83 research outputs found

    A study of 54 cases of left displacement of the abomasum: February to July 2005

    Get PDF
    Fifty-four cows with left displacement of the abomasum (LDA) submitted to the hospital facility at Riverview Veterinary Clinic from February to July 2005 were treated by right flank laparotomy and omentopexy. Five cows died (a survival rate 90.7%) and one cow (1.8%) was culled due to recurrence of the LDA post-operatively. Forty-one cows (76%) returned to good production post-operatively. Thirty-nine cows (72%) were pregnant six months after corrective surgery

    In silico modelling to differentiate the contribution of sugar frequency versus total amount in driving biofilm dysbiosis in dental caries

    Get PDF
    Dental caries is the most prevalent infection globally and a substantial economic burden in developed countries. Dietary sugars are the main risk factor, and drive increased proportions of acid-producing and acid-tolerating (aciduric) bacterial species within dental bio lms. Recent longitudinal studies have suggested that caries is most strongly correlated with total sugar intake, contrasting with the prevailing view that intake frequency is the primary determinant. To explore this possibility, we employed a computational model for supragingival plaque to systematically sample combinations of sugar frequency and total amount, allowing their independent contributions on the ratio of aciduric (i.e. cariogenic) to non-aciduric bacteria to be unambiguously determined. Sugar frequency was found to be irrelevant for either very high or very low daily total amounts as the simulated bio lm was predicted to be always or never cariogenic, respectively. Frequency was a determining factor for intermediate total amounts of sugar, including the estimated average human consumption. An increased risk of caries (i.e. high prevalence of aciduric/non-aciduric species) was predicted for high intake frequencies. Thus, both total amount and frequency of sugar intake may combine to in uence plaque cariogenicity. These ndings could be employed to support public guidance for dietary change, leading to improved oral healthcare

    Non-lethal control of the cariogenic potential of an agent-based model for dental plaque

    Get PDF
    Dental caries or tooth decay is a prevalent global disease whose causative agent is the oral biofilm known as plaque. According to the ecological plaque hypothesis, this biofilm becomes pathogenic when external challenges drive it towards a state with a high proportion of acid-producing bacteria. Determining which factors control biofilm composition is therefore desirable when developing novel clinical treatments to combat caries, but is also challenging due to the system complexity and the existence of multiple bacterial species performing similar functions. Here we employ agent-based mathematical modelling to simulate a biofilm consisting of two competing, distinct types of bacterial populations, each parameterised by their nutrient uptake and aciduricity, periodically subjected to an acid challenge resulting from the metabolism of dietary carbohydrates. It was found that one population was progressively eliminated from the system to give either a benign or a pathogenic biofilm, with a tipping point between these two fates depending on a multiplicity of factors relating to microbial physiology and biofilm geometry. Parameter sensitivity was quantified by individually varying the model parameters against putative experimental measures, suggesting non-lethal interventions that can favourably modulate biofilm composition. We discuss how the same parameter sensitivity data can be used to guide the design of validation experiments, and argue for the benefits of in silico modelling in providing an additional predictive capability upstream from in vitro experiments

    Can international health programmes be sustained after the end of international funding? The case of eye care interventions in Ghana

    Get PDF
    There is general agreement amongst major international policy makers that sustainability is a key component of health interventions in developing countries. However, there is little evidence on the factors enabling or constraining sustainability. Diffusion of innovation theory can help explain how the continuation of activities is related to the attributes of innovations. Innovations are characterised by five attributes: (i) relative advantage; (ii) compatibility; (iii) complexity; (iv) triability; and (v) observability. An eye care programme was selected as a case study. The programme was implemented in the Brong Ahafo region of Ghana and had been funded over a ten-year period by an international organisation

    Zinc uptake promotes myoblast differentiation via Zip7 transporter and activation of Akt signalling transduction pathway

    Get PDF
    [EN] Myogenic regeneration occurs through a chain of events beginning with the output of satellite cells from quiescent state, formation of competent myoblasts and later fusion and differentiation into myofibres. Traditionally, growth factors are used to stimulate muscle regeneration but this involves serious off-target effects, including alterations in cell homeostasis and cancer. In this work, we have studied the use of zinc to trigger myogenic differentiation. We show that zinc promotes myoblast proliferation, differentiation and maturation of myofibres. We demonstrate that this process occurs through the PI3K/Akt pathway, via zinc stimulation of transporter Zip7. Depletion of zinc transporter Zip7 by RNA interference shows reduction of both PI3K/Akt signalling and a significant reduction of multinucleated myofibres and myotubes development. Moreover, we show that mature myofibres, obtained through stimulation with high concentrations of zinc, accumulate zinc and so we hypothesise their function as zinc reservoirs into the cell.P.R. and R.S. acknowledges support from the Spanish Ministry of Economy and Competitiveness (MINECO) (MAT2015-69315-C3-1-R). P.R. acknowledges the Fondo Europeo de Desarrollo Regional (FEDER). CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. R.S. acknowledges the support from the Spanish MECD through the PRX16/00208 grant. MSS acknowledges support from the European Research Council (ERC - HealInSynergy 306990) and the UK Engineering and Physical Sciences Research Council (EPSRC - EP/P001114/1)Mnatsakanyan, H.; Sabater I Serra, R.; Rico Tortosa, PM.; Salmerón Sánchez, M. (2018). Zinc uptake promotes myoblast differentiation via Zip7 transporter and activation of Akt signalling transduction pathway. Scientific Reports. 8:1-14. https://doi.org/10.1038/s41598-018-32067-0S1148Frontera, W. R. & Ochala, J. Skeletal muscle: a brief review of structure and function. Calcif. Tissue Int. 96, 183–195 (2015).Wolfe, R. R., Frontera, W. R. & Ochala, J. The underappreciated role of muscle in health and disease. Am. J. Clin. Nutr. 84, 475–82 (2006).Sciorati, C., Rigamonti, E., Manfredi, A. A. & Rovere-Querini, P. Cell death, clearance and immunity in the skeletal muscle. Cell Death Differ. 23, 927–937 (2016).Wang, Y. X. & Rudnicki, M. A. Satellite cells, the engines of muscle repair. Nat. Rev. Mol. Cell Biol. 13, 127–133 (2011).Yin, H., Price, F. & Rudnicki, M. A. Satellite cells and the muscle stem cell niche. Physiol. Rev. 93, 23–67 (2013).Dhawan, J. & Rando, T. A. Stem cells in postnatal myogenesis: Molecular mechanisms of satellite cell quiescence, activation and replenishment. Trends Cell Biol. 15, 666–673 (2005).Yun, K. & Wold, B. Skeletal muscle determination and differentiation: Story of a core regulatory network and its context. Curr. Opin. Cell Biol. 8, 877–889 (1996).Gharaibeh, B. et al. Biological approaches to improve skeletal muscle healing after injury and disease. Birth Defects Res. Part C Embryo Today Rev. 96, 82–94 (2012).Schiaffino, S. & Mammucari, C. Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Skelet. Muscle 1, 4 (2011).Sandri, M. Signaling in muscle atrophy and hypertrophy. Physiology (Bethesda). 23, 160–70 (2008).Karalaki, M., Fili, S., Philippou, A. & Koutsilieris, M. Muscle regeneration: cellular and molecular events. In Vivo 23, 779–96 (2009).Fujio, Y. et al. Cell cycle withdrawal promotes myogenic induction of Akt, a positive modulator of myocyte survival. Mol. Cell. Biol. 19, 5073–82 (1999).Wilson, E. M. & Rotwein, P. Control of MyoD function during initiation of muscle differentiation by an autocrine signaling pathway activated by insulin-like growth factor-II. J. Biol. Chem. 281, 29962–29971 (2006).Sun, L., Liu, L., Yang, X. & Wu, Z. Akt binds prohibitin 2 and relieves its repression of MyoD and muscle differentiation. J. Cell Sci. 117, 3021–3029 (2004).Milner, D. & Cameron, J. Muscle repair and regeneration: stem cells, scaffolds, and the contributions of skeletal muscle to amphibian limb regeneration. Curr. Top. Microbiol. Immunol. 367, 133–159 (2013).Liu, C. et al. PI3K/Akt signaling transduction pathway is involved in rat vascular smooth muscle cell proliferation induced by apelin-13. Acta Biochim Biophys Sin 42, 396–402 (2010).Eriksson, M., Taskinen, M. & Leppä, S. Mitogen Activated Protein Kinase-Dependent Activation of c-Jun and c-Fos is required for Neuronal differentiation but not for Growth and Stress Reposne in PC12 cells. J. Cell. Physiol. 207, 12–22 (2006).Arsic, N. et al. Vascular endothelial growth factor stimulates skeletal muscle regeneration in Vivo. Mol. Ther. 10, 844–854 (2004).Borselli, C. et al. Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors. Proc. Natl. Acad. Sci. USA 107, 3287–3292 (2010).Hanft, J. R. et al. Phase I trial on the safety of topical rhVEGF on chronic neuropathic diabetic foot ulcers. J. Wound Care 17(30–2), 34–7 (2008).Simón-Yarza, T. et al. Vascular endothelial growth factor-delivery systems for cardiac repair: An overview. Theranostics 2, 541–552 (2012).Briquez, P. S., Hubbell, J. A. & Martino, M. M. Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing. Adv. Wound Care 4, 479–489 (2015).Barthel, A., Ostrakhovitch, E. A., Walter, P. L., Kampkötter, A. & Klotz, L. O. Stimulation of phosphoinositide 3-kinase/Akt signaling by copper and zinc ions: Mechanisms and consequences. Arch. Biochem. Biophys. 463, 175–182 (2007).Ostrakhovitch, E. A., Lordnejad, M. R., Schliess, F., Sies, H. & Klotz, L.-O. Copper ions strongly activate the phosphoinositide-3-kinase/Akt pathway independent of the generation of reactive oxygen species. Arch. Biochem. Biophys. 397, 232–239 (2002).Kaur, K., Gupta, R., Saraf, S. A. & Saraf, S. K. Zinc: The metal of life. Compr. Rev. Food Sci. Food Saf. 13, 358–376 (2014).Coleman, J. E. Zinc proteins: enzymes, storage proteins, transcription factors, and replication proteins. Annu. Rev. Biochem. 61, 897–946 (1992).Fukada, T. & Kambe, T. Molecular and genetic features of zinc transporters in physiology and pathogenesis. Metallomics 3, 662–674 (2011).Murakami, M. & Hirano, T. Intracellular zinc homeostasis and zinc signaling. Cancer Sci. 99, 1515–1522 (2008).Hogstrand, C., Kille, P., Nicholson, R. I. & Taylor, K. M. Zinc transporters and cancer: a potential role for ZIP7 as a hub for tyrosine kinase activation. Trends Mol. Med. 15, 101–111 (2009).Kolenko, V., Teper, E., Kutikov, A. & Uzzo, R. Zinc and zinc transporters in prostate carcinogenesis. Nat. Rev. Urol. 10, 219–26 (2013).Myers, S. A., Nield, A., Chew, G. S. & Myers, M. A. The zinc transporter, Slc39a7 (Zip7) is implicated in glycaemic control in skeletal muscle cells. Plos One 8 (2013).Kambe, T., Tsuji, T., Hashimoto, A. & Itsumura, N. The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism. Physiol. Rev. 95, 749–784 (2015).Jinno, N., Nagata, M. & Takahashi, T. Marginal zinc deficiency negatively affects recovery from muscle injury in mice. Biol. Trace Elem. Res. 158, 65–72 (2014).Taylor, K. M., Hiscox, S., Nicholson, R. I., Hogstrand, C. & Kille, P. Protein Kinase CK2 Triggers Cytosolic Zinc Signaling Pathways by Phosphorylation of Zinc Channel ZIP7. Sci. Signal. 5, ra11–ra11 (2012).Yamasaki, S. et al. Zinc is a novel intracellular second messenger. J. Cell Biol. 177, 637–45 (2007).Sumitani, S., Goya, K., Testa, J. R., Kouhara, H. & Kasayama, S. Akt1 and Akt2 differently regulate muscle creatine kinase and myogenin gene transcription in insulin-induced differentiation of C2C12 myoblasts. Endocrinology 143, 820–828 (2002).Ohashi, K. et al. Zinc promotes proliferation and activation of myogenic cells via the PI3K/Akt and ERK signaling cascade. Exp. Cell Res. 333, 228–237 (2015).Chesters, J. K. In Zinc in human biology 53, 109–118 (1989).Burattini, S. et al. C2C12 murine myoblasts as a model of skeletal muscle development: Morpho-functional characterization. Eur. J. Histochem. 48, 223–233 (2004).Mnatsakanyan, H. et al. Controlled Assembly of Fibronectin Nanofibrils Triggered by Random Copolymer Chemistry. ACS Appl. Mater. Interfaces 7, 18125–18135 (2015).Jeong, J. & Eide, D. J. The SLC39 family of zinc transporters. Molecular Aspects of Medicine 34, 612–619 (2013).Huang, L., Kirschke, C. P., Zhang, Y. & Yan, Y. Y. The ZIP7 gene (Slc39a7) encodes a zinc transporter involved in zinc homeostasis of the Golgi apparatus. J. Biol. Chem. 280, 15456–15463 (2005).Vallee, B. L. & Falchuk, K. H. The biochemical basis of zinc physiology. Physiological reviews 73 (1993).Ganju, N. & Eastman, A. Zinc inhibits Bax and Bak activation and cytochrome c release induced by chemical inducers of apoptosis but not by death-receptor-initiated pathways. Cell Death Differ. 10, 652–61 (2003).Chai, F., Truong-Tran, A. Q., Ho, L. H. & Zalewski, P. D. Regulation of caspase activation and apoptosis by cellular zinc fluxes and zinc deprivation: A review. Immunol. Cell Biol. 77, 272–278 (1999).Smith, P. J., Wiltshire, M., Furon, E., Beattie, J. H. & Errington, R. J. Impact of overexpression of metallothionein-1 on cell cycle progression and zinc toxicity. Am. J. Physiol. Cell Physiol. 295, C1399–C1408 (2008).Bozym, R. A. et al. Free zinc ions outside a narrow concentration range are toxic to a variety of cells in vitro. Exp. Biol. Med. (Maywood). 235, 741–50 (2010).Plum, L. M., Rink, L. & Hajo, H. The essential toxin: Impact of zinc on human health. Int. J. Environ. Res. Public Health 7, 1342–1365 (2010).Chen, C.-J. & Liao, S.-L. Zinc toxicity on neonatal cortical neurons: involvement of glutathione chelation. J. Neurochem. 85, 443–453 (2003).Chassot, A. A. et al. Confluence-induced cell cycle exit involves pre-mitotic CDK inhibition by p27Kip1 and cyclin D1 downregulation. Cell Cycle 7, 2038–2046 (2008).Spencer, S. L. et al. XThe proliferation-quiescence decision is controlled by a bifurcation in CDK2 activity at mitotic exit. Cell 155, 369–383 (2013).Walsh, K. & Perlman, H. Cell cycle exit upon myogenic differentiation. Curr. Opin. Genet. Dev. 7, 597–602 (1997).Puri, P. L. & Sartorelli, V. Regulation of muscle regulatory factors by DNA-binding, interacting proteins, and post-transcriptional modifications. Journal of Cellular Physiology 185, 155–173 (2000).Zammit, P. S., Partridge, T. A. & Yablonka-Reuveni, Z. The skeletal muscle satellite cell: the stem cell that came in from the cold. J Histochem Cytochem 54, 1177–1191 (2006).McCord, M. C. & Aizenman, E. The role of intracellular zinc release in aging, oxidative stress, and Alzheimer’s disease. Front. Aging Neurosci. 6, 1–16 (2014).Dirksen, R. T. Sarcoplasmic reticulum–mitochondrial through-space coupling in skeletal muscle. This paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic. Appl. Physiol. Nutr. Metab. 34, 389–395 (2009).Groth, C., Sasamura, T., Khanna, M. R., Whitley, M. & Fortini, M. E. Protein trafficking abnormalities in Drosophila tissues with impaired activity of the ZIP7 zinc transporter Catsup. Development 140, 3018–3027 (2013).Ellis, C. D. et al. Zinc and the Msc2 zinc transporter protein are required for endoplasmic reticulum function. J. Cell Biol. 166, 325–335 (2004).Koch, U., Lehal, R. & Radtke, F. Stem cells living with a Notch. Development 140, 689–704 (2013).Gardner, S., Anguiano, M. & Rotwein, P. Defining Akt actions in muscle differentiation. Am. J. Physiol. Physiol. 303, C1292–C1300 (2012).Knight, J. D. & Kothary, R. The myogenic kinome: protein kinases critical to mammalian skeletal myogenesis. Skelet. Muscle 1, 29 (2011).Roth, S. M. Genetic aspects of skeletal muscle strength and mass with relevance to sarcopenia. Bonekey Rep. 1, 1–7 (2012).Mebratu, Y. & Tesfaigzi, Y. How ERK1/2 Activation Controls Cell Proliferation and Cell Death Is Subcellular Localization the Answer? Cell Cycle 8, 1168–1175 (2009)

    Diffusion patterns of new anti-diabetic drugs into hospitals in Taiwan: the case of Thiazolidinediones for diabetes

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Diffusion of new drugs in the health care market affects patients' access to new treatment options and health care expenditures. We examined how a new drug class for diabetes mellitus, thiazolidinediones (TZDs), diffused in the health care market in Taiwan.</p> <p>Methods</p> <p>Assuming that monthly hospital prescriptions of TZDs could serve as a micro-market to perform drug penetration studies, we retrieved monthly TZD prescription data for 580 hospitals in Taiwan from Taiwan's National Health Insurance Research Database for the period between March 1, 2001 and December 31, 2005. Three diffusion parameters, time to adoption, speed of penetration (monthly growth on prescriptions), and peak penetration (maximum monthly prescription) were evaluated. Cox proportional hazards model and quantile regressions were estimated for analyses on the diffusion parameters.</p> <p>Results</p> <p>Prior hospital-level pharmaceutical prescription concentration significantly deterred the adoption of the new drug class (HR: 0.02, 95%CI = 0.01 to 0.04). Adoption of TZDs was slower in district hospitals (HR = 0.43, 95%CI = 0.24 to 0.75) than medical centers and faster in non-profit hospitals than public hospitals (HR = 1.79, 95%CI = 1.23 to 2.61). Quantile regression showed that penetration speed was associated with a hospital's prior anti-diabetic prescriptions (25%Q: 18.29; 50%Q: 25.57; 75%Q: 30.97). Higher peaks were found in hospitals that had adopted TZD early (25%Q: -40.33; 50%Q: -38.65; 75%Q: -32.29) and in hospitals in which the drugs penetrated more quickly (25%Q: 16.53; 50%Q: 24.91; 75%Q: 31.50).</p> <p>Conclusions</p> <p>Medical centers began to prescribe TZDs earlier, and they prescribed more TZDs at a faster pace. The TZD diffusion patterns varied among hospitals depending accreditation level, ownership type, and prescription volume of Anti-diabetic drugs.</p

    Diffusion patterns of new anti-diabetic drugs into hospitals in Taiwan: the case of Thiazolidinediones for diabetes

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Diffusion of new drugs in the health care market affects patients' access to new treatment options and health care expenditures. We examined how a new drug class for diabetes mellitus, thiazolidinediones (TZDs), diffused in the health care market in Taiwan.</p> <p>Methods</p> <p>Assuming that monthly hospital prescriptions of TZDs could serve as a micro-market to perform drug penetration studies, we retrieved monthly TZD prescription data for 580 hospitals in Taiwan from Taiwan's National Health Insurance Research Database for the period between March 1, 2001 and December 31, 2005. Three diffusion parameters, time to adoption, speed of penetration (monthly growth on prescriptions), and peak penetration (maximum monthly prescription) were evaluated. Cox proportional hazards model and quantile regressions were estimated for analyses on the diffusion parameters.</p> <p>Results</p> <p>Prior hospital-level pharmaceutical prescription concentration significantly deterred the adoption of the new drug class (HR: 0.02, 95%CI = 0.01 to 0.04). Adoption of TZDs was slower in district hospitals (HR = 0.43, 95%CI = 0.24 to 0.75) than medical centers and faster in non-profit hospitals than public hospitals (HR = 1.79, 95%CI = 1.23 to 2.61). Quantile regression showed that penetration speed was associated with a hospital's prior anti-diabetic prescriptions (25%Q: 18.29; 50%Q: 25.57; 75%Q: 30.97). Higher peaks were found in hospitals that had adopted TZD early (25%Q: -40.33; 50%Q: -38.65; 75%Q: -32.29) and in hospitals in which the drugs penetrated more quickly (25%Q: 16.53; 50%Q: 24.91; 75%Q: 31.50).</p> <p>Conclusions</p> <p>Medical centers began to prescribe TZDs earlier, and they prescribed more TZDs at a faster pace. The TZD diffusion patterns varied among hospitals depending accreditation level, ownership type, and prescription volume of Anti-diabetic drugs.</p
    corecore