text:
Management of stable chronic obstructive pulmonary disease
- Authors
- Gary T Ferguson, MD
Gary T Ferguson, MD
- Director, Pulmonary Research Institute of Southeast Michigan
- Barry Make, MD
Barry Make, MD
- Professor of Medicine, University of Colorado Denver School of Medicine
- Co-Director, COPD Program, National Jewish Health
- Section Editor
- James K Stoller, MD, MS
James K Stoller, MD, MS
- Section Editor — Chronic Obstructive Pulmonary Disease
- Jean Wall Bennett Professor of Medicine, Samson Global Leadership Academy Endowed Chair
- Cleveland Clinic Lerner College of Medicine
- Chairman, Education Institute, Cleveland Clinic
- Deputy Editor
- Helen Hollingsworth, MD
Helen Hollingsworth, MD
- Deputy Editor — Pulmonary, Critical Care, and Sleep Medicine
- Associate Professor of Medicine
- Boston University School of Medicine
Chronic obstructive pulmonary disease (COPD) is a common condition with a high and continually increasing mortality, affecting men and women equally. It is estimated that approximately 7 percent of all individuals have COPD, including approximately 10 percent of individuals 65 years of age or older [1-3]. The true prevalence is likely higher because COPD is both under-recognized and under-diagnosed. COPD is the third leading cause of death among adults in the US and is expected to become the third leading cause of death worldwide by 2020 [4,5].
The management of stable COPD will be reviewed here. The diagnosis, natural history, and prognosis of COPD, risk factors for COPD, and treatment of acute exacerbations are discussed separately. (See "Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging" and "Chronic obstructive pulmonary disease: Prognostic factors and comorbid conditions" and "Chronic obstructive pulmonary disease: Risk factors and risk reduction" and "Management of exacerbations of chronic obstructive pulmonary disease".)
We share the philosophy of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) that pharmacologic and nonpharmacologic therapies should be guided by disease severity and aim to control symptoms, decrease exacerbations, and improve patient function and quality of life [6]. Both pharmacologic and non-pharmacologic interventions are key to the management of COPD patients. Non-pharmacologic interventions include: (1) smoking cessation, (2) reduction of other risk factors, (3) vaccinations, (4) oxygen therapy, and (5) pulmonary rehabilitation. In the discussion that follows, the formal assessment of COPD severity, the various therapies for COPD, and the clinical evidence for each therapy are reviewed. Pharmacotherapy is generally added in a stepwise fashion. However, for patients who present with severe disease, a stepwise approach may not always be the best choice, as it may be necessary to initiate several medications at once to achieve symptom control. An approach to the management of patients with stable COPD is outlined below. (See 'Summary and recommendations' below.)
The mainstays of drug therapy of stable symptomatic COPD are inhaled bronchodilators (beta agonists and anticholinergics) given alone or in combination with inhaled glucocorticoids depending upon the severity and impact of disease, risk of exacerbations, and response to therapy (table 1 and table 2). These are generally administered via inhalation in the form of metered dose, soft mist, or dry powder inhalers, and some may be administered by nebulization. For maintenance therapy, long-acting agents are recommended. The oral bronchodilator theophylline, which is only modestly effective and has more side effects than inhaled bronchodilators, is occasionally used for patients with refractory COPD; it is more widely employed in developing countries with limited resources.
Education about the purpose and dosing of regularly-prescribed and as-needed medications and about proper inhaler technique is essential. (See "Delivery of inhaled medication in adults" and "The use of inhaler devices in adults" and "Patient education: Asthma inhaler techniques in adults (Beyond the Basics)".)
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- Short-acting bronchodilators
- - Beta agonists
- - Anticholinergics
- - Comparison
- - Combination therapy
- Long-acting bronchodilators
- - Beta agonists
- - Anticholinergics
- - Comparison
- - Combined bronchodilator therapy
- Efficacy
- Comparison with LAMA-LABA
- Theophylline
- PDE-4 inhibitors
- Systemic glucocorticoids
- Mucoactive agents
- Chronic antibiotic therapy
- Oxygen
- Secretion clearance
- Smoking cessation
- Vaccinations
- Rehabilitation
- Patient education
- Nutrition
- Noninvasive positive pressure ventilation
- Lung volume reduction surgery
- Transplantation
- Antiproteases


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Xanthones are a group of oxygen-containing heterocyclic compounds with remarkable pharmacological effects such as anti-cancer, antioxidant, anti-inflammatory, and antimicrobial activities.
A xanthones extract (81% α-mangostin and 16% γ-mangostin), was prepared by crystallization of a toluene extract of
The extract showed potent cytotoxicity (median inhibitory concentration 6.5 ± 1.0 μg/ml), due to induction of the mitochondrial pathway of apoptosis. Three key steps in tumor metastasis including the cell migration, cell invasion and clonogenicity, were also inhibited. The extract and α-mangostin up-regulate the MAPK/ERK, c-Myc/Max, and p53 cell signalling pathways. The xanthones extract, when fed to nude mice, caused significant growth inhibition of the subcutaneous tumor of HCT 116 colorectal carcinoma cells.
Our data suggest new mechanisms of action of α-mangostin and the
Mangosteen fruit rinds contain high concentration of xanthones. α-Mangostin (1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9 H-xanthen-9-one), and γ-mangostin (1,3,6,7-tetrahydroxy-2,8-bis(3-methylbut-2-enyl)xanthen-9-one) (Figure
Figure 1
Chemical structure of α-mangostin and γ-mangostin, the main constituents of the
Chemical structure of α-mangostin and γ-mangostin, the main constituents of the
Colorectal cancer is the third in incidence after lung and breast cancers and accounts for almost 10% of total cases of cancer and almost 8% of total cancer deaths
Anti-cancer properties of
This study aims to investigate the
Cell lines and reagents
Human colorectal carcinoma cell line HCT 116; Catalogue number (CCL-247) and CCD-18Co normal colonic fibroblast; Catalogue number (CRL-1459) were purchased from the American Type Culture Collection (ATCC; Manassas, Virginia). RPMI 1640, Opti-MEM® and DMEM cell culture media, heat inactivated fetal bovine serum (HI-FBS), and phosphate buffered saline (PBS) without calcium and magnesium were purchased from Bio-Diagnostics (Petaling Jaya, Selangor, Malaysia). Cignal finder™ 10-pathway reporter-array system, and matrigel matrix (10 mg/ml) were purchased from SABiosciences (Frederick, Maryland). Wizard® SV genomic DNA purification system, caspases-3/7, -8 and −9 reagents, trans fast liposome, and dual luciferase reporter system were purchased from Promega (Petaling Jaya, Selangor, Malaysia). Cisplatin, Hoechst 33258, Rhodamine 123, agarose, ethidium bromide, penicillin/streptomycin (PS) solution, dimethylsulfoxide (DMSO), phenazine methosulfate (PMS), and 2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2
Plant material and extraction
Athymic NCR nu/nu nude mice were obtained from Taconic Farms Inc. (Hudson, New York). Mice were housed in specific pathogen free (SPF) cages supplied with high efficiency particulate air (HEPA) filters. Free access to autoclaved food and water was provided and the autoclaved bedding was changed twice weekly. The procedures were approved by the USM Animal Ethics Committee with a reference number PPSG/07(A)/044/(2010) (59).
Liquid chromatography-mass spectrometry (LC-MS)
The xanthones extract was analyzed by a Dionex-Ultimate® 3000 Rapid Separation LC system (Dionex, Sunnyvale, California), connected with a Micro TOF-Q mass spectrometer (Bruker, Madison, Wisconsin). Chromatographic separation was performed using Nucleosil C18 column (5 μm, 4.6 × 250 mm) (Macherey-Nagel, Bethlehem, Pennsylvania), at 30°C, the mobile phase was consisting of 95% acetonitrile and 5% of 0.1% formic acid in water. The flow rate was set at 0.5 ml/min for 15 min, and spectral data were collected at 244 nm. Mass analysis was performed in the range 50–1000 m/z, under negative ion mode, and the nebulizer was set at 3.0 bar and heated to 150°C. The capillary voltage was set at 3000 V using a nitrogen dry gas at 8.0 L/min. The end plate offset was maintained at −500 V.
Cell culture
HCT 116 cells were maintained in RPMI 1640 medium supplemented with 10% HI-FBS and 1% PS, and the CCD-18Co cells were maintained in DMEM medium supplemented with 10% HI-FBS and 1% PS. Cells were cultured in a 5% CO2 in a humidified atmosphere at 37°C.
Cell viability
Cell viability was determined by the XTT test as described previously
The median inhibitory concentrations (IC50s) were calculated from the dose response curves (n = 3).
Caspases-3/7, -8 and −9
HCT 116 cells were treated in a white 96-well plate for 90 min. Subsequently, the caspases activity was measured by caspase Glo 3/7, Glo 8 and Glo 9 as described previously
Mitochondrial membrane potential and chromatin condensation
Rhodamine 123 and Hoechst 33258 were used as probes to study the effect on mitochondrial membrane potential and chromatin condensation
DNA fragmentation
HCT 116 (2 × 106) cells were treated for 48 h. Subsequently, the floating and attached cells were collected by centrifugation at 3000 rpm for 10 min, the total genomic DNA was extracted using Wizard® SV genomic DNA purification system, and analyzed by electrophoresis on 1.2% agarose gel stained with 0.5 μg/ml ethidium bromide.
Anti-tumorigenicity studies including clonogenicity, cell migration, and cell invasion were investigated on HCT 116 cells. Effect on the clonogenicity was evaluated by the colony formation assay as previously described
The effect on cell migration was studied by the wound healing assay as described previously
Effect on cell invasion was studied by a modification of the Boyden chamber assay using matrigel matrix
Effect on cell signalling pathways
The assay was performed in 96-well plate format according to the manufacturer's instructions. Briefly, HCT 116 cells were transfected by reverse transfection with DNA constructs of 10 signalling pathways, a positive control, and a negative control. After overnight incubation, cells were treated for 6 h in complete RPMI medium. Subsequently, the activity of Firefly and
Twenty four nude mice aged 6–8 weeks with average weight of 25 g were injected subcutaneously in right flank with 5 × 106 cells in 150 μl RPMI. After 7–10 days, animals with uniform tumor size were divided into 3 groups of 6 animals. Tumor size and body weight were recorded before starting the treatment and at 5-days intervals for 20 days. Animals were treated by mixing the extract with the animal food at 0.25% and 0.5% extract: food ratio (wt/wt). Tumor dimensions were measured by a calibre in 2 angles, length and width
Statistical analysis
The results are presented as mean ± SD. The differences between groups were compared by One-way ANOVA, and were considered significant at P < 0.05. Data analysis was carried out using SSPS 16.0 software.
Phytochemical analysis
The extract was obtained at 5% yield (wt/wt) relative to the dry plant material. LC-MS analysis indicates the presence of 5 compounds; α-mangostin, was 81%, γ-mangostin was 16%, and the other 3 compounds were 3%, the percentage of the compounds was calculated based on the peak area (Table
The xanthones extract, α-mangostin, and γ-mangostin caused dose dependent killing of the colon cancer cells (Figure
Figure 2
Cytotoxic and apoptotic effects of α-mangostin and the xanthones extract on HCT 116 cells
Cytotoxic and apoptotic effects of α-mangostin and the xanthones extract on HCT 116 cells. Dose response curves of the xanthones extract on HCT 116 and CCD-18Co cells in the concentration range 2.5 – 30 μg/ml (a). Effect on caspases-3/7 (b), and caspases-8 and −9 (c). Effect on DNA fragmentation (d): the negative control was 0.5% DMSO, the positive control was α-mangostin at 20 μg/ml, and the xanthones extract was applied at 10, 20, 30 and 40 μg/ml. (*) indicates
Effect on caspases-3/7,-8 and −9
α-Mangostin and the xanthones extract at 10 and 20 μg/ml, showed a rapid enhancement of the caspases-3/7 activity after a treatment for 90 min (Figure
Effect on DNA fragmentation
Analysis of the total genomic DNA by agarose gel electrophoresis revealed apparent DNA fragmentation in HCT 116 cells (Figure
Effect on mitochondrial membrane potential of HCT 116 cells
The rhodamine staining showed a distinct morphology of the apoptotic cells, which were stained more brightly than the non-apoptotic cells (Figure
Figure 3
Effect of the xanthones extracts on mitochondrial membrane potential and chromatin condensation
Effect the xanthones extracts on mitochondrial membrane potential and chromatin condensation. The mitochondrial membrane potential (a): negative control (1), α-mangostin at 20 μg/ml (2) and the xanthones extract at 20 μg/ml (3). Chromatin condensation (b): negative control (1), α-mangostin at 20 μg/ml (2) and the xanthones extract at 20 μg/ml (3).
Effect on chromatin condensation and nuclear fragmentation
α-Mangostin at 20 μg/ml, and the xanthones extract caused significant and dose dependent induction of chromatin condensation and nuclear fragmentation in HCT 116 cells after 2 h treatment. Staining with the DNA probe Hoechst 33258 produced a distinct nuclear morphology of the apoptotic cells, which were stained more brightly, with or without nuclear fragmentation, whereas the non-apoptotic cells showed uniformly stained nuclei at lower intensely (Figure
The compounds inhibited the clonogenicity of HCT 116 cells (Figure
Figure 4
Anti-tumorigenicity effect of the xanthones extract on HCT 116 cells
Anti-tumorigenicity effect of the xanthones extract on HCT 116 cells. Clonogenicity (a): negative control (1), α-mangostin at 5 μg/ml (2) and the xanthones extract at 5 μg/ml (3). Cell migration (b): wounds photographed at zero time (1), and the treated cells after 24 h; negative control (2), α-mangostin at 5 μg/ml (3) and the xanthones extract at 5 μg/ml (4). Matrigel invasion (c): untreated cells (1), α-mangostin at 6 μg/ml (2) xanthones extract at 6 μg/ml (3) and at 4.5 μg/ml (4).
Cell migration was also inhibited in both treatments (Figure
Effect on cell signalling pathways
The transfected HCT 116 cells were treated at 2 concentrations 7.5 and 10 μg/ml for 6 h, and the results in the treated cells were compared to those treated with the vehicle alone (0.5% DMSO). The transcription factor activity of the 10 pathways is reduced by treating the cells with 10 μg/ml of the xanthones extract and α-mangostin. However, the treated cells showed apoptotic morphology, which indicates the downregulation of signalling pathways occurred as a consequence of apoptosis. Treatment at 7.5 μg/ml did not induce apoptotic changes in the treated cells, but resulted in differential effects on the signalling pathways. The fold changes in the transcription factor activity in cells treated at 7.5 μg/ml is displayed in Figure
Figure 5
Effect of the xanthones extract and α-mangostin (7.5 μg/ml) on the transcription factor activity of 10 cell signalling pathways
Effect of the xanthones extract and α-mangostin (7.5 μg/ml) on the transcription factor activity of 10 cell signalling pathways. The fold changes in the transcription factor activity were calculated by dividing the relative light units in the treated cells by that of the untreated cells. The fold change of (1) indicates no activity.
Figure 6
The subcutaneous tumors in NCR nude mice (a): Untreated group (1), and the treated group at 0.5% wt/wt of the xanthones extract (2)
The subcutaneous tumors in NCR nude mice (a): Untreated group (1), and the treated group at 0.5% wt/wt of the xanthones extract (2). Analysis of tumor size (b): analysis of tumor size versus time (days) after treatment with the xanthones extract at 2 doses 0.5% and 0.25% wt/wt compared to the control group (untreated). (*) refers to significant difference between both treated groups (P < 0.05) and the control, and (#) refers to significant difference between the 0.5% group and the control in each corresponding interval. Cross sections of tumor tissues (c): untreated animals (1), 0.5% treated group (2) and the 0.25% treated group (3). The tissues were stained with Hematoxylin-eosin and the pictures were captured at 5× magnification. (N) refers to necrotic cells and (V) refers to viable tumor cells.
The average number of intratumor blood vessels was 3.9 ± 0.6/microscopic field (0.5% wt/wt) and 4 ± 0.3/microscopic field (0.25% wt/wt), was significantly lower than that in the control group (7.8 ± 1.2), P = 0.0.
Additionally, effect on the animal body weight was also investigated and the results are presented as average percentage of weight gain or loss. The data showed a slight, but not statistically significant weight loss in the treated groups −4.4 ± 10% (0.5% wt/wt) and −1.5 ± 2.4% (0.25% wt/wt), compared to 5.3 ± 6% (control group), P = 0.1 and 0.4, respectively.
The xanthones extract of
Apoptosis studies revealed enhancement of the executioner caspases-3/7, activation of the initiator caspase-9, induction of DNA fragmentation and chromatin condensation, and loss of mitochondrial membrane potential. These results indicate the role of the mitochondrial pathway of apoptosis in mediating cytotoxicity of the compounds. Our results are consistent with the previous results of other researchers
Sub-cytotoxic concentrations of α-mangostin and the xanthones extract inhibited 3 key steps in tumor metastasis including the cell migration, cell invasion and clonogenicity. These results, in combination the results of other researchers
In order to gain deeper insights into the mechanism of action, a cell-based reporter assay was used to study the effect of α-mangostin and the xanthones extract on the transcription factor activity of the Notch, Wnt/β-Catenin, TGFβ, p53, HIF, Myc, E2F, NFKB, MAPK/ERK (SRE), and MAPK/JNK (AP-1) signalling pathways. The compounds enhanced the transcription factor activity of the MAPK/ERK, Myc/Max, and p53/DNA damage signalling pathways. Previous research showed that the activated ERK pathway is associated with increased stability and activity of p53, and increased stability of c-Myc that in turn increases the proapoptotic effects of p53 tumor suppressor gene
Different mechanisms of action of mangostins have been reported including upregulation of the ERK ½ in DLD-1 colon cancer cells
Taken together, our data suggest new mechanisms of action of α-mangostin and suggest the xanthones extract of
Competing interests
The authors declare no conflict of interest related to this work.
Authors' contributions
AFA carried out the experiments, performed the statistical analysis, and drafted the manuscript. KM interpreted the results of cell signalling pathways and helped in editing the manuscript. ZI interpreted the LC-MS data. AMS participated in the design of the study and edited the manuscript. All authors read and approved the final manuscript.
Abdalrahim F. A. Aisha would like to acknowledge Universiti Sains Malaysia (USM) for providing fellowship for the academic year 2010/2011. The Authors would like to thank Dr. Tan Mei Lan and Mr. Ahmad Ismail (IPHARM, USM) for providing and helping in fluorescent microscopy, Associate Prof. Dr. Gurjeet Kaur (INFORMM, USM) for helping in analysis of tumor cross sections. This work was financially supported by the USM-Research University Grant [1001/PFARMASI/81144], and was supported partially by the research chair funded by King Saud University on drug targeting and treatment of cancer using nanoparticles.
Quantitative and qualitative determination of six xanthones in Garcinia mangostana L. by LC-PDA and LC-ESI-MS
Medicinal properties of mangosteen (Garcinia mangostana)
Garcinia mangostana L.: a phytochemical and pharmacological review
New medicinal properties of mangostins: analgesic activity and pharmacological characterization of active ingredients from the fruit hull of Garcinia mangostana L
Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen)
Anti-inflammatory activity of mangostins from Garcinia mangostana
Anti-cancer effects of xanthones from pericarps of mangosteen
Panaxanthone isolated from pericarp of Garcinia mangostana L. suppresses tumor growth and metastasis of a mouse model of mammary cancer
Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines
[alpha]- and [gamma]-Mangostin Inhibit the Proliferation of Colon Cancer Cells via [beta]-Catenin Gene Regulation in Wnt/cGMP Signalling
Inhibitions of histamine release and prostaglandin E2 synthesis by mangosteen, a Thai medicinal plant
Antibacterial activity of alpha-mangostin against vancomycin resistant Enterococci (VRE) and synergism with antibiotics
Antimycobacterial activity of prenylated xanthones from the fruits of Garcinia mangostana
Antifungal activity of alpha-mangostin against Candida albicans
Active constituents against HIV-1 protease from Garcinia mangostana
Cardioprotective effect of alpha-mangostin, a xanthone derivative from mangosteen on tissue defense system against isoproterenol-induced myocardial infarction in rats
Antioxidative and neuroprotective activities of extracts from the fruit hull of mangosteen (Garcinia mangostana Linn.)
Effect of a mangosteen dietary supplement on human immune function: a randomized, double-blind, placebo-controlled trial
α-Mangostin, a xanthone from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growth
Improved short- and long-term XTT-based colorimetric cellular cytotoxicity assay for melanoma and other tumor cells
Cytotoxic and anti-angiogenic properties of the stem bark extract of Sandoricum koetjape
Xanthorrhizol exhibits antiproliferative activity on MCF-7 breast cancer cells via apoptosis induction
Localization of mitochondria in living cells with rhodamine 123
Clonogenic assay of cells in vitro
In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro
Tumor cell invasion assays
Determination of subcutaneous tumor size in athymic (nude) mice
The therapeutic response of three human tumor lines maintained in immune-suppressed mice
Activity of mitozolomide (NSC 353451), a new imidazotetrazine, against xenografts from human melanomas, sarcomas, and lung and colon carcinomas
Characterization of HCT116 human colon cancer cells in an orthotopic model
Preferential target is mitochondria in alpha-mangostin-induced apoptosis in human leukemia HL60 cells
Alpha-mangostin suppresses PC-3 human prostate carcinoma cell metastasis by inhibiting matrix metalloproteinase-2/9 and urokinase-plasminogen expression through the JNK signaling pathway
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ERK activation mediates cell cycle arrest and apoptosis after DNA damage independently of p53
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Benzyl isothiocyanate-mediated generation of reactive oxygen species causes cell cycle arrest and induces apoptosis via activation of MAPK in human pancreatic cancer cells
NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps
alpha-Mangostin Induces Apoptosis in Human Chondrosarcoma Cells through Downregulation of ERK/JNK and Akt Signaling Pathway
Pre-publication history
The pre-publication history for this paper can be accessed here:


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At the Triangle Residential Option for Substance Abusers (TROSA), a North Carolina residential treatment program, Executive Director Kevin McDonald and his colleagues have advanced a social entrepreneurial model for nearly a decade. In the process, they've built hundreds of active, engaged citizens, not just sober individuals.
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- Copyright 2005 Research Center for Leadership in Action. All rights reserved.
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Publication date 2005-01-06
Publication Year 2005
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Keywords kevin , floor new , addicts , center for leadership , world research
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A Shift in Veterinary Trends
- Nov 1, 2011
- Basic
- Topics:
Photo: Erica Larson, News Editor
The landscape of veterinary medicine is changing as it adapts to economic and societal shifts. You might be accustomed to the following: Your veterinarian travels to where your horse lives for checkups and treatments, unless the horse needs more intensive procedures or therapy, in which case you might load him up and take him to a referral clinic. However, that traditional scenario has given way to appointments at large clinics with boarded specialists, more veterinarians considering the public sector, and practitioners struggling to keep up with all the veterinary information now available to horse owners online. Here, sources from the industry reflect on these trends and the ways in which equine veterinarians have been impacted and are responding.
The Overall Numbers
In 2006 the American Veterinary Medical Association (AVMA) began compiling current U.S. veterinary statistics for review. That year there were 81,468 licensed veterinarians in the United States, a figure that rose to 90,201 by 2010. Of those numbers, 56,092 (69.8%) and 61,502 (68.2%), respectively, were in private practice. The number in the "mixed animal" category, which is a combination of large and small animal practice, has dropped slightly from 4,376 (7.8% of the total) to 4,326 (7.0% of the total). The greatest increase in licensed veterinarians appears to be in the companion animal exclusive segment, which covers the cats, dogs, other small mammals, and exotics. This category has grown by more than 1% in the last four years. Public and corporate employment includes veterinarians that work for the federal, state, or local governments, colleges or universities, and other corporate industries. These numbers also increased from 13,789 in 2006 to 15,301 in 2010.
While there isn't an overall shortage of veterinarians, there is one of large animal practitioners in rural areas. These vets are typically mobile and specialize in livestock, which includes food animals: beef, sheep, swine, and dairy, but a livestock veterinarian's practice population often includes horses, as well. The number of food animal veterinarians has declined by more than 1% in the last four years, and those numbers are expected to continue shrinking. According to W. Ron DeHaven, DVM, MBA, AVMA executive vice president, one of the big reasons for this is that the nation's changing demographics show more people living in urban areas and fewer in rural areas. There are also the drawbacks of long hours on the road compounded by seemingly ever-increasing gas prices. As a result, fewer students consider working for a mobile large animal practice, he notes.
And while the number of equine veterinarians has risen from 3,404 to 3,743 over four years, the percent of the total ¬number in the veterinary industry--6.1%--remains constant. Nathaniel A. White II, DVM, MS, Dipl. ACVS, Jean Ellen Shehan professor and director at Virginia Tech's Marion DuPont Scott Equine Medical Center, in Leesburg, believes this is most likely due to the current economy and the lower salary for veterinary school graduates entering as equine practitioners. "Though I am not aware of surveys that indicate the number of equine practitioners switching to alternatives such as small animal practice, individuals have reported expanding into other types of work, necessary due to less spending by owners for equine medical problems," he explains.
Gender Shift
In 2006, 52.9% of all veterinarians in the United States were male and 47.1% were female. By 2010 the balance had shifted almost equally in the other direction: 52.1% were female and 47.9% were male. Another noteworthy statistic is that the number of female equine veterinarians rose 3.7% from 2006 to 2010 while the number of male equine veterinarians declined, possibly due to the number of male veterinarians reaching retirement age and an influx of female additions to the industry. White says current veterinary school classes consist of 70-80% women. "Time will tell if the trend for more women than men to become veterinarians continues," he says. "Either way, the profession is fortunate to be attracting some of the best minds."
Specialization in the Field
In response to a public that demands a higher level of care and increasingly advanced treatments, more veterinarians are delaying starting or joining a practice to continue their schooling to become board-certified specialists. Again, the AVMA has compiled statistics covering a wide variety of areas. The total number of active board-certified diplomates as of December 2006 was 8,510, and as of December 2010 it was up to 10,210. The number of American Board of Veterinary Practitioners- (ABVP) certified vets, for instance, has risen from 800 to 868, with the number of those in equine rising only slightly from 87 to 89.
The greatest increases among specialties seem to be in internal medicine. The number of veterinarians specializing in large animal internal medicine with the American College of Veterinary Internal Medicine (ACVIM) has increased from 410 in 2006 to 480 in 2010 (17%). Similarly, the sum of large animal specialists from the American College of Veterinary Surgeons (ACVS) has risen from 67 to 171 (155%) in only four years.
The Financial Situation
The AVMA also tracks median professional income before taxes. While the average annual income for a veterinarian in private practice has risen from $79,000/year in 2006 to $97,000/year in 2010, the average salary among equine veterinarians has actually declined significantly from $91,000 to $85,000. Reasons for that are not obvious, but again it could be a factor of the current economic shift in the horse industry.
"The horse economy is responding to the economy with reports suggesting less horses being bred, less foals being born, and a lack of new horse owners," says White. "This shift ... makes hiring new (equine veterinary) graduates a difficult decision. Income for new graduate veterinarians just starting in the profession is significantly less than can be found in food animal or small animal practice."
Working in the public sector continues to be lucrative. The average salary in 2006 for a public employee was $97,000 and in 2010 was $109,000. That might sound good, but the amount of debt a new veterinarian has acquired coming out of veterinary school can be staggering. DeHaven quoted that the average veterinary school graduate's student debt in 2008 was higher than $120,000. This was up from the previous year's estimate of $106,000. Add to that the ever-increasing cost of fuel, drugs, and supplies, and a veterinarian doesn't have much left over to live on.
The Horse Owner
Veterinarians are also faced with owners who can find more information on the Internet, which can be both good and bad when it comes to distinguishing fact from opinion. White believes easy access to this information can benefit the practitioner as well as the client, but it also means that veterinarians need to keep up with current information on veterinary medical treatments. To help keep costs down, some owners might be reading more online and attempting to treat their horses themselves. On the other hand, according to White, there is at times pressure from owners for veterinarians to provide maintenance treatments such as joint injections even if no there is no problem or diagnosis.
"This is challenging because this provides a source of income but may be in conflict with what is actually needed or what is best for the horse," he says. "The veterinarian needs to remain the guardian of the horse's welfare in the face of owner demand."
Equine Mobile Practice
Equine mobile practice has changed drastically over the years as well. Before cars, veterinarians served clients by horse and buggy or even on foot. Eventually the station wagon, with its ample storage room, became the main mode of transportation. But the pickup truck soon became the new standard, and it continues to be to a certain extent. Three companies, Bowie, Part-Vet, and LaBoit, have provided the majority of mobile fiberglass units that fit into truck beds. These provide greater storage capacity and easy access to and protection of inventory and tools. However, about 10 years ago the movement started toward smaller SUVs in response to steeply climbing gas prices and practitioners (particularly the growing female population) desiring a smaller vehicle. The gas mileage on a large, fully loaded truck can be 12-14 mpg or less, whereas that of a midsize SUV is around 20 mpg. This adds up to significant savings for a mobile vet traveling 100 miles or more per day.
The next step in mobility is likely smaller flexfuel or alternative fuel vehicles. Although the trend is toward a smaller vehicle, high-tech mobile vets need room to carry items such as digital X ray machines, thermography cameras, and ultrasound machines. With a storage insert weighing upwards of 200 pounds plus the weight of equipment and supplies, the vehicle must also be built to handle the weight.
The Next Generation
According to DeHaven's testimony, the United States' 28 accredited veterinary colleges graduate about 2,600 veterinarians annually. This number has stayed relatively constant over the last 20 years. "This lack of growth in veterinary graduates is not due to a lack of applicants," he stated. "According to the Association of American Veterinary Medical Colleges, these 28 veterinary schools in the United States are at full capacity, with qualified applicants outnumbering available seats three to one."
One limiting factor for expansion is these schools need unique spaces that can be used for research, teaching, and diagnostics. They need areas to safely house animals, and with budgets being slashed the prospects of constructing new buildings are slim.
"Equine practitioners can offer more and better medical science and benefits to horses and their owners than ever before," says White. "The advances in imaging and regenerative medicine have opened up new possibilities that were only imagined 10 or 15 years ago. Surgical procedures offer life- and performance-saving solutions for problems which once only frustrated veterinarians. Continuing these advances requires horse owners and the industry to support equine research, which ultimately allows the veterinarian to deliver the best medical care."
About the Author
Stephanie J. Corum, MS
Stephanie J. Corum received a MS in animal science from the University of Kentucky in Lexington. She has worked in various aspects of the horse industry, including Thoroughbred and Arabian racing, for nearly 20 years. More information about her work can be found at www.theridingwriter.com. She has also published the illustrated children's story Goats With Coats. Currently she and her husband own Charisma Ridge, a small horse farm in Maryland, and she competes in dressage.
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pellprop avait besoin d'un nouveau design de logo et a lancé un concours sur 99designs.
Un gagnant a été sélectionné de 295 designs proposés par 80 designers freelance.
Sunset Gardens Apartments logo
Sunset Gardens Apartments is a southern californian apartment building. With palm trees, lagoons and fountains. Sunset Gardens Apartments are the idea beach community and the logo needs to reflect that.
Potential tenants in california between the ages of 25-65.
Please Look at the attachments for examples. please incorporate one of the folowing in the logo: Must Have a Palm Tree and Sunset. Logo needs to embrace the warm of the sun while maintaining a corporate image. The Palm Tree is the main focus of the logo.
The logo will be used for Print, Web, Embroidery and Street Signs. Logo must be able to work for all mediums.


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Keith Urban ready to take fans on carnival ride
By Vernell Hackett
NASHVILLE, Tennessee (Reuters) - Keith Urban hits the road this summer on his "Get Closer" tour with a carnival stage set befitting a country music star, but he still has memories of paying for his own props at a hardware store.
"I was putting on a show at a club in Nashville and I had no money, so I went to a hardware store and bought a couple sections of this fake white picket fence and wire to hang them from the ceiling at these odd angles," Urban said.
The 43-year-old performer, who was born in New Zealand and came to the United States from Australia in 1992, has come a long way since his three-member band "The Ranch" released their lone U.S. album in 1997. He has developed a huge following thanks to hits such as "Memories of Us," "You Look Good in My Shirt" and "Start A Band" with Brad Paisley.
Urban's 2010 Grammy-winning hit song "'Til Summer Comes Around" inspired the carnival theme of the upcoming 70-stop tour, which features a Ferris wheel equipped with a video screen and a roller coaster used to hang stage lights.
To try to make audiences feel they are in an intimate club and not a giant arena, Urban installs satellite stages and ambles through the audience to sing and give away a guitar.
"I just love getting out among everybody, even though sometimes it's chaotic. A few times I have thought, 'What am I doing out here?' There's something about the adrenaline and the electricity and being on edge and the unpredictability of it that I really love," he said.
"Part of the problem (is) when you get to this level of a show everything is so thought out, there's not much spontaneity left. Everything is predictable and you can feel it. I'm just trying to keep some moments in the show when who knows what will happen?" he said.
As Urban's current single, "Without You," climbed to the top of the country music charts, he took a break from rehearsals in Nashville to speak with Reuters. Continued...


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Edinburgh Yarn Festival 2013
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ColorDesigner PLUS v2.0 - Patch 4
Download: ColorDesigner PLUS v2.0 - Patch 4
Version: NA
Previous Version: v2.0 - Patch 3
Release Date: 10/8/2013
File Type: PC - ZIP File
Download: PC Version
Notes: Click Here to access the instructions for installing this patch.Significant bug fixes in this version:
- With some Color Matching Databases, when a formula was saved to Customer Files, the wrong base would be displayed. This affected Color Matching Databases in which the product was not the last selection in the menu flow. The issue occurred in Color Match and Manual Entry. Note that the correct base was saved in Customer Files.
Patch #4 also includes all prior software updates.p>


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Daniel Levine: The augmented reality trend is pushing in to our lives
The trends expert is seeing a rise in the helping life improvement apps
"The technology is now out there to make this possible," says trends expert Levine. "A smart device user can literally have a whole new interaction with the world with the touch of a button."
Several apps have been developed that give the shopper an idea of what furniture will look like at home before it is purchased. IKEA is one of the biggest users of the technology, which allows shoppers to combine pictures of furniture and their homes to see if the right purchase is being made.
Other developers are using this technology to put real meaning on abstract concepts. For example, an app gives drivers extra safety information, including distance measurement between vehicles and how much time stopping time is available before a collision occurs. Another app gives physical control to virtual objects, allowing users to open menus with the wave of a hand. Even newspapers are adopting the technology- In Japan, print is coming to life to make the news more accessible for children.
Apps have also been developed that allow women to try out makeup styles virtually before attempting them in reality. The same technology is available for children, allowing them to play with makeup without the mess.
"So far, many of these trends are being used to test ideas and interact with environments,"
About Daniel Levine
Daniel is a trends expert who shares his observations and experiences with audiences and corporations as a keynote speaker and consultant. Learn more at http://DanielLevine.com
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Miner Family The Oracle 2009
Bordeaux Red Blends from Napa Valley, California
Winemaker's Notes
The Oracle is an exceptionally balanced, full-bodied red blend made from grapes grown at Stagecoach Vineyard in the eastern hills of Napa Valley. In Greek mythology, the oracle was a source of inspiration and revelation. We hope that you will find the answers to life's most compelling questions while enjoying The Oracle with friends and family.
Blend: 50% Cabernet Sauvignon, 25% Cabernet Franc, 15% Merlot, 5% Malbec and 5% Petit Verdot
Critical Acclaim
Connoisseurs' Guide - "There is a good deal of character to this ample, fairly full-bodied effort not the least of which is a full measure of curranty fruit, a bit of briary spice and plenty of creamy, vanilla-bean oak. There is more than a bit of youthful tannin at work too, yet even though a touch rough and ragged at the finish, the wine ends on a positive note as its basic fruit emerges unscathed. It is not long on manners just now, but will find some much needed smoothing with age, and it is best left alone for six to eight years."
Miner Family Winery
Founded in 1988 by Dave Miner, president of Oakville Ranch Vineyards, along with his wife Emily and his parents, Ed and Norma, Miner Family Vineyards produces small lot, handcrafted wines using fruit from Oakville Ranch, Ed and Norma's vineyard and other carefully selected California vineyards. Best known for their Cabernet Sauvignon and Chardonnay, they also produce limited quantities of other varietals using a combination of old world winemaking techniques and modern technology. Their focus is on producing high end, reserve-style wines that reflect the unique characteristics of individual vineyards or terrior where those specific varietals grow best. View all Miner Family Wines
About Napa ValleyView a map of Napa Valley wineries
It's hard not to think of Napa Valley when thinking of California wines. The region is, after all, the one that brought world recognition to California wine making. The area was settled by a few choice wine families in the 1960's who bet that the wines of the area would grow and flourish. They were right. The Napa wine industry really took off in the 1980's, when vineyard lands were scooped up and vines were planted throughout the county. A number of wineries emerged, from large conglomerates to small boutiques to cult classics. Cabernet Sauvignon is definitely the grape of choice here, with many winemakers also focusing on Bordeaux Blends. Whites are usually Chardonnay and Sauvignon Blanc.
Notable FactsWithin the Napa Valley lie smaller sub-AVAs that lend even more character specifics to the wines. Furthest south is Carneros, followed by Yountville, Oakville & Rutherford. Above those two is St.-Helena and finally, just granted an AVA, Calistoga. These areas are situated on the valley floor and are known for creating rich, smooth Cabernet Sauvignon, Merlot and Chardonnay. There are a few mountain regions as well, nestled on the slopes overlooking the valley AVAs. Those include Howell Mountain, Stags Leap and Mount Veeder. Wines from the mountain regions are often more structured and firm, benefiting from more time in the bottle to evolve and soften.
About CaliforniaIt's not rare to see a wine's country of origin listed as "California." A country into itself in the wine world, California makes enough varieties and styles to match many European wine countries. It produces a diverse range of wines that span the quality spectrum.
The most famous of the California wine regions is Napa Valley, and these wines are certainly outstanding – but it's not as broad and diverse as its larger neighbor, Sonoma County. Down south, Santa Barbara's Santa Maria Valley is well-known for its Rhône blends, as well as cool-climate varieties like Pinot and Chardonnay. The Central Coast, the largest California AVA, has many different microclimates that lead to a wide range of wines with many sub-AVAs.
Customer ReviewsSign In to Add Your Review4.54.5 out of 5 stars


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This is the complete list of ads for used Akpil used Farming Equipment for sale on Mascus in New Zealand and other countries. If you have registered, you can add your selections to favourites or compare items of interest by clicking on the checkboxes next to used Akpil used Farming Equipment of interest and then select one of the options above. If you want to change your query, please go back to the top of the page and use the "new search" option.
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Reset My Password
This will send a password reset to your email address on file. A reminder that your email address on your account must be valid and working to receive the reset request.
We would love to hear your feedback and any suggestions you may have for our new VWVortex store.
Let us know if there is a color option you would like added or a particular merchandise item you would like to see in the store. Have you had a chance to buy an item from our store? Then we want to hear what you think about the merchandise you bought.
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Anyone is selling driver side fender or can tell me where to buy? Metallic Blue !!
wrong forum.
Originally Posted by therockdrummer
wrong forum.
Yea buddy, you have MKIV not MKVI. See the difference?
Btw, your best bet for color matched OEM parts is car-part.com
Oops! thanks for pointing out.
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Check Out the new Remax App
Ask About This Home
This 2.08 acre lot lies between Waxler Rd and Overlook Terrace. With tremendous views make this an ideal location for an environmental "green" home or earth shelter construction. Also suitable for more traditional build. Water line runs along Overlook and lot was perked. Enjoy a truly relaxed lifestyle from this rural, mountain setting.


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Add some more excitement to your Holiday with excursions, your chance to get out and explore all that the Riviera Maya has to offer.
Excursions are no longer available to reserve in advance however can still be purchased on site at the event, based upon availability!
Magical Temples of Coba and Breathtaking Cenote
Date: February 5th
Time: 9:30am - 3:30pm
Price: $158
Visit the ancient Mayan City of Coba, home of the tallest pyramid on the Yucatan Peninsula. Climb the pyramid if you dare, then head to the nearby cenote and enjoy a calming swim or beautiful snorkeling experience.
Snorkeling Xtreme Adventure
Date: February 5th
Time: 10:00am - 3:30pm
Price: $126
Fly above the jungle canopy on a thrilling zip line ride and test your tenacity as you rappel into the Mayan jungle! Then snorkel in a stunning river in the middle of the jungle and be surprised by Mexico's biodiversity as you are surrounded by exotic marine life. You will be accompanied at all times by professional guides who will share the best snorkeling techniques and information on the flora and fauna that inhabit these unique ecosystems.
Jungle Maya
Date: February 5th
Time: 10:00am- 3:00pm
Price: $126
Swim & snorkel through awesome rock formations and crystal clear water. The adventure continues zip lining, rappelling and riding a 4x4 Mercedes Benz truck through the jungle.
Xel-Ha Tour
Date: February 6th
Time: 10:00am - 3:30pm
Price: $129
Find yourself in water paradise at Xel-Ha (which means "Water Spring") and explore the extraordinary network of natural pools and waterways. Journey through the walking paths of a tropical forest and jump into an incredible "natural aquarium" where you can refresh and snorkel in calm waters while bearing witness to the natural beauty around you.
Positive Legacy Day of Service and Cultural Connection
Date: February 6th
Time: 10:00 am - 3:30pm
Price: $50 USD
Join Positive Legacy for a day of community connection, cultural emersion and celebration as we venture to the nearby traditional Mayan community of Dos Plamas! Community members from Campamento Hidalgo will make a 2-hour journey to join us and share their cultural heritage with us. We will be treated to a traditional Mayan meal and music performance by the children. Guests can participate in arts and crafts, tortilla making, mural painting and a traditional Temazcal ceremony. We will have the opportunity to take a swim in a cenote to cool off at the end of afternoon. On sale now!
Playa Del Carmen Shuttle
Date: February 6th
Time: 11am - 4pm (departs every 45 minutes)
Price: $25
Take advantage of all the dining, shopping, and culture that awaits just up the road in Playa Del Carmen! This convenient shuttle picks up and drops off right at the resort and at the heart of downtown Playa. Get out and see Mexico!
Deep Sea Fishing
Date: February 7th
Time: 8:30am - 1:30pm
Price: $138
Head out onto the Caribbean for a sportsman's afternoon! These waters are teeming with wahoo, mahi, and other prize fish. Let the captain be your guide!
Ek Balem Cenote Maya
Date: February 7th
Time: 9:00am - 4:15pm
Price: $150
This is a very special tour we're offering for the first time this year that's considered the best of Mayan world sightseeing & worth the extra transportation time. Enjoy the beautiful Mayan temples at the archaeological site of Ek Balam combined with a visit to the huge underground Cenote Maya.


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| Hakim Hayat |
VISUALLY impaired Bruneian, Norali Ali Yusop defied the odds when he successfully completed the Standard Chartered Dubai Marathon recently by crossing the finish line in 63 minutes in the 10km category.
Sharing his experience with the Borneo Bulletin, the 2012/2013 Chevening Scholar who is also an Education Officer at the Special Education Unit, Ministry of Education (MoE) said he felt privileged to be invited by Standard Chartered Dubai to take part in the prestigious event, and fortunate to be able to rub shoulders with the world's best marathon athletes while running alongside thousands of tough amateur runners like himself.
Norali alongside his running guide, Marcus Bailey, crossed the finish line eight minutes behind their initial target of 55 minutes, but running with 25,000 other runners in the marathon that took to the streets of Dubai was already a good challenge.
"You can probably imagine trying to run in a clear path at our regular pace was quite a challenge for the both of us. In spite of that, it still felt like a worthwhile experience knowing that we were raising awareness and contributing to the cause of 'Seeing is Believing'," Norali said.
The Standard Chartered Dubai Marathon was Norali's first, for he has participated in numerous 21km and 10km challenges at the national, regional and international arena.
"Besides the unique vibrant and energetic feel each event has to offer, I think one obvious difference between them is the weather factor. In London, I was running at temperatures below zero; the opposite of Brunei and Singapore, where the weather is always hot and humid. Dubai at this time of the year however, is just nice with temperatures ranging from 10 to 15 Celsius, which to me felt like the ideal running condition," he added.
In Dubai, Norali was also invited to share his life story with students at schools, special needs community centres and corporate organisations.
Together with Norali were Henry Wanyoike and Joseph Kibunja, gold medallist and currently the fastest blind marathon runner in the world.
He is also Standard Chartered's goodwill global ambassador for 'Seeing is Believing'.
Norali shared that during each visit, they had a chance to share their inspirational story, reveal the challenges they faced as people with disabilities and most importantly shared the life lessons they had learnt from overcoming their own difficulties.
"According to the feedback received by the organiser, the audience was very much inspired and touched by our resilience to go beyond our blindness to achieve success despite the hardship we had to endure. And this gave some of the parents hope for their children, particularly those with severe special needs," he said.
Norali who lost his sight following a severe case of meningitis when he was 17 years old said ever since, he persevered to not only carry on as normal, but also to achieve great things by continuously setting personal challenges for himself.
"People with disabilities like me are often seen as inactive, withdrawn or angry. But people forget that just because I am officially disabled doesn't necessarily mean that I cannot be truly enabled. When I show them the sort of things I am able to do, they immediately think it's extraordinary.
"They think that I am living life as if I have no limits and this shatters their preset perception about what people with disabilities can actually do. This forces them to abandon their negative assumptions and low expectations towards people with disabilities, and rebuild it from the ground up to a more positive view on our abilities. And this is why I do what I do – to change attitudes so we can be accepted as part of human diversity, not as human deficits," he said
When he lost his eyesight, Norali said he thought his life was over.
"But now, instead of wallowing in the dark, I have decided to believe that better days would come and all that had happened was for a divine purpose – a blessing in disguise. I believe that there was a reason why it had happened to me and now I know that I'm fulfilling that purpose," he said.
Norali further added that to him, it was not what happens to us that makes or breaks us.
"It is what we do after that. So whatever happens to us, whether it's an unexpected health issue, bad business deals or failed relationships, always remember to never put your life on hold just so you can dwell on the unfairness of past hurts.
"Move forward despite the adversities of life and always be guided by your own aspirations and vision. I may have lost my eyesight but I never lost my vision to succeed in life."


text: It was all a hoax.That's what the young man who claims to be behind the Bucksport Bay White Youth Pride Party says.A man claiming to be 21-year-old Matthew Laue of Bucksport says he made up the hate group to get people talking and elicit a reaction.Laue posted fliers around the town that included swastikas and those fliers encouraged people ages 15 to 35 to join the white supremacist group. He also made up the name "Propietor Mutt."Laue says he wanted to show people how far someone will go to get attention.He also claims he wanted to show people that controversial topics should be discussed."Anybody who questions the way things work as a norm and questions anything and really no one seems to have the gall to try to challenge it and speak up and I'm trying to encourage everyone to be active because I know everybody has a thing and I definitely want to empower people I guess to be able to voice those opinions and to do something about how they feel about whatever their opinion is," the man told TV5 in a phone interview.Laue says he got the reaction he was looking for. He claims he received e-mails from people looking to join the group, as well as e-mails from people against the group.Laue says he does not support the beliefs of the hate group. He claims he chose to promote that type of organization in his hoax because he knew it would get a passionate response.


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Destination green tea has the Orangerie 80g
Green tea with fruity taste.Manufacturer: Destination Bio
SKU 1205838 destination tea Green A the Orangerie 80 g
Tea, fruits, plants, spices have their perfumes, nothing between them to the contrary. Each association reveals the fantasies of life and found in our most beautiful delicate palate memories or desires. The Orangery is a bouquet of green tea, flowers of concern and blueberries associated notes round and fleshy fruits of spring.
operating tips:
Infuse 3 minutes at 80 .
Green tea * (89.5%), cornflower petals * (3%), natural aroma Strawberry * (2.5%), apricot natural flavour * (2.5%), natural flavour orange * (1.5%), flower petals *-* from organic farming - system of control this.Feedback on this page ?