Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
1.
Food Secur ; 14(4): 1027-1043, 2022.
Article in English | MEDLINE | ID: mdl-35371348

ABSTRACT

The impact of the first wave of the Covid-19 pandemic and the response of government and non-government actors, from February-September 2020, offers critical insights into the current state of England's food policy processes and operations, and in particular the coordination of national food policy approaches. This study aims to clarify and solidify the discourse around food policy coordination by differentiating between routine coordination of the activities of government, and strategic coordination of such policy activities with higher-level strategic goals, such as those associated with a healthy and sustainable food system. This framework is applied to the case study based on documentary analysis. In detailing the evidence of coordination in the response, including examples of cross-government working, and collaboration across the public, private and third sectors, the findings illustrate the breadth of actors which constituted the policy and governance response. These included public policymakers in national and local governments, and from a range of different government departments; private sector food businesses; and third sector organisations. There was a high level of routine coordination, but also instances of disconnection and delay. A lack of strategic coordination provides an explanatory device for several instances of disconnection and incoherence, including interventions which failed to prioritise nutrition-related health, and the working conditions of those employed in the food sector. The routine-strategic distinction can be deployed to inform discussions on the types of policy coordination mechanisms, such as cross-cutting taskforces or bodies, which might be instituted to support connected working on food.

2.
Gerontol Geriatr Med ; 8: 23337214211068290, 2022.
Article in English | MEDLINE | ID: mdl-35024382

ABSTRACT

Mild cognitive impairment (MCI) or dementia often leads to behavioral and psychiatric symptoms of dementia (BPSD). Sensory processing abnormalities may be associated with BPSD. The purpose of this study was to explore relationships among sensory processing, behavior, and environmental features within the homes of people with MCI or dementia. This project used mixed methods to assess participants' sensory processing, care partner perspectives on behaviors, and in situ observations of the home environment. Nine participants with cognitive impairment (MCI n = 8, early dementia = 1) and their care partners were included. Seven participants with cognitive impairment were reported to have abnormal sensory processing. Findings suggest that unique environmental adaptations, tailored to personal and sensory preferences for each participant, were associated with a decreased level of behavioral disruption during the observation periods. Implementing sensory-based approaches to maximize environment adaptation may be beneficial in reducing disruptive behaviors for adults with cognitive impairment.

3.
J Appl Gerontol ; 40(8): 814-817, 2021 08.
Article in English | MEDLINE | ID: mdl-33648357

ABSTRACT

Social distancing guidelines during COVID can be isolating, especially for older adults, with potential for poor health outcomes. Technology offers opportunities for remote connection, yet, older adults' use of and perspectives on technology during this time remain largely unknown. The purpose of this study was to gain insight into older adults' technology use and preferences to inform the development of a technology training intervention to support older adult well-being. Semi-structured interviews were conducted with 30 older adults. Interviews were analyzed using an iterative, constant comparison approach. Findings were consistent with Socioemotional Selectivity Theory; respondents were primarily interested in technology to support emotionally meaningful goals. Participants indicated limited interest in technology training, referencing diminished future time perspectives to explain disinterest. Findings suggest that efforts to encourage older adults' expanded technology adoption should highlight how use supports emotionally meaningful goals and provide low-effort, timely training, tied to specific and clear applications.


Subject(s)
COVID-19 , Physical Distancing , Aged , Humans , SARS-CoV-2
4.
Clin Gerontol ; 44(3): 345-353, 2021.
Article in English | MEDLINE | ID: mdl-33583362

ABSTRACT

Objectives: This study sought to explore changes in longitudinal cognitive status in relation to baseline measures of intimacy and sexuality in cognitively intact, married older adults.Methods: Baseline intimacy and sexuality survey data from 155, cognitively intact, married, older adults were collected using a novel survey instrument that explored the domains of: 1) romance with one's partner, 2) sexual satisfaction, 3) beliefs about sexuality, and 4) social support and emotional intimacy. These data were analyzed in relation to change in cognitive status over a 10-year follow-up period using binary logistic regression modeling. Exploratory factor analysis was used to assess the shared variance of survey items attributable to intimacy and sexuality without specification of an a priori hypothesis regarding the association of intimacy and sexuality with future change in cognitive status.Results: Over the 10-year study period, 33.5% (n = 52) of individuals developed cognitive impairment. Participants with greater sexual satisfaction scores at baseline were statistically less likely to convert from cognitively intact to mild cognitive impairment or dementia in the future (p = .01). The domains of romance with one's partner, beliefs about sexuality, and social support/emotional intimacy were not predictive of future longitudinal changes in cognitive status.Conclusions: Sexual satisfaction is associated with longitudinal cognitive outcomes in cognitively intact, married, older adults.Clinical implications: Clinicians should routinely assess for sexual satisfaction among older adults and refer to appropriate providers, such as couples or sex therapists, when appropriate.


Subject(s)
Cognitive Dysfunction , Orgasm , Aged , Humans , Sexual Behavior , Sexual Partners , Sexuality
5.
J Rural Health ; 37(2): 406-411, 2021 03.
Article in English | MEDLINE | ID: mdl-32246530

ABSTRACT

OBJECTIVES: The prevalence of Alzheimer's disease and associated disorders is increasing. Rural residents in the United States have less access to memory care specialists and educational and community resources than in other areas of the country. Over a decade ago, we initiated an interdisciplinary rural caregiving telemedicine program to reach Kentucky residents in areas of the state where resources for supporting individuals with dementia are limited. Telemedicine programs involve a short informational presentation followed by a question and answer session; programs are offered 4 times a year. The purpose of this study was to explore questions asked over 1 year of the rural caregiving telemedicine program-encompassing 5 programs-to identify the scope of dementia-related knowledge gaps among attendees. METHODS: Questions from the 5 programs were recorded and content analyzed to identify areas of frequent informational requests. RESULTS: There were a total of 69 questions over the 5 sessions. For each program, questions ended due to time constraints rather than exhausting all inquiries. The most common topical areas of questions related to risk factors, behavioral management, diagnosis, and medications. DISCUSSION AND IMPLICATIONS: This study highlights that rural caregivers in Kentucky have diverse dementia educational needs. Rural communities may benefit from additional, targeted resources addressing these common areas of unmet informational needs.


Subject(s)
Alzheimer Disease , Telemedicine , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Alzheimer Disease/therapy , Caregivers , Humans , Kentucky , Rural Population , United States
6.
Gerontologist ; 60(4): 693-703, 2020 05 15.
Article in English | MEDLINE | ID: mdl-31322657

ABSTRACT

BACKGROUND AND OBJECTIVES: Recruitment and retention of research participant serve as a significant challenge in the search for ways to slow or prevent Alzheimer's disease. While barriers to participation are well documented, less is known about motivations for Alzheimer's disease clinical research participation. The purpose of this study was to explore what motivates individuals-who ultimately develop an ongoing connection to research and frequently participate-to engage and stay involved in Alzheimer's disease research. RESEARCH DESIGN AND METHODS: Individuals who had participated in multiple Alzheimer's disease-related clinical trials, or their study partners, were interviewed about their decisions to engage and remain in research. FINDINGS: Interviews were completed with 33 individuals, 28 research participants, and 5 study partners. All interviews were audio-recorded and transcribed verbatim for analysis. Respondents indicated learning about research opportunities through the media, community events, doctors, and other research participants. While many were initially motivated by a family history or knowing someone with Alzheimer's disease, others had no personal exposure. Individuals in prevention studies were generally proactive and viewed research as a constructive way to address memory concerns. While several individuals acknowledged personal benefits of research participation, most indicated an understanding of the importance of research and being motivated to help others in the future, frequently referencing a sense of social responsibility or moral obligation to help. Positive relationships with personnel at the site encouraged continued involvement. DISCUSSION AND IMPLICATIONS: These findings suggest that efforts to identify research participants should highlight the value of research and help illuminate how participation may contribute to well-being of future generations.


Subject(s)
Alzheimer Disease , Clinical Trials as Topic , Motivation , Patient Selection , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Qualitative Research
7.
Health Systems and Policy Analysis: policy brief; 31
Monography in English | WHO IRIS | ID: who-331979

ABSTRACT

This policy brief was prepared in support of the Austrian EU Presidency to explore how food systems can combine diet-related health with environmental and economic policy goals. It builds on considerable earlier work by analysing the connections between different policy goals and between policy goals and food systems. Through this process, the authors identify three core aspects of food systems functioning which would need to connect (economic benefits for farmers and businesses derived from the production and delivery of nutritious food using sustainable methods) in order to produce co-benefits.


Subject(s)
Diet , Food , Food Supply , Nutrition Policy , Health Policy
8.
Curr Med Res Opin ; 31(9): 1633-43, 2015.
Article in English | MEDLINE | ID: mdl-26086890

ABSTRACT

OBJECTIVES: The objective of this project was to determine pharmacy cost savings and improvement in adherence based on a combinatorial pharmacogenomic test (CPGx ) in patients who had switched or added a new psychiatric medication after having failed monotherapy for their psychiatric disorder. RESEARCH DESIGN AND METHODS: The prospective project compared 1 year pharmacy claims between a GeneSight CPGx guided cohort and a propensity-matched control group. Patients were project eligible if they augmented or switched to a different antidepressant or antipsychotic medication within the previous 90 days. Following the medication switch or augmentation, pharmacogenomic (PGx) testing was offered to each patient's treating clinician. Pharmacy claims were extracted from the Medco pharmacy claims database for each patient (n = 2168) for 1 year following testing and compared to a 5-to-1 propensity-matched treatment as usual (TAU), standard of care control group (n = 10,880). MAIN OUTCOME MEASURES: Total pharmacy spend per member per year; adherence. RESULTS: Patients who received PGx testing saved $1035.60 in total medication costs (both CNS and non-CNS medications) over 1 year compared to the non-tested standard of care cohort (p = 0.007). PGx testing improved adherence compared to standard of care (ΔPDCCPGx = 0.11 vs ΔPDCTAU = -0.01; p < 0.0001). Pharmacy cost savings averaged $2774.53 for patients who were changed to a CPGx congruent medication regimen, compared to those who were not (p < 0.0001). CONCLUSIONS: PGx testing provides significant 'real world' cost savings, while simultaneously improving adherence in a difficult to treat psychiatric population. Limitations of this study include the lack of therapeutic efficacy follow-up data and possible confounding due to matching only on demographic and psychiatric variables.


Subject(s)
Antidepressive Agents , Antipsychotic Agents , Genetic Testing/economics , Pharmacogenetics , Adult , Aged , Antidepressive Agents/economics , Antidepressive Agents/therapeutic use , Antipsychotic Agents/economics , Antipsychotic Agents/therapeutic use , Cost Savings/statistics & numerical data , Drug Costs/statistics & numerical data , Fees, Pharmaceutical/statistics & numerical data , Female , Genetic Testing/methods , Humans , Male , Medication Adherence/psychology , Medication Adherence/statistics & numerical data , Mental Disorders/drug therapy , Mental Disorders/psychology , Middle Aged , Outcome Assessment, Health Care , Pharmacogenetics/economics , Pharmacogenetics/methods , Prospective Studies , United States
9.
Glob Adv Health Med ; 3(3): 25-32, 2014 May.
Article in English | MEDLINE | ID: mdl-24891991

ABSTRACT

PRIMARY STUDY OBJECTIVE: To evaluate the economic utility of a fecal biomarker panel structured to suggest alternative, treatable diagnoses in patients with symptoms of irritable bowel syndrome (IBS) by quantifying, comparing, and contrasting health service costs between tested and non-tested patients. STUDY DESIGN: Retrospective, matched cohort study comparing direct medical costs for IBS patients undergoing fecal biomarker testing with those of matched control subjects. METHODS: We examined de-identified medical and pharmacy claims of a large American pharmacy benefit manager to identify plan members who underwent panel testing, were eligible for covered benefits for at least 180 days prior to the test date, and had data available for 30, 90, and 365 days after that date. We used propensity score matching to develop population-based control cohorts for each tested cohort, comprised of records with IBS-related diagnoses but for which panel testing was not performed. Primary outcome measures were diagnostic and medical services costs as determined from claims data. RESULTS: Two hundred nine records from tested subjects met inclusion criteria. The only significant baseline differences between groups were laboratory costs, which were significantly higher in each tested cohort. At each follow-up time point, total medical and gastrointestinal procedural costs were significantly higher in non-tested cohorts. Within tested cohorts, costs declined significantly from baseline, while costs rose significantly in non-tested control cohorts; these differences were also significant between groups at each time point. CONCLUSIONS: Structured fecal biomarker panel testing was associated with significantly lower medical and gastrointestinal procedural costs in this study of patients with IBS symptoms.

10.
Res Social Adm Pharm ; 8(1): 60-75, 2012.
Article in English | MEDLINE | ID: mdl-21511543

ABSTRACT

BACKGROUND: Medication reconciliation has been recognized as an important process in care transitions to prevent adverse health outcomes. Because older adults have multiple comorbid conditions and use multiple medications, they are more likely to experience complicated transitions between acute and long-term care settings. Hence, it is important to develop effective interventions to protect older adults at transition points of care. OBJECTIVE: To systematically review the literature and evaluate studies performing medication reconciliation interventions in patients transferred to and from long-term care settings. METHODS: The literature search focused on studies that evaluated an intervention involving medication reconciliation in patients transferred to and/or from long-term care settings, such as nursing homes, skilled nursing facilities, residential care facilities, assisted living facilities, homes for the aged, and hospice care. A search was conducted on Ovid MEDLINE (1950-August 2010), Ovid HealthSTAR (1966-August 2010), Cumulative Index to Nursing and Allied Health Literature (1982-August 2010), PubMed (1980-August 2010), The Cochrane Database of Systematic Reviews (2005-August 2010), the Agency for Healthcare Research and Quality website, and reference lists of relevant articles were hand-searched. Two reviewers screened the titles and abstracts for potentially relevant studies. Data abstraction from the included articles was performed independently by 4 reviewers. RESULTS: Seven studies met the inclusion criteria. Four studies were performed in the United States, whereas 3 studies were performed in other countries. A clinical pharmacist proved to be useful in providing medication reconciliation interventions by adopting specialized responsibilities such as serving as a transition pharmacist coordinator or working through a call center. Although improvement in the outcome(s) examined was shown in all of the studies, there were study design flaws. CONCLUSION: There is a need for well-designed studies demonstrating the effectiveness of medication reconciliation interventions in long-term care settings. Future studies should focus on employing appropriate methods so that their interventions can be evaluated more effectively.


Subject(s)
Long-Term Care , Medication Reconciliation , Patient Transfer , Continuity of Patient Care , Humans
11.
Front Psychol ; 2: 17, 2011.
Article in English | MEDLINE | ID: mdl-21713179

ABSTRACT

Although shared storybook reading is a common activity believed to improve the language skills of preschool children, how children learn new vocabulary from such experiences has been largely neglected in the literature. The current study systematically explores the effects of repeatedly reading the same storybooks on both young children's fast and slow mapping abilities. Specially created storybooks were read to 3-year-old children three times during the course of 1 week. Each of the nine storybooks contained two novel name-object pairs. At each session, children either heard three different stories with the same two novel name-object pairs or the same story three times. Importantly, all children heard each novel name the same number of times. Both immediate recall and retention were tested with a four-alternative forced-choice task with pictures of the novel objects. Children who heard the same stories repeatedly were very accurate on both the immediate recall and retention tasks. In contrast, children who heard different stories were only accurate on immediate recall during the last two sessions and failed to learn any of the new words. Overall, then, we found a dramatic increase in children's ability to both recall and retain novel name-object associations encountered during shared storybook reading when they heard the same stories multiple times in succession. Results are discussed in terms of contextual cueing effects observed in other cognitive domains.

12.
Hypertension ; 57(3): 577-85, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21242463

ABSTRACT

Vascular injury and remodeling are common pathological sequelae of hypertension. Previous studies have suggested that the renin-angiotensin system acting through the type 1 angiotensin II (AT(1)) receptor promotes vascular pathology in hypertension. To study the role of AT(1) receptors in this process, we generated mice with cell-specific deletion of AT(1) receptors in vascular smooth muscle cells using Cre/Loxp technology. We crossed the SM22α-Cre transgenic mouse line expressing Cre recombinase in smooth muscle cells with a mouse line bearing a conditional allele of the Agtr1a gene (Agtr1a (flox)), encoding the major murine AT(1) receptor isoform (AT(1A)). In SM22α-Cre(+)Agtr1a (flox/flox) (SMKO) mice, AT(1A) receptors were efficiently deleted from vascular smooth muscle cells in larger vessels but not from resistance vessels such as preglomerular arterioles. Thus, vasoconstrictor responses to angiotensin II were preserved in SMKO mice. To induce hypertensive vascular remodeling, mice were continuously infused with angiotensin II for 4 weeks. During infusion of angiotensin II, blood pressures increased significantly and to a similar extent in SMKO and control mice. In control mice, there was evidence of vascular oxidative stress indicated by enhanced nitrated tyrosine residues in segments of aorta; this was significantly attenuated in SMKO mice. Despite these differences in oxidative stress, the extent of aortic medial expansion induced by angiotensin II infusion was virtually identical in both groups. Thus, vascular AT(1A) receptors promote oxidative stress in the aortic wall but are not required for remodeling in angiotensin II-dependent hypertension.


Subject(s)
Aorta/metabolism , Hypertension/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Receptor, Angiotensin, Type 1/metabolism , Analysis of Variance , Angiotensin II/pharmacology , Animals , Aorta/drug effects , Aorta/pathology , Aorta/physiopathology , Blood Pressure/drug effects , Blood Pressure/physiology , Hypertension/chemically induced , Hypertension/pathology , Hypertension/physiopathology , Mice , Mice, Transgenic , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Muscle, Smooth, Vascular/physiopathology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/pathology , Oxidative Stress/drug effects , Oxidative Stress/physiology , Vasoconstriction/drug effects , Vasoconstriction/physiology , Vasoconstrictor Agents/pharmacology
13.
Hypertension ; 54(6): 1360-8, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19822795

ABSTRACT

Glutathione S-transferase-micro1, GSTM1, belongs to a superfamily of glutathione S-transferases that metabolizes a broad range of reactive oxygen species and xenobiotics. Across species, genetic variants that result in decreased expression of the Gstm1 gene are associated with increased susceptibility for vascular diseases, including atherosclerosis in humans. We previously identified Gstm1 as a positional candidate in our gene mapping study for susceptibility to renal vascular injury characterized by medial hypertrophy and hyperplasia of the renal vessels. To determine the role of Gstm1 in vascular smooth muscle cells (VSMCs), we isolated VSMCs from mouse aortas. We demonstrate that VSMCs from the susceptible C57BL/6 mice have reduced expression of Gstm1 mRNA and its protein product compared with that of the resistant 129 mice. After serum stimulation, C57BL/6 VSMCs proliferate and migrate at a much faster rate than 129 VSMCs. Furthermore, C57BL/6 VSMCs have higher levels of reactive oxygen species and exhibit exaggerated p38 mitogen-activated protein kinase phosphorylation after exposure to H(2)O(2). To establish causality, we show that knockdown of Gstm1 by small interfering RNA results in increased proliferation of VSMCs in a dose-dependent manner, as well as in increased reactive oxygen species levels and VSMC migration. Moreover, Gstm1 small interfering RNA causes increased p38 mitogen-activated protein kinase phosphorylation and attenuates the antiproliferative effect of Tempol. Our data suggest that Gstm1 is a novel regulator of VSMC proliferation and migration through its role in handling reactive oxygen species. Genetic variants that cause a decremental change in expression of Gstm1 may permit an environment of exaggerated oxidative stress, leading to susceptibility to vascular remodeling and atherosclerosis.


Subject(s)
Atherosclerosis/metabolism , Atherosclerosis/pathology , Glutathione Transferase/metabolism , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/enzymology , Animals , Antioxidants/pharmacology , Aorta/cytology , Cell Division/physiology , Cell Movement/physiology , Cells, Cultured , Cyclic N-Oxides/pharmacology , Glutathione Transferase/genetics , Hydrogen Peroxide/pharmacology , Mice , Mice, Inbred C57BL , Oxidants/pharmacology , Oxidative Stress/drug effects , Oxidative Stress/physiology , Phosphorylation/physiology , RNA, Small Interfering , Reactive Oxygen Species/metabolism , Species Specificity , Spin Labels , p38 Mitogen-Activated Protein Kinases/metabolism
14.
J Clin Invest ; 119(4): 943-53, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19287096

ABSTRACT

Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we generated MRL-Faslpr/lpr (lpr) mice lacking the major murine type 1 angiotensin receptor (AT1A); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, AT1A deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of AT1A-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by AT1A deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, AT1B, and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of AT1A-deficient lpr mice, and they showed evidence of exaggerated AT1B receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since AT1A-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension.


Subject(s)
Autoimmune Diseases/etiology , Nephritis/etiology , Receptor, Angiotensin, Type 1/physiology , Animals , Autoimmune Diseases/immunology , Autoimmune Diseases/pathology , Autoimmune Diseases/physiopathology , Chemokines/genetics , Cytokines/genetics , Female , Kidney/injuries , Kidney/pathology , Kidney/physiopathology , Male , Mice , Mice, Inbred MRL lpr , Mice, Knockout , Nephritis/immunology , Nephritis/pathology , Nephritis/physiopathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor, Angiotensin, Type 1/deficiency , Receptor, Angiotensin, Type 1/genetics , Renin-Angiotensin System/physiology
15.
J Clin Invest ; 117(4): 873-6, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17404616

ABSTRACT

Components of the renin-angiotensin system (RAS) are expressed in a number of areas in the brain involved in cardiovascular control. However, it has been difficult to link RAS actions in circumscribed brain regions to specific physiological functions. In a study appearing in this issue of the JCI, Sakai and associates use a combination of sophisticated transgenic techniques and stereotaxic microinjection of recombinant viral vectors to demonstrate a pivotal role in the regulation of thirst and salt appetite of angiotensin II generated in the subfornical organ in the brain (see the related article beginning on page 1088).


Subject(s)
Brain/physiology , Renin-Angiotensin System/physiology , Blood Pressure , Cardiovascular Physiological Phenomena , Humans
16.
Am J Physiol Lung Cell Mol Physiol ; 291(2): L144-56, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16473862

ABSTRACT

Prostacyclin is one of a number of lipid mediators elaborated from the metabolism of arachidonic acid by the cyclooxygenase (COX) enzymes. This prostanoid is a potent inhibitor of platelet aggregation, and its production by endothelial cells and protective role in the vasculature are well established. In contrast, much less is known regarding the function of this prostanoid in other disease processes. We show here that COX-2-dependent production of prostacyclin plays an important role in the development of fibrotic lung disease, limiting both the development of fibrosis and the consequential alterations in lung mechanics. In stark contrast, loss of prostaglandin E(2) synthesis and signaling through the G(s)-coupled EP2 and EP4 receptors had no effect on the development of disease. These findings suggest that prostacyclin analogs will protect against bleomycin-induced pulmonary fibrosis in COX-2(-/-) mice. If such protection is observed, investigation of these agents as a novel therapeutic approach to pulmonary fibrosis in humans may be warranted.


Subject(s)
Antibiotics, Antineoplastic/toxicity , Bleomycin/toxicity , Cyclooxygenase 2/metabolism , Epoprostenol/metabolism , Pulmonary Fibrosis , Animals , Cyclooxygenase 1/genetics , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/genetics , Lung/cytology , Lung/pathology , Lung/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Prostaglandins/metabolism , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/metabolism
17.
Am J Physiol Endocrinol Metab ; 290(6): E1131-9, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16352673

ABSTRACT

The mouse has become the most important model organism for the study of human physiology and disease. However, until the recent generation of mice lacking the enzyme gulanolactone oxidase (Gulo), the final enzyme in the ascorbic acid biosynthesis pathway, examination of the role of ascorbic acid in various biochemical processes using this model organism has not been possible. In the mouse, similar to most mammals but unlike humans who carry a mutant copy of this gene, Gulo produces ascorbic acid from glucose. We report here that, although ascorbic acid is essential for survival, its absence does not lead to measurable changes in proline hydroxylation. Vitamin C deficiency had no significant effect on the hydroxylation of proline and collagen production during tumor growth or in angiogenesis associated with tumor or mammary gland growth. This suggests that factors other than ascorbic acid can support proline hydroxylation and collagen synthesis in vivo. Furthermore, the failure of Gulo-/- mice to thrive on a vitamin C-deficient diet therefore suggests that ascorbic acid plays a critical role in survival other than the maintenance of the vasculature.


Subject(s)
Ascorbic Acid/physiology , Collagen/biosynthesis , Mammary Glands, Animal/blood supply , Mammary Neoplasms, Experimental/blood supply , Animals , Ascorbic Acid/genetics , Ascorbic Acid/metabolism , Female , Hydroxylation , Hydroxyproline/metabolism , Mammary Glands, Animal/growth & development , Mammary Glands, Animal/metabolism , Mammary Neoplasms, Experimental/metabolism , Mice , Mice, Inbred BALB C , Mice, Knockout , Neovascularization, Pathologic/metabolism , Neovascularization, Physiologic , Proline/metabolism , Proline/pharmacokinetics , Skin/metabolism , Weight Loss
SELECTION OF CITATIONS
SEARCH DETAIL
...