To see the other types of publications on this topic, follow the link: Glucosamine - Therapeutic use.
Journal articles on the topic 'Glucosamine - Therapeutic use'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 21 journal articles for your research on the topic 'Glucosamine - Therapeutic use.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Machado, Eduardo, Patricia Machado, and Paulo Afonso Cunali. "Use of chondroitin sulphate and glucosamine sulphate in degenerative changes in TMJ: a systematic review." Dental Press Journal of Orthodontics 17, no. 4 (August 2012): e1-e5. http://dx.doi.org/10.1590/s2176-94512012000400006.
Full textAbstract:
INTRODUCTION: Degenerative changes in Temporomandibular Joint (TMJ) have increased in prevalence and severity over the years. Within this context, it's necessary to obtain safe and effective therapies for control and management of the patient in cases of osteoarthritis and osteoarthrosis of the TMJ. Therapeutic options range from intra-articular infiltration protocols, occlusal splints, pharmacological therapies and physiotherapy and educational measures. The alternative treatment with structure-modifying agents, like as chondroitin and glucosamine sulphates, showed promising results, and especially safety. Thus, through a systematic literature review, this study aimed to analyze and discuss effectiveness and safety of chondroitin and glucosamine in degenerative changes of the TMJ. METHODS: Survey in research bases MEDLINE, Cochrane, EMBASE, Pubmed, Lilacs and BBO, between the years of 1966 and January 2009, with focus in randomized clinical trial (RCTs) and quasi-randomized clinical trials, systematic reviews and meta-analysis. RESULTS: After application of the inclusion criteria 2 articles were selected, both randomized controlled double-blind clinical trials, which evaluated the effectiveness of chondroitin and glucosamine in degenerative changes of the TMJ. CONCLUSIONS: There is the necessity of further RCT, with representative samples and long follow-up time, to obtainment more precise cause-effect relationships and to achieve an effective and objective protocol involving chondroitin and glucosamine in cases of degenerative changes of the TMJ.
2
Hsu, Chia-Hao, Nin-Chieh Hsu, Chia-Lung Shih, Hsuan-Ti Huang, Chung-Hwan Chen, and Pei-Hsi Chou. "Medication-Taking Habit and Outcome of Glucosamine Sulfate for Osteoarthritis Patients Influenced by National Health Insurance Regulations in Taiwan." Journal of Clinical Medicine 8, no. 10 (October 19, 2019): 1734. http://dx.doi.org/10.3390/jcm8101734.
Full textAbstract:
This study compared the dosage and different medication-taking habits of glucosamine sulfate (GS) for osteoarthritis patients and evaluated the influence of the National Health Insurance (NHI) prescription guidelines. The subjects were collected from the Taiwan NHI Research Database from 1 January 2004, to 31 December 2008, and 10,501 osteoarthritis patients were included. Then, 271 patients who continuously used nonsteroidal anti-inflammatory drug (NSAIDs) and started to receive glucosamine for the first time since 2005 (no glucosamine use in 2004) were compared with 593 age-matched patients who continuously used NSAIDs but never received any glucosamine drugs from 2004 to 2008. The mean treatment duration of the glucosamine-treated and NSAID-treated groups was 40.38 ± 7.89 and 45.82 ± 3.89 months, respectively. The most common medication-taking habit was 250 mg 3 times a day for 3 months and discontinued for 3 months. It was as indicated and covered by the NHI. Only 0.7% of patients used the recommended daily dosage of 1500 mg. Patients using GS surprisingly had a higher incidence rate of joint replacement surgery than those who did not use GS. The NHI prescription guidelines may cause patient selection bias, which decreases the efficacy of GS. Moreover, patients tend to have an altered medication-taking habit, with a daily dosage of 750 mg, which is lower than the recommended therapeutic dose.
3
da Camara, Carlos C., and Gregory V. Dowless. "Glucosamine Sulfate for Osteoarthritis." Annals of Pharmacotherapy 32, no. 5 (May 1998): 580–87. http://dx.doi.org/10.1345/aph.17214.
Full textAbstract:
OBJECTIVE: To characterize the usefulness of glucosamine sulfate in the treatment of patients with osteoarthritis (OA). DATA SOURCES AND STUDY SELECTION: Pertinent citations were identified via a MEDLINE search (January 1975–March 1997). Only trials available in the English language involving human subjects, OA, and glucosamine sulfate were selected for review. DATA SYNTHESIS: OA is the most common form of arthritis and represents a major cause of morbidity and disability in the elderly. The main symptom of OA is pain and most of the commonly prescribed medications (e.g, acetaminophen, nonsteroidal antiinflammatory drugs) have been targeted at relieving the pain. Some of these medications have serious adverse effects and do not necessarily change the natural course of the disease. Glucosamine sulfate, a nutritional supplement, has recently emerged as an alternative treatment option for patients with OA. The beneficial effects of this chondroprotective agent have been reported to reverse or at least stop the progression of the disease without inducing serious adverse effects. Limited data from short-term human trials suggest that glucosamine sulfate administered orally, intravenously, intramuscularly, and intraarticularly may produce a gradual and progressive reduction in joint pain and tenderness, as well as improved range of motion and walking speed. Results of the trials have also shown that glucosamine has produced consistent benefits (>50% overall improvement in symptom scores) in patients with OA and that, in some cases, it may be equal or superior to ibuprofen in controlling symptoms. CONCLUSIONS: There is evidence that glucosamine sulfate may provide pain relief, reduce tenderness, and improve mobility in patients with OA. Most of the current data, however, are derived from the European and Asian literature and there are no studies supporting the use of this agent in the US. The studies published to date have been done in small numbers of patients; adequate long-term trials examining the safety, efficacy, and optimal dosage requirements of glucosamine sulfate are lacking. Most of the available clinical data are difficult to interpret due to serious deficiencies in study design. Furthermore, studies evaluating the appropriate place of glucosamine sulfate in the therapeutic armamentarium of OA remain to be done.
4
Salazar, Juan, Luis Bello, Mervin Chávez, Roberto Añez, Joselyn Rojas, and Valmore Bermúdez. "Glucosamine for Osteoarthritis: Biological Effects, Clinical Efficacy, and Safety on Glucose Metabolism." Arthritis 2014 (February 11, 2014): 1–13. http://dx.doi.org/10.1155/2014/432463.
Full textAbstract:
Osteoarthritis is a chronic degenerative disorder that currently represents one of the main causes of disability within the elderly population and an important presenting complaint overall. The pathophysiologic basis of osteoarthritis entails a complex group of interactions among biochemical and mechanical factors that have been better characterized in light of a recent spike in research on the subject. This has led to an ongoing search for ideal therapeutic management schemes for these patients, where glucosamine is one of the most frequently used alternatives worldwide due to their chondroprotective properties and their long-term effects. Its use in the treatment of osteoarthritis is well established; yet despite being considered effective by many research groups, controversy surrounds their true effectiveness. This situation stems from several methodological aspects which hinder appropriate data analysis and comparison in this context, particularly regarding objectives and target variables. Similar difficulties surround the assessment of the potential ability of glucosamine formulations to alter glucose metabolism. Nevertheless, evidence supporting diabetogenesis by glucosamine remains scarce in humans, and to date, this association should be considered only a theoretical possibility.
5
Morozenko, D. V., and E. V. Glebova. "КЛІНІЧНА ЕФЕКТИВНІСТЬ ПРЕПАРАТУ, ЩО МІСТИТЬ ГЛЮКОЗАМІНУ ГІДРОХЛОРИД, У ЛІКУВАННІ СЕЧОКАМ’ЯНОЇ ХВОРОБИ ДОМАШНІХ КОТІВ." Scientific Messenger of LNU of Veterinary Medicine and Biotechnology 18, no. 3(70) (September 14, 2016): 184–87. http://dx.doi.org/10.15421/nvlvet7044.
Full textAbstract:
In the article the question of the effectiveness of treatment of domestic cats with urolithiasis which a preparation containing glucosamine hydrochloride was used in the scheme of therapeutic interventions (Uri–Easy). According to the research, it was found that the treatment regimen with the use of drug Uri–Easy containing glucosamine hydrochloride, promotes more rapid clinical recovery of the animals, as well as the dissolution of crystals of calcium tripelfosfat glycosaminoglycans and increasing concentration in urine. This is confirmed by the fact that the 14 day treatment the animals in the second group with glucosamine hydrochloride concentration glycosaminoglycan in urine was lower by 12.3% than that in healthy cats with only single crystals of calcium tripelfosfat encountered in urine sediment. In the first group of glycosaminoglycans content in urine on day 14 were 62.6% lower than the clinically healthy cats, the precipitate thus maintained a moderate amount of calcium tripelfosfat crystals. In this second group of glycosaminoglycan concentration on the 14th day it was closer to normal, and only a few crystals were observed in urine. Thus, we can say that the introduction to the treatment regimen of the drug containing glucosamine hydrochloride, to accelerate healing cats with urolithiasis, which is confirmed by laboratory tests. This allows us to recommend the drug Uri–Easy for the comprehensive treatment of domestic cats suffering from struvite urolithiasis.
6
Blanco, Francisco J., María Camacho-Encina, Lucía González-Rodríguez, Ignacio Rego-Pérez, Jesús Mateos, Patricia Fernández-Puente, Lucía Lourido, et al. "Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis." Therapeutic Advances in Chronic Disease 10 (January 2019): 204062231987001. http://dx.doi.org/10.1177/2040622319870013.
Full textAbstract:
Background: In the present study, we explored potential protein biomarkers useful to predict the therapeutic response of knee osteoarthritis (KOA) patients treated with pharmaceutical grade Chondroitin sulfate/Glucosamine hydrochloride (CS+GH; Droglican, Bioiberica), in order to optimize therapeutic outcomes. Methods: A shotgun proteomic analysis by iTRAQ labelling and liquid chromatography–mass spectrometry (LC-MS/MS) was performed using sera from 40 patients enrolled in the Multicentre Osteoarthritis interVEntion trial with Sysadoa (MOVES). The panel of proteins potentially useful to predict KOA patient’s response was clinically validated in the whole MOVES cohort at baseline ( n = 506) using commercially available enzyme-linked immunosorbent assays kits. Logistic regression models and receiver-operating-characteristics (ROC) curves were used to analyze the contribution of these proteins to our prediction models of symptomatic drug response in KOA. Results: In the discovery phase of the study, a panel of six putative predictive biomarkers of response to CS+GH (APOA2, APOA4, APOH, ITIH1, C4BPa and ORM2) were identified by shotgun proteomics. Data are available via ProteomeXchange with identifier PXD012444. In the verification phase, the panel was verified in a larger set of KOA patients ( n = 262). Finally, ITIH1 and ORM2 were qualified by a blind test in the whole MOVES cohort at baseline. The combination of these biomarkers with clinical variables predict the patients’ response to CS+GH with a specificity of 79.5% and a sensitivity of 77.1%. Conclusions: Combining clinical and analytical parameters, we identified one biomarker that could accurately predict KOA patients’ response to CS+GH treatment. Its use would allow an increase in response rates and safety for the patients suffering KOA.
7
Djunaedi, Mochamad, and Syed Azhar Syed Sulaiman. "THE PHARMACIST’S ASSESSMENT ON PATIENTS WHO CONSUME SUPPLEMENTS AND HERBAL WHILE UNDERGOING WARFARIN THERAPY." Asian Journal of Pharmaceutical and Clinical Research 11, no. 13 (April 26, 2018): 49. http://dx.doi.org/10.22159/ajpcr.2018.v11s1.26566.
Full textAbstract:
Objective: The supplements and herbal medicines used should be monitored in a patient taking warfarin, to achieve the goal of warfarin anticoagulation. This study aims to evaluate the impacts of the supplement and the herbs used on the performance of anticoagulation.Methods: There were 214 eligible patients for having CHADS2 score >2 registered at warfarin-medication therapy adherence clinic coordinated by Cardiac Hospitals in Malaysia in 2012 included for this study. They have been assessed using a trained pharmacist regarding the safety and efficacy of warfarin as per guideline. Results: Supplements and herbs are commonly used by the patient (61.2%) who is taking warfarin. Some patients (23%) have decided not to use or stop using it after being consulted by the pharmacist. Some are even starting to use it (37%). Effects of supplements and herbal medicines were found to decrease in the International normalized ratio (INR) reading as 33%, increasing in 37% the INR reading. Further, pharmacist action is to do a dose adjustment to reach INR in the therapeutic range 2.0–3.0. Supplements consumed as categorized as phytomedicine-containing herbs, such as Omega3 and glucosamine. Whereas herbs used as beetle leaves and the product of extracted herbs, for example, Gingko biloba, Cordyceps, etc. Conclusion: Monitoring by pharmacist is needed to achieve the goal of warfarin as well as to minimize the INR out of therapeutic. The use of herbal and supplement is found to be a factor contributes to the performance of anticoagulation control which has been successfully achieved 71.2%.
8
Lippiello, Louis. "Collagen Synthesis in Tenocytes, Ligament Cells and Chondrocytes Exposed to a Combination of Glucosamine HCl and Chondroitin Sulfate." Evidence-Based Complementary and Alternative Medicine 4, no. 2 (2007): 219–24. http://dx.doi.org/10.1093/ecam/nel081.
Full textAbstract:
Clinical testing of the nutraceuticals glucosamine (glcN) and chondroitin sulfate (CS) has shown efficacy in providing relief from symptoms in osteoarthritic patients.In vitroandin vivostudies support existence of a synergistic relationship upregulating synthetic activity in chondrocytes. A combination of glcN and CS may also be useful as adjunct therapy in sports-related injuries if similar upregulation of collagen synthesis is elicited in accessory ligament and tendon joint tissue. Collagen and non-collagenous protein (NCP) synthesis in cultures of bovine tenocytes, ligament cells and chondrocytes exposed to glcN + CS were assayed by uptake of radiolabeled proline into collagenase-sensitive material. Assay of radiolabel in hydroxyproline (a specific marker for collagen synthesis) following HPLC isolation confirmed the specificity of the metabolic effect. Synthesis of total collagenase-sensitive material was maximally upregulated at physiologically obtainable doses of glcN + CS. Tissue response followed the sequence ligament cells (+69%) > chondrocytes (+56%) > tenocytes (+22%). Labeled hydroxyproline increased by 132% in ligament cells, 27% in tenocytes and 49% in epitendon cells after a 48 h exposure to 5 μg ml−1glcN + 4 μg ml−1CS. Low dose combinations of glcN and CS effectively stimulatein vitrocollagen and NCP synthesis by ligament cells, tenocytes and chondrocytes. Hence, therapeutic use following accessory joint tissue trauma may help augment repair processes.
9
Dydykina, I. S., E. V. Arutyunova, P. S. Kovalenko, and E. G. Zotkin. "The clinical significance of and prospects for the use of biopolymer-based microheterogeneous collagen-containing injectable hydrogel in the therapy of osteoarthritis." Modern Rheumatology Journal 14, no. 4 (November 25, 2020): 132–37. http://dx.doi.org/10.14412/1996-7012-2020-4-132-137.
Full textAbstract:
The paper gives the current definition of osteoarthritis (OA), which reflects the pathogenetic and clinical characteristics of this disease, as well as general principles for choosing an OA treatment. It describes the effect of glucosamine and chondroitin on the key pathogenetic mechanisms of OA. It is noted that one of the promising areas of therapy for OA is the intra-articular administration of biopolymer-based hydrogels that provide not only an anti-inflammatory, but also regenerative effect that has been experimentally confirmed during their injection into the tendon sheaths. There are data on the efficacy and safety of the Russian drug Sphero®gel, a biopolymer-based microheterogeneous collagen-containing hydrogel that belongs to a class of multicomponent biopolymer-based extracellular matrix mimetics. It consists of the cross-linked farm animal tissue-derived collagen microparticles placed in the gel base. The gel is not only a structural base for collagen microparticles; it also has its own therapeutic potential, since it is structurally similar to the natural extracellular matrix. The drug contains collagen, biologically active components of the extracellular matrix, such as proteoglycans, glycoproteins, uronic acids, growth factors, monosaccharides, and chondroitin sulfate. Extended-release symptomatic agents, Sphero®gel among them, are currently recommended for the treatment of OA. Application of Sphero®gel contributes to increased joint mobility and reduced pain, which allows the limited use of nonsteroidal anti-inflammatory drugs that cause adverse reactions, especially in the presence of comorbid diseases.
10
Kanneppady, Sowmya Sham, Sham Kishor Kanneppady, Vijaya Raghavan, Aung Myo Oo, and Ohn Mar Lwin. "Prescription Pattern of Primary Osteoarthritis in Tertiary Medical Centre." Journal of Health and Allied Sciences NU 07, no. 04 (December 2017): 037–42. http://dx.doi.org/10.1055/s-0040-1708734.
Full textAbstract:
Abstract Objectives: Osteoarthritis (OA) is one of the commonest joint/musculoskeletal disorders, affecting the middle aged and elderly, although younger people may be affected as a result of injury or overuse. The study aimed to analyze the data, evaluate the prescription pattern and rationality of the use of drugs in the treatment of primary OA with due emphasis on the available treatment regimens. Materials and methods: Medical case records of patients suffering from primary OA attending the department of Orthopedics of a tertiary medical centre were the source of data. The study was carried out prospectively for a period of 20 months (from December 2012 to July 2014). Results: 296 case records were collected in which the total number of drugs prescribed were 550. OA was more common in females (51.7%) and was more prevalent in the age group of 30–40 years (39%). Out of 550 drugs prescribed, Aceclofenac was the most frequently prescribed NSAID (29%) followed by Diclofenac (23%). Nimesulide and Paracetamol was the most commonly prescribed fixed dose combination (53). Among gastroprotectives, Ranitidine figured in 66 prescriptions. Glucocorticoids were prescribed orally and intraarticularly in 17 and 14 cases respectively. Dietary supplements like Calcium+Vitamin D (42) and Glucosamine Sulfate + Chondroitin Sulfate complex (19) were also prescribed. Conclusion: The above study highlights the rational use of therapeutic agents for primary OA.
11
Kovacevic, Strahinja, Milica Karadzic, Lidija Jevric, and Sanja Podunavac-Kuzmanovic. "Molecular docking analysis of newly synthesized 2- morpholinoquinoline derivatives with antifungal potential toward Aspergillus fumigatus." Acta Periodica Technologica, no. 48 (2017): 155–65. http://dx.doi.org/10.2298/apt1748155k.
Full textAbstract:
The present paper is concerned with the molecular docking analysis of newly synthesized 2-morpholinoquinoline derivatives with antifungal potential toward Aspergillus fumigatus. The purpose of the molecular docking analysis was to determine potential interactions between the analyzed compounds and the active site of the enzyme glucosamine-6-phosphate synthase, as well as to reveal which molecular features (the presence of different substituents or isomers) could be responsible for significant antifungal activity of the tested compounds. The compounds with the highest antifungal potential toward pathogenic and saprotrophic fungus Aspergillus fumigatus were docked, and the results were compared with the docking of griseofulvin, which is an antifungal drug used in the treatment of various types of dermatophytoses. Newly discovered antifungal agents are very important in medicine, as well as in agriculture. The prevention of the presence of mycotoxins in food and feed products is one of the urgent tasks. Therefore, every effort which leads to discovery of their mechanism of action and determination of side effects is precious. The present study can be considered a contribution to the analysis and selection of newly discovered antifungals from the 2-morpholinoquinoline family, and one step forward to their practical use in medicine and agriculture. The obtained results reveal the possible reason why the newly synthesized 2-morpholinoquinoline expresses even higher antifungal activity toward Aspergillus fumigatus than griseofulvin, a commercially available antifungal therapeutic.
12
Belova, K. Yu, and A. V. Nazarova. "Strategy for the management of osteoarthritis in multimorbid patients: the balance of effectiveness and safety while choosing drug therapy." Meditsinskiy sovet = Medical Council, no. 11 (August 8, 2020): 164–76. http://dx.doi.org/10.21518/2079-701x-2020-11-164-176.
Full textAbstract:
Due to the increase in life expectancy, the number of elderly and senile people with various chronic diseases is growing. One of the most common diseases of the musculoskeletal system is osteoarthritis. According to existing recommendations among all medications the leading place in the treatment of patients with osteoarthritis is given to symptomatic slowacting drugs (SYSADOA). Data from numerous studies show that these patients are often multimorbid, and this fact significantly restricts the appointment of many medications. In such cases, the use of drugs from the SYSADOA group becomes the basis of therapy due to their safety. Medications of this group include chondroitin sulfate and glucosamine sulfate. They are the main structural components of cartilage and synovial fluid and they are used for the synthesis of glycosaminoglycans, they reduce the degradation of cartilage, and also exhibit analgesic and anti-inflammatory effects. In addition, a number of other pleiotropic effects of these drugs have been shown, including a positive effect on muscles in sarcopenia, on reducing the risk of death from several cancers and complications of diabetes mellitus. In recent years, there has also been evidence of the use of the natural egg membrane preparation (NEM), which contains natural glycosaminoglycans and proteins necessary for maintaining the condition of the cartilage and synovial membrane. Studies have shown its anti-inflammatory effect, reducing the intensity of pain and improving functional indicators in patients with osteoarthritis. There was also a decrease in the production of pro-inflammatory cytokines in osteoarthritis for the plant-derived substance harpagophytum, which has therapeutic potential in the treatment of diseases associated with inflammation and oxidative stress.
13
Pham, Lan V., Jerry Bryant, Archito Tamayo, Richard Mendez, Edna Chum, David Yang, David Rollo, and Richard J. Ford. "Metabolic Targeted Therapy for Aggressive B-Cell Lymphomas: Evaluating Glucose Metabolism and the Potential of 187rhenium- Ethylenedicysteine –N-AcetylGlucosamine (187Re-ECG) for Therapy." Blood 116, no. 21 (November 19, 2010): 117. http://dx.doi.org/10.1182/blood.v116.21.117.117.
Full textAbstract:
Abstract Abstract 117 Aggressive non-Hodgkin lymphomas (NHL), such as diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), are very common in the US with increasing incidences. Although these lymphomas are now potentially curable, almost half the treated patients still develop relapsed/refractory (r/r) disease with poor survival outcomes, indicating an urgent need for better therapeutic approaches with improved efficacy, particularly in r/r lymphomas. The emerging area in lymphoma biology involving energy metabolism, has begun to identify likely potential molecular targets for novel therapeutics that can fundamentally change the conventional treatment of cancer. Glucose metabolism, besides its basic metabolic functions in cell physiology, has been shown to provide the major energy source fueling tumor cell growth and survival. We show here that aggressive B-cell lymphomas highly expressed glucose transporters types 1(Glut1) and 3 (Glut3) and hexokinase II (HKII) in both cell lines and primary cases. Since glucose metabolism is highly active and utilized in aggressive B-cell lymphomas, we explored exploiting this bi-functional pathway(s) as a targeted therapy. Previous studies have shown that 99mTc-ethylenedicysteine-N-Acetylglucosamine (ECG), a synthetic glucose analogue, accumulates in cancer cell nuclei and various tumors in animal models. Its' also been shown to differentiate tumor vs inflammation in animal models. Rhenium (Re-therapeutic metal) metal displays similar chemical properties to 99mTc (diagnostic metal), allowing the use of the same backbone (synthetic glucose analogue) for diagnostic and potential therapy. This analogue provides the capability to simultaneously monitor therapeutic activity during induction of tumor treatment therapy while assessing its efficacy. Re-ECG was synthesized by reacting Re-EC with glucosamine tetraacetate. After deprotection of tetraacetate, Re-ECG was produced. Thymidine incorporation assays indicated that Re-ECG inhibits cell proliferation of aggressive dividing lymphoma cells, but was less effective in slow growing lymphoma cells. Further analysis showed that Re-ECG uptake is also more prominent in highly proliferative lymphoma cells, where Re-ECG enters the nucleus and causes DNA damage that leads to lymphoma cell apoptosis. We also evaluated the biodistribution pattern of Re-ECG in a lymphoma SCID mouse model through imaging by single-photon emission computed tomography (SPECT), accelerator mass spectrometry (AMS) and liquid scintillation counting (LSC). The bio-distribution data revealed that radioactivity (14C-187Re-ECG) was retained well in tumor tissue 2 hours post-injection with little to no uptake in the plasma when compared to tumor. The compound was excreted over longer incubation time. Over all, we observed that the lymphoma tumor has an extended drug retention time when compared to other tissues. These results suggest that the metallic pharmaceutical agent 187Re-ECG is an excellent potential candidate for targeted therapy in aggressive r/r lymphomas. This application further defines the term theranostic for personalized medicine approaches utilizing bifunctional imaging/therapeutic agents. Disclosures: Bryant: Cell Point: Employment. Yang:UT MD Anderson Cancer Center: Patents & Royalties. Rollo:Cell Point: Employment. Ford:Cell Point: Research Funding.
14
Mousa, Shaker A., Seema Mohamed, Laura O’Connor, and Eric Block. "Sulfur- and Selenium-Containing Compounds Derived from Natural and Synthetic Sources in Angiogenesis Modulation." Blood 104, no. 11 (November 16, 2004): 3924. http://dx.doi.org/10.1182/blood.v104.11.3924.3924.
Full textAbstract:
Abstract Increases in serum sulfate may explain some of the therapeutic effects of methylsulfonyl methane (MSM), dimethyl sulfoxide, and glucosamine sulfate. Organic sulfur, as sulfur-containing amino acids, can be used to increase synthesis of S-adenosylmethionine, glutathione, taurine, and N-acetylcysteine. MSM may be effective for the treatment of allergy, pain syndromes, athletic injuries, and bladder disorders. Epidemiological studies have suggested that brassica vegetables are protective against cancers of the lungs and alimentary tract. Cruciferous vegetables are the dietary source of glucosinolates, a large group of sulfur-containing glycosides. However, dosages, mechanisms of action, and rationales for the use of various sulfur-containing compounds from natural or food products need to be better defined. The low toxicological profiles of these sulfur compounds, combined with promising therapeutic effects, warrant continued preclinical and clinical investigations. In this current study the angiostatic (antiangiogenesis) efficacy for individual sulfur-containing compounds derived from natural or synthetic sources was determined using in vitro (endothelial cell [EC] tube formation assay) and in vivo (chick chorioallantoic membrane [CAM] model). In vitro EC tube formation studies demonstrated significant inhibition of fibroblast growth factor-2 (FGF-2) stimulated EC tube formation by the different sulfur- and selenium-containing compounds, with different potency depending on the oxidation state of the sulfur or selenium. Furthermore, utilizing the CAM model, similar inhibitory efficacy of FGF-2 induced angiogenesis. These data suggest that sulfur and selenium compounds derived from natural sources might be a useful therapy for the inhibition of angiogenesis associated with human tumor growth and other pathological angiogenesis-mediated disorders, such as ocular and inflammatory diseases. Antiangiogenesis Efficacy of Sulfone/Sulfoxide and Selenone/Selenoxide in the Chick Chorioallantoic Membrane Model Treatment Branch Points ± SEM % Inhibition ± SEM FGF = fibroblast growth factor; PBS = phosphate-buffered saline. PBS control 64.67 ± 3.00 ----- FGF-2 (1.5 ug/ml) 178.20 ± 5.32 ----- FGF-2 + diphenyl sulfoxide (100 uM) 145.65 ± 11.10 34.12 ± 4.8 FGF-2 + diphenyl sulfone (3 uM) 82.56 ± 4.4 84.25 ± 3.6 FGF-2 + dimethyl selenoxide (30 uM) 120.86 ± 3.1 50.74 ± 2.7 FGF-2 + dimethyl selenone (3 uM) 71.63 ± 3.8 93.87 ± 3.3
15
van Der Wal, Dianne E., Guangheng Zhu, June Li, Brian Vadasz, Yougbare Issaka, Sean Lang, John Freedman, and Heyu Ni. "Desialylation: A Novel Platelet Clearance Mechanism and a Potential New Therapeutic Target in Anti-GPIb Antibody Mediated Thrombocytopenia." Blood 120, no. 21 (November 16, 2012): 265. http://dx.doi.org/10.1182/blood.v120.21.265.265.
Full textAbstract:
Abstract Abstract 265 Background: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibodies directed at patient's own platelet antigens, primarily glycoprotein (GP)IIbIIIa-integrin (70–80%) and GPIb-complex (20–40%). Current paradigm suggests that clearance of opsonized platelets through the reticuloendothelial system via Fcγ-receptors results in thrombocytopenia and bleeding disorders. However, evidence from others and our group demonstrated that anti-GPIbα, but not anti-GPIIbIIIa, can induce thrombocytopenia via an Fc-independent pathway, which is resistant to intravenous IgG (IVIG) therapy in murine ITP-models (Blood 2006). These observations are consistent with subsequent IVIG studies in human ITP patients. Interestingly, human anti-GPIb-mediated ITP patients seem also resistant to steroid therapy in our recent retrospective study (American Journal of Hematology 2012). This suggests that binding of anti-GPIbα antibodies may induce platelet clearance through a different mechanism which is currently poorly understood. Methods: We developed unique mouse anti-mouse monoclonal antibodies (mAbs) in GPIIIa or GPIba deficient mice. Some of the mAbs have cross-reactivity to both mouse and human GPIIbIIIa and GPIba. Flow cytometry was used to evaluate whether these mAbs were able to induce platelet activation, apoptosis and desialylation. GPIbα is heavily glycosylated and the role of desialylation and exposure of underlying galactose and β-N-acetyl-D-glucosamine (βGN) residues on GPIbα in platelet clearance was assessed using the sialidase neuraminidase (NA) and it's inhibitor N-acetyl-2,3-dehydro-2-deoxy neuraminic acid (DANA). Desialyation effects on platelet activation and apoptosis was measured by flow cytometry. We also repeated these experiments with human platelets and plasma from human ITP-patients. We also investigated the effects of anti-GPIbα antibodies on platelet activation, apoptosis and clearance in vivo. Briefly, BALB/c mice were injected with anti-GPIbαor anti-GPIIIa mAbs and 24 hrs later, platelet desialylation, activation and apoptosis were measured by flow cytometry. The effect of desialylation on platelet clearance was assessed with DANA. The possible roles of Ashwell-Morell and MAC-1 receptors in GPIbα-mediated platelet clearance in the liver were examined using immunohistochemistry (anti-CD11b) or blocking of the Ashwell-Morell receptor with asialofetuin. Results and Discussion: We found that anti-GPIbα, but not anti-GPIIbIIIa mAbs, induced significant P-selectin expression and phosphatidylserine (PS)-exposure, and increased inner membrane mitochondrial depolarization (ΔYm). Interestingly, platelets were desialylated in the presence of anti-GPIbα but not anti-GPIIbIIIa mAbs. Moreover, we found that desialylation of GPIbα lies directly upstream of platelet activation and apoptosis, as prior treatment with DANA diminished PS-exposure, and P-selectin expression. Most importantly, incubations of human platelets with ITP-patient plasma showed similar effects. In vivo, we found significant increases in PS-exposure and ΔYm induced by anti-GPIbα, but not by anti-GPIIIa mAbs, independent of IgG subclass. Interestingly, prior injection with DANA rescued platelets numbers in anti-GPIbα, but not in anti-GPIIIa injected mice. A significant role for the Ashwell-Morell and MAC-1 receptors in the clearance of deglycosylated platelets was observed; blocking of the Ashwell-Morell receptors by asialofetuin, decreased platelet clearance in anti-GPIbα, but not anti-GPIIbIIIa antibody injected mice, there was also increased staining for MAC-1 on Kupffer cells, exclusively in the presence of an anti-GPIbα mAb tested. Thus, we demonstrate for the first time that anti-GPIbα antibodies induce GPIbα desialyation, leading to platelet activation and apoptosis. Therefore, we identified novel Fc-independent platelet clearance pathways, more specifically, via Ashwell-Morell and MAC-1 receptors on hepatocytes and liver macrophages. These findings may lead to novel therapeutic regimens including the potential use of sialidase inhibitors as a solution for anti-GPIb-mediated ITP patients previously refractory to both steroid and IVIG therapies. Disclosures: No relevant conflicts of interest to declare.
16
Olson, Kim E., Joan H. F. Drosopoulos, Marinus J. Broekman, Naziba Islam, Dianne Pulte, and Aaron J. Marcus. "Generation of a Novel Engineered Murine Apyrase in Pichia Pastoris. Enzymatic Profile and Inhibition of Human Platelet Reactivity." Blood 104, no. 11 (November 16, 2004): 1846. http://dx.doi.org/10.1182/blood.v104.11.1846.1846.
Full textAbstract:
Abstract To study thrombogenesis in wild-type and transgenic mice we engineered a recombinant, soluble form of murine ENTPDase1/CD39 for use as a therapeutic agent. ENTPDase1 contains N- and C-terminal intracellular and transmembrane regions flanking an extracellular domain containing the 5 enzymatically active apyrase-conserved regions. The soluble portion of murine CD39 was amplified using PCR with 5′-XhoI and 3′-XbaI linked primers and cloned into the XhoI/XbaI-digested yeast expression vector pGAPZα. The vector, which features the constitutive GAP promoter and α factor secretion signal, was modified by elimination of the Ste13 cleavage sites and by introduction of a 5′-6His tag separated from the murine solCD39 coding sequence by an enterokinase cleavage site. Stably expressing clones were selected. Aliquots of 30-fold concentrated conditioned medium, obtained following 72 h culture of a yeast clone, were assayed for ADPase and ATPase activity and for the ability to inhibit platelet reactivity. Nucleotidase activity was monitored by native gel electrophoresis and staining using ATP metabolism to phosphate and conversion of Ca-phosphate into PbS, as well as by radio-TLC analyses. Platelet aggregation was quantitated using ADP and collagen as stimuli in heparinized and citrated human platelet-rich plasma (PRP). SolCD39 produced in mammalian cells (CHO, or COS-1) yields an active enzyme that is heavily N-glycosylated. Similarly, Pichia pastoris-produced (murine) solCD39 yields a comparably active protein that is also heavily glycosylated, albeit with the yeast-specific high mannose-type N-glycans. Its ADPase to ATPase activity ratio was ~1.2. Yeast-derived murine solCD39 was treated with PNGase F, an amidase that cleaves between the innermost N-acetyl glucosamine of complex oligosaccharides and asparagine residues of glycoproteins. This removed all saccharides from solCD39, as shown by PAS staining, and by mobility shifts by Western blot analysis and Pb staining in native gels. Interestingly, the deglycosylated protein retained ~60% of both enzymatic and biological activities as compared to the parent molecule. The figures shows platelet aggregation to 5 μM ADP in citrated PRP for control (no murine solCD39), isolated solCD39, and equal quantites of solCD39 that was deglycosylated, as well as subjected to the deglycosylation reaction in the absence of PNGase F. These data are similar for the present murine yeast-produced molecule and COS-produced human solCD39. Our data indicate the possibility of high scale production of solCD39 in yeast, with excellent yield, stability and antithrombotic activity. Figure Figure
17
Sapra, Puja, Patricia Kraft, Mary Mehlig, Zhihua Zhang, Lee M. Greenberger, and Ivan D. Horak. "Recombinant Human Mannose-Binding Lectin (rhMBL) Binds to Human and Mouse Cancer Cells and Elicits Antitumor Activity in a MBL Knockout Mouse Model of Murine Cancer." Blood 108, no. 11 (November 16, 2006): 1259. http://dx.doi.org/10.1182/blood.v108.11.1259.1259.
Full textAbstract:
Abstract Mannose-binding lectin (MBL), a human plasma protein, plays a role in innate immune defense. MBL recognises microorganisms through surface carbohydrate structures leading to either direct opsonisation or activation of complement system. Since MBL deficiency is associated with increased susceptibility to infections in immunosuppressed individuals, e.g., during chemotherapy induced neutropenia, replacement therapy with recombinant human MBL (rhMBL) may be beneficial in this patient group. MBL has also been shown to bind to cancer cell lines. Therefore, we hypothesized that MBL binding to cancer cells may lead to direct opsonisation or activation of the innate immune system leading to cell kill. In this study, we aim to determine the binding and therapeutic efficacy of rhMBL in cancer cells and animals models respectively. The in vitro binding of rhMBL was evaluated on human cancer cell lines by flow cytometry using a specific anti-MBL antibody. rhMBL demonstrated binding to 6 of 7 cancer cells lines tested. These included human ovarian (OVCAR-3, SK-OV-3), pancreatic (MiaPaCa-2), colorectal (COLO-205), lymphoma (Daudi) and murine melanoma (B16-F0) cancer cells. The binding of rhMBL appeared to be specific since it was partially inhibited by 100mM mannose, 100mM N-acetyl glucosamine, 20mM mannan, use of Ca2+-free buffer or with 10mM EDTA. The antitumor effects of rhMBL were evaluated in MBL knockout (MBL/KO) transgenic mice, which lack both MBL-1 and MBL-2 genes, and corresponding MBL wildtype mice injected subcutaneously with B16-F0 mouse melanoma cells. MBL wildtype mice injected with B16-F0 mouse melanoma cells did not develop subcutaneous tumors. However, MBL/KO mice had robust tumor growth suggesting that MBL deficient individuals may be more susceptible to development of cancers. Treatment of MBL/KO mice with 75 μg MBL/mouse (q2dx5) resulted in 63% tumor growth inhibition compared with the control mice (P<0.05). Moreover, MBL/KO mice treated with rhMBL had a significant prolongation of life span compared with the control group (P<0.05). In conclusion, rhMBL binds to mouse and human tumor cells and inhibits tumor cell growth in a MBL/KO murine melanoma model. This phenomenon may not take place in MBL-deficient individuals, and these individuals may thus be more susceptible to development of tumors. Replacement therapy with rhMBL in these individuals may have anticancer effects. rhMBL should thus be further evaluated for prevention and treatment of infection complications in MBL deficient immunocompromised patients as well as potential anticancer therapy.
18
Kampa-Schittenhelm, Kerstin Maria, Hans-Joerg Buehring, Michael Bonin, Wichard Vogel, Lothar Kanz, Thomas Haverkamp, and Marcus M. Schittenhelm. "Epigenetic Upregulation of the O-Linked Beta-N-Acetylglucosamine Transferase (OGT) in Response to Dronabinol Results in Antileukemic Efficacy In Vivo." Blood 126, no. 23 (December 3, 2015): 2437. http://dx.doi.org/10.1182/blood.v126.23.2437.2437.
Full textAbstract:
Abstract The O-linked β-N-acetyl glucosamine (O-GlcNAc) transferase (OGT) is a master regulator enzyme adding O-GlcNAc to serine or threonine residues in a multitude of target proteins. Aberrant O-GlcNAc modification is implicated in pathologies of metabolic and neurodegenerative diseases as well as cancers and autoimmunity. We herein provide evidence that dronabinol (FDA approval as Marinol), the natural (−)-Δ9-Tetrahydrocannabinol, is a potent inducer of OGT via epigenetic hypomethylation of the transcription start site -thereby exerting antileukemic activity in acute leukemia in vivo. We have recently shown, that dronabinol, the natural (−)-Δ9-Tetrahydrocannabinol, has growth-inhibiting antitumor efficacy - including acute leukemia. We now reveal a novel mechanism-of-action via epigenetic modulation of OGT, an enzyme linked to genes involved in leukemogenesis such as AKT, MLL5, TET2 or ASXL1, releasing leukemia blasts from differentiation blockage in vivo and sensitizing cells towards induction of apoptosis. gDNA methylation gene arrays using Jurkat leukemia cells revealed global modulation of methylation patterns upon dronabinol treatment. OGT was identified as the highest altered gene (-42%, pval 3,68E-38) - correlating with an increase of OGT protein expression in Western immunoblots. Consistently, hypomethylation of the transcription start site of OGT and induction of OGT protein expression upon dronabinol were confirmed in an independent array using native patient samples. To study whether epigenetic activity is driven via the cannabinoid receptors, Jurkat cells were pretreated with CB1 (LY320135) and/or CB2 (JTE-907) antagonists, and exposed to dronabinol. Importantly, upregulation of OGT protein expression upon dronabinol was suppressed by inhibition of either receptor. Even more, inhibition of CB1 and/or CB2 reduced induction of apoptosis - and was most profound when inhibiting both receptors simultaneously. Similarly, retroviral knockdown of OGT in Jurkat and native leukemia blasts rendered cells less susceptible towards induction of apoptosis. Furthermore, we have evidence, that OGT has lead to release of the differentiation block in leukemia cells in vivo. Supportive treatment with dronabinol of an unfit patient with secondary acute myeloid leukemia resulted in direct disease control: Tantalizingly, besides a proapoptotic effect, the leukemic clone was maturing - with loss of CD34 and upregulation of CD11c, CD14 and CD15. Remarkably, immunophenotypic and genotypic (using NGS) profiling of the predominant monocyte population present two months after start of treatment, revealed that these mature monocytes derived from the leukemia clone (presenting mutations in EZH2 and ASXL1 among others - both known candidate genes of OGT). Mimicking this observation, we treated cells of this and other patients as well as defined leukemia models such as MOLM14 with dronabinol ex vivo and revealed upregulation of differentiation markers, such as CD11c, CD15 or CEBPA by flow cytometry and immunoblots - which was abrogated by lentiviral OGT-interference. Our findings provide a strong rationale for further exploring dronabinol as an agent with remarkable antileukemic efficacy achievable in vivo. In specific, overriding the differentiation blockage in leukemia cells may open up alternative therapeutic approaches similar to promyelocytic leukemia. Disclosures Off Label Use: Marinol: FDA approved for chemotherapy related nausea... here we demonstrate significant anti-leukemic effects.
19
Bruyère, Olivier, Johann Detilleux, and Jean-Yves Reginster. "Cost-Effectiveness Assessment of Different Glucosamines in Patients with Knee Osteoarthritis: a Simulation Model Adapted to Germany." Current Aging Science 14 (April 15, 2021). http://dx.doi.org/10.2174/1874609814666210415092845.
Full textAbstract:
Background: The use of symptomatic slow-acting drugs for osteoarthritis (OA) (e.g., glucosamine, chondroitin) is largely debated in the scientific literature. Indeed, multiple formulations of these agents are available, both as pharmaceutical-grade products and as nutritional supplements, but while all preparations may claim to deliver a therapeutic effect, not all are supported by clinical evidence. Moreover, few data are available regarding the cost-effectiveness of all these formulations. Usually, access to individual patient data is required to perform economic evaluations of treatments, but it can be difficult to obtain. We previously developed a model to simulate individual health utility scores from aggregated data obtained from published OA trials. Objective: In the present study, using our new simulation model, we investigated the cost-effectiveness of different glucosamines used in Germany. Methods: We used our validated model to simulate the utility scores of 10 published trials that used different glucosamine preparations. Using the simulated utility scores, the quality-adjusted life years (QALYs) were calculated using the area-under-the-curve method. We used the 2018 public costs of glucosamine products available in Germany to calculate the Incremental Cost/Effectiveness Ratio (ICER). We performed analyses for pharmaceutical-grade Crystalline Glucosamine Sulfate (pCGS) and other formulations of glucosamine (OFG). A cost-effectiveness cut-off of 30,000 €/QALY was considered. Results: Of 10 studies in which utility was simulated, four used pCGS, and six used OFG. The ICER analyses showed that pCGS was cost-effective compared to a placebo, with an ICER of 4489 €/QALY at month 3, 4112 €/QALY at month 6 and 9983 €/QALY at year 3. The use of OFG was not cost-effective at any of the time points considered. Conclusion: Using our previously published model to simulate the individual health utility scores of patients, we showed that, in the German context, the use of pCGS could be considered cost-effective, while the use of OFG could not. These results highlight the importance of the formulation of glucosamine.
20
Asthana, Chhavi, Gregory M. Peterson, Madhur D. Shastri, and Rahul P. Patel. "Quality of Glucosamine Products: Is it a Potential Reason for Inconsistent Clinical Outcomes in Osteoarthritis?" Journal of AOAC INTERNATIONAL, June 19, 2020. http://dx.doi.org/10.1093/jaoacint/qsaa081.
Full textAbstract:
Abstract Background Clinical studies have reported inconsistent outcomes of glucosamine therapy in osteoarthritis patients. One possible reason could be the use of glucosamine products of varying quality. Objective Hence, this study aimed to assess the quality of glucosamine products marketed in Australia and India. This is the first study to investigate both the content and dissolution profiles of glucosamine products. Method The content and dissolution analysis of Australian (n = 25 brands) and Indian (n = 21 brands) glucosamine products was performed according to the criteria specified in the United States Pharmacopoeia (USP). Results The quality analysis revealed that 16% and 18% of Australian brands, as well as 24% and 19% of Indian brands, did not fulfil the USP content and dissolution criteria, respectively. In approximately half of these cases, the glucosamine content was only slightly below (<3%) that specified by the USP and dissolution was achieved within 15 min after the duration specified by the USP. Conclusions The majority of the brands did meet both the content and dissolution analysis criteria of the USP. The extent of deviation from the specified criteria for the other brands was probably insufficient to account for the significant variability in clinical effects. Hence, the study proposed that inter-patient pharmacokinetic variations in glucosamine could be another potential reason for inconsistent therapeutic effects. Highlights
21
Utami, Pratiwi, Sonny J. R. Kalangi, and Taufiq Pasiak. "PERAN GLUKOSAMIN PADA OSTEOARTRITIS." JURNAL BIOMEDIK (JBM) 4, no. 3 (March 16, 2013). http://dx.doi.org/10.35790/jbm.4.3.2012.1202.
Full textAbstract:
Abstract: Osteoarthritis is a degenerative disease and manifests itself as the most common type of arthritis affecting older people. This disease can cause significant pain and functional disability in the affected individuals. The therapy for osteoarthritis is easily available but the results are without certainty. Symptomatically therapeutic agents such as acetaminophen and NSAIDs are only beneficial for relieving the symptoms. Unfortunately, these agents can trigger severe side effects in some patients or may be contraindicated. Glucosamine has been evaluated in several studies as an agent to relieve pain, increase functional activity, and slow the progression of osteoarthritis, especially in the knees. Studies have reported some improvement in pain and disability in osteoarthritic patients related to the use of glucosamine. Based on the current evidence, a combination of glucosamine sulfate and chondroitin sulfate shows the greatest potential as a therapeutic intervention for patients who might risk side effects from other oral medications currently in vogue. However, research is still needed to explore the benefits of glucosamine or its combination forms in order to ensure safety for long-term use. Keywords: osteoarthritis, glucosamine, pain. Abstrak: Osteoartritis merupakan penyakit degeneratif yang menyebabkan rasa nyeri dan cacat fungsional pada individu yang terkena dan umumnya mempengaruhi lanjut usia. Kemajuan dalam pengobatan osteoartritis relatif tersedia tetapi belum secara pasti untuk mengobatinya. Terapi andalan seperti asetaminofen dan obat NSAID hanya untuk mengobati gejala, tetapi dapat memicu efek samping yang parah pada pasien atau mungkin merupakan kontraindikasi. Beberapa studi mengemukakan glukosamin sebagai agen untuk menghilangkan rasa nyeri, meningkatkan aktivitas fungsional, dan memperlambat progresivitas osteoarthritis, terutama pada lutut. Juga telah dilaporkan perbaikan dalam rasa nyeri dan kecacatan yang terkait dengan penggunaan glukosamin baik sebagai agen tunggal maupun bentuk kombinasi glukosamin sulfat dengan kondroitin sulfat. Penggunaan produk kombinasi tersebut tampaknya memiliki potensi besar untuk pasien yang berisiko akibat efek samping terapi oral. Masih dibutuhkan penelitian lanjut mengenai manfaat dan kemanan glukosamin terutama pada pemakaian jangka panjang. Kata kunci: osteoartritis, glukosamin, nyeri.