from the inorganic sediment and, examined the complexation capacity of humic acids derived from a sediment source in relation to the heavy metal content and extraction technique.