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Sample records for acid re-differentiation therapy

  1. Pancreatic β-cell Dedifferentiation in Diabetes and Re-differentiation following Insulin Therapy

    Science.gov (United States)

    Wang, Zhiyu; York, Nathaniel W.; Nichols, Colin G.; Remedi, Maria S.

    2014-01-01

    Diabetes is characterized by ‘glucotoxic’ loss of pancreatic β-cell function and insulin content, but underlying mechanisms remain unclear. A mouse model of insulin-secretory deficiency induced by β-cell inexcitability (KATP gain-of-function) demonstrates development of diabetes and reiterates the features of human neonatal diabetes. In the diabetic state, β-cells lose their mature identity and dedifferentiate to neurogenin3-positive and insulin-negative cells. Lineage-tracing experiments show that dedifferentiated cells can subsequently re-differentiate to mature neurogenin3-negative, insulin-positive, β-cells after lowering of blood glucose by insulin therapy. We demonstrate here that β-cell dedifferentiation, rather than apoptosis, is the main mechanism of loss of insulin-positive cells, and re-differentiation accounts for restoration of insulin content and antidiabetic-drug responsivity in these animals. These results may help explain gradual decrease in β-cell mass in long-standing diabetes, and recovery of β-cell function and drug responsivity in type-2 diabetic patients following insulin therapy, and suggest an approach to rescuing ‘exhausted’ β-cells in diabetes. PMID:24746806

  2. Evaluation of ventilatory therapy for acid aspiration.

    Science.gov (United States)

    Flint, L; Gosdin, G; Carrico, C J

    1975-10-01

    Aspiration of hydrochloric acid in experimental animals results in severe, progressive hypoxia which is due to intrapulmonary shunting and depressed cardiac output. This preparation is useful therefore in studying the therapy of hypoxia. Mongrel dogs were subjected to acid aspiration and the effects of several ventilatory patterns on intrapulmonary shunt fractions and lung water accumulation observed. The combination of large tidal volumes (30 c.c. per kilogram) with positive end-expiratory pressure was effective in preventing intrapulmonary shunting and other ventilatory patterns were ineffective. Pulmonary edema uniformly followed acid aspiration and was not affected by ventilatory therapy. When ventilatory therapy was delayed for 4 hours, the progression of shunting apparently was limited, but the existing shunt was not reduced.

  3. Uric acid lowering therapy in cardiovascular diseases.

    Science.gov (United States)

    Volterrani, Maurizio; Iellamo, Ferdinando; Sposato, Barbara; Romeo, Franco

    2016-06-15

    Recent evidence would indicate that high serum uric acid (SUA) levels can be a significant and independent risk factor for hypertension and cardiovascular diseases, such as ischemic heart disease and heart failure. In the last few years an independent risk relationship between hyperuricemia, cardiovascular disease and mortality has also been reported. Hyperuricemia has been shown as an independent risk factor for acute myocardial infarction and an independent and conjoint association of either gout and SUA with total and cardiovascular mortality has been reported, with mortality impact in gout patients increasing with rising SUA concentrations, even for SUA levels in the normal to high range. These findings prompted a growing research interest on the possible benefits of uric acid lowering drugs in cardiovascular diseases. Indeed, clinical studies have reported on the beneficial effects of uric acid lowering drugs, in particular of xanthine oxidase inhibitors, in hypertension, ischemic heart disease and heart failure. Two main mechanisms have been claimed to explain the dangerous effects of hyperuricemia and, as a consequence, the benefits of uric acid lowering therapy: endothelial dysfunction and systemic inflammation. This brief review aims to summarize current evidence from human studies on the role of acid uric lowering therapy in cardiovascular diseases for practical and clinical purposes. The possible mechanisms underlying the benefits of acid uric lowering therapy are also addressed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. The regulation of expanded human nasal chondrocyte re-differentiation capacity by substrate composition and gas plasma surface modification

    NARCIS (Netherlands)

    Woodfield, Tim B.F.; Miot, Sylvie; Martin, Ivan; Blitterswijk, van Clemens A.; Riesle, Jens

    2006-01-01

    Optimizing re-differentiation of clinically relevant cell sources on biomaterial substrates in serum containing (S+) and serum-free (SF) media is a key consideration in scaffold-based articular cartilage repair strategies. We investigated whether the adhesion and post-expansion re-differentiation of

  5. Hyaluronic acid: A boon in periodontal therapy

    Directory of Open Access Journals (Sweden)

    Parveen Dahiya

    2013-01-01

    Full Text Available Hyaluronic acid is a naturally occurring linear polysaccharide of the extracellular matrix of connective tissue, synovial fluid, and other tissues. Its use in the treatment of the inflammatory process is established in medical areas such as orthopedics, dermatology, and ophthalmology. The Pubmed/Medline database was searched for keywords "Hyaluronic acid and periodontal disease" and "Hyaluronic acid and gingivitis" which resulted in 89 and 22 articles respectively. Only highly relevant articles from electronic and manual search in English literature were selected for the present review article. In the field of dentistry, hyaluronic acid has shown anti-inflammatory and anti-bacterial effects in the treatment of periodontal diseases. Due to its tissue healing properties, it could be used as an adjunct to mechanical therapy in the treatment of periodontitis. Further studies are required to determine the clinical efficacy of hyaluronic acid in healing of periodontal lesion. The aim of the present review, article is to discuss the role of hyaluronic acid in periodontal therapy.

  6. Epigenetic reprogramming and re-differentiation of a Ewing sarcoma cell line

    Directory of Open Access Journals (Sweden)

    Joseph Brady Moore IV

    2015-03-01

    Full Text Available Developmental reprogramming techniques have been used to generate induced pluripotent stem (iPS cells from both normal and malignant cells. The derivation of iPS cells from cancer has the potential to provide a unique scientific tool to overcome challenges associated with the establishment of cell lines from primary patient samples and a readily expandable source of cells that may be used to model the initial disease. In the current study we developmentally reprogrammed a metastatic Ewing sarcoma (EWS cell line to a meta-stable embryonic stem (ES-like state sharing molecular and phenotypic features with previously established ES and iPS cell lines. EWS-iPS cells exhibited a pronounced drug resistant phenotype despite persistent expression of the oncogenic EWS-FLI1 fusion transcript. This included resistance to compounds that specifically target downstream effector pathways of EWS-FLI1, such as MAPK/ERK and PI3K/AKT, which play an important role in EWS pathogenesis. EWS-iPS cells displayed tumor initiation abilities in vivo and formed tumors exhibiting characteristic Ewing histopathology. In parallel, EWS-iPS cells re-differentiated in vitro recovered sensitivity to molecularly targeted chemotherapeutic agents, which reiterated pathophysiological features of the cells from which they were derived. These data suggest that EWS-iPS cells may provide an expandable disease model that could be used to investigate processes modulating oncogenesis, metastasis, and chemotherapeutic resistance in EWS.

  7. Fracture risk and zoledronic acid therapy in men with osteoporosis

    DEFF Research Database (Denmark)

    Boonen, Steven; Reginster, Jean-Yves; Kaufman, Jean-Marc

    2012-01-01

    Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis.......Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis....

  8. Hyaluronic Acid: A Boon in Periodontal Therapy

    OpenAIRE

    Parveen Dahiya; Reet Kamal

    2013-01-01

    Hyaluronic acid is a naturally occurring linear polysaccharide of the extracellular matrix of connective tissue, synovial fluid, and other tissues. Its use in the treatment of the inflammatory process is established in medical areas such as orthopedics, dermatology, and ophthalmology. The Pubmed/Medline database was searched for keywords "Hyaluronic acid and periodontal disease" and "Hyaluronic acid and gingivitis" which resulted in 89 and 22 articles respectively. Only highly relevant articl...

  9. 5-Aminolevulinic acid-mediated photodynamic therapy for bladder cancer.

    Science.gov (United States)

    Inoue, Keiji

    2017-02-01

    Photodynamic therapy using 5-aminolevulinic acid is a treatment method in which the fluorescent substance of protoporphyrin IX excessively accumulated specifically in cancer cells is excited by visible red or green light irradiation, and reactive oxygen is produced and injures cancer cells. Photodynamic therapy using 5-aminolevulinic acid less markedly influences the surrounding normal cells and tissue as a result of no accumulation of protoporphyrin IX, being a low-invasive, less harmful treatment localized to cancer. Furthermore, photodynamic therapy using 5-aminolevulinic acid is painless, requiring no anesthesia because localized lesions are treated at a low-energy level, and repeatedly applicable, unlike radiotherapy, and so is expected to be a new low-invasive treatment based on a concept completely different from existing treatments. In fact, photodynamic therapy using 5-aminolevulinic acid for bladder cancer was clinically demonstrated mainly for treatment-resistant bladder carcinoma in situ, and favorable outcomes have been obtained. Photodynamic therapy using 5-aminolevulinic acid are photodynamic technologies based on the common biological characteristic of cancers, and are expected as novel therapeutic strategies for many types of cancer. © 2017 The Japanese Urological Association.

  10. Nucleic acid therapy for lifespan prolongation: Present and future

    Indian Academy of Sciences (India)

    Wing-Fu Lai

    2011-09-01

    Lifespan prolongation is a common desire of the human race. With advances in biotechnology, the mechanism of aging has been gradually unraveled, laying the theoretical basis of nucleic acid therapy for lifespan prolongation. Regretfully, clinically applicable interventions do not exist without the efforts of converting theory into action, and it is the latter that has been far from adequately addressed at the moment. This was demonstrated by a database search on PubMed and Web of Science, from which only seven studies published between 2000 and 2010 were found to directly touch on the development of nucleic acid therapy for anti-aging and/or longevity enhancing purposes. In light of this, the objective of this article is to overview the current understanding of the intimate association between genes and longevity, and to bring the prospect of nucleic acid therapy for lifespan prolongation to light.

  11. Nucleic acid aptamers: an emerging frontier in cancer therapy.

    Science.gov (United States)

    Zhu, Guizhi; Ye, Mao; Donovan, Michael J; Song, Erqun; Zhao, Zilong; Tan, Weihong

    2012-11-04

    The last two decades have witnessed the development and application of nucleic acid aptamers in a variety of fields, including target analysis, disease therapy, and molecular and cellular engineering. The efficient and widely applicable aptamer selection, reproducible chemical synthesis and modification, generally impressive target binding selectivity and affinity, relatively rapid tissue penetration, low immunogenicity, and rapid systemic clearance make aptamers ideal recognition elements for use as therapeutics or for in vivo delivery of therapeutics. In this feature article, we discuss the development and biomedical application of nucleic acid aptamers, with emphasis on cancer cell aptamer isolation, targeted cancer therapy, oncology biomarker identification and drug discovery.

  12. [Use of organic acids in acne and skin discolorations therapy].

    Science.gov (United States)

    Kapuścińska, Alicja; Nowak, Izabela

    2015-03-22

    Acne is one of the most frequent skin disorders that occurs in puberty, but often adults also have acne. The most important factors responsible for acne are elevated production of sebum by hyperactive sebaceous glands and blockage of the follicle because of hyperkeratosis [14]. The third etiopathogenic factor of acne is excessive microflora reproduction [8]. The most significant bacterium that is responsible for formation of skin lesions is Propionibacterium acnes, a rod-shaped Gram-positive and aerotolerant anaerobic bacterium. It is estimated that P. acnes is responsible for acne in approximately 80% of people aged 11 to 30 [27,40]. Even healed skin lesions can often cause skin discolorations and scar formation [51]. Exfoliating chemical substances that are commonly used in dermatology and cosmetology are organic acids. Exfoliating treatment using organic acids is called "chemical peeling" and consists of controlled application of those substances on the skin [38]. The depth of exfoliation depends on organic acid concentration, type of substance and contact time with the skin [41]. Using exfoliating agents seems to be helpful in excessive keratinization - one of several factors responsible for acne. Moreover, epidermis exfoliation is a popular method of removing skin discoloration [22]. Considering chemical structure, exfoliating substances that are most often used in cosmetology contain alpha-hydroxyacids (glycolic acid, lactic acid, mandelic acid and citric acid), beta-hydroxyacids (salicylic acid) and other organic acids, such as trichloroacetic acid and pyruvic acid [47]. In this article, a literature review of use of organic acids in acne and skin discoloration therapy is presented.

  13. Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer

    Directory of Open Access Journals (Sweden)

    El Saghir Nagi S

    2005-12-01

    Full Text Available Abstract Background Zoledronic acid is very widely used in patients with metastatic bone disease and osteoporosis. Only one case of bilateral uveitis was recently reported related to its use. Case presentation We report the first case of severe unilateral anterior uveitis in a patient with breast cancer and an intraocular lens. Following zoledronic acid infusion, the patient developed severe and dramatic right eye pain with decreased visual acuity within 24 hours and was found to have a fibrinous anterior uveitis of moderate severity The patient was treated with topical prednisone and atropine eyedrops and recovered slowly over several months. Conclusion Internists, oncologists, endocrinologists, and ophtalmologists should be aware of uveitis as a possible complication of zoledronic acid therapy. Patients should be instructed to report immediately to their physicians and treatment with topical prednisone and atropine eyedrops should be instituted immediately at the onset of symptoms. This report documents anterior uveitis as a complication of zoledronic acid therapy. This reaction could be an idiosyncratic one but further research may shed more light on the etiology.

  14. Glycolic acid peel therapy – a current review

    Science.gov (United States)

    Sharad, Jaishree

    2013-01-01

    Chemical peels have been time-tested and are here to stay. Alpha-hydroxy peels are highly popular in the dermatologist’s arsenal of procedures. Glycolic acid peel is the most common alpha-hydroxy acid peel, also known as fruit peel. It is simple, inexpensive, and has no downtime. This review talks about various studies of glycolic acid peels for various indications, such as acne, acne scars, melasma, postinflammatory hyperpigmentation, photoaging, and seborrhea. Combination therapies and treatment procedure are also discussed. Careful review of medical history, examination of the skin, and pre-peel priming of skin are important before every peel. Proper patient selection, peel timing, and neutralization on-time will ensure good results, with no side effects. Depth of the glycolic acid peel depends on the concentration of the acid used, the number of coats applied, and the time for which it is applied. Hence, it can be used as a very superficial peel, or even a medium depth peel. It has been found to be very safe with Fitzpatrick skin types I–IV. All in all, it is a peel that is here to stay. PMID:24399880

  15. Hydroxamic acid - A novel molecule for anticancer therapy

    Directory of Open Access Journals (Sweden)

    Dilipkumar Pal

    2012-01-01

    Full Text Available Hydroxamic acid is a potent moiety not only in the field of cancer therapy but also as a mutagenic agent. Among the various derivatives of hydroxamic acid, SAHA (Suberoylanilide Hydroxamic Acid is considered as a potent anticancer agent. Scientists from the different corner synthesized different hydroxamic acid moieties with some straight chain oxazole, thiadiazole, biphenyl moieties in the terminal position. Acetylation and deacetylation of histones of the core proteins of nucleosomes in chromatin play an important role in the regulation of gene expression. The level of acetylation of histones is established and maintained by two classes of enzymes, histone acetyltransferase and histone deacetylases, which have been identified as transcriptional coactivators and transcriptional corepressors, respectively. There is increasing evidence that aberrant histone acetylation has been linked to various malignant diseases. Great efforts are currently underway for the design of more potent and less toxic candidates for the treatment of cancer. In recent years, hydroxamic acid derivatives have attracted increasing attention for their potential as highly efficacious in combating various etiological factors associated with cancer. Our main intention to draw an attention is that this single functional moiety has not only fit in the receptor but also create a diversified activity.

  16. Glycolic acid peel therapy – a current review

    Directory of Open Access Journals (Sweden)

    Sharad J

    2013-11-01

    Full Text Available Jaishree Sharad Skinfiniti Aesthetic Skin and Laser Clinic, Mumbai, India Abstract: Chemical peels have been time-tested and are here to stay. Alpha-hydroxy peels are highly popular in the dermatologist's arsenal of procedures. Glycolic acid peel is the most common alpha-hydroxy acid peel, also known as fruit peel. It is simple, inexpensive, and has no downtime. This review talks about various studies of glycolic acid peels for various indications, such as acne, acne scars, melasma, postinflammatory hyperpigmentation, photoaging, and seborrhea. Combination therapies and treatment procedure are also discussed. Careful review of medical history, examination of the skin, and pre-peel priming of skin are important before every peel. Proper patient selection, peel timing, and neutralization on-time will ensure good results, with no side effects. Depth of the glycolic acid peel depends on the concentration of the acid used, the number of coats applied, and the time for which it is applied. Hence, it can be used as a very superficial peel, or even a medium depth peel. It has been found to be very safe with Fitzpatrick skin types I–IV. All in all, it is a peel that is here to stay. Keywords: acne scar, melasma, photoaging, chemical peel, alpha-hydroxy peel

  17. Prescribing of acid suppressive therapy: interactions between hospital and primary care

    DEFF Research Database (Denmark)

    Krag, Aleksander; Teglbjerg, LS; Malchow-Moller, A

    2006-01-01

    BACKGROUND: Overuse of acid suppressive therapy in the hospital setting and in primary care is well documented. AIM: To describe interactions between prescriptions of acid suppressive therapy in hospital and in primary care. METHODS: All patients admitted to hospital over a 24-month period were...... suppressive therapy within the following 12 months. Of all subjects treated with acid suppressive therapy in the hospital catchment area, 7.8% were seen in our department. CONCLUSIONS: Decisions about acid suppressive therapy prescribing in hospital has little influence on prescribing in primary care....

  18. Herbert Falk: a vital force in the renaissance of bile acid research and bile acid therapy.

    Science.gov (United States)

    Hofmann, Alan F

    2011-01-01

    Herbert Falk died on August 8, 2008, after a long illness. It was his vision that initiated the Bile Acid Meetings and brought to market chenodeoxycholic acid and ursodeoxycholic acid for the dissolution of cholesterol gallstones as well as the successful treatment of cholestatic liver disease. The 1st Bile Acid Meeting was a small workshop held at the University Hospital of Freiburg in 1970. Great interest in the topic was evident at that small meeting and led to a larger meeting in 1972, whose scope included both the basic and clinical aspects of bile acids. These meetings have continued at biennial intervals, the 2010 meeting being the 21st. The program has always included discussions of the most fundamental aspects of bile acid biosynthesis and metabolism as well as clinical applications of bile acid therapy. The meetings featured brief presentations, ample time for discussion, and imaginative social programs. They have always been flawlessly organized. Social programs usually included a hike through the beautiful countryside of the Black Forest followed by dinner in a rustic restaurant. Herbert Falk took part in these programs, personally welcoming every participant. In the warm glow of the 'Badische' hospitality, friendships developed, and scientific collaborations were often arranged. From a scientific standpoint, there has been enormous progress in understanding the chemistry and biology of bile acids. Herbert Falk established the Windaus Prize in 1978, and the prize has been given to individuals whose contributions moved the field forward. These bile acid meetings have been marvelous, rewarding experiences. We must all be grateful to Herbert Falk's vision in establishing the Falk Foundation that has so generously sponsored these meetings. We also express our gratitude to his widow, Ursula Falk, who continues this worthy tradition.

  19. Nucleic Acid-Based Therapy Approaches for Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Tatyana Vagner

    2012-01-01

    Full Text Available Huntington's disease (HD is caused by a dominant mutation that results in an unstable expansion of a CAG repeat in the huntingtin gene leading to a toxic gain of function in huntingtin protein which causes massive neurodegeneration mainly in the striatum and clinical symptoms associated with the disease. Since the mutation has multiple effects in the cell and the precise mechanism of the disease remains to be elucidated, gene therapy approaches have been developed that intervene in different aspects of the condition. These approaches include increasing expression of growth factors, decreasing levels of mutant huntingtin, and restoring cell metabolism and transcriptional balance. The aim of this paper is to outline the nucleic acid-based therapeutic strategies that have been tested to date.

  20. Omega-3 fatty acids as adjunctive therapy in Crohns disease.

    Science.gov (United States)

    Macdonald, Angie

    2006-01-01

    Crohns disease is an inflammatory bowel disease that can have a significant impact on the health of those afflicted. The etiology of the disease is unknown, but genetic, environmental, dietary, and immunological factors are thought to be involved. Multiple nutrients can become depleted during active disease due to inadequate intake or malabsorption. Preventing these deficiencies is paramount in the care of those suffering from Crohns disease. Often the traditional treatments (medications) have limited effectiveness and negative side effects that inhibit their use. Enteral nutrition has promising therapeutic benefits, but its use is often limited to the pediatric population due to poor patient acceptability. Omega-3 fatty acids have been investigated for their anti-inflammatory properties as an alternative to traditional care. This article reviews the etiology of Crohns disease, nutritional deficiencies, traditional treatments, and the use of omega-3 fatty acids in the prevention of Crohns recurrence. The results from clinical trials have been conflicting, but a new fish oil preparation that limits the side effects of traditional fish oil therapy shows promise as an adjunctive treatment for Crohns disease. Continued research is needed to validate these findings.

  1. Synoviocyte Derived-Extracellular Matrix Enhances Human Articular Chondrocyte Proliferation and Maintains Re-Differentiation Capacity at Both Low and Atmospheric Oxygen Tensions.

    Directory of Open Access Journals (Sweden)

    Thomas J Kean

    Full Text Available Current tissue engineering methods are insufficient for total joint resurfacing, and chondrocytes undergo de-differentiation when expanded on tissue culture plastic. De-differentiated chondrocytes show poor re-differentiation in culture, giving reduced glycosaminoglycan (GAG and collagen matrix accumulation. To address this, porcine synoviocyte-derived extracellular matrix and low (5% oxygen tension were assessed for their ability to enhance human articular chondrocyte expansion and maintain re-differentiation potential.Porcine synoviocyte matrices were devitalized using 3 non-detergent methods. These devitalized synoviocyte matrices were compared against tissue culture plastic for their ability to support human chondrocyte expansion. Expansion was further compared at both low (5%, and atmospheric (20% oxygen tension on all surfaces. Expanded cells then underwent chondrogenic re-differentiation in aggregate culture at both low and atmospheric oxygen tension. Aggregates were assessed for their GAG and collagen content both biochemically and histologically.Human chondrocytes expanded twice as fast on devitalized synoviocyte matrix vs. tissue culture plastic, and cells retained their re-differentiation capacity for twice the number of population doublings. There was no significant difference in growth rate between low and atmospheric oxygen tension. There was significantly less collagen type I, collagen type II, aggrecan and more MMP13 expression in cells expanded on synoviocyte matrix vs. tissue culture plastic. There were also significant effects due to oxygen tension on gene expression, wherein there was greater collagen type I, collagen type II, SOX9 and less MMP13 expression on tissue culture plastic compared to synoviocyte matrix. There was a significant increase in GAG, but not collagen, accumulation in chondrocyte aggregates re-differentiated at low oxygen tension over that achieved in atmospheric oxygen conditions

  2. Efficacy of 5-Aminolevulinic Acid Photodynamic Therapy in treatment of nasal inverted papilloma.

    Science.gov (United States)

    Zhang, Yunjie; Yang, Yuguang; Zou, Xianbiao

    2013-12-01

    Evaluate the efficacy of 5-Aminolevulinic Acid Photodynamic Therapy (PDT) in medical treatment of nasal inverted papilloma (NIP). Three patients with nasal inverted papilloma were treated with 5-Aminolevulinic Acid Photodynamic Therapy at our department from April to September 2012. The efficacy and adverse effects of 5-Aminolevulinic Acid Photodynamic Therapy were evaluated during 6-8 months of follow-up medical examination. After treated with 5-Aminolevulinic Acid Photodynamic Therapy, the nasal inverted papillomas were removed. No recurrence was found during the 6-8 months of follow-up medical examination. The major adverse effects were mild erosion, pain, and exudation. 5-Aminolevulinic Acid Photodynamic Therapy appears to be an effective treatment of nasal inverted papilloma. It can clear the papilloma lesions and is well tolerated by the patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells

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    Shuichi Kitayama

    2016-02-01

    Full Text Available Vα24 invariant natural killer T (iNKT cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer. Conversely, reduced iNKT cell numbers and function have been observed in many patients with cancer. To recover these numbers, we reprogrammed human iNKT cells to pluripotency and then re-differentiated them into regenerated iNKT cells in vitro through an IL-7/IL-15-based optimized cytokine combination. The re-differentiated iNKT cells showed proliferation and IFN-γ production in response to α-galactosylceramide, induced dendritic cell maturation and downstream activation of both cytotoxic T lymphocytes and NK cells, and exhibited NKG2D- and DNAM-1-mediated NK cell-like cytotoxicity against cancer cell lines. The immunological features of re-differentiated iNKT cells and their unlimited availability from induced pluripotent stem cells offer a potentially effective immunotherapy against cancer.

  4. Comparative study of trichloroacetic acid vs. photodynamic therapy with topical 5-aminolevulinic acid for actinic keratosis of the scalp.

    Science.gov (United States)

    Di Nuzzo, Sergio; Cortelazzi, Chiara; Boccaletti, Valeria; Zucchi, Alfredo; Conti, Maria Luisa; Montanari, Paola; Feliciani, Claudio; Fabrizi, Giuseppe; Pagliarello, Calogero

    2015-09-01

    Photodynamic therapy with 5-methyl-aminolevulinate and photodynamic therapy with trichloroacetic acid 50% are the two techniques utilized in the management of actinic keratosis. This study was planned to compare the efficacy, adverse effects, recurrence and cosmetic outcome of these option therapies in patients with multiple actinic keratosis of the scalp. Thirteen patients with multiple actinic keratosis were treated with one of the two treatments on half of the scalp at baseline, while the other treatment was performed on the other half 15 days apart, randomly. Efficacy, adverse effects, cosmetic outcome and recurrence were recorded at follow-up visit at 1, 3, 6 and 12 months. Photodynamic therapy with 5 methyl-aminolevulinate was more effective than trichloroacetic acid although less tolerated by patients as it was more painful. Early adverse effects were almost the same even if trichloroacetic acid leads also to crust formation and to a worse cosmetic outcome characterized by hypopigmentation. Recurrence was lower in the area treated with photodynamic therapy. Trichloroacetic acid 50% is less effective than photodynamic therapy with 5 methyl-aminolevulinate in the treatment of multiple actinic keratosis of the scalp although better tolerated by patients. As this technique is less painful and less expensive than photodynamic therapy, we hypothesize and suggest that more sequential treatments could lead to better results. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic levels in postmenopausal women

    NARCIS (Netherlands)

    Giltay, E.J.; Duschek, E.J.J.; Katan, M.B.; Neele, S.J.; Netelenbos, J.C.; Zock, P.L.

    2004-01-01

    Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized, double-blin

  6. Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic levels in postmenopausal women

    NARCIS (Netherlands)

    Giltay, E.J.; Duschek, E.J.J.; Katan, M.B.; Neele, S.J.; Netelenbos, J.C.; Zock, P.L.

    2004-01-01

    Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized,

  7. Bile acid signaling in metabolic disease and drug therapy.

    Science.gov (United States)

    Li, Tiangang; Chiang, John Y L

    2014-10-01

    Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid-activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein-coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver.

  8. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy

    DEFF Research Database (Denmark)

    Reimer, Christina; Søndergaard, Bo; Hilsted, Linda

    2009-01-01

    BACKGROUND & AIMS: Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). If RAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications. METHODS: A randomized, double-blind, placebo...... dyspepsia, heartburn, or acid regurgitation in the PPI group was 13 of 59 (22%) at week 10, 13 of 59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). CONCLUSIONS: PPI therapy...

  9. Antifungal mechanisms supporting boric acid therapy of Candida vaginitis.

    Science.gov (United States)

    De Seta, Francesco; Schmidt, Martin; Vu, Bao; Essmann, Michael; Larsen, Bryan

    2009-02-01

    Boric acid is a commonly cited treatment for recurrent and resistant yeast vaginitis, but data about the extent and mechanism of its antifungal activity are lacking. The aim of this study was to use in vitro methods to understand the spectrum and mechanism of boric acid as a potential treatment for vaginal infection. Yeast and bacterial isolates were tested by agar dilution to determine the intrinsic antimicrobial activity of boric acid. Established microbial physiology methods illuminated the mechanism of the action of boric acid against Candida albicans. C. albicans strains (including fluconazole-resistant strains) were inhibited at concentrations attainable intravaginally; as were bacteria. Broth dilution MICs were between 1563 and 6250 mg/L and boric acid proved fungistatic (also reflected by a decrease in CO(2) generation); prolonged culture at 50,000 mg/L was fungicidal. Several organic acids in yeast nitrogen broth yielded a lower pH than equimolar boric acid and sodium borate but were less inhibitory. Cold or anaerobic incubation protected yeast at high boric acid concentrations. Cells maintained integrity for 6 h in boric acid at 37 degrees C, but after 24 h modest intrusion of propidium iodide occurred; loss of plate count viability preceded uptake of vital stain. Growth at sub-MIC concentrations of boric acid decreased cellular ergosterol. The drug efflux pump CDR1 did not protect Candida as CDR1 expression was abrogated by boric acid. Boric acid interfered with the development of biofilm and hyphal transformation. Boric acid is fungistatic to fungicidal depending on concentration and temperature. Inhibition of oxidative metabolism appears to be a key antifungal mechanism, but inhibition of virulence probably contributes to therapeutic efficacy in vivo.

  10. Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients

    DEFF Research Database (Denmark)

    Lødrup, A; Pottegård, A; Hallas, J

    2015-01-01

    BACKGROUND: Guidelines recommend that patients with gastro-oesophageal reflux disease are adequately treated with acid-suppressive therapy before undergoing anti-reflux surgery. Little is known of the use of acid-suppressive drugs before anti-reflux surgery. AIM: To determine the use of proton pump...

  11. Nucleic Acid Therapy: from humble beginnings a dynamic technology

    CSIR Research Space (South Africa)

    Millroy, L

    2011-02-01

    Full Text Available The term “nucleic acid therapy” encompasses a wide range of technologies for the treatment of a range of plant and animal ailments. As the name implies, it makes use of nucleic acid (either DNA or RNA) as a therapeutic agent. There are six branches...

  12. Serum uric acid levels and hormone therapy type: a retrospective cohort study of postmenopausal women.

    Science.gov (United States)

    Jung, Jae H; Song, Gwan G; Lee, Young H; Kim, Jae-Hoon; Hyun, Myung H; Choi, Sung J

    2017-08-07

    Serum uric acid levels increase in postmenopausal women, but decrease when hormone therapy (HT) is administered. No study has, however, evaluated the effects of different types of HT on serum uric acid levels. We therefore examined whether estrogen therapy (ET), estrogen plus progestogen therapy (EPT), and tibolone use affected serum uric acid levels in this population. We performed a retrospective cohort study of postmenopausal women. From 2005 to 2015, postmenopausal women who had undergone blood uric acid-level testing at least twice were enrolled. Participants were grouped according to HT regimen: ET, EPT, or tibolone. The nonhormone therapy group did not receive HT. Differences in serum uric acid levels were examined in each group. Our analysis was adjusted to accommodate different follow-up intervals for individual participants. Multiple variables were adjusted using the Tukey-Kramer method. Age, body mass index, hypertension, diabetes mellitus, dyslipidemia, estimated glomerular filtration rate, alcohol consumption, smoking status, and comedications were also adjusted. After adjusting for multiple variables, the serum uric acid level increased to 0.87 ± 0.27 mg/dL (least squares mean ± standard error) in the nonhormone therapy group, and serum uric levels in the EPT group were found to be significantly lower (-0.38 ± 0.29 mg/dL, P uric acid levels in the ET and tibolone groups did not, however, differ significantly from the nonhormone therapy group level. We attribute our findings to the effects of progestogen, rather than estrogen.

  13. Multifunctional combinatorial-designed nanoparticles for nucleic acid therapy

    Science.gov (United States)

    Amiji, Mansoor M.

    2016-05-01

    Recent advances in biomedical sciences, especially in the field of human genetics, is increasingly considered to facilitate a new frontier in development of novel disease-modifying therapeutics. One of major challenges in the development of nucleic acid therapeutics is efficient and specific delivery of the molecules to the target tissue and cell upon systemic administration. In this report, I discuss our strategy to develop combinatorial-designed multifunctional nanoparticle assemblies based on natural biocompatible and biodegradable polymers for nucleic acid delivery in: (1) overcoming tumor drug resistance and (2) genetic modulation of macrophage functional phenotype from M1 to M2 in treatment of inflammatory diseases.

  14. Solutions for therapy-resistant warts. Squaric acid dibutylester (SADBE)

    NARCIS (Netherlands)

    Van Roon, E.N.; Schootstra, R.; Blanken, R.

    2002-01-01

    Squaric acid dibutylester (SADBE) is a strongly sensitizing compound, activating the immune system by inducing a type 4 hypersensitivity reaction. SADBE has been applied in the treatment of alopecia areate and resistant warts. From the results of clinical trials in children and adults the use of

  15. Mucosal Vaccination and Therapy with Genetically Modified Lactic Acid Bacteria

    NARCIS (Netherlands)

    Wells, J.

    2011-01-01

    Lactic acid bacteria (LAB) have proved to be effective mucosal delivery vehicles that overcome the problem of delivering functional proteins to the mucosal tissues. By the intranasal route, both live and killed LAB vaccine strains have been shown to elicit mucosal and systemic immune responses that

  16. Acetylsalicylic acid as an adjuvant therapy for schizophrenia

    NARCIS (Netherlands)

    Laan, Wijnand; Selten, Jean-Paul; Kahn, Rene S.; Huisman, Anne-Margriet; Heijnen, Cobi J.; Grobbee, Diederick E.; Burger, Huibert

    2006-01-01

    Background: Findings from both epidemiological and basic research point to the possibility that NSAIDS impede the deterioration in schizophrenia. Methods: To study the efficacy of acetylsalicylic acid we will perform a randomized placebo controlled double- blind add- on trial of 80 inpatients and ou

  17. Mucosal Vaccination and Therapy with Genetically Modified Lactic Acid Bacteria

    NARCIS (Netherlands)

    Wells, J.

    2011-01-01

    Lactic acid bacteria (LAB) have proved to be effective mucosal delivery vehicles that overcome the problem of delivering functional proteins to the mucosal tissues. By the intranasal route, both live and killed LAB vaccine strains have been shown to elicit mucosal and systemic immune responses that

  18. Place of hyaluronic acid preparations in therapy for osteoarthrosis

    Directory of Open Access Journals (Sweden)

    R. M. Balabanova

    2014-01-01

    Full Text Available The paper gives data on the positive role of hyaluronic acid (HA preparations in the treatment of knee and hip osteoarthrosis (OA. The clinical effect of intraarticular agents is not only due to their lumbricative, but also, to a greater degree, anti-inflammatory and chondroprotective activities. The efficacy of HA preparations do not practically depend on their molecular weight. Long-term HA cycles can delay the risk of joint replacement in OA.

  19. Place of hyaluronic acid preparations in therapy for osteoarthrosis

    OpenAIRE

    R. M. Balabanova

    2014-01-01

    The paper gives data on the positive role of hyaluronic acid (HA) preparations in the treatment of knee and hip osteoarthrosis (OA). The clinical effect of intraarticular agents is not only due to their lumbricative, but also, to a greater degree, anti-inflammatory and chondroprotective activities. The efficacy of HA preparations do not practically depend on their molecular weight. Long-term HA cycles can delay the risk of joint replacement in OA.

  20. Uric Acid as a Target of Therapy in CKD

    Science.gov (United States)

    Jalal, Diana I.; Chonchol, Michel; Chen, Wei; Targher, Giovanni

    2012-01-01

    The prevalence of chronic kidney disease (CKD) has risen and will continue to rise in the United States and worldwide. This is alarming considering that CKD remains an irreversible condition and patients who progress to chronic kidney failure suffer reduced quality of life and high mortality rates. As such, it is imperative to identify modifiable risk factors to develop strategies to slow CKD progression. One such factor is hyperuricemia. Recent observational studies have associated hyperuricemia with kidney disease. In addition, hyperuricemia is largely prevalent in patients with CKD. Data from experimental studies have revealed several potential mechanisms by which hyperuricemia may contribute to the development and progression of CKD. In this manuscript we offer a critical review of the experimental evidence linking hyperuricemia to CKD, we highlight the gaps in our knowledge on the topic as it stands today, and we review the observational and interventional studies that have examined the potential nephro-protective effect of lowering uric acid in CKD patients . While uric acid may also be linked to cardiovascular disease and mortality in patients with CKD, this review will focus only on uric acid as a potential therapeutic target to prevent kidney disease onset and progression. PMID:23058478

  1. Molecular targeting of acid ceramidase: implications to cancer therapy.

    Science.gov (United States)

    Zeidan, Youssef H; Jenkins, Russell W; Korman, John B; Liu, Xiang; Obeid, Lina M; Norris, James S; Hannun, Yusuf A

    2008-08-01

    Increasingly recognized as bioactive molecules, sphingolipids have been studied in a variety of disease models. The impact of sphingolipids on cancer research facilitated the entry of sphingolipid analogues and enzyme modulators into clinical trials. Owing to its ability to regulate two bioactive sphingolipids, ceramide and sphingosine-1-phosphate, acid ceramidase (AC) emerges as an attractive target for drug development within the sphingolipid metabolic pathway. Indeed, there is extensive evidence supporting a pivotal role for AC in lipid metabolism and cancer biology. In this article, we review the current knowledge of the biochemical properties of AC, its relevance to tumor promotion, and its molecular targeting approaches.

  2. High serum palmitic acid is associated with low antiviral effects of interferon-based therapy for hepatitis C virus.

    Science.gov (United States)

    Miyake, Teruki; Hiasa, Yoichi; Hirooka, Masashi; Tokumoto, Yoshio; Watanabe, Takao; Furukawa, Shinya; Ueda, Teruhisa; Yamamoto, Shin; Kumagi, Teru; Miyaoka, Hiroaki; Abe, Masanori; Matsuura, Bunzo; Onji, Morikazu

    2012-11-01

    Hepatitis C virus (HCV) infection alters fatty acid synthesis and metabolism in association with HCV replication. The present study examined the effect of serum fatty acid composition on interferon (IFN)-based therapy. Fifty-five patients with HCV were enrolled and received IFN-based therapy. Patient characteristics, laboratory data (including fatty acids), and viral factors that could be associated with the anti-HCV effects of IFN-based therapy were evaluated. The effects of individual fatty acids on viral replication and IFN-based therapy were also examined in an in-vitro system. Multivariate logistic regression analysis showed that the level of serum palmitic acid before treatment and HCV genotype were significant predictors for rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR). High levels of palmitic acid inhibited the anti-HCV effects of IFN-based therapy. HCV replication assays confirmed the inhibitory effects of palmitic acid on anti-HCV therapy. The concentration of serum palmitic acid is an independent predictive factor for RVR, EVR, and SVR in IFN-based antiviral therapy. These results suggest that the effect of IFN-based antiviral therapy in patients with HCV infection might be enhanced by treatment that modulates palmitic acid levels.

  3. Photodynamic therapy with 5-aminolevulinic acid: basic principles and applications

    Science.gov (United States)

    Pottier, Roy H.; Kennedy, James C.

    1996-01-01

    Numerous photosensitizing pigments that absorb visible light and are selectively retained in neoplastic tissue are being investigated as potential photochemotherapeutic agents. While much emphasis is being placed on the synthesis of new, far-red absorbing photosensitizers, an alternative approach has been to stimulate the human body to produce its own natural photosensitizer, namely protoporphyrin IX (PpIX). Exogenous 5-aminolevulinic acid (ALA) is rapidly bioconverted into PP by mitochondria, the process being particularly efficient in tumor cells. Since PpIX has a natural and rapid clearing mechanism (via the capture of iron in the process of being converted into heme), ALA-PDT does not suffer from lingering skin phototoxicity. ALA may be introduced orally, intravenously, or topically, and ALA-PDT has been shown to be effective in the treatment of both malignant and non-malignant lesions.

  4. Graphene Oxide-Gallic Acid Nanodelivery System for Cancer Therapy

    Science.gov (United States)

    Dorniani, Dena; Saifullah, Bullo; Barahuie, Farahnaz; Arulselvan, Palanisamy; Hussein, Mohd Zobir Bin; Fakurazi, Sharida; Twyman, Lance J.

    2016-11-01

    Despite the technological advancement in the biomedical science, cancer remains a life-threatening disease. In this study, we designed an anticancer nanodelivery system using graphene oxide (GO) as nanocarrier for an active anticancer agent gallic acid (GA). The successful formation nanocomposite (GOGA) was characterized using XRD, FTIR, HRTEM, Raman, and UV/Vis spectroscopy. The release study shows that the release of GA from the designed anticancer nanocomposite (GOGA) occurs in a sustained manner in phosphate-buffered saline (PBS) solution at pH 7.4. In in vitro biological studies, normal fibroblast (3T3) and liver cancer cells (HepG2) were treated with different concentrations of GO, GOGA, and GA for 72 h. The GOGA nanocomposite showed the inhibitory effect to cancer cell growth without affecting normal cell growth. The results of this research are highly encouraging to go further for in vivo studies.

  5. The influence of Helicobacter pylori on oesophageal acid exposure in GERD during acid suppressive therapy

    NARCIS (Netherlands)

    Peters, FTM; Kuipers, EJ; Ganesh, S; Sluiter, WJ; Klinkenberg-Knol, EC; Lamers, CBHW; Kleibeuker, JH

    Background: Helicobacter pylori exaggerates the effect of acid suppressive drugs on intragastric pH. It is unknown whether this is relevant for the treatment of GERD. Aim: To compare oesophageal acid exposure and symptoms in H. pylori-negative and H. pylori-positive GERD patients during low and

  6. The influence of Helicobacter pylori on oesophageal acid exposure in GERD during acid suppressive therapy

    NARCIS (Netherlands)

    Peters, FTM; Kuipers, EJ; Ganesh, S; Sluiter, WJ; Klinkenberg-Knol, EC; Lamers, CBHW; Kleibeuker, JH

    1999-01-01

    Background: Helicobacter pylori exaggerates the effect of acid suppressive drugs on intragastric pH. It is unknown whether this is relevant for the treatment of GERD. Aim: To compare oesophageal acid exposure and symptoms in H. pylori-negative and H. pylori-positive GERD patients during low and prof

  7. Evaluation of fusidic acid in therapy of experimental Staphylococcus aureus meningitis

    DEFF Research Database (Denmark)

    Østergaard, Christian; Yieng-Kow, Runa Vavia; Knudsen, Jenny Dahl

    2003-01-01

    Combination therapy that includes fusidic acid, an antimicrobial agent highly active against staphylococci, has been recommended in the treatment of patients with Staphylococcus aureus meningitis. The aim of this study was to evaluate the pharmacokinetic, CSF bactericidal and anti-inflammatory pr...

  8. Photodynamic therapy with 5-aminolaevulinic acid or placebo for recalcitrant foot and hand warts

    DEFF Research Database (Denmark)

    Stender, I M; Na, R; Fogh, H

    2000-01-01

    Photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (ALA) followed by irradiation with incoherent light (ALA-PDT) for recalcitrant warts have had beneficial results. Therefore, we undertook a randomised, parallel, double-blind clinical trial of ALA-PDT versus placeboPDT for recalcitrant...... foot and hand warts....

  9. Coating nanocarriers with hyaluronic acid facilitates intravitreal drug delivery for retinal gene therapy

    NARCIS (Netherlands)

    Martens, T.F.; Remaut, K.; Deschout, H.; Engbersen, Johannes F.J.; Hennink, W.E.; van Steenbergen, M.J.; Demeester, J.; de Smedt, S.C.; Braeckmans, K.

    2015-01-01

    Retinal gene therapy could potentially affect the lives of millions of people suffering from blinding disorders. Yet, one of the major hurdles remains the delivery of therapeutic nucleic acids to the retinal target cells. Due to the different barriers that need to be overcome in case of topical or

  10. Inherited Retinal Disease Therapies Targeting Precursor Messenger Ribonucleic Acid

    Directory of Open Access Journals (Sweden)

    Di Huang

    2017-09-01

    Full Text Available Inherited retinal diseases are an extremely diverse group of genetically and phenotypically heterogeneous conditions characterized by variable maturation of retinal development, impairment of photoreceptor cell function and gradual loss of photoreceptor cells and vision. Significant progress has been made over the last two decades in identifying the many genes implicated in inherited retinal diseases and developing novel therapies to address the underlying genetic defects. Approximately one-quarter of exonic mutations related to human inherited diseases are likely to induce aberrant splicing products, providing opportunities for the development of novel therapeutics that target splicing processes. The feasibility of antisense oligomer mediated splice intervention to treat inherited diseases has been demonstrated in vitro, in vivo and in clinical trials. In this review, we will discuss therapeutic approaches to treat inherited retinal disease, including strategies to correct splicing and modify exon selection at the level of pre-mRNA. The challenges of clinical translation of this class of emerging therapeutics will also be discussed.

  11. Hyaluronic acid ion-pairing nanoparticles for targeted tumor therapy.

    Science.gov (United States)

    Li, Wenhao; Yi, Xiaoli; Liu, Xing; Zhang, Zhirong; Fu, Yao; Gong, Tao

    2016-03-10

    Hyaluronic acid (HA)-based doxorubicin (DOX) nanoparticles (HA-NPs) were fabricated via ion-pairing between positively charged DOX and negatively charged HA, which displayed near-spherical shapes with an average size distribution of 180.2nm (PDI=0.184). Next, HA-NPs were encapsulated in liposomal carriers to afford HA-based DOX liposomes (HA-LPs), which also showed near-spherical morphology with an average size of 130.5nm (PDI=0.201). HA-NPs and HA-LPs displayed desirable sustained-release profiles compared to free DOX, and moreover, HA-LPs were proven to prevent premature release of DOX from HA-NPs. Cell based studies demonstrated HA-NPs and HA-LPs were selectively taken up by CD44(+) tumor cells, and DOX was released intracellularly to target the cell nuclei. Both HA-NPs and HA-LPs showed comparable levels of penetration efficiency in tumor spheroids. In vivo studies revealed that HA-NPs and HA-LPs significantly prolonged the blood circulation time of DOX, decreased accumulation in the normal tissues and enriched drugs into the tumors. Furthermore, HA-NPs and HA-LPs greatly enhanced therapeutic efficacy of DOX in tumor-bearing mice and minimized systemic toxicity against vital organs. In sum, HA-NPs and HA-LPs represent promising nanocarriers for CD44(+) tumor-targeted delivery.

  12. Polymeric microcapsules poduction from sodium alginic acid for cell therapy

    Directory of Open Access Journals (Sweden)

    Ana Carolina Vale Campos Lisboa

    2007-12-01

    Full Text Available Development of polymeric materials has been increasingly emphasized in Biomedicine. Here, we evaluate the use of microcapsules made of Biodritin®, a biocompatible polymer compound which contains sodium alginic acid, a natural polymer extracted from algae, and Cis-Chondroitin sulfate, a glycosaminoglycan from the extracellular matrix. Gelation of this polymer into microcapsules is achieved by dropping the compound into BaCl2 or CaCl2 gelling solutions. A functional microcapsule is dependent on its permeability, mechanical stability, immunoisolation capacity and biocompatibility. The mechanical stability of Biodritin-barium and Biodritin-calcium microcapsules was investigated after rotational stress upon in vitro culture and in vivo implantation. Viability studies of encapsulated cells were also performed to assess other functional parameters of the microcapsules. When subject to rotational stress, Biodritin-barium microcapsules exhibited breaks, whereas the Biodritin-calcium microcapsules did not. Both kinds of Biodritin® microcapsules proved to be mechanically resistant in in vitro and in vivo studies. However, the Biodritin-calcium material was found to be more elastic while the Biodritin-barium microcapsules displayed a more plastic behavior. These properties seem to be determinant for viability of the encapsulated cell’s, since the Biodritin-calcium microcapsules presented more viable cells than the Biodritin-barium microcapsules.

  13. Preclinical Evaluation of Bioabsorbable Polyglycolic Acid Spacer for Particle Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Akasaka, Hiroaki [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Hyogo Japan (Japan); Sasaki, Ryohei, E-mail: rsasaki@med.kobe-u.ac.jp [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Hyogo Japan (Japan); Miyawaki, Daisuke; Mukumoto, Naritoshi; Sulaiman, Nor Shazrina Binti [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Hyogo Japan (Japan); Nagata, Masaaki [Division of Gastroenterology, Kobe University Graduate School of Medicine, Hyogo Japan (Japan); Yamada, Shigeru [Research Center Hospital, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Murakami, Masao [Radiation Oncology Center, Dokkyo Medical University, Tochigi (Japan); Demizu, Yusuke [Department of Radiology, Hyogo Ion Beam Medical Center, Hyogo (Japan); Fukumoto, Takumi [Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Hyogo Japan (Japan)

    2014-12-01

    Purpose: To evaluate the efficacy and safety of a polyglycolic acid (PGA) spacer through physical and animal experiments. Methods and Materials: The spacer was produced with surgical suture material made of PGA, forming a 3-dimensional nonwoven fabric. For evaluation or physical experiments, 150-MeV proton or 320-MeV carbon-ion beams were used to generate 60-mm width of spread-out Bragg peak. For animal experiments, the abdomens of C57BL/6 mice, with or without the inserted PGA spacers, were irradiated with 20 Gy of carbon-ion beam (290 MeV) using the spread-out Bragg peak. Body weight changes over time were scored, and radiation damage to the intestine was investigated using hematoxylin and eosin stain. Blood samples were also evaluated 24 days after the irradiation. Long-term thickness retention and safety were evaluated using crab-eating macaques. Results: No chemical or structural changes after 100 Gy of proton or carbon-ion irradiation were observed in the PGA spacer. Water equivalency of the PGA spacer was equal to the water thickness under wet condition. During 24 days' observation after 20 Gy of carbon-ion irradiation, the body weights of mice with the PGA spacer were relatively unchanged, whereas significant weight loss was observed in those mice without the PGA spacer (P<.05). In mice with the PGA spacer, villus and crypt structure were preserved after irradiation. No inflammatory reactions or liver or renal dysfunctions due to placement of the PGA spacer were observed. In the abdomen of crab-eating macaques, thickness of the PGA spacer was maintained 8 weeks after placement. Conclusions: The absorbable PGA spacer had water-equivalent, bio-compatible, and thickness-retaining properties. Although further evaluation is warranted in a clinical setting, the PGA spacer may be effective to stop proton or carbon-ion beams and to separate normal tissues from the radiation field.

  14. Allergic contact dermatitis to 5-aminolaevulinic acid methylester but not to 5-aminolaevulinic acid after photodynamic therapy.

    Science.gov (United States)

    Wulf, H C; Philipsen, P

    2004-01-01

    We report a patient with an allergy induced by photodynamic therapy (PDT) following simultaneous treatment with both 5-aminolaevulinic acid (ALA) and ALA methylester (ALA-ME). After several PDT treatments the patient presented with acute eczema of the treated areas and itch and hyper-reactivity of the untreated skin. Patch testing demonstrated a strong +++ reaction to ALA-ME only, indicating that derivatives common to ALA and ALA-ME were not involved. This is the first case of allergy to ALA-ME.

  15. Addition of omega-3 carboxylic acids to statin therapy in patients with persistent hypertriglyceridemia.

    Science.gov (United States)

    Davidson, Michael H; Phillips, Alyssa K; Kling, Douglas; Maki, Kevin C

    2014-09-01

    The incidence of hypertriglyceridemia has grown alongside that of obesity. Statin therapy has been widely recommended for the treatment of dyslipidemias. Omega-3 (OM3) fatty acid concentrates are commonly prescribed concurrently with statins in patients with persistent hypertriglyceridemia for additional lowering of triglyceride and non-HDL cholesterol. The bioavailability of currently available OM3 ethyl ester drugs is limited by their need for hydrolysis by pancreatic lipases, largely stimulated by dietary fat, prior to intestinal absorption. This review will discuss the chemistry, pharmacokinetics and clinical efficacy of a novel OM3 carboxylic acid drug that provides polyunsaturated docosahexaenoic and eicosapentaenoic acids in the free fatty acid form, which is readily absorbed by the intestine. This drug was approved in May 2014 as an adjunct to diet to reduce triglyceride levels in adults with severe (≥500 mg/dl) hypertriglyceridemia.

  16. Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

    Directory of Open Access Journals (Sweden)

    Joana R. Viola

    2013-01-01

    Full Text Available Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed.

  17. 5-aminolevulinic acid in photodynamic diagnosis and therapy of urological malignancies

    Science.gov (United States)

    Nelius, Thomas; de Riese, Werner T. W.

    2003-06-01

    Completeness and certainty of tumor detection are very important issues in clinical oncology. Recent technological developments in ultrasound, radiologic and magnetic resonance imaging diagnostics are very promising, but could not improve the detection rate of early stage malignancies. One of the most promising new approaches is the use of 5-aminolevulinic acid, a potent photosensitizer, in photodynamic diagnosis and therapy. 5-aminolevulinic acid is meanwhile a well-established tool in the photodynamic diagnosis of bladder cancer. It has been shown to improve the sensitivity of detection of superficial tumors and carcinoma in situ, which enables to reduce the risk of tumor recurrence related to undetected lesions or incomplete transurethral resection of the primary lesions. The use of 5-aminolevulinic acid is steadily expanding in diagnostics of urological malignancies. First clinical results are now reported in detection of urethral and ureteral lesions as well as in urine fluorescence cytology. Furthermore, due to the selective accumulation in transitional cell carcinoma of the bladder, 5-aminolevulinic acid may be an ideal candidate for photodynamic therapy in superficial bladder cancer. Summarizing the data of multiple clinical trials, 5-aminolevulinic acid is a promising agent in photodynamic diagnostics and treatment of superficial bladder cancer.

  18. Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy.

    Science.gov (United States)

    Ishizuka, Masahiro; Abe, Fuminori; Sano, Yuki; Takahashi, Kiwamu; Inoue, Katsushi; Nakajima, Motowo; Kohda, Takeo; Komatsu, Naoki; Ogura, Shun-ichiro; Tanaka, Tohru

    2011-03-01

    Early detection and intervention are needed for optimal outcomes in cancer therapy. Improvements in diagnostic technology, including endoscopy, photodynamic diagnosis (PDD), and photodynamic therapy (PDT), have allowed substantial progress in the treatment of cancer. 5-Aminolevulinic acid (ALA) is a natural, delta amino acid biosynthesized by animal and plant mitochondria. ALA is a precursor of porphyrin, heme, and bile pigments, and it is metabolized into protoporphyrin IX (PpIX) in the course of heme synthesis. PpIX preferentially accumulates in tumor cells resulting in a red fluorescence following irradiation with violet light and the formation of singlet oxygen. This reaction, utilized to diagnose and treat cancer, is termed ALA-induced PDD and PDT. In this review, the biological significance of heme metabolites, the mechanism of PpIX accumulation in tumor cells, and the therapeutic potential of ALA-induced PDT alone and combined with hyperthermia and immunotherapy are discussed.

  19. Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer through apoptosis induction.

    Science.gov (United States)

    Shi, Bin; Wang, Li-Fang; Meng, Wen-Shu; Chen, Liang; Meng, Zi-Li

    2017-06-01

    Carnosic acid is a phenolic diterpene with anti-inflammation, anticancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, which is generated by many species from Lamiaceae family. Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally flavonoid is abundantly produced in different vegetables and fruits. Fisetin has been reported to have various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Lung cancer is reported as the most common neoplasm in human world-wide. In the present study, the possible benefits of carnosic acid combined with fisetin on lung cancer in vitro and in vivo was explored. Carnosic acid and fisetin combination led to apoptosis in lung cancer cells. Caspase-3 signaling pathway was promoted in carnosic acid and fisetin co-treatment, which was accompanied by anti-apoptotic proteins of Bcl-2 and Bcl-xl decreasing and pro-apoptotic signals of Bax and Bad increasing. The death receptor (DR) of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was enhanced in carnosic acid and fisetin combined treatment. Furthermore, the mouse xenograft model in vivo suggested that carnosic acid and fisetin combined treatment inhibited lung cancer growth in comparison to the carnosic acid or fisetin monotherapy. This study supplies a novel therapy to induce apoptosis to inhibit lung cancer through caspase-3 activation.

  20. Clinical experience with ursodeoxycholic acid (Urdoxa) in complex therapy of chronic viral hepatitis

    OpenAIRE

    E. V. Esaulenko; O. E. Nikitina; N. V. Dunaeva; A. N. Uskov; T. L. Mogilevets

    2011-01-01

    Patients with chronic virus hepatitis (32 patients, 13 with chronic hepatitis B and 19 with chronic hepatitis C) ages from 20 to 72 with elevated levels of bilirubin and active alanine aminotransferase, aspartate aminotransferase, gamma- glutamyl transpeptidase, received ursodeoxycholic acid (Urdoxa) over the course of 12 weeks. During therapy alanine aminotransferase, aspartate aminotransferase, bilirubin and gamma-glutamyl transpeptidase levels decreased. Urdoxa demonstrated good tolerance,...

  1. Polycation cytotoxicity: a delicate matter for nucleic acid therapy-focus on polyethylenimine

    DEFF Research Database (Denmark)

    Parhamifar, Ladan; Larsen, Anna K.; Hunter, A. Christy;

    2010-01-01

    This article provides a critical assessment of the major challenges facing nucleic acid therapeutics, focusing on the safety and efficacy of delivery strategies using synthetic polycations and particularly polyethylenimines. Deficiencies in the field and avenues for further research are identified...... that could help with design and selection of an expanded and improved library of safer polycationic vectors for clinical gene therapy and RNA interference delivery....

  2. Combination photodynamic therapy of human breast cancer using salicylic acid and methylene blue

    Science.gov (United States)

    Hosseinzadeh, Reza; Khorsandi, Khatereh; Jahanshiri, Maryam

    2017-09-01

    The objective of this study was to evaluate the effects of combination therapy with methylene blue (MB) assisted photodynamic therapy (PDT) and salicylic acid (SA) as chemo-therapy anticancer agent. The binding of salicylic acid to methylene blue was studied using spectrophotometric method. The results show the 1:2 complex formation between SA and MB. The binding constants and related Gibbs free energies o are obtained (Kb1 = 183.74, Kb2 = 38.13 and ∆ Gb1° = 12.92 kJ·mol- 1, ∆ Gb2° =9.02 kJ·mol- 1). The spectrophotometric results show the improvement in solubilization and reduction prevention for SA and MB in the complex form. These results are in agreements with cellular experiments. The dark toxicity measurements represent the improve efficacy of chemotherapy using combination of SA and MB. The photodynamic therapy results (using red LED as light source (630 nm; power density: 30 mW cm- 2)) show that the cancer cell killing efficiency of MB increases in the combination with SA due to reduction prevention and stabilization of monomeric form of MB.

  3. Photosensitizer-Conjugated Hyaluronic Acid-Shielded Polydopamine Nanoparticles for Targeted Photomediated Tumor Therapy.

    Science.gov (United States)

    Han, Jieun; Park, Wooram; Park, Sin-Jung; Na, Kun

    2016-03-01

    Photodynamic therapy (PDT) is a widely used clinical option for tumor therapy. However, the clinical utilization of conventional small-molecule photosensitizers (PSs) for PDT has been limited by their low selectivity for disease sites, and undesirable photoactivation. To overcome these limitations, we demonstrated a tumor-specific and photoactivity-controllable nanoparticle photomedicine based on a combination of PS-biomacromolecule conjugates and polydopamine nanoparticles (PD-NP) for an effective tumor therapy. This novel photomedicine consisted of a PD-NP core and a PS-conjugated hyaluronic acid (PS-HA) shell. The PD-NP and the PS-HA play roles as a quencher for PSs and a cancer targeting moiety, respectively. The synthesized PS-HA-shielded PD-NPs (PHPD-NPs) had a relatively narrow size distribution (approximately 130 nm) with uniform spherical shapes. In response to cancer-specific intracellular enzymes (e.g., hyaluronidase), the PHPD-NPs exhibited an excellent singlet oxygen generation capacity for PDT. Furthermore, an efficient photothermal conversion ability for photothermal therapy (PTT) was also shown in the PHPD-NPs system. These properties provide superior therapeutic efficacy against cancer cells. In mice tumor model, the photoactive restorative effects of the PHPD-NPs were much higher in cancer microenvironments compared to that in the normal tissue. As a result, the PHPD-NPs showed a significant antitumor activity in in vivo mice tumor model. The nanoparticle photomedicine design is a novel strategy for effective tumor therapy.

  4. Decreased vitamin B12 and folic Acid concentrations in acne patients after isotretinoin therapy: a controlled study.

    Science.gov (United States)

    Gökalp, Hilal; Bulur, I; Gürer, Ma

    2014-11-01

    Oral isotretinoin treatment might influence the levels of vitamin B12 and folic acid. The aim of this study is to compare vitamin B12 and folic acid levels in patients with moderate and severe acne vulgaris with those of the healthy control group and to investigate the effect of isotretinoin treatment on these vitamins. Patients who completed 6 months of isotretinoin therapy for moderate and severe forms of acne vulgaris and a control group consisting of healthy individuals between February 2011 and March 2012 were included in the study. Before isotretinoin therapy and at 6.- months of the therapy, serum vitamin B12 and folic acid levels were measured. In the healthy control group, vitamin B12 and folic acid levels were assessed only once. In total, 120 patients with moderate and severe acne vulgaris who completed 6 months isotretinoin therapy and 100 healthy individuals who constituted the control group were included in the study. Pre-treatment vitamin B12 values of the patient group were found to be statistically significantly higher (P = 0.002), but any statistically significant difference was not detected in folic acid measurements (P = 0.566). A statistically significant decrease was detected in post-treatment vitamin B12 and folic acid levels (P Vitamin B12/folic acid treatment should be given under medical surveillance before and during isotretinoin therapy. Supplementation of these vitamins should be recommended in cases of their deficiency, so as to decrease the risks of neuropsychiatric and occlusive vascular diseases.

  5. Amino acid deprivation using enzymes as a targeted therapy for cancer and viral infections.

    Science.gov (United States)

    Fernandes, H S; Silva Teixeira, C S; Fernandes, P A; Ramos, M J; Cerqueira, N M F S A

    2017-03-01

    Amino acid depletion in the blood serum is currently being exploited and explored for therapies in tumors or viral infections that are auxotrophic for a certain amino acid or have a metabolic defect and cannot produce it. The success of these treatments is because normal cells remain unaltered since they are less demanding and/or can synthesize these compounds in sufficient amounts for their needs by other mechanisms. Areas covered: This review is focused on amino acid depriving enzymes and their formulations that have been successfully used in the treatment of several types of cancer and viral infections. Particular attention will be given to the enzymes L-asparaginase, L-arginase, L-arginine deiminase, and L-methionine-γ-lyase. Expert opinion: The immunogenicity and other toxic effects are perhaps the major limitations of these therapies, but they have been successfully decreased either through the expression of these enzymes from other organisms, recombination processes, pegylation of the selected enzymes or by specific mutations in the proteins. In 2006, FDA has already approved the use of L-asparaginase in the treatment of acute lymphoblastic leukemia. Other enzymes and in particular L-arginase, L-arginine deiminase, and L-methioninase have been showing promising results in vitro and in vivo studies.

  6. Medical therapy with tranexamic acid in autosomal dominant polycystic kidney disease patients with severe haematuria.

    Science.gov (United States)

    Peces, Ramón; Aguilar, Ana; Vega, Cristina; Cuesta, Emilio; Peces, Carlos; Selgas, Rafael

    2012-01-01

    Gross haematuria is a common manifestation of autosomal dominant polycystic kidney disease (ADPKD). It can be spontaneous or the result of trauma, renal calculi, tumour, or infection. Spontaneous cyst bleeding is important in this particular group of patients, since it can be prolonged by local activation of fibrinolysis by urokinase. The management of haematuria in ADPKD is usually conservative, including bed rest, blood transfusion, correction of blood disorders, and use of vasopressin and erythropoiesis-stimulating agents. In some patients, the management of gross or life-threatening haematuria may require embolisation and/or nephrectomy. Nonetheless, other methods have been tried to avoid prolonged hospitalisation and nephrectomy and preserve kidney function, such as the use of anti-fibrinolytics. Tranexamic acid was recently suggested as a tool to treat gross haematuria in ADPKD in isolated cases. The aim of this study was to evaluate prospectively the response to tranexamic acid in a group of 8 patients with ADPKD and gross haematuria unresponsive to conventional treatment. The massive bleeding stopped within 2 to 5 days in all patients. The haemoglobin level and renal function subsequently stabilised. There were no side effects or thromboembolic events. In this case series, the largest prospective study so far published and the only one including different degrees of renal function, tranexamic acid is confirmed as a promising tool for treating haematuria due to intracystic bleeding in ADPKD. In summary, tranexamic acid can be used safely in ADPKD patients with chronic renal impairment or preserved renal function to treat severe haematuria poorly responsive to conventional therapy. Tranexamic acid can be administered orally or IV; and dose adjustment for renal impairment is important. Tranexamic acid therapy may preserve renal function in ADPKD directly, by stopping haematuria episodes, or indirectly, by preventing embolisation and/or nephrectomy. The major

  7. Acid suppression therapy does not predispose to Clostridium difficile infection: the case of the potential bias.

    Directory of Open Access Journals (Sweden)

    Lena Novack

    Full Text Available OBJECTIVE: An adverse effect of acid-suppression medications on the occurrence of Clostridium difficile infection (CDI has been a common finding of many, but not all studies. We hypothesized that association between acid-suppression medications and CDI is due to the residual confounding in comparison between patients with infection to those without, predominantly from non-tested and less sick subjects. We aimed to evaluate the effect of acid suppression therapy on incidence of CDI by comparing patients with CDI to two control groups: not tested patients and patients suspected of having CDI, but with a negative test. METHODS: We conducted a case-control study of adult patients hospitalized in internal medicine department of tertiary teaching hospital between 2005-2010 for at least three days. Controls from each of two groups (negative for CDI and non-tested were individually matched (1:1 to cases by primary diagnosis, Charlson comorbidity index, year of hospitalization and gender. Primary outcomes were diagnoses of International Classification of Diseases (ICD-9-coded CDI occurring 72 hours or more after admission. RESULTS: Patients with CDI were similar to controls with a negative test, while controls without CDI testing had lower clinical severity. In multivariable analysis, treatment by acid suppression medications was associated with CDI compared to those who were not tested (OR = 1.88, p-value = 0.032. Conversely, use of acid suppression medications in those who tested negative for the infection was not associated with CDI risk as compared to the cases (OR = 0.66; p = 0.059. CONCLUSIONS: These findings suggest that the reported epidemiologic associations between use of acid suppression medications and CDI risk may be spurious. The control group choice has an important impact on the results. Clinical differences between the patients with CDI and those not tested and not suspected of having the infection may explain the different conclusions

  8. Ear Keloid Treated with Infiltrated Non-cross-linked Hyaluronic Acid and Cortisone Therapy.

    Science.gov (United States)

    DI Stadio, Arianna

    Several treatments are available to treat the keloid scar. Keloids have the tendency to recur after surgical removal and new treatments for keloid scars include radiotherapy, cryotherapy or compressive therapy. Topical treatments have been also used to treat this pathology, such as injections or medical device applications. A 33-year-old man came to our attention and we treated him for a keloid scar located between the ear's helical tubercle and the ante-helix upper root of the left ear. This keloid arose 20 years earlier following a bilateral otoplasty. We proposed an association therapy using a non-cross-linked hyaluronic acid and cortisone. The associated treatment was able to determine a complete resolution of the keloid without recurrence several months later. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. GASTROENTEROPATHIES ASSOCIATED WITH ACETYLSALICYLIC ACID: HOW TO IMPROVE SAFETY OF THERAPY

    Directory of Open Access Journals (Sweden)

    A. L. Komarov

    2016-01-01

    Full Text Available Lesion of gastrointestinal mucous coat is the main factor limited acetylsalicylic acid (ASA use in patients with atherothrombosis. Up to date the mostly comprehensible way to decrease gastrointestinal complications is taking ASA in the lowest effective dose, which is not higher than 75-81 mg daily. It is necessary if possible to avoid ASK usage in combination with other antiaggregants, anticoagulants, non-steroid and steroid anti-inflammatory drugs. Routine antiulcer therapy is not indicated for patients treated with ASA because there is a lack of clinical research data about efficacy of this approach. In high risk of dangerous gastrointestinal complications H. pylori eradication is recommended in combination with long term preventive therapy with gastric secretion inhibitors. Proton pump inhibitors are more preferred.

  10. GASTROENTEROPATHIES ASSOCIATED WITH ACETYLSALICYLIC ACID: HOW TO IMPROVE SAFETY OF THERAPY

    Directory of Open Access Journals (Sweden)

    A. L. Komarov

    2009-01-01

    Full Text Available Lesion of gastrointestinal mucous coat is the main factor limited acetylsalicylic acid (ASA use in patients with atherothrombosis. Up to date the mostly comprehensible way to decrease gastrointestinal complications is taking ASA in the lowest effective dose, which is not higher than 75-81 mg daily. It is necessary if possible to avoid ASK usage in combination with other antiaggregants, anticoagulants, non-steroid and steroid anti-inflammatory drugs. Routine antiulcer therapy is not indicated for patients treated with ASA because there is a lack of clinical research data about efficacy of this approach. In high risk of dangerous gastrointestinal complications H. pylori eradication is recommended in combination with long term preventive therapy with gastric secretion inhibitors. Proton pump inhibitors are more preferred.

  11. Enhanced cellular uptake of protoporphyrine IX/linolenic acid-conjugated spherical nanohybrids for photodynamic therapy.

    Science.gov (United States)

    Lee, Hye-In; Kim, Young-Jin

    2016-06-01

    Protoporphyrin IX (PpIX) has wide applications in photodynamic diagnosis and photodynamic therapy (PDT) in many human diseases. However, poor water solubility and cancer cell localization limit its direct application for PDT. We improved the water-solubility and cellular internalization of PpIX to enhance PDT efficacy by developing biocompatible PpIX/linolenic acid-conjugated polyhedral oligomeric silsesquioxane (PPLA) nanohybrids. The resulting PPLA nanohybrids exhibited a quasi-spherical shape with a size of gastric cancer cells. These results imply that the PPLA nanohybrid system may be applicable in PDT.

  12. Endocrine effects of valproic acid therapy in girls with epilepsy: a prospective study.

    Science.gov (United States)

    Goldberg-Stern, Hadassa; Yaacobi, Eyal; Phillip, Moshe; de Vries, Liat

    2014-11-01

    It is controversial whether the endocrine dysfunction in epilepsy patients is caused by the epilepsy itself, the antiepileptic therapy, or both. We prospectively evaluated the long-term impact of valproic acid monotherapy compared to other anti-epileptic drugs on anthropometric, metabolic, hormonal, and ultrasonographic parameters in girls with epilepsy. Fifty-seven female patients with epilepsy who had started therapy at mean age of 11.5 ± 3.3 years, 42 with valproic acid (mean dose 13.1 ± 7.0 mg/kg/day and 15 with other anti-epileptic agents were followed for a mean of 3.2 years (range 1.0-8.5 years) in our center. Clinical, hormonal and transabdominal pelvic ultrasound data were collected at 3 time points: before and 6-12 months after onset of anti-epileptic drug treatment; and at the last visit while patients were still taking anti-epileptic drugs. There were no significant between-group differences regarding changes in height, body mass index standard deviation score, levels of glucose and insulin, or lipid and endocrine profile from first to last visits. Mean thyroid-stimulating hormone level increased significantly between first and last visit only in the valproic acid group (p endocrine function over an average follow-up of 3.2 years. Valproic acid appears to be safe for use in girls with epilepsy. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  13. Combination Therapy with Oleanolic Acid and Metformin as a Synergistic Treatment for Diabetes

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    Xue Wang

    2015-01-01

    Full Text Available Aims and Background. Type 2 diabetes is a chronic disease that cannot be treated adequately using the known monotherapies, especially when the disease progresses to an advanced stage. In this study, we explore the possibility of treating the disease with a novel combination approach of oleanolic acid (OA, a glycogen phosphorylase (GP inhibitor, and metformin. Methods. Db/db mice were randomly divided into four groups: a db/db control group, db/db mice treated with OA (250 mg/kg, db/db mice treated with metformin (100 mg/kg, and db/db mice treated with a combination of OA and metformin. All mice were treated for four weeks. The effects of the treatments on glucose homeostasis were measured using an OGTT, an assessment of insulin sensitivity and signaling in the liver, and the hepatic glucose production. Results. Combination therapy with OA and metformin significantly reduced the blood glucose and insulin levels and improved the liver pathology compared with that for the monotherapy in the db/db diabetic mouse model. We also found that the combination therapy significantly increased the mRNA expression of glycogen synthesis and decreased the GP, PGC-1α, PEPCK1, and G-6-Pase levels. In addition, the combination therapy with OA and metformin significantly increased the phosphorylation of AKT, PI3K, AMPK, and ACC and decreased the protein expression levels of G-6-Pase, PEPCK1, and TORC compared with those for either monotherapy. The combination therapy also reduced the phosphorylation of mTOR and CREB. Conclusions. Our results suggest that the combination therapy with OA and metformin has synergistic effects on the symptoms of db/db diabetic mice by improving glucose and insulin homeostasis.

  14. A novel biocompatible hyaluronic acid-chitosan hybrid hydrogel for osteoarthrosis therapy.

    Science.gov (United States)

    Kaderli, S; Boulocher, C; Pillet, E; Watrelot-Virieux, D; Rougemont, A L; Roger, T; Viguier, E; Gurny, R; Scapozza, L; Jordan, O

    2015-04-10

    A conventional therapy for the treatment of osteoarthrosis is intra-articular injection of hyaluronic acid, which requires repeated, frequent injections. To extend the viscosupplementation effect of hyaluronic acid, we propose to associate it with another biopolymer in the form of a hybrid hydrogel. Chitosan was chosen because of its structural similarity to synovial glycosaminoglycans, its anti-inflammatory effects and its ability to promote cartilage growth. To avoid polyelectrolyte aggregation and obtain transparent, homogeneous gels, chitosan was reacetylated to a 50% degree, and different salts and formulation buffers were investigated. The biocompatibility of the hybrid gels was tested in vitro on human arthrosic synoviocytes, and in vivo assessments were made 1 week after subcutaneous injection in rats and 1 month after intra-articular injection in rabbits. Hyaluronic acid-chitosan polyelectrolyte complexes were prevented by cationic complexation of the negative charges of hyaluronic acid. The different salts tested were found to alter the viscosity and thermal degradation of the gels. Good biocompatibility was observed in rats, although the calcium-containing formulation induced calcium deposits after 1 week. The sodium chloride formulation was further tested in rabbits and did not show acute clinical signs of pain or inflammation. Hybrid HA-Cs hydrogels may be a valuable alternative viscosupplementation agent.

  15. Effect of α-lipoic acid combined with conventional therapy on serum markers of early diabetic nephropathy patients

    Institute of Scientific and Technical Information of China (English)

    Xin-Dong Jin; Xiang-Dong Liu; Xi-Ping Niu

    2015-01-01

    Objective: To study the effect ofα-lipoic acid combined with conventional therapy on serum markers of early diabetic nephropathy patients.Methods: Patients with early diabetic nephropathy treated in our hospital from May 2012 to May 2014 were chosen for study and randomly divided into two groups. Lipoic acid group received α-lipoic acid combined with conventional drug therapy; conventional group received conventional drug therapy. Then renal function, oxidative stress, podocyte injury degree, mitochondrial fusion and fission protein contents of both groups were compared.Results:(1) renal function and oxidative stress indicators: serum CysC, RBP, 8-OHdG, NT, MDA and F2-aisoprostanes contents of lipoic acid group showed a decreasing trend; (2) podocyte injury indicators: serum Nephrin, Podocin, Desmin and CD2AP contents of lipoic acid group showed a significantly increasing trend; (3) mitochondrial indicators: serum Mfs1, Mfs2 and Opa1 contents of lipoic acid group significantly increased; Fis1, Mff and GDAP1 contents significantly decreased.Conclusion:α-lipoic acid combined with conventional therapy is helpful to improve renal function, relieve oxidative stress and protect podocyte structure and mitochondrial function; it’s an ideal method in treating early diabetic nephropathy.

  16. Enhanced 5-aminolevulinic acid-gold nanoparticle conjugate-based photodynamic therapy using pulse laser

    Science.gov (United States)

    Xu, Hao; Yao, Cuiping; Wang, Jing; Chang, Zhennan; Zhang, Zhenxi

    2016-02-01

    The low bioavailability is a crucial limitation for the application of 5-aminolevulinic acid (ALA) in theranostics. In this research, 5-aminolevulinic acid and gold nanoparticle conjugates (ALA-GNPs) were synthesized to improve the bioavailability of ALA and to investigate the impact of ALA photodynamic therapy (ALA-PDT) in Hela cells. A 532 nm pulse laser and light-emitting diode (central wavelengths 502 nm) were jointly used as light sources in PDT research. The results show a 532 nm pulse laser can control ALA release from ALA-GNPs by adjusting the pulse laser dose. This laser control release may be attributed to the heat generation from GNPs under pulse laser irradiation, which indicates accurately adjusting the pulse laser dose to control the drug release in the cell interior can be considered as a new cellular surgery modality. Furthermore, the PDT results in Hela cells indicate the enhancement of ALA release by pulse laser before PDT can promote the efficacy of cell eradication in the light-emitting diode PDT (LED-PDT). This laser mediated drug release system can provide a new online therapy approach in PDT and it can be utilized in the optical monitor technologies based individual theranostics.

  17. Efficacy, dosage and duration of action of branched chain amino acid therapy for traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Jaclynn eElkind

    2015-03-01

    Full Text Available Traumatic brain injury (TBI results in long-lasting cognitive impairments for which there is currently no accepted treatment. A well-established mouse model of mild to moderate TBI, lateral fluid percussion injury (FPI, shows changes in network excitability in the hippocampus including a decrease in net synaptic efficacy in area CA1 and an increase in net synaptic efficacy in dentate gyrus. Previous studies identified a novel therapy consisting of branched chain amino acids (BCAAs which restored normal mouse hippocampal responses and ameliorated cognitive impairment following FPI. However, the optimal BCAA dose and length of treatment needed to improve cognitive recovery is unknown. In the current study mice underwent FPI then consumed 100 mM BCAA supplemented water ad libitum for 2, 3, 4, 5 and 10 days. BCAA therapy ameliorated cognitive impairment at 5 and 10 days duration. Neither BCAA supplementation at 50 mM, nor BCAAs when dosed 5 days on then 5 days off, was sufficient to ameliorate cognitive impairment. These results suggest that brain injury causes alterations in hippocampal function which underlie and contribute to hippocampal cognitive impairment which are reversible with at least 5 days of BCAA treatment, and that sustaining this effect is dependent on continuous treatment. Our findings have profound implications for the clinical investigation of TBI therapy.

  18. Acute promyelocytic leukemia and differentiation therapy: molecular mechanisms of differentiation, retinoic acid resistance and novel treatments

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    Bülent Özpolat

    2009-06-01

    Full Text Available Incorporation of all-trans-retinoic acid (ATRA into the treatment of acute promyelocytic leukemia (APL, a type of acute myeloid leukemia (AML, revolutionized the therapy of cancer in the last decade and introduced the concept of differentiation therapy. ATRA, a physiological metabolite of vitamin A (retinol, induces complete clinical remissions (CRs in about 90% of patients with APL. In contrast to the cytotoxic chemotherapeutics, ATRA can selectively induce terminal differentiation of promyelocytic leukemic cells into normal granulocytes without causing bone marrow hypoplasia or exacerbation of the frequently occurring fatal hemorrhagic syndromes in patients with APL. However, remissions induced by ATRA alone are transient and the patients commonly become resistant to the therapy, leading to relapses in most patients and thus limiting the use of ATRA as a single agent. Therefore, ATRA is currently combined with anthracycline-based chemotherapy, and this regimen dramatically improves patient survival compared to chemotherapy alone, curing about 70% of the patients. However, 30% of APL patients still relapse and die in five years. Recently, arsenic trioxide (As2O3 was proven to be highly effective in inducing CRs not only in APL patients relapsed after ATRA treatment and conventional chemotherapy but also in primary APL patients. Despite the well-documented clinical efficacy of ATRA, molecular mechanisms responsible for development of ATRA resistance are not well understood. Based on in vitro and clinical observations, several mechanisms, including induction of accelerated metabolism of ATRA, decreased bioavailability and plasma drug levels, point mutations in the ATRA-binding domain of promyelocytic leukemia (PML-retinoic acid receptor-alpha (RARα and other molecular events have been proposed to explain ATRA resistance. In this review, the molecular mechanisms of ATRA-induced myeloid cell differentiation and resistance are discussed, together

  19. Response of preclinical medulloblastoma models to combination therapy with 13-cis retinoic acid and suberoylanilide hydroxamic acid (SAHA).

    Science.gov (United States)

    Spiller, Susan E; Ditzler, Sally H; Pullar, Barbara J; Olson, James M

    2008-04-01

    Current medulloblastoma therapy, surgery, radiation, and chemotherapy, is unacceptably toxic. However, 13-cis retinoic acid (RA) and SAHA, a histone deacetylase inhibitor, have each been shown to induce apoptosis in medulloblastoma cultures and mouse models. Both drugs cross the blood brain barrier, have been given safely to children, and achieve brain concentrations that are at or near therapeutic levels. Retinoic acid acts by transcriptionally activating bone morphogenetic protein-2 (BMP-2) and SAHA facilitates transcriptional activity through chromatin accessibility. We tested the hypothesis that these drugs additively induce BMP-2 transcription and apoptosis. RA + SAHA induction of BMP-2 transcription and apoptosis in medulloblastoma cultures was evaluated. Subsequently the response of mouse medulloblastomas to these two agents in the presence and absence of cisplatin was evaluated. BMP-2 transcription multiplied 3-fold with addition of RA to culture, and 7-fold with both agents. The IC50 of SAHA was reduced by 40% when low dose RA was added. Interestingly, a p38 MAP kinase inhibitor that partially blocks RA-induced apoptosis did not inhibit the activity of RA + SAHA. Flank D283 tumors in athymic mice had slower growth in the RA + SAHA arm than single drug or control arms. Intracranial tumors in ND2:SmoA1 mice treated with RA + SAHA + cisplatin showed a 4-fold increase in apoptosis over controls, and a 2-fold increase over animals receiving only SAHA or RA + SAHA. RA + SAHA additively induce BMP-2 transcription and medulloblastoma apoptosis. The combination may act through a p38 MAPK independent mechanism. Efficacy increased with cisplatin, which has implications for clinical trial design.

  20. Construction and Evaluation of a Targeted Hyaluronic Acid Nanoparticle/Photosensitizer Complex for Cancer Photodynamic Therapy.

    Science.gov (United States)

    Gao, Shi; Wang, Jingjing; Tian, Rui; Wang, Guohao; Zhang, Liwen; Li, Yesen; Li, Lu; Ma, Qingjie; Zhu, Lei

    2017-09-12

    Photodynamic therapy (PDT) is a novel treatment modality that is under intensive preclinical investigations for a variety of diseases, including cancer. Despite extensive studies in this area, selective and effective photodynamic agents that can specifically accumulate in tumors to reach a therapeutic concentration are limited. Although recent attempts have produced photosensitizers (PSs) complexed with various nanomaterials, the tedious preparation steps and poor tumor efficiency of therapy hamper their utilization. Here, we developed a CD44-targeted nanophotodynamic agent by physically encapsulating a photosensitizer, Ce6, into a hyaluronic acid nanoparticle (HANP), which was hereby denoted HANP/Ce6. Its physical features and capability for photodynamic therapy were characterized in vitro and in vivo. Systemic delivery of HANP/Ce6 resulted in its accumulation in a human colon cancer xenograft model. The tumor/muscle ratio reached 3.47 ± 0.46 at 4 h post injection, as confirmed by fluorescence imaging. Tumor growth after HANP/Ce6 treatment with laser irradiation (0.15 W/cm(2), 630 nm) was significantly inhibited by 9.61 ± 1.09-fold compared to that in tumor control groups, which showed no change in tumor growth. No apparent systemic and local toxic effects on the mice were observed. HANP/Ce6-mediated tumor growth inhibition was accessed and observed for the first time by (18)F-fluoro-2-deoxy-d-glucose positron emission tomography as early as 1 day after treatment and persisted for 14 days within our treatment time window. In sum, our results highlight the imaging properties and therapeutic effects of the novel HANP/Ce6 theranostic nanoparticle for CD44-targeted PDT cancer therapy that may be potentially utilized in the clinic. This HANP system may also be applied for the delivery of other hydrophobic PSs, particularly those that could not be chemically modified.

  1. Bile Acid Malabsorption After Pelvic and Prostate Intensity Modulated Radiation Therapy: An Uncommon but Treatable Condition

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Victoria [Academic Urology Unit, Institute of Cancer Research and The Royal Marsden Hospital, London and Sutton (United Kingdom); Benton, Barbara [Gastroenterology Unit, Institute of Cancer Research and The Royal Marsden Hospital, London and Sutton (United Kingdom); Sohaib, Aslam [Department of Radiology, Institute of Cancer Research and The Royal Marsden Hospital, London and Sutton (United Kingdom); Dearnaley, David [Academic Urology Unit, Institute of Cancer Research and The Royal Marsden Hospital, London and Sutton (United Kingdom); Andreyev, H. Jervoise N., E-mail: j@andreyev.demon.co.uk [Gastroenterology Unit, Institute of Cancer Research and The Royal Marsden Hospital, London and Sutton (United Kingdom)

    2012-12-01

    Purpose: Intensity modulated radiation therapy (IMRT) is a significant therapeutic advance in prostate cancer, allowing increased tumor dose delivery and increased sparing of normal tissues. IMRT planning uses strict dose constraints to nearby organs to limit toxicity. Bile acid malabsorption (BAM) is a treatable disorder of the terminal ileum (TI) that presents with symptoms similar to radiation therapy toxicity. It has not been described in patients receiving RT for prostate cancer in the contemporary era. We describe new-onset BAM in men after IMRT for prostate cancer. Methods and Materials: Diagnosis of new-onset BAM was established after typical symptoms developed, selenium-75 homocholic acid taurine (SeHCAT) scanning showed 7-day retention of <15%, and patients' symptoms unequivocally responded to a bile acid sequestrant. The TI was identified on the original radiation therapy plan, and the radiation dose delivered was calculated and compared with accepted dose-volume constraints. Results: Five of 423 men treated in a prospective series of high-dose prostate and pelvic IMRT were identified with new onset BAM (median age, 65 years old). All reported having normal bowel habits before RT. The volume of TI ranged from 26-141 cc. The radiation dose received by the TI varied between 11.4 Gy and 62.1 Gy (uncorrected). Three of 5 patients had TI treated in excess of 45 Gy (equivalent dose calculated in 2-Gy fractions, using an {alpha}/{beta} ratio of 3) with volumes ranging from 1.6 cc-49.0 cc. One patient had mild BAM (SeHCAT retention, 10%-15%), 2 had moderate BAM (SeHCAT retention, 5%-10%), and 2 had severe BAM (SeHCAT retention, <5%). The 3 patients whose TI received {>=}45 Gy developed moderate to severe BAM, whereas those whose TI received <45 Gy had only mild to moderate BAM. Conclusions: Radiation delivered to the TI during IMRT may cause BAM. Identification of the TI from unenhanced RT planning computed tomography scans is difficult and may impede

  2. [Gastric acid secretion and absorption of levodopa in patients with Parkinson's disease--the effect of supplement therapy to gastric acid].

    Science.gov (United States)

    Yazawa, I; Terao, Y; Sai, I; Hashimoto, K; Sakuta, M

    1994-03-01

    Since an oral regimen of levodopa has been instituted for treatment of Parkinson's disease, its absorption and metabolism has been well demonstrated. However, its chemical characteristics of high solubility in acid solution and low solubility in water have not been well known. We paid attention to this characteristic and studied the relationship between its absorption and gastric acid secretion in 38 patients with Parkinson's disease who became refractory to therapy of levodopa. We measured the pH and amount of collected fasting gastric juice. Gastric acid secretion was decreased in 22 patients (58%). In ten of these 22 patients, 30 ml of lemon juice was prescribed in every administration of levodopa as a supplement to gastric acid for two weeks. Increases of L-dopa concentration after 60 min. and 180 min. were observed after lemon juice supplement therapy. Among the Parkinson symptoms, rigidity, akinesia, and small step gait were improved in every case except one patient who showed decrease of L-dopa concentration at 180 minutes. However, improvement of tremor was less remarkable. We consider this supplement therapy to gastric acid is one of the effective and useful methods in the management of Parkinson's disease.

  3. Decreased vitamin B 12 and folic acid concentrations in acne patients after isotretinoin therapy: A controlled study

    Directory of Open Access Journals (Sweden)

    Hilal Gökalp

    2014-01-01

    Full Text Available Background: Oral isotretinoin treatment might influence the levels of vitamin B 12 and folic acid. Aims and Objectives: The aim of this study is to compare vitamin B 12 and folic acid levels in patients with moderate and severe acne vulgaris with those of the healthy control group and to investigate the effect of isotretinoin treatment on these vitamins. Materials and Methods: Patients who completed 6 months of isotretinoin therapy for moderate and severe forms of acne vulgaris and a control group consisting of healthy individuals between February 2011 and March 2012 were included in the study. Before isotretinoin therapy and at 6.- months of the therapy, serum vitamin B 12 and folic acid levels were measured. In the healthy control group, vitamin B 12 and folic acid levels were assessed only once. Results: In total, 120 patients with moderate and severe acne vulgaris who completed 6 months isotretinoin therapy and 100 healthy individuals who constituted the control group were included in the study. Pre-treatment vitamin B 12 values of the patient group were found to be statistically significantly higher (P = 0.002, but any statistically significant difference was not detected in folic acid measurements (P = 0.566. A statistically significant decrease was detected in post-treatment vitamin B 12 and folic acid levels (P < 0.05. Conclusion: Vitamin B 12 /folic acid treatment should be given under medical surveillance before and during isotretinoin therapy. Supplementation of these vitamins should be recommended in cases of their deficiency, so as to decrease the risks of neuropsychiatric and occlusive vascular diseases.

  4. [Acne conglobata: personality and psychological sequelae in 13-cis-retinoic acid therapy. Initial results].

    Science.gov (United States)

    Studt, H H; Riehl, A; Gollnick, H

    1986-05-15

    16 patients suffering from acne conglobata were prospectively examined by means of analytical interviews and 5 psychometric procedures before and 6 months after oral treatment with 13-cis retinoic acid (isotretinoin). In comparison with a control group of psychosomatic patients, acne conglobata patients are more frequently affected by childhood influences leading to a neurotic personality structure already before the outbreak of acne; the patients more often complain of disturbed social contact, depressive moods, or general disorders. After successful treatment with isotretinoin, we observed augmented self-confidence and positive aggressiveness, on one hand, and increase of anxiety depressive moods, and general complaints, on the other. These effects are not drug related in a pharmacological way. These observations suggest the influence of psychic factors in the pathogenesis of acne conglobata. Regarding the medical management of these patients, it should be considered that psychic and psychosomatic disorders might be intensified after successful drug therapy.

  5. Treatment of actinic cheilitis by photodynamic therapy with 5-aminolevulinic acid and blue light activation.

    Science.gov (United States)

    Zaiac, Martin; Clement, Annabelle

    2011-11-01

    Actinic cheilitis (AC), a common disorder of the lower lip, should be treated early to prevent progression to invasive squamous cell carcinoma. This study evaluated the safety and efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) activated by blue light for the treatment of AC. Fifteen patients with clinically evident or biopsy-proven AC received two treatments with ALA PDT with blue light activation. Treatments were spaced three to five weeks apart. Most patients achieved 65% to 75% clearance three to five weeks after the first treatment and all achieved more than 75% clearance one month after the second treatment. Three patients achieved complete clearance. Pain and burning during irradiation were absent or mild. All patients said they would repeat the procedure. ALA PDT with 417 nm blue light is a promising option for the treatment of AC of the lower lip.

  6. Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke.

    Science.gov (United States)

    Llull, Laura; Laredo, Carlos; Renú, Arturo; Pérez, Belén; Vila, Elisabet; Obach, Víctor; Urra, Xabier; Planas, Anna; Amaro, Sergio; Chamorro, Ángel

    2015-08-01

    It is unknown whether women and men with acute ischemic stroke respond similar to an antioxidant regimen administered in combination with thrombolysis. Here, we investigated the independent effect of sex on the response to uric acid (UA) therapy in patients with acute stroke treated with alteplase. In the Efficacy Study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke (URICO-ICTUS) trial, 206 women and 205 men were randomized to UA 1000 mg or placebo. In this reanalysis of the trial, the primary outcome was the rate of excellent outcome at 90 days (modified Rankin Scale, 0-1, or 2, if premorbid score of 2) in women and men using regression models adjusted for confounders associated with sex. The interaction of UA levels by treatment on infarct growth was assessed in selected patients. Excellent outcome occurred in 47 of 111 (42%) women treated with UA, and 28 of 95 (29%) treated with placebo, and in 36 of 100 (36%) men treated with UA and 38 of 105 (34%) treated with placebo. Treatment and sex interacted significantly with excellent outcome (P=0.045). Thus, UA therapy doubled the effect of placebo to attain an excellent outcome in women (odd ratio [95% confidence interval], 2.088 [1.050-4.150]; P=0.036), but not in men (odd ratio [95% confidence interval], 0.999 [0.516-1.934]; P=0.997). The interactions between treatment and serum UA levels (Pacute ischemic stroke treated with alteplase, the administration of UA reduced infarct growth in selected patients and was better than placebo to reach excellent outcome. URL: https://clinicaltrials.gov. Unique identifier: NCT00860366. © 2015 American Heart Association, Inc.

  7. Ex vivo modeling of the effects of mycophenolic acid on HIV infection: considerations for antiviral therapy.

    Science.gov (United States)

    Kaur, Rupinderjeet; Klichko, Vladimir; Margolis, David

    2005-02-01

    Mycophenolate mofetil (MMF), the bioavailable form of mycophenolic acid (MPA), has been proposed as adjuvant therapy for human immunodeficiency virus type 1 (HIV-1) infection. MPA can inhibit viral replication and might blunt virus-induced immunopathology. However, other effects of this inhibitor might be detrimental in an HIV-infected patient. We therefore studied the effect of MPA on selected cellular processes of relevance to HIV infection. We found that MPA did not alter the expression of the primary HIV coreceptor CCR5 on primary resting lymphocytes, but modestly increased CCR5 expression after activation. Conversely, MPA modestly decreased the secretion of the CCR5 ligand RANTES in resting lymphocytes, but had no effect after activation. It has been suggested that the use of inhibitors of host nucleoside metabolism may enhance clinical toxicities induced by HIV-1 nucleoside reverse transcriptase inhibitors (NRTIs). We found no evidence that MPA induced mitochondrial dysfunction or enhanced dysfunction induced by NRTIs in an HepG2 cell line model of mitochondrial toxicity. Further, MPA did not selectively enhance apoptosis in HIV-1-infected lymphocytes. Our findings support the testing of MMF to augment suppression of viral replication. However, careful study will be required to demonstrate that MMF is beneficial when used without antiretroviral therapy, to inhibit residual replication, or to deplete the pool of latently infected nonactivated cells.

  8. Potential of using boric acid as a boron drug for boron neutron capture therapy for osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, C.F.; Lin, S.Y. [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China); Peir, J.J. [Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China); Liao, J.W. [Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, Taiwan (China); Lin, Y.C. [Department of Veterinary Medicine, National Chung Hsing University, Taiwan (China); Chou, F.I., E-mail: fichou@mx.nthu.edu.tw [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China)] [Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China)

    2011-12-15

    Osteosarcoma is a malignant tumor commonly found in human and animals. The ability of boric acid (BA) to accumulate in osteosarcoma due to the mechanism of the bone formation of cancer cells would make boron neutron capture therapy (BNCT) an alternative therapy for osteosarcoma. This study evaluated the feasibility of using BA as the boron drug for BNCT of bone cancer. The cytotoxicity of BA to L929 cells exceeded that of UMR-106 cells. With 25 {mu}g {sup 10}B/mL medium of BA treatment, the boron concentration in UMR-106 cells was higher than that in L929 cells. The biodistribution and pharmacokinetics of BA in Sprague-Dawley (SD) rats were studied by administrating 25 mg {sup 10}B/kg body weight to SD rats. Blood boron level decreased rapidly within one hour after BA injection. Boron concentration in the long bone was 4-6 time higher than that of blood. Results of this study suggest that BA may be a potential drug for BNCT for osteosarcoma.

  9. 5-aminolaevulinic Acid-photodynamic Therapy for the Treatment of Cervical Condylomata Acuminata

    Institute of Scientific and Technical Information of China (English)

    Yong-xin Liu; He-yi Zheng; Xiu-rong Liu

    2009-01-01

    Objective To investigate the efficacy and safety of photodynamic therapy(PDT)with topical 5-aminolaevulinic acid(ALA)on cervical condylomata acuminata.Methods Patients with cervical condylomata(n=30)were allocated into primary and recurrent group,and were given topical ALA under occlusive dressing for 3 hours followed by irradiation with semiconductor laser at a dose of 100 Jcm2 and a power of 100 mW.The treatment was repeated 7 days later if the lesion was not completely removed after the first treatment.Complete response rate and recurrence rate of wart lesions as well as rate of adverse reaction were analyzed.Results The total complete response rate of PDT was 100% and the total recurrence rate was 5% after 3 months of follow-up.Recurrence rate of recurrent group was significantly lower than that of prior managements(100% ,P<0.01).The side effects of PDT in patients mainly included mild burning and/or stinging restricted to the illuminated areas,and was significant lower than their own control(25% vs.100% ,P<0.05).Conclusion Compared with conventional therapies,topical application of ALA-PDT is a simple,effective,safe,well-tolerated,and low recurrence rate treatment for cervical condylomata acuminata.

  10. The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid.

    Directory of Open Access Journals (Sweden)

    Maiko Hayashi

    Full Text Available Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects.

  11. The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid.

    Science.gov (United States)

    Hayashi, Maiko; Fukuhara, Hideo; Inoue, Keiji; Shuin, Taro; Hagiya, Yuichiro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun-ichiro

    2015-01-01

    Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC) with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects.

  12. Use of hyaluronic acid preparations in the combination therapy of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Yu. A. Olyunin

    2016-01-01

    Full Text Available The current recommendations for the pharmacotherapy of osteoarthritis (OA primarily focus on analgesics and main concern is with the use of paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs. Intraarticular injections of first of all hyaluronic acid (HA preparations that have proven to be effective in clinical practice are a promising treatment for OA. By taking into account the favorable safety profile of HA preparations, it may be suggested that these injections may be an acceptable alternative to NSAIDs or successfully used in combination with the latter. There have been recently the recommendations for the administration of HA preparations in OA treatment, which characterize the current practice of HA use for OA and had been prepared by a group of experts from 5 European countries. The experts consider that there is today rather solid evidence to demonstrate the efficacy of HA in mild and moderately severe knee OA; moreover, its effect is clinically significant in such patients. In the authors’ view, topical HA therapy should be a compulsory component of treatment for knee OA, since the alternative possibilities of therapy for this disease are limited. Although the optimal effect of HA is observed when it is applied in the early stage of OA, this treatment may be also useful in its late stage. HA should be regarded as an adjunct method that must be applied if surgery cannot be performed in these patients.

  13. Retinoic acid therapy resistance progresses from unilineage to bilineage in HL-60 leukemic blasts.

    Directory of Open Access Journals (Sweden)

    Holly A Jensen

    Full Text Available Emergent resistance can be progressive and driven by global signaling aberrations. All-trans retinoic acid (RA is the standard therapeutic agent for acute promyelocytic leukemia, but 10-20% of patients are not responsive, and initially responsive patients relapse and develop retinoic acid resistance. The patient-derived, lineage-bipotent acute myeloblastic leukemia (FAB M2 HL-60 cell line is a potent tool for characterizing differentiation-induction therapy responsiveness and resistance in t(15;17-negative cells. Wild-type (WT HL-60 cells undergo RA-induced granulocytic differentiation, or monocytic differentiation in response to 1,25-dihydroxyvitamin D3 (D3. Two sequentially emergent RA-resistant HL-60 cell lines, R38+ and R38-, distinguishable by RA-inducible CD38 expression, do not arrest in G1/G0 and fail to upregulate CD11b and the myeloid-associated signaling factors Vav1, c-Cbl, Lyn, Fgr, and c-Raf after RA treatment. Here, we show that the R38+ and R38- HL-60 cell lines display a progressive reduced response to D3-induced differentiation therapy. Exploiting the biphasic dynamic of induced HL-60 differentiation, we examined if resistance-related defects occurred during the first 24 h (the early or "precommitment" phase or subsequently (the late or "lineage-commitment" phase. HL-60 were treated with RA or D3 for 24 h, washed and retreated with either the same, different, or no differentiation agent. Using flow cytometry, D3 was able to induce CD38, CD11b and CD14 expression, and G1/G0 arrest when present during the lineage-commitment stage in R38+ cells, and to a lesser degree in R38- cells. Clustering analysis of cytometry and quantified Western blot data indicated that WT, R38+ and R38- HL-60 cells exhibited decreasing correlation between phenotypic markers and signaling factor expression. Thus differentiation induction therapy resistance can develop in stages, with initial partial RA resistance and moderate vitamin D3 responsiveness

  14. Retinoic acid therapy resistance progresses from unilineage to bilineage in HL-60 leukemic blasts.

    Science.gov (United States)

    Jensen, Holly A; Bunaciu, Rodica P; Ibabao, Christopher N; Myers, Rebecca; Varner, Jeffrey D; Yen, Andrew

    2014-01-01

    Emergent resistance can be progressive and driven by global signaling aberrations. All-trans retinoic acid (RA) is the standard therapeutic agent for acute promyelocytic leukemia, but 10-20% of patients are not responsive, and initially responsive patients relapse and develop retinoic acid resistance. The patient-derived, lineage-bipotent acute myeloblastic leukemia (FAB M2) HL-60 cell line is a potent tool for characterizing differentiation-induction therapy responsiveness and resistance in t(15;17)-negative cells. Wild-type (WT) HL-60 cells undergo RA-induced granulocytic differentiation, or monocytic differentiation in response to 1,25-dihydroxyvitamin D3 (D3). Two sequentially emergent RA-resistant HL-60 cell lines, R38+ and R38-, distinguishable by RA-inducible CD38 expression, do not arrest in G1/G0 and fail to upregulate CD11b and the myeloid-associated signaling factors Vav1, c-Cbl, Lyn, Fgr, and c-Raf after RA treatment. Here, we show that the R38+ and R38- HL-60 cell lines display a progressive reduced response to D3-induced differentiation therapy. Exploiting the biphasic dynamic of induced HL-60 differentiation, we examined if resistance-related defects occurred during the first 24 h (the early or "precommitment" phase) or subsequently (the late or "lineage-commitment" phase). HL-60 were treated with RA or D3 for 24 h, washed and retreated with either the same, different, or no differentiation agent. Using flow cytometry, D3 was able to induce CD38, CD11b and CD14 expression, and G1/G0 arrest when present during the lineage-commitment stage in R38+ cells, and to a lesser degree in R38- cells. Clustering analysis of cytometry and quantified Western blot data indicated that WT, R38+ and R38- HL-60 cells exhibited decreasing correlation between phenotypic markers and signaling factor expression. Thus differentiation induction therapy resistance can develop in stages, with initial partial RA resistance and moderate vitamin D3 responsiveness (unilineage

  15. Predicting, Monitoring, and Managing Hypercalcemia Secondary to 13-Cis-Retinoic Acid Therapy in Children With High-risk Neuroblastoma.

    Science.gov (United States)

    Chen, Suet Ching; Murphy, Dermot; Sastry, Jairam; Shaikh, Mohamad G

    2015-08-01

    13-cis-retinoic acid is an established component of treatment for children with high-risk neuroblastoma. However, significant hypercalcemia is increasingly recognized as a potentially life-threatening dosage-related side effect. We present 2 patients with significant hypercalcemia secondary to 13-cis-retinoic acid and their management, and identified the predictive factors for susceptibility to hypercalcemia. Assessing glomerular filtration rate and concomitant medication help predict individual susceptibility to hypercalcemia. Calcium levels should be monitored at days 1, 7, and 14 of each course of retinoic acid. An algorithm for the management of hypercalcemia during the affected and subsequent cycles of retinoid therapy is proposed.

  16. Homology modeling of human γ-butyric acid transporters and the binding of pro-drugs 5-aminolevulinic acid and methyl aminolevulinic acid used in photodynamic therapy.

    Directory of Open Access Journals (Sweden)

    Yan Baglo

    Full Text Available Photodynamic therapy (PDT is a safe and effective method currently used in the treatment of skin cancer. In ALA-based PDT, 5-aminolevulinic acid (ALA, or ALA esters, are used as pro-drugs to induce the formation of the potent photosensitizer protoporphyrin IX (PpIX. Activation of PpIX by light causes the formation of reactive oxygen species (ROS and toxic responses. Studies have indicated that ALA and its methyl ester (MAL are taken up into the cells via γ-butyric acid (GABA transporters (GATs. Uptake via GATs into peripheral sensory nerve endings may also account for one of the few adverse side effects of ALA-based PDT, namely pain. In the present study, homology models of the four human GAT subtypes were constructed using three x-ray crystal structures of the homologous leucine transporter (LeuT as templates. Binding of the native substrate GABA and the possible substrates ALA and MAL was investigated by molecular docking of the ligands into the central putative substrate binding sites in the outward-occluded GAT models. Electrostatic potentials (ESPs of the putative substrate translocation pathway of each subtype were calculated using the outward-open and inward-open homology models. Our results suggested that ALA is a substrate of all four GATs and that MAL is a substrate of GAT-2, GAT-3 and BGT-1. The ESP calculations indicated that differences likely exist in the entry pathway of the transporters (i.e. in outward-open conformations. Such differences may be exploited for development of inhibitors that selectively target specific GAT subtypes and the homology models may hence provide tools for design of therapeutic inhibitors that can be used to reduce ALA-induced pain.

  17. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-07-01

    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

  18. Aminolevulinic Acid-Mediated Photodynamic Therapy Causes Cell Death in MG-63 Human Osteosarcoma Cells.

    Science.gov (United States)

    White, Bradley; Rossi, Vince; Baugher, Paige J

    2016-09-01

    The aim of this study was to test the efficacy of aminolevulinic acid-mediated photodynamic therapy (PDT) against the human osteosarcoma cell line MG-63. Osteosarcoma is the most common type of primary malignant bone tumor diagnosed in the United States among adolescents and children. Treatments for osteosarcoma often result in diminished limb use or amputation. Because ALA-mediated PDT exhibits dual specificity in the context of tumor killing, this therapy could represent a less invasive, but effective, treatment for this disease. To assess ALA dark toxicity in MG-63 cells, cells were incubated with varying concentrations of ALA, and cell viability was determined by crystal violet assay. Protoporphyrin IX (PpIX) accumulation was assessed subsequent to ALA incubation at various concentrations using spectrofluorometry. Cell death subsequent to ALA-PDT was determined by illuminating cells at a wavelength of 635 nm at various light intensities subsequent to ALA incubation. Cell viability was assessed using the MTT assay. ALA dark toxicity was observed only at the highest concentrations of 2, 5, and 10 mM. Maximal PpIX concentration was observed at 0.5 and 1 mM ALA, subsequent to a 24-h incubation. Maximal cell death with minimal light toxicity was observed at 0.5 and 1 mM ALA after illumination with 0.6 and 3 J/cm(2) light. Collectively, our data indicate that ALA-PDT can result in the death of MG-64 human osteosarcoma cells in vitro.

  19. All-trans retinoic acid enhances bystander effect of suicide gene therapy in the treatment of breast cancer.

    Science.gov (United States)

    Kong, Heng; Liu, Xia; Yang, Liucheng; Qi, Ke; Zhang, Haoyun; Zhang, Jingwen; Huang, Zonghai; Wang, Hongxian

    2016-03-01

    All-trans retinoic acid (ATRA) has been shown to enhance the expression of connexin 43 (Cx43) and the bystander effect (BSE) in suicide gene therapy. These in turn improve effects of suicide gene therapies for several tumor types. However, whether ATRA can improve BSE remains unclear in suicide gene therapy for breast cancer. In the present study, MCF-7, human breast cancer cells were treated with ATRA in combination with a VEGFP-TK/CD gene suicide system developed by our group. We found that this combination enhances the efficiency of cell killing and apoptosis of breast cancer by strengthening the BSE in vitro. ATRA also promotes gap junction intercellular communication (GJIC) in MCF-7 cells by upregulation of the connexin 43 mRNA and protein in MCF-7 cells. These results indicate that enhancement of GJIC by ATRA in suicide gene system might serve as an attractive and cost-effective strategy of therapy for breast cancer cells.

  20. OPTIMIZATIONS FOR 5-AMINOLEVULINIC ACID BASED PHOTODYNAMIC THERAPY IN PURGING LEUKEMIA CELL HL60

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To optimize experimental parameters for the photosensitization of 5-aminolevulinic acid (ALA) in promyelocytic leukemia cell HL60 and compare them with normal human peripheral blood mononuclear cell (PBMC). Methods ALA incubation time, wavelength applied to irradiate, concentration of ALA incubated, irradiation fluence may modulate the effect of 5-aminolevulinic acid based Photodynamic Therapy (ALA-PDT).The high-pressure mercury lamps of 400W served as light source, the interference filter of 410nm, 432nm, 545nm, 577nm were used to select the specific wavelength. Fluorescence microscope was used to detect the fluorescence intensity and location of protoporphyrin IX (PpIX) endogenously produced by ALA. MTT assay was used to measure the survival of cell. Flow cytometry with ANNEXIN V FITC kit (contains annexin V FITC, binding buffer and PI) was used to detect the mode of cell death. Results ① 1mmol/L ALA incubated 1×105/mL HL60 cell line for 4 hours, the maximum fluorescence of ALA induced PpIX was detected in cytomembrane. ② Irradiated with 410nm for 14.4J/cm2 can result in the minimum survivability of HL60 cell. ③ The main mode of HL60 cell death caused by ALA-PDT is necrosis. Conclusion ALA for 1mmol/L, 4 hours for dark incubation time, 410nm for irradiation wavelength, 14.4J/cm2 for irradiation fluence were the optimal parameters to selectively eliminate promyelocytic leukemia cell HL60 by ALA based PDT. The photosensitization of ALA based PDT caused the necrosis of HL60 cell, so it could be used for inactivation of certain leukemia cells.

  1. Managing potential drug-drug interactions between gastric acid-reducing agents and antiretroviral therapy: experience from a large HIV-positive cohort.

    Science.gov (United States)

    Lewis, J M; Stott, K E; Monnery, D; Seden, K; Beeching, N J; Chaponda, M; Khoo, S; Beadsworth, M B J

    2016-02-01

    Drug-drug interactions between antiretroviral therapy and other drugs are well described. Gastric acid-reducing agents are one such class. However, few data exist regarding the frequency of and indications for prescription, nor risk assessment in the setting of an HIV cohort receiving antiretroviral therapy. To assess prevalence of prescription of gastric acid-reducing agents and drug-drug interaction within a UK HIV cohort, we reviewed patient records for the whole cohort, assessing demographic data, frequency and reason for prescription of gastric acid-reducing therapy. Furthermore, we noted potential drug-drug interaction and whether risk had been documented and mitigated. Of 701 patients on antiretroviral therapy, 67 (9.6%) were prescribed gastric acid-reducing therapy. Of these, the majority (59/67 [88.1%]) were prescribed proton pump inhibitors. We identified four potential drug-drug interactions, which were appropriately managed by temporally separating the administration of gastric acid-reducing agent and antiretroviral therapy, and all four of these patients remained virally suppressed. Gastric acid-reducing therapy, in particular proton pump inhibitor therapy, appears common in patients prescribed antiretroviral therapy. Whilst there remains a paucity of published data, our findings are comparable to those in other European cohorts. Pharmacovigilance of drug-drug interactions in HIV-positive patients is vital. Education of patients and staff, and accurate data-gathering tools, will enhance patient safety.

  2. Prostate Hypofractionated Radiation Therapy: Injection of Hyaluronic Acid to Better Preserve The Rectal Wall

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Udrescu, Corina [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Devonec, Marian [Department of Urology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Tanguy, Ronan [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Sotton, Marie-Pierre [Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Enachescu, Ciprian [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Colombel, Marc [Department of Urology, Hopital Edouard Herriot, Lyon (France); Azria, David [Department of Radiation Oncology, Centre Val d' Aurelle, Montpellier (France); Jalade, Patrice [Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Ruffion, Alain [Department of Urology, Centre Hospitalier Lyon Sud, Pierre Benite (France)

    2013-05-01

    Purpose: The aim of this study was to evaluate the contribution of an injection of hyaluronic acid (HA) between the rectum and the prostate for reducing the dose to the rectal wall in a hypofractionated irradiation for prostate cancer. Methods and Materials: In a phase 2 study, 10 cc of HA was injected between the rectum and prostate. For 16 patients, the same intensity modulated radiation therapy plan (62 Gy in 20 fractions) was optimized on 2 computed tomography scans: CT1 (before injection) and CT2 (after injection). Rectal parameters were compared: dose to 2.5 cc (D2.5), 5 cc (D5), 10 cc (D10), 15 cc (D15), and 20 cc (D20) of rectal wall and volume of rectum covered by the 90% isodose line (V90), 80% (V80), 70% (V70), 60% (V60), and 50% (V50). Results: The mean V90, V80, V70, V60, and V50 values were reduced by 73.8% (P<.0001), 55.7% (P=.0003), 43.0% (P=.007), 34% (P=.002), and 25% (P=.036), respectively. The average values of D2.5, D5, D10, D15, and D20 were reduced by 8.5 Gy (P<.0001), 12.3 Gy (P<.0001), 8.4 Gy (P=.005), 3.7 Gy (P=.026), and 1.2 Gy (P=.25), respectively. Conclusions: The injection of HA significantly limited radiation doses to the rectal wall.

  3. 5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice.

    Science.gov (United States)

    Li, Yongning; Zhou, Qi; Hu, Zheng; Yang, Bin; Li, Qingsong; Wang, Jianhua; Zheng, Jinhua; Cao, Wenwu

    2015-01-01

    Sonodynamic therapy (SDT) is promising for treatment of cancer, but its effect on osteosarcoma is unclear. This study examined the effect of 5-Aminolevulinic Acid (5-ALA)-based SDT on the growth of implanted osteosarcoma and their potential mechanisms in vivo and in vitro. The dose and metabolism of 5-ALA and ultrasound periods were optimized in a mouse model of induced osteosarcoma and in UMR-106 cells. The effects of ALA-SDT on the proliferation and apoptosis of UMR-106 cells and the growth of implanted osteosarcoma were examined. The levels of mitochondrial membrane potential (ΔψM), ROS production, BcL-2, Bax, p53 and caspase 3 expression in UMR-106 cells were determined. Treatment with 5-ALA for eight hours was optimal for ALA-SDT in the mouse tumor model and treatment with 2 mM 5-ALA for 6 hours and ultrasound (1.0 MHz 2.0 W/cm2) for 7 min were optimal for UMR-106 cells. SDT, but not 5-ALA, alone inhibited the growth of implanted osteosarcoma in mice (Ptreatment with 5-ALA significantly enhanced the SDT-mediated apoptosis (posteosarcoma cells and BcL-2 expression, but increased levels of Bax, p53 and caspase 3 expression in the implanted osteosarcoma tissues (posteosarcoma growth in vivo and reduced UMR-106 cell survival by inducing osteosarcoma cell apoptosis through the ROS-related mitochondrial pathway.

  4. Examining the efficacy and safety of squaric acid therapy for treatment of recalcitrant warts in children.

    Science.gov (United States)

    Pandey, Shaily; Wilmer, Erin N; Morrell, Dean S

    2015-01-01

    The objective of the study was to determine the safety and efficacy of squaric acid dibutyl ester (SADBE) therapy on the treatment of recalcitrant warts in children. This retrospective chart review examined 72 patients treated using SADBE from July 2002 to December 2012. Patients were followed for 6 months to 11 years. Patients were treated at a pediatric dermatology outpatient clinic at the University of North Carolina at Chapel Hill. Seventy-two children with verrucae who failed initial treatment for warts were selected for the study. Full long-term follow-up was obtained in 48 patients. Four patients discontinued the use of SADBE because of adverse effects. The primary study outcome was efficacy of SADBE treatment. Adverse effects, dosages administered, type of wart, other cutaneous disease present, and level of immunosuppression were measured. Forty of 48 (83%) patients in whom treatment outcomes could be obtained reported complete resolution of their warts. Seventy percent of patients used a maximum concentration of 0.4% SADBE and 60% of patients reported no adverse effects. The majority of patients treated with SADBE reported complete resolution of warts. Most patients reported no adverse effects even while receiving doses as high as 2% daily. This study shows that SADBE is a safe and effective treatment for recalcitrant warts in children. © 2014 Wiley Periodicals, Inc.

  5. In vitro skin permeation and retention of 5-aminolevulinic acid ester derivatives for photodynamic therapy.

    Science.gov (United States)

    De Rosa, Fernanda Scarmato; Tedesco, Antônio Cláudio; Lopez, Renata Fonseca Vianna; Pierre, Maria Bernadete Riemma; Lange, Norbert; Marchetti, Juliana Maldonado; Rotta, Jeane Cristina Gomes; Bentley, Maria Vitória Lopes Badra

    2003-04-29

    In photodynamic therapy (PDT), 5-aminiolevulinic acid (5-ALA) applied topically is converted, via the heme cycle, into protoporphyrin IX (PpIX), a photosensitizing agent, which upon excitation with light can induce tumor destruction. Due to its hydrophilic and zwitterionic characteristics, 5-ALA has limited penetration into the skin. More lipophilic 5-ALA ester derivatives are expected to cross stratum corneum more easily than 5-ALA. According to the determination of the partition coefficients of 5-ALA methyl, n-butyl, n-hexyl and n-octyl esters, these compounds showed an increased affinity to the SC, with 5-ALA hexyl ester and 5-ALA-octyl ester having the highest partition coefficients. Our in vitro skin permeation studies demonstrated an increased permeated amount for hexyl-ALA after 6 h of incubation, compared to other esters and 5-ALA. After 6 h, more 5-ALA-hexyl ester and -octyl ester were retained at viable epidermis and dermis than 5-ALA. According to these results, and considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, it can be supposed that topical use of ester derivatives with longer chains (C(6) or C(8)) is an interesting proposal to optimize topical 5-ALA-PDT

  6. Monitoring lamivudine therapy in HBV-infected patients by the quantity and structures of circulating viral nucleic acids

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei(张伟); Hans Jorg Hacker; Maria Mildenberger; Claus H.Schroder; SU Qin(苏勤)

    2003-01-01

    To monitor the progression of lamivudine therapy by demonstrating HBV DNAs and RNAs in the serum of a chronically infected patient.Viral nucleic acids were extracted from serum samples taken during a 14-week treatment period and analyzed via competitive PCR and RT/PCR.The dynamic changes n the amount as well as in the structures can monitor therapy process very well.Our study indicated the level of polyadenylated viral RNA can be a marker for expression in general,and the appearance of replicative intermediates as a mirror of the mode of action of an antiviral drug.

  7. Amino Acid requirements in critically ill patients with acute kidney injury treated with continuous renal replacement therapy.

    Science.gov (United States)

    Btaiche, Imad F; Mohammad, Rima A; Alaniz, Cesar; Mueller, Bruce A

    2008-05-01

    Acute kidney injury in critically ill patients is often a complication of an underlying condition such as organ failure, sepsis, or drug therapy. In these patients, stress-induced hypercatabolism results in loss of body cell mass. Unless nutrition support is provided, malnutrition and negative nitrogen balance may ensue. Because of metabolic, fluid, and electrolyte abnormalities, optimization of nutrition to patients with acute kidney injury presents a challenge to the clinician. In patients treated with conventional intermittent hemodialysis, achieving adequate amino acid intake can be limited by azotemia and fluid restriction. With the use of continuous renal replacement therapy (CRRT), however, better control of azotemia and liberalization of fluid intake allow amino acid intake to be maximized to support the patient's metabolic needs. High amino acid doses up to 2.5 g/kg/day in patients treated with CRRT improved nitrogen balance. However, to our knowledge, no studies have correlated increased amino acid intake with improved outcomes in critically ill patients with acute kidney injury. Data from large, prospective, randomized, controlled trials are needed to optimize the dosing of amino acids in critically ill patients with acute kidney injury who are treated with CRRT and to study the safety of high doses and their effects on patient morbidity and survival.

  8. Use of acid suppressive therapy in hospitalized non-critically ill patients

    Institute of Scientific and Technical Information of China (English)

    Marwan; Sheikh-Taha; Sarah; Alaeddine; Julie; Nassif

    2012-01-01

    AIM: To assess the appropriateness of prescribing acid suppressive therapy (AST) in a general medicine service in a tertiary care hospital. METHODS: In this retrospective observational study, we reviewed the inpatient records of all patients admitted to the general medical service in a tertiary care hospital in Beirut, Lebanon, from April 1 to May 31, 2011. Treatment with AST was considered appropriate if the patient had a specific indication or appropriate treatment purpose [e.g. , gastro-esophageal reflux disease (GERD), peptic ulcer disease, dyspepsia, acute or suspected gastrointestinal (GI) bleeding]. Appropriate administration of stress ulcer prophylaxis (SUP) was derived from an internal guideline that is based on the American Society of Health System Pharmacists guidelines. Prophylaxis was considered appropriate if a patient had 1 absolute indication (coagulopathy or requiring mechanical ventilation), or 2 or more relative indications (sepsis, occult bleeding, use of high dose corticosteroids, recent use of non-steroidal anti-inflammatory drugs for more than 3 mo, renal or liver failure, enteral feeding and anticoagulant use). RESULTS: Of the 153 patient admissions during the study period, 130 patients (85%) were started on AST, out of which 11 (8.5%) had a diagnosis that sup-ports the use of this therapy (GI bleed, gastritis and GERD), 16 (12.3%) had an absolute indication for SUP, 59 (45.4%) had 2 or more relative indications for SUP, and 44 (33.8%) received AST without an appropriate indication. In addition, one patient with an absolute indication for SUP and four with two or more relative indications did not receive AST. Rabeprazole was the most frequently used AST (59.2%), followed by omeprazole (24.6%), esomeprazole (11.6%) and ranitidine (4.6%). The dose of AST was appropriate in 126 patients (96.9%) and the route of administration was appropriate in 123 patients (94.6%). Fifteen of the admitted patients (10%) were discharged on AST, 7 of which (47

  9. Usage of U7 small nuclear ribonucleic acid in gene therapy of hemoglobin D Punjab disorder: Rationale?

    Directory of Open Access Journals (Sweden)

    Viroj Wiwanitkit

    2013-01-01

    Full Text Available Background: Hemoglobin (Hb D Punjab disorder is a congenital hemoglobinopathy described in India. It is a disorder due to defect in beta-globin gene. Materials and Methods: Here, the author assesses the possibility of U7.623 gene therapy for Hb D Punjab disorder. A standard bioinformatic analysis to study the effect of co-expression between nucleic acid sequence for human Hb D Punjab beta-globin chain and U7.623 was performed. Result: It can be seen that fully recovery of Hb function and biological process can be derived via gene ontology study. Conclusion: Here, there is a rationale to use U7 small nuclear ribonucleic acid as a possible tool for gene therapy in Hb D Punjab disorder.

  10. Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation.

    Science.gov (United States)

    Liu, Kai; Wang, Zhi-qi; Wang, Shi-jiang; Liu, Ping; Qin, Yue-hong; Ma, Yan; Li, Xiao-Chen; Huo, Zhi-Jun

    2015-01-01

    Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU) is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA)-conjugated silica nanoparticles (SiNPs) to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP) was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage) compared with only 20% for 5-FU/silica nanoparticles (SNP)-treated group. The HA-conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer

  11. alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy.

    Science.gov (United States)

    Alleva, Renata; Nasole, Emanuele; Di Donato, Ferruccio; Borghi, Battista; Neuzil, Jiri; Tomasetti, Marco

    2005-07-29

    Hyperbaric oxygen (HBO) therapy is successfully used for the treatment of a variety of conditions. However, prolonged exposure to high concentrations of oxygen induces production of reactive oxygen species, causing damage to the cells. Thus, antioxidant supplementation has been proposed as an adjuvant to attenuate such deleterious secondary effects. We evaluated the effects of alpha-lipoic acid (LA) in patients affected by chronic wounds undergoing HBO treatment. LA supplementation efficiently reduces both the lipid and DNA oxidation induced by oxygen exposure. LA exerted its antioxidant activity by directly interacting with free radicals or by recycling vitamin E. An inhibitory effect of LA on the pro-inflammatory cytokine interleukin-6 was observed. Taken together, we demonstrated an adjuvant effect of LA in HBO therapy used for impaired wound healing treatment. We propose that LA may be used to further promote the beneficial effects of HBO therapy.

  12. Effects of 5-aminolevulinic acid-mediated sonodynamic therapy on macrophages

    Directory of Open Access Journals (Sweden)

    Cheng J

    2013-02-01

    Full Text Available Jiali Cheng,1,* Xin Sun,1,2,* Shuyuan Guo,1,* Wei Cao,1 Haibo Chen,1 Yinghua Jin,1 Bo Li,1 Qiannan Li,1 Huan Wang,1 Zhu Wang,3 Qi Zhou,3 Peng Wang,3 Zhiguo Zhang,3 Wenwu Cao,3,4 Ye Tian1,21Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, People’s Republic of China; 2Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, People’s Republic of China; 3Laboratory of Photo- and Sono-theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, People’s Republic of China; 4Materials Research Institute, The Pennsylvania State University, University Park, PA, USA*These authors contributed equally to this workBackground: Inflammatory cells exhibit an elevated level of protoporphyrin IX (PpIX after the administration of 5-aminolevulinic acid (ALA. Here, we investigate the sonodynamic effects of ALA-derived PpIX (ALA-PpIX on macrophages, which are the pivotal inflammatory cells in atherosclerosis.Methods and results: Cultured THP-1 macrophages were incubated with ALA. Fluorescence microscope and fluorescence spectrometer detection showed that intracellular PpIX increased with the concentration of ALA in the incubation solution in a time dependent manner; the highest level of intracellular PpIX was observed after 3-hour incubation. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays demonstrated that lower concentrations (less than 2 mM of ALA have no influence on cell viability (more than 90% of cells survived, but sonodynamic therapy (SDT with a low concentration of ALA significantly decreased the survival rate of cells, and the effect was increased with both ALA concentration and ultrasound exposure time. Cell apoptosis and necrosis induced by ALA-mediated SDT (ALA-SDT were measured using

  13. Combined therapy with {sup 131}I and retinoic acid in Korean patients with radioiodine-refractory papillary thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oh, So Won [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University Boramae Medical Center, Department of Nuclear Medicine, Seoul (Korea, Republic of); Moon, Seung-hwan; Chung, June-Key [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Park, Do Joon; Cho, Bo Youn [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Jung, Kyeong Cheon [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Lee, Dong Soo [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University WCU Graduate School of Convergence Science and Technology, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul (Korea, Republic of)

    2011-10-15

    The aim of this study was to assess the clinical outcome of redifferentiation therapy using retinoic acid (RA) in combination with {sup 131}I therapy, and to identify biological parameters that predict therapeutic response in Korean patients with radioiodine-refractory papillary thyroid carcinoma (PTC). A total of 47 patients (13 men, 34 women; age 54.2 {+-} 13.6 years) with radioiodine-refractory PTC underwent therapy consisting of consecutive treatment with {sup 131}I and RA. Each {sup 131}I/RA treatment cycle involved the administration of oral isotretinoin for 6 weeks at 1-1.5 mg/kg daily followed by a single oral dose of {sup 131}I (range 5.5-16.7 GBq). Therapeutic responses were determined using serum thyroglobulin (Tg) levels and the change in tumour size 6 months after completing the {sup 131}I/RA therapy. Biological parameters and pathological parameters before and after combined therapy were compared. After completing {sup 131}I/RA therapy, 1 patient showed a complete response, 9 partial response, 9 stable disease, and 28 progressive disease, representing an overall response rate of 21.3%. Univariate analysis revealed that an age of <45 years and a persistently high serum Tg level were related to a good response. No clinical response was achieved when metastases showing no iodine uptake were present. Multivariate regression analysis showed that an age of <45 years was significantly associated with a good response. Of the 24 patients with well-differentiated carcinoma, 5 (20.8%) responded to {sup 131}I/RA therapy, whereas all 6 patients with poorly differentiated carcinoma failed to respond. {sup 131}I/RA therapy was found to elicit a response rate of 21.3% among patients with radioiodine-refractory PTC, and an age of <45 years was found to be significantly associated with a good response. (orig.)

  14. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); EMR3738, Université Lyon 1, Lyon (France); Decullier, Evelyne; Bin, Sylvie [Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon (France); Université Lyon 1, Lyon (France); EA SIS, Université de Lyon, Lyon (France); Faix, Antoine [Department of Urology, Clinique Beausoleil, Montpellier (France); Ruffion, Alain [Université Lyon 1, Lyon (France); Department of Urology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Jalade, Patrice [Department of Medical Physics, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France); Udrescu, Corina; Enachescu, Ciprian [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France)

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  15. Spray Dried Aerosol Particles of Pyrazinoic Acid Salts for Tuberculosis Therapy. [Corrected].

    Science.gov (United States)

    Durham, P G; Zhang, Y; German, N; Mortensen, N; Dhillon, J; Mitchison, D A; Fourie, P B; Hickey, A J

    2015-08-03

    Tuberculosis is the most serious infectious disease caused by a single organism, Mycobacterium tuberculosis (Mtb). The standard of care is a protracted and complex drug treatment regimen made more complicated and of longer duration by the incidence of multiple and extensively drug resistant disease. Pulmonary delivery of aerosols as a supplement to the existing regimen offers the advantage of delivering high local drug doses to the initial site of infection and most prominent organ system involved in disease. Pyrazinamide is used in combination with other drugs to treat tuberculosis. It is postulated that the action of pyrazinoic acid (POA), the active moiety of pyrazinamide, may be enhanced by local pH adjustment, when presented as a salt form. POA was prepared as leucine (POA-leu) and ammonium salts (POA-NH4), spray dried, and characterized in terms of physicochemical properties (melting point, crystallinity, moisture content), aerodynamic performance (aerodynamic particle size distribution, emitted dose), and in vitro inhibitory effect on two mycobacteria (Mtb and Mycobacterium bovis). Particles were prepared in sizes suitable for inhalation (3.3 and 5.4 μm mass median aerodynamic diameter and 61 and 40% of the aerodynamic particle size distribution less than 4.46 μm, as measured by inertial impaction, for POA-leu and POA-NH4, respectively) and with properties (stoichiometric 1:1 ratio of salt to drug, melting points at ∼180 °C, with water content of <1%) that would support further development as an inhaled dosage form. In addition, POA salts demonstrated greater potency in inhibiting mycobacterial growth compared with POA alone, which is promising for therapy.

  16. Efficacy of microencapsulated lactic acid bacteria in Helicobater pylori eradication therapy

    Directory of Open Access Journals (Sweden)

    Maha A Khalil

    2015-01-01

    Full Text Available Background: Probiotic delivery systems are widely used nutraceutical products for the supplementation of natural intestinal flora. These delivery systems vary greatly in the effectiveness to exert health benefits for a patient. This study focuses on providing probiotic living cells with a physical barrier against adverse environmental conditions. Materials and Methods: Microencapsulation of the selected lactic acid bacteria (LAB using chitosan and alginate was performed. Physical examination of the formulated LAB microcapsules was observed using phase contrast inverted microscope and scanning electron microscope (SEM. Finally, the survival of microencapsulated and noncapsulated bacteria was cheeked in the simulated human gastric tract (GT. The potential antimicrobial activity of the most potent microencapsulated LAB strain was in vivo evaluated in rabbit models. Results: Microencapsulated L. plantarum, L. acidophilus, and L. bulgaricus DSMZ 20080 were loaded with 1.03 × 10 10 CFU viable bacteria/g, 1.9 × 10 10 CFU viable bacteria/g, and 5.5 × 10 9 CFU viable bacteria/g, respectively. The survival of microencapsulated cells was significantly higher than that of the free cells after exposure to simulated gastric juice (SGJ at pH 2. Additionally, in simulated small intestine juice (SSJ, larger amounts of the selected LAB cells were found, whereas in simulated colon juice (SCJ, the released LAB reached the maximum counts. In vivo results pointed out that an 8-week supplementation with a triple therapy of a microencapsulated L. plantarum, L. acidophilus, and L. bulgaricus DSMZ 20080 might be able to reduce H. pylori. Conclusion: Microencapsulated probiotics could possibly compete with and downregulate H. pylori infection in humans.

  17. Cell cycle phase influences tumour cell sensitivity to aminolaevulinic acid-induced photodynamic therapy in vitro.

    Science.gov (United States)

    Wyld, L.; Smith, O.; Lawry, J.; Reed, M. W.; Brown, N. J.

    1998-01-01

    Photodynamic therapy (PDT) is a form of cancer treatment based on the destruction of cells by the interaction of light, oxygen and a photosensitizer. Aminolaevulinic acid (ALA) is the prodrug of the photosensitizer protoporphyrin IX (PpIX). ALA-induced PDT depends on the rate of cellular synthesis of PpIX, which may vary with cell cycle phase. This study has investigated the relationship between cell cycle phase, PpIX generation and phototoxicity in synchronized and unsynchronized bladder cancer cells (HT1197). In unsynchronized cells, relative PpIX fluorescence values (arbitrary units) were significantly different between cell cycle phases after a 1-h ALA incubation (G1 24.8 +/- 0.7; S-phase, 32.7 +/- 0.8, P < 0.05; G2 35.4 +/- 0.8, P < 0.05). In synchronized cells after a 1-h ALA incubation, cells in G1 produced less PpIX than those in S-phase or G2 [6.65 +/- 1.1 ng per 10(5) cells compared with 15.5 +/- 2.1 (P < 0.05), and 8.1 +/- 1.8 ng per 10(5) cells (not significant) respectively] and were significantly less sensitive to ALA-induced PDT (% survival, G1 76.2 +/- 8.3; S-phase 49.7 +/- 4.6, P < 0.05; G2 44.2 +/- 2.4, P < 0.05). This differential response in tumour cells may have implications for clinical PDT, resulting in treatment resistance and possible failure in complete tumour response. PMID:9662250

  18. Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation

    Directory of Open Access Journals (Sweden)

    Liu K

    2015-10-01

    -conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer therapy. Keywords: colon cancer, 5-fluorouracil, nanoparticles, hyaluronic acid, apoptosis

  19. Effect of low-level laser therapy on tissue repair after dental extraction in rats administered zoledronic acid and dexamethasone

    Science.gov (United States)

    Weber, João Batista Blessmann; Camilotti, Renata Stifelman; Jasper, Juliana; Casagrande, Liliane Cristina Onofre; Maito, Fábio Luiz Dal Moro

    2017-05-01

    Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic and oncological pathologies involving the skeletal system. Because of the severity of the BP associated osteonecrosis of the jaws, the difficulties of treatment, and patient discomfort, additional support methods for their management are needed. Laser therapy has an easy handling, photobiostimulator effect on tissues healing, so it can be considered a preferred therapy. The aim of this study was to evaluate the influence of low-level laser therapy in the 685- and 830-nm wavelength in the healing process of the bone and soft tissues in rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that underwent a surgery for the extraction of upper molars. There were statistically significant differences in the clinical evaluation of the wound and the weight of the animals. Regarding the histological evaluation, it was possible to observe the different maturations of the healing stage between groups. The effect of drug therapy with ZA and dexamethasone in the bone tissue repair process induces osteonecrosis of the jaw in rats and slows down the healing process. In the laser groups, at the stipulated dosimetry, a positive influence on the bone and soft tissue repair process was observed.

  20. Omega-3 fatty acid supplementation in cancer therapy. Does eicosapentanoic acid influence the radiosensitivity of tumor cells?

    Energy Technology Data Exchange (ETDEWEB)

    Manda, Katrin; Kriesen, Stephan; Hildebrandt, Guido [Rostock Univ. (Germany). Dept. of Radiotherapy; Fietkau, Rainer; Klautke, Gunther [Univ. Hospital Erlangen, Erlangen (Germany). Dept. of Radiation Oncology

    2011-02-15

    Purpose: The aim of this study was to evaluate whether the omega-3 polyunsaturated fatty acid cis-5,8,11,14,17-eicosapentanoic acid (EPA) can enhance the radiosensitivity of different human tumor cell lines. Materials and Methods: Colon adenocarcinoma cells HT-29, and two glioblastoma multiforme tumor cells T98G and U251 were cultured under standard conditions. Cell growth was observed during administration with different concentrations of EPA, using it as the free fatty acid dissolved in ethanol or bound to bovine serum albumin. To investigate the influence of EPA (free and bound) on radiosensitivity, tumor cells were pretreated 30 minutes or 24 hours prior to irradiation with the fatty acid. Cell survival was measured by colony-forming assays. Results: When combined with irradiation, incubation with EPA was found to result in enhanced radiosensitivity with substantial variation: while there was strong radiosensitization for HT-29 and U251 cells, almost no effect for T98G cells was observed. A marked radiosensitization was clearly dependent on the treatment schedule. Conclusion: The observations suggest that EPA is not only a nutritional adjuvant but also may be a potential candidate to enhance the efficacy of irradiation on human cancer cells. (orig.)

  1. 5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice.

    Directory of Open Access Journals (Sweden)

    Yongning Li

    Full Text Available Sonodynamic therapy (SDT is promising for treatment of cancer, but its effect on osteosarcoma is unclear. This study examined the effect of 5-Aminolevulinic Acid (5-ALA-based SDT on the growth of implanted osteosarcoma and their potential mechanisms in vivo and in vitro.The dose and metabolism of 5-ALA and ultrasound periods were optimized in a mouse model of induced osteosarcoma and in UMR-106 cells. The effects of ALA-SDT on the proliferation and apoptosis of UMR-106 cells and the growth of implanted osteosarcoma were examined. The levels of mitochondrial membrane potential (ΔψM, ROS production, BcL-2, Bax, p53 and caspase 3 expression in UMR-106 cells were determined.Treatment with 5-ALA for eight hours was optimal for ALA-SDT in the mouse tumor model and treatment with 2 mM 5-ALA for 6 hours and ultrasound (1.0 MHz 2.0 W/cm2 for 7 min were optimal for UMR-106 cells. SDT, but not 5-ALA, alone inhibited the growth of implanted osteosarcoma in mice (P<0.01 and reduced the viability of UMR-106 cells (p<0.05. ALA-SDT further reduced the tumor volumes and viability of UMR-106 cells (p<0.01 for both. Pre-treatment with 5-ALA significantly enhanced the SDT-mediated apoptosis (p<0.01 and morphological changes. Furthermore, ALA-SDT significantly reduced the levels of ΔψM, but increased levels of ROS in UMR-106 cells (p<0.05 or p<0.01 vs. the Control or the Ultrasound. Moreover, ALA-SDT inhibited the proliferation of osteosarcoma cells and BcL-2 expression, but increased levels of Bax, p53 and caspase 3 expression in the implanted osteosarcoma tissues (p<0.05 or p<0.01 vs. the Control or the Ultrasound.The ALA-SDT significantly inhibited osteosarcoma growth in vivo and reduced UMR-106 cell survival by inducing osteosarcoma cell apoptosis through the ROS-related mitochondrial pathway.

  2. 5-Aminolevulinic acid-mediated photodynamic therapy for oral cancers and precancers

    Directory of Open Access Journals (Sweden)

    Hsin-Ming Chen

    2012-12-01

    Full Text Available Previous studies have used both systemic and topical 5-aminolevulinic acid (ALA-mediated photodynamic therapy (PDT to treat oral precancers including oral leukoplakia (OL, oral erythroleukoplakia (OEL, and oral verrucous hyperplasia (OVH as well as oral cancers including oral verrucous carcinoma (OVC and oral squamous cell carcinoma (OSCC. Systemic ALA-PDT has been used to treat oral dysplastic lesions and oral cancers with promising clinical outcomes. The efficacy of a regular topical ALA-PDT (fluence rate, 100 mW/cm2; light dose, 100 J/cm2 was tested on an extensive buccal OVC and an enhanced topical ALA-PDT (fluence rate, 200 mW/cm2; light dose, 200 J/cm2 on an early-invasive OSCC; complete regression of the carcinomas was demonstrated after 28 and 18 PDT treatments, respectively. Several previous studies showed relatively good outcomes for OL lesions treated with topical ALA-PDT. However, it was found that the regular topical ALA-PDT is very effective for OVH and OEL lesions but less so for OL lesions. Better PDT outcomes are significantly associated with OVH and OEL lesions with smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer. Moreover, the thicker surface keratin layer on the OL lesions is responsible for the relatively poorer PDT outcomes for OL lesions. In addition, both light emitting diode light- and laser light-mediated topical ALA-PDTs are comparative treatment modalities for OVH and OEL lesions. Methotrexate- or vitamin D3-preconditioned prostate or skin carcinoma cells can accumulate more intracellular protoporphyrin IX, resulting in an increased killing of these preconditioned cells by subsequent ALA-PDT. Because chemotherapy can help destroy carcinoma cells and tumor-associated vasculatures and cryotherapy pretreatment may help the diffusion of ALA into lesional epithelial cells, the chemotherapy or cryotherapy-combined topical ALA-PDT may be a new effective PDT alternative for

  3. Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schieferstein, Hanno

    2013-07-01

    Folic acid, also known as vitamin B9, is the oxidized form of 5,6,7,8-tetrahydrofolate, which serves as methyl- or methylene donor (C1-building blocks) during DNA synthesis. Under physiological conditions the required amount of 5,6,7,8-tetrahydrofolate for survival of the cell is accomplished through the reduced folate carrier (RFC). In contrast, the supply of 5,6,7,8-tetrahydrofolate is insufficient under pathophysiological conditions of tumors due to an increased proliferation rate. Consequently, many tumor cells exhibit an (over)expression of the folate receptor. This phenomenon has been applied to diagnostics (PET, SPECT, MR) to image FR-positive tumors and on the other hand to treat malignancies related to a FR (over)expression. Based on this concept, a new {sup 18}F-labeled folate for PET imaging has been developed and was evaluated in vivo using tumor-bearing mice. The incorporation of oligoethylene spacers into the molecular structure led to a significant enhancement of the pharmacokinetics in comparison to previously developed {sup 18}F-folates. The liver uptake could be reduced by one sixth by remaining a tumor uptake of 3%ID/g leading to better contrast ratios. Encouraged by these results, a clickable {sup 18}F-labeled serine-based prosthetic group has been synthesized, again with the idea to improve the metabolic and pharmacokinetic profile of hydrophilic radiotracers. Therefore, an alkyne-carrying azido-functionalized serine derivative for coupling to biomolecules was synthesized and a chlorine leaving group for {sup 18}F-labeling, which could be accomplished using a microwave-assisted synthesis, a [K is contained in 2.2.2]{sup +}/carbonate system in DMSO. Radiochemical yields of 77±6% could be achieved. The promising results obtained from the FR-targeting concept in the diagnostic field have been transferred to the boron neutron capture therapy. Therefore, a folate derivative was coupled to different boron clusters and cell uptake studies were

  4. Assessment of the Effects of Zoledronic Acid Therapy on Bone Metabolic Indicators in Hormone-Resistant Prostate Cancer Patients with Bone Metastatasis

    Science.gov (United States)

    Demirtas, Abdullah; Sahin, Nurettin; Caniklioglu, Mehmet; Kula, Mustafa; Ekmekcioglu, Oguz; Tatlisen, Atila

    2011-01-01

    Purpose. Assessment of effects of zoledronic acid therapy on bone metabolic indicators in hormone-resistant prostate cancer patients with bone metastasis. Material and Methods. Hormone-resistant prostate cancer patients who were identified to have metastases in their bone scintigraphy were taken to trial group. Before administration of zoledronic acid, routine tests for serum calcium, total alkalen phosphates were studied. Sample sera for bone metabolic indicators BALP, PINP, and ICTP were collected. Bone pain was assessed via visual analogue scale and performance via Karnofsky performance scale. Four mg zoledronic acid was administered intravenously once a month. Results. When serum levels of bone forming indicators PINP; BALP were compared before and after therapy, there were insignificant decreases (P = .33, P = .21, resp.). Serum levels of bone destruction indicator ICTP was compared, and there was a significant decrease after zoledronic acid therapy (P = .04). When performances of the patients were compared during therapy period, performances decreased significantly due to progress of illness (P = .01). All patients had ostalgia caused by bone metastases at various degrees. Significant decrease in pain scores was observed (P < .01). Conclusion. Zoledronic acid therapy decreased bone destruction and was effective in palliation of pain in patient with bone metastasis. Using bone metabolic indicators during followup of zoledronic acid therapy might be useful. PMID:22084798

  5. The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment

    Directory of Open Access Journals (Sweden)

    Shi J

    2013-07-01

    Full Text Available Jinjin Shi,* Rourou Ma,* Lei Wang, Jing Zhang, Ruiyuan Liu, Lulu Li, Yan Liu, Lin Hou, Xiaoyuan Yu, Jun Gao, Zhenzhong Zhang School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, People's Republic of China*These authors contributed equally to this workAbstract: Carbon nanotubes (CNTs have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME, was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy.Keywords: photodynamic therapy, photothermal therapy, HA-derivatized carbon nanotubes, tumor targeting, synergistic effect, hematoporphyrin monomethyl ether

  6. Methylaminolaevulinic acid photodynamic therapy in the treatment of erythroplasia of Queyrat

    OpenAIRE

    Feldmeyer, L; Krausz-Enderlin, V; Töndury, B; Hafner, J.; French, L.E.; Hofbauer, G.F.L.

    2011-01-01

    BACKGROUND: Erythroplasia of Queyrat (EQ) is an intra-epithelial carcinoma of the penis. Progression to invasive carcinoma may occur. Its cause is unknown but some evidence suggests infection with human papillomavirus in the pathogenesis of EQ; however, recent data do not confirm this. Therapy is difficult and associated with important recurrence rates. Photodynamic therapy (PDT) employs a photosensitizer excited by visible light. The resulting photodynamic reaction selectively destroys atyp...

  7. Acquired resistance of Nocardia brasiliensis to clavulanic acid related to a change in beta-lactamase following therapy with amoxicillin-clavulanic acid.

    Science.gov (United States)

    Steingrube, V A; Wallace, R J; Brown, B A; Pang, Y; Zeluff, B; Steele, L C; Zhang, Y

    1991-01-01

    Previous studies have demonstrated that Nocardia brasiliensis is susceptible to amoxicillin-clavulanic acid and that its beta-lactamases are inhibited in vitro by clavulanic acid. A cardiac transplant patient with disseminated infection caused by N. brasiliensis was treated with this drug combination with good response, but relapsed while still on therapy. The relapse isolate was found to be identical to the initial isolate by using genomic DNA restriction fragment patterns obtained by pulsed field gel electrophoresis, but it was resistant to amoxicillin-clavulanic acid. On isoelectric focusing, the beta-lactamase from the relapse isolate exhibited a shift in the isoelectric point (pI) of its major band from 5.10 to 5.04 compared with the enzyme from the pretreatment isolate. As determined by using values of the amount of beta-lactamase inhibitor necessary to give 50 +/- 5% inhibition of beta-lactamase-mediated hydrolysis of 50 microM nitrocefin, the beta-lactamase of the relapse isolate was also 200-fold more resistant than the enzyme from the pretreatment isolate to clavulanic acid and was more resistant to sulbactam, tazobactam, cloxacillin, and imipenem. The beta-lactamase of the relapse isolate exhibited a 10-fold decrease in hydrolytic activity for cephaloridine and other hydrolyzable cephalosporins compared with that for nitrocefin. Acquired resistance to amoxicillin-clavulanic acid in this isolate of N. brasiliensis appears to have resulted from a mutational change affecting the inhibitor and active site(s) in the beta-lactamase. Images PMID:2039203

  8. Continuous renal replacement therapy amino acid, trace metal and folate clearance in critically ill children

    Science.gov (United States)

    We hypothesized that continuous veno-venous hemodialysis (CVVHD) results in amino acid, trace metals, and folate losses, thereby adversely impacting nutrient balance. Critically ill children receiving CVVHD were studied prospectively for 5 days. Blood concentrations, amino acids, copper, zinc, man...

  9. Synthesis of esters of androgens with unsaturated fatty acids for androgen requiring therapy.

    Science.gov (United States)

    Aiello, F; Garofalo, A; Aloisi, A M; Lamponi, S; Magnani, A; Petroni, A

    2013-06-01

    Androgens' metabolism and activity are gaining a more and more important role in human physiology particularly referring to aging and to neurodegenerative diseases. Androgen treatment is often required for long-lasting disorders. In order to improve their duration and effects, androgens can be administered as esters of carboxylic acids. The novelty of our research is the use of esters of androgens with specific unsaturated fatty acids, in order to reduce possible side effects particularly related to chronic pathologies with altered lipid homeostasis such as X-linked adrenoleukodystrophy and cardiovascular disorders. Thus the esters of the main androgenic substances testosterone, dihydrotestosterone (DHT) and their metabolite 5α-androstan-3α,17β-diol were chemically obtained by coupling with different unsaturated fatty acids. To this aim, fatty acids with various degree of unsaturation and belonging to different series were selected. Specifically, oleic acid (18:1, n-9), linoleic acid (18:2, n-6), and the n-3 fatty acids, α-linolenic acid (18:3), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6) were used obtaining corresponding esters with acceptable yields and good degree of purity. All the synthesized compounds were tested for their cytotoxic activities in mouse NIH3T3 and human astrocyte cell lines. The esters demonstrated good tolerability and no in vitro cytotoxic effect in both cell cultures. After these promising preliminary results, the esters will be suitable for in vivo studies in order to ascertain their pharmacokinetic characteristics and their biological effects.

  10. Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy.

    Science.gov (United States)

    Walters, Julian R F

    2014-07-01

    Chronic diarrhoea induced by bile acids is common and the underlying mechanisms are linked to homeostatic regulation of hepatic bile acid synthesis by fibroblast growth factor 19 (FGF19). Increasing evidence, including that from several large case series using SeHCAT (selenium homocholic acid taurine) tests for diagnosis, indicates that bile acid diarrhoea (BAD) accounts for a sizeable proportion of patients who would otherwise be diagnosed with IBS. Studies of other approaches for diagnosis of BAD have shown increased bile acid synthesis, increased faecal levels of primary bile acids, dysbiosis and different urinary volatile organic compounds when compared with healthy controls or with other diseases. The role of the ileal hormone FGF19 in BAD has been strengthened: a prospective clinical study has confirmed low FGF19 levels in BAD, and so a test to measure these levels could be developed for diagnosis. In animal models, FGF19 depletion by antibodies produces severe diarrhoea. Bile acids affect colonic function through farnesoid X receptor (FXR) and TGR5 receptors. As well as these effects in the colon, FXR-dependent stimulation of ileal FGF19 production could be a logical mechanism to provide therapeutic benefit in BAD. Further studies of FGF19 in humans hold promise in providing novel treatments for this cause of chronic diarrhoea.

  11. Gastric exocrine and endocrine cell morphology under prolonged acid inhibition therapy

    DEFF Research Database (Denmark)

    Fiocca, R; Mastracci, L; Attwood, S E;

    2012-01-01

    Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals.......Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals....

  12. Therapeutic efficacy for hepatocellular carcinoma by boric acid-mediated boron neutron capture therapy in a rat model.

    Science.gov (United States)

    Lin, Sy-Yu; Lin, Chen-Jou; Liao, Jiunn-Wang; Peir, Jinn-Jer; Chen, Wei-Lin; Chi, Chin-Wen; Lin, Yung-Chang; Liu, Yu-Ming; Chou, Fong-In

    2013-11-01

    Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Boron neutron capture therapy (BNCT) may provide an alternative therapy for HCC. This study investigated the therapeutic efficacy of boric acid (BA)-mediated BNCT for HCC in a rat model. The pharmacokinetic and biodistribution of BA in N1S1 tumor-bearing rats were analyzed. Rats were injected with 25 mg B/kg body weight via tail veins before neutron irradiation at the Tsing Hua Open-pool Reactor, and the efficacy of BNCT was evaluated from the tumor size, tumor blood flow, and biochemical analyses. HCC-bearing rats administered BNCT showed reductions in tumor size on ultrasound imaging, as well as an obvious reduction in the distribution of tumor blood flow. The lesion located in livers had disappeared on the 80th day after BNCT; a recovery of values to normal levels was also recorded. BA-mediated BNCT is a promising alternative for liver cancer therapy since the present study demonstrated the feasibility of curing a liver tumor and restoring liver function in rats. Efforts are underway to investigate the histopathological features and the detailed mechanisms of BA-mediated BNCT.

  13. D-amino acid oxidase gene therapy sensitizes glioma cells to the antiglycolytic effect of 3-bromopyruvate.

    Science.gov (United States)

    El Sayed, S M; Abou El-Magd, R M; Shishido, Y; Chung, S P; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

    2012-01-01

    Glioma tumors are refractory to conventional treatment. Glioblastoma multiforme is the most aggressive type of primary brain tumors in humans. In this study, we introduce oxidative stress-energy depletion (OSED) therapy as a new suggested treatment for glioblastoma. OSED utilizes D-amino acid oxidase (DAO), which is a promising therapeutic protein that induces oxidative stress and apoptosis through generating hydrogen peroxide (H2O2). OSED combines DAO with 3-bromopyruvate (3BP), a hexokinase II (HK II) inhibitor that interferes with Warburg effect, a metabolic alteration of most tumor cells that is characterized by enhanced aerobic glycolysis. Our data revealed that 3BP induced depletion of energetic capabilities of glioma cells. 3BP induced H2O2 production as a novel mechanism of its action. C6 glioma transfected with DAO and treated with D-serine together with 3BP-sensitized glioma cells to 3BP and decreased markedly proliferation, clonogenic power and viability in a three-dimensional tumor model with lesser effect on normal astrocytes. DAO gene therapy using atelocollagen as an in vivo transfection agent proved effective in a glioma tumor model in Sprague-Dawley (SD) rats, especially after combination with 3BP. OSED treatment was safe and tolerable in SD rats. OSED therapy may be a promising therapeutic modality for glioma.

  14. MRI evaluation of injectable hyaluronic acid-based hydrogel therapy to limit ventricular remodeling after myocardial infarction.

    Science.gov (United States)

    Dorsey, Shauna M; McGarvey, Jeremy R; Wang, Hua; Nikou, Amir; Arama, Leron; Koomalsingh, Kevin J; Kondo, Norihiro; Gorman, Joseph H; Pilla, James J; Gorman, Robert C; Wenk, Jonathan F; Burdick, Jason A

    2015-11-01

    Injectable biomaterials are an attractive therapy to attenuate left ventricular (LV) remodeling after myocardial infarction (MI). Although studies have shown that injectable hydrogels improve cardiac structure and function in vivo, temporal changes in infarct material properties after treatment have not been assessed. Emerging imaging and modeling techniques now allow for serial, non-invasive estimation of infarct material properties. Specifically, cine magnetic resonance imaging (MRI) assesses global LV structure and function, late-gadolinium enhancement (LGE) MRI enables visualization of infarcted tissue to quantify infarct expansion, and spatial modulation of magnetization (SPAMM) tagging provides passive wall motion assessment as a measure of tissue strain, which can all be used to evaluate infarct properties when combined with finite element (FE) models. In this work, we investigated the temporal effects of degradable hyaluronic acid (HA) hydrogels on global LV remodeling, infarct thinning and expansion, and infarct stiffness in a porcine infarct model for 12 weeks post-MI using MRI and FE modeling. Hydrogel treatment led to decreased LV volumes, improved ejection fraction, and increased wall thickness when compared to controls. FE model simulations demonstrated that hydrogel therapy increased infarct stiffness for 12 weeks post-MI. Thus, evaluation of myocardial tissue properties through MRI and FE modeling provides insight into the influence of injectable hydrogel therapies on myocardial structure and function post-MI.

  15. Comparison of tranexamic acid (Transamin and traditional therapy for sudden deafness.

    Directory of Open Access Journals (Sweden)

    Ohsaki,Katsuichiro

    1980-11-01

    Full Text Available The effectiveness of tranexamic acid treatment for sudden deafness was studied in detail. The results of treatment with tranexamic acid administration in 19 cases (25 ears of sudden deafness and two historical control groups using various treatments were compared by the chi square contingency test. The data suggested that tranexamic acid treatment may be superior to traditional treatments especially if treatment is begun early. Among ears treated with tranexamic acid, 11 ears (44% were healed or recovered remarkably, 8 ears (32% recovered slightly and 6 ears (24% were unchanged or worsened. Fibrinolysis in the inner ear may be the pathophysiology of sudden deafness. Treatment with tranexamic acid starting within 4 days after onset of symptoms was most effective in patients whose initial audiogram was flat or concave, initial average hearing loss at 5 frequencies (250 Hz, 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz was between 23 dB and 76 dB (mean; 45.1 dB and was not accompanied by dizziness.

  16. Tailoring folic acid and methotrexate-attributed quantum dots for integrated cancer cell imaging and therapy

    Science.gov (United States)

    Fahmi, Mochamad Zakki; Chang, Jia-Yaw

    2016-03-01

    Potential application of folic acid and methotrexate-attributed AgInS2-ZnS quantum dots on both detection and therapeutic of cancer cell were intensively investigated on this study. In the initial step, the bright luminescent of QDs, with % QY up to 55.3, were synthesized with one-pot two-step process resulting narrow particle distribution and successfully transferred to water phase without significant effect on optical properties. The water-soluble AgInS2-ZnS quantum dots (QDs) encapsulated with oleylamine have been successfully prepared by ultrasonication assisting. Several aspect including QDs characterization, pH stability, ionic strength, and bonding properties were investigated to reach desired condition of water-soluble AgInS2-ZnS QDs. Folic acid was further conjugated to QDs for HeLa and MCF7 cancer cell imaging to performs the targeting capability. Moreover, folic acid is efficiently internalized into cell through the receptor-mediated endocytosis even when conjugated with a wide variety of molecules. Confocal imaging characterization further informs folic acid-conjugated AgInS2-ZnS QDs could most specific targeted to the human cervical (HeLa) cells. The therapeutic feature of QDs on HeLa cancer cell was conjugated by attributing methotrexate on the QDs, instead of folic acid, and the design could improve on inhibiting the cancer cell viability as well as its fluorescent intensity.

  17. Carglumic acid: an additional therapy in the treatment of organic acidurias with hyperammonemia?

    Directory of Open Access Journals (Sweden)

    Guffon Nathalie

    2008-01-01

    Full Text Available Abstract Background Hyperammonemia in patients with methylmalonic aciduria (MMA and propionic aciduria (PA is caused by accumulation of propionyl-CoA which decreases the synthesis of N-acetyl-glutamate, the natural activator of carbamyl phosphate synthetase 1. A treatment approach with carglumic acid, the structural analogue of N-acetyl-glutamate, has been proposed to decrease high ammonia levels encountered in MMA and PA crises. Case presentation We described two patients (one with MMA and one with PA with hyperammonemia at diagnosis. Carglumic acid, when associated with standard treatment of organic acidurias, may be helpful in normalizing the ammonia level. Conclusion Even though the usual treatment which decreases toxic metabolites remains the standard, carglumic acid could be helpful in lowering plasma ammonia levels over 400 micromol/L more rapidly.

  18. Carglumic acid: an additional therapy in the treatment of organic acidurias with hyperammonemia?

    Science.gov (United States)

    Levrat, Virginie; Forest, Isabelle; Fouilhoux, Alain; Acquaviva, Cécile; Vianey-Saban, Christine; Guffon, Nathalie

    2008-01-01

    Background Hyperammonemia in patients with methylmalonic aciduria (MMA) and propionic aciduria (PA) is caused by accumulation of propionyl-CoA which decreases the synthesis of N-acetyl-glutamate, the natural activator of carbamyl phosphate synthetase 1. A treatment approach with carglumic acid, the structural analogue of N-acetyl-glutamate, has been proposed to decrease high ammonia levels encountered in MMA and PA crises. Case presentation We described two patients (one with MMA and one with PA) with hyperammonemia at diagnosis. Carglumic acid, when associated with standard treatment of organic acidurias, may be helpful in normalizing the ammonia level. Conclusion Even though the usual treatment which decreases toxic metabolites remains the standard, carglumic acid could be helpful in lowering plasma ammonia levels over 400 micromol/L more rapidly. PMID:18234091

  19. Hyaluronic acid as a rescue therapy for trinitrobenzene sulfonic acid-induced colitis through Cox-2 and PGE2 in a Toll-like receptor 4-dependent way

    Institute of Scientific and Technical Information of China (English)

    Huan CHEN; Mahesh MAHASETH; Yah ZHANG

    2011-01-01

    We hypothesized whether systemic administration of high-molecular-weight hyaluronic acid (HMW HA) could rescue trinitrobenzene sulfonic acid (TNBS)-induced colitis through Toll-like receptor 4 (TLR4) signal.C3H/HeN mice and C3H/HeJ mice were used.Mice were divided into four groups:control,50% ethanol treatment group,TNBS treatment group,and TNBS plus HA treatment group.The weight changes,clinical scores,macroscopic scores,and histological scores were recorded.Cyclooxygenase 2 (Cox-2) and prostaglandin E2 (PGE2) expressions were measured both in colons and peritoneal macrophages from these mice.HA was a rescue therapy for the colitis induced by TNBS only in C3H/HeN mice.The clinical score,macroscopic score,and histological score were much lower in C3H/HeN mice receiving TNBS plus HA treatment.Cox-2 and PGE2 expressions only increased in C3H/HeN mice.These Cox-2 expressing cells were macrophages.HA can also promote the production of Cox-2 and PGE2 in peritoneal macrophages from C3H/HeN mice.Our data demonstrated that HMW HA can rescue TNBS-induced colitis through inducing Cox-2 and PGE2 expressions in a TLR4-dependent way.Macrophages may be the effector cells of HMW HA.

  20. Boronated unnatural cyclic amino acids as potential delivery agents for neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kabalka, George W.; Shaikh, Aarif L. [Departments of Radiology and Chemistry, University of Tennessee, Knoxville, TN (United States); Barth, Rolf F.; Huo Tianyao; Yang Weilian [Department of Pathology, Ohio State University, Columbus, OH (United States); Gordnier, Pamela M. [Department of Biomedical Engineering and Cornell SIMS Laboratory, Cornell University, Ithaca, NY (United States); Chandra, Subhash, E-mail: sc40@cornell.edu [Department of Biomedical Engineering and Cornell SIMS Laboratory, Cornell University, Ithaca, NY (United States)

    2011-12-15

    Boron delivery characteristics of cis and trans isomers of a boronated unnatural amino acid, 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC) were tested in the B16 mouse model for human melanoma. Both ABCPC isomers delivered comparable boron to B16 melanoma tumor cells as L-p-boronophenylalanine (BPA). Secondary ion mass spectrometry (SIMS) analysis revealed the presence of boron throughout the tumor from these compounds, and a near homogeneous distribution between the nucleus and cytoplasm of B16 cells grown in vitro. These encouraging observations support further studies of these new boron carriers in BNCT.

  1. Survivin mRNA antagonists using locked nucleic acid, potential for molecular cancer therapy

    DEFF Research Database (Denmark)

    Fisker, Niels; Westergaard, Majken; Hansen, Henrik Frydenlund;

    2007-01-01

    synergistic effect when combining the mRNA antagonists against Survivin with the chemotherapeutic Taxol. This effect was demonstrated at concentrations of antagonists far lower than any previously demonstrated, indicating the high potential of locked nucleic acid for therapeutic use. Further characterisations...

  2. Immunopharmacology of 5-aminosalicylic acid and of glucocorticoids in the therapy of inflammatory bowel disease.

    Science.gov (United States)

    Nikolaus, S; Fölscn, U; Schreiber, S

    2000-01-01

    Glucocorticoids as well as 5-aminosalicylic acid have been used successfully in different formulations during the past 40 years for the treatment of both acute and chronic inflammation in inflammatory bowel disease. The mechanism by which the drugs exert their actions are only partially known. Recent studies of the immunoregulation in the lamina propria provide evidence that numerous therapeutic mechanisms contribute to the efficacy of these drugs including the inhibition of arachidonic acid metabolism, a decrease in radical formation by oxygen radical scavenging, an inhibition of both in vivo and in vitro activation of peripheral and intestinal lymphocytes. Moreover direct immunoregulatory effects exerted by the drug may be important in influencing the complex balance of pro-inflammatory mechanisms during active intestinal inflammation. Such effects are the inhibition of both peripheral and intestinal B lymphocyte immunoglobulin secretion as well as the inhibition of pro-inflammatory cytokine production and their binding to receptors. Some of these immunoregulatory effects appear to be mediated by an inhibition of the activation of the nuclear factor kappa B transcription factor family by steroids and (less potent) aminosalicylic acid. Activation of nuclear factor kappa B appears to be pivotal for the sustained upregulation of inflammation molecule expression in many inflammatory diseases. It seems, therefore, most likely that the enormous therapeutic potency of steroids, as well as the anti-inflammatory properties of 5-aminosalicylic acid, are not achieved by a single action of the drug. The complex orchestration of numerous inhibitory interactions with pro-inflammatory principles will add to the therapeutic potential of steroids and of 5-aminosalicylic acid in the treatment of both acute and chronic intestinal inflammation.

  3. Effect of vitamin D therapy on interleukin-6, visfatin, and hyaluronic acid levels in chronic hepatitis C Egyptian patients

    Directory of Open Access Journals (Sweden)

    Sabry D

    2015-02-01

    Full Text Available Dina Sabry,1 Mohamed AS Al-Ghussein,2 Gehan Hamdy,3 Amr Abul-Fotouh,4 Tarek Motawi,5 Amany Y El Kazaz,6 Ahmed Eldemery,7 Marwa Shaker8,9 1Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Giza, Egypt; 2Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, Gaza, State of Palestine, 3Internal Medicine Department, 4Tropical Medicine Department, Faculty of Medicine, 5Biochemistry Department, Faculty of Pharmacy, Cairo University, Giza, Egypt; 6Medical Biochemistry Department, Faculty of Medicine, Suez Canal University, Ismaileya, Egypt; 7Medical Biochemistry Department, Faculty of Medicine, October 6 University, Giza, Egypt; 8Tropical Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt; 9Tropical Medicine Department, Bny Swif University, Bny Swif, Egypt Objectives: We aimed to compare serum levels of interleukin-6, visfatin, and hyaluronic acid in chronic hepatitis C Egyptian patients who received standard of care (SOC therapy for chronic hepatitis C virus (HCV consisting of pegylated interferon (PEG-IFN and ribavirin (RBV and in those who received SOC with vitamin D (vit D for 48 weeks in HCV genotype 4a subjects. Design and methods: One hundred chronic HCV patients were classified into two groups: study 50 patients received SOC therapy PEG-IFN/RBV + vit D and control 50 patients received SOC PEG-IFN/RBV without vit D. Both groups were followed up at 12 weeks, 24 weeks, and 48 weeks of treatment. Results: Results showed a significant elevation in vit D levels in the group treated with SOC and vit D compared to SOC group and a reduction in HCV RNA from the 12th week to reach zero level in the 24th week. Interleukin-6, visfatin, and hyaluronic acid levels were also reduced significantly. Alanine transaminase and aspartate transaminase biomarkers were significantly reduced, indicating decreased liver injury. Conclusion: SOC PEG-IFN/RBV + vit D therapy for chronic HCV led

  4. Efficacy of microencapsulated lactic acid bacteria in Helicobater pylori eradication therapy

    OpenAIRE

    Maha A Khalil; El-Sheekh, Mostafa M.; El-Adawi, Hala I.; EL-Deeb, Nehal M.; Hussein, Mohamed Z.

    2015-01-01

    Background: Probiotic delivery systems are widely used nutraceutical products for the supplementation of natural intestinal flora. These delivery systems vary greatly in the effectiveness to exert health benefits for a patient. This study focuses on providing probiotic living cells with a physical barrier against adverse environmental conditions. Materials and Methods: Microencapsulation of the selected lactic acid bacteria (LAB) using chitosan and alginate was performed. Physical examination...

  5. Acid-suppressing therapies and subsite-specific risk of stomach cancer.

    Science.gov (United States)

    Wennerström, E Christina M; Simonsen, Jacob; Camargo, M Constanza; Rabkin, Charles S

    2017-04-25

    Associations of stomach cancer risk with histamine type-2 receptor antagonists (H2RA) and proton-pump inhibitors (PPI) are controversial. We hypothesised that proximal extension of Helicobacter pylori infection from acid suppression would disproportionately increase cancers at proximal subsites. A total of 1 563 860 individuals in the Danish Prescription Drug Registry first prescribed acid-suppressive drugs 1995-2011 were matched to unexposed population-based controls. Hazard ratios (HR) were calculated by Cox proportional hazard regression for stomach cancers diagnosed more than one year after first prescription. There were 703 stomach cancers among H2RA-exposed individuals and 1347 among PPI-exposed. Restricted to individuals with five or more prescriptions, subsite-specific HRs for H2RA and PPI were 4.1 and 6.4 for proximal subsites vs 8.0 and 10.3 for distal subsites, respectively. Moderate exposures to acid-suppressive drugs did not favour proximal tumour localisation. Given confounding by indication, these findings do not resolve potential contribution to gastric carcinogenesis overall.

  6. Hyaluronic acid levels predict increased risk of non-AIDS death in hepatitis-coinfected persons interrupting antiretroviral therapy in the SMART Study

    DEFF Research Database (Denmark)

    Peters, Lars; Neuhaus, Jacqueline; Mocroft, Amanda

    2011-01-01

    In the SMART study, HIV-viral-hepatitis-coinfected persons were, compared with HIV-monoinfected persons, at higher risk of non-AIDS death if randomized to the antiretroviral therapy (ART) interruption strategy. We hypothesized that a marker of liver fibrosis, hyaluronic acid (HA), would be predic......In the SMART study, HIV-viral-hepatitis-coinfected persons were, compared with HIV-monoinfected persons, at higher risk of non-AIDS death if randomized to the antiretroviral therapy (ART) interruption strategy. We hypothesized that a marker of liver fibrosis, hyaluronic acid (HA), would...... be predictive of development of non-AIDS-related outcomes in coinfected participants in the SMART study....

  7. New proposal for the treatment of viral warts with intralesional injection of 5-aminolevulinic acid photodynamic therapy.

    Science.gov (United States)

    Kim, Jung Eun; Kim, Sun Ji; Hwang, Jong Ik; Lee, Kyung Jin; Park, Hyun Jeong; Cho, Baik Kee

    2012-06-01

    Although photodynamic therapy (PDT) using intralesional injection (ILI) can theoretically enhance the efficacy of the PDT, the effect of ILI-PDT on warts has not been reported in the literature so far. Eight patients with multiple viral warts were enrolled in the study. PDT was performed after the incubation for 1 h, followed by the ILI of aminolevulinic acid (ALA) into the warts. The treatment was repeated at 2-3 week intervals. Fifty percent of patients showed good to cure response. Complete remission was observed in two patients. There was no apparent correlation between the initial severity of warts and the likelihood of response. No one reported severe adverse reaction. The present study suggests that intralesional administration of ALA might be a safe and effective treatment option of thick treatment-resistant warts and can be performed with a shorter incubation period.

  8. Photodynamic therapy of tumors with pyropheophorbide-a-loaded polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles

    Science.gov (United States)

    Liu, Hui; Zhao, Mei; Wang, Jin; Pang, Mingpei; Wu, Zhenzhou; Zhao, Liqing; Yin, Zhinan; Hong, Zhangyong

    2016-01-01

    Photodynamic therapy (PDT) has many advantages in treating cancers, but the lack of ideal photosensitizers continues to be a major limitation restricting the clinical utility of PDT. This study aimed to overcome this obstacle by generating pyropheophorbide-a-loaded polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles (NPs) for efficient tumor-targeted PDT. The fabricated NPs were efficiently internalized in the mitochondrion by cancer cells, and they efficiently killed cancer cells in a dose-dependent manner when activated with light. Systemically delivered NPs were highly enriched in tumor sites, and completely ablated the tumors in a xenograft KB tumor mouse model when illuminated with 680 nm light (156 mW/cm2, 10 minutes). The results suggested that this tumor-specific NP-delivery system for pyropheophorbide-a has the potential to be used in tumor-targeted PDT. PMID:27729788

  9. 5-aminolevulinic acid-incorporated poly(vinyl alcohol nanofiber-coated metal stent for application in photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Kang DH

    2012-05-01

    Full Text Available Jin Ju Yoo*, Chan Kim*, Chung-Wook Chung, Young-Il Jeong, Dae Hwan KangNational Research and Development Center for Hepatibiliary Disease, Pusan National University Yangsan Hospital, Gyeongnam 626-770, Korea *These authors contributed equally to this work.Background: The study investigated the use of combined photodynamic therapy (PDT and stent placement for the treatment of cholangiocarcinoma (CC. For this purpose, 5-aminolevulinic acid (ALA was incorporated into poly(vinyl alcohol (PVA nanofiber, and coated onto metal stents. Their efficacy was assessed in PDT towards HuCC-T1 CC cells.Methods: Fabrication of ALA-PVA nanofiber, and simultaneous coating onto metal stents, was performed through electrospinning. The dark-toxicity, generation of protoporphyrin IX (PpIX, and PDT effect of ALA and ALA-PVA nanofiber were studied in vitro, using HuCC-T1 CC cells.Results: The ALA-PVA nanofibers were coated onto metal stents less than 1000 nm in diameter. ALA-only displayed marginal cytotoxicity; ALA-PVA nanofiber showed less cytotoxicity. PpIX generation was not sigficantly different between ALA and ALA-PVA nanofiber treatments. PVA itself did not generate PpIX in tumor cells. ALA and ALA-PVA nanofiber displayed a similar PDT effect on tumor cells. Cell viability was decreased, dose-dependently, until ALA concentration reached 100 µg/mL. Necrosis and apoptosis of tumor cells occurred similarly for ALA and ALA- PVA nanofiber treatments.Conclusion: The ALA-PVA nanofiber-coated stent is a promising candidate for therapeutic use with cholangiocarcinoma.Keywords: nanofiber, photodynamic therapy, 5-aminolevulinic acid, poly(vinyl alcohol

  10. Nutrigenomics of Neuradaptogen Amino-Acid-Therapy and Neurometabolic Optimizers: Overcoming carbohydrate bingeing and overeating through neurometabolic mechanisms

    Directory of Open Access Journals (Sweden)

    Eric R. Braverman

    2011-09-01

    Full Text Available Despite progress that has been made in the treatment of obesity, the epidemic continues to rise worldwide. While pharmacological treatment of obesity may be effective, medications may have significant side effects and can be potentially fatal. This review will provide significant evidence to substantiate the existence of Reward Deficiency Syndrome in Obesity and the role of catecholaminergic pathways in aberrant substance seeking behavior, in particular cravings for carbohydrates. The genetic basis for generalized craving behavior will be established. Evidence to support the augmentation of precursor amino acid therapy and enkephalinase, MOA and COMT inhibition leading to enhanced levels of neurotransmitters: serotonin, enkephalins, GABA and dopamine/norepinephrine as well increasing insulin sensitivity (affecting dopamineFunctional Foods in Health and Disease: 9:310-378neuronal synthesis regulation through the use of certain neurometabolic optimizers will also be provided. This review article cites many published studies to support a conceptual paradigm shift towards the use of this proposed nutrigenomic formula. The analysis and research preceding this formulation is outlined. This formulation has a generalized anti-craving effect and can inhibit carbohydrate bingeing, inducing significant healthy fat loss and prevention of relapse. This is the first time that components of this formula have been combined, at the dosage levels indicated with the goal of promoting successful and sustainable body recomposition. We are encouraging other laboratories to further evaluate Neuroadtagen Amino-Acid Therapy (NAAT/Nurometabolic optimizers as a putative anti-obesity complex in larger controlled blinded studies and await interpretation of must these needed studies.

  11. In vivo systemic chlorogenic acid therapy under diabetic conditions: Wound healing effects and cytotoxicity/genotoxicity profile.

    Science.gov (United States)

    Bagdas, Deniz; Etoz, Betul Cam; Gul, Zulfiye; Ziyanok, Sedef; Inan, Sevda; Turacozen, Ozge; Gul, Nihal Yasar; Topal, Ayse; Cinkilic, Nilufer; Tas, Sibel; Ozyigit, Musa Ozgur; Gurun, Mine Sibel

    2015-07-01

    Oxidative stress occurs following the impairment of pro-oxidant/antioxidant balance in chronic wounds and leads to harmful delays in healing progress. A fine balance between oxidative stress and endogenous antioxidant defense system may be beneficial for wound healing under redox control. This study tested the hypothesis that oxidative stress in wound area can be controlled with systemic antioxidant therapy and therefore wound healing can be accelerated. We used chlorogenic acid (CGA), a dietary antioxidant, in experimental diabetic wounds that are characterized by delayed healing. Additionally, we aimed to understand possible side effects of CGA on pivotal organs and bone marrow during therapy. Wounds were created on backs of streptozotocin-induced diabetic rats. CGA (50 mg/kg/day) was injected intraperitoneally. Animals were sacrificed on different days. Biochemical and histopathological examinations were performed. Side effects of chronic antioxidant treatment were tested. CGA accelerated wound healing, enhanced hydroxyproline content, decreased malondialdehyde/nitric oxide levels, elevated reduced-glutathione, and did not affect superoxide dismutase/catalase levels in wound bed. While CGA induced side effects such as cyto/genotoxicity, 15 days of treatment attenuated blood glucose levels. CGA decreased lipid peroxidation levels of main organs. This study provides a better understanding for antioxidant intake on diabetic wound repair and possible pro-oxidative effects.

  12. Dosimetric Implications of an Injection of Hyaluronic Acid for Preserving the Rectal Wall in Prostate Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Udrescu, Corina [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Tanguy, Ronan [Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Ruffion, Alain [Department of Urology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology, Centre Val d' Aurelle, Montpellier (France); Sotton, Marie-Pierre [Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Devonec, Marian [Department of Urology, Centre Hospitalier Lyon Sud, Pierre Benite (France); Colombel, Marc [Department of Urology, Hopital Edouard Herriot, Lyon (France); Jalade, Patrice [Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology, Centre Val d' Aurelle, Montpellier (France)

    2014-02-01

    Purpose: This study assessed the contribution of ahyaluronic acid (HA) injection between the rectum and the prostate to reducing the dose to the rectal wall in stereotactic body radiation therapy (SBRT). Methods and Materials: As part of a phase 2 study of hypofractionated radiation therapy (62 Gy in 20 fractions), the patients received a transperineal injection of 10 cc HA between the rectum and the prostate. A dosimetric computed tomographic (CT) scan was systematically performed before (CT1) and after (CT2) the injection. Two 9-beam intensity modulated radiation therapy-SBRT plans were optimized for the first 10 patients on both CTs according to 2 dosage levels: 5 × 6.5 Gy (PlanA) and 5 × 8.5 Gy (PlanB). Rectal wall parameters were compared with a dose–volume histogram, and the prostate–rectum separation was measured at 7 levels of the prostate on the center line of the organ. Results: For both plans, the average volume of the rectal wall receiving the 90% isodose line (V90%) was reduced up to 90% after injection. There was no significant difference (P=.32) between doses received by the rectal wall on CT1 and CT2 at the base of the prostate. This variation became significant from the median plane to the apex of the prostate (P=.002). No significant differences were found between PlanA without HA and PlanB with HA for each level of the prostate (P=.77, at the isocenter of the prostate). Conclusions: HA injection significantly reduced the dose to the rectal wall and allowed a dose escalation from 6.5 Gy to 8.5 Gy without increasing the dose to the rectum. A phase 2 study is under way in our department to assess the rate of acute and late rectal toxicities when SBRT (5 × 8.5 Gy) is combined with an injection of HA.

  13. Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

    Science.gov (United States)

    Žiberna, Lovro; Šamec, Dunja; Mocan, Andrei; Nabavi, Seyed Fazel; Bishayee, Anupam; Farooqi, Ammad Ahmad; Sureda, Antoni; Nabavi, Seyed Mohammad

    2017-01-01

    Nowadays, much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil, as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Main molecular mechanisms underlying anticancer effects of oleanolic acid are mediated by caspases, 5′ adenosine monophosphate-activated protein kinase, extracellular signal–regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-κB, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3, as well as aforementioned signaling pathways . In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in the prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical. PMID:28300756

  14. Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

    Directory of Open Access Journals (Sweden)

    Lovro Žiberna

    2017-03-01

    Full Text Available Nowadays, much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil, as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Main molecular mechanisms underlying anticancer effects of oleanolic acid are mediated by caspases, 5′ adenosine monophosphate-activated protein kinase, extracellular signal–regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-κB, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3, as well as aforementioned signaling pathways . In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in the prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical.

  15. Scrotal ulceration following all-trans retinoic acid therapy for acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Illias Tazi

    2011-01-01

    Full Text Available All-trans retinoic acid (ATRA induces complete remission in most cases of acute promyelocytic leukemia. Toxicity of ATRA has been shown to be mild, consisting of headache, dry skin, dermatitis, and gastrointestinal disorders. We describe a case of scrotal ulceration with ATRA use in a Moroccan patient, an occurrence that has been rarely reported in the medical literature. The pathogenesis of scrotal ulceration remains unknown. Our experience indicates the importance of recognizing genital ulcers associated with ATRA in order that appropriate countermeasures can be taken.

  16. Expression of lysophosphatidic acid and its receptor in human pancreatic cancer and its clinical evaluation of diagnosis and therapy

    Institute of Scientific and Technical Information of China (English)

    WANG Shao-kai; TAO Chen-jie; WANG Wei-dong; L(U)Guang-mei; GONG Yong-ling

    2011-01-01

    Lysophosphatidic acid(LPA) is a naturally occurring phospholipid with diverse effects in various cells, ranging from immediate morphological alteration to long lasting cellular function changes, such as induction of stimulation of cell proliferation, survival, drug resistance and motility. Like many other biomediators, LPA interacts with cells through specific cell surface receptors(G protein-coupled receptors). LPA1/Edg-2,LPA2/Edg-4 and LPA3/Edg-7, named as Edg/LP subfamily, are the three most common lysophosphatidic acid receptors. LPA plays a critical role as a general growth, survival and pro-angiogenic factor in the regulation of pathophysiological processes in vivo and in vitro. Recent literatures suggest that abnormalities in LPA metabolism and function in pancreatic cancer patients may contribute to the initiation and progression of the disease. Thus, LPA might be a potential target for clinical pancreatic cancer diagnosis and therapy. Herein we review the expression of LPA and its receptors in the carcinogenesis of human malignancies, with focus on human pancreatic cancer, and also clinical diagnosis and treatment has been evaluated.

  17. Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer.

    Science.gov (United States)

    Cho, Eun Jung; Sun, Bo; Doh, Kyung-Oh; Wilson, Erin M; Torregrosa-Allen, Sandra; Elzey, Bennett D; Yeo, Yoon

    2015-01-01

    Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of solid carcinomas confined within the peritoneal cavity, with potential benefits in locoregional and systemic management of residual tumors. In this study, we intended to increase local retention of platinum in the peritoneal cavity over a prolonged period of time using a nanoparticle form of platinum and an in-situ crosslinkable hyaluronic acid gel. Hyaluronic acid was chosen as a carrier due to the biocompatibility and biodegradability. We confirmed a sustained release of platinum from the nanoparticles (PtNPs) and nanoparticle/gel hybrid (PtNP/gel), receptor-mediated endocytosis of PtNPs, and retention of the gel in the peritoneal cavity over 4 weeks: conditions desirable for a prolonged local delivery of platinum. However, PtNPs and PtNP/gel did not show a greater anti-tumor efficacy than CDDP solution administered at the same dose but rather caused a slight increase in tumor burdens at later time points, which suggests a potential involvement of empty carriers and degradation products in the growth of residual tumors. This study alerts that although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of drug carriers.

  18. A Glycyrrhetinic Acid-Modified Curcumin Supramolecular Hydrogel for liver tumor targeting therapy

    Science.gov (United States)

    Chen, Guoqin; Li, Jinliang; Cai, Yanbin; Zhan, Jie; Gao, Jie; Song, Mingcai; Shi, Yang; Yang, Zhimou

    2017-03-01

    Curcumin (Cur), a phenolic anti-oxidant compound obtained from Curcuma longa plant, possesses a variety of therapeutic properties. However, it is suffered from its low water solubility and low bioavailability property, which seriously restricts its clinical application. In this study, we developed a glycyrrhetinic acid (GA) modified curcumin supramolecular pro-gelator (GA-Cur) and a control compound Nap-Cur by replacing GA with the naphthylacetic acid (Nap). Both compounds showed good water solubility and could form supramolecular gels by disulfide bond reduction triggered by glutathione (GSH) in vitro. Both formed gels could sustainedly release Cur in buffer solutions. We also investigated the cytotoxicity of pro-gelators to HepG2 cells by a MTT assay and determined the cellular uptake behaviours of them by fluorescence microscopy and LC-MS. Due to the over expression of GA receptor in liver cancer cells, our pro-gelator of GA-Cur showed an enhanced cellular uptake and better inhibition capacity to liver tumor cells than Nap-Cur. Therefore, the GA-Cur could significantly inhibit HepG2 cell growth. Our study provides a novel nanomaterial for liver tumor chemotherapy.

  19. Is it time to reassess alpha lipoic acid and niacinamide therapy in schizophrenia?

    Science.gov (United States)

    Seybolt, Sheila E J

    2010-12-01

    As sulfur containing thiols, alpha lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are powerful antioxidants and free radical scavengers capable of performing many of the same functions as glutathione (GSH). ALA supplementation may help protect mitochondria from oxidative stress, a possible mechanism contributing to certain forms of brain diseases called schizophrenia. Shortly before the advent of antipsychotic medications, two small studies found ALA relieved psychiatric symptoms in schizophrenia. More recently, animal studies have shown ALA augmentation improves mitochondrial function. At pharmaceutical levels, niacinamide helps preserve mitochondrial membrane integrity and acts as an antioxidant. ALA is a precursor for lipoamide, an essential mitochondrial coenzyme and niacinamide is a component of niacinamide adenine dinucleotide (NAD). NADH, the reduced form of NAD, is involved in the reduction of ALA to DHLA within the mitochondria. This is relevant to contemporary research because DHLA increases GSH and low GSH levels contribute to mitochondrial dysfunction and oxidative stress which have been implicated in the pathophysiology of schizophrenia.

  20. Combined therapy of Ulmo honey (Eucryphia cordifolia and ascorbic acid to treat venous ulcers

    Directory of Open Access Journals (Sweden)

    Mariano del Sol Calderon

    2015-04-01

    Full Text Available OBJECTIVE: to assess the clinical effect of topical treatment using Ulmo honey associated with oral ascorbic acid in patients with venous ulcers. METHOD: longitudinal and descriptive quantitative study. During one year, 18 patients were assessed who were clinically diagnosed with venous ulcer in different stages, male and female, adult, with a mean injury time of 13 months. Ulmo honey was topically applied daily. The dressing was applied in accordance with the technical standard for advanced dressings, combined with the daily oral consumptions of 500 mg of ascorbic acid. The monitoring instrument is the assessment table of venous ulcers. RESULTS: full healing was achieved in 100% of the venous ulcers. No signs of complications were observed, such as allergies or infection. CONCLUSION: the proposed treatment showed excellent clinical results for the healing of venous ulcers. The honey demonstrated debriding and non-adherent properties, was easy to apply and remove and was well accepted by the users. The described results generated a research line on chronic wound treatment.

  1. A Glycyrrhetinic Acid-Modified Curcumin Supramolecular Hydrogel for liver tumor targeting therapy

    Science.gov (United States)

    Chen, Guoqin; Li, Jinliang; Cai, Yanbin; Zhan, Jie; Gao, Jie; Song, Mingcai; Shi, Yang; Yang, Zhimou

    2017-01-01

    Curcumin (Cur), a phenolic anti-oxidant compound obtained from Curcuma longa plant, possesses a variety of therapeutic properties. However, it is suffered from its low water solubility and low bioavailability property, which seriously restricts its clinical application. In this study, we developed a glycyrrhetinic acid (GA) modified curcumin supramolecular pro-gelator (GA-Cur) and a control compound Nap-Cur by replacing GA with the naphthylacetic acid (Nap). Both compounds showed good water solubility and could form supramolecular gels by disulfide bond reduction triggered by glutathione (GSH) in vitro. Both formed gels could sustainedly release Cur in buffer solutions. We also investigated the cytotoxicity of pro-gelators to HepG2 cells by a MTT assay and determined the cellular uptake behaviours of them by fluorescence microscopy and LC-MS. Due to the over expression of GA receptor in liver cancer cells, our pro-gelator of GA-Cur showed an enhanced cellular uptake and better inhibition capacity to liver tumor cells than Nap-Cur. Therefore, the GA-Cur could significantly inhibit HepG2 cell growth. Our study provides a novel nanomaterial for liver tumor chemotherapy. PMID:28281678

  2. Design, synthesis, and biological evaluation of folic acid targeted tetraphenylporphyrin as novel photosensitizers for selective photodynamic therapy.

    Science.gov (United States)

    Schneider, Raphaël; Schmitt, Frédéric; Frochot, Céline; Fort, Yves; Lourette, Natacha; Guillemin, François; Müller, Jean-François; Barberi-Heyob, Muriel

    2005-04-15

    Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate light wavelength, interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. Targeted PDT offers the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues. Two new conjugates of three components, folic acid/hexane-1,6-diamine/4-carboxyphenylporphyrine 1 and folic acid/2,2'-(ethylenedioxy)-bis-ethylamine/4-carboxyphenylporphyrine 2 were synthesized. The conjugates were characterized by 1H NMR, MALDI, UV-visible spectroscopy, and fluorescence quantum yield. The targeted delivery of these photoactive compounds to KB nasopharyngeal cell line, which is one of the numerous tumor cell types that overexpress folate receptors was studied. It was found that after 24 h incubation, conjugates 1 and 2 cellular uptake was on average 7-fold higher than tetraphenylporphyrin (TPP) used as reference and that 1 and 2 cellular uptake kinetics increased steadily over the 24 h period, suggesting an active transport via receptor-mediated endocytosis. In corresponding results, conjugates 1 and 2 accumulation displayed a reduction of 70% in the presence of a competitive concentration of folic acid. Survival measurements demonstrated that KB cells were significantly more sensitive to conjugated porphyrins-mediated PDT. Under the same experimental conditions and the same photosensitizer concentration, TPP displayed no photocytotoxicity while conjugates 1 and 2 showed photodynamic activity with light dose values yielding 50% growth inhibition of 22.6 and 6.7 J/cm2, respectively.

  3. Hydroxyurea Therapy Mobilises Arachidonic Acid from Inner Cell Membrane Aminophospholipids in Patients with Homozygous Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    A. A. Daak

    2011-01-01

    Full Text Available The cytotoxic compound hydroxyurea (HU is effective therapy for sickle cell disease. However, its effect on unsaturated membrane lipids is unknown. Red cell fatty acids were investigated in HU-treated (n=19 and HU-untreated (n=17 sickle cell patients and controls (n=20. The HU-treated compared with the HU-untreated patients had lower arachidonic (AA acid level in ethanolamine, physphoglycerids (EPG (22.9±1.2   versus   24.0±1.1%,  P<0.05 serine SPG (22.13±2.2   versus   24.9±2.3%,  P<0.01 phosphoglycerides. The treated patients and controls had comparable levels of docosahexaenoic (DHA and total n-3 fatty acids in EPG and choline phosphoglycerides (CPG. In contrast, the untreated group had significantly (P<0.05 lower DHA and total n-3 compared with the controls in EPG (2.7±0.4   versus   3.2±0.6% and 4.6±0.5   versus   5.2±0.7% and CPG (0.7±0.2   versus   1.0±0.2% and 1.2±0.2   versus   1.4±0.3. HU is known to activate cytosolic phospholipase A2 and cyclooxygenase 2, and from this study, it appears to induce mobilisation of AA from the inner cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may play a role in clinical improvements which occur in HU-treated patients.

  4. A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Krauze, Andra V. [Radiation Oncology Branch, National Cancer Institute/National Institutes of Health, Bethesda, Maryland (United States); Myrehaug, Sten D. [Department of Radiation Oncology, Lakeridge Health Durham Regional Cancer Centre, Oshawa, Ontario (Canada); Chang, Michael G.; Holdford, Diane J. [Massey Cancer Center Virginia Commonwealth University, Richmond, Virginia (United States); Smith, Sharon; Shih, Joanna; Tofilon, Philip J. [Radiation Oncology Branch, National Cancer Institute/National Institutes of Health, Bethesda, Maryland (United States); Fine, Howard A. [New York University Langone Medical Center, New York, New York (United States); Camphausen, Kevin, E-mail: camphauk@mail.nih.gov [Radiation Oncology Branch, National Cancer Institute/National Institutes of Health, Bethesda, Maryland (United States)

    2015-08-01

    Purpose: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models. We evaluated the addition of VPA to standard radiation therapy (RT) plus temozolomide (TMZ) in patients with newly diagnosed GBM. Methods and Materials: Thirty-seven patients with newly diagnosed GBM were enrolled between July 2006 and April 2013. Patients received VPA, 25 mg/kg orally, divided into 2 daily doses concurrent with RT and TMZ. The first dose of VPA was given 1 week before the first day of RT at 10 to 15 mg/kg/day and subsequently increased up to 25 mg/kg/day over the week prior to radiation. VPA- and TMZ-related acute toxicities were evaluated using Common Toxicity Criteria version 3.0 (National Cancer Institute Cancer Therapy Evaluation Program) and Cancer Radiation Morbidity Scoring Scheme for toxicity and adverse event reporting (Radiation Therapy Oncology Group/European Organization for Research and Treatment). Results: A total of 81% of patients took VPA according to protocol. Median overall survival (OS) was 29.6 months (range: 21-63.8 months), and median progression-free survival (PFS) was 10.5 months (range: 6.8-51.2 months). OS at 6, 12, and 24 months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24 months was 70%, 43%, and 38% respectively. The most common grade 3/4 toxicities of VPA in conjunction with RT/TMZ therapy were blood and bone marrow toxicity (32%), neurological toxicity (11%), and metabolic and laboratory toxicity (8%). Younger age and class V recursive partitioning analysis (RPA) results were significant for both OS and PFS. VPA levels were not correlated with grade 3 or 4 toxicity levels. Conclusions: Addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may result in improved outcomes compared to historical data and merits further study.

  5. Utilization of 5-aminolevulinic acid in the photodynamic therapy of tumors: biochemical and photobiological aspects

    Science.gov (United States)

    Pottier, Roy H.; Kennedy, James C.

    1994-03-01

    Inherent in both plants and animals is the natural porphyrin, Protoporphyrin IX (Pp). Although Pp does not appear to have any intrinsic biological activity, it is a potent natural photosensitizer. When activated with ultraviolet or visible light, this photosensitizer can induce significant photodynamic effects on tissues, cells, subcellular elements, and macromolecules via the production of singlet oxygen. The biosynthesis of endogenous Pp is under strict enzymatic control. It is possible to bypass a rate controlling step and induce large, transient concentrations of Pp by the addition of exogenous 5-aminolevulinic acid (ALA). ALA may be administered systemically or topically. Much larger amounts of Pp are produced in certain types of tumor tissue than in adjacent normal tissue. Topically applied ALA can be used to treat a variety of skin lesions, including actinic keratosis, basal cell carcinomas and psoriasis.

  6. Effect of adjuvantα-keto acid therapy on serum renal function indexes and nutritional status in patients with early diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    Min Zhang; Lu Wang

    2016-01-01

    Objective:To analyze the effect of adjuvantα-keto acid therapy on serum renal function indexes and nutritional status in patients with early diabetic nephropathy.Methods:A total of 86 patients with early diabetic nephropathy were divided into observation group and control group, control group received conventional therapy, observation group received conventional therapy + adjuvantα-keto acid therapy, and then differences in serum renal function indexes, nutrition index, vascular endothelial function indexes, micro-inflammation indexes and so on were compared between two groups of patients after 2 months of treatment.Results: Serum renal function indexes UAER level as well as BUN, SCr, CysC andβ2-MG content of observation group was lower than those of control group while GFR level was higher than that of control group; nutrition indexes ALB, PA and Hb content were higher than those of control group while nPCR level was lower than that of control group; vascular endothelial function indexes NO and CGRP content were higher than those of control group while ET-1, MCP-1 and resistin content were lower than those of control group; micro-inflammation indexes hs-CRP, IL-1β, IL-17, IL-22, TGF-β1 and SAA content were lower than those of control group. Conclusions:Adjuvantα-keto acid therapy helps to improve the renal function and nutritional status of patients with early diabetic nephropathy, and has positive significance in optimizing the overall treatment effect.

  7. Combination Intravenous and Intra-Articular Tranexamic acid compared with Intravenous Only Administration and No Therapy in Total Knee Arthroplasty: A Case Series Study

    Directory of Open Access Journals (Sweden)

    Chris Buntting

    2016-07-01

    This study supports the existing literature and suggests that the use of IV Tranexamic acid alone or in combination with intra-articular dose in TKA may reduce the requirement for transfusion (Level IV evidence. Furthermore, this study suggests that the use of tranexamic acid as a combination of Intravenous and intra-articular administration has no effect on range of motion, or medical complications during hospital stay. Although it was not a statistically significant finding, our study suggested a trend towards a greater reduction in haemoglobin and haematocrit fall in the combination therapy group when compared to IV Tranexamic acid alone

  8. Cell adhesion molecules and hyaluronic acid as markers of inflammation, fibrosis and response to antiviral therapy in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Esther Granot

    2001-01-01

    Full Text Available Objective: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1 and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long-term response to therapy.

  9. Effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Jia-Lun Zhu; Zhi-Yong Deng; Chuan-Zhou Yang

    2016-01-01

    Objective:To find the effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis.Methods: A total of 102 lung cancer patients with bone metastases were included in the study and randomly divided into observation group and control group (n=51) according to different treatment they received. Control group received zoledronic acid injection therapy alone, observation group received zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy, and then differences in the growth of lung cancer bone metastasis, bone metabolism, tumor markers and alkaline phosphatase, pain score and pain-related mediator levels,etc. were compared between two groups.Results: Number of metastases of observation group after treatment was less than that of control group, and serum bone metabolism indexes OPG, BSP, TRACP-5b, ICTP and BAP levels, serum tumor markers CYFRA21-1, CEA, NSE, CA125 and BALP levels as well as serum pain-related mediators PGE2, ET-1 and TNF-α levels were lower than those of control group (P<0.05).Conclusions:Zoledronic acid injection combined with radiopharmaceutical89SrCI2 therapy can contain the growth of lung cancer bone metastasis, optimize bone metabolism state while alleviate patients’ perception of pain.

  10. Severe chest pain in a pediatric ulcerative colitis patient after 5-aminosalicylic acid therapy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis (UC) diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram (ECG) revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram (ECHO) revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries (< 3.5 mm). Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.

  11. Homocysteine, an indicator of methylation pathway alternation in Down syndrome and its regulation by folic acid therapy

    Directory of Open Access Journals (Sweden)

    Hala M El-Gendy

    2007-06-01

    Full Text Available

    BACKGROUND: Down syndrome (DS is a complex genetic disease. Some clinical features of patients with this syndrome could be related to functional folate deficiency. The purpose of this study was to evaluate the total homocysteine (T-Hcy metabolism in DS children and to determine whether the supplementation with folic acid therapy would shift the genetically induced metabolic imbalance or not.

    METHODS: Thirty-five infants with DS, with the mean age of 17.66 ± 12.24 months were included in this study. They were selected from those attending the Genetic Outpatients Clinic in Children hospital.

    RESULTS: Our results revealed that Down syndrome children had a significant decrease in serum plasma T-Hcy level after the treatment with folic acid [11.79 ± 0.92 vs. 14.41 ± 4.93 μmol/L]. A significant negative correlation was found between T-Hcy and folic acid serum levels [r = -0.112; P<0.05].

    CONCLUSIONS: We concluded that the regulation of methylation pathways in Down syndrome patients becomes important in the light of possible normalization of the metabolic imbalance and the detection of increased sensitivity to therapeutic interventions.

    KEY WORDS: Down syndrome, hyperhomocysteine, folic acid, vitamin B-12.

  12. Ferulic Acid: A Hope for Alzheimer’s Disease Therapy from Plants

    Directory of Open Access Journals (Sweden)

    Antonella Sgarbossa

    2015-07-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder characterized by the deposition of extracellular amyloid-beta peptide (Aβ and intracellular neurofibrillar tangles, associated with loss of neurons in the brain and consequent learning and memory deficits. Aβ is the major component of the senile plaques and is believed to play a central role in the development and progress of AD both in oligomer and fibril forms. Inhibition of the formation of Aβ fibrils as well as the destabilization of preformed Aβ in the Central Nervous System (CNS would be an attractive therapeutic target for the treatment of AD. Moreover, a large number of studies indicate that oxidative stress and mitochondrial dysfunction may play an important role in AD and their suppression or reduction via antioxidant use could be a promising preventive or therapeutic intervention for AD patients. Many antioxidant compounds have been demonstrated to protect the brain from Aβ neurotoxicity. Ferulic acid (FA is an antioxidant naturally present in plant cell walls with anti-inflammatory activities and it is able to act as a free radical scavenger. Here we present the role of FA as inhibitor or disaggregating agent of amyloid structures as well as its effects on biological models.

  13. Hyaluronic Acid (HA)-Polyethylene glycol (PEG) as injectable hydrogel for intervertebral disc degeneration patients therapy

    Science.gov (United States)

    Putri Kwarta, Cityta; Widiyanti, Prihartini; Siswanto

    2017-05-01

    Chronic Low Back Pain (CLBP) is one health problem that is often encountered in a community. Inject-able hydrogels are the newest way to restore the disc thickness and hydration caused by disc degeneration by means of minimally invasive surgery. Thus, polymers can be combined to improve the characteristic properties of inject-able hydrogels, leading to use of Hyaluronic Acid (a natural polymer) and Polyethylene glycol (PEG) with Horse Radish Peroxide (HRP) cross linker enzymes. The swelling test results, which approaches were the ideal disc values, were sampled with variation of enzyme concentrations of 0.25 µmol/min/mL. The enzyme concentrations were 33.95%. The degradation test proved that the sample degradation increased along with the decrease of the HRP enzyme concentration. The results of the cytotoxicity assay with MTT assay method showed that all samples resulted in the 90% of living cells are not toxic. In vitro injection, models demonstrated that higher concentration of the enzymes was less state of gel which would rupture when released from the agarose gel. The functional group characterization shows the cross linking bonding in sample with enzyme adding. The conclusion of this study is PEG-HA-HRP enzyme are safe polymer composites which have a potential to be applied as an injectable hydrogel for intervertebral disc degeneration.

  14. Hyaluronic acid-serum albumin conjugate-based nanoparticles for targeted cancer therapy.

    Science.gov (United States)

    Edelman, Ravit; Assaraf, Yehuda G; Levitzky, Inna; Shahar, Tal; Livney, Yoav D

    2017-02-15

    Multiple carcinomas including breast, ovarian, colon, lung and stomach cancer, overexpress the hyaluronic acid (HA) receptor, CD44. Overexpression of CD44 contributes to key cancer processes including tumor invasion, metastasis, recurrence, and chemoresistance. Herein, we devised novel targeted nanoparticles (NPs) for delivery of anticancer chemotherapeutics, comprised of self-assembling Maillard reaction-based conjugates of HA and bovine serum albumin (BSA). HA served as the hydrophilic block, and as the ligand for actively targeting cancer cells overexpressing CD44. We demonstrate that Maillard reaction-based covalent conjugates of BSA-HA self-assemble into NPs, which efficiently entrap hydrophobic cytotoxic drugs including paclitaxel and imidazoacridinones. Furthermore, BSA-HA conjugates stabilized paclitaxel and prevented its aggregation and crystallization. The diameter of the NPs was < 15 nm, thus enabling CD44 receptor-mediated endocytosis. These NPs were selectively internalized by ovarian cancer cells overexpressing CD44, but not by cognate cells lacking this HA receptor. Moreover, free HA abolished the endocytosis of drug-loaded BSA-HA conjugates. Consistently, drug-loaded NPs were markedly more cytotoxic to cancer cells overexpressing CD44 than to cells lacking CD44, due to selective internalization, which could be competitively inhibited by excess free HA. Finally, a CD44-targeted antibody which blocks receptor activity, abolished internalization of drug-loaded NPs. In conclusion, a novel cytotoxic drug-loaded nanomedicine platform has been developed, which is based on natural biocompatible biopolymers, capabale of targeting cancer cells with functional surface expression of CD44.

  15. Gangrenous cheilitis associated with all-trans retinoic acid therapy for acute promyelocytic leukemia.

    Science.gov (United States)

    Tanaka, Mariko; Fukushima, Noriyasu; Itamura, Hidekazu; Urata, Chisako; Yokoo, Masako; Ide, Masaru; Hisatomi, Takashi; Tomimasu, Rika; Sueoka, Eisaburo; Kimura, Shinya

    2010-01-01

    A 67-year-old Japanese woman who presented with erythema on the abdomen and pancytopenia was found to have acute promyelocytic leukemia (APL). A skin biopsy revealed invasion of APL cells. She was started on induction treatment with all-trans retinoic acid (ATRA) at 45 mg/m(2). On day 4, the leukemic cell number had increased to over 1.0 x 10(9)/L. Consequently, chemotherapy with idarubicin and cytarabine was initiated. On day 10, dryness of the lips appeared. The lower lip swelled and developed painful black eschars. A high fever was also present. Despite discontinuing ATRA on day 20 and administering antibiotics, an anti-fungal agent and valaciclovir, these signs did not improve. Histopathologically, the biopsied lip revealed infiltration of neutrophils and vasculitis. The patient was given ATRA on days 29 and 30 due to an increase in APL cell numbers, after which the gangrenous cheilitis extended over the whole lip. On day 49, the patient was started on re-induction treatment with arsenic trioxide. She achieved complete remission and the gangrenous cheilitis slowly healed over the following 8 weeks. Since the clinical features of the gangrenous cheilitis in this case were similar to those of ATRA-associated scrotal ulcers, it appears that activated neutrophils derived from differentiated APL cells may have caused the gangrenous cheilitis. Physicians should be alert to the development of gangrenous cheilitis during treatment with ATRA.

  16. In vitro study of cell death with 5-aminolevulinic acid based photodynamic therapy to improve the efficiency of cancer treatment

    Science.gov (United States)

    Firdous, S.; Nawaz, M.; Ikram, M.; Ahmed, M.

    2012-03-01

    Photodynamic therapy (PDT) is a kind of photochemo therapeutic treatment that exerts its effect mainly through the induction of cell death. Distinct types of cell death may be elicited by different PDT regimes. In this study, efforts are underway to optimize PDT protocols for improved efficacy and combination of all three PDT mechanisms involved in the different human carcinomas cell narcosis. Our in vitro cell culture experiments with 5-aminolevulanic acid (ALA) a clinically approved photiosensitizer (PS) and 635 nm laser light have yielded promising results, as follow: (1) (human cervical cancer (HeLa) cell line incubated, for 18 h, with 30 μg/ml of 5-ALA, treated with laser light dose of 50 J/cm2 can produce 85% of cell killing (2) human larynx carcinoma (Hep2c) cell line incubated, for 7 h, with 55 μg/ml of 5-ALA, treated with laser light dose of 85 J/cm2 can produce 75% of cell killing (3) human liver cancer (HepG2) cell line incubated, for 22-48 h, with 262 μg/ml of 5-ALA, treated with laser light dose of 120 J/cm2 can produce 95% of cell killing (4) human muscle cancer (RD) cell line incubated, for 47 h, with 250 μg/ml of 5-ALA, treated with laser light dose of 80 J/cm2 can produce 76% of cell killing (5) Human embryonic kidney (HEK293T) cell line incu-bated, for 18 h, with 400 μg/ml of 5-ALA, treated with laser light dose of 40 J/cm2 can produce 82% of cell killing confirming the efficacy of photodynamic therapy.

  17. Multifunctional nanosheets based on hyaluronic acid modified graphene oxide for tumor-targeting chemo-photothermal therapy

    Science.gov (United States)

    Hou, Lin; Feng, Qianhua; Wang, Yating; Zhang, Huijuan; Jiang, Guixiang; Yang, Xiaomin; Ren, Junxiao; Zhu, Xiali; Shi, Yuyang; Zhang, Zhenzhong

    2015-03-01

    Graphene oxide (GO) with strong optical absorption in the near-infrared (NIR) region has shown great potential both in photothermal therapy and drug delivery. In this work, hyaluronic acid (HA)-functionalized GO (HA-GO) was successfully synthesized and controlled loading of mitoxantrone (MIT) onto HA-GO via π- π stacking interaction was investigated. The results revealed that drug-loaded nanosheets with high loading efficiency of 45 wt% exhibited pH-sensitive responses to tumor environment. Owing to the receptor-mediated endocytosis, cellular uptake analysis of HA-GO showed enhanced internalization. In vivo optical imaging test demonstrated that HA-GO nanosheets could enhance the targeting ability and residence time in tumor site. Moreover, the anti-tumor activity of free MIT, MIT/GO, and MIT/HA-GO in combination with NIR laser was investigated using human MCF-7 cells. In vitro cytotoxicity study revealed that HA-GO could stand as a biocompatible nanocarrier and MIT/HA-GO demonstrated remarkably higher toxicity than free MIT and MIT/GO, with IC50 of 0.79 µg ml-1. Tumor cell-killing potency was enhanced when MIT/HA-GO were combined with NIR irradiation, and the IC50 of MIT/HA-GO plus laser irradiation was 0.38 µg ml-1. In vivo, MIT/HA-GO plus NIR laser irradiation with the tumor growth inhibition of 93.52 % displayed greater anti-tumor effect compared with free MIT and MIT/GO with or without laser irradiation. Therefore, the MIT/HA-GO nanosheets may potentially be useful for further development of synergistic cancer therapy.

  18. Multifunctional nanosheets based on hyaluronic acid modified graphene oxide for tumor-targeting chemo-photothermal therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Lin; Feng, Qianhua; Wang, Yating; Zhang, Huijuan; Jiang, Guixiang; Yang, Xiaomin; Ren, Junxiao; Zhu, Xiali; Shi, Yuyang; Zhang, Zhenzhong, E-mail: zhangzz-pharm@163.com [Zhengzhou University, School of Pharmaceutical Sciences (China)

    2015-03-15

    Graphene oxide (GO) with strong optical absorption in the near-infrared (NIR) region has shown great potential both in photothermal therapy and drug delivery. In this work, hyaluronic acid (HA)-functionalized GO (HA-GO) was successfully synthesized and controlled loading of mitoxantrone (MIT) onto HA-GO via π–π stacking interaction was investigated. The results revealed that drug-loaded nanosheets with high loading efficiency of 45 wt% exhibited pH-sensitive responses to tumor environment. Owing to the receptor-mediated endocytosis, cellular uptake analysis of HA-GO showed enhanced internalization. In vivo optical imaging test demonstrated that HA-GO nanosheets could enhance the targeting ability and residence time in tumor site. Moreover, the anti-tumor activity of free MIT, MIT/GO, and MIT/HA-GO in combination with NIR laser was investigated using human MCF-7 cells. In vitro cytotoxicity study revealed that HA-GO could stand as a biocompatible nanocarrier and MIT/HA-GO demonstrated remarkably higher toxicity than free MIT and MIT/GO, with IC{sub 50} of 0.79 µg ml{sup −1}. Tumor cell-killing potency was enhanced when MIT/HA-GO were combined with NIR irradiation, and the IC{sub 50} of MIT/HA-GO plus laser irradiation was 0.38 µg ml{sup −1}. In vivo, MIT/HA-GO plus NIR laser irradiation with the tumor growth inhibition of 93.52 % displayed greater anti-tumor effect compared with free MIT and MIT/GO with or without laser irradiation. Therefore, the MIT/HA-GO nanosheets may potentially be useful for further development of synergistic cancer therapy.

  19. Low-Dose Topical 5-Aminolevulinic Acid Photodynamic Therapy in the Treatment of Different Severity of Acne Vulgaris.

    Science.gov (United States)

    Tao, Shi-Qin; Li, Fei; Cao, Lei; Xia, Ru-Shan; Fan, Hua; Fan, Ying; Sun, Hui; Jing, Cheng; Yang, Li-Jia

    2015-12-01

    The objective of this article is to investigate the effectiveness and safety of photodynamic therapy (PDT) with 3.6 % topical aminolevulinic acid (ALA) and a short incubation time with red light in moderate to severe acne. One hundred and thirty-six patients with moderate to severe acne were treated with 3.6 % topical ALA-PDT for three sessions with an interval of 2 weeks. Patients were evaluated for efficacy and safety on week 2, 4, 6, 8, and 12 after the initial treatment. Most patients showed apparent clearance of acne lesions at the treated site after three sessions. The effective treatment rates were increased after the multiple therapies. The clinical outcomes are the best at 4 weeks after the final treatment. The total effectiveness rate and cure rate of the low-dose ALA-PDT procedure is 92.65 and 47.06 %, respectively. Thirty-one patients and nineteen patients showed apparent exacerbation of acne lesions before the 2nd and 3rd treatment, respectively, but all of them showed good or excellent improvement after a three-course treatment. A few patients showed mild relapse including papules and comedos at 8 weeks after the final treatment. No significant differences are found in the effects of different acne severity and different genders. Adverse reactions are mild and transient. A 3.6 % topical ALA-PDT with a short time incubation with red light is a simple and an effective treatment option for moderate to severe acne with mild side effects in Chinese people.

  20. Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia.

    Science.gov (United States)

    Tóth, Štefan; Šajty, Matej; Pekárová, Tímea; Mughees, Adil; Štefanič, Peter; Katz, Matan; Spišáková, Katarína; Pella, Jozef; Pella, Daniel

    2017-07-26

    Statins represent a group of drugs that are currently indicated in the primary and secondary prevention of cardiovascular events. Their administration can be associated with side effects and the insufficient reduction of triacylglyceride (TAG) levels. This study aimed to assess the effect of the triple combination of statins with omega-3 fatty acids and coenzyme Q10 (CoQ10) on parameters associated with atherogenesis and statin side effects. In this pilot randomized double-blind trial, 105 subjects who met the criteria of combined dislipidemia and elevated TAG levels were randomly divided into three groups. In the control group, unaltered statin therapy was indicated. In the second and third groups, omega-3 PUFA 2.52 g/day (Zennix fa Pleuran) and omega-3 PUFA 2.52 g+CoQ10 200 mg/day (Pharma Nord ApS) were added, res//. At the end of the 3-month period (±1 week), all patients were evaluated. Significant reduction of hepatic enzymes activity, systolic blood preasure, inflammatory markers and TAG levels were detected in both groups in comparison to the control group. Activity of SOD and GPx increased significantly after additive therapy. Coenzyme Q10 addition significantly reduced most of the abovementioned parameters (systolic blood preasure, total cholesterol, LDL, hsCRP, IL-6, SOD) in comparison with the statin+omega-3 PUFA group. The intensity of statin adverse effects were significantly reduced in the group with the addition of CoQ10. The results of this pilot study suggest the possible beneficial effects of triple combination on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.

  1. Influence of CaNa2 EDTA on topical 5-aminolaevulinic acid photodynamic therapy

    Institute of Scientific and Technical Information of China (English)

    刘辉峰; 徐世正; 张春荣

    2004-01-01

    Background We asssessed whether the CaNa2 EDTA could improve the accumulation of protoporphyrin Ⅸ (PpⅨ) and photosensitisation in HEp-2 cells as well as the depth of treatment of skin cancers on the topical 5-Aminolaevulinic acid (5-ALA) PDT.Methods HEp-2 cells were incubated with 5-ALA (0-1mmol/L) and CaNa2EDTA (0-1mmol/L) for 4 hours, intracellular protoporphyrin Ⅸ content was quantified by extraction, and cell viability was assessed by use of the methyl-tetrazolium (MTT) assay four hours after exposure to light. In comparison with the pictures before and after treatment, depth of treatment could be determined using a Acuson Sequioa 512 phase-array system in paired experiments.Results PpⅨ accumulation increased with increasing extracellular concentrations of ALA (0-1mmol/L). Adding 1mmol/L of CaNa2EDTA increased 30% PpⅨ accumulation over the same period of incubation in the concentration of 1mmol/L ALA. Significant difference was observed between the 5-ALA alone group and 5-ALA combined CaNa2 EDTA group in the PpⅨ accumulation (P<0.01). Cell viability after exposure to light decreased with adding CaNa2 EDTA, a statistical difference in a same fluence above 1.2 J/cm2 between two groups was demonstrated (P<0.05, P<0.01 respectively). Depth of treatment of skin cancers were increased in CaNa2 EDTA-treated group.conclusion CaNa2 EDTA could improve the PpⅨ accumulation and photosensitisation in HEp-2 cells. Clinically, CaNa2 EDTA could increase the depth of treatment in the cutaneous cancers.

  2. Omega-3 fatty acid therapy reduces triglycerides and interleukin-6 in hypertriglyeridemic HIV patients.

    Science.gov (United States)

    Metkus, T S; Timpone, J; Leaf, D; Bidwell Goetz, M; Harris, W S; Brown, T T

    2013-10-01

    Cardiovascular disease and osteoporosis are common in HIV-infected patients and residual systemic inflammation is thought to contribute to both of these disorders. We performed a randomized placebo-controlled trial of omega-3-acid (O3A) ethyl esters in HIV-infected patients with hypertriglyceridaemia, hypothesizing that O3A would decrease serum levels of triglycerides, markers of systemic inflammation, and markers of bone turnover. HIV-infected patients (n = 48 recruited at three sites) with CD4 count >200 cells/μL, suppressed viral load, and triglycerides >200 mg/dL were randomized to placebo or 3.6 g/d of O3A. Fasting lipid profiles and markers of inflammation and bone turnover were assessed at baseline and after 8 weeks of treatment. Baseline HIV status, lipid profile, bone metabolism and cardiovascular risk factors were similar between the groups. Inflammatory markers were similar between the treatment groups at baseline, except for interleukin (IL)-6 and tumour necrosis factor (TNF)-α, which were higher in the O3A group. The concentration of triglycerides in patients receiving O3A decreased by a median (interquartile range (IQR)) of -34 (-149, 9.5) mg/dL vs. a median increase of 46.5 (-51, 123) mg/dL in the placebo group (P = 0.01). The median percentage change in IL-6 was greater in the O3A group compared with the placebo group [-39% (-63, 12%) vs. 29% (10, 177%), respectively; P = 0.006]. Similar results were observed for TNF-α, but not other inflammatory or bone turnover markers. O3A ethyl esters decreased the concentrations of triglycerides, IL-6 and TNF-α in patients with well-controlled HIV infection and hypertriglyceridaemia. Larger studies are required to confirm these findings and investigate their clinical significance. © 2013 British HIV Association.

  3. A longitudinal assessment of adherence with immunosuppressive therapy following kidney transplantation from the Mycophenolic Acid Observational REnal Transplant (MORE) study.

    Science.gov (United States)

    Tsapepas, Demetra; Langone, Anthony; Chan, Laurence; Wiland, Anne; McCague, Kevin; Chisholm-Burns, Marie

    2014-04-17

    Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions. Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; model was used to identify factors associated with nonadherence. In total, 808/946 recipients (85.4%) provided ≥1 ITAS score. Nonadherence was reported by 24.8%, 31.5%, 33.0%, 39.8%, 35.4% and 26.4% at months 3, 6, 12, 24, 36 and 48, respectively. Mean ITAS score was higher with EC-MPS vs. MMF at months 24 (11.3[1.0] vs. 10.9[1.4], p=0.001) and 36 (11.4[1.0] vs. 11.1[11.3], p=0.024). The odds ratio for nonadherence was 1.60 (95% CI 1.17, 2.19; p=0.003) for African Americans vs. non-African Americans. The rate of biopsy-proven acute rejection was 12.7% (51/401) in nonadherent recipients vs. 11.3% (46/406) in adherent recipients (p=0.59); graft loss was 4.7% (19/402) vs. 3.0% (12/406) (p=0.20); death was 1.5% (6/402) vs. 4.7% (19/406) (p=0.013). Adherence to the immunosuppressive regimen decreases over time, highlighting the need to monitor and encourage adherence even in long-term maintenance kidney transplant patients. Other than African American race, demographic factors may be of limited value in predicting nonadherence.

  4. Relationship between evaluation by quantitative fatty acid myocardial scintigraphy and response to {beta}-blockade therapy in patients with dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Tatsuo; Hoshida, Shiro; Nishino, Masami; Aoi, Toshiyuki; Egami, Yasuyuki; Takeda, Toshihiro; Kawabata, Masayoshi; Tanouchi, Jun; Yamada, Yoshio; Kamada, Takenobu [Div. of Cardiology, Osaka Rosai Hospital (Japan)

    2001-12-01

    Predicting the effect of {beta}-blockade therapy on the clinical outcome of patients with dilated cardiomyopathy (DCM) is difficult prior to the initiation of therapy. Myocardial fatty acid metabolism has been shown to be impaired in patients with DCM. We examined whether the extent of myocardial injury, as assessed by iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy, is related to the response of patients with DCM to {beta}-blockade therapy. Thirty-seven patients with DCM were examined using BMIPP myocardial scintigraphy before and after 6 months of treatment with metoprolol. Myocardial BMIPP uptake (%BM uptake) was estimated quantitatively as a percentage of the total injected count ratio. The left ventricular end-diastolic and end-systolic dimensions (LVDd, LVDs) and ejection fraction (LVEF) were also evaluated. The patients were divided into two groups according to their functional improvement (>10% elevation of LVEF) after 6 months of metoprolol therapy. Twenty-eight patients responded to the therapy, while nine did not. Prior to the therapy, no significant differences in LVDd, LVDs or LVEF were observed between the responders and non-responders. However, the %BM uptake was significantly lower in the non-responders than in the responders (1.0%{+-}0.2% vs 2.1%{+-}0.5%, P<0.001). The %BM uptake could be used to distinguish the responders from the non-responders with a sensitivity of 0.93 and a specificity of 1.00 at a threshold value of 1.4. After the metoprolol therapy, the %BM uptake improved significantly in the responders (2.5%{+-}0.5%, P<0.01) but did not change in the non-responders. These results indicate that myocardial BMIPP uptake could predict the response of DCM patients to {beta}-blockade therapy. (orig.)

  5. Effect of omega-3 fatty acids versus 5-hydroxytryptophan as add on therapy to sertraline in controlling suicidal ideation in patients with depression: A comparative study

    Directory of Open Access Journals (Sweden)

    Jyoti Prakash Sahoo

    2016-04-01

    Full Text Available Background: Omega-3 fatty acids and 5-hydroxytryptophan have been gaining attention as promising alternative treatment for depressive illness. These agents are given as as add on treatment to conventional antidepressant drugs. The present study was carried out to evaluate efficacy of omega-3 fatty acids versus 5-hydroxytryptophan as add on therapy in controlling suicidal ideation in depressive patients on sertraline.Methods: This was a prospective, open label, randomized, parallel group study conducted in department of Psychiatry. Ninety treatment naïve patients (18-65 years age were divided into 3 groups of 30 each. Group I: Sertraline, Group II: Sertraline plus omega-3 fatty acids, Group III: Sertraline plus 5-hydroxytryptophan. Suicidal ideations were assessed with Beck’s scale for suicidal ideation (BSI at weeks 0, 4 and 8. Data were analyzed using repeated measures ANOVA (SPSS version 20.0. Post hoc analysis was done using Bonferroni test.Results: Baseline parameters in patients of all groups were comparable. Administration of sertraline resulted in reduction of Beck’s scale for suicidal ideation scores as compared to baseline. Addition of omega-3 fatty acids and 5-hydroxytryptophan also showed reduction in BSI scores. Effect of sertraline monotherapy was more as compared to omega-3 fatty acids or 5-hydroxytryptophan as add on therapy, which was statistically significant (p value < 0.05.Conclusion: Both omega-3 fatty acids and 5-hydroxytryptophan produce significant effect in controlling suicidal ideations in patients with depression.

  6. Adjunct therapy of n-3 fatty acids to 5-ASA ameliorates inflammatory score and decreases NF-κB in rats with TNBS-induced colitis.

    Science.gov (United States)

    Mbodji, Khaly; Charpentier, Cloé; Guérin, Charlène; Querec, Coraline; Bole-Feysot, Christine; Aziz, Moutaz; Savoye, Guillaume; Déchelotte, Pierre; Marion-Letellier, Rachel

    2013-04-01

    5-aminosalicylic acid (5-ASA) is widely used for the treatment of inflammatory bowel disease (IBD). Recent studies have evaluated the potential of nutritional intervention as adjunct therapy to 5-ASA in IBD. N-3 polyunsaturated fatty acids (PUFA) have shown potent anti-inflammatory properties in gut inflammation. Therefore, we aimed to evaluate the efficacy of the dual therapy (n-3 PUFA plus 5-ASA) in rats with 2, 4, 6-trinitrobenzen sulfonic acid (TNBS)-induced colitis. Colitis was induced by intrarectal injection of TNBS while control rats received the vehicle. Rats received by gavage a fish oil-rich formula (n-3 groups) or an isocaloric and isolipidic oil formula supplemented with 5-ASA for 14 days. A dose response of 5-ASA (5-75 mg. suppression mg kg(-1) d(-1)) was tested. Colitis was evaluated and several inflammatory markers were quantified in the colon. COX-2 expression (Pinducing peroxisome proliferator-activated receptor-γ (PPARγ) expression (Pinduce PPARγ. By contrast, the dual therapy did not improve the effects of individual treatments on eicosanoids or cytokine production. Use of n-3 PUFA in addition to 5-ASA may reduce dose of standard therapy.

  7. Effect of folic acid combined with VitB12 therapy on serum biochemical indexes and carotid atherosclerosis in patients with hypertension and hyperhomocysteinemia

    Institute of Scientific and Technical Information of China (English)

    Hui Peng; Su Chen; Si-Kun Wang; Heng-You Liu; Yu-Zhen Sun; Xiao-Jun Hu

    2016-01-01

    Objective:To analyze the effect of folic acid combined with VitB12 therapy on serum biochemical indexes and carotid atherosclerosis in patients with hypertension and hyperhomocysteinemia.Methods:A total of 112 patients with hypertension and hyperhomocysteinemia who received treatment in our hospital from January 2013 to January 2016 were included in the study and divided into observation group and control group (n=56) according to random number table. Control group received routine therapy, observation group received folic acid combined with VitB12 therapy, and then differences in carotid atherosclerosis-related indicators, vascular endothelial function parameters, serum biochemical indicators and so on were compared between two groups.Results: Color Doppler ultrasound IMT, Dis, DC and PWV values of observation group after treatment were lower than those of control group patients, and CC value was higher than that of control group; D0 value of observation group after treatment was lower than that of control group, and FMD value was higher than that of control group; serum HDL-C and NO values of observation group after treatment were higher than those of control group while LDL-C and Hcy values were lower than those of control group.Conclusion:Folic acid combined with VitB12 therapy can optimize the serum biochemical indexes and reduce the degree of carotid atherosclerosis in patients with hypertension and hyperhomocysteinemia, and it helps to reduce disease risk.

  8. Synergistic combination of valproic acid and oncolytic parvovirus H-1PV as a potential therapy against cervical and pancreatic carcinomas.

    Science.gov (United States)

    Li, Junwei; Bonifati, Serena; Hristov, Georgi; Marttila, Tiina; Valmary-Degano, Séverine; Stanzel, Sven; Schnölzer, Martina; Mougin, Christiane; Aprahamian, Marc; Grekova, Svitlana P; Raykov, Zahari; Rommelaere, Jean; Marchini, Antonio

    2013-10-01

    The rat parvovirus H-1PV has oncolytic and tumour-suppressive properties potentially exploitable in cancer therapy. This possibility is being explored and results are encouraging, but it is necessary to improve the oncotoxicity of the virus. Here we show that this can be achieved by co-treating cancer cells with H-1PV and histone deacetylase inhibitors (HDACIs) such as valproic acid (VPA). We demonstrate that these agents act synergistically to kill a range of human cervical carcinoma and pancreatic carcinoma cell lines by inducing oxidative stress, DNA damage and apoptosis. Strikingly, in rat and mouse xenograft models, H-1PV/VPA co-treatment strongly inhibits tumour growth promoting complete tumour remission in all co-treated animals. At the molecular level, we found acetylation of the parvovirus nonstructural protein NS1 at residues K85 and K257 to modulate NS1-mediated transcription and cytotoxicity, both of which are enhanced by VPA treatment. These results warrant clinical evaluation of H-1PV/VPA co-treatment against cervical and pancreatic ductal carcinomas. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  9. The influence of photodynamic therapy (PDT) with δ-aminolevulinic acid (ALA) on J-774A.1 macrophage cell line

    Science.gov (United States)

    Kawczyk-Krupka, Aleksandra; Czuba, Zenon; Ledwon, Aleksandra; Latos, Wojciech; Sliszka, Ewelina; Mianowska, Marta; Krol, Wojciech; Sieron, Aleksander

    2008-02-01

    Introduction. The whole mechanism of the cellular level of tumor destruction by photodynamic therapy (PDT) is still unknown. Despite necrotic and apoptotic ways of cell death, there is a variety of events leading to and magnifying the inactivation of tumor cells. Material and methods. J-774A.1 were incubated with δ-aminolevulinic acid (ALA) at different concentrations (125, 250, 500, 1000 μM) and then irradiated with VIS (400 - 750 nm) at the dose of 5,10 and 30 J/cm2 delivered from the incoherent light source. The effects of the application of ALA-PDT were evaluated on the basis of cell viability, nitric oxide (NO), tumor necrosis factor α- (TNF-α) and interleukin-1β (IL-1β) produced by the J-774A.1 cells. Results. The cell viability (assessed using MTT test) was comparable with control group at 5,10 and 30 J/cm2. At these doses of energy using different concentrations of ALA we have observed that at the higher energy doses, the greater increase of TNF-α release, lowering of the level of IL-1β production and decrease of NO release were observed. There was also observed the dependence of the secretional activity of the cells on the ALA concentrations. Conclusion. The cell viability and production of cytokines depended on ALA concentrations and energy doses of the light. The higher some cytokines' release after PDT could be an additional factor for the complete eradication of tumor.

  10. Effects of 5-aminolevulinic acid photodynamic therapy on TLRs in acne lesions and keratinocytes co-cultured with P. acnes.

    Science.gov (United States)

    Ma, Ying; Chen, Qinyi; Liu, Ye; Wang, Qianqian; Huang, Zheng; Xiang, Leihong

    2016-09-01

    To investigate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on the expression of Toll like receptors (TLRs) in human keratinocytes and its role in acne treatment. TLR2 and TLR4 expression in acne lesions before and after ALA-PDT were examined by immunohistochemical assay. Primary keratinocytes were obtained from acne lesions, co-cultured with P. acnes and then treated with ALA-PDT using red or blue LED. Cytokines production were examined by ELISA, TLR2 and TLR4 gene expression by real-time PCR, and TLR2 and TLR4 protein expression by Western-blot assay. The overexpression of TLR2 and TLR4 in acne lesion were detected, which became negative or weaker after ALA-PDT. The infection of P. acnes in keratinocytes could significantly increase the levels of early inflammatory cytokines (e.g. IL-1α, TNF-α and IL-8) (Pkeratinocytes (Pkeratinocytes treated with P. acnes via TLRs pathways. Copyright © 2016. Published by Elsevier B.V.

  11. Styrene-maleic acid-copolymer conjugated zinc protoporphyrin as a candidate drug for tumor-targeted therapy and imaging.

    Science.gov (United States)

    Fang, Jun; Tsukigawa, Kenji; Liao, Long; Yin, Hongzhuan; Eguchi, Kanami; Maeda, Hiroshi

    2016-01-01

    Previous studies indicated the potential of zinc protoporphyrin (ZnPP) as an antitumor agent targeting to the tumor survival factor heme oxygenase-1, and/or for photodynamic therapy (PDT). In this study, to achieve tumor-targeted delivery, styrene-maleic acid-copolymer conjugated ZnPP (SMA-ZnPP) was synthesized via amide bond, which showed good water solubility, having ZnPP loading of 15%. More importantly, it forms micelles in aqueous solution with a mean particle size of 111.6 nm, whereas it has an apparent Mw of 65 kDa. This micelle formation was not detracted by serum albumin, suggesting it is stable in circulation. Further SMA-ZnPP conjugate will behave as an albumin complex in blood with much larger size (235 kDa) by virtue of the albumin binding property of SMA. Consequently, SMA-ZnPP conjugate exhibited prolonged circulating retention and preferential tumor accumulation by taking advantage of enhanced permeability and retention (EPR) effect. Clear tumor imaging was thus achieved by detecting the fluorescence of ZnPP. In addition, the cytotoxicity and PDT effect of SMA-ZnPP conjugate was confirmed in human cervical cancer HeLa cells. Light irradiation remarkably increased the cytotoxicity (IC50, from 33 to 5 μM). These findings may provide new options and knowledge for developing ZnPP based anticancer theranostic drugs.

  12. Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

    Science.gov (United States)

    Basso, F. G.; Pansani, T. N.; Turrioni, A. P. S.; Kurachi, C.; Bagnato, V. S.; Hebling, J.; de Souza Costa, C. A.

    2013-05-01

    Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm-2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions.

  13. Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy

    Directory of Open Access Journals (Sweden)

    Myung Won Lee

    2013-06-01

    Full Text Available Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C, additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL particle size and triglyceride (TG level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P=0.049. Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.

  14. Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy

    Directory of Open Access Journals (Sweden)

    Qu CY

    2015-06-01

    Full Text Available Chun-Ying Qu,1,* Min Zhou,1,* Ying-wei Chen,2 Mei-mei Chen,3 Feng Shen,1 Lei-Ming Xu11Digestive Endoscopic Diagnosis and Treatment Center, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, People’s Republic of China; 3Digestive Department, Xinhua Hospital, School of medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China*These authors contributed equally to this workPurpose: The first-line chemotherapy treatment protocol for gastric cancer is combination chemotherapy of 5-fluorouracil (5-FU and cisplatin (CDDP. The aim of this study was to engineer prodrug-based nanostructured lipid carriers (NLC platform for codelivery of 5-FU and CDDP to enhance therapy and decrease toxicity.Methods: First, 5-FU-stearic acid lipid conjugate was synthesized by two steps. Second, 5-FU-stearic acid prodrug and CDDP were loaded in NLC. Finally, hyaluronic acid (HA was coated onto NLC surface. Average size, zeta potential, and drug loading capacity of NLC were evaluated. Human gastric cancer cell line BGC823 (BGC823 cells was used for the testing of in vitro cytotoxicity assays. In vivo antitumor activity of NLC was evaluated in mice bearing BGC823 cells model.Results: HA-coated 5-FU-stearic acid prodrug and CDDP-loaded NLC (HA-FU/C-NLC showed a synergistic effect in combination therapy and displayed the greatest antitumor activity than all of the free drugs or uncoated NLC in vitro and in vivo.Conclusion: This work reveals that HA-coated NLC could be used as a novel carrier to codeliver 5-FU and CDDP for gastric cancer therapy. HA-FU/C-NLC could be a promising targeted and combinational therapy in nanomedicine.Keywords: gastric cancer, nanostructured lipid carriers, hyaluronic acid, combination chemotherapy, lipid prodrug

  15. Photodynamic therapy using systemic administration of 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode for methicillin-resistant Staphylococcus aureus-infected ulcers in mice.

    Science.gov (United States)

    Morimoto, Kuniyuki; Ozawa, Toshiyuki; Awazu, Kunio; Ito, Nobuhisa; Honda, Norihiro; Matsumoto, Sohkichi; Tsuruta, Daisuke

    2014-01-01

    Bacterial resistance to antibiotics has become a worldwide problem. One potential alternative for bacterial control is photodynamic therapy. 5-aminolevulinic acid is a natural precursor of the photosensitizer protoporphyrin IX. Relatively little is known about the antibacterial efficacy of photodynamic therapy using the systemic administration of 5-aminolevulinic acid; a few reports have shown that 5-aminolevulinic acid exerts photodynamic effects on methicillin-resistant Staphylococcus aureus (MRSA) in vitro. In this study, we evaluated the effectiveness of photodynamic therapy using 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode in vitro and in vivo for the treatment of MRSA. We found that 5-aminolevulinic acid photodynamic therapy with the light-emitting diode had an in-vitro bactericidal effect on MRSA. In vivo, protoporphyrin IX successfully accumulated in MRSA on ulcer surfaces after intraperitoneal administration of 5-aminolevulinic acid to mice. Furthermore, 5-aminolevulinic acid photodynamic therapy accelerated wound healing and decreased bacterial counts on ulcer surfaces; in contrast, vancomycin treatment did not accelerate wound healing. Our findings indicate that 5-aminolevulinic acid photodynamic therapy may be a new treatment option for MRSA-infected wounds.

  16. Effect ofα-lipoic acid combined with mecobalamine therapy on urodynamics and oxidative damage of nerve in patients with diabetic neurogenic bladder

    Institute of Scientific and Technical Information of China (English)

    Ming-Bao Ye; Chang-Guo Du; Qun-Feng Yan; Jia-Mei Gui

    2016-01-01

    Objective:To analyze the effect ofα-lipoic acid combined with mecobalamine therapy on urodynamics and oxidative damage of nerve in patients with diabetic neurogenic bladder. Methods:A total of 78 patients with diabetic neurogenic bladder were randomly divided into observation group and control group (n=39), control group received conventional therapy and observation group received conventional therapy +α-lipoic acid combined with mecobalamine therapy. Before treatment and after one course of treatment, urodynamic indexes, peripheral nerve conduction latency time and serum indexes of two groups were detected respectively. Results: After one course of treatment, RUV, Pdet, FS, T and C value as well as ROS, MDA, SP, NPY and ChAT content of both groups were significantly lower than those before treatment, MFR value as well as GSH, SOD, BDNF and CNTF content was significantly higher than those before treatment, and the sensory conduction latency time of median nerve and ulnar nerve as well as motor conduction latency time of median nerve and peroneal nerve were shorter than those before treatment (P<0.05); RUV, Pdet, FS, T and C value as well as ROS, MDA, SP, NPY and ChAT content of observation group were significantly lower than those of control group, MFR value as well as GSH, SOD, BDNF and CNTF content was significantly higher than those of control group, and the sensory conduction latency time of median nerve and ulnar nerve as well as motor conduction latency time of median nerve and peroneal nerve were significantly shorter than those of control group (P<0.05).Conclusions:α-lipoic acid combined with mecobalamine therapy can optimize the urodynamics in patients with diabetic neurogenic bladder and also reduce the oxidative damage of nerve, and it is an effective solution for treatment of such disease.

  17. Cystic acne improved by photodynamic therapy with short-contact 5-aminolevulinic acid and sequential combination of intense pulsed light and blue light activation.

    Science.gov (United States)

    Melnick, Stuart

    2005-01-01

    Photodynamic therapy with short-contact 5-aminolevulinic acid (Levulan Kerastick, Dusa Pharmaceuticals, Inc.) and activation by intense pulsed light in an initial treatment and blue light in 3 subsequent treatments has resulted in significant improvement in severity of acne, reduction in the number of lesions, improvement in skin texture, and smoothing of scar edges in an Asian patient with severe (class 4) facial cystic acne and scarring.

  18. Comparative Study of Photodynamic Therapy with Topical Methyl Aminolevulinate versus 5-Aminolevulinic Acid for Facial Actinic Keratosis with Long-Term Follow-Up

    OpenAIRE

    Ko, Dong-Yeob; Kim, Ki-Ho; Song, Ki-Hoon

    2014-01-01

    Background Few studies have compared the efficacy, cosmetic outcomes, and adverse events between 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and methyl aminolevulinate-PDT (MAL-PDT) for actinic keratoses (AKs) in Asian ethnic populations with dark-skin. Objective We retrospectively compared the long-term efficacy, recurrence rates, cosmetic outcomes, and safety of ALA-PDT versus MAL-PDT for facial AKs in Koreans. Methods A total of 222 facial AKs in 58 patients were included in this ...

  19. Long-Term γ-Hydroxybutyric Acid (GHB) and Disulfiram Combination Therapy in GHB Treatment-Resistant Chronic Alcoholics

    Science.gov (United States)

    Maremmani, Angelo Giovanni Icro; Pani, Pier Paolo; Rovai, Luca; Pacini, Matteo; Dell’Osso, Liliana; Maremmani, Icro

    2011-01-01

    Leading Italian studies support the use of γ-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30–40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of ‘antagonist’ effect by using the ‘psychological threat’ of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its ‘non-blockade’ effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis. PMID:21845160

  20. Long-Term γ-Hydroxybutyric Acid (GHB and Disulfiram Combination Therapy in GHB Treatment-Resistant Chronic Alcoholics

    Directory of Open Access Journals (Sweden)

    Icro Maremmani

    2011-07-01

    Full Text Available Leading Italian studies support the use of γ-hydroxybutyric acid (GHB, not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30–40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of ‘antagonist’ effect by using the ‘psychological threat’ of disulfiram (adversative effect while taking advantage of the anticraving effect of GHB, despite the limitation of its ‘non-blockade’ effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4% successfully completed the protocol and were considered to be responders; 18 (34.6% left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.

  1. Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus

    Science.gov (United States)

    Walford, Geoffrey A.; Davis, Jaclyn; Warner, A. Sofia; Ackerman, Rachel J.; Billings, Liana K.; Chamarthi, Bindu; Fanelli, Rebecca R.; Hernandez, Alicia M.; Huang, Chunmei; Khan, Sabina Q.; Littleton, Katherine R.; Lo, Janet; McCarthy, Rita M.; Rhee, Eugene P.; Deik, Amy; Stolerman, Elliot; Taylor, Andrew; Hudson, Margo S.; Wang, Thomas J.; Altshuler, David; Grant, Richard W.; Clish, Clary B.; Gerszten, Robert E.; Florez, Jose C.

    2013-01-01

    Objective Elevated circulating levels of branched chain and aromatic amino acids (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/AAAs also signal an early response to commonly used medical therapies for T2D. Materials and Methods A liquid chromatography-mass spectrometry approach was used to measure BCAA/AAAs in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: 1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; 2) two days of twice daily metformin 500 mg orally; and 3) a 75-gram OGTT. Percent change in BCAA/AAAs was determined after each intervention. Results Following glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/AAAs decreased in the IS subjects only (all P<0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/AAAs increased in the IR subjects at or below P=0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/AAAs decreased in all subjects (P<0.05). Conclusions BCAA/AAAs changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/AAAs may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D. PMID:23953891

  2. A Patient-Specific Polylactic Acid Bolus Made by a 3D Printer for Breast Cancer Radiation Therapy.

    Science.gov (United States)

    Park, So-Yeon; Choi, Chang Heon; Park, Jong Min; Chun, MinSoo; Han, Ji Hye; Kim, Jung-In

    2016-01-01

    The aim of this study was to assess the feasibility and advantages of a patient-specific breast bolus made using a 3D printer technique. We used the anthropomorphic female phantom with breast attachments, which volumes are 200, 300, 400, 500 and 650 cc. We simulated the treatment for a right breast patient using parallel opposed tangential fields. Treatment plans were used to investigate the effect of unwanted air gaps under bolus on the dose distribution of the whole breast. The commercial Super-Flex bolus and 3D-printed polylactic acid (PLA) bolus were applied to investigate the skin dose of the breast with the MOSFET measurement. Two boluses of 3 and 5 mm thicknesses were selected. There was a good agreement between the dose distribution for a virtual bolus generated by the TPS and PLA bolus. The difference in dose distribution between the virtual bolus and Super-Flex bolus was significant within the bolus and breast due to unwanted air gaps. The average differences between calculated and measured doses in a 200 and 300 cc with PLA bolus were not significant, which were -0.7% and -0.6% for 3mm, and -1.1% and -1.1% for 5 mm, respectively. With the Super-Flex bolus, however, significant dose differences were observed (-5.1% and -3.2% for 3mm, and -6.3% and -4.2% for 5 mm). The 3D-printed solid bolus can reduce the uncertainty of the daily setup and help to overcome the dose discrepancy by unwanted air gaps in the breast cancer radiation therapy.

  3. Long-term γ-hydroxybutyric acid (GHB) and disulfiram combination therapy in GHB treatment-resistant chronic alcoholics.

    Science.gov (United States)

    Maremmani, Angelo Giovanni Icro; Pani, Pier Paolo; Rovai, Luca; Pacini, Matteo; Dell'Osso, Liliana; Maremmani, Icro

    2011-07-01

    Leading Italian studies support the use of γ-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30-40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of 'antagonist' effect by using the 'psychological threat' of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its 'non-blockade' effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.

  4. Topical 5-aminolevulinic acid photodynamic therapy improved refractory acne conglobata and perifolliculitis capitis abscedens et suffodiens rather than hidradenitis suppurativa

    Directory of Open Access Journals (Sweden)

    Linglin Zhang

    2016-01-01

    Full Text Available Acne conglobata (AC, perifolliculitis capitis abscedens et suffodiens (PCAS and hidradenitis suppurativa (HS are uncommon refractory chronic, inflammatory, scarring diseases but cause serious damage to the quality of life. These three diseases are associated with follicular occlusion. Several studies indicated topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT improved follicular occlusion besides acne treatment. So we attempted to apply ALA-PDT to medicine resistant AC, PCAS and HS. Topical ALA-PDT was applied to 10 patients with AC, seven patients with PCAS and three patients with HS for more than three sessions. All the patients completed the dermatology life quality index (DLQI questionnaire and were assessed for the efficacy at the baseline and on two weeks after each treatment. Adverse effects were recorded at each visit. The results showed 25.5% (5/20, two cases of AC and three cases of PCAS of patients achieved excellent improvement after three sessions of PDT and another 60.0% (12/20, eight cases of AC and four cases of PCAS of patients achieved good improvement. 15.0% (3/20, three cases of HS got poor response (< 20% lesions clearance. Another five cases (three cases of AC and two cases of PCAS also achieved excellent response after 5–7 sessions of PDT. We also found that papular/nodular, cyst/abscess showed higher clearance rate than sinus/fistula (88.5%, 86.1% versus 11.1%. DLQI was reduced after three sessions of PDT in AC and PCAS patients rather than HS patients. 5-ALA-PDT could improve refractory AC and PCAS but could not lead to improvement in late stage of HS. The efficacy increased with more treatment sessions.

  5. Effects of a Combined Therapy With D-002 (Beeswax Alcohols) Plus D-003 (Sugarcane Wax Acids) on Osteoarthritis Symptoms.

    Science.gov (United States)

    Puente, Roberto Antonio; Illnait, José; Mas, Rosa María; Carbajal, Daisy María; Mendoza, Sarahí; Ceballos, Alfredo; Fernández, Julio César; Mesa, Meilis; Reyes, Pablo; Ruiz, Dalmer

    2016-06-01

    Context • Nonsteroidal, anti-inflammatory drugs effectively relieve osteoarthritis (OA) symptoms but also induce adverse effects (AEs) that limit their long-term use, which drives a search for safer treatments. D-002, a mixture of beeswax alcohols, and D-003, a mixture of sugarcane wax acids, have been effective in experimental and clinical studies for patients with OA. Objective • The study intended to investigate the effects on OA symptoms of a combined therapy using D-002 and D-003 (D-002/D-003), which were administered for 6 wk. Design • The study was a randomized, double-blind, placebo-controlled trial. Setting • The study was conducted at the Surgical Medical Research Center in Havana, Cuba. Participants • Participants were patients with mild-to-moderate OA. Intervention • Participants were randomly assigned to 1 of 4 groups-(1) a control group, which received a placebo; (2) the D-002 group (intervention group), which received 50 mg/d of D-002; (3) the D-003 group (intervention group), which received 10 mg/d of D-003; or (4) the D-002/D-003 group (intervention group), which received a combined therapy of 50 mg/d of D-002 plus 10 mg/d of D-003. The control group received tablets that were indistinguishable in appearance from the D-002 and D-003 tablets and had a similar composition, except that the active ingredients were replaced by lactose. The groups took the medications once per day for 6 wk. Outcome Measures • Symptoms were assessed using the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and a visual analogue scale (VAS). The primary outcome was the reduction in the total WOMAC score. The subscale scores on the WOMAC for pain, stiffness, and physical function, the VAS scores, and the use of rescue medications were secondary outcomes. Results • Of the 120 enrolled participants, 116 completed the study. The treatments with D-002, D-003, and D-002/D-003 reduced the mean total WOMAC scores significantly from baseline to

  6. Effect of folic acid adjuvant therapy on Hcy as well as lipid metabolism and endothelial injury in coronary heart disease patients with stable angina pectoris

    Institute of Scientific and Technical Information of China (English)

    Liang Wen; Yi Xie; Xian-Jun Wu; Rui-Feng Wang; Jian Cao

    2016-01-01

    Objective:To analyze the effect of folic acid adjuvant therapy on Hcy as well as lipid metabolism and endothelial injury in coronary heart disease patients with stable angina pectoris. Methods:A total of 98 cases of coronary heart disease patients with stable angina pectoris who received treatment in our hospital from March 2014 to August 2015 were selected as research subjects and randomly divided into observation group 49 cases and control group 49 cases. Control group received conventional clinical treatment, observation group received folic acid adjuvant therapy, and then differences in levels of Hcy, lipid metabolism, endothelial injury and adhesion molecules were compared between two groups after treatment. Results:Hcy, TC, LDL-C and ApoB values of observation group were lower than those of control group while HDL-C and ApoA1/ApoB values were higher than those of control group;Flow-vel and FMD values of observation group after treatment were higher than those of control group;serum E-selectin, ICAM-1, VCAM-1 and sICAM-1 values of observation group after treatment were lower than those of control group. Conclusion:Folic acid adjuvant therapy for coronary heart disease patients with stable angina pectoris can reduce plasma Hcy level and optimize lipid metabolism, further protects vascular endothelium, and has positive clinical significance.

  7. Maintenance therapy with all-trans retinoic acid and arsenic trioxide improves relapse-free survival in adults with low- to intermediate-risk acute promyelocytic leukemia who have achieved complete remission after consolidation therapy.

    Science.gov (United States)

    Liang, Bin; Zheng, Zhouyi; Shi, Yifen; Chen, Jingjing; Hu, Xudong; Qian, Honglan; Shen, Zhijian; Jiang, Songfu; Yu, Kang; Feng, Jianhua

    2017-01-01

    Currently, the optimal maintenance therapy for patients with acute promyelocytic leukemia (APL) who have achieved complete remission (CR) after completing consolidation chemotherapy remains controversial. The comparative effectiveness of the all-trans retinoic acid (ATRA) plus arsenic trioxide (As2O3) maintenance strategy with classic ATRA plus chemotherapy has not been evaluated. In this study, we compared the efficacy and toxicity of maintenance therapy with ATRA plus As2O3 and classic ATRA plus chemotherapy in low- to intermediate-risk APL patients reaching the first CR after induction and consolidation therapy. A retrospective review of 58 adult patients diagnosed with APL was conducted. After receiving consolidation therapy and achieving CR, 30 patients were administered maintenance therapy with an ATRA plus As2O3 regimen (ATRA+As2O3 group), whereas 28 patients were administered 3-monthly cycles of an ATRA plus chemotherapy regimen (ATRA+chemotherapy group). Grade 3-4 neutropenia was significantly more frequent in the ATRA+chemotherapy group (N=9, 32.1%) than in the ATRA+As2O3 group (N=0) (P=0.001). At a median follow-up of 49.1 months (range: 9.7-97.4 months) from the completion of consolidation, no relapses were observed in the ATRA+As2O3 group, whereas seven relapses occurred in the ATRA+chemotherapy group. The risk of relapse in the patients administered ATRA+As2O3 maintenance was significantly lower than that in those administered ATRA+chemotherapy maintenance (P=0.004). Based on log-rank analysis, only maintenance therapy with ATRA and As2O3 was associated with a significantly higher relapse-free survival (P=0.0159). Maintenance therapy with ATRA and As2O3 was beneficial in low- to intermediate-risk APL patients who were effectively treated to achieve CR. Further clinical trials with reliable designs are needed to confirm these observations.

  8. 5-Amino-4-oxopentanoic acid photodynamic diagnosis guided microsurgery and photodynamic therapy on VX2 brain tumour implanted in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    XIAO Hong; LIAO Qiong; CHENG Ming; LI Fei; XIE Bing; LI Mei; FENG Hua

    2009-01-01

    Background Complete tumour resection is important for improving the prognosis of brain tumour patients. However,extensive resection remains controversial because the tumour margin is difficult to be distinguished from surrounding brain tissue. It has been established that 5-amino-4-oxopentanoic acid (5-aminolevulinic acid, ALA) can be used as a photodynamic diagnostic marker and a photosensitizer for photodynamic therapy in surgical treatment of brain tumours. We investigated the efficacy of ALA photodynamically guided microsurgery and photodynamic therapy on VX2 brain tumour implanted in a rabbit model.Methods Eighty New Zealand rabbits implanted with VX2 brain tumours were randomly assigned to five groups: control, conventional white light microsurgery, a photodynamic therapy group, a photodynamically guided microsurgery group and a group in which guided microsurgery was followed by photodynamic therapy. The VX2 tumour was resected under a surgical microscope. The tumour resection was confirmed with histological analysis. All animals were examined with MRI for presence of any residual tumour tissue. The survival time of each rabbit was recorded.Results All treatment groups showed a significantly extended survival time compared with the control group.Photodynamically guided microsurgery combined with photodynamic therapy significantly prolonged survival time, compared with guided microsurgery alone. MRI and the autopsy results confirmed removal of most of the tumours.Conclusions Our results suggest that photodynamically guided surgery and photodynamic therapy significantly reduce or delay local recurrence, increase the effectiveness of radical resection and prolong the survival time of tumour bearing rabbits, Their combination has the potential to be used as a rapid and highly effective treatment of metastatic brain tumours.

  9. Effect of branched-chain amino acid-enriched nutritional supplementation on interferon therapy in Japanese patients with chronic hepatitis C virus infection: a retrospective study

    Directory of Open Access Journals (Sweden)

    Nagao Yumiko

    2012-11-01

    Full Text Available Abstract Background The aims of this study were to evaluate the effects of nutritional supplementation with branched-chain amino acids (BCAA with zinc component (Aminofeel® on adherence to and outcome of therapy in patients treated with interferon (IFN for chronic hepatitis C and cirrhosis and to determine whether to recommend the supplement. Methods In this retrospective study, 51 patients who received IFN therapy were investigated among 203 consecutive patients who visited our hospital and were advised regarding the potential benefit of taking Aminofeel®. Each patient was free to choose whether to purchase and take Aminofeel®. Results Twenty four patients (group 1-A took Aminofeel® during standard IFN therapy and 13 (group 1-B did not. Low-dose, long-term IFN (maintenance therapy, mainly peglated (Peg-IFN alpha 2a, was administered to 14 patients who were difficult to treat, because of no effect or harmful side effects with standard IFN therapy, and who had advanced liver fibrosis. Among the 14, 11 patients (group 2-A took Aminofeel® and 3 (group 2-B did not. The prevalence of obesity was significantly higher (P=0.04 in group 1-A than in group 1-B. The rate of adherence to IFN therapy was higher in group 1-A (83.3% than in group 1-B (53.8%, P=0.05. There were no significant differences between the two groups in the rates of sustained virological response (SVR to IFN therapy. According to multivariate analysis, two factors, SVR and intake of Aminofeel®, were associated with successful adherence to IFN therapy. The adjusted odds ratios for these two factors were 13.25 and 12.59, respectively, and each was statistically significant. The SVR rate of maintenance IFN therapy was in 18.2% group 2-A and 0% in group 2-B. Conclusion Our data show that BCAA intake is useful for adherence to and effect of IFN therapy for patients with chronic hepatitis C. Nutritional supplementation with BCAA seems to be useful for HCV-infected patients receiving

  10. Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy

    Directory of Open Access Journals (Sweden)

    Jurkić Lela Munjas

    2013-01-01

    Full Text Available Abstract Silicon (Si is the most abundant element present in the Earth's crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4, as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and with some other disorders or pharmacological effects. Beside the ortho-silicic acid and its stabilized formulations such as choline chloride-stabilized ortho-silicic acid and sodium or potassium silicates (e.g. M2SiO3; M= Na,K, the most important sources that release ortho-silicic acid as a bioavailable form of silicon are: colloidal silicic acid (hydrated silica gel, silica gel (amorphous silicon dioxide, and zeolites. Although all these compounds are characterized by substantial water insolubility, they release small, but significant, equilibrium concentration of ortho-silicic acid (H4SiO4 in contact with water and physiological fluids. Even though certain pharmacological effects of these compounds might be attributed to specific structural characteristics that result in profound adsorption and absorption properties, they all exhibit similar pharmacological profiles readily comparable to ortho-silicic acid effects. The most unusual ortho-silicic acid-releasing agents are certain types of zeolites, a class of aluminosilicates with well described ion(cation-exchange properties. Numerous biological activities of some types of zeolites documented so far might probably be attributable to the ortho-silicic acid-releasing property. In this review, we therefore discuss biological and potential therapeutic effects of ortho-silicic acid and ortho-silicic acid -releasing silicon compounds as its major natural sources.

  11. Fatty acid synthase is a key target in multiple essential tumor functions of prostate cancer: uptake of radiolabeled acetate as a predictor of the targeted therapy outcome.

    Directory of Open Access Journals (Sweden)

    Yukie Yoshii

    Full Text Available Fatty acid synthase (FASN expression is elevated in several cancers, and this over-expression is associated with poor prognosis. Inhibitors of FASN, such as orlistat, reportedly show antitumor effects against cancers that over-express FASN, making FASN a promising therapeutic target. However, large variations in FASN expression levels in individual tumors have been observed, and methods to predict FASN-targeted therapy outcome before treatment are required to avoid unnecessary treatment. In addition, how FASN inhibition affects tumor progression remains unclear. Here, we showed the method to predict FASN-targeted therapy outcome using radiolabeled acetate uptake and presented mechanisms of FASN inhibition with human prostate cancer cell lines, to provide the treatment strategy of FASN-targeted therapy. We revealed that tumor uptake of radiolabeled acetate reflected the FASN expression levels and sensitivity to FASN-targeted therapy with orlistat in vitro and in vivo. FASN-targeted therapy was noticeably effective against tumors with high FASN expression, which was indicated by high acetate uptake. To examine mechanisms, we established FASN knockdown prostate cancer cells by transduction of short-hairpin RNA against FASN and investigated the characteristics by analyses on morphology and cell behavior and microarray-based gene expression profiling. FASN inhibition not only suppressed cell proliferation but prevented pseudopodia formation and suppressed cell adhesion, migration, and invasion. FASN inhibition also suppressed genes involved in production of intracellular second messenger arachidonic acid and androgen hormones, both of which promote tumor progression. Collectively, our data demonstrated that uptake of radiolabeled acetate is a useful predictor of FASN-targeted therapy outcome. This suggests that [1-(11C]acetate positron emission tomography (PET could be a powerful tool to accomplish personalized FASN-targeted therapy by non

  12. Combination Therapy of Ursodeoxycholic Acid and Corticosteroids for Primary Biliary Cirrhosis with Features of Autoimmune Hepatitis: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2013-01-01

    Full Text Available A meta-analysis was performed of RCTs comparing therapies that combine UDCA and corticosteroids with UDCA monotherapy. In this paper, we found that the combination therapy of UDCA and corticosteroids was more effective for PBC-AIH.

  13. Aminolevulinic Acid-Mediated Photodynamic Therapy of Human Meningioma: An in Vitro Study on Primary Cell Lines

    Directory of Open Access Journals (Sweden)

    Mustafa El-Khatib

    2015-04-01

    Full Text Available Objective: Five-aminolevulinic acid (5-ALA-induced porphyrins in malignant gliomas are potent photosensitizers. Promising results of ALA-PDT (photodynamic therapy in recurrent glioblastomas have been published. Recently, 5-ALA-induced fluorescence was studied in meningioma surgery. Here, we present an experimental study of ALA-PDT in an in vitro model of primary meningioma cell lines. Methods: We processed native tumor material obtained intra-operatively within 24 h for cell culture. Epithelial membrane antigen (EMA immunohistochemistry was performed after the first passage to confirm that cells were meningioma cells. For 5-ALA-PDT treatment, about 5000 cells per well were seeded in 20 wells of a blank 96-well plate. Each block of 4 wells was inoculated with 150 µL of 0, 25, 50 and 100 µg/mL 5-ALA solutions; one block was used as negative control without 5-ALA and without PDT. Following incubation for 3 h PDT was performed using a laser (635 nm, 18.75 J/cm2. The therapeutic response was analyzed by the water soluble tetrazolium salt (WST-1 cell viability assay 90 min after PDT. Results: 5-ALA-PDT was performed in 14 primary meningioma cell lines. EMA expression was verified in 10 primary cell cultures. The remaining 4 were EMA negative and PDT was without any effect in these cultures. All 10 EMA-positive cell lines showed a significant and dose-dependent decrease in viability rate (p < 0.001. Cell survival at 5-ALA concentrations of 12.5, 25, 50 and 100 μg/mL was 96.5% ± 7.6%, 67.9% ± 29.9%, 24.0% ± 16.7% and 13.8% ± 7.5%, respectively. For the negative controls (no 5-ALA/PDT and ALA/no PDT, the viability rates were 101.72% ± 3.5% and 100.17% ± 3.6%, respectively. The LD50 for 5-ALA was estimated between 25 and 50 µg/mL. Conclusion: This study reveals dose-dependent cytotoxic effects of 5-ALA-PDT on primary cell lines of meningiomas. Either 5-ALA or PDT alone did not affect cell survival. Further efforts are necessary to study the

  14. Effects of a new intravenous electrolyte solution for veterinary therapy on the electrolyte and acid-base balances of healthy horses

    Directory of Open Access Journals (Sweden)

    Priscilla Fajardo Valente Pereira

    2016-01-01

    Full Text Available ABSTRACT: The effects of a new intravenous electrolyte solution for veterinary therapy on electrolyte and acid-base balances of horses were evaluated, assessing the potential of the use of this solution as a rational alternative in fluid therapy. Eight healthy adult horses, including 4 males and 4 females, received two treatments in a cross-over design: isotonic saline solution (IS and a test solution (TS containing 145mEq of Na+, 5mEq of K+, 4mEq of Ca++, 2mEq of Mg++, 96mEq of Cl-, 60mEq of lactate, 50g of dextrose, and 4mg of cyanocobalamin per liter. Solutions were IV infused in a volume corresponding to 5% of BW, over 3 hours. Venous blood samples were taken 5 times before and after the infusion (at 0, 3, 6, 9 e 24h, for pHv, pCO2v, HCO3 -v, BEv, Na+, K+, Cl-, Ca++, Ca, P, Mg, glucose and L-lactate measurements, and AG and SID calculations. The data were analyzed through repeated measures ANOVA. The IS caused mild acidifying effect by increasing Cl- and decreasing plasma SID. In contrast, the TS induced mild and transient hypochloremia without changes in acid-base balance. Hyperglycemia was present at the end of the TS infusion and reversed 6 hours later. The horses did not exhibit any clinical changes. We concluded that TS is an option for fluid therapy in horses.

  15. Combination therapy using fexofenadine, disodium cromoglycate, and a hypoallergenic amino acid-based formula induced remission in a patient with steroid-dependent, chronically active ulcerative colitis.

    Science.gov (United States)

    Raithel, M; Winterkamp, S; Weidenhiller, M; Müller, S; Hahn, E G

    2007-07-01

    Corticosteroids and 5-aminosalicylic acid are the primary standard therapy for inflammatory bowel disease. Recent immunologic data implicate an involvement of mast cell activation followed by increased histamine secretion and elevated tissue concentrations of histamine in the pathogenesis of ulcerative colitis. In the present case, the clinical course of a 35-year-old man with steroid-dependent chronic active ulcerative colitis, who did not respond to high-dose steroids, antibiotics, or azathioprine during 3 years, is reported. Clinical disease activity and established serological markers were recorded during 6 weeks of unsuccessful therapy and during the next 6 weeks, as a new nonsedative antihistaminergic drug, a mast cell stabilizer, and an hypoallergenic diet were implemented in addition to conventional therapy. Induction of remission was achieved within 2 weeks after treatment with fexofenadine, disodium cromoglycate, and an amino acid-based formula. Clinical disease activity, stool frequency, leukocytes, c-reactive protein, and orosomucoid levels in serum decreased rapidly. Daily steroid administration could be gradually reduced along with 6 weeks of this treatment. This report suggests that histamine and mast cell activity may be important pathophysiological factors responsible for persistent clinical and mucosal inflammatory activity in ulcerative colitis despite the use of steroids. In ulcerative colitis, patients unresponsive to conventional treatment, therapeutic considerations should also include an antiallergic approach when further signs of atopy or intestinal hypersensitivity are present.

  16. Effect of Zishenjianpihuayu prescription combined with retinal photocoagulation therapy on visual field defect, amino acid metabolism and serum cytokines in patient with NPDR

    Institute of Scientific and Technical Information of China (English)

    Qiu-Hong Liu; Yang-Gui Yu; Jing Guan; Ming-Wei Liu; Wei-Kun Chen

    2016-01-01

    Objective:To analyze the effect of Zishenjianpihuayu prescription combined with retinal photocoagulation therapy on visual field defect, amino acid metabolism and serum cytokines in patient with NPDR.Methods: A total of 80 cases of NPDR patients treated in our hospital from August 2012 to August 2015 were included in the study and divided into observation group and control group (n=40) according to the random number table. Control group received retinal photocoagulation treatment alone, observation group received Zishenjianpihuayu prescription combined with retinal photocoagulation treatment, and then the differences in visual field defect, amino acid metabolism and serum levels of cytokines were compared between two groups.Results: MD and CPSD values of observation group after treatment were lower than those of control group, and MS value was higher than that of control group; serum glutamic acid, arginine, tyrosine, valine, isoleucine and leucine values of observation group after treatment were lower than those of control group; serum sVCAM-1, sICAM-1, VEGF, Ang-2 and SDF-1 values of observation group after treatment were lower than those of control group, and APN value was higher than that of control group.Conclusion:Zishenjianpihuayu prescription combined with retinal photocoagulation therapy can reduce the visual field defect in patients with NPDR, and plays a positive role in optimizing the disease and balancing the body metabolism.

  17. Ambulant photodynamic therapy of superficial malignomas with 5-ALA in combination with folic acid and use of noncoherent light.

    Science.gov (United States)

    Jindra, R H; Kubin, A; Kolbabek, H; Alth, G; Dobrowsky, W

    1999-01-01

    This study reports our first results of ambulant photodynamic treatment with 5-aminolevulinic acid (5-ALA) in combination with folic acid and subsequent illumination with a noncoherent light source. The compound was topically applied to avoid total body skin sensitivity which occurs in the case of systemic administration. If no therapeutic response could be proved, we added folic acid to 5-ALA for a further treatment attempt. Illumination was performed by broad band red thermic light to also excitate reaction products with absorption bands located near to that of the sensitizer. As a result, we observed a response in all cases, however, in some cases only after the addition of folic acid.

  18. Non-physiological amino acid (NPAA) therapy targeting brain phenylalanine reduction: pilot studies in PAHENU2 mice.

    Science.gov (United States)

    Vogel, Kara R; Arning, Erland; Wasek, Brandi L; Bottiglieri, Teodoro; Gibson, K Michael

    2013-05-01

    Transport of large neutral amino acids (LNAA) across the blood brain barrier (BBB) is facilitated by the L-type amino acid transporter, LAT1. Peripheral accumulation of one LNAA (e.g., phenylalanine (phe) in PKU) is predicted to increase uptake of the offending amino acid to the detriment of others, resulting in disruption of brain amino acid homeostasis. We hypothesized that selected non-physiological amino acids (NPAAs) such as DL-norleucine (NL), 2-aminonorbornane (NB; 2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid), 2-aminoisobutyrate (AIB), and N-methyl-aminoisobutyrate (MAIB), acting as competitive inhibitors of various brain amino acid transporters, could reduce brain phe in Pah (enu2) mice, a relevant murine model of PKU. Oral feeding of 5 % NL, 5 % AIB, 0.5 % NB and 3 % MAIB reduced brain phe by 56 % (p amino acids) were also observed, however, with MAIB displaying the mildest effects. Of interest, MAIB represents an inhibitor of the system A (alanine) transporter that primarily traffics small amino acids and not LNAAs. Our studies represent the first in vivo use of these NPAAs in Pah (enu2) mice, and provide proof-of-principle for their further preclinical development, with the long-term objective of identifying NPAA combinations and concentrations that selectively restrict brain phe transport while minimally impacting other LNAAs and downstream intermediates.

  19. Co-delivery of all-trans-retinoic acid and doxorubicin for cancer therapy with synergistic inhibition of cancer stem cells.

    Science.gov (United States)

    Sun, Rong; Liu, Yang; Li, Shi-Yong; Shen, Song; Du, Xiao-Jiao; Xu, Cong-Fei; Cao, Zhi-Ting; Bao, Yan; Zhu, Yan-Hua; Li, Ya-Ping; Yang, Xian-Zhu; Wang, Jun

    2015-01-01

    Combination treatment through simultaneous delivery of two or more drugs with nanoparticles has been demonstrated to be an elegant and efficient approach for cancer therapy. Herein, we employ a combination therapy for eliminating both the bulk tumor cells and the rare cancer stem cells (CSCs) that have a high self-renewal capacity and play a critical role in cancer treatment failure. All-trans-retinoic acid (ATRA), a powerful differentiation agent of cancer stem cells and the clinically widely used chemotherapy agent doxorubicin (DOX) are simultaneously encapsulated in the same nanoparticle by a single emulsion method. It is demonstrated that ATRA and DOX simultaneous delivery-based therapy can efficiently deliver the drugs to both non-CSCs and CSCs to differentiate and kill the cancer cells. Differentiation of CSCs into non-CSCs can reduce their self-renewal capacity and increase their sensitivity to chemotherapy; with the combined therapy, a significantly improved anti-cancer effect is demonstrated. Administration of this combinational drug delivery system can markedly augment the enrichment of drugs both in tumor tissues and cancer stem cells, prodigiously enhancing the suppression of tumor growth while reduce the incidence of CSC in a synergistic manner.

  20. Treatment of Sweat gland carcinoma with Topical Aminolevulinic Acid Photodynamic therapy: An effective treatment method to improve surgical outcomes.

    Science.gov (United States)

    He, Xian; Yang, Yadong; Yang, Yang; Wang, Yuanyuan; Wang, Wensheng; Song, Yanying; Zeng, Yongfang; Yang, Yunchuan; Zhang, Xingcun; Li, Guoling; Gao, Yang; Lu, Yuangang

    2017-03-01

    Sweat gland carcinoma is an extremely rare skin cancer, which is hard to diagnose and completely resect without causing functional and cosmetic problems. Moreover, the high rate of recurrence is hard to handle in the treatment of sweat gland carcinoma. Photodynamic therapy is a novel treatment protocol which can selectively destroy tumor cells with good functional and cosmetic outcomes. This is a case about a 53 years old patient with sweat gland carcinoma on his right foot, which received surgery and photodynamic therapy. There is no recurrence one year after treatment of surgery and photodynamic therapy. Excision combined with photodynamic therapy during operation is a promising strategy towards tumors which are hard to resect thoroughly and have a high risk of recurrence. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Effect of supplemented intake of omega-3 fatty acids on arrhythmias in patients with ICD: fish oil therapy may reduce ventricular arrhythmia.

    Science.gov (United States)

    Weisman, Dalit; Beinart, Roy; Erez, Aharon; Koren-Morag, Nira; Goldenberg, Ilan; Eldar, Michael; Glikson, Michael; Luria, David

    2017-09-01

    The aim of this study was to evaluate the effects of fish oils, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on ventricular tachyarrhythmic episodes (VTEs) in implantable cardioverter defibrillator (ICD) recipients with ischemic cardiomyopathy. One hundred five ICD recipients with ischemic cardiomyopathy received 3.6 g of EPA and DHA and placebo for 6 months, each at a random order, with a 4-month washout period between treatments. Eighty-seven patients completed the 16-month study protocol. The primary end point was any VTE (including sustained and non-sustained ventricular tachycardias at a rate of >150 bpm) as recorded by the ICDs. Secondary end points included device therapy (anti-tachycardia pacing (ATP) or shocks). During treatment with fish oils, there was a significant increase in EPA and DHA concentrations in red blood cells (RBCs) and subcutaneous fat tissue. Among 87 patients who completed the study protocol, the mean number of VTEs was significantly lower during treatment with fish oil (1.7) vs. placebo (5.6; p = 0.035). Appropriate device therapy for VTE occurred in 18 (21%) patients. Fish oil therapy was associated with a trend toward fewer VTEs terminated with ATP (2.8 ± 13.7 vs. 0.5 ± 2.1, respectively; p = 0.077). VTE terminated by ICD shocks, however, was rare, and rates were similar between both groups (0.11 ± 0.6 vs. 0.10 ± 0.4, p = not significant, respectively). Our data suggest that fish oil therapy may be associated with a reduction in the frequency of VTE in ICD recipients with ischemic cardiomyopathy.

  2. Proton-pump inhibitor therapy for acetylsalicylic acid associated upper gastrointestinal symptoms: a randomized placebo-controlled trial.

    NARCIS (Netherlands)

    Laheij, R.J.F.; Rossum, L.G.M. van; Jansen, J.B.M.J.; Verheugt, F.W.A.

    2003-01-01

    OBJECTIVE: Patients using acetylsalicylic acid (aspirin) have an increased risk of upper gastrointestinal discomfort. The aim of this study was to assess whether gastric acid suppression improves upper gastrointestinal symptoms in patients using low-dose aspirin for cardiovascular disease. METHODS:

  3. Norfloxacin, amoxycillin, cotrimoxazole and nalidixic acid. A summary of 3-day and 7-day therapy studies in the treatment of urinary tract infections.

    Science.gov (United States)

    Vogel, R; Deaney, N B; Round, E M; VandenBurg, M J; Currie, W J

    1984-05-01

    The results of clinical trials in which norfloxacin was used for 7 days compared with amoxycillin or cotrimoxazole, or for 3 days compared with citrated nalidixic acid, are presented. Additionally, the results of a concurrent open study of 3 days of norfloxacin in the management of simple urinary tract infections are discussed. Resistance to norfloxacin was only encountered in 0.2% of pathogens isolated. Norfloxacin was as effective in eradicating bacteriuria as amoxycillin, cotrimoxazole or citrated nalidixic acid. The response to 3 days of norfloxacin was similar to that seen after 7 days therapy with this compound, or to 7 days of cotrimoxazole. The incidence of adverse experiences to norfloxacin in 758 patients was below 10%.

  4. Systemic oxidative stress to nucleic acids is unaltered following radioiodine therapy of patients with benign nodular goiter

    DEFF Research Database (Denmark)

    Bonnema, Steen J; Stovgaard, Elisabeth S; Fast, Søren;

    2015-01-01

    BACKGROUND: Little is known about the whole body oxidative stress burden following radioactive iodine ((131)I) therapy of thyroid diseases. METHODS: We studied 17 patients with benign nodular goiter treated with (131)I therapy. The targeted thyroid dose was 50 Gy in 11 patients pretreated with 0....... in the thyroid gland, but the study supports that (131)I therapy of benign nodular goiter carries no or only a minute risk of developing subsequent malignancies. It remains to be explored whether our findings also apply to hyperthyroid disorders.......BACKGROUND: Little is known about the whole body oxidative stress burden following radioactive iodine ((131)I) therapy of thyroid diseases. METHODS: We studied 17 patients with benign nodular goiter treated with (131)I therapy. The targeted thyroid dose was 50 Gy in 11 patients pretreated with 0.......1 mg of recombinant human TSH (rhTSH). In 6 patients, the applied thyroid dose was 100 Gy without rhTSH prestimulation. Well-established biomarkers of oxidative stress to RNA (8-oxo-7,8-dihydroguanosine; 8-oxoGuo) and DNA (8-oxo-7,8-dihydro-2'-deoxyguanosine; 8-oxodG) were measured in freshly voided...

  5. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    Science.gov (United States)

    Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

  6. Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity

    Science.gov (United States)

    Sodhi, Komal; Hilgefort, Jordan; Banks, George; Gilliam, Chelsea; Stevens, Sarah; Ansinelli, Hayden A.; Getty, Morghan; Abraham, Nader G.; Shapiro, Joseph I.

    2016-01-01

    Increased uric acid levels have been implicated in the pathogenesis of metabolic syndrome. To examine the mechanisms by which this occurs, we hypothesized that an increase in heme oxygenase 1, a potent antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase (XO) levels. We examined the effect of uric acid on adipogenesis in human mesenchymal stem cells (MSCs) in the presence and absence of cobalt protoporphyrin (CoPP), an HO-1 inducer, and tin mesoporphyrin (SnMP), an HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers C/EBPα, PPARγ, and Mest, while decreasing small lipid droplets and Wnt10b levels. We treated MSCs with fructose, a fuel source that increases uric acid levels. Our results showed that fructose increased XO expression as compared to the control and concomitant treatment with CoPP significantly decreased XO expression and uric acid levels. These beneficial effects of CoPP were reversed by SnMP, supporting a role for HO activity in mediating these effects. These findings demonstrate that increased levels of HO-1 appear crucial in modulating the phenotype of adipocytes exposed to uric acid and in downregulating XO and NADPH oxidase levels. PMID:26681956

  7. Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity

    Directory of Open Access Journals (Sweden)

    Komal Sodhi

    2016-01-01

    Full Text Available Increased uric acid levels have been implicated in the pathogenesis of metabolic syndrome. To examine the mechanisms by which this occurs, we hypothesized that an increase in heme oxygenase 1, a potent antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase (XO levels. We examined the effect of uric acid on adipogenesis in human mesenchymal stem cells (MSCs in the presence and absence of cobalt protoporphyrin (CoPP, an HO-1 inducer, and tin mesoporphyrin (SnMP, an HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers C/EBPα, PPARγ, and Mest, while decreasing small lipid droplets and Wnt10b levels. We treated MSCs with fructose, a fuel source that increases uric acid levels. Our results showed that fructose increased XO expression as compared to the control and concomitant treatment with CoPP significantly decreased XO expression and uric acid levels. These beneficial effects of CoPP were reversed by SnMP, supporting a role for HO activity in mediating these effects. These findings demonstrate that increased levels of HO-1 appear crucial in modulating the phenotype of adipocytes exposed to uric acid and in downregulating XO and NADPH oxidase levels.

  8. The effect of hyaluronic acid (Cicatridine) on healing and regeneration of the uterine cervix and vagina and vulvar dystrophy therapy.

    Science.gov (United States)

    Markowska, J; Madry, R; Markowska, A

    2011-01-01

    Procedures aimed at the treatment of precancerous lesions and ectopia on the uterine cervix are frequently linked to lesions of anatomical structures. The application of hyaluronic acid (Cicatridine vaginal ovules) promotes accelerated healing of the uterine cervix and acquisition of a normal shape in the uterine cervix canal. Local application of hyaluronic acid in the vagina following radiotherapy due to cancer in the uterine cervix or endometrium favourably affects the healing of post-irradiation lesions in the vagina and improves quality of life. Over 90% of patients responded positively to the application of hyaluronic acid in the form of a cream on dystrophic lesions in the vulva. Hyaluronic acid aids the healing process of post-procedural wounds in the uterine cervix, following radiotherapy applied due to cancer of the uterine cervix, endometrium and in vulvar dystrophy.

  9. [The essential fatty acids omega-6 and omega-3: from their discovery to their use in therapy].

    Science.gov (United States)

    Caramia, G

    2008-04-01

    In 1929 Burr and Burr discovered the essential fatty acids omega-6 and omega-3. Since then, researchers have shown a growing interest in unsaturated essential fatty acids as they form the framework for the organism's cell membranes, particularly the neurones in the brain, are involved in the energy-transformation process, regulate the information flows between cells. Polyunsaturated fatty acids are also precursors of ''hormonal'' molecules, often with opposing effects, prostaglandins, prostacyclins, thromboxanes, leukotrienes, lipossines, resolvines, protectines that regulate immunity, platelet aggregation, inflammation, etc. They showed that raised levels of polyunsaturated fatty acids omega-3 in tissue correlate with a reduced incidence of degenerative cardiovascular disease, some mental illnesses such as depression, and neuro-degenerative diseases such as Alzheimer's. The balance between omega-3 and omega-6 acids allows the cell membranes to develop with exactly the right flexibility and fluidity, to carry messages between neurones, that is a determining factor in physical and mental well-being and has a profound influence on all the body's inflammatory responses. The results of a number of scientific studies suggest that omega-3 acids contribute to measuring and restricting inflammatory symptoms, whereas omega-6 acids (and saturated fats) give free range to inflammatory responses and amplify allergic reactions. Today in the Western countries, the ratio of omega-3 acids to omega-6 in the diet is weighted 1:10 in favour of omega-6 to up to 1:25 in some areas, while for proper functioning a 4:1 ratio of omega-6 acids to omega-3 acids is generally considered the optimum. In addition, the type of diet followed in the Western countries is very rich in saturated fats like butter and animal fats, but because of an excessive supply of these less noble fats, the cell membranes lose flexibility and this can affect the way they work. An appropriate supplement can be an

  10. Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study

    Directory of Open Access Journals (Sweden)

    Bentley M Vitória LB

    2001-08-01

    Full Text Available Abstract Background Photodynamic therapy (PDT using 5-aminolevulinic acid (5-ALA is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs in order to optimize its skin delivery in Photodynamic Therapy (PDT of skin cancers. Methods SCLLs were obtained by reverse phase evaporation technique and size distribution of the vesicles was determinated by photon correlation spectroscopy. In vitro permeation profile was characterized using hairless mouse skin mounted in modified Franz diffusion cell. Results Size exclusion chromatography on gel filtration confirmed vesicle formation. SCLLs obtained by presented a degree of encapsulation of 5-ALA around 5.7%. A distribution of vesicle size centering at around 500 nm and 400 nm respectively for SCLLs and SCLLs containing 5-ALA was found. In vitro 5-ALA permeation study showed that SCLLs preparations presented higher skin retention significantly (p Conclusions The in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis to be treated by topical PDT of skin cancer.

  11. Bucher's indirect comparison of daylight photodynamic therapy with methyl aminolevulinate cream versus diclofenac plus hyaluronic acid gel for the treatment of multiple actinic keratosis.

    Science.gov (United States)

    Calzavara-Pinton, Piergiacomo; Zane, Cristina; Pacou, Maud; Szeimies, Rolf-Markus

    2016-10-01

    Actinic keratosis (AK) is a pre-cancerous condition characterised by patches of thick, scaly skin developing on sun-exposed areas of the body. When multiple AKs develop on severely photodamaged skin, commonly used treatments include photodynamic therapy and diclofenac plus hyaluronic acid gel (DHA). Methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) is an alternative to conventional photodynamic therapy (MAL c-PDT). Trials have indicated that MAL DL-PDT is as effective as MAL c-PDT but reduces treatment-related pain and dermatological side effects. To indirectly compare between MAL DL-PDT and DHA in patients with AK. A total of three randomised trials were collected using a systematic literature review. An adjusted indirect comparison was conducted on complete lesion response rate at 12 weeks. The data indicated that mild lesions, moderate lesions, and mild and moderate lesions treated with MAL DL-PDT were more than four times more likely to undergo a complete response than lesions treated with DHA at 12 weeks, with ORs ranging from 4.23 to 4.81. Results were all statistically significant. This is the first indirect comparison demonstrating the effectiveness of MAL-PDT over DHA for the treatment of AK, and further research is needed to assess the long-term efficacy of these interventions (i.e. six months and beyond), as well as safety and patient-reported outcomes.

  12. Effect of combined teriparatide and monthly minodronic acid therapy on cancellous bone mass in ovariectomized rats: a bone histomorphometry study.

    Science.gov (United States)

    Iwamoto, Jun; Seki, Azusa; Sato, Yoshihiro

    2014-07-01

    The purpose of the present study was to determine whether teriparatide and monthly minodronic acid would have an additive effect on cancellous bone mass in ovariectomized rats. Seven-week-old female Sprague-Dawley rats were randomized into five groups of 10 animals each, including a sham-operation+vehicle group, an ovariectomy (OVX)+vehicle group, an OVX+minodronic acid (6 μg/kgs.c., every 4 weeks) group, an OVX+teriparatide (20 μg/kgs.c., daily) group, and an OVX+minodronic acid+teriparatide group. After the 12-week experimental period, static and dynamic histomorphometric analyses were performed on the cancellous bone of the tibial proximal metaphysis. OVX decreased the bone volume per total volume (BV/TV) and the trabecular number (Tb.N) and increased the trabecular separation (Tb.Sp) as a result of increased bone remodeling. Minodronic acid prevented the OVX-induced decreases in BV/TV, while teriparatide increased the BV/TV and trabecular width (Tb.Wi) beyond the values of the sham controls. Minodronic acid prevented, but teriparatide only mitigated, the OVX-induced decrease in Tb.N, although both drugs similarly prevented the OVX-induced increase in Tb.Sp. A combination of teriparatide and minodronic acid further increased the BV/TV and Tb.N and decreased the Tb.Sp as a result of the suppression of bone remodeling, compared with teriparatide alone. These results suggest the differential effect of teriparatide and monthly minodronic acid on cancellous bone structure and the additive effect of the two drugs on cancellous bone mass in OVX rats. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Uric Acid Therapy Prevents Early Ischemic Stroke Progression: A Tertiary Analysis of the URICO-ICTUS Trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke).

    Science.gov (United States)

    Amaro, Sergio; Laredo, Carlos; Renú, Arturo; Llull, Laura; Rudilosso, Salvatore; Obach, Víctor; Urra, Xabier; Planas, Anna M; Chamorro, Ángel

    2016-11-01

    Identification of neuroprotective therapies in acute ischemic stroke is imperative. We report a predefined analysis of the URICO-ICTUS trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke) assessing the efficacy of uric acid (UA) compared with placebo to prevent early ischemic worsening (EIW) and the relevance of collateral circulation. URICO-ICTUS was a double-blind, placebo-controlled, phase 2b trial where a total of 411 patients treated with alteplase within 4.5 hours of stroke onset were randomized (1:1) to receive UA 1000 mg (n=211) or placebo (n=200) before the end of alteplase infusion. EIW defined an increment ≥4 points in the National Institutes of Health Stroke Scale score within 72 hours of treatment in the absence of hemorrhage or recurrent stroke. Logistic regression models assessed the interaction between therapy and the collateral circulation in 112 patients who had a pretreatment computed tomographic angiography. EIW occurred in 2 of 149 (1%) patients with good outcome and 23 of 262 (9%) patients with poor outcome (χ(2); P=0.002). EIW occurred in 7 of 204 (3%) patients treated with UA and in 18 of 200 (9%) patients treated with placebo (χ(2); P=0.01). There was a significant interaction between the efficacy of UA to prevent EIW and collaterals (P=0.029), with lower incidence in patients with good collaterals treated with UA compared with placebo (2% versus 15%, respectively; P=0.048). UA therapy may prevent EIW after acute stroke in thrombolysed patients. Optimal access of UA to its molecular targets through appropriate collaterals may modify the magnitude of the neuroprotective effect. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00860366. © 2016 American Heart Association, Inc.

  14. Gastrointestinal bleeding after high intake of omega-3 fatty acids, cortisone and antibiotic therapy: a case study.

    Science.gov (United States)

    Detopoulou, Paraskevi; Papamikos, Vasilios

    2014-06-01

    Omega-3 fatty acids exert a plethora of physiological actions including triglycerides lowering, reduction of inflammatory indices, immunomodulation, anti- thrombotic effects and possibly promotion of exercise performance. Their use is widespread and for commonly ingested doses their side- effects are minimal. We report a case of a 60 y amateur athlete who consumed about 20 g omega-3 fatty acids daily from supplements and natural sources for a year. After the intake of cortisone and antibiotics he presented duodenum ulcer and bleeding although he had no previous history of gastrointestinal problems. Although several animal data support gastro-protective effects of omega-3 fatty acids in the present case they were not able to prevent ulcer generation. The present observation may be explained by (i) the high dose of omega-3 fatty acids and their effect on bleeding, (ii) the fact that cortisone increases their oxidation and may render them proinflammatory, (iii) other antithrombotic microconstituents included in the consumed cod-oil and/or the diet of the subject and (iv) the differences in the coagulation and fibrinolytic systems of well- trained subjects. Further studies are needed to substantiate any possible interaction of cortisone and omega-3 fatty acids in wide ranges of intake.

  15. Boric acid irrigation as an adjunct to mechanical periodontal therapy in patients with chronic periodontitis: a randomized clinical trial.

    Science.gov (United States)

    Sağlam, Mehmet; Arslan, Uğur; Buket Bozkurt, Şerife; Hakki, Sema S

    2013-09-01

    The purpose of this single-masked, randomized, controlled clinical trial was to evaluate the effects of boric acid irrigation as an adjunct to scaling and root planing (SRP) on clinical and microbiologic parameters and compare this method with chlorhexidine irrigation and SRP alone in patients with chronic periodontitis (CP). Forty-five systemically healthy patients with CP are included in this study. They were divided into three groups: 1) SRP + saline irrigation (C); 2) SRP + chlorhexidine irrigation (CHX); and 3) SRP + boric acid irrigation (B). To determine an ideal concentration of boric acid, a preclinical analysis was conducted. At baseline, 1 month, and 3 months after treatment, clinical measurements, including plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP), were performed, and subgingival plaque samples were taken. Quantitative analysis of Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), and Treponema denticola (Td) was performed using real-time polymerase chain reaction (PCR) procedures. The concentration of boric acid is 0.75% in this study. All clinical parameters showed statistically significant reduction at all time points compared to baseline in all groups (P 0.05). The PD and CAL reductions for moderately deep pockets (PD ≥5 and 0.05). BOP (percentage) was significantly lower in the B group compared with the CHX and C groups in the first month after treatment (P 0.05). The results of this study suggest that boric acid could be an alternative to chlorhexidine, and it might be more favorable because boric acid was superior in whole-mouth BOP as well as PD and CAL reduction for moderate pockets in early time periods.

  16. Omega-3 fatty acid supplementation as an adjunctive therapy in the treatment of chronic kidney disease: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Jing Hu

    Full Text Available The aim of this study was to evaluate the benefits and risks of omega-3 fatty acid supplementation in patients with chronic kidney disease. A systematic search of articles in PubMed, Embase, the Cochrane Library, and reference lists was performed to find relevant literature. All eligible studies assessed proteinuria, the serum creatinine clearance rate, the estimated glomerular filtration rate, or the occurrence of end-stage renal disease. Standard mean differences with 95% confidence intervals for continuous data were used to estimate the effects of omega-3 fatty acid supplementation on renal function, as reflected by the serum creatinine clearance rate, proteinuria, the estimated glomerular filtration rate, and relative risk. Additionally, a random-effects model was used to estimate the effect of omega-3 fatty acid supplementation on the risk of end-stage renal disease. Nine randomized controlled trials evaluating 444 patients with chronic kidney disease were included in the study. The follow-up duration ranged from 2 to 76.8 months. Compared with no or low-dose omega-3 fatty acid supplementation, any or high-dose omega-3 fatty acid supplementation, respectively, was associated with a lower risk of proteinuria (SMD: -0.31; 95% CI: -0.53 to -0.10; p=0.004 but had little or no effect on the serum creatinine clearance rate (SMD: 0.22; 95% CI: -0.40 to 0.84; p=0.482 or the estimated glomerular filtration rate (SMD: 0.14; 95% CI: -0.13 to 0.42; p=0.296. However, this supplementation was associated with a reduced risk of end-stage renal disease (RR: 0.49; 95% CI: 0.24 to 0.99; p=0.047. In sum, omega-3 fatty acid supplementation is associated with a significantly reduced risk of end-stage renal disease and delays the progression of this disease.

  17. Omega-3 fatty acid supplementation as an adjunctive therapy in the treatment of chronic kidney disease: a meta-analysis

    Science.gov (United States)

    Hu, Jing; Liu, Zuoliang; Zhang, Hao

    2017-01-01

    The aim of this study was to evaluate the benefits and risks of omega-3 fatty acid supplementation in patients with chronic kidney disease. A systematic search of articles in PubMed, Embase, the Cochrane Library, and reference lists was performed to find relevant literature. All eligible studies assessed proteinuria, the serum creatinine clearance rate, the estimated glomerular filtration rate, or the occurrence of end-stage renal disease. Standard mean differences with 95% confidence intervals for continuous data were used to estimate the effects of omega-3 fatty acid supplementation on renal function, as reflected by the serum creatinine clearance rate, proteinuria, the estimated glomerular filtration rate, and relative risk. Additionally, a random-effects model was used to estimate the effect of omega-3 fatty acid supplementation on the risk of end-stage renal disease. Nine randomized controlled trials evaluating 444 patients with chronic kidney disease were included in the study. The follow-up duration ranged from 2 to 76.8 months. Compared with no or low-dose omega-3 fatty acid supplementation, any or high-dose omega-3 fatty acid supplementation, respectively, was associated with a lower risk of proteinuria (SMD: -0.31; 95% CI: -0.53 to -0.10; p=0.004) but had little or no effect on the serum creatinine clearance rate (SMD: 0.22; 95% CI: -0.40 to 0.84; p=0.482) or the estimated glomerular filtration rate (SMD: 0.14; 95% CI: -0.13 to 0.42; p=0.296). However, this supplementation was associated with a reduced risk of end-stage renal disease (RR: 0.49; 95% CI: 0.24 to 0.99; p=0.047). In sum, omega-3 fatty acid supplementation is associated with a significantly reduced risk of end-stage renal disease and delays the progression of this disease.

  18. Amphiphilic chitosan-grafted-functionalized polylactic acid based nanoparticles as a delivery system for doxorubicin and temozolomide co-therapy.

    Science.gov (United States)

    Di Martino, Antonio; Sedlarik, Vladimir

    2014-10-20

    The aim of this work was to investigate the potential of an amphiphilic system comprising chitosan-grafted polylactide and carboxyl-functionalized polylactide acid as a carrier for the controlled release and co-release of two DNA alkylating drugs: doxorubicin and temozolomide. Polylactide and carboxyl-functionalized polylactide acid were obtained through direct melt polycondensation reaction, using methanesulfonic acid as a non-toxic initiator, and subsequently these were grafted to the chitosan backbone through a coupling reaction, utilizing 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as a condensing agent. ATR-FTIR analysis and conductometric titration confirmed that a reaction between CS and PLA, PLACA2% and PLACA5% occurred. Chitosan-grafted-polylactide and polylactide-citric acid nanoparticles were prepared via the polyelectrolyte complex technique, applying dextran sulphate as a polyanion, and loaded with doxorubicin and temozolomide. The diameter of particles, ζ-potential and their relationship to temperature and pH were analysed in all formulations. Encapsulation, co-encapsulation efficiency and release studies were conducted in different physiological simulated environments and human serum. Results showed the continuous release of drugs without an initial burst in different physiological media.

  19. Phenylacetic acid and arterial vascular properties in patients with chronic kidney disease stage 5 on hemodialysis therapy

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Jankowski, Vera; Henning, Lars;

    2007-01-01

    Phenylacetic acid (PAA) is a recently described uremic toxin that inhibits inducible nitric oxide synthase expression and plasma membrane calcium ATPase and may therefore also be involved in remodeling of arteries. Such vascular effects have not been evaluated yet in patients with chronic kidney...

  20. The use of negative pressure therapy and hyaluronic acid for the management of post-traumatic lower limb injury.

    Science.gov (United States)

    Cigna, Emanuele; Maruccia, Michele; Sorvillo, Valentina; Parisi, Paola; Palumbo, Francesca; Onesti, Maria Giuseppina

    2013-10-01

    Management of severe limb trauma continues to challenge surgeons. Suitable treatment should be individualised for each patient, taking into consideration not only the wound extremity but also the associated injuries, age and socioeconomic status of the patient with the goal to recover function and to improve patient quality of life. The aim of this report is to present a severe degloving multiplane lower limb injury case in which a conservative treatment of the wound was performed with negative pressure therapy and dermal substitute, avoiding amputation and restoring limb function.

  1. Insulinotropic and Muscle Protein Synthetic Effects of Branched-Chain Amino Acids: Potential Therapy for Type 2 Diabetes and Sarcopenia

    Directory of Open Access Journals (Sweden)

    Darren G. Candow

    2012-11-01

    Full Text Available The loss of muscle mass and strength with aging (i.e., sarcopenia has a negative effect on functional independence and overall quality of life. One main contributing factor to sarcopenia is the reduced ability to increase skeletal muscle protein synthesis in response to habitual feeding, possibly due to a reduction in postprandial insulin release and an increase in insulin resistance. Branched-chain amino acids (BCAA, primarily leucine, increases the activation of pathways involved in muscle protein synthesis through insulin-dependent and independent mechanisms, which may help counteract the “anabolic resistance” to feeding in older adults. Leucine exhibits strong insulinotropic characteristics, which may increase amino acid availability for muscle protein synthesis, reduce muscle protein breakdown, and enhance glucose disposal to help maintain blood glucose homeostasis.

  2. Porous Silicon and Polymer Nanocomposites for Delivery of Peptide Nucleic Acids as Anti-MicroRNA Therapies.

    Science.gov (United States)

    Beavers, Kelsey R; Werfel, Thomas A; Shen, Tianwei; Kavanaugh, Taylor E; Kilchrist, Kameron V; Mares, Jeremy W; Fain, Joshua S; Wiese, Carrie B; Vickers, Kasey C; Weiss, Sharon M; Duvall, Craig L

    2016-09-01

    Self-assembled polymer/porous silicon nanocomposites overcome intracellular and systemic barriers for in vivo application of peptide nucleic acid (PNA) anti-microRNA therapeutics. Porous silicon (PSi) is leveraged as a biodegradable scaffold with high drug-cargo-loading capacity. Functionalization with a diblock polymer improves PSi nanoparticle colloidal stability, in vivo pharmacokinetics, and intracellular bioavailability through endosomal escape, enabling PNA to inhibit miR-122 in vivo.

  3. Aromatic Amino Acid Decarboxylase Deficiency Not Responding to Pyridoxine and Bromocriptine Therapy: Case Report and Review of Response to Treatment

    OpenAIRE

    2014-01-01

    Aromatic L-amino acid decarboxylase (AADC) deficiency (MIM #608643) is an autosomal recessive inborn error of monoamines. It is caused by a mutation in the DDC gene that leads to a deficiency in the AADC enzyme. The clinical features of this condition include a combination of dopamine, noradrenaline, and serotonin deficiencies, and a patient may present with hypotonia, oculogyric crises, sweating, hypersalivation, autonomic dysfunction, and progressive encephalopathy with severe developmental...

  4. From proteins to nucleic acid-based drugs: the role of biotech in anti-VEGF therapy.

    Science.gov (United States)

    Gatto, Barbara; Cavalli, Marco

    2006-07-01

    Cancer cells, by releasing pro-angiogenic factors, stimulate the growth of the thick capillary net necessary for the nourishment of the tumor mass. The battle to defeat cancer uses today different approaches based on the inhibition of pathological angiogenesis: several compounds, either synthetic or biotech, aimed at this complex process, are under development. Vascular endothelial growth factor (VEGF) is considered the main target for an anti-cancer therapy based on angiogenesis inhibition; the goal is to block the interaction between this cytokine and its receptors in order to stop the intracellular signaling pathways leading to endothelium remodeling. FDA recently approved two drugs specifically aimed at VEGF, bevacizumab, a humanized monoclonal antibody, and pegaptinib, a pegylated aptamer with application in ophthalmic pathologies. These two approvals validate anti-VEGF therapy for clinical use, and show how biotech companies are investing on angiogenesis using different approaches, i.e. exploiting protein drugs and oligonucleotide-based therapeutics. Monoclonal antibodies, as well as other high molecular weight products like cytokine-traps, aptamers and short interfering RNA (siRNA), are designed to target VEGF and its receptors. Their design, production and clinical advancement in cancer and other pathological conditions linked to angiogenesis will be specifically addressed in this review.

  5. Ursodeoxycholic acid therapy in intrahepatic cholestasis of pregnancy: Results in real-world conditions and factors predictive of response to treatment.

    Science.gov (United States)

    Bacq, Yannick; le Besco, Matthieu; Lecuyer, Anne-Isabelle; Gendrot, Chantal; Potin, Jérôme; Andres, Christian R; Aubourg, Alexandre

    2017-01-01

    Ursodeoxycholic acid (UDCA) therapy is commonly used in intrahepatic cholestasis of pregnancy (ICP). To evaluate the efficacy and tolerance of UDCA in real-world conditions and to search for factors predictive of response to treatment. This observational study included 98 consecutive patients suffering from pruritus during pregnancy associated with increased ALT levels or total bile acid (TBA) concentrations, without other causes of cholestasis. The entire ABCB4 gene coding sequence was analyzed by DNA sequencing. UDCA was prescribed until delivery in all patients (mean dose 14.0mg/kg/day; mean duration 30.4 days). Pruritus improved in 75/98 (76.5%) patients, and totally disappeared before delivery in 25/98 (25.5%). After 2-3 weeks of treatment, ALT levels decreased by more than 50% of base line in 67/86 (77.9%) patients and normalized in 34/86 (39.5%), and TBA concentrations decreased in 28/81 (34.6%). Only one patient stopped the treatment before delivery. On multivariate analysis, ALT >175IU/l before treatment was associated with improvement of pruritus (OR 2.97, 95% CI 1.12-7.89, P=0.029) and with decreased ALT (OR 18.61, 95% CI 3.94-87.99, P=0.0002). ABCB4 gene mutation was not associated with response to treatment. This study supports the use of UDCA as first line therapy in ICP. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  6. Effect ofγ-aminobutyric acid combined with conventional aerosol inhalation therapy on serum indicators and induced sputum indicators of patients with asthma

    Institute of Scientific and Technical Information of China (English)

    Jun-Ning Li

    2016-01-01

    Objective:To analyze the effect ofγ-aminobutyric acid combined with conventional aerosol inhalation therapy on serum indicators and induced sputum indicators of patients with asthma. Methods:A total of 116 asthma patients receiving treatment in our hospital from July 2011 to August 2014 were included for study, and then all patients were divided into observation group (n=60) and control group (n=56). Differences in illness-related factor and protein expression in serum and induced sputum were compared between two groups.Results: Serum PDGF-BB, SP, LTE4 and CGRP levels of observation group after treatment were lower than those of control group, and TGFβ1 level was higher than that of control group (P<0.05); serum OPN, HSP70, Eotaxin and ECP expression levels of observation group after treatment were lower than those of control group, and VDBP and CC16 expression levels were higher than those of control group (P<0.05); SCF, M-CSF, CKLF1 and ICAM-1 levels in induced sputum of observation group after treatment were lower than those of control group (P<0.05); MCP-1, Gal-3, RAGE, HMGB1 and SDF-1 levels in induced sputum of observation group after treatment were lower than those of control group (P<0.05).Conclusions:After patients with asthma receivedγ-aminobutyric acid combined with conventional aerosol inhalation therapy, the levels of disease severity-related indicators in serum and induced sputum are optimized, and it has significant effect on disease treatment.

  7. Catalytic therapy of cancer by ascorbic acid involves redox cycling of exogenous/endogenous copper ions and generation of reactive oxygen species.

    Science.gov (United States)

    Hadi, S M; Ullah, M F; Shamim, U; Bhatt, S H; Azmi, A S

    2010-01-01

    Catalytic therapy is a cancer treatment modality based on the generation of reactive oxygen species (ROS) through administration of ascorbate/medicinal herbal extracts and copper. It is known that antioxidants such as ascorbate also exhibit prooxidant activity in the presence of transition metals such as copper. Based on our work and that in the literature, in this review we propose a mechanism for the cytotoxic action of ascorbate against cancer cells. It involves redox cycling of exogenous/endogenous copper ions and the consequent generation of ROS leading to oxidative DNA breakage. Using human peripheral lymphocytes and the Comet assay, we have shown that ascorbic acid is able to cause oxidative breakage in cellular DNA. Such DNA degradation is inhibited by neocuproine (a Cu(I) sequestering agent) and scavengers of ROS indicating that the cellular DNA breakage involves the generation of Cu(I) and formation of ROS. Similar results are also obtained with plant polyphenol antioxidants that are important constituents of medicinal herbal extracts. Copper is an essential component of chromatin and can take part in redox reactions. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and ascorbate/plant polyphenols to generate ROS. In this review we cite evidence to indicate that in catalytic therapy cytotoxic action against cancer cells involves redox cycling of exogenous/endogenous copper ions.

  8. Induced Protoporphyrin IX Accumulation by the δ-Aminolevulinic Acid in Bacteria and its Potential Use in the Photodynamic Therapy

    Science.gov (United States)

    Brígido-Aparicio, Cyntiha; Ramón-Gallegos, Eva; Arenas-Huertero, Francisco Jesús; Uribe-Hernández, Raúl

    2008-08-01

    The increasing incident of resistant strains to antibiotic has encouraged the search of new antibacterial treatments, such as the photodynamic therapy. In recent years, photodynamic therapy has demonstrated being a good technology for the treatment of recurrent bacteria infection. PDT presents a hopeful approach to eliminate Gram positive and negative bacteria in immunological compromised patients. This therapy uses a laser in combination with a photosensibilizer in presence of intracellular molecular oxygen. The process generates an effect of phototoxicity in bacterial cells. The aim of this work was to determine the in vitro conditions to accumulate PpIX in effective concentrations in Staphylococcus aureus ATCC25923 and Streptococcus pyogenes, which are responsible of human cutaneous diseases. A cellular suspension of both strains was prepared in TSB to obtain growth in Log-phase, then, the suspensions were adjusted to a final concentration of 2.61×108 cells/mL. The strains were exposed to increasing concentrations from 0 to 160μg/mL of δ-ALA in order to determinate the concentration that induces the biggest accumulation of PpIX. PpIX was measured using the Piomelli method modified for bacteria. The concentration selected was 40 mg/mL of ALA. It was found that in basal concentration of δ-ALA (0 μg/mL) both strains accumulated similar amount of PpIX. In concentrations of 5 mg/mL of δ-ALA it was observed a significant (p<0.001) increment in PpIX concentration. Finally it was realized a kinetic to determinate the optimal accumulation over the time at 0, 5, 10, 15 and 30 min, and 1, 2, 4, 8, 16 and 32 h. It was found that the ideal time for PDT application, in both strains, was 24 h because in smaller times there was not statistically significant difference. The S. aureus ATCC25923 accumulated significantly the biggest concentration of PpIX with regard to S. pyogenes. In conclusion, it was found that the optimal conditions to apply PDT will be to expose both

  9. Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

    Directory of Open Access Journals (Sweden)

    Bwatanglang IB

    2016-01-01

    Full Text Available Ibrahim Birma Bwatanglang,1,2 Faruq Mohammad,3 Nor Azah Yusof,1,3 Jaafar Abdullah,1 Mohd Zobir Hussein,3 Noorjahan Banu Alitheen,4 Nadiah Abu4 1Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Department of Chemistry, Faculty of Science, Adamawa State University, Mubi, Nigeria; 3Institute of Advanced Technology, 4Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange–red fluorescence around 600 nm and investigated to the highest intensity at Mn2+ doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not

  10. Treatment of hidradenitis suppurativa with intralesional photodynamic therapy with 5-aminolevulinic acid and 630nm laser beam.

    Science.gov (United States)

    Suárez Valladares, María Jesús; Eiris Salvado, Noemi; Rodríguez Prieto, Manuel Angel

    2017-03-01

    Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease with multiple treatment options that have been used with mixed results. To evaluate the effectiveness, safety and tolerability of intralesional photodynamic therapy (I-PDT) in the management of HS. Also, to assess the effect of this technique on the different areas treated. Case series of 38 HS patients treated with I-PDT between 2011-2015 following a standardized protocol to assess response at the treated areas RESULTS: 29 patients achieved a complete response, while persistence was noted on 8 cases and only 1 suffered a recurrence. Difference between basal (median 28.5) and final (0) Hidradenitis Severity Score showed a significant reduction of 24.5 points (ptreatment option for localized HS lesions, achieving a high rate of remission with an adequate maintenance of response i and few complications. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  11. DOTA conjugate with an albumin-binding entity enables the first folic acid-targeted 177Lu-radionuclide tumor therapy in mice.

    Science.gov (United States)

    Müller, Cristina; Struthers, Harriet; Winiger, Christian; Zhernosekov, Konstantin; Schibli, Roger

    2013-01-01

    The folate receptor (FR) has proven a valuable target for nuclear imaging using folic acid radioconjugates. However, using folate-based radiopharmaceuticals for therapy has long been regarded as an unattainable goal because of their considerable renal accumulation. Herein, we present a novel strategy in which a DOTA-folate conjugate with an albumin-binding entity (cm09) was designed with the aim of prolonging circulation in the blood and therewith potentially improving tumor-to-kidney ratios. The folate conjugate cm09 was radiolabeled with (177)LuCl(3), and stability experiments were performed in plasma. Cell uptake studies were performed on FR-positive KB tumor cells, and an ultrafiltration assay was used to determine the plasma protein-binding properties of (177)Lu-cm09. In vivo, (177)Lu-cm09 was tested in KB tumor-bearing mice using SPECT/CT. The therapeutic anticancer effect of (177)Lu-cm09 (20 MBq) applied as a single injection or as fractionated injections was investigated in different groups of mice (n = 5) by monitoring tumor size and the survival time of treated mice, compared with untreated controls. Compound cm09 was radiolabeled at a specific activity of 40 MBq/nmol, a radiochemical yield of more than 98%, and a stability of more than 99% over 5 d in plasma. Ultrafiltration revealed significant binding of (177)Lu-cm09 to serum proteins (∼91%) in plasma, compared with folate radioconjugate without an albumin-binding entity. Cell uptake and internalization of (177)Lu-cm09 was FR-specific and comparable to other folate radioconjugates. In vivo studies resulted in high tumor uptake (17.56 percentage injected dose per gram [%ID/g] at 4 h after injection), which was almost completely retained for at least 72 h. Renal accumulation was significantly reduced (28 %ID/g at 4 h after injection), compared with folate conjugates that lack an albumin-binding entity (∼70 %ID/g at 4 h after injection). These circumstances enabled SPECT imaging of excellent quality

  12. pH-Sensitive Delivery Vehicle Based on Folic Acid-Conjugated Polydopamine-Modified Mesoporous Silica Nanoparticles for Targeted Cancer Therapy.

    Science.gov (United States)

    Cheng, Wei; Nie, Junpeng; Xu, Lv; Liang, Chaoyu; Peng, Yunmei; Liu, Gan; Wang, Teng; Mei, Lin; Huang, Laiqiang; Zeng, Xiaowei

    2017-06-07

    In this study, we introduced a targeting polymer poly(ethylene glycol)-folic acid (PEG-FA) on the surface of polydopamine (PDA)-modified mesoporous silica nanoparticles (MSNs) to develop the novel nanoparticles (NPs) MSNs@PDA-PEG-FA, which were employed as a drug delivery system loaded with doxorubicin (DOX) as a model drug for cervical cancer therapy. The chemical structure and properties of these NPs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, N2 adsorption/desorption, dynamic light scattering-autosizer, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The pH-sensitive PDA coating served as a gatekeeper. The in vitro drug release experiments showed pH-dependent and sustained drug release profiles that could enhance the therapeutic anticancer effect and minimize potential damage to normal cells due to the acidic microenvironment of the tumor. These MSNs@PDA-PEG-FA achieved significantly high targeting efficiency, which was demonstrated by the in vitro cellular uptake and cellular targeting assay. Compared with that of free DOX and DOX-loaded NPs without the folic targeting ligand, the FA-targeted NPs exhibited higher antitumor efficacy in vivo, implying that they are a highly promising potential carrier for cancer treatments.

  13. Phenylboronic acid-sugar grafted polymer architecture as a dual stimuli-responsive gene carrier for targeted anti-angiogenic tumor therapy.

    Science.gov (United States)

    Kim, Jinhwan; Lee, Yeong Mi; Kim, Hyunwoo; Park, Dongsik; Kim, Jihoon; Kim, Won Jong

    2016-01-01

    We present a cationic polymer architecture composed of phenylboronic acid (PBA), sugar-installed polyethylenimine (PEI), and polyethylene glycol (PEG). The chemical bonding of PBA with the diol in the sugar enabled the crosslinking of low-molecular-weight (MW) PEI to form high-MW PEI, resulting in strong interaction with anionic DNA for gene delivery. Inside the cell, the binding of PBA and sugar was disrupted by either acidic endosomal pH or intracellular ATP, so gene payloads were released effectively. This dual stimuli-responsive gene release drove the polymer to deliver DNA for high transfection efficiency with low cytotoxicity. In addition, PBA moiety with PEGylation facilitated the binding of polymer/DNA polyplexes to sialylated glycoprotein which is overexpressed on the tumor cell membrane, and thus provided high tumor targeting ability. Therapeutic application of our polymer was demonstrated as an anti-angiogenic gene delivery agent for tumor growth inhibition. Our judicious designed polymer structure based on PBA provides enormous potential as a gene delivery agent for effective gene therapy by stimuli-responsiveness and tumor targeting.

  14. Synthesis of multifunctional Ag@Au@phenol formaldehyde resin particles loaded with folic acids for photothermal therapy.

    Science.gov (United States)

    Yang, Ping; Xu, Qi-Zhi; Jin, Sheng-Yu; Lu, Yang; Zhao, Yang; Yu, Shu-Hong

    2012-07-23

    Multifunctional Ag@Au@ phenol formaldehyde resin (PFR) particles loaded with folic acids (FA) have been designed for killing tumor cells through photothermy conversion under the irradiation of near-infrared (NIR) light. Possessing the virtue of good fluorescence, low toxicity, and good targeting, the nanocomposite consists of an Ag core, an Au layer, a PFR shell, and folic acids on the PFR shell. The Ag@PFR core-shell structure can be prepared with a simple hydrothermal method after preheating. We then filled the PFR shell with a layer of Au by heating and modified the shell with polyelectrolyte to change its surface charge state. To capture tumor cells actively, FA molecules were attached onto the surface of the Ag@Au@PFR particles in the presence of 1-ethyl-3-(3-dimethly aminopropyl) carbodiimide (EDAC) and N-hydroxysuccinimide (NHS). Owing to the excellent property of Au NPs and Ag NPs as photothermal conversion agents, the Ag@Au@ PFR@FA particles can be utilized to kill tumor cells when exposed to NIR light.

  15. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study

    Science.gov (United States)

    Murakami, Kazunari; Sakurai, Yuuichi; Shiino, Madoka; Funao, Nobuo; Nishimura, Akira; Asaka, Masahiro

    2016-01-01

    Objective The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. Design A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment. Results Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated. Conclusion Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer. Trial registration number NCT01505127. PMID:26935876

  16. Topical therapy of molluscum contagiosum as a comparative therapeutic study using 15% phenol in lactic acid, 5% tincture iodine and pricking alone

    Directory of Open Access Journals (Sweden)

    Khalifa E. Sharquie

    2016-07-01

    Full Text Available Introduction: Molluscum contagiosum is a common viral infection of the skin, caused by poxvirus, commonly affects young children. Although there was no specific treatment for molluscum contagiosum virus, many therapeutic modalities were used with different response rates. Aims: To evaluate the effectiveness of topical 15% phenol in lactic acid, 5% tincture iodine and pricking alone through comparative treatments of molluscum contagiosum. Materials and Methods: This randomized, therapeutic, single, blinded, comparative study was conducted in the Department of Dermatology–Baghdad Teaching Hospital Baghdad, Iraq, during the period from October 2007 to October 2008. Seventy-five patients with molluscum contagiosum were included in this study. They were diagnosed on clinical bases. Patients with prior treatment in the last 2 weeks and patients who had inflamed lesions were excluded. Full history and physical examination were done for all Patients. The patients were divided into 3 equal groups according to the mode of therapy (25 patients for each group: Group 1 patients treated by pricking the lesions with orange stick dipped in 15% phenol in lactic acid. Group 2 patients treated by pricking the lesions with orange stick dipped in 5% tincture iodine. Group 3 patients treated by pricking with orange stick alone. The treatment sessions were done at the time of presentation and then every week until complete cure was achieved, but not more than three sessions. The patients were followed up after one month from the last session to record the clinical cure and any local or systemic side effects. Results: Seventy five patients with molluscum contagiosum, 43 (57% males and 32 (43% females with male to female ratio 1.3-1, their ages ranged from 2-35 years(median:6 years. The most common age groups affected were below 10 years; 57 (76% patients. The most common affected body sites were the face and neck 58 (77.3% patients. Atopic diseases like atopic

  17. Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy.

    Science.gov (United States)

    Bwatanglang, Ibrahim Birma; Mohammad, Faruq; Yusof, Nor Azah; Abdullah, Jaafar; Hussein, Mohd Zobir; Alitheen, Noorjahan Banu; Abu, Nadiah

    2016-01-01

    In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange-red fluorescence around 600 nm and investigated to the highest intensity at Mn(2+) doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we

  18. Validation of an amino-acid-based radionuclide therapy plus external beam radiotherapy in heterotopic glioblastoma models

    Energy Technology Data Exchange (ETDEWEB)

    Israel, Ina [Department of Nuclear Medicine, University of Wuerzburg, D-97080 Wuerzburg (Germany); Blass, Georg [Department of Radiotherapy and Radiooncology, Saarland University Medical Center, Homburg (Germany); Reiners, Christoph [Department of Nuclear Medicine, University of Wuerzburg, D-97080 Wuerzburg (Germany); Samnick, Samuel, E-mail: samnick_s@klinik.uni-wuerzburg.d [Department of Nuclear Medicine, University of Wuerzburg, D-97080 Wuerzburg (Germany)

    2011-05-15

    Background and purpose: Malignant gliomas represent a major therapeutic challenge because no efficient treatment is currently available. p-[{sup 131}I]iodo-L-phenylalanine ([{sup 131}I]IPA) is a glioma avid radiopharmaceutical that demonstrated antiproliferative and tumoricidal effects in gliomas. The present study validated the therapeutic efficiency of [{sup 131}I]IPA combined with external beam radiotherapy in experimental gliomas. Materials and methods: Glioma cells derived from the primary human A1207, T5135, Tx3868 and M059K glioblastoma cell lines or rat F98 glioma cell line were treated with various doses of [{sup 131}I]IPA, external photon irradiation (RT) or combined [{sup 131}I]IPA/RT treatment. Responsiveness of glioma cells to the different therapy modalities was investigated at 24, 48 and 72 h after treatments by trypan blue, WST-1 assay, propidium iodide and bisbenzimide staining as well as by clonogenic assay. In addition, the therapy-induced DNA damage and repair were evaluated using phosphorylated histone H2AX ({gamma}-H2AX). In vivo, the effectiveness of the combination treatment was validated in human Tx3868 and A1207 glioblastoma xenografts in CD1 nu/nu mice and RNU rats. Results: In vitro, the combination treatment resulted in a greater than additive increase in cytotoxic effect in glioma cell lines. Cell survival rate following a treatment with 1.0 {mu}Ci (37 kBq) of [{sup 131}I]IPA amounted to 70%{+-}15% and 60%{+-}10% after 48 and 72 h, respectively, and decreased under 20% after additional RT with 5 Gy. At higher RT doses, cell survival rate decreased below 5%. As a measure of DNA double-strand break, nuclear {gamma}-H2AX foci were determined as a function of time. Within 24 h, the number of {gamma}-H2AX foci per cell was significantly greater after combined modality compared with the individual treatments. In vivo, when combined with RT, the radionuclide therapy with [{sup 131}I]IPA resulted in an extended tumor growth delay, a reduction

  19. Clinical and microbiological effects of initial periodontal therapy in conjunction with amoxicillin and clavulanic acid in patients with adult periodontitis : A randomised double-blind, placebo-controlled study

    NARCIS (Netherlands)

    Winkel, EG; van Winkelhoff, AJ; Barendregt, DS; van der Weijden, GA; Timmerman, MF; van der Velden, U

    1999-01-01

    The aim of the present study was to investigate the clinical and microbiological effects of initial periodontal therapy in conjunction with systemic amoxicillin plus clavulanic acid in adult periodontitis patients using a double-blind, parallel-group, and placebo-controlled protocol. 21 patients wit

  20. Compliance with iron-folic acid (IFA) therapy among pregnant women in an urban area of south India.

    Science.gov (United States)

    Mithra, P; Unnikrishnan, B; Rekha, T; Nithin, K; Mohan, K; Kulkarni, V; Kulkarni, V; Agarwal, D

    2013-12-01

    Anaemia is highly prevalent among pregnant women and iron deficiency is the most important cause. Like many other countries, India has policies to give pregnant women iron supplements. Non-compliance is one important challenging factor in combating anaemia. To estimate the compliance for IFA tablets among pregnant women and to study the social factors influencing it. This study included 190 pregnant women seeking ante-natal care in tertiary health centres in the Mangalore city in south India. After Institutional Ethics Committee (IEC) approval, data was collected by personal interview. Missing >2 doses consecutively was considered non-compliance. The data was analyzed using SPSS (Statistical Package for Social Sciences) version 11.5. The mean age of the study population was 25.8 years (SD: 4.1). Most of the subjects consumed mixed diet and 72.1% belonged to lower socioeconomic status. Overall, compliance with IFA tablets was 64.7%. Compliance increased with the increase in age, birth order and single daily dose. Forgetfulness and both perceived as well as experienced side effects of IFA therapy were the important factors for non-compliance. There was a moderate level of compliance towards IFA tablets with key social and demographic factors playing an important role.

  1. Effects of α-lipoic acid therapy on sympathetic heart innervation in patients with previous experience of transient takotsubo cardiomyopathy.

    Science.gov (United States)

    Marfella, Raffaele; Barbieri, Michelangela; Sardu, Celestino; Rizzo, Maria Rosaria; Siniscalchi, Mario; Paolisso, Pasquale; Ambrosino, Maria; Fava, Ilaria; Materazzi, Crescenzo; Cinquegrana, Giorgio; Gottilla, Rossella; Elia, Luigi Raffaele; D'andrea, Davide; Coppola, Antonino; Rambaldi, Pier Francesco; Mauro, Ciro; Mansi, Luigi; Paolisso, Giuseppe

    2016-02-01

    Takotsubo syndrome is a stress cardiomyopathy, characterized by reversible left ventricle (LV) apical ballooning in the absence of significant angiographic coronary artery stenosis. The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement. We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance. From January 2010 to June 2012, 886 patients were consecutively evaluated at Cardarelli Hospital, Naples, Italy. Among these, 48 patients met takotsubo cardiomyopathy (TCM) criteria. Each patient was assessed with history and physical examination, 12-lead electrocardiogram, serum troponin, coronary arteriography, and left ventricular angiogram, perfusion myocardial scintigraphy with technetium 99m, with echocardiography and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. At discharge, the surviving patients were randomly assigned to α-lipoic acid (ALA) treatment (600mg once daily) or placebo. Following discharge, after the initial TCM event, patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months. Routine analysis, myocardial damage serum markers, oxidative stress serum markers, pro-inflammatory cytokines, and sympathetic tone activity were evaluated in all patients. ALA administration improved MIBG defect size at 12 months compared to placebo. Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction. ALA treatment improves the adrenergic cardiac innervation. This study evaluates whether sympatho-vagal alterations are TCM event-related. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  2. Modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy

    Directory of Open Access Journals (Sweden)

    Jiang X

    2015-04-01

    Full Text Available Xueyun Jiang,1 Yuji Wang,1 Haimei Zhu,1 Yaonan Wang,1 Ming Zhao,1,2 Shurui Zhao,1 Jianhui Wu,1 Shan Li,1 Shiqi Peng11Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, TaiwanAbstract: With the help of pharmacophore analysis and docking investigation, 15 novel 1-(4,4,5,5-tetramethyl-2-(3-nitrophenyl-4,5-dihydroimidazol-1-yl-oxyacetyl-L-amino acids (6a–o were designed, synthesized, and assayed. On tail-flick and xylene-induced ear edema models, 10 µmol/kg 6a–o exhibited excellent oral anti-inflammation and analgesic activity. The dose-dependent assay of their representative 6f indicates that the effective dose should be 3.3 µmol/kg. The correlation of the three-dimensional quantitative structure–activity relationship with the docking analysis provides a basis for the rational design of drugs to treat inflammatory pain.Keywords: tetramethylimidazoline, analgesic, anti-inflammatory, 3D-QSAR

  3. Polyethylene glycol–polylactic acid nanoparticles modified with cysteine–arginine–glutamic acid–lysine–alanine fibrin-homing peptide for glioblastoma therapy by enhanced retention effect

    Directory of Open Access Journals (Sweden)

    Wu J

    2014-11-01

    Full Text Available Junzhu Wu,1,2,* Jingjing Zhao,1,3,* Bo Zhang,1 Yong Qian,1 Huile Gao,1 Yuan Yu,1 Yan Wei,1 Zhi Yang,1 Xinguo Jiang,1 Zhiqing Pang1 1Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 2School of Pharmacy, Dali University, Xiaguan, 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: For a nanoparticulate drug-delivery system, crucial challenges in brain-glioblastoma therapy are its poor penetration and retention in the glioblastoma parenchyma. As a prevailing component in the extracellular matrix of many solid tumors, fibrin plays a critical role in the maintenance of glioblastoma morphology and glioblastoma cell differentiation and proliferation. We developed a new drug-delivery system by conjugating polyethylene glycol–polylactic acid nanoparticles (NPs with cysteine–arginine–glutamic acid–lysine–alanine (CREKA; TNPs, a peptide with special affinity for fibrin, to mediate glioblastoma-homing and prolong NP retention at the tumor site. In vitro binding tests indicated that CREKA significantly enhanced specific binding of NPs with fibrin. In vivo fluorescence imaging of glioblastoma-bearing nude mice, ex vivo brain imaging, and glioblastoma distribution demonstrated that TNPs had higher accumulation and longer retention in the glioblastoma site over unmodified NPs. Furthermore, pharmacodynamic results showed that paclitaxel-loaded TNPs significantly prolonged the median survival time of intracranial U87 glioblastoma-bearing nude mice compared with controls, Taxol, and NPs. These findings suggested that TNPs were able to target the glioblastoma and enhance retention, which is a valuable strategy for tumor therapy. Keywords: CREKA peptide, nanoparticles, retention effect, paclitaxel, glioblastoma

  4. Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA on SIV-infected Chinese rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Binhua Ling

    Full Text Available Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM treated with intensive combination antiretroviral therapy (cART and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA.SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations.Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters.The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

  5. AT-33A PHASE II STUDY OF CONCURRENT RADIATION THERAPY, TEMOZOLOMIDE AND THE HISTONE DEACETYLASE INHIBITOR VALPROIC ACID FOR PATIENTS WITH GLIOBLASTOMA MULTIFORME

    Science.gov (United States)

    Krauze, Andra V.; Myrehaug, Sten D.; Chang, Michael G.; Holdford, Diane J.; Smith, Sharon; Shih, Joanna; Tofilon, Peter; Fine, Howard; Camphausen, Kevin A.

    2014-01-01

    BACKGROUND: Glioblastoma (GBM) remains an aggressive brain tumor with poor prognosis. Valproic acid (VPA) is an antiepileptic agent that has been shown to have HDACi activity and to radiosensitize GBM cells in preclinical models. This phase II study aimed to determine if the addition of VPA to standard radiation therapy and temozolomide would improve OS and PFS. METHODS: We prospectively assessed survival, radiological and clinical progression in 37 newly diagnosed glioblastoma patients with the administration of VPA at 25 mg/kg orally BID concurrent with radiation therapy (RT) and temozolomide (TMZ). The first dose of VPA was given 1 week before the first day of RT at 10 to 15 mg/kg/day and subsequently tapered up to 25 mg/kg/day over the week prior to radiation. RESULTS: 81% of patients took VPA according to protocol. Median OS was 29.6 months (21- 63.8), median PFS was 10.5 (6.8 - 51.2). OS at 6, 12, 24 months was 97%, 86%, 56% respectively. PFS at 6, 12, 24 months was 70%, 43%, 38% respectively. The most common grade 3 or 4 toxicities of VPA in conjunction with TMZ were blood/ bone marrow toxicity (32%), neurological (11%), metabolic/laboratory (8%). At the end of the study 26 (70%) patients were dead, 7 were live without disease, 4 alive with disease. Younger age (<= 50 years) compared to older age and class V RPA were significant for both OS and PFS. Using a landmark analysis, an early progression was related to a shorter interval between progression and death, whereas, a later progression was related to a longer interval between progression and death (p = 0.0002) HR 4.7. CONCLUSION: The addition of VPA to concurrent RT and TMZ in the treatment of newly diagnosed GBM may result in superior outcomes as compared to contemporary and historical data and merits further study.

  6. Carboxymethyl-β-cyclodextrin conjugated nanoparticles facilitate therapy for folate receptor-positive tumor with the mediation of folic acid.

    Science.gov (United States)

    Su, Chang; Li, Hongdan; Shi, Yijie; Wang, Guan; Liu, Liwei; Zhao, Liang; Su, Rongjian

    2014-10-20

    Currently, clinical operation treatments, chemotherapy and radiotherapy just could eliminate local tumor cells. However, chemotherapy and radiotherapy also injury normal cells and lead to serious side effects and toxicities. So, it is necessary to find an effective target cancer carrier that delivers the anticancer agents into tumor cells and reduces normal cells' injury. Folic acid (FA) is a classical targeting agent mediates internalization of chemical drugs into tumor cells which over-express folate receptor (FR) on their surface. We herein report that based on host-guest interaction, NPs decorated by novel folate enhance antitumor drug delivery. BSA-NPs were prepared by desolvation method and carboxymethyl-β-cyclodextrin (CM-β-CD) was conjugated to the surface of NPs by carbodiimide coupling to hold FA. From in vitro cytotoxicity assay, cell apoptosis study, intracellular ATP level assay and western blot, we can see that FA-CM-β-CD-BSA NPs as good monodispersity, negative charge, and homogenous particle size have a high encapsulation efficiency. The results showed that MTT and cell apoptosis demonstrated that FA-decorated NPs exhibit stronger inhibition rate and induce obvious apoptosis in FR positive Hela cells as compared to free drug and FA undecorated NPs. Moreover, 5-fluorouracil (5-Fu) loaded FA-CM-β-CD-BSA NPs down-regulate ATP levels and increase the expression of caspase-3. Taken together, FA-CM-β-CD-BSA NPs enhance FR receptor-mediated endocytosis and lead to more intracellular uptake of drug, inducing the higher apoptosis ratio of cells than free 5-Fu.

  7. Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy.

    Science.gov (United States)

    Chen, Wei-Hong; Lo, Wen-Cheng; Hsu, Wei-Che; Wei, Hong-Jian; Liu, Hen-Yu; Lee, Chian-Her; Tina Chen, Szu-Yu; Shieh, Ying-Hua; Williams, David F; Deng, Win-Ping

    2014-12-01

    Osteoarthritis (OA) is a common disease associated with tissue inflammation, physical disability and imbalanced homeostasis in cartilage. For advanced treatments, biological approaches are currently focused on tissue regeneration and anti-inflammation. This study was undertaken to evaluate the therapeutic efficacies of hyaluronic acid (HA) and platelet-rich plasma (PRP) (HA+PRP) on OA. Articular chondrocytes were obtained from five OA patients. The optimal HA and PRP concentrations were evaluated by MTT assay. The expressions of chondrogenic and inflammatory genes were analyzed by RT-PCR. Signaling pathway was examined by immunoblotting and the expressions of OA pathology-related chemokines and cytokines was demonstrated by real-time PCR-based SuperArray. The therapeutic efficacies of HA+PRP were then demonstrated in 3D arthritic neo-cartilage and ACLT-OA model. Here we showed that HA+PRP could greatly retrieve pro-inflammatory cytokines-reduced articular chondrocytes proliferation and chondrogenic phenotypes, the mechanism of which involve the sequential activation of specific receptors CD44 and TGF-βRII, downstream mediators Smad2/3 and Erk1/2, and the chondrogenic transcription factor SOX9. The real-time PCR-based SuperArray results also indicated that OA pathology-related chemokines and cytokines could be efficiently suppressed by HA+PRP. Moreover, the cartilaginous ECM could be retrieved from inflammation-induced degradation by HA+PRP in both 2D monolayer and 3D neo-cartilage model. Finally, the intra-articular injection of HA+PRP could strongly rescue the meniscus tear and cartilage breakdown and then decrease OA-related immune cells. The combination of HA+PRP can synergistically promote cartilage regeneration and inhibit OA inflammation. This study might offer an advanced and alternative OA treatment based on detailed regenerative mechanisms.

  8. Combination therapy of fenofibrate and ursodeoxycholic acid in patients with primary biliary cirrhosis who respond incompletely to UDCA monotherapy: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-05-01

    Full Text Available Yan Zhang,1,2,* Sainan Li,1,* Lei He,1 Fan Wang,1 Kan Chen,1 Jingjing Li,1 Tong Liu,1 Yuanyuan Zheng,1 Jianrong Wang,1,3 Wenxia Lu,1,3 Yuqing Zhou,1,4 Qin Yin,1,4 Yujing Xia,1 Yingqun Zhou,1 Jie Lu,1 Chuanyong Guo1 1Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 2Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 3The First Clinical Medical College of Nanjing Medical University, Nanjing, 4The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China *These authors contributed equally to this work Background: Although the effectiveness of treatment with ursodeoxycholic acid (UDCA and fenofibrate for primary biliary cirrhosis (PBC has been suggested by small trials, a systematic review to summarize the evidence has not yet been carried out.Methods: A meta-analysis of all long-term randomized controlled trials comparing the combination of UDCA and fenofibrate with UDCA monotherapy was performed via electronic searches.Results: Six trials, which included 84 patients, were assessed. Combination therapy with UDCA and fenofibrate was more effective than UDCA monotherapy in improving alkaline phosphatase (mean difference [MD]: -90.44 IU/L; 95% confidence interval [CI]: -119.95 to -60.92; P<0.00001, gamma-glutamyl transferase (MD: -61.58 IU/L; 95% CI: -122.80 to -0.35; P=0.05, immunoglobulin M (MD: -38.45 mg/dL; 95% CI: -64.38 to -12.51; P=0.004, and triglycerides (MD: -0.41 mg/dL; 95% CI: -0.82 to -0.01; P=0.05. However, their effects on pruritus (odds ratio [OR]: 0.39; 95% CI: 0.09–1.78; P=0.23, total bilirubin (MD: -0.05 mg/dL; 95% CI: -0.21 to 0.12; P=0.58, and alanine aminotransferase (MD: -3.31 IU/L; 95% CI: -14.60 to 7.97; P=0.56 did not differ significantly. This meta-analysis revealed no significant differences in the incidence of adverse events (OR: 0.21; 95% CI: 0.03–1.25; P=0.09 between patients treated with

  9. Irinotecan and 5-fluorouracil-co-loaded, hyaluronic acid-modified layer-by-layer nanoparticles for targeted gastric carcinoma therapy

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    Gao Z

    2017-09-01

    Full Text Available Zhuanglei Gao,1 Zhaoxia Li,2 Jieke Yan,3 Peilin Wang1 1Department of General Surgery, 2Department of Pediatrics, 3Department of Renal Transplantation, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China Abstract: For targeted gastric carcinoma therapy, hyaluronic acid (HA-modified layer-by-layer nanoparticles (NPs are applied for improving anticancer treatment efficacy and reducing toxicity and side effects. The aim of this study was to develop HA-modified NPs for the co-loading of irinotecan (IRN and 5-fluorouracil (5-FU. A novel polymer–chitosan (CH–HA hybrid formulation (HA–CH–IRN/5-FU NPs consisting of poly(D,L-lactide-co-glycolide (PLGA and IRN as the core, CH and 5-FU as a shell on the core and HA as the outmost layer was prepared. Its morphology, average size, zeta potential and drug encapsulation ability were evaluated. Human gastric carcinoma cells (MGC803 cells and cancer-bearing mice were used for the testing of in vitro cytotoxicity and in vivo antitumor efficiency of NPs. HA–CH–IRN/5-FU NPs displayed enhanced antitumor activity in vitro and in vivo than non-modified NPs, single drug-loaded NPs and drugs solutions. The results demonstrate that HA–CH–IRN/5-FU NPs can achieve impressive antitumor activity and the novel targeted drug delivery system offers a promising strategy for the treatment of gastric cancer. Keywords: gastric carcinoma, irinotecan, 5-fluorouracil, hyaluronic acid, layer-by-layer nanoparticles

  10. GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy.

    Science.gov (United States)

    Hu, Danrong; Mezghrani, Omar; Zhang, Lei; Chen, Yi; Ke, Xue; Ci, Tianyuan

    Novel breast carcinoma dual-targeted redox-responsive nanoparticles (NPs) based on cholesteryl-hyaluronic acid conjugates were designed for intracellular delivery of the antitumor drug doxorubicin (DOX). A series of reduction-responsive hyaluronic acid derivatives grafted with hydrophobic cholesteryl moiety (HA-ss-Chol) and GE11 peptide conjugated HA-ss-Chol (GE11-HA-ss-Chol) were synthesized. The obtained conjugates showed attractive self-assembly characteristics and high drug loading capacity. GE11-HA-ss-Chol NPs were highly stable under conditions mimicking normal physiological conditions, while showing a fast degradation of the vehicle's structure and accelerating the drug release dramatically in the presence of intracellular reductive environment. Furthermore, the cellular uptake assay confirmed GE11-HA-ss-Chol NPs were taken up by MDA-MB-231 cells through CD44- and epidermal growth factor receptor-mediated endocytosis. The internalization pathways of GE11-HA-ss-Chol NPs might involve clathrin-mediated endocytosis and macropinocytosis. The intracellular distribution of DOX in GE11-HA-ss-Chol NPs showed a faster release and more efficient nuclear delivery than the insensitive control. Enhanced in vitro cytotoxicity of GE11-HA-ss-Chol DOX-NPs further confirmed the superiority of their dual-targeting and redox-responsive capacity. Moreover, in vivo imaging investigation in MDA-MB-231 tumor-bearing mice confirmed that GE11-HA-ss-Chol NPs labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide, a near-infrared fluorescence dye, possessed a preferable tumor accumulation ability as compared to the single-targeting counterpart (HA-ss-Chol NPs). The antitumor efficacy showed an improved therapy efficacy and lower systemic side effect. These results suggest GE11-HA-ss-Chol NPs provide a good potential platform for antitumor drugs.

  11. The value of surrogate markers to monitor cholesterol absorption, synthesis and bioconversion to bile acids under lipid lowering therapies.

    Science.gov (United States)

    Stellaard, Frans; von Bergmann, Klaus; Sudhop, Thomas; Lütjohann, Dieter

    2017-05-01

    Regulation of cholesterol (Chol) homeostasis is controlled by three main fluxes, i.e. intestinal absorption, de novo synthesis (ChS) and catabolism, predominantly as bile acid synthesis (BAS). High serum total Chol and LDL-Chol concentrations in particular are considered risk factors and markers for the development of atherosclerosis. Pharmaceutical treatments to lower serum Chol have focused on reducing absorption or ChS and increasing BAS. Monitoring of these three parameters is complex involving isotope techniques, cholesterol balance experiments and advanced mass spectrometry based analysis methods. Surrogate markers were explored that require only one single fasting blood sample collection. These markers were validated in specific, mostly physiological conditions and during statin treatment to inhibit ChS. They were also applied under cholesterol absorption restriction, but were not validated in this condition. We retrospectively evaluated the use of serum campesterol (Camp), sitosterol (Sit) and cholestanol (Cholol) as markers for cholesterol absorption, lathosterol (Lath) as marker for ChS and 7α-hydroxycholesterol (7α-OH-Ch) and 27-hydroxycholesterol (27-OH-Ch) as markers for BAS under conditions of Chol absorption restriction. Additionally, their values were corrected for Chol concentration (R_sterol or oxysterols). Thirty-seven healthy male omnivore subjects were studied under treatments with placebo (PLAC), ezetimibe (EZE) to inhibit cholesterol absorption, simvastatin (SIMVA) to reduce cholesterol synthesis and a combination of both (EZE+SIMVA). Results were compared to those obtained in 18 pure vegetarian subjects (vegans) whose dietary Chol intake is extremely low. Relative or fractional Chol absorption (FrChA) was measured with the continuous feeding stable isotope procedure, ChS and BAS with the cholesterol balance method. The daily Chol intake (DICh) was inventoried and the daily Chol absorption (DACh) calculated. Monitoring cholesterol

  12. Indication of acid suppression therapy and predictors for the prophylactic use of proton-pump inhibitors vs. histamine-2 receptor antagonists in a Malaysian tertiary hospital

    Directory of Open Access Journals (Sweden)

    Oh AL

    2015-09-01

    Full Text Available Background: Proton-pump inhibitors (PPI and histamine-2 receptor antagonists (H2RA are common acid suppressants used in gastrointestinal disorders. The trend of usage in Malaysia has changed from predominantly H2RA to PPI from 2007 to 2008, 3.46 versus 2.87 and 2.99 versus 3.24 DDD (Defined Daily Dose/1000 population/day respectively. This raises concerns as PPI overutilization amounts to higher cost expenditure and are associated with various untoward consequences such as Clostridium difficile-associated diarrhea, pneumonia, and osteoporosis. Objectives: To evaluate the indication of acid suppression therapy (AST and to look for predictors associated with the prophylactic use of PPI as compared to H2RA. Methods: Data collection was conducted via a standardized surveillance form over a 2-month period in the general medical wards of Sarawak General Hospital. All patients who received at least one dose of PPI or H2RA in any dosage form were included in the study. Appropriateness of prophylaxis was determined using current available guidelines. Selected risk factors were analysed using simple logistic regression to look for predictors associated with the choice of PPI in prophylactic AST. Results: Out of 212 cases in the present cohort, about three quarters (75.5%, n=160 of acid suppressants were given as prophylaxis. Over half of these did not have appropriate indications for prophylactic AST (58.1%, n=93. Among all cases given prophylactic AST, 75.0% (n=120 of them were given PPI. Renal insufficiency was identified as the only predictor associated with the use of prophylactic PPI in preference to H2RA (OR=2.86, 95%CI 1.21:6.72, p=0.011. Conclusion: Inappropriate prophylactic AST is a major concern and may even be underestimated due to the lack of appropriate guidelines. More data is required to guide the selection between PPI and H2RA, specifically the more cost-effective use of H2RA in patients with lower gastrointestinal risk or in whom PPI has

  13. Chemical reconstruction of skin scars therapy using 100% trichloroacetic acid in the treatment of atrophic facial post varicella scars: A pilot study

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    Nidheesh Agarwal

    2013-01-01

    Full Text Available Context: Chickenpox (varicella is a common viral disease caused by Varicella zoster virus. Facial atrophic scars after varicella infection are not uncommon and pose a cosmetic problem. Like atrophic scars of other aetiologies, they are a difficult condition to treat. There are not enough references in the literature regarding efficient treatment of post varicella scars. High strength Trichloroacetic acid (TCA, which is known to cause dermal collagen remodelling, was used to treat varicella scars in the present study. Aims: The study was undertaken to assess the efficiency of Chemical Reconstruction of Skin Scars (CROSS technique using 100% TCA in the treatment of atrophic facial post varicella scars. Settings and Design: Open label, pilot study. Materials and Methods: A total of 16 patients with atrophic facial post varicella scars were treated by focal application of 100% TCA solution by pressing down upon the scar surface by a toothpick (CROSS technique. Total 4 sittings were given at 2 weekly intervals and the results evaluated after 3 months of follow-up. Statistical analysis was carried out using Fischer′s exact t-test. Results: All of the 13 patients who completed the study showed good clinical improvement, with 69% patients grading the response as excellent (>75% improvement, whereas the rest 31% patients reporting good (51-75% improvement. No significant complications were seen in any patient. Conclusions: CROSS technique using 100% TCA is a safe, cheap and effective therapy for the treatment of post varicella scars.

  14. Valine, a Branched-Chain Amino Acid, Reduced HCV Viral Load and Led to Eradication of HCV by Interferon Therapy in a Decompensated Cirrhotic Patient

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    Takumi Kawaguchi

    2012-10-01

    Full Text Available A decreased serum level of branched-chain amino acid (BCAA is a distinctive metabolic disorder in patients with liver cirrhosis. Recently, BCAA has been reported to exert various pharmacological activities, and valine, which is a BCAA, has been shown to affect lipid metabolism and the immune system in in vivo experiments. However, the clinical impact of valine supplementation on viral hepatitis C virus (HCV load has never been reported. Here, we first describe a case of HCV-related advanced liver cirrhosis that was treated by an oral valine agent. The administration of valine resulted in an improvement of fatigue and a reduction in hepatic fibrosis indexes as well as serum α-fetoprotein level. Furthermore, a marked reduction in HCV RNA levels was seen after valine treatment. The patient was then treated by interferon β, resulting in the successful eradication of chronic HCV infection. Thus, valine may be involved in the reduction of HCV viral load and could support a sustained virologic response to interferon therapy.

  15. No-Needle Jet Intradermal Aminolevulinic Acid Photodynamic Therapy for Recurrent Nodular Basal Cell Carcinoma of the Nose: A Case Report

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    Daniel Barolet

    2011-01-01

    Full Text Available Photodynamic therapy (PDT with aminolevulinic acid (ALA to treat nodular basal cell carcinoma (BCC has been shown to be beneficial. The success rate of ALA-PDT in the treatment of nodular BCC is dependent on optimal penetration of the photosensitizing agent and subsequent PpIX production. To enhance topical delivery of drugs intradermally, a needleless jet injection (NLJI, which employs a high-speed jet to puncture the skin without the side effects of needles, was used in one patient with recurrent BCC of the nose. Photoactivation was then performed using red light emitting diode [CW @ λ 630 nm, irradiance 50 mW/cm2, total fluence 51 J/cm2] for 17 minutes. Excellent cosmesis was obtained. Aside from mild crusting present for six days, no other adverse signs were noted. Clinically, there was no recurrent lesion up two years postintervention. Additional studies in larger samples of subjects are needed to further evaluate this promising technique.

  16. X-ray visible and doxorubicin-loaded beads based on inherently radiopaque poly(lactic acid)-polyurethane for chemoembolization therapy.

    Science.gov (United States)

    Sang, Lin; Luo, Dongdong; Wei, Zhiyong; Qi, Min

    2017-06-01

    The aim of current study was to develop drug-loaded polymeric beads with intrinsic X-ray visibility as embolic agents, targeting for noninvasive intraoperative location and postoperative examination during chemoembolization therapy. To endow polymer with inherent radiopacity, 4,4'-isopropylidinedi-(2,6-diiodophenol) (IBPA) was firstly synthesized and employed as a contrast agent, and then a set of radiopaque iodinated poly(lactic acid)-polyurethanes (I-PLAUs) via chain extender method were synthesized and characterized. These I-PLAU copolymers possessed sufficient radiopacity, in vitro non-cytotoxicity with human adipose-derived stem cells, and in vivo biocompatibility and degradability in rabbit model via intramuscular implantation. Doxorubicin (DOX), as a chemotherapeutic agent, was further incorporated into I-PLAU beads via a double emulsification (W/O/W) method. For drug release, two ratios of DOX-loaded I-PLAU beads exhibited calibrated size (200-550μm), porous internal structure, good X-ray visibility, evenly drug loading as well as tunable drug release. A preliminary test on in vitro tumor cell toxicity demonstrated that the DOX-loaded I-PLAU beads performed efficient anti-tumor effect. This study highlights novel X-ray visible drug-loaded I-PLAU beads used as promising embolic agents for non-invasive in situ X-ray tracking and efficient chemotherapy, which could bring opportunities to the next generation of multifunctional embolic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Effects of long term hydrophilic bile acid therapy on in vitro contraction of gallbladder muscle strips in patients with cholesterol gallstones

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate ursodeoxycholic acid (UDCA) therapy on the in vitro contraction of gallbladder smooth muscle strips from cholesterol gallstone patients.METHODS: The contraction forces of gallbladder smooth muscle strips from 28 patients with cholesterol gallstones treated with UDCA were compared with contraction forces from 14 untreated patients. The strips were stimulated with increasing concentrations of cholecystokinin-8 (CCK-8).RESULTS: Although the contraction forces that developed in response to CCK-8 were higher in strips from specimens of UDCA treated patients compared to untreated patients, longer treatment periods (6-wk)caused more contraction responses than the short treatment period of 3-wk (F = 19.297, 1.85 ± 0.22 g vs1.70 ± 0.10 g, P < 0.01). Contraction forces developed with maximal stimulation with KCl in the 6-wk treatment group were also higher than contraction forces in the untreated group (F = 4.274, 3.77 ± 0.45 g vs 3.30 ± 0.30g, P < 0.05).CONCLUSION: Six-week UDCA treatment caused an increase in contractions of muscle strips from patients with cholesterol gallstones when compared to shorter treatment administration or controls. We suggest that extending UDCA treatment periods may cause more effective contractions in the gallbladder, and thereby increase the rate of response to treatment.

  18. Consequence of nigrostriatal denervation and L-dopa therapy on the expression of glutamic acid decarboxylase messenger RNA in the pallidum.

    Science.gov (United States)

    Herrero, M T; Levy, R; Ruberg, M; Luquin, M R; Villares, J; Guillen, J; Faucheux, B; Javoy-Agid, F; Guridi, J; Agid, Y; Obeso, J A; Hirsch, E C

    1996-07-01

    To examine the consequences of nigrostriatal denervation and L-dopa treatment on the basal ganglia output system, we analyzed, by quantitative in situ hybridization, the messenger RNA coding for glutamic acid decarboxylase (Mr 67,000) (GAD67 mRNA) in pallidal cells from patients with Parkinson's disease (PD), monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) receiving or not receiving L-dopa, and their respective control subjects. In MPTP-treated monkeys, the expression of GAD67 mRNA was increased in cells from the internal pallidum, and this effect was abolished by L-dopa treatment. There were no differences in the levels of GAD67 mRNA between patients with PD, who were all treated with L-dopa, and control subjects. These results indicate that the level of GAD67 mRNA is increased in the cells of the internal pallidum after nigrostriatal dopaminergic denervation and that this increase can be reversed by L-dopa therapy.

  19. In vitro cultivation of canine multipotent mesenchymal stromal cells on collagen membranes treated with hyaluronic acid for cell therapy and tissue regeneration

    Directory of Open Access Journals (Sweden)

    T.I. Wodewotzky

    2012-12-01

    Full Text Available Support structures for dermal regeneration are composed of biodegradable and bioresorbable polymers, animal skin or tendons, or are bacteria products. The use of such materials is controversial due to their low efficiency. An important area within tissue engineering is the application of multipotent mesenchymal stromal cells (MSCs to reparative surgery. The combined use of biodegradable membranes with stem cell therapy may lead to promising results for patients undergoing unsuccessful conventional treatments. Thus, the aim of this study was to test the efficacy of using membranes composed of anionic collagen with or without the addition of hyaluronic acid (HA as a substrate for adhesion and in vitro differentiation of bone marrow-derived canine MSCs. The benefit of basic fibroblast growth factor (bFGF on the differentiation of cells in culture was also tested. MSCs were collected from dog bone marrow, isolated and grown on collagen scaffolds with or without HA. Cell viability, proliferation rate, and cellular toxicity were analyzed after 7 days. The cultured cells showed uniform growth and morphological characteristics of undifferentiated MSCs, which demonstrated that MSCs successfully adapted to the culture conditions established by collagen scaffolds with or without HA. This demonstrates that such scaffolds are promising for applications to tissue regeneration. bFGF significantly increased the proliferative rate of MSCs by 63% when compared to groups without the addition of the growth factor. However, the addition of bFGF becomes limiting, since it has an inhibitory effect at high concentrations in culture medium.

  20. In vitro cultivation of canine multipotent mesenchymal stromal cells on collagen membranes treated with hyaluronic acid for cell therapy and tissue regeneration.

    Science.gov (United States)

    Wodewotzky, T I; Lima-Neto, J F; Pereira-Júnior, O C M; Sudano, M J; Lima, S A F; Bersano, P R O; Yoshioka, S A; Landim-Alvarenga, F C

    2012-12-01

    Support structures for dermal regeneration are composed of biodegradable and bioresorbable polymers, animal skin or tendons, or are bacteria products. The use of such materials is controversial due to their low efficiency. An important area within tissue engineering is the application of multipotent mesenchymal stromal cells (MSCs) to reparative surgery. The combined use of biodegradable membranes with stem cell therapy may lead to promising results for patients undergoing unsuccessful conventional treatments. Thus, the aim of this study was to test the efficacy of using membranes composed of anionic collagen with or without the addition of hyaluronic acid (HA) as a substrate for adhesion and in vitro differentiation of bone marrow-derived canine MSCs. The benefit of basic fibroblast growth factor (bFGF) on the differentiation of cells in culture was also tested. MSCs were collected from dog bone marrow, isolated and grown on collagen scaffolds with or without HA. Cell viability, proliferation rate, and cellular toxicity were analyzed after 7 days. The cultured cells showed uniform growth and morphological characteristics of undifferentiated MSCs, which demonstrated that MSCs successfully adapted to the culture conditions established by collagen scaffolds with or without HA. This demonstrates that such scaffolds are promising for applications to tissue regeneration. bFGF significantly increased the proliferative rate of MSCs by 63% when compared to groups without the addition of the growth factor. However, the addition of bFGF becomes limiting, since it has an inhibitory effect at high concentrations in culture medium.

  1. In vitro cultivation of canine multipotent mesenchymal stromal cells on collagen membranes treated with hyaluronic acid for cell therapy and tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Wodewotzky, T.I.; Lima-Neto, J.F. [Departamento de Reprodução Animal e Radiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil); Pereira-Júnior, O.C.M. [Departamento de Reprodução Animal e Radiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil); Departamento de Cirurgia e Anestesiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil); Sudano, M.J.; Lima, S.A.F. [Departamento de Reprodução Animal e Radiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil); Bersano, P.R.O. [Departamento de Patologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil); Yoshioka, S.A. [Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP (Brazil); Landim-Alvarenga, F.C. [Departamento de Reprodução Animal e Radiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil)

    2012-09-21

    Support structures for dermal regeneration are composed of biodegradable and bioresorbable polymers, animal skin or tendons, or are bacteria products. The use of such materials is controversial due to their low efficiency. An important area within tissue engineering is the application of multipotent mesenchymal stromal cells (MSCs) to reparative surgery. The combined use of biodegradable membranes with stem cell therapy may lead to promising results for patients undergoing unsuccessful conventional treatments. Thus, the aim of this study was to test the efficacy of using membranes composed of anionic collagen with or without the addition of hyaluronic acid (HA) as a substrate for adhesion and in vitro differentiation of bone marrow-derived canine MSCs. The benefit of basic fibroblast growth factor (bFGF) on the differentiation of cells in culture was also tested. MSCs were collected from dog bone marrow, isolated and grown on collagen scaffolds with or without HA. Cell viability, proliferation rate, and cellular toxicity were analyzed after 7 days. The cultured cells showed uniform growth and morphological characteristics of undifferentiated MSCs, which demonstrated that MSCs successfully adapted to the culture conditions established by collagen scaffolds with or without HA. This demonstrates that such scaffolds are promising for applications to tissue regeneration. bFGF significantly increased the proliferative rate of MSCs by 63% when compared to groups without the addition of the growth factor. However, the addition of bFGF becomes limiting, since it has an inhibitory effect at high concentrations in culture medium.

  2. A spermine conjugated stearic acid-g-chitosan oligosaccharide polymer with different types of amino groups for efficient p53 gene therapy.

    Science.gov (United States)

    Meng, Tingting; Wu, Jie; Yi, Hanxi; Liu, Jingwen; Lu, Binbin; Yuan, Ming; Huang, Xuan; Yuan, Hong; Hu, Fuqiang

    2016-09-01

    The effect of various amino groups on gene vector is different. In order to combine their effect in one vector and finally promote the transfection efficiency, a biogenic tetra-amine spermine was introduced to modify the stearic acid-grafted chitosan oligosaccharide (CSOSA) polymer to build a new gene delivery system. The spermine linked CSOSA (SP-CSOSA) polymer consists two types of amino groups with 73.3%, 19.3% of all nitrogen atoms for primary and secondary amine groups, respectively. The SP modified CSOSA showed strong DNA condensation capability and obviously enhanced proton binding ability especially at about pH 5.0, which significantly promoted the escape of SP-CSOSA/pDNA complexes from endo-lysosoms. Moreover, the transfection efficiency at the N/P ratio of 10 could compete with that of Lipofectamine 2000 and PEI 25K, but with lower cytotoxicities. The therapeutic wild type p53 gene transfected by the SP-CSOSA polymer restored the function of aberrant p53 gene and induced obvious cell apoptosis and G1 phase arrest. We concluded that the new vector SP-CSOSA polymer proved to be a potential delivery system for gene therapy.

  3. Folic acid-conjugated TiO2-doped mesoporous carbonaceous nanocomposites loaded with Mitoxantrone HCl for chemo-photodynamic therapy.

    Science.gov (United States)

    Li, Zhi; Ou-Yang, Ya; Liu, Yang; Wang, Yi-Qiu; Zhu, Xia-Li; Zhang, Zhen-Zhong

    2015-06-01

    Recently, porous carbons have showed great potential in many areas. In this study, TiO2-doped mesoporous carbonaceous (TiO2@C) nanoparticles were obtained by a simple one-pot hydrothermal treatment, folic acid (FA) was conjugated to TiO2@C through an amide bond, then Mitoxantrone HCl (MTX) was adsorbed onto TiO2@C-FA and a drug delivery system, TiO2@C-FA/MTX was obtained. TiO2@C-FA/MTX showed a much faster MTX release at pH 4.5 than at pH 6.0 and pH 7.4. Furthermore, compared with free MTX, this drug delivery system showed a dose-dependent cytotoxicity by varying the irradiance, and afforded higher antitumor efficacy in cultured PC3 cells in vitro. The ability of TiO2@C-FA/MTX to combine chemotherapy with photodynamic activity enhanced the cancer cell killing effect in vitro, demonstrating that TiO2@C-FA/MTX has a great potential for cancer therapy in the future.

  4. Serum level changes of insulin-like growth factor-1 and amino acids in children with cerebral palsy following functional exercise plus head acupuncture therapy

    Institute of Scientific and Technical Information of China (English)

    Lihua Zhang; Jiaojiao Du; Xiaojie Li; Zhimei Jiang

    2006-01-01

    BACKGROUND:In the past few years,there were many studies about the pathophysiology of insulin-like growth factor-1(Lgf-1), as well as glutamic acid (GLU) and γ-aminobutydc acid(GABA)in hypoxic-ischemic brain damage (HIBD).IGF-1 plays a protective role in brain damage.The over release of excitatory amino acids (EAA) plays an important role in acute neuronal death,which delays neuronal death.The disproportion of increasing of excitatory and inhibitory amino acids can cause different extent HIBD.However,there is rare report about the change of IGF-1 and neurotransmitter Ievelin serum of cerebral palsy (CP) children.OBJECTIVE:To observe the levels of serum IGF-1.GABA and GLU before and after functional exercise plus head acupuncture therapy and single functional exercise,then study the effective mechanism of IGF-1.GABA and GLU in the occurrence and development of CP,and compare those with normal control group.DESIGN:Case-control study.SETTING:College of Rehabilitation Medicine,Jiamusi University,Prevention and Treatment Center of Child Cerebral Palsy in Heilongjiang Province.PARTICIPANTS:CP group:Sixty CP children came from Prevention and Treatment Center of Child Cerebral Palsy in Heilongjiang Province between April 2005 and March 2006 were selected in this study.All the cases were consistent with the diagnostic criteria and the type of cerebral palsy and finally diagnosed with CT and MRI examinations.There were 35 males and 25 females aged from 8 months to 4 years with the mean age of (2.0±0.5)years.And then,they were randomly divided into two groups.Twenty-six cases were received functional exercise,and the other 34 cases were treated with functional exercise and head acupuncture.Control group: Thirty healthy children were from kindergarten and community for health examination in June 2005.There were 15 males and 15 females aged from 8 month to 4 years with the mean age of(2.0±0.5)years.All guardians agreed with the participation of this experiment.METHODS:

  5. Effect of cell cycle phase on the sensitivity of SAS cells to sonodynamic therapy using low-intensity ultrasound combined with 5-aminolevulinic acid in vitro.

    Science.gov (United States)

    Li, Nan; Sun, Miao; Wang, Yao; Lv, Yanhong; Hu, Zheng; Cao, Wenwu; Zheng, Jinhua; Jiao, Xiaohui

    2015-08-01

    Sonodynamic therapy (SDT) with 5-aminolevulinic acid (5-ALA) can effectively inhibit various types of tumor in vitro and in vivo. However, the association between the efficacy of SDT and the phase of the cell cycle remains to be elucidated. 5-ALA may generate different quantities of sonosensitizer, protoporphyrin IX (PpIX), in different phases of the cell cycle, which may result in differences in sensitivity to 5-ALA-induced SDT. The present study aimed to investigate the effect of the cell cycle on the susceptibility of SAS cells to SDT following synchronization to different cell cycle phases. These results indicates that the rates of cell death and apoptosis of the SAS cells in the S and G2/M phases were significantly higher following SDT, compared with those in the G1-phase cells and unsynchronized cells, with a corresponding increase in PpIX in the S and G2/M cells. In addition, the expression of caspase-3 increased, while that of B-cell lymphoma (Bcl)-2 decreased markedly in theS and G2/M cells following SDT. Cyclin A was also expressed at higher levels in the S and G2/M cells, compared with the G1-phase cells. SDT also caused a significant upregulation of cyclin A in all phases of the cell cycle, however this was most marked in the S and G2/M cells. It was hypothesized that high expression levels of cyclin A in the S and G2/M cells may promote the induction of caspase-3 and reduce the induction of Bcl-2 by SDT and, therefore, enhance apoptosis. Taken together, these data demonstrated that cells in The S and G2/M phases generate more intracellular PpIX, have higher levels of cyclin A and are, therefore, more sensitive to SDT-induced cytotoxicity. These findings indicate the potential novel approach to preventing the onset of cancer by combining cell-cycle regulators with SDT. This sequential combination therapy may be a simple and cost-effective way of enhancing the effects of SDT in clinical settings.

  6. Biocompatible cationic pullulan-g-desoxycholic acid-g-PEI micelles used to co-deliver drug and gene for cancer therapy.

    Science.gov (United States)

    Chen, Lili; Ji, Fangling; Bao, Yongming; Xia, Jing; Guo, Lianying; Wang, Jingyun; Li, Yachen

    2017-01-01

    The greatest crux in the combination of chemotherapy and gene therapy is the construction of a feasible and biocompatible carrier for loading the therapeutic drug and gene simultaneously. Here, a new amphiphilic bifunctional pullulan derivative (named as PDP) synthesized by grafting lipophilic desoxycholic acid and low-molecular weight (1kDa) branched polyethylenimine onto the backbone of pullulan was evaluated as a nano-carrier for the co-delivery of drug and gene for potential cancer therapy. PDP exhibited good blood compatibility and low cytotoxicity in the hemolysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. By self-assembly process, the amphiphilic PDP polymer formed cationic core-shell nanomicelles in aqueous solution with an average diameter of 160.8nm and a zeta potential of approximate 28mV. The PDP micelles had relative higher drug encapsulation efficiency (84.05%) and loading capacity (7.64%) for doxorubicin (DOX), an effective anti-tumor drug, demonstrating sustained drug release profile and good DNA-binding ability. The flow cytometry and confocal laser scanning microscopy showed that PDP/DOX micelles could be successfully internalized by MCF-7 cells, and presenting higher cytotoxicity against MCF-7 cells than that of free DOX. Furthermore, PDP micelles could efficiently transport tumor suppressor gene p53 into MCF-7 cells, and the expressed exogenous p53 protein induced MCF-7 cells to die. More excitedly, in comparison with single DOX or p53 delivery, the co-delivery of DOX and gene p53 using PDP micelles displayed higher cytotoxicity, induced higher apoptosis rate of tumor cells and blocked more effectively the migration of cancer cells in vitro. In tumor-bearing mice, co-delivery of DOX and p53 also exhibited enhanced antitumor efficacy as compared with single delivery of DOX or p53 alone. In summary, these results demonstrated that it is highly promising to use cationic PDP micelles for effectively

  7. Pre-clinical evaluation of 2,3-dimercaptosuccinic acid as a radiation nephrotoxicity protective agent during radiopeptide therapy of neuroendocrine malignancy.

    Science.gov (United States)

    Moorin, Rachael E; Meyrick, Danielle P; Rose, Alison

    2007-04-01

    To determine if dimercaptosuccinic acid (DMSA), an agent originally developed as a safe non-toxic antidote for heavy metal poisoning, would be useful as a kidney radiation dose reduction agent in patients undergoing radiopeptide therapy for cancer. Thirty-six adult male Wistar rats were injected via the penile vein with 10 MBq of 177Lu-DOTA-tyr(3)-octreotate. At 30 min after the radiopeptide injection, 18 of the animals (intervention group) were injected with 0.15 mg x g(-1) of DMSA (i.p.). Samples were collected for gamma counting at 24 (n=12), 48 (n=12) and 72 h (n=12) after administration of the radiopeptide. At each time point, the percentage injected dose per gram of tissue in each sample of the six control animals was compared with that of the six animals from the DMSA injection regimen. The i.p. injection of 0.15 mg x g(-1) of DMSA 30 min following the administration of the 177Lu-DOTATATE reduced the mean (95% CI) kidney retention of radiopeptide by 15.6% (2.6-24.6) at 72 h while not significantly affecting uptake in other organs. Statistical testing of the difference between the two groups of animals (DMSA versus controls) at 72 h post-administration of the radiopeptide indicated only a 3% chance that the magnitude of the reduction in kidney radiopeptide retention observed would be expected due to natural variation (i.e., if there was no difference between the groups). This study has indicated that DMSA has the potential to selectively reduce radiopeptide kidney retention. Further work is necessary to determine the most effective dose of DMSA and the most effective timing regimen, and to examine the clinical efficacy of several other chelating agents.

  8. Comparing Papanicolau smear, visual inspection with acetic acid and human papillomavirus cervical cancer screening methods among HIV-positive women by immune status and antiretroviral therapy.

    Science.gov (United States)

    Chung, Michael H; McKenzie, Kevin P; De Vuyst, Hugo; Richardson, Barbra A; Rana, Farzana; Pamnani, Ritesh; Njoroge, Julia W; Nyongesa-Malava, Evans; Sakr, Samah R; John-Stewart, Grace C; Mugo, Nelly R

    2013-11-28

    A rigorous comparison of cervical cancer screening methods utilizing data on immune status, antiretroviral therapy (ART) and colposcopy-directed biopsy has not been performed among HIV-positive women. Between June and November 2009, 500 HIV-positive women were enrolled at an HIV treatment clinic in Nairobi, Kenya, and underwent Papanicolau (Pap) smear, visual inspection with acetic acid (VIA), human papillomavirus (HPV) and colposcopy-directed biopsy (gold standard). Positive Pap smear (ASCUS+, LSIL+, HSIL+), VIA, HPV and their combinations were compared with CIN2/3+. Sensitivity, specificity and AUC (sensitivity and 1-specificity) were compared using pairwise tests and multivariate logistic regression models that included age, CD4⁺ cell count and ART duration. Of 500 enrolled, 498 samples were collected. On histology, there were 172 (35%) normal, 186 (37%) CIN1, 66 (13%) CIN2, 47 (9%) CIN3 and 27 (5%) indeterminate. Pap (ASCUS+) was the most sensitive screening method (92.7%), combination of both Pap (HSIL+) and VIA positive was the most specific (99.1%) and Pap (HSIL+) had the highest AUC (0.85). In multivariate analyses, CD4⁺ cell count of 350 cells/μl or less was associated with decreased HPV specificity (P = 0.002); ART duration of less than 2 years was associated with decreased HPV (P = 0.01) and VIA (P = 0.03) specificity; and age less than 40 years was associated with increased VIA sensitivity (P < 0.001) and decreased HPV specificity (P = 0.005). Pap smear is a robust test among HIV-positive women regardless of immune status or ART duration. Results should be cautiously interpreted when using HPV among those younger, immunosuppressed or on ART less than 2 years, and when using VIA among those aged 40 years or more.

  9. 5-氨基酮戊酸光动力学疗法在皮肤科的应用进展%Applied advances of 5-aminolevulinic acid photodynamic therapy in dermatology

    Institute of Scientific and Technical Information of China (English)

    张立坤; 竺炯; 张萍

    2012-01-01

    To explore the mechanism and application of photodynamic therapy using aminolevulinic acid (5-ALA) in skin diseases, and provide reference for the rational use in clinic. Summarize the reported articles of mechanism and clinical application of photodynamic therapy in recent ten years, analysis the mechanism in the photodynamic therapy treatment for various skin disease, sort the types of skin disease cured by photodynamic therapy and the side effect related with photodynamic therapy. Photodynamic therapy have good clinical curative effect in skin cancer, erythema scaly skin neoplasms, psoriasis, viral warts, acne, nevus flammeus, etc. and have fewer adverse reactions. Photodynamic therapy is a safe, efficient treatment of psoriasis, and have great application prospects in skin diseases.%探讨5-氨基酮戊酸(ALA)光动力学疗法(PDT)治疗皮肤病的作用原理及应用范围,为临床合理使用ALA-PDT提供参考依据.对近10余年来文献报道的有关PDT研究进展及其临床应用的文献进行总结和分析,综述ALA-PDT治疗各类皮肤病的作用原理和机制,以及ALA-PDT治疗皮肤病的范围,所引起的不良反应.PDT对皮肤肿瘤、红斑鳞屑性皮肤病、人乳头瘤病毒(HPV)感染性皮肤病、痤疮、鲜红斑痣等均有良好的临床效果,不良反应相对较小,在皮肤科有很大的应用前景.

  10. Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trial

    Directory of Open Access Journals (Sweden)

    Fushida S

    2016-07-01

    -free survival was 4.5 months in the wPTX group and 3.0 months in the wPTX plus VPA group (hazard ratio 1.29; 95% CI 0.753–2.211; P=0.35. Grade 3–4 adverse events were neutropenia (3.1%, pneumonia (1.6%, liver injury (1.6%, brain infarction (1.6%, and rupture of aorta (1.6%.Conclusion: No statistically significant difference was observed between wPTX and wPTX plus VPA for OS. Keywords: valproic acid, paclitaxel, second- or third-line therapy, advanced gastric cancer

  11. Safety and efficacy of an add-on therapy with curcumin phytosome and piperine and/or lipoic acid in subjects with a diagnosis of peripheral neuropathy treated with dexibuprofen

    Directory of Open Access Journals (Sweden)

    Di Pierro F

    2013-07-01

    Full Text Available Francesco Di Pierro,1 Roberto Settembre2 1Scientific Department, Velleja Research, Milan, Italy; 2Neurosurgery Department, Di Venere Hospital, Bari, Italy Abstract: We conducted an 8-week, open, randomized controlled clinical trial on 141 subjects affected by neuropathic pain to investigate the role of an adjunctive therapy added to the administration of dexibuprofen (400 mg twice a day and based on a multi-ingredient formula (Lipicur, consisting of lipoic acid plus curcumin phytosome and piperine, in patients with a diagnosis of lumbar sciatica, lumbar disk herniation, and/or lumbar canal stenosis (96 subjects, or with carpal tunnel syndrome (45 subjects. A total of 135 participants completed the study. Treatment with the multi-ingredient formula (Lipicur reduced neuropathic pain by more than 66% in both conditions (subjects with lumbar sciatica and with carpal tunnel syndrome, and these reductions were statistically significant. Moreover, the treatment reduced dexibuprofen use by about 40%. An add-on therapy with only lipoic acid has not shown any significant results. On the basis of its safety and efficacy, Lipicur could be considered an effective complementary therapy to be added to conventional treatments to achieve better efficacy in reducing neuropathic pain. Keywords: curcumin, phytosome, piperine, dexibuprofen, neuropathic pain

  12. Safety and efficacy of an add-on therapy with curcumin phytosome and piperine and/or lipoic acid in subjects with a diagnosis of peripheral neuropathy treated with dexibuprofen

    Science.gov (United States)

    Di Pierro, Francesco; Settembre, Roberto

    2013-01-01

    We conducted an 8-week, open, randomized controlled clinical trial on 141 subjects affected by neuropathic pain to investigate the role of an adjunctive therapy added to the administration of dexibuprofen (400 mg twice a day) and based on a multi-ingredient formula (Lipicur), consisting of lipoic acid plus curcumin phytosome and piperine, in patients with a diagnosis of lumbar sciatica, lumbar disk herniation, and/or lumbar canal stenosis (96 subjects), or with carpal tunnel syndrome (45 subjects). A total of 135 participants completed the study. Treatment with the multi-ingredient formula (Lipicur) reduced neuropathic pain by more than 66% in both conditions (subjects with lumbar sciatica and with carpal tunnel syndrome), and these reductions were statistically significant. Moreover, the treatment reduced dexibuprofen use by about 40%. An add-on therapy with only lipoic acid has not shown any significant results. On the basis of its safety and efficacy, Lipicur could be considered an effective complementary therapy to be added to conventional treatments to achieve better efficacy in reducing neuropathic pain. PMID:23861596

  13. Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia.

    Science.gov (United States)

    Oh, Pyung Chun; Koh, Kwang Kon; Sakuma, Ichiro; Lim, Soo; Lee, Yonghee; Lee, Seungik; Lee, Kyounghoon; Han, Seung Hwan; Shin, Eak Kyun

    2014-10-20

    Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. Copyright © 2014. Published by Elsevier Ireland Ltd.

  14. Fat malabsorption in cystic fibrosis patients receiving enzyme replacement therapy is due to impaired intestinal uptake of long-chain fatty acids

    NARCIS (Netherlands)

    Kalivianakis, M; Minich, DM; Bijleveld, CMA; van Aalderen, WMC; Stellaard, F; Vonk, RJ; Verkade, HJ

    1999-01-01

    Background: Pancreatic enzyme replacement therapy frequently fails to correct intestinal fat malabsorption completely in cystic fibrosis (CF) patients. The reason for this failure is unknown. Objective: We investigated whether fat malabsorption in CF patients treated with pancreatic enzymes is cause

  15. Usefulness of {sup 131}I-SPECT/CT and {sup 18}F-FDG PET/CT in evaluating successful {sup 131}I and retinoic acid combined therapy in a patient with metastatics struma ovarii

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hyo Jung; Lee, In Ki; Kang, Keon Wook; Lee, Dong Soo; Chung, June Key [Dept. of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Ryu, Young Hoon [Dept. of Nuclear Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Min, Hye Sook [Dept. of Pathology, Seoul National University Hospital, Seoul (Korea, Republic of); Lee, Dae Hee [Dept. of Oncology, GSAM Hosptial, Gunpo (Korea, Republic of)

    2015-03-15

    Metastatic struma ovarii is an extremely rare disease, and the treatment of choice has not been established. Here, we introduce the case of a 36-year-old female pregnant patient with metastatic struma ovarii. Initial treatment was an exploratory laparotomy to remove multiple peritoneal masses. After delivery, a total thyroidectomy was done for the further {sup 131}I-therapy. {sup 131}I-SPECT/CT and {sup 18}F-FDG PET/CT showed multiple hepatic metastases and extensive peritoneal seeding nodules. Multiple {sup 131}I and retinoic acid combination therapies were performed, resulting in marked improvement. {sup 131}I-SPECT/CT and {sup 18}F-FDG PET/CT were quite useful for evaluating the biologic characteristics of the metastase.

  16. Myocardial scintigraphy using iodine-123 15-(p-Iodophenyl)-3-R, S-methylpentadecanoic acid predicts the response to beta-blocker therapy in patients with dilated cardiomyopathy but does not reflect therapeutic effect

    Energy Technology Data Exchange (ETDEWEB)

    Yoshinaga, Keiichiro; Tahara, Minoru; Torii, Hiroyuki; Akimoto, Masaki [Kagoshima City Medical Association Hopital (Japan); Kihara, Koichi; Tei, Chuwa

    2000-05-01

    Myocardial fatty acid metabolism is disturbed in patients with idiopathic dilated cardiomyopathy. Myocardial scintigraphy using iodine-123 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP) was used to assess the response to {beta}-blocker therapy in 19 patients with dilated cardiomyopathy. BMIPP myocardial scintigraphy was performed before and 6 months after initiating {beta}-blocker therapy with metoprolol. Cardiac BMIPP uptake was assessed as the total defect score (TDS) and heart-to-mediastinum activity (H/M) ratio. Patients were classified retrospectively as responders with an improvement of at least one functional class (New York Heart Association) or an increase in ejection fraction of {>=}0.10 at 6 months, or as nonresponders meeting neither criterion. Responders had a significantly better pretreatment TDS (p<0.005) and H/M ratio (p<0.0001) than nonresponders. TDS exhibited no significant changes over 6 months in either group (responders: 13.2{+-}3.7 vs 12.5{+-}3.3; nonresponders: 20.8{+-}6.5 vs 20.5{+-}3.0). Responders showed no significant changes in H/M ratio (2.47{+-}0.28 vs 2.43{+-}0.42); paradoxically, nonresponders showed a significant increase from 1.82{+-}0.11 to 2.10{+-}0.19 (p<0.05), suggesting that {beta}-blocker therapy protected the myocardial fatty acid metabolism even in the absence of clinical improvement. BMIPP myocardial scintigraphy provides a prediction of response to {beta}-blocker treatment, but does not reflect the therapeutic effect in responders at 6 months. (author)

  17. Parenteral Nutrition: Amino Acids

    Science.gov (United States)

    Hoffer, Leonard John

    2017-01-01

    There is growing interest in nutrition therapies that deliver a generous amount of protein, but not a toxic amount of energy, to protein-catabolic critically ill patients. Parenteral amino acids can achieve this goal. This article summarizes the biochemical and nutritional principles that guide parenteral amino acid therapy, explains how parenteral amino acid solutions are formulated, and compares the advantages and disadvantages of different parenteral amino acid products with enterally-delivered whole protein products in the context of protein-catabolic critical illness. PMID:28287411

  18. Parenteral Nutrition: Amino Acids.

    Science.gov (United States)

    Hoffer, Leonard John

    2017-03-10

    There is growing interest in nutrition therapies that deliver a generous amount of protein, but not a toxic amount of energy, to protein-catabolic critically ill patients. Parenteral amino acids can achieve this goal. This article summarizes the biochemical and nutritional principles that guide parenteral amino acid therapy, explains how parenteral amino acid solutions are formulated, and compares the advantages and disadvantages of different parenteral amino acid products with enterally-delivered whole protein products in the context of protein-catabolic critical illness.

  19. Higher dietary cholesterol and ω-3 fatty acid intakes are associated with a lower success rate of Helicobacter pylori eradication therapy in Japan.

    Science.gov (United States)

    Ikezaki, Hiroaki; Furusyo, Norihiro; Jacques, Paul F; Shimizu, Motohiro; Murata, Masayuki; Schaefer, Ernst J; Urita, Yoshihisa; Hayashi, Jun

    2017-08-01

    Background:Helicobacter pylori infection is a known risk factor for duodenal ulcers, gastritis, and gastric cancer. The eradication of H. pylori is successful in treating these disorders; however, the success rate of eradication therapy is declining. There may be an interaction with nutrient intake to account for this decline.Objective: We investigated the influence of food and nutrient intake on H. pylori eradication therapy.Design: In this study, 4014 subjects underwent endoscopy, were tested for serum antibodies to H. pylori (2046 positive; 51.0%), and had their food intake assessed with the use of a food-frequency questionnaire (FFQ). Of the positive subjects, endoscopies showed that 389 (19.0%) had gastritis and/or duodenal ulcers and were also positive for a (13)C-urea breath test (UBT). These 389 subjects received 1-wk H. pylori eradication therapy with lansoprazole, amoxicillin, and clarithromycin and a second UBT 8 wk after treatment. Complete demographic characteristics, serum lipid, insulin, glycated hemoglobin, C-reactive protein (CRP), and creatinine concentrations as well as complete FFQs were available for 352 subjects. Multivariate logistic regression analyses were performed to determine factors that were associated with successful H. pylori eradication therapy.Results: The success rate of eradication therapy was 60.4% (235 of 389). Factors associated with the failure of eradication therapy included increased age (P = 0.02), higher CRP concentrations (P pylori eradication therapy in H. pylori-positive subjects with gastritis and/or duodenal ulcers. © 2017 American Society for Nutrition.

  20. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

    Science.gov (United States)

    James, Nicholas D; Sydes, Matthew R; Clarke, Noel W; Mason, Malcolm D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Parker, Christopher C; Russell, J Martin; Attard, Gerhardt; de Bono, Johann; Cross, William; Jones, Rob J; Thalmann, George; Amos, Claire; Matheson, David; Millman, Robin; Alzouebi, Mymoona; Beesley, Sharon; Birtle, Alison J; Brock, Susannah; Cathomas, Richard; Chakraborti, Prabir; Chowdhury, Simon; Cook, Audrey; Elliott, Tony; Gale, Joanna; Gibbs, Stephanie; Graham, John D; Hetherington, John; Hughes, Robert; Laing, Robert; McKinna, Fiona; McLaren, Duncan B; O'Sullivan, Joe M; Parikh, Omi; Peedell, Clive; Protheroe, Andrew; Robinson, Angus J; Srihari, Narayanan; Srinivasan, Rajaguru; Staffurth, John; Sundar, Santhanam; Tolan, Shaun; Tsang, David; Wagstaff, John; Parmar, Mahesh K B

    2016-01-01

    Summary Background Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. Methods Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m2) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). Findings 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60–71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6

  1. Nanomedicine and cancer therapies

    CERN Document Server

    Sebastian, Mathew; Elias, Eldho

    2012-01-01

    Introduction Nanotechnological-Based Systems for CancerIn vivo Spectroscopy for Detection and Treatment of GBM with NPt® ImplantationNanobiotechnology for Antibacterial Therapy and DiagnosisChitosan NanoparticlesSynthesis and Biomedical Application of Silver NanoparticlesRecent Advances in Cancer Therapy Using PhytochemicalsMitochondrial Dysfunction and Cancer: Modulation by Palladium-Lipoic Acid ComplexUnity of Mind and Body: The Concept of Life Purpose DominantThuja Occidentalis and Breast Cancer ChemopreventionAntioxidants and Com

  2. Antitumor effect of conditioned media derived from murine MSCs and 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy in breast cancer in vitro.

    Science.gov (United States)

    Mohammadpour, Hemn; Majidzadeh-A, Keivan

    2015-06-01

    Mesenchymal stem cells are multi-potent progenitor cells that inhibit tumor growth by some ligands and releasing factors including TRAIL, DKK-1 and DKK-3. On other hands, photodynamic therapy is commonly used for treatment of different types of cancer. The aims of this study are to investigate of MSCs conditioned media and ALA mediated photodynamic therapy in breast cancer. Condition media was derived after documentation of mouse adipose derived MSCs. For photodynamic therapy (PDT), ALA was used at the final concentrations of 1mM for 4-h followed by exposure to red light with a peak wave length of 632-nm, delivered from diode laser located at 2 cm to achieve a total light dose of 5 Joules (J)/cm(2). Apoptosis and growth of 4T1 cancer cells were analyzed in different groups including MSCs derived condition media, PDT and MSCs derived condition media plus PDT by flow cytometry. Growth of cancer cells were assessed using MTT test. Our findings showed expression of TRAIL on mouse adipose-derived MSCs surfaces. Furthermore, treatment of 4T1 cancer cells with MSCs conditioned media cause to inhibit the cancer cells growth. Also, MSCs conditioned media with PDT have significantly synergic effects to induce apoptosis in breast cancer cells (P photodynamic therapy. This study showed that MSCs conditioned media combined with PDT may be useful as a novel treatment modality into the development of therapeutic strategies for treatment of breast cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Attempt to validate breakpoint MIC values estimated from pharmacokinetic data obtained during oxolinic acid therapy of winter ulcer disease in Atlantic salmon ( Salmo salar )

    DEFF Research Database (Denmark)

    Coyne, R.; Bergh, Ø.; Samuelsen, O.

    2004-01-01

    . On the basis of their behaviour, the fish were classified as healthy (n=18), moribund (n=20), or dead (n=10). There was a dramatic difference in the OXA concentrations in the healthy fish and those classified as moribund or dead. There was no evidence of bacterial infection in the 18 healthy fish, all of which...... administration of OXA. A numerical description of the concentration of the antimicrobial agent achieved in therapy is necessary to determine the resistance or sensitivity of the bacteria involved in the infection. The degree of fish-to-fish variation in the concentrations of OXA, both within the healthy fish...... to the outcome of the therapy and the susceptibility of the bacteria isolated from infected fish....

  4. Cold-knife conization versus photodynamic therapy with topical 5-aminolevulinic acid (5-ALA) in cervical intraepithelial neoplasia (CIN) II with associated human papillomavirus infection: a comparison of preliminary results.

    Science.gov (United States)

    Bodner, Klaus; Bodner-Adler, Barbara; Wierrani, Franz; Kubin, Andreas; Szölts-Szölts, Josef; Spängler, Babette; Grünberger, Werner

    2003-01-01

    The optimal treatment of preinvasive cervical lesions is still not clear as all surgical techniques cause substantial cervical stroma destruction with the risk of a possible incompetent cervix. Photodynamic therapy can preserve fertility due to selective tissue destruction. The aim of the present study was to compare the efficacy of cold-knife conization versus photodynamic therapy with topical 5-aminolevulinic acid in eradicating cervical intraepithelial neoplasia (CIN) II and associated HPV infection. Eleven HPV-positive non-pregnant women were selected for photodynamic therapy (PDT). To be eligible for this procedure superficial cervical PAP smears as well as colposcopic biopsies performed before therapy had to show CIN II with the lesion involving at least 15% of the cervix and being colposcopically visible. The deep endocervical PAP smear had to show normal endocervical epithelium. The next (following each PDT) 11 HPV-positive women with CIN II treated with cold-knife conization were used as a control group. The cervical sampling for HPV DNA was performed 3 months after conization and PDT. Patients were followed-up for 1 year with cytological smears and colposcopy at the outpatient department of the hospital. Follow-up at three months revealed that HPV was eradicated by both techniques in 73%. After 12 months follow-up, 100 vs. 91% (conization vs. PDT) of the patients were disease-free. No systemic side-effects and no local necrosis, sloughing or scarring occurred due to PDT. One patient treated with PDT presented with a relapsing suspicious PAP smear and an abnormal white colposcopic lesion after application of acetic acid 6 months post-PDT. A subsequent conization was performed and revealed a CIN I lesion. No statistically significant differences concerning HPV eradication (p > 0.05) and recurrence (p > 0.05) could be observed between the two methods. The results presented in this study indicate that topical PDT with 5-ALA is in most cases a successful

  5. Feasibility of omega-3 fatty acid supplementation as an adjunct therapy for people with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial

    OpenAIRE

    Fulton, Ashley S; Hill, Alison M.; Williams, Marie T; Howe, Peter RC; Frith, Peter A; Wood, Lisa G.; Garg, Manohar L.; Coates, Alison M.

    2013-01-01

    Background There is evidence to support the use of supplementation with long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) from oily fish or fish oil for the treatment of various inflammatory diseases such as rheumatoid arthritis. Chronic obstructive pulmonary disease (COPD) is a progressive, terminal disease characterized by persistent airflow limitation, lung and systemic inflammation. To date, one randomized controlled trial has been published that assessed the efficacy of LCn-3PUF...

  6. Effect of combination therapy consisting of enalapril, α-lipoic acid, and menhaden oil on diabetic neuropathy in a high fat/low dose streptozotocin treated rat.

    Science.gov (United States)

    Davidson, Eric P; Holmes, Amey; Coppey, Lawrence J; Yorek, Mark A

    2015-10-15

    We have previously demonstrated that treating diabetic rats with enalapril, an angiotensin converting enzyme (ACE) inhibitor, α-lipoic acid, an antioxidant, or menhaden oil, a natural source of omega-3 fatty acids can partially improve diabetic peripheral neuropathy. In this study we sought to determine the efficacy of combining these three treatments on vascular and neural complications in a high fat fed low dose streptozotocin treated rat, a model of type 2 diabetes. Rats were fed a high fat diet for 8 weeks followed by a 30 mg/kg dose of streptozotocin. Eight weeks after the onset of hyperglycemia diabetic rats were treated with a combination of enalapril, α-lipoic acid and menhaden oil. Diabetic rats not receiving treatment were continued on the high fat diet. Glucose clearance was impaired in diabetic rats and significantly improved with treatment. Diabetes caused steatosis, elevated serum lipid levels, slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber profiles, decrease in cornea sub-basal nerve fiber length and corneal sensitivity and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treating diabetic rats with the combination of enalapril, α-lipoic acid and menhaden oil reversed all these deficits to near control levels except for motor nerve conduction velocity which was also significantly improved compared to diabetic rats but remained significantly decreased compared to control rats. These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.

  7. Hyaluronic acid intra-articular injection and exercise therapy: effects on pain and disability in subjects affected by lower limb joints osteoarthritis. A systematic review by the Italian Society of Physical and Rehabilitation Medicine (SIMFER).

    Science.gov (United States)

    Monticone, Marco; Frizziero, Antonio; Rovere, Giancarlo; Vittadini, Filippo; Uliano, Domenico; LA Bruna, Silvano; Gatto, Renato; Nava, Claudia; Leggero, Vittorio; Masiero, Stefano

    2016-06-01

    It is debated whether intra-articular viscosupplementation with hyaluronic acid (HA) can lead to improvements in subjects with osteoarthritis (OA) undergoing physical and rehabilitative interventions. To assess the effects of intra-articular viscosupplementation on disability in subjects with OA undergoing physical and rehabilitative interventions. Information on pain and quality of life were also collected. The databases of PubMed, Medline, EMbase and CINAHL were searched for English language full-text randomized controlled trials comparing intra-articular viscosupplementation alone or associated with physical and rehabilitative interventions to viscosupplementation alone, shame treatment, waiting lists, and any type of rehabilitative interventions. Methodological quality of each study was assessed by using the Physiotherapy Evidence Database (PEDro) Scale. A total of 115 references were retrieved, and 8 studies were selected. Three trials compared HA injection and physical therapy in knee OA, with disability and pain improvements in all studies, and between-group differences in favor of physical therapy in two studies; two trials compared HA injection and home exercises in knee OA, with improvements in pain, disability and quality of life in all studies, without between-group differences; two trials compared HA injection plus physical therapy agents and exercises to exercises plus physical therapy agents in knee OA, with improvements in disability and pain in both studies, and between-group differences in favor of the inclusion HA in one study; one trial compared HA injection and home exercises in ankle OA, with improvements in disability and pain in both arms without between-group differences. Physical therapy agents seemed to have greater effects than intra-articular viscosupplementation on disability and pain. In the other cases both intra-articular viscosupplementation and physical and rehabilitative interventions seemed to be equally effective in improving

  8. Effects and feasibility of exercise therapy combined with branched-chain amino acid supplementation on muscle strengthening in frail and pre-frail elderly people requiring long-term care: a crossover trial.

    Science.gov (United States)

    Ikeda, Takashi; Aizawa, Junya; Nagasawa, Hiroshi; Gomi, Ikuko; Kugota, Hiroyuki; Nanjo, Keigo; Jinno, Tetsuya; Masuda, Tadashi; Morita, Sadao

    2016-04-01

    This study examined the effects and feasibility of a twice-weekly combined therapy of branched-chain amino acids (BCAAs) and exercise on physical function improvement in frail and pre-frail elderly people requiring long-term care. We used a crossover design in which the combination of exercise and nutritional interventions was carried out twice a week during cycles A (3 months) and B (3 months) and the exercise intervention alone was performed during the washout period. The exercise intervention entailed the following 5 training sets: 3 sets of muscle training at 30% of maximum voluntary contraction, 1 set of aerobic exercise, and 1 set of balance training. For the nutritional intervention, 6 g of BCAAs or 6 g of maltodextrin was consumed 10 min before starting the exercise. We determined upper and lower limb isometric strength, performance on the Functional Reach Test (FRT) and the Timed Up and Go test, and activity level. In the comparison between the BCAA group and the control group after crossover, the improvement rates in gross lower limb muscle strength (leg press, knee extension) and FRT performance were significantly greater (by approximately 10%) in the BCAA group. In the comparison between different orders of BCAA administration, significant effects were shown for the leg press in both groups only when BCAAs were given. The combination of BCAA intake and exercise therapy yielded significant improvements in gross lower limb muscle strength and dynamic balance ability.

  9. Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer.

    Science.gov (United States)

    Coleman, R; Woodward, E; Brown, J; Cameron, D; Bell, R; Dodwell, D; Keane, M; Gil, M; Davies, C; Burkinshaw, R; Houston, S J; Grieve, R J; Barrett-Lee, P J; Thorpe, H

    2011-06-01

    The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3-1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.

  10. AS1411 aptamer and folic acid functionalized pH-responsive ATRP fabricated pPEGMA-PCL-pPEGMA polymeric nanoparticles for targeted drug delivery in cancer therapy.

    Science.gov (United States)

    Lale, Shantanu V; R G, Aswathy; Aravind, Athulya; Kumar, D Sakthi; Koul, Veena

    2014-05-12

    Nonspecificity and cardiotoxicity are the primary limitations of current doxorubicin chemotherapy. To minimize side effects and to enhance bioavailability of doxorubicin to cancer cells, a dual-targeted pH-sensitive biocompatible polymeric nanosystem was designed and developed. An ATRP-based biodegradable triblock copolymer, poly(poly(ethylene glycol) methacrylate)-poly(caprolactone)-poly(poly(ethylene glycol) methacrylate) (pPEGMA-PCL-pPEGMA), conjugated with doxorubicin via an acid-labile hydrazone bond was synthesized and characterized. Dual targeting was achieved by attaching folic acid and the AS1411 aptamer through EDC-NHS coupling. Nanoparticles of the functionalized triblock copolymer were prepared using the nanoprecipitation method, resulting in an average particle size of ∼140 nm. The biocompatibility of the nanoparticles was evaluated using MTT cytotoxicity assays, blood compatibility studies, and protein adsorption studies. In vitro drug release studies showed a higher cumulative doxorubicin release at pH 5.0 (∼70%) compared to pH 7.4 (∼25%) owing to the presence of the acid-sensitive hydrazone linkage. Dual targeting with folate and the AS1411 aptamer increased the cancer-targeting efficiency of the nanoparticles, resulting in enhanced cellular uptake (10- and 100-fold increase in uptake compared to single-targeted NPs and non-targeted NPs, respectively) and a higher payload of doxorubicin in epithelial cancer cell lines (MCF-7 and PANC-1), with subsequent higher apoptosis, whereas a normal (noncancerous) cell line (L929) was spared from the adverse effects of doxorubicin. The results indicate that the dual-targeted pH-sensitive biocompatible polymeric nanosystem can act as a potential drug delivery vehicle against various epithelial cancers such as those of the breast, ovary, pancreas, lung, and others.

  11. Non-viral gene delivery strategies for gene therapy: a 'menage a trois' among nucleic acids, materials, and the biological environment

    Energy Technology Data Exchange (ETDEWEB)

    Pezzoli, Daniele; Candiani, Gabriele, E-mail: gabriele.candiani@polimi.it [INSTM (National Interuniversity Consortium of Materials Science and Technology), Research Unit Milano Politecnico (Italy)

    2013-03-15

    Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription-translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors.

  12. Family Therapy

    Science.gov (United States)

    ... may be credentialed by the American Association for Marriage and Family Therapy (AAMFT). Family therapy is often short term. ... challenging situations in a more effective way. References Marriage and family therapists: The friendly mental health professionals. American Association ...

  13. Hormone Therapy

    Science.gov (United States)

    ... types of estrogen therapy relieve vaginal dryness. • Systemic estrogen protects against the bone loss that occurs early in menopause and helps prevent hip and spine fractures. • Combined estrogen and progestin therapy may reduce the risk of ...

  14. Radiation Therapy

    Science.gov (United States)

    ... the area is stitched shut. Another treatment, called proton-beam radiation therapy , focuses the radiation on the ... after radiation treatment ends. Sore mouth and tooth decay. If you received radiation therapy to the head ...

  15. Electroconvulsive therapy

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007474.htm Electroconvulsive therapy To use the sharing features on this page, please enable JavaScript. Electroconvulsive therapy (ECT) uses an electric current to treat depression ...

  16. Proton Therapy

    Science.gov (United States)

    ... IMRT) Brain Tumor Treatment Brain Tumors Prostate Cancer Lung Cancer Treatment Lung Cancer Head and Neck Cancer Images related to Proton Therapy Videos related to Proton Therapy Sponsored by Please ...

  17. In vitro study of 5-aminolevulinic acid-based photodynamic therapy for apoptosis in human cervical HeLa cell line

    Science.gov (United States)

    Atif, M.; Firdous, S.; Khurshid, A.; Noreen, L.; Zaidi, S. S. Z.; Ikram, M.

    2009-12-01

    5-aminolevulanic acid (ALA), belonging among the promising second generation of sensitizers, was evaluated as an inducer of photodamage on HeLa (human cervical adenocarcinoma) cell line. A diode laser (635 nm) was used as a source for initiation of the photodynamic effect. We studied the influence of different incubation times, various concentrations of sensitizer, different irradiation doses and various combinations of sensitizer and light doses on the photodamage of HeLa cells. Viability of cells was determined by means of neutral red assay. The quantitative cellular uptake of ALA sensitizer was done by spectrophotometric measurements. No prominent cytotoxic or phototoxic effects on HeLa were observed due to sensitizer or light doses when studied independently of each other. However phototoxicity evoked by laser irradiated sensitizer was detected in HeLa cell line.

  18. Enriched cultures of lactic acid bacteria from selected Zimbabwean fermented food and medicinal products with potential as therapy or prophylaxis against yeast infections

    Directory of Open Access Journals (Sweden)

    Alec Chabwinja

    2017-10-01

    Full Text Available Objective: To investigate the antifungal activity of crude cultures of putative strains of lactic acid bacteria (LAB from a selection of Zimbabwean traditional and commercial food/ medicinal products against yeasts (strains of environmental isolates of Candida albicans and Rhodotorula spp.. Methods: Cultures of putative LAB from our selection of fermented products were enriched in de Man, Rogosa and Sharpe and isolated on de Man, Rogosa and Sharpe agar. Results: The crude microbial cultures from the products that showed high antifungal activities (zone of inhibition, mm were as follows: supernatant-free microbial pellet (SFMP from an extract of Melia azedarach leaves [(27.0 ± 2.5 mm] > cell-free culture supernatants (CFCS from Maaz Dairy sour milk and Mnandi sour milk [approximately (26.0 ± 1.8/2.5 mm] > CFCS and SFMP from Amansi hodzeko [(25.0 ± 1.5 mm] > CFCS from Parinari curatellifolia fruit [(24.0 ± 1.5 mm], SFMP from Parinari curatellifolia fruit [(24.0 ± 1.4 mm] and SFMP from mahewu [(20.0 ± 1.5 mm]. These cultures also showed high tolerance to acidic conditions (pH 4.0 and pH 5.0. However, culture from WAYA LGG (shown elsewhere to harbour antimicrobial activities showed no antifungal activity. The LAB could have inhibited yeasts by either competitive exclusion or the release of antimicrobial metabolites. Conclusions: Our cultures of LAB from a selection of Zimbabwean fermented products, especially Ziziphus mauritiana and fermented milk products have great potential for use as antifungal probiotics against yeast infections. Studies are ongoing to determine the exact mechanisms that are employed by the putative LAB to inhibit Candida albicans.

  19. Feminist Therapy.

    Science.gov (United States)

    Laidlaw, Toni; Malmo, Cheryl

    1991-01-01

    Traces roots of feminist therapy and its independence from traditional and prevalent theories and therapy practices. Asserts that Freudian theory and humanistic assumptions are sexist and contribute to powerlessness of women. In contrast, feminist therapy is seen as dealing directly with client-counselor relationships, trust, advocacy, and…

  20. Medical nutrition therapy: use of sourdough lactic acid bacteria as a cell factory for delivering functional biomolecules and food ingredients in gluten free bread

    Directory of Open Access Journals (Sweden)

    Moroni Alice

    2011-08-01

    Full Text Available Abstract Celiac disease (CD is an immune-mediated disease, triggered in genetically susceptible individuals by ingesting gluten from wheat, rye, barley, and other closely related cereal grains. Currently, the estimated prevalence of CD is around 1 % of the population in the western world and medical nutritional therapy (MNT is the only accepted treatment for celiac disease. To date, the replacement of gluten in bread presents a significant technological challenge for the cereal scientist due to the low baking performance of gluten free products (GF. The increasing demand by the consumer for high quality gluten-free (GF bread, clean labels and natural products is rising. Sourdough has been used since ancient times for the production of rye and wheat bread, its universal usage can be attributed to the improved quality, nutritional properties and shelf life of sourdough based breads. Consequently, the exploitation of sourdough for the production of GF breads appears tempting. This review will highlight how sourdough LAB can be an efficient cell factory for delivering functional biomolecules and food ingredients to enhance the quality of gluten free bread.

  1. Medical nutrition therapy: use of sourdough lactic acid bacteria as a cell factory for delivering functional biomolecules and food ingredients in gluten free bread

    LENUS (Irish Health Repository)

    2011-08-30

    Abstract Celiac disease (CD) is an immune-mediated disease, triggered in genetically susceptible individuals by ingesting gluten from wheat, rye, barley, and other closely related cereal grains. Currently, the estimated prevalence of CD is around 1 % of the population in the western world and medical nutritional therapy (MNT) is the only accepted treatment for celiac disease. To date, the replacement of gluten in bread presents a significant technological challenge for the cereal scientist due to the low baking performance of gluten free products (GF). The increasing demand by the consumer for high quality gluten-free (GF) bread, clean labels and natural products is rising. Sourdough has been used since ancient times for the production of rye and wheat bread, its universal usage can be attributed to the improved quality, nutritional properties and shelf life of sourdough based breads. Consequently, the exploitation of sourdough for the production of GF breads appears tempting. This review will highlight how sourdough LAB can be an efficient cell factory for delivering functional biomolecules and food ingredients to enhance the quality of gluten free bread.

  2. Medical nutrition therapy: use of sourdough lactic acid bacteria as a cell factory for delivering functional biomolecules and food ingredients in gluten free bread.

    Science.gov (United States)

    Arendt, Elke K; Moroni, Alice; Zannini, Emanuele

    2011-08-30

    Celiac disease (CD) is an immune-mediated disease, triggered in genetically susceptible individuals by ingesting gluten from wheat, rye, barley, and other closely related cereal grains. Currently, the estimated prevalence of CD is around 1 % of the population in the western world and medical nutritional therapy (MNT) is the only accepted treatment for celiac disease. To date, the replacement of gluten in bread presents a significant technological challenge for the cereal scientist due to the low baking performance of gluten free products (GF). The increasing demand by the consumer for high quality gluten-free (GF) bread, clean labels and natural products is rising. Sourdough has been used since ancient times for the production of rye and wheat bread, its universal usage can be attributed to the improved quality, nutritional properties and shelf life of sourdough based breads. Consequently, the exploitation of sourdough for the production of GF breads appears tempting. This review will highlight how sourdough LAB can be an efficient cell factory for delivering functional biomolecules and food ingredients to enhance the quality of gluten free bread.

  3. Lactic Acid Bacteria in Health and Disease

    African Journals Online (AJOL)

    reports demonstrating the health promoting effects of ... therapy. In 1908, élie Metchinkoff, proposed that the acid-producing organisms (lactic acid bacteria) ... Phage resistance aids in .... In a study conducted [29] in children aged 3 it was found.

  4. 5-aminolevulinic acid-mediated photodynamic therapy combined with CO2 laser therapy in treatment of condyloma acuminatum%5-氨基酮戊酸光动力疗法联合二氧化碳激光治疗尖锐湿疣的疗效观察

    Institute of Scientific and Technical Information of China (English)

    顾俊瑛; 史玉玲; 李秀丽; 李晓建; 刘至昱; 高飞

    2011-01-01

    目的 比较5-氨基酮戊酸光动力疗法(5-aminolevulinic acid-mediated photodynamic therapy,ALA-PDT)和二氧化碳( CO2)激光治疗尖锐湿疣(CA)的临床疗效.方法 将同济大学附属第十人民医院皮肤科2010年4月至2010年12月就治的111例尖锐湿疣患者分为3组,第一组为特殊部位(尿道口、系带或宫颈部位)的疣体患者,共17例,单用ALA-PDT治疗;余94例患者随机分为两组,每组47例,分别采用ALA-PDT联合CO2激光治疗和单一CO2激光治疗.ALA-PDT每周治疗1次,3次为1个疗程.CO2激光治疗根据疣体大小一次或分次清除疣体.3组患者治疗结束后每1、2、3个月分别电话随访一次.结果 单用ALA-PDT组一个疗程结束后的清除率为93.4%(16/17),3个月后总复发率为11.8%(2/17).联合治疗组和CO2激光单一治疗组3个月后的总复发率分别为14.9%(7/47)和55.3%(26/47),差异有统计学意义(x2=16.857,P<0.001).结论 ALA-PDT联合CO2激光治疗CA疗效确切,复发率低;ALA-PDT可有效治疗特殊部位的疣体,临床适用范围广.%Objective To evaluate the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) combined with CO2 laser therapy in treatment of condyloma acuminatum. Methods One hundred and eleven patients with condyloma acuminatum admitted from April to December 2010 were enrolled in the study. Seventeen cases whose condylomas are at urethral orifice, vinculum or cervix uteri were treated with ALA-PDT alone. Other 94 cases were randomly assigned into two groups with 47 in each, who were treated by ALA-PDT combined with CO2 laser therapy or CO2 laser alone, respectively. Results The clearance rate was 93. 4% (16/17) and the relapse rate was 11.8% (2/17) in patients treated with ALA-PDT alone. The relapse rates of ALA-PDT combined with CO2 laser and CO2 laser alone were 14. 9% (7/47 ) and 55. 3% (26/47 ) , respectively (x2 = 16. 857, P < 0. 001). Conclusion ALA-PDT is effective in treatment of condyloma

  5. Nanoparticles deliver RNAi therapy

    Directory of Open Access Journals (Sweden)

    Martin C. Woodle

    2005-08-01

    Full Text Available Nanotechnology-based advanced materials are rapidly expanding development of better medicines. Long-standing efforts with lipid and polymer colloidal delivery systems, i.e. nanoparticles, have yielded better imaging and therapy. These benefits of nanotechnology, though limited, have driven efforts to develop advanced nanoparticles. This is particularly the case for targeted nucleic acid (gene therapeutics based on short interfering ribonucleic acid (siRNA, which is a new gene inhibitor that is highly potent and selective. Here, we evaluate the use of modular conjugates to construct targeted nanoparticle therapeutics for nucleic acids. These nanoparticles are beginning to emulate the sophistication of virus particles – nature's own nanoscale assemblies for nucleic acids. For medicine, they promise the creation of a new generation of ‘targeted’ therapeutics that can offer multiple levels of selectivity.

  6. Inhibition of VDAC1 prevents Ca²⁺-mediated oxidative stress and apoptosis induced by 5-aminolevulinic acid mediated sonodynamic therapy in THP-1 macrophages.

    Science.gov (United States)

    Chen, Haibo; Gao, Weiwei; Yang, Yang; Guo, Shuyuan; Wang, Huan; Wang, Wei; Zhang, Shuisheng; Zhou, Qi; Xu, Haobo; Yao, Jianting; Tian, Zhen; Li, Bicheng; Cao, Wenwu; Zhang, Zhiguo; Tian, Ye

    2014-12-01

    Ultrasound combined with endogenous protoporphyrin IX derived from 5-aminolevulinic acid (ALA-SDT) is known to induce apoptosis in multiple cancer cells and macrophages. Persistent retention of macrophages in the plaque has been implicated in the pathophysiology and progression of atherosclerosis. Here we investigated the effects of inhibition of voltage-dependent anion channel 1 (VDAC1) on ALA-SDT-induced THP-1 macrophages apoptosis. Cells were pre-treated with VDAC1 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) disodium salt for 1 h or downregulated VDAC1 expression by small interfering RNA and exposed to ultrasound. Cell viability was assessed by MTT assay, and cell apoptosis along with necrosis was evaluated by Hoechst 33342/propidium iodide staining and flow cytometry. Levels of cytochrome c release was assessed by confocal microscope and Western blot. The levels of full length caspases, caspase activation, and VDAC isoforms were analyzed by Western blot. Intracellular reactive oxygen species generation, mitochondrial membrane permeability, and intracellular Ca(2+) [Ca(2+)]i levels were measured with fluorescent probes. We confirmed that the pharmacological inhibition of VDAC1 by DIDS notably prevented ALA-SDT-induced cell apoptosis in THP-1 macrophages. Additionally, DIDS significantly inhibited intracellular ROS generation and apoptotic biochemical changes such as inner mitochondrial membrane permeabilization, loss of mitochondrial membrane potential, cytochrome c release and activation of caspase-3 and caspase-9. Moreover, ALA-SDT elevated the [Ca(2+)]i levels and it was also notably reduced by DIDS. Furthermore, both of intracellular ROS generation and cell apoptosis were predominately inhibited by Ca(2+) chelating reagent BAPTA-AM. Intriguingly, ALA-treatment markedly augmented VDAC1 protein levels exclusively, and the downregulation of VDAC1 expression by specific siRNA also significantly abolished cell apoptosis. Altogether, these

  7. Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study.

    Science.gov (United States)

    Sundy, John S; Schumacher, H Ralph; Kivitz, Alan; Weinstein, Steven P; Wu, Richard; King-Davis, Shirletta; Evans, Robert R

    2014-08-01

    To evaluate the safety and efficacy of once-weekly subcutaneous rilonacept 160 mg for prevention of gout flares in patients initiating or continuing urate-lowering therapy (ULT). This phase III study was conducted in the United States, South Africa, Europe, and Asia. Adults (n = 1315, 18-80 yrs) with gout, who were initiating or continuing ULT, were randomized to treatment with weekly subcutaneous injections of rilonacept 160 mg or placebo for 16 weeks followed by a 4-week safety followup. The primary endpoint was safety, assessed by adverse events (AE) and laboratory values. Efficacy was a secondary endpoint. Demographic and clinical characteristics were similar between treatments; predominantly male (87.8%), mean age 52.7 ± 11.3 years. Patients with ≥ 1 AE were 66.6% with rilonacept versus 59.1% placebo, with slightly more AE-related withdrawals with rilonacept (4.7% vs 3.0%) because of the greater incidence of injection site reactions (15.2% rilonacept, 3.3% placebo). Serious AE were similar in both groups, as were serious infections (0.9% placebo, 0.5% rilonacept); no tuberculosis or opportunistic infections occurred. Most common AE were headache, arthralgia, injection site erythema, accidental overdose, and pain in extremity. Of the 6 deaths, only 1 in the placebo group was considered treatment-related. At Week 16, rilonacept resulted in 70.3% fewer gout flares per patient (p gout flares (p gout flare days (p gout flares. Clinicaltrials.gov identifier NCT00856206; EudraCT No. 2008-007784-16.

  8. What Is Music Therapy?

    Science.gov (United States)

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login About Music Therapy & AMTA What is Music Therapy? Definition and ... is Music Therapy? Print Email Share What is Music Therapy What is Music Therapy? Music Therapy is ...

  9. Post-ischaemic angiogenic therapy using in vivo prevascularized ascorbic acid-enriched myocardial artificial grafts improves heart function in a rat model.

    Science.gov (United States)

    Martinez, Eliana C; Wang, Jing; Lilyanna, Shera; Ling, Lieng H; Gan, Shu U; Singh, Rajeev; Lee, Chuen N; Kofidis, Theo

    2013-03-01

    Angiogenesis plays a key role in post-ischaemic myocardial repair. We hypothesized that epicardial implantation of an ascorbic acid (AA)-enriched myocardial artificial graft (MAG), which has been prevascularized in the recipients' own body, promotes restoration of the ischaemic heart. Gelatin patches were seeded with GFP-luciferase-expressing rat cardiomyoblasts and enriched with 5 μm AA. Grafts were prevascularized in vivo for 3 days, using a renal pouch model in rats. The MAG patch was then implanted into the same rat's ischaemic heart following myocardial infarction (MI). MAG-treated animals (MAG group, n = 6) were compared to untreated infarcted animals as injury controls (MI group, n = 6) and sham-operated rats as healthy controls (healthy group, n = 7). In vivo bioluminescence imaging indicated a decrease in donor cell survival by 83% during the first week post-implantation. Echocardiographic and haemodynamic assessment 4 weeks after MI revealed that MAG treatment attenuated left ventricular (LV) remodelling (LV end-systolic volume, 0.31 ± 0.13 vs 0.81 ± 0.01 ml, p hearts, attenuated LV remodelling and preserved LV function.

  10. Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles.

    Science.gov (United States)

    Wang, Lei; Hao, Yongwei; Li, Haixia; Zhao, Yalin; Meng, Dehui; Li, Dong; Shi, Jinjin; Zhang, Hongling; Zhang, Zhenzhong; Zhang, Yun

    2015-01-01

    It is very challenging to treat brain cancer because of the blood-brain barrier (BBB) restricting therapeutic drug or gene to access the brain. In this research project, angiopep-2 (ANG) was used as a brain-targeted peptide for preparing multifunctional ANG-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which encapsulated both doxorubicin (DOX) and epidermal growth factor receptor (EGFR) siRNA, designated as ANG/PLGA/DOX/siRNA. This system could efficiently deliver DOX and siRNA into U87MG cells leading to significant cell inhibition, apoptosis and EGFR silencing in vitro. It demonstrated that this drug system was capable of penetrating the BBB in vivo, resulting in more drugs accumulation in the brain. The animal study using the brain orthotopic U87MG glioma xenograft model indicated that the ANG-targeted co-delivery of DOX and EGFR siRNA resulted in not only the prolongation of the life span of the glioma-bearing mice but also an obvious cell apoptosis in glioma tissue.

  11. Efficient siRNA delivery and tumor accumulation mediated by ionically cross-linked folic acid-poly(ethylene glycol)-chitosan oligosaccharide lactate nanoparticles: for the potential targeted ovarian cancer gene therapy.

    Science.gov (United States)

    Li, Tony Shing Chau; Yawata, Toshio; Honke, Koichi

    2014-02-14

    For effective ovarian cancer gene therapy, systemic administrated tumor-targeting siRNA/folic acid-poly(ethylene glycol)-chitosan oligosaccharide lactate (FA-PEG-COL) nanoparticles is vital for delivery to cancer site(s). siRNA/FA-PEG-COL nanoparticles were prepared by ionic gelation for effective FA receptor-expressing ovarian cancer cells transfection and in vivo accumulation. The chemical structure of FA-PEG-COL conjugate was characterized by MALDI-TOF-MS, FT-IR and (1)H NMR. The average size of siRNA/FA-PEG-COL nanoparticles was approximately 200 nm, and the surface charge was +8.4 mV compared to +30.5 mV with siRNA/COL nanoparticles. FA-PEG-COL nanoparticles demonstrated superior compatibility with erythrocytes in terms of degree of aggregation and haemolytic activity and also effects on cell viability was lower when compared with COL nanoparticles. FA grafting significantly facilitated the uptake of nanoparticles via receptor mediated endocytosis as demonstrated by flow cytometry. The in vitro transfection and gene knockdown efficiency of HIF-1α were superior to COL nanoparticles (76-62%, respectively) and was comparable to Lipofectamine 2000 (79%) as demonstrated by RT-qPCR and Western blot. Gene knockdown at the molecular level translated into effective inhibition of proliferation in vitro. Accumulation efficiency of FA-PEG-COL nanoparticles was investigated in BALB/c mice bearing OVK18 #2 tumor xenograft using in vivo imaging. The active targeting FA-PEG-COL nanoparticles showed significantly greater accumulation than the passive targeting COL nanoparticles. Based on the results obtained, siRNA/FA-PEG-COL nanoparticles show much potential for effective ovarian cancer treatment via gene therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Surface modification of biomaterials based on high-molecular polylactic acid and their effect on inflammatory reactions of primary human monocyte-derived macrophages: perspective for personalized therapy.

    Science.gov (United States)

    Stankevich, Ksenia S; Gudima, Alexandru; Filimonov, Victor D; Klüter, Harald; Mamontova, Evgeniya M; Tverdokhlebov, Sergei I; Kzhyshkowska, Julia

    2015-06-01

    Polylactic acid (PLA) based implants can cause inflammatory complications. Macrophages are key innate immune cells that control inflammation. To provide higher biocompatibility of PLA-based implants with local innate immune cells their surface properties have to be improved. In our study surface modification technique for high-molecular PLA (MW=1,646,600g/mol) based biomaterials was originally developed and successfully applied. Optimal modification conditions were determined. Treatment of PLA films with toluene/ethanol=3/7 mixture for 10min with subsequent exposure in 0.001M brilliant green dye (BGD) solution allows to entrap approximately 10(-9)mol/cm(2) model biomolecules. The modified PLA film surface was characterized by optical microscopy, SERS, FT-IR, UV and TG/DTA/DSC analysis. Tensile strain of modified films was determined as well. The effect of PLA films modified with BGD on the inflammatory reactions of primary human monocyte-derived macrophages was investigated. We developed in vitro test-system by differentiating primary monocyte-derived macrophages on a coating material. Type 1 and type 2 inflammatory cytokines (TNFα, CCL18) secretion and histological biomarkers (CD206, stabilin-1) expression were analyzed by ELISA and confocal microscopy respectively. BGD-modified materials have improved thermal stability and good mechanical properties. However, BGD modifications induced additional donor-specific inflammatory reactions and suppressed tolerogenic phenotype of macrophages. Therefore, our test-system successfully demonstrated specific immunomodulatory effects of original and modified PLA-based biomaterials, and can be further applied for the examination of improved coatings for implants and identification of patient-specific reactions to implants.

  13. Effect of combination therapy of fatty acids, calcium, vitamin D and boron with regular physical activity on cardiovascular risk factors in rat.

    Science.gov (United States)

    Naghii, M R; Darvishi, P; Ebrahimpour, Y; Ghanizadeh, G; Mofid, M; Hedayati, M; Asgari, A R

    2012-01-01

    The effect of consumption of fatty acids and selected nutrients, along with regular physical activity, on cardiovascular risk factors in rats was investigated.Male rats were divided into the seven groups: Group 1: regular food and drinking water, Group 2: same as Group. 1 + physical activity (whole body vibration; WBV), Group 3: same as Group. 2 + calcium, vitamin D, boron, Group 4: same as Group. 3 + canola oil, Group 5: same as Group. 3 + sunflower oil, Group 6: same as Group. 3 + mix of sunflower oil and canola oil, Group 7: same as Group. 3 + coconut oil. Rats were treated for 8 weeks, and analysis of the frozen plasmas was performed. A- Analysis between the treatment groups and control revealed that vibration training in Group 2 increased body weight (P = 0.04), plasma creatin kinase (CK), (P = 0.02), and estradiol (E2), (P = 0.03). Rats in Group 5 consumed less food and plasma levels of cholesterol and LDL-cholesterol (LDL-C) increased significantly (P = 0.02) in Group 6 and in Group 7 (poil consuming groups) and Group 3 revealed significant differences in cholesterol (Chol), LDL-C, HDL-cholesterol (HDL-C), triglycerides (TG), C- reactive protein (hs-CRP), estradiol (E2), atherogenic index (AI), and risk factor (RF), (phealth status by influencing cardiovascular disease (CVD) risk factors. Moreover, canola oil and sunflower oil, separately, showed beneficial impacts on CVD risk factors; whereas their combination had negative impacts on lipid profile. Coconut oil revealed to be efficient to provide health benefits in terms of CVD treatments.

  14. During Hepatitis C Virus (HCV) Infection and HCV-HIV Coinfection, an Elevated Plasma Level of Autotaxin Is Associated With Lysophosphatidic Acid and Markers of Immune Activation That Normalize During Interferon-Free HCV Therapy.

    Science.gov (United States)

    Kostadinova, Lenche; Shive, Carey L; Judge, Chelsey; Zebrowski, Elizabeth; Compan, Anita; Rife, Kelsey; Hirsch, Amy; Falck-Ytter, Yngve; Schlatzer, Daniela M; Li, Xiaolin; Chance, Mark R; Rodriguez, Benigno; Popkin, Daniel L; Anthony, Donald D

    2016-11-01

     Immune activation predicts morbidity during hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection, although mechanisms underlying immune activation are unclear. Plasma levels of autotaxin and its enzymatic product, lysophosphatidic acid (LPA), are elevated during HCV infection, and LPA activates immunocytes, but whether this contributes to immune activation is unknown.  We evaluated plasma levels of autotaxin, interleukin 6 (IL-6), soluble CD14 (sCD14), soluble CD163 (sCD163), and Mac2 binding protein (Mac2BP) during HCV infection, HIV infection, and HCV-HIV coinfection, as well as in uninfected controls, before and after HIV antiretroviral therapy (ART) initiation and during interferon-free HCV therapy.  We observed greater plasma autotaxin levels in HCV-infected and HCV-HIV-coinfected participants, compared with uninfected participants, primarily those with a higher ratio of aspartate aminotransferase level to platelet count. Autotaxin levels correlated with IL-6, sCD14, sCD163, Mac2BP, and LPA levels in HCV-infected participants and with Mac2BP levels in HCV-HIV-coinfected participants, while in HIV-infected individuals, sCD14 levels correlated with Mac2BP levels. Autotaxin, LPA, and sCD14 levels normalized, while sCD163 and Mac2BP levels partially normalized within 6 months of starting interferon-free HCV therapy. sCD163 and IL-6 levels normalized within 6 months of starting ART for HIV infection. In vitro, LPA activated monocytes.  These data indicate that elevated levels of autotaxin and soluble markers of immune activation during HCV infection are partially reversible within 6 months of initiating interferon-free HCV treatment and that autotaxin may be causally linked to immune activation during HCV infection and HCV-HIV coinfection. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. [Dietary therapy of epilepsy].

    Science.gov (United States)

    Imai, Katsumi; Ishihara, Eiko; Ikeda, Hiroko

    2014-05-01

    Reappraisal of ketogenic diets (KD) were delayed in Japan compared to USA and Korea. The reasons are unknown, but possible explanations are (1) Japanese food culture prefers rice and less fat and (2) ACTH therapy is preferred for West syndrome in Japan. Since Japanese child neurologists were surprised at dramatic effects on glucose transporter 1 deficiency syndrome (Glut-1DS) in 2003, KD have been slowly accepted for treatment of epilepsy in Japan. New generation KD including modified Atkins diet (mAD) are preferred to classical KD. KD can be causal therapy in Glut-1DS and some of mitochondrial disorders, though anti-epileptic drugs are symptomatic therapy. KD can alleviate intractable seizures in epilepsies with brain malformation in addition to West syndrome and Dravet syndrome, etc. KD may work for brain tumor, cancer, neurodegenerative disorders including Alzheimer's disease. C7-8 triglycerides or fatty acid esters are under development as medicines replacing KD.

  16. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy

    Science.gov (United States)

    Chu, Qiuchen; Xu, Hong; Gao, Meng; Guan, Xin; Liu, Hongyan; Deng, Sa; Huo, Xiaokui; Liu, Kexin; Tian, Yan; Ma, Xiaochi

    2016-01-01

    Liver cancer remains a major problem around the world. Resibufogenin (RBG) is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison), which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid) (PLGA)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN) to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN), and RBG/coumarin-6-loaded PLGA-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN) were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS), and 5-fluorouracil solution (used as the negative controls), as assayed using flow cytometry. LD50 (median lethal dose) values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in anticancer efficacy, and RPTN performed much better than RPN. The detection indexes for drug concentration and fluorescence inversion microscopy images both demonstrated that RCPTN was much better at targeting the liver than RS. The liver-targeting RPTN, which displayed enhanced pharmacological effects and

  17. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy

    Directory of Open Access Journals (Sweden)

    Chu QC

    2016-01-01

    Full Text Available Qiuchen Chu,1,* Hong Xu,2,* Meng Gao,1 Xin Guan,1 Hongyan Liu,1 Sa Deng,1 Xiaokui Huo,1 Kexin Liu,1 Yan Tian,1 Xiaochi Ma1 1College of Pharmacy, 2College of Basic Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China *These authors contributed equally to this work Abstract: Liver cancer remains a major problem around the world. Resibufogenin (RBG is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison, which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid (PLGA-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN, and RBG/coumarin-6-loaded PLGA-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS, and 5-fluorouracil solution (used as the negative controls, as assayed using flow cytometry. LD50 (median lethal dose values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in

  18. Pharmacokinetics, biodistribution and in vivo efficacy of cisplatin loaded poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) complex nanoparticles for tumor therapy.

    Science.gov (United States)

    Yu, Haiyang; Tang, Zhaohui; Zhang, Dawei; Song, Wantong; Zhang, Ying; Yang, Yan; Ahmad, Zaheer; Chen, Xuesi

    2015-05-10

    Platinum-based polymeric nano-drugs, especially cisplatin-loaded polymeric nanoparticles (CDDP-NPs), have been extensively exploited for the treatment of solid tumors. However, it is still unclear what role the processing procedure and the properties of the polymeric carrier materials may play in influencing the plasma pharmacokinetics, biodistribution and in vivo efficacy of CDDP-NPs. In this study, a series of poly(l-glutamic acid)-g-methoxy poly(ethylene glycol) (PLG-g-mPEG) copolymers were synthesized for the preparation of CDDP-loaded PLG-g-mPEG (CDDP/PLG-g-mPEG) nanoparticles. All of the parameters, including PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length, ultrafiltration purification and cisplatin loading content, were found to have a significant influence on the plasma pharmacokinetics of the CDDP/PLG-g-mPEG nanoparticles. The blood circulation time of the nanoparticles was prolonged with increases in PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length and CDDP loading content. The use of ultrafiltration purification could prolong the blood circulation time of the nanoparticles as well. Experiments to measure the pharmacokinetics and biodistribution demonstrated that the selected CDDP/PLG-g-mPEG nanoparticles, NP10, had a long blood circulation time and could achieve selective and significant accumulation in Lewis lung carcinoma (LLC) tumors. The platinum plasma concentrations in the LLC tumor-bearing mice receiving NP10 remained up to 46-fold higher than that of mice receiving equivalent doses of free CDDP. In addition, the plasma area under the concentration time curve (AUC) of NP10 was 31-fold higher than that of free CDDP in 48h. The platinum concentration ratio of NP10 to free CDDP in tumors reached as high as 9.4. The tumor AUC ratio of NP10 to CDDP was 6. Using a mouse C26 tumor model, here we demonstrate that NP10 improves the safety and tolerance in vivo when compared to CDDP and effectively inhibits the growth of C26

  19. Acidic deposition ("acid rain")

    Science.gov (United States)

    Schreiber, R. Kent; LaRoe, Edward T.; Farris, Gaye S.; Puckett, Catherine E.; Doran, Peter D.; Mac, Michael J.

    1995-01-01

    Acidic deposition, or "acid rain," describes any form of precipitation, including rain, snow, and fog, with a pH of 5.5 or below (Note: pH values below 7 are acidic; vinegar has a pH of 3). It often results when the acidity of normal precipitation is increased by sulfates and nitrates that are emitted into the atmosphere from burning fossil fuels. This form of airborne contamination is considered harmful, both directly and indirectly, to a host of plant and animal species.Although acid rain can fall virtually anywhere, ecological damages in environmentally sensitive areas downwind of industrial and urban emissions are a major concern. This includes areas that have a reduced capacity to neutralize acid inputs because of low alkalinity soils and areas that contain species with a low tolerance to acid conditions. To determine the distribution of acidic deposition and evaluate its biological effects, research and monitoring are being conducted by the federal government with support from states, universities, and private industry.            The national extent of the acid rain problem has been estimated by sampling water from 3,000 lakes and 500 streams (Irving 1991), representing more than 28,000 lakes and 56,000 stream reaches with a total of 200,000 km (125,000 mi). Some particularly sensitive areas, such as the Adirondack Mountain region, have been more intensively sampled and the biota examined in detail for effects from acidity.         To identify trends in aquatic ecosystems, present and historical survey data on water chemistry and associated biota are compared. In lakes, the chemical and biological history and pH trends may be inferred or reconstructed in some cases by examining assemblages of fossil diatoms and aquatic invertebrates in the sediment layers. In terrestrial ecosystems, vegetation damage is surveyed and effects of acidic deposition to plants and animals are determined from laboratory and field exposure experiments. Natural

  20. Fusidic acid in dermatology

    DEFF Research Database (Denmark)

    Schöfer, Helmut; Simonsen, Lene

    1995-01-01

    efficacy and tolerability. Similarly, plain fusidic acid cream or ointment used two or three times daily in SSTIs such as impetigo are clinically and bacteriologically effective, with minimal adverse events. Combination formulations of fusidic acid with 1% hydrocortisone or 0.1% betamethasone achieve...... excellent results in infected eczema by addressing both inflammation and infection. A new lipid-rich combination formulation provides an extra moisturizing effect. Development of resistance to fusidic acid has remained generally low or short-lived and can be minimized by restricting therapy to no more than...

  1. Photodynamic Therapy

    Science.gov (United States)

    ... Oncol . 2004;5:497-508. Hopper C. Photodynamic therapy: a clinical reality in the treatment of cancer. Lancet Oncol . 2000;1:212-219. Huang Z. A review of progress in clinical photodynamic therapy. Technol Cancer Res Treat . 2005;4:283-293. ...

  2. Sweat Therapy.

    Science.gov (United States)

    Colmant, Stephen A.; Merta, Rod J.

    2000-01-01

    A study combined group sweating and group counseling. Four adolescent boys with disruptive behavior disorders participated in 12 sweat therapy sessions. They reported the sessions useful for sharing personal concerns and receiving assistance with problem solving. Three boys showed improvement in self-esteem. Advantages of sweat therapy over other…

  3. Clinical analysis of patients received pemetrexed therapy without the advised folic acid premedication%培美曲塞治疗未提前补充叶酸的晚期非小细胞肺癌35例

    Institute of Scientific and Technical Information of China (English)

    叶亮; 杨振华; 方苏榕; 谭焰; 谷伟

    2015-01-01

    Objective To explore whether 5 to -7-day of folic acid supplementation prior to pemetrexed therapy is needed. Methods We retrospectively evaluate the outcomes of non-small cell lung cancer patients received less than the advised folic acid premedication. Seventy patients with Ⅲ-Ⅳ NSCLC were randomly divided into two groups: patients who initiated vitamin supplementation on 7 days before the first dose of pemetrexed (group A) and patients who initiated vitamin supplementation on the day of the first dose of pemetrexed (group B). Results In group A and group B, CR 0 and 0, PR 10 and 8, the response rates of 28.6% and 22.9% were observed, respectively. There was no statistically significant differences between these two groups. No significant differences were observed in the incidence of hematologic and non-hematologic toxicities. Conclusions The initiation of pemetrexed-based chemotherapy does not need to accommodate a vitamin supplementation schedule.%目的:探讨培美曲塞化疗前是否需要提前5~7 d 补充叶酸预处理。方法:对比分析2010年1月至2013年12月就诊于南京市第一医院呼吸科接受培美曲塞治疗的晚期非鳞状非小细胞肺癌70例,根据培美曲塞首次化疗时补充叶酸时间分为提前补充叶酸组(35例)和未提前补充叶酸组(35例)。观察并分析两组患者化疗后不良反应及疗效的差异。结果:提前补充叶酸组无完全缓解(CR)病例,部分缓解(PR)22例,有效率为63%;非提前补充叶酸组无CR 病例,PR 23例,有效率为63%,两组患者有效率的比较差异无统计学意义。两组之间血液性及非血液性毒性差异亦无显著性。结论:培美曲塞首次化疗前可能不必提前1周进行补充叶酸治疗。

  4. Radiation Therapy

    Science.gov (United States)

    Radiation therapy is a cancer treatment. It uses high doses of radiation to kill cancer cells and stop them from ... half of all cancer patients receive it. The radiation may be external, from special machines, or internal, ...

  5. Gene Therapy

    Science.gov (United States)

    ... or improve your body's ability to fight disease. Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Researchers are still studying how and ...

  6. Proton therapy

    Science.gov (United States)

    ... TF. Charged particle radiotherapy. In: Gunderson LL, Tepper JE, eds. Gunderson and Tepper: Clinical Radiation Oncology . 4th ... March 22, 2017. Zeman EM, Schreiber EC, Tepper JE. Basics of radiation therapy. In: Niederhuber JE, Armitage ...

  7. Oxygen Therapy

    Science.gov (United States)

    Oxygen therapy is a treatment that provides you with extra oxygen. Oxygen is a gas that your body needs to function. Normally, your lungs absorb oxygen from the air you breathe. But some conditions ...

  8. Physical Therapy and Occupational Therapy in Progeria

    Science.gov (United States)

    Physical Therapy and Occupational Therapy in Progeria Information for Families and Caretakers from The Progeria Research Foundation Written ... accelerated aging in children. Children with Progeria need Physical Therapy (PT) and Occupational Therapy (OT) as often as ...

  9. Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit?

    Science.gov (United States)

    Delishaj, Durim; Fabrini, Maria Grazia; Gonnelli, Alessandra; Morganti, Riccardo; Perrone, Franco; Tana, Roberta; Paiar, Fabiola; Gadducci, Angiolo

    2016-01-01

    Purpose The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA) in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR) vaginal brachytherapy (BT). Material and methods Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/– adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week). Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02. Results According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9%) and in stage IB (57.9%). Thirty-three patients (26.2%) received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3%) and dyspareunia (7 patients, 5.5%). Two patients (1.6%) had more than one toxicity. Late toxicity occurred in 20 patients (15.9%). Grade 1-2 late toxicities were fibrosis (14 patients, 11.1%) and telangiectasias (7 patients, 5.5%). Six patients (4.8%) had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed. Conclusions These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity. PMID:28115957

  10. Advances in the treatment of skin diseases with δ-aminolevulinic acid-based photodynamic therapy%δ-氨基酮戊酸光动力学疗法治疗皮肤病的研究进展

    Institute of Scientific and Technical Information of China (English)

    夏育民; 徐世正

    2008-01-01

    δ-氨基酮戊酸光动力学疗法是一种非创伤性局部治疗技术,可特异性杀死病变细胞.近年研究表明,该疗法对靶细胞某些生物学特征的影响是重要作用机制之一.除非色素细胞性皮肤恶性肿瘤外,δ-氨基酮戊酸光动力学疗法的适应症逐渐扩展至癌前病变、病毒疣、痤疮、结缔组织病、光化性疾病等范围.升高温度、促溶剂、金属离子螫合物、电离子导入、脂质体载体等因素可促进其疗效.%δ-aminolevulinic acid(ALA)-based photodynamic therapy(PDT)is a noninvasive topical treatment choice that can selectively kill target cells.One important mechanism for its therapeutic effect is to intluence some biological characteristics of target cells.Besides nonpigment cell malignant tumors of skin,ALA-PDT could be used in the treatment of premalignant lesions,viral warts,acne,connective tissue diseases,actinic skin diseases,and SO on.Appropriate higher temperature,cosolvents,metal chelating agents.iontoplaoretic delivery and liposome vector may enhance the therapeutic efrect of ALA-PDT.

  11. Fluid therapy in small ruminants and camelids.

    Science.gov (United States)

    Jones, Meredyth; Navarre, Christine

    2014-07-01

    Body water, electrolytes, and acid-base balance are important considerations in the evaluation and treatment of small ruminants and camelids with any disease process, with restoration of these a priority as adjunctive therapy. The goals of fluid therapy should be to maintain cardiac output and tissue perfusion, and to correct acid-base and electrolyte abnormalities. Hypoglycemia, hyperkalemia, and acidosis are the most life-threatening abnormalities, and require most immediate correction.

  12. An overview of gene therapy in head and neck cancer

    OpenAIRE

    2013-01-01

    Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA) and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction...

  13. Lateral epicondylitis: review of injection therapies.

    Science.gov (United States)

    Judson, Christopher H; Wolf, Jennifer Moriatis

    2013-10-01

    Lateral epicondylitis has several different treatment methods, with no single agreed upon therapy. This article summarizes the current literature on injection therapies for lateral epicondylitis. Glucocorticoid, botulinum toxin, autologous blood, platelet-rich plasma, hyaluronic acid, polidocanol, glycosaminoglycan, and prolotherapy injections are discussed.

  14. Efficacy of folic acid supplementation as an adjuvant therapy in treatment of children with autism%叶酸对孤独症儿童的辅助治疗效果研究

    Institute of Scientific and Technical Information of China (English)

    李楠楠; 夏薇; 孙彩虹; 赵栋; 吴坤

    2013-01-01

    [Objective] To study the efficacy of folic acid supplementation as an adjuvant therapy in treatment of children with autism participated in structured teaching. [Methods] The method of open trial was used in this study. 66 autistic children participated in structured teaching were divided into folic acid intervention group and control group based on the principle of voluntariness. Developmental progress was measured by Autism Behavior Scale (ABC), Children's Autism Rating Scale (CARS) .Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-Third Edition (PEP-3) before and after 3 months' treatment. [Results] Compared with 3 months before,the overall scores of ABC,CARS and ATEC of both groups were significantly lower than before (P<0. 05), while the scores of all items of PEP-3 scale were higher than before (P<0. 05) .except for character motor behavior. According to the differentials of each scale before and after treatment,intervention group showed greater progress in language of ATEC and cognition,expressive language and receptive language of PEP-3 scale than those of control group (P<0. 05). [Conclusions] Autism children participated in structured teaching with folic acid intervention presents greater progress in cognition and language than those in independent structured teaching.%[目的]探讨叶酸对参与结构化教育的孤独症儿童的辅助治疗效果,为进行靶向营养干预及综合辅助治疗提供科学依据. [方法]采用开放性试验方法.随访66名参与结构化教学的孤独症儿童,遵循自愿原则分为叶酸干预组和对照组,采用孤独症行为量表(Autism Behavior Scale,ABC)、儿童孤独症评定量表(Children's Autism Rating Scale,CARS)、孤独症治疗评估量表(Autism Treatment Evaluation Checklist,ATEC)和自闭症儿童心理教育评核第3版(PEP-3)对其3个月前后的发育水平进行评估比较. [结果]经过3个月的康复训练后,两组儿童ABC

  15. [Drug therapy of acne].

    Science.gov (United States)

    Ochsendorf, F R; Degitz, K

    2008-07-01

    Acne is treated according to the clinical picture and the pathophysiologically relevant mechanisms, such as seborrhea, follicular hyperkeratosis, P. acnes colonisation,and inflammation. In mild forms of acne, topical therapy is most appropriate. Comedonal acne can be treated with topical retinoids; papulopustular acne with a combination of retinoids and topical antimicrobial substances (benzoyl peroxide, antibiotics, or azelaic acid). Moderate forms or those with extrafacial involvement can be treated with oral antibiotics combined with topical retinoids or benzoyl peroxide. Acne conglobata and other severe manifestations are treated with oral isotretinoin. Women are also treated with oral contraceptives containing anti-androgenic progestins. If inflammation is prominent, initial short term treatment with oral glucocorticoids is helpful. Second-line agents include oral zinc or dapsone. Following successful treatment, topical retinoids are suitable for maintenance therapy.

  16. Maintenance Therapy in IBD

    Science.gov (United States)

    ... Help Center Home > Resources > Maintenance Therapy Go Back Maintenance Therapy Email Print + Share The term "maintenance therapy" ... are referred to as "maintenance therapies." Why is Maintenance Therapy Needed in IBD? Both Crohn's disease and ...

  17. Maintenance Therapy in IBD

    Science.gov (United States)

    ... Help Center Home > Resources > Maintenance Therapy Go Back Maintenance Therapy Email Print + Share The term "maintenance therapy" ... are referred to as "maintenance therapies." Why is Maintenance Therapy Needed in IBD? Both Crohn's disease and ...

  18. Gene Therapy.

    Science.gov (United States)

    Thorne, Barb; Takeya, Ryan; Vitelli, Francesca; Swanson, Xin

    2017-03-14

    Gene therapy refers to a rapidly growing field of medicine in which genes are introduced into the body to treat or prevent diseases. Although a variety of methods can be used to deliver the genetic materials into the target cells and tissues, modified viral vectors represent one of the more common delivery routes because of its transduction efficiency for therapeutic genes. Since the introduction of gene therapy concept in the 1970s, the field has advanced considerably with notable clinical successes being demonstrated in many clinical indications in which no standard treatment options are currently available. It is anticipated that the clinical success the field observed in recent years can drive requirements for more scalable, robust, cost effective, and regulatory-compliant manufacturing processes. This review provides a brief overview of the current manufacturing technologies for viral vectors production, drawing attention to the common upstream and downstream production process platform that is applicable across various classes of viral vectors and their unique manufacturing challenges as compared to other biologics. In addition, a case study of an industry-scale cGMP production of an AAV-based gene therapy product performed at 2,000 L-scale is presented. The experience and lessons learned from this largest viral gene therapy vector production run conducted to date as discussed and highlighted in this review should contribute to future development of commercial viable scalable processes for vial gene therapies.

  19. [Testosterone therapy].

    Science.gov (United States)

    Diemer, T; Hauptmann, A; Wagenlehner, F M E

    2016-04-01

    Hormone replacement therapy with testosterone has become well-established over the course of time. The initial substantial concerns with respect to complications and potential adverse events, particularly in older patients, were proven to be unfounded over time. Testosterone therapy has therefore gradually become a regular treatment modality in urological practice. It has also been shown to represent a valuable tool as supportive treatment for patients with erectile dysfunction and hypogonadism. A variety of testosterone preparations are available for treatment. Recent pharmaceutical developments have greatly improved the practicability and ease of administration for patients. Several guidelines have been developed that provide clearly formulated standards and instructions for indications, contraindications, application, risk factors and monitoring of testosterone therapy. Adverse events affecting the cardiovascular system and especially diseases of the prostate gland are of great importance, thus making the urologist the primary partner in the treatment of patients with testosterone deficiency.

  20. Art Therapy

    DEFF Research Database (Denmark)

    Skov, Vibeke; Pedersen, Inge Nygaard

    2014-01-01

    Abstract Based on a Jungian approach, this article will introduce an integrative model to therapeutic change using art therapy methods as practical tools, with the aim of improving quality of life and in the prevention of depression. In a research study involving six participants, painting, clay...... work and drumming were used together with imagination and personal dialogues linked to the artwork. These art therapy processes attempted to combine the participant’s experience of inner and outer reality. The effect of gaining more knowledge about their inner reality using dreams and symbols......, was that participants gained a new understanding about their personal life. In addition, some participants were able to continue to use art therapy experiences as selfdevelopmental tools after the research study terminated. Jung’s description of the interactive relationship between the two living parts of the psyche...

  1. Art Therapy

    DEFF Research Database (Denmark)

    Skov, Vibeke; Pedersen, Inge Nygaard

    2014-01-01

    Abstract Based on a Jungian approach, this article will introduce an integrative model to therapeutic change using art therapy methods as practical tools, with the aim of improving quality of life and in the prevention of depression. In a research study involving six participants, painting, clay...... work and drumming were used together with imagination and personal dialogues linked to the artwork. These art therapy processes attempted to combine the participant’s experience of inner and outer reality. The effect of gaining more knowledge about their inner reality using dreams and symbols...... model of Art Therapy with this population. This article focuses on the psychological aspect of creativity related to mild depression with an emphasis on the interaction between the conscious and the unconscious part of the psyche....

  2. Music therapy

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    alternate with clear and lucid mental states. These states are important as it is here that it is possible to meet the person’s psychosocial needs. Ketil Normann’s conceps of periods of lucidity are presented and connected to clinical music therapy practice and how it is possible to use music in order...... as a consequence of person-centred care. Umeå University Medical Dissertations. New Series. Ridder, H.M. (2005). Music therapy as a way to enhance lucidity in persons with dementia in advanced stages. In: Esch, A.; Frohne-Hagemann, I.; Laqua, M.; Schirmer, H.; Seitz, E. (Eds.) Jahrbuch Musicktherapie. Forschung...... und Entwicklung Music Therapy Annual. Research and Development. 2005 (1), pp. 25-40. Reichert Verlag Wiesbaden....

  3. Music therapy

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    alternate with clear and lucid mental states. These states are important as it is here that it is possible to meet the person’s psychosocial needs. Ketil Normann’s conceps of periods of lucidity are presented and connected to clinical music therapy practice and how it is possible to use music in order...... as a consequence of person-centred care. Umeå University Medical Dissertations. New Series. Ridder, H.M. (2005). Music therapy as a way to enhance lucidity in persons with dementia in advanced stages. In: Esch, A.; Frohne-Hagemann, I.; Laqua, M.; Schirmer, H.; Seitz, E. (Eds.) Jahrbuch Musicktherapie. Forschung...... und Entwicklung Music Therapy Annual. Research and Development. 2005 (1), pp. 25-40. Reichert Verlag Wiesbaden....

  4. [Bimatoprost therapy in glaucoma].

    Science.gov (United States)

    Călugăru, D; Călugăru, M

    2009-01-01

    Bimatoprost is a neutral lipid, a fatty acid amide that pharmacologically acts in both its paternal amide form and through its hydrolysis product (active free fatty acid of bimatoprost). Hypotensive ocular efficacy of bimatoprost is significantly superior to that of timolol and latanoprost. Mean ocular pressure decreases as well as percentages of reaching and sustaining the low targeting ocular pressures are higher comparing with travoprost. Conjunctival hyperemia produced by bimatoprost is statistically greater than that caused by timolol, latanoprost and travoprost; nevertheless it is well tolerated and mild in severity. Bimatoprost prostamide lowers ocular tension significantly and clinically relevant in patients uncontrolled with latanoprost; that is why bimatoprost can be used as additive or replacement therapy in patients who already receive maximal tolerated dose of latanoprost.

  5. 考来烯胺对2型糖尿病大鼠胆汁酸代谢的影响%Cholestyramine therapy alters bile acid metabolism in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    王晓凌; 崔海平

    2012-01-01

    目的:探讨考来烯胺对2型糖尿病大鼠肝胆汁酸代谢的影响.方法:高脂饲料和小剂量链脲佐菌素(streptozotocin,STZ)注射成功诱导2型糖尿病后,SD♂大鼠随机分糖尿病组(diabetes mellitus group,DM组)和考来烯胺治疗组(cholestyramine treatment group,CT组)各10只,分别喂以高脂饲料和含2.5%考来烯胺的高脂饲料.另外10只正常SD♂大鼠作为对照组(control group,Con组),喂养标准饲料.继续饲养4 wk,各组大鼠麻醉后,股动脉采血并留取部分肝组织.RT-PCR检测胆汁酸代谢有关基因LXRα、FXR、SHP、CYP7A1、CYP27A1、ABCG5和ABCG8的mRNA表达,Western blot检测CYP7A1和CYP27A1的蛋白表达.结果:与Con组相比,DM组大鼠LXRα、CYP7A1、ABCG5和ABCG8的mRNA表达增加(均P<0.05),而FXR和RXR的mRNA表达减少(均P<0.05).与DM组相比,CT组LXRα和CYP7A1 mRNA表达进一步增加(均P<0.05),FXR和SHP的mRNA进一步减少(均P<0.05),ABCG5和ABCG8的mRNA表达不变.各组CYP27A1的mRNA表达没有差异.Westernblot表明Con组、DM组、CT组CYP7A1的蛋白表达依次增加(均P<0.05),而各组CYP27A1蛋白表达均未改变.结论:2型糖尿病状态下,肝胆汁酸合成增加是CYP7A1表达增加的结果,而与CYP27A1无关,考来烯胺治疗进一步促进了CYP7A1表达.核受体LXRα的mRNA表达增加,FXR的mRNA表达减少与CYP7A1表达增加有关.%AIM: To investigate the effect of cholestyramine therapy on bile acid metabolism in rats with type 2 diabetes. METHODS: Type 2 diabetes was induced in Sprague-Dawley (SD) rats by feeding a high-fat diet and intraperitoneally injecting streptozoto-cin (30 mg/kg). The rats were then randomly divided into diabetes mellitus group (DM group) and cholestyramine treatment group (CT group), with 10 rats in each group. Rats in the DM group and CT group were fed a high-fat diet and a high-fat diet containing 2.5% cholestyramine, respectively. Ten normal male SD rats were used as controls (Con group) and fed

  6. Truth therapy/lie therapy.

    Science.gov (United States)

    Langs, R

    In this paper an attempt is made to conceptualize a basic dimension of various psychotherapeutic treatment modalities, especially psychoanalysis and psychoanalytically oriented psychotherapy. The central variable under consideration is the extent to which each endeavors to approach the truth within both patient and therapist as it exists dynamically in terms of their spiraling unconscious communicative interaction. That treatment modality which takes into account every possible dimension of such truths is termed truth therapy. Treatment modalities that make no attempt to arrive at these truths or that deliberately or inadvertently falsify their nature are termed lie or barrier therapies. Extensive consideration is given to truth therapy and the truth system on which it is based. The basis for the need for lie therapies is explored, and lie systems, which may arise from either patient or therapist, or both, are identified. A classification of common types of lie patients and lie therapists (and their main techniques) is offered. The implications of this delineation for our understanding of the dynamic therapies are discussed, and a number of new clinical issues arising from this perspective are addressed.

  7. Inhibitory effect of 5-aminolevulinic acid photodynamic therapy on Candida albicans%5-氨基酮戊酸光动力疗法对白念珠菌抑制效应的实验研究

    Institute of Scientific and Technical Information of China (English)

    梁义; 卢丽明; 陈勇; 尹琦

    2013-01-01

    Objective To evaluate the inhibitory effect of 5-aminolevulinic acid Photodynamic therapy on Candida albicans in vitro. Methods 96-well cell culture plates were used for experimental carriers, and Candida albicans suspension was added to these wells, which were divided into experimental group and four control groups. With He-Ne laser as the excitation source, ALA as photosensitizer, DMSO as penetration enhancer and a solvent, ALA-PDT was performed. Results The growth of Candida albicans was inhibited in experimental group, with MIC of 500 mg/ml (50%). At concentration of 200 mg/ml (20%), ALA began to inhibit the growth of Candida albicans in experimental group, and ALA inhibited the growth of Candida albicans in a concentration-dependent way. The growth of Candida albicans was not inhibited in four control groups, and the CFU of Candida albicans showed no statistically significant difference between the groups. Conclusion ALA-PDT can effectively inhibit the growth of Candida albicans.%目的 评估5-氨基酮戊酸光动力疗法(5-ALA-PDT)在体外对白念珠菌的抑制效应.方法 以96孔细胞培养板为实验载体,加入白念珠菌悬液,分为治疗组和4个对照组,以氦氖激光为激发光源,ALA为光敏剂,使用DMSO作为ALA的溶剂兼穿透增强剂,进行ALA-PDT.结果 治疗组白念珠菌的生长受到抑制,其MIC值为500mg/ml(50%),ALA浓度在200mg/ml(20%)时,开始使治疗组白念珠菌的生长受到抑制,且抑制作用对ALA的浓度呈剂量依赖关系.而对照组中白念珠菌的生长未受到抑制,四组的白念珠菌的CFU数量变化无明显差异.结论 按本实验所使用的方法进行的ALA-PDT能有效地抑制白念珠菌.

  8. Dance Therapy.

    Science.gov (United States)

    Leventhal, Marcia B.

    1980-01-01

    Dance therapy deals with personal growth via body-mind interaction. A change in movement expression is believed to result in a personality or behavior change. The therapist is trained to become sensitive to movement expression as it relates to the psychological, motor, and cognitive development of the child. (JN)

  9. Pet Therapy.

    Science.gov (United States)

    Kavanagh, Kim

    1994-01-01

    This resource guide presents information on a variety of ways that animals can be used as a therapeutic modality with people having disabilities. Aspects addressed include: pet ownership and selection criteria; dogs (including service dogs, hearing/signal dogs, seeing leader dogs, and social/specialty dogs); horseriding for both therapy and fun;…

  10. What Is Music Therapy?

    Science.gov (United States)

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login About Music Therapy & AMTA What is Music Therapy? Definition and Quotes ... is Music Therapy? Print Email Share What is Music Therapy What is Music Therapy? Music Therapy is the ...

  11. Topical tranexamic acid improves the permeability barrier in rosacea

    Directory of Open Access Journals (Sweden)

    Shaomin Zhong

    2015-06-01

    Conclusion: Topical tranexamic acid could improve the epidermal permeability barrier function and clinical signs of rosacea, likely resulting from inhibition of PAR-2 activation and consequent calcium influx. Thus, tranexamic acid could serve as an adjuvant therapy for rosacea.

  12. Anecdotal therapies.

    Science.gov (United States)

    Millikan, L E

    1999-01-01

    Traditionally, many advances in medicine have been serendipitous. Are serendipitous and anecdotal synonymous? Many of our materia medica today relate to initial probes and anecdotal reports that matured to full investigation and therapeutic indications. The recent situation regarding Skin Cap is one that highlights the downside of this scenario. Several drugs in the US continue usage largely related to anecdotal indications, and anecdotal extension of legend indications is a standard for American Dermatology. The situation with systemic drugs, such as Trental, zinc preparations, imidazoles for extended indications, lysine and melatonin, all will be discussed. Topical preparations such as skin cap, cantharone, Vioform, all also are included in this category. It is important to place this topic in perspective in regards to geographic variation and therapeutic need. Many diseases lacking specific therapy are important targets for anecdotal therapy, and this will foster continued approaches in this area. The growing standardization of medicine and pharmaceutical regulation, threatens the anecdotal approach, but it provides still an important link to the future for some forms of therapy in diseases that are difficult to treat. Traditionally, the anecdote has been the first step in the therapeutic chain. Withering discovery of the benefits of the common fox glove in dropsy, was followed by many other anecdotes arriving via folk-medicine in the New World. This approach of utilizing folk medicine has now reached new heights, with very active searches by major pharmaceutical companies throughout the third world for remedies that may have potential. Couched with this is the history of anecdotal "snake-oil" remedies, that clearly had no benefit to anyone except the huckster marketing same. The excesses in this area of unproven and false therapies, led to the gradual organization of therapeutic trials and the Food and Drug Administration in the US as we know it today. The

  13. [Topical therapy of rosacea].

    Science.gov (United States)

    Schöfer, H

    2013-07-01

    Metronidazole and azelaic acid are the only topical medications approved for rosacea. All other topical treatments for rosacea and its special forms are used off-label. Topical steroids are not indicated in rosacea, because of their side effects (induction of steroid rosacea, high risk of facial skin atrophy, and high risk of rebound after cessation of therapy). Topical as well as systemic steroids are allowed only as initial and short term therapy for acute forms of rosacea (e.g. rosacea fulminans). Papular and pustular rosacea is the major indication for topical therapy. Sebaceous gland and connective tissue hyperplasia in glandular-hypertrophic rosacea as well as erythema in erythematous rosacea do not respond well to topical measures. A new active substance, the alpha-2-adrenoreceptor agonist brimonidine, will be approved soon for the topical treatment of erythema in rosacea. All severe forms of rosacea should initially be treated with a combination of topical and systemic agents. After improvement of the clinical symptoms, topical treatment alone is usually adequate to maintain the control.

  14. Narrative therapy, family therapy and history

    OpenAIRE

    Harper, David J.

    2009-01-01

    This article was inspired by listening to the interesting plenary on the influence of narrative therapy on family therapy at the AFT annual conference in Manchester in September 2008. One of the issues raised concerned the historical connections between narrative therapy and the broader family therapy field. The contributors seemed keen to avoid a split between narrative therapy and the broader family therapy field and, instead, to find connections but this issue seemed difficult to negotiate...

  15. Proton Therapy

    Science.gov (United States)

    Oelfke, Uwe

    Proton therapy is one of the most rapidly developing new treatment technologies in radiation oncology. This treatment approach has — after roughly 40 years of technical developments — reached a mature state that allows a widespread clinical application. We therefore review the basic physical and radio-biological properties of proton beams. The main physical aspect is the elemental dose distribution arising from an infinitely narrow proton pencil beam. This includes the physics of proton stopping powers and the concept of CSDA range. Furthermore, the process of multiple Coulomb scattering is discussed for the lateral dose distribution. Next, the basic terms for the description of radio-biological properties of proton beams like LET and RBE are briefly introduced. Finally, the main concepts of modern proton dose delivery concepts are introduced before the standard method of inverse treatment planning for hadron therapy is presented.

  16. Particle therapy

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.

    1993-09-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics.

  17. Music Therapy

    DEFF Research Database (Denmark)

    Trondalen, Gro; Bonde, Lars Ole

    2012-01-01

    Music therapy (MT) is most commonly defined as an intervention where “the therapist helps the client to promote health, using music experiences and the relationships developing through them” (Bruscia 1998). Also other definitions of MT agree that a therapeutic relationship is important for a music...... intervention to be considered MT. Other interventions that “use music for health-related goals, but in ways that do not qualify as music therapy” (Gold 2009), may be described as music medicine, or simply as music listening. In this text we elaborate on an overview chapter covering some of the different major...... music therapy orientations/models (Guided Imagery and Music, Nordoff-Robbins, Psychoanalytic, Cognitive-behavioral etc), their theoretical foundations and their practical approaches to health and wellbeing or ‘health musicking’. The relational context – the interplay of (expressive as well as receptive...

  18. Music Therapy

    DEFF Research Database (Denmark)

    Sanfi, Ilan

    2012-01-01

    may cause detrimental long-term effects. Three studies have examined the effect of music therapy procedural support (MTPS) under needle procedures. Consequently, this study aims at examining the effects of MTPS in an RCT. Moreover, the study addresses clinical aspects of the applied MT intervention...... and provides research-based clinical tools. Methods 41 children (1 to 10 years) were enrolled and underwent a single PIVA procedure. The children were randomly assigned to either an MT or a comparable control group receiving PIVA. In addition, the music therapy (MT) group received individualised MTPS (i.......e. music alternate engagement) before, during, and after PIVA. The intervention was performed by a trained music therapist and comprised preferred songs, improvised songs/music, and instrument playing. The study was carried out in accordance with the rules in force regarding research ethics and clinical MT...

  19. Antiproton therapy

    CERN Document Server

    Knudsen, Helge V; Bassler, Niels; Alsner, Jan; Beyer, Gerd-Jürgen; DeMarco, John J; Doser, Michael; Hajdukovic, Dragan; Hartley, Oliver; Iwamoto, Keisuke S; Jäkel, Oliver; Kovacevic, Sandra; Møller, Søren Pape; Overgaard, Jens; Petersen, Jørgen B; Ratib, Osman; Solberg, Timothy D; Vranjes, Sanja; Wouters, Bradly G

    2008-01-01

    Radiotherapy is one of the most important means we have for the treatment of localised tumours. It is therefore essential to optimize the technique, and a lot of effort goes into this endeavour. Since the proposal by Wilson in 1946 [R.R. Wilson, Radiology use of fast protons, Radiology 47 (1946) 487.] that proton beams might be better than photon beams at inactivating cancer cells, hadron therapy has been developed in parallel with photon therapy and a substantial knowledge has been gained on the effects of pions, protons and heavy ions (mostly carbon ions). Here we discuss the recent measurements by the CERN ACE collaboration of the biological effects of antiprotons, and argue that these particles very likely are the optimal agents for radiotherapy.

  20. Gene therapy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005147 CNHK200-hA-a gene-viral therapeutic system and its antitumor effect on lung cancer. WANG Wei-guo(王伟国),et al. Viral & Gene Ther Center, Eastern Hepatobilli Surg Instit 2nd Milit Univ, Shanghai 200438. Chin J Oncol,2005:27(2):69-72. Objective: To develop a novel vector system, which combines the advantages of the gene therapy,

  1. About Occupational Therapy

    Science.gov (United States)

    ... if}} {{{tweet}}} About Occupational Therapy What Is Occupational Therapy? Occupational therapy practitioners ask, "What matters to you?" not, " ... about our science-driven and evidence-based profession. Occupational Therapy: Improving Function While Controlling Costs 4 4 The ...

  2. Novel ketone body therapy for managing Alzheimer's disease: An Editorial Highlight for Effects of a dietary ketone ester on hippocampal glycolytic and tricarboxylic acid cycle intermediates and amino acids in a 3xTgAD mouse model of Alzheimer's disease.

    Science.gov (United States)

    Puchowicz, Michelle A; Seyfried, Thomas N

    2017-03-15

    Read the highlighted article 'Effects of a dietary ketone ester on hippocampal glycolytic and tricarboxylic acid cycle intermediates and amino acids in a 3xTgAD mouse model of Alzheimer's disease' on doi: 10.1111/jnc.13958.

  3. An overview of gene therapy in head and neck cancer.

    Science.gov (United States)

    Bali, Amit; Bali, Deepika; Sharma, Ashutosh

    2013-07-01

    Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA) and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction and expression, mediation of apoptosis and clinical response including pathological complete responses. The objective of this article is to provide an overview of the current available gene therapies for head and neck cancer.

  4. 5-氨基酮戊酸光动力疗法治疗寻常痤疮临床应用研究%Topical photodynamic therapy with 5-aminolevnlinic acid for acne vulgaris

    Institute of Scientific and Technical Information of China (English)

    王秀丽; 王宏伟; 苏丽娜; 张玲琳; 过明霞; Herbert Stepp

    2009-01-01

    目的 探索5-氨基酮戊酸光动力疗法(ALA-PDT)治疗寻常痤疮的ALA最适浓度和最佳敷药时间.方法 将30例中、重度寻常痤疮患者随机分为两组,第一组15例,给以10%ALA乳膏外敷,分别在不同时间点(1、2、3、4、5 h)和不同皮损进行原卟啉Ⅸ(PpⅨ)荧光光动力诊断和皮损组织PpⅨ荧光采集与定量分析;第二组15例,在每例患者的右侧面颊、左侧面颊、前额的痤疮皮损上分别给以3%、5%、10%ALA乳膏外敷3 h后进行PpⅨ荧光光动力诊断和荧光定量研究;同时对该组患者不同部位采用不同浓度ALA-PDT的疗效和不良反应进行临床研究.结果 第一组痤疮患者经10%ALA乳膏外敷,暗室环境下采用激发光源照射皮损后发现,炎性丘疹、脓疱和囊肿均显示PpⅨ强砖红色荧光;粉刺、炎性丘疹、脓疱和囊肿的PpⅨ荧光强度分别为1.3、4.3,5.1和5.8校准单位,PpⅨ荧光强度随着皮损严重程度的增加而增强;同时,随着外敷时间的延长,PpⅨ荧光强度逐渐增强,敷药3 h,4 h、5 h时PpⅨ荧光强度明显高于1 h和2 h(P0.05);分别以3%、5%、10%ALA乳膏外涂于15例患者右侧面颊、左侧面颊、前额部位,经过两次ALA-PDT治疗后,痊愈5例、显效6例,总有效率为73%;每例患者的不同部位皮损之间,疗效改善情况无明显差异.副作用表现为轻至中度的红斑、肿胀,严重时少许渗出,仅2例出现暂时性色素沉着,所有病例均未出现溃疡和瘢痕等严重不良反应.结论 ALA-PDT适用于以炎性丘疹、脓疱和囊肿为主要表现的寻常痤疮治疗,宜采用3%ALA浓度和3 h敷药时间.%Objective To investigate the optimal concentration and incubation time of 5-aminole-vulinic acid (ALA) in photodynamic therapy of acne vulgaris. Methods Thirty patients with facial acne vulgaris were equally divided into two groups. In group 1, ALA (10%)cream was applied to acne lesions and protoporphyrin Ⅸ (PpⅨ) fluorescence was

  5. 5-氨基乙酰丙酸介导的光动力学治疗胃癌的实验研究%Effect of photodynamic therapy with 5-aminolevulinic acid on human gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    黄宗海; 周广军; 俞金龙; 厉周; 丁涟沭; 徐如祥; 姜晓丹

    2006-01-01

    目的探讨5-氨基乙酰丙酸(5-ALA)介导的光动力学对人胃癌细胞MGC-803的治疗作用.方法将不同浓度的5-ALA加入细胞培养基中,随之给予相同剂量的激光辐射;之后用固定浓度的5-ALA处理细胞,并给予不同剂量的激光辐射.MTT法测定细胞生存率.结果在相同的辐射剂量下,经0.25、0.5、1.0、2.0、4.0 mmol/L的5-ALA处理的细胞生存率分别为(70.07±5.37)%、(50.04±4.99)%、(34.53±5.30)%、(26.89±4.44)%和23.90%±2.80%,除2.0和4.0 mmol/L5-ALA两组间外,其余各组间具有显著性差异(F=266.39,P<0.001).在相同的5-ALA的浓度下,辐射剂量为6.25、12.5、25.0、50.0、100 J/cm2的细胞生存率分别为(83.50±10.43)%、(67.96±9.23)%、(33.80±8.26)%、(23.31±5.98)%和(14.96±3.50)%,各组之间有显著性差异(F=226.31,P<0.0001).而单用5-ALA处理细胞,对应于其浓度为0.25、0.5、1.0、2.0,和4.0 mmol/L时的细胞生存率分别为(96.46±6.72)%、(97.48±5.27)%、(98.33±6.67)%、(99.47±6.97)%和(95.66±7.72)%,各浓度之间无显著性差异(F=0.79,P=0.5383).单纯激光辐射,其剂量为6.25、12.5、25.0、50.0、100.0 J/cm2时的细胞生存率也无显著性差异(F=0.61,P=0.6551).结论在较低的浓度范围内,5-ALA介导的光动力学治疗对人胃癌MGC-803细胞的杀伤作用随着5-ALA浓度的增加而增加,在较高浓度时则存在饱和现象,杀伤力与光剂量成正比.单纯激光不能产生光动力效应,5-ALA本身对细胞无毒性作用.5-ALA介导的光动力学治疗是很有希望的胃癌治疗方法.%Objective To investigate the effect of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) on MGC-803 human gastric cancer cells in vitro. Methods MGC-803 human gastric cancer cells were treated with 5-ALA at various concentrations followed by laser irradiation. The cells were also treated with 5-ALA at the same concentration before laser exposure at various doses. PDT-induced phototoxicity of the cells was

  6. Oxygen Therapy

    OpenAIRE

    2000-01-01

    LTOT is prescribed for people with chronic lung disease in whom there is a decrease in the ability of the lungs to supply enough oxygen to the body. The heart is obliged to pump faster to meet the body's oxygen requirements. This may place undue stress on the heart, resulting in palpitations, dizziness and fatigue. A low oxygen level in arterial blood is also harmful to the heart, the brain and the pulmonary blood vessels. Oxygen therapy is used to break this cycle. A person with low blood ox...

  7. [Gestalt therapy.].

    Science.gov (United States)

    Corbeil, J; Poupard, D

    1978-01-01

    The authors describe Gestalt Therapy. They retrace its fundamental theoretical axes. These are psychoanalysis, character analysis, the german Gestalt theory of perception, existentialism, and the Orient. Some principal concepts are then elaborated more fully such as the cycle of awareness, desensitization, excitation anxiety and the five defense mechanisms: retroflection, introjection, projection, deflection, and confluence. The nature and goals of the therapeutic process are also described before the presentation of some techniques specific to this approach such as enactment and role playing. Finally, certain basic Gestalt rules, which aim at facilitating and intensifying the communication process among group members, are enunciated.

  8. Nutritional Therapy.

    Science.gov (United States)

    Schwartz, Julie

    2016-03-01

    This article provides the reader with steps needed to accurately assess patient nutrition behaviors that contribute to weight gain, inability to lose weight, or inability to sustain weight loss. Evidence-based approaches in nutrition therapy that can create the daily energy deficit needed to produce 1/2 to 2 pounds of weight loss per week, and the strategies to create the energy deficit, are presented. To optimize health, long-term weight loss maintenance is needed. The benefits of using a multidisciplinary team approach in treating obesity are highlighted.

  9. Valproic Acid

    Science.gov (United States)

    ... acid is in a class of medications called anticonvulsants. It works by increasing the amount of a ... older (about 1 in 500 people) who took anticonvulsants such as valproic acid to treat various conditions ...

  10. Amino acids

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002222.htm Amino acids To use the sharing features on this page, please enable JavaScript. Amino acids are organic compounds that combine to form proteins . ...

  11. Obeticholic Acid

    Science.gov (United States)

    Obeticholic acid is used alone or in combination with ursodiol (Actigall, Urso) to treat primary biliary cholangitis (PBC; a ... were not treated successfully with ursodiol alone. Obeticholic acid is in a class of medications called farnesoid ...

  12. Ascorbic Acid

    Science.gov (United States)

    Ascorbic acid is used to prevent and treat scurvy, a disease caused by a lack of vitamin C in ... Ascorbic acid comes in extended-release (long-acting) capsules and tablets, lozenges, syrup, chewable tablets, and liquid drops to ...

  13. Mefenamic Acid

    Science.gov (United States)

    Mefenamic acid is used to relieve mild to moderate pain, including menstrual pain (pain that happens before or during a menstrual period). Mefenamic acid is in a class of medications called NSAIDs. ...

  14. Acid mucopolysaccharides

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003368.htm Acid mucopolysaccharides To use the sharing features on this page, please enable JavaScript. Acid mucopolysaccharides is a test that measures the amount ...

  15. Ethacrynic Acid

    Science.gov (United States)

    Ethacrynic acid, a 'water pill,' is used to treat swelling and fluid retention caused by various medical problems. It ... Ethacrynic acid comes as a tablet to take by mouth. It is usually taken once or twice a day ...

  16. Aminocaproic Acid

    Science.gov (United States)

    Aminocaproic acid is used to control bleeding that occurs when blood clots are broken down too quickly. This type ... the baby is ready to be born). Aminocaproic acid is also used to control bleeding in the ...

  17. Aspartic acid

    Science.gov (United States)

    ... body work. It plays a role in: Hormone production and release Normal nervous system function Plant sources of aspartic acid include: avocado, asparagus, and molasses. Animal sources of aspartic acid include: ...

  18. Music Therapy: A Career in Music Therapy

    Science.gov (United States)

    About Music Therapy & Music Therapy Training M usic therapy is a healthcare profession that uses music to help individuals of all ages improve physical, ... grateful I chose a career as rewarding as music therapy. I love what I do each day!” Where ...

  19. [Photodynamic therapy for actinic cheilitis].

    Science.gov (United States)

    Castaño, E; Comunión, A; Arias, D; Miñano, R; Romero, A; Borbujo, J

    2009-12-01

    Actinic cheilitis is a subtype of actinic keratosis that mainly affects the lower lip and has a higher risk of malignant transformation. Its location on the labial mucosa influences the therapeutic approach. Vermilionectomy requires local or general anesthetic and is associated with a risk of an unsightly scar, and the treatment with 5-fluorouracil or imiquimod lasts for several weeks and the inflammatory reaction can be very intense. A number of authors have used photodynamic therapy as an alternative to the usual treatments. We present 3 patients with histologically confirmed actinic cheilitis treated using photodynamic therapy with methyl aminolevulinic acid as the photosensitizer and red light at 630 nm. The clinical response was good, with no recurrences after 3 to 6 months of follow-up. Our experience supports the use of photodynamic therapy as a good alternative for the treatment of actinic cheilitis.

  20. A study in vitro on radiation effects by Er:YAG laser combined with the fluorine therapy in the acid resistance of the dental enamel submitted to orthodontical brackets; Um estudo in vitro sobre os efeitos da irradiacao pelo laser de Er:YAG combinado com a terapia com fluor na resistencia acida do esmalte de dentes submetidos a aparelho ortodontico fixo

    Energy Technology Data Exchange (ETDEWEB)

    Yoshiyasu, Roseli Y.A

    2001-07-01

    Several researches have been demonstrating an increase in the resistance acid of the enamel surface when irradiated by some lasers types as Nd:YAG, C0{sub 2}, Er:YAG, and others, mainly when combined with the fluoride therapy after the irradiation of the laser. This study in vitro used the laser of Er:YAG which density of energy of 8.1 J/cm{sup 2} on the enamel about of orthodontical brackets of teeth extracted pre-molars. These teeth were then submitted to a rich way in S. mutans for twenty one days. The cases were analyzed: (1) enamel surface without any treatment, (2) enamel surface without any irradiation laser, but with therapy with acidulated phosphate fluoride, (3) enamel surface irradiated with laser of Er:YAG and (4) enamel surface irradiated by laser of Er:YAG and with application of acidulated phosphate fluoride. The results were analyzed through optical microscopy and scanning electron microscopy. The morphologic changes observed to the scanning electron microscopy suggest increase in the acid resistance of the enamel surface. However, to the optical microscopy, it was still possible to visualize undesirable white stains in the surface of the enamel. (author)

  1. Fatty acids - trans fatty acids

    Science.gov (United States)

    The data supporting a negative effect of dietary trans fatty acids on cardiovascular disease risk is consistent. The primary dietary sources of trans fatty acids include partially hydrogenated fat and rudiment fat. The adverse effect of trans fatty acids on plasma lipoprotein profiles is consisten...

  2. Camouflage therapy.

    Science.gov (United States)

    Rayner, V L

    1995-04-01

    Camouflage therapy is a system of cosmetic techniques designed for patients to use to assist themselves in coping constructively with the psychological and physical trauma of their disfigurements. It is described as a "system" because these techniques are interrelated. A camouflage therapist may teach the patient to use one, two, or all of the techniques at the same time in order to normalize their appearance. Four basic techniques have been described in this article. They are as follows: (1) the use of opaque, waterproof cover creams to conceal scarring; (2) the application of pancake makeup for patients with oily or acne-prone skin; (3) color correctors to obliterate discoloration from postoperative trauma; and (4) recreating imperfections on the skin. For more information about the use of cosmetics to normalize the appearance of physical disfigurements, the following books are recommended.

  3. Terapêutica fotodinâmica com ácido delta-aminolevulínico em neoplasias queratinocíticas superficiais Photodynamic therapy with delta-aminolevulinic acid for superficial keratinocytic neoplasms

    Directory of Open Access Journals (Sweden)

    Renato Marchiori Bakos

    2003-04-01

    %, dor em cinco (6,7% e prurido em um caso (1,3%. A maioria dos casos (60% apresentou boa tolerância ao tratamento, não havendo efeitos paralelos dignos de nota. CONCLUSÕES: Os resultados obtidos no trabalho assemelham-se, em parte, aos relatados na literatura com aplicação única da terapêutica fotodinâmica com ácido delta-aminolevulínico em neoplasias queratinocíticas superficiais, principalmente nas ceratoses actínicas e na doença de Bowen.BACKGROUND: Photodynamic therapy (PDT is a treatment technique in which photosensitizing substances are applied in tissues and excited with specific wavelengths of light energy to obtain cell destruction through photoactive cytotoxic substances. This method has been used in several skin neoplasms, with quite successful results. OBJECTIVES: To study the effects of one single session of topical delta-aminolevulinic acid (ALA irradiated with incoherent light, in actinic keratosis (AK, superficial basal cell carcinoma (BCC and Bowen's disease (BD. PATIENT AND METHODS: Eighty skin lesions, in 52 patients, were treated with an incoherent light source prototype built by the Service of Biomedical Engineering of Hospital de Clínicas de Porto Alegre (HCPA, after the application of 20% ALA under occlusion. Thirty two (40% were superficial BCC, 37 (46.3% AK, and 11 (13.7% BD. Diagnosis was confirmed by biopsy and histology in 23 cases (28.7%. RESULTS: Follow up was not available in five lesions. From the remaining 75, 41 (54.6% were completely resolved, 22 (29.4% showed partial remission, and 12 (16.0% were considered as treatment failures. Considering the 35 treated AK, 23 (65.7% presented complete response, 7 (20% improved, and 5 (14.3% showed no benefit after treatment. Thirty BCC were treated, 10 (33.3% completely resolved, 13 (43.4% improved, and 7 (23.3% remained unaffected. From 10 treated BD, 8 (80% resolved and 2 (20% improved. Observed side effects were burning sensation in 24 lesions (32%, pain in 5 (6.7%, and itch in

  4. Therapies for diabetic dyslipidaemia.

    Science.gov (United States)

    Bell, D S H; Al Badarin, F; O'Keefe, J H

    2011-04-01

    Correction of diabetic dyslipidaemia in diabetic patients is the most important factor in reducing cardiac risk. Diabetic dyslipidaemia is characterized by elevated triglycerides, low total high-density lipoprotein (HDL) and small dense low-density lipoprotein (LDL) particles. The most important therapeutic goal in diabetic dyslipidaemia is correction of the non-HDL-cholesterol (HDL-C) level. Glycaemic control with particular attention to postprandial glucose control plays a role not only in improving dyslipidaemia but also in lowering cardiac events. Pioglitazone is particularly effective for improving the manifestations of diabetic dyslipidaemia, in addition to its favorable effects on systemic inflammation and hyperglycaemia. Use of statins in addition to lifestyle change is recommended in most if not all type 2 diabetic patients and the goal should be to lower the LDL to a level recommended for the patient with existing cardiovascular disease (CVD) (non-HDL-C level HDL and triglyceride levels should be deployed. Most patients with type 2 diabetes (T2D) will require combining a lipid-lowering therapy with therapeutic lifestyle changes to achieve optimal lipid levels. Combinations usually include two or more of the following: a statin, nicotinic acid, omega-3 fats and bile acid sequestrants (BASs). Fibrates may also be of use in diabetic patients with persistently elevated triglycerides and depressed HDL-C levels, although their role in lowering adverse CV events is questionable. © 2011 Blackwell Publishing Ltd.

  5. THE NEWS IN THERAPY OF AUTISM

    Directory of Open Access Journals (Sweden)

    Vladimir TRAJKOVSKI

    2004-12-01

    Full Text Available There is no specifically marked medicine for the treatment of autism. A number of approaches have been used in evaluating the safety and efficiency of pharmacological treatments of both children and adults with autism. Two study parameters are particularly important, the presence of “blind” and control groups. The highest quality studies utilize equally “blind” and control procedures as well. They have to be performed at multiple sites with a large number of subjects.Research evaluating medicine proposed for treatment of autism, is on the increase. There is accelerated emphasis on medicine testing and better information on treatments should be more available than in the past. In this article, the following classes of medicine and therapies will be discussed: possible future medicine treatments - such as oxytocin, tetrahydrobiopterin and ampakines, hormone therapies, anti-yeast therapies, vitamin therapies, dimethylglycine, alpha lipoic acid and diet therapies.

  6. Newer and upcoming therapies for melasma

    OpenAIRE

    Rashmi Sarkar; Shikha Chugh; Vijay K Garg

    2012-01-01

    Melasma is one of the most common and distressing pigmentary disorders presenting to dermatology clinics. The precise cause of melasma remains unknown; however, there are many possible contributing factors. It is notably difficult to treat and has a tendency to relapse. The existing and most tried topical therapy is hydroquinone and the triple combination with tretinoin and corticosteroids, which is considered the gold standard for melasma. Besides that, azelaic acid, kojic acid, arbutin, asc...

  7. Occupational Therapy (For Parents)

    Science.gov (United States)

    ... Habits for TV, Video Games, and the Internet Occupational Therapy KidsHealth > For Parents > Occupational Therapy Print A A ... for some kids. continue Kids Who Might Need Occupational Therapy According to the AOTA, kids with these medical ...

  8. American Music Therapy Association

    Science.gov (United States)

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login Quick Links Facts About Music Therapy Qualifications ... with AMTA Sponsor AMTA Events Social Networking Support Music Therapy When you shop at AmazonSmile, Amazon will ...

  9. Laser therapy for cancer

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000905.htm Laser therapy for cancer To use the sharing features ... Lasers are also used on the skin. How Laser Therapy is Used Laser therapy can be used ...

  10. [Physical therapy].

    Science.gov (United States)

    Chohnabayashi, Naohiko

    2008-01-01

    Recently, pulmonary rehabilitation program is widely considered one of the most effective and evidence-based treatment for not only chronic obstructive pulmonary disease (COPD) but many clinical situations including neuro-muscular disease, post-operative status and weaning period from the ventilator, etc. The essential components of a pulmonary rehabilitation program are team assessment, patient training, psycho-social intervention, exercise, and follow-up. In 2003, Japanese medical societies (J. Thoracic Society, J. Pul. Rehabilitation Society and J. Physiotherapist Society) made a new guideline for pulmonary rehabilitation, especially how to aproach the execise training. As for the duration after surgical operation, airway cleaning is the important technique to prevent post-operative complications including pneumonia. Postural dranage technique is well known for such condition, at the same time, several instruments (flutter vulve, positive expiratory mask, high frequecy oscillation, etc) were also used for the patient to expectrate airway mucus easier. Lung transplantation is a new method of treatment for the critically-ill patients with chronic respiratoy failure. Several techniques of physical therapy are must be needed before and after lung transplantation to prevent both pulmonary infection and osteoporosis.

  11. [Nutritional therapy of gout].

    Science.gov (United States)

    Nickolai, Beate; Kiss, Caroline

    2016-01-01

    Nutrition and nutritional behaviours have been found to play a major role in the development of gout. Studies show that body mass index (BMI), as well as excessive intake of alcoholic beverages, meat, soft drinks and fruit juices increase the risk of developing gout. Similarly, dairy products and coffee have been seen to decrease the risk of hyperuricemia and gout, as they increase the excretion of uric acid. Flares of gout are often caused by large meals and high alcohol consumption. Each additional intake of meat portion per day increases the risk of gout by 21 %. Taking total alcohol consumption into account, the risk of gout increases after one to two standard drinks. In contrast to previous assumptions purine-rich plant foods like legumes and vegetables do not increase the risk of gout. The current dietary guidelines take into account nutritional factors, which not only consider purine intake, but also their endogenous production and their influence on renal excretion. A balanced diet based on the Swiss healthy eating guideline pyramid as well as the Mediterranean diet is appropriate for this patient population. The treatment of gout is multi-faceted, since this patient population presents other comorbidities such as obesity, diabetes mellitus, dyslipidemia and hypertension. Collectively, these risk factors are diet dependent and require a treatment strategy that is centered on modifying one's nutrition and nutritional behaviours. The aim of such therapy is to educate the patient as well as treat the accompanying comorbidities with the goal of decreasing serum uric acid values. Motivated patients require consultation and follow-up care in order to be able to actively decrease the serum uric acid.

  12. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: Further improvements in treatment outcome

    NARCIS (Netherlands)

    M.A. Sanz (Miguel Angel); P. Montesinos (Pau); C. Rayón (Chelo); A. Holowiecka (Aleksandra); J. De La Serna (Javier); G. Milone (Gustavo); E. de Lisa (Elena); S. Brunet (Salut); V. Rybio (Vicente); J.M. Ribera (Josep Maria); C. Rivas (Concha); I. Krsnik (Isabel); J.M. Bergua (Juan Miguel); J.D. González (José David); J. Díaz-Mediavilla (Joaquín); R. Rojas (Rafael); F. Manso (Félix); G.J. Ossenkoppele (Gert); B. Löwenberg (Bob)

    2010-01-01

    textabstractA risk-adapted strategy based on all-trans retinoic acid (ATRA) and anthracycline monochemotherapy (PETHEMALPA99 trial) has demonstrated a high antileukemic efficacy in acute promyelocytic leukemia. We designed a new trial (LPA2005) with the objective of achieving stepwise improvements i

  13. Folic Acid

    Science.gov (United States)

    ... damage. 10 Do I need folic acid after menopause? Yes. Women who have gone through menopause still need 400 micrograms of folic acid every ... United States: 2003–2006 . American Journal of Clinical Nutrition; 91(1): 231–237. Hamner, H.C., Cogswell, ...

  14. The therapy of gefitinib towards breast cancer partially through ...

    African Journals Online (AJOL)

    The therapy of gefitinib towards breast cancer partially through reversing ... Department of Medical Oncology, Affiliated Yuhuangding Hospital, Medical College of Qingdao University, ... solution containing isotope labeled amino acid internal.

  15. Mechanisms of buffer therapy resistance.

    Science.gov (United States)

    Bailey, Kate M; Wojtkowiak, Jonathan W; Cornnell, Heather H; Ribeiro, Maria C; Balagurunathan, Yoganand; Hashim, Arig Ibrahim; Gillies, Robert J

    2014-04-01

    Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, we confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  16. [Nutritional therapy in diabetes mellitus].

    Science.gov (United States)

    Toeller, M

    1993-03-01

    Most aspects of the nutritional therapy of diabetes mellitus apply equally to IDDM and NIDDM patients and are also appropriate for people with high risk of cardiovascular diseases. A restriction of energy, a reduction of saturated fatty acids as well as of alcoholic drinks and simple sugars are the most important measures. This modification of nutritional intake together with increased fibre consumption is not only appropriate to avoid hyperglycaemia in diabetic patients but has also its benefits in patients presenting with the metabolic syndrome (possible reduction of hyperinsulinaemia, hypertension and hyperlipoproteinaemia). Diabetic patients should have regular screening for microalbuminuria. At first signs of an early stage of nephropathy patients should be advised to restrict their protein intake. About 50% of daily energy intake should be derived from carbohydrates and fat intake should be no more than 35% of total energy (saturated fatty acids less than 10% of energy). Carbohydrate exchange units are usually not necessary in NIDDM patients. In addition diabetes specialty foods are not an essential part of the nutritional therapy. The success of the nutritional therapy in diabetic patients is substantially dependent upon qualified counselling and education of the patients by the physician (as far as possible with the assistance of a dietitian).

  17. Interventional anoxia therapy; Interventionelle Therapie des Schlaganfalls

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, Olav [Universitaetsklinikum Schleswig-Holstein (UKSH), Kiel (Germany). Inst. fuer Neuroradiologie; Brueckmann, Hartmut (eds.) [Univ. Muenchen-Grosshadern Klinikum, Muenchen (Germany). Abt. fuer Neuroradiologie

    2011-07-01

    The book on interventional anoxia therapy covers the following issues: (1) Neuroradiologic diagnostics: Closure of the carotid artery; closure of the cerebral arteries, vertebrobasilary closure; dissections, sinus and brain vein thrombosis; (2) therapy of the acute ischemic anoxia: thrombolysis; intra-arterial thrombolysis, mechanical re-channelization materials; stroke-stent; therapy concepts and results; (3) therapy for acute venous obliterations; (4) therapy for extra and intra-cranial artery stenosis: stents, filters, balloons; extra-cranial carotid stenosis; intra-cranial stenosis; sub-clavian Steal syndrome; proximal vertebral artery stenosis; aortic arch stenosis.

  18. Pain induced by photodynamic therapy of warts

    DEFF Research Database (Denmark)

    Stender, I-M; Borgbjerg, F Molke; Villumsen, J

    2006-01-01

    Photodynamic therapy with topical 5-aminolevulinic acid (ALA), followed by irradiation with red light (ALA-PDT), is used for non-melanoma skin cancer and other dermatological diseases. Pain during and after light exposure is a well-known adverse advent that may be a limiting factor for treatment,...

  19. 复方α酮酸辅助治疗对早期糖尿病肾病患者血清肾功能指标以及营养状态的影响%Effect of adjuvant α-keto acid therapy on serum renal function indexes and nutritional status in patients with early diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    张敏; 王璐

    2016-01-01

    Objective:To analyze the effect of adjuvant α-keto acid therapy on serum renal function indexes and nutri-tional status in patients with early diabetic nephropathy.Methods:A total of 86 patients with early diabetic nephropathy were divided into observation group and control group,control group received conventional therapy,observation group received con-ventional therapy + adjuvantα-keto acid therapy,and then differences in serum renal function indexes,nutrition index,vascu-lar endothelial function indexes,micro-inflammation indexes and so on were compared between two groups of patients after 2 months of treatment.Results:Serum renal function indexes UAER level as well as BUN,SCr,CysC andβ2-MG content of ob-servation group was lower than those of control group while GFR level was higher than that of control group;nutrition indexes ALB,PA and Hb content were higher than those of control group while nPCR level was lower than that of control group;vas-cular endothelial function indexes NO and CGRP content were higher than those of control group while ET-1,MCP-1 and re-sistin content were lower than those of control group;micro-inflammation indexes hs-CRP,IL-1β,IL-1 7,IL-22,TGF-β1 and SAA content were lower than those of control group.Conclusions:Adjuvant α-keto acid therapy helps to improve the renal function and nutritional status of patients with early diabetic nephropathy,and has positive significance in optimizing the overall treatment effect.%目的::分析复方α酮酸辅助治疗对早期糖尿病肾病患者血清肾功能指标以及营养状态的影响。方法:86例早期糖尿病肾病患者分为观察组及对照组,对照组接受常规治疗,观察组接受常规+复方α酮酸辅助治疗,对比两组患者的治疗2月后血清肾功能指标、营养指标、血管内皮功能指标、微炎症指标等差异。结果:观察组患者的血清肾功能指标 UAER 水平,BUN、SCr、CysC、β2-MG 含量低于对照组患者,GFR 水

  20. A terapia fotodinâmica com ácido 5-aminolevulínico como modalidade de tratamento para neoplasias cutâneas não-melanoma Topical 5-aminolevulinic acid photodynamic therapy as a treatment modality for nonmelanoma skin cancer

    Directory of Open Access Journals (Sweden)

    Lília Bernardini Antunes de Felício

    2008-08-01

    Full Text Available FUNDAMENTOS: A terapia fotodinâmica baseia-se na associação de fonte de luz e fotossensibilizador para destruir seletivamente as células. OBJETIVO: Avaliar os efeitos imediatos e tardios, a resposta clínica e os resultados estéticos da terapia fotodinâmica com ácido 5-aminolevulínico em neoplasias cutâneas não-melanoma. MÉTODOS: Trinta e quatro lesões, sendo 19 disceratoses de Bowen e 15 carcinomas basocelulares, foram submetidas à aplicação tópica e oclusiva do ácido 5-aminolevulínico a 20%, por seis horas, e posteriormente a sessão única de laser de diodo (630nm. RESULTADOS: Foram registrados: sensação de queimação durante as sessões; eritema, edema e erosões, nas primeiras 72 horas; cicatrização em média de quatro semanas; resultados estéticos variáveis de excelentes a bons. Aos três meses, a resposta clínica foi de 91,2%, sendo reduzida, aos 18 meses, para 73,3%, de modo similar tanto para disceratose de Bowen (72,2% quanto para carcinoma basocelular (75%. Foi evidenciada relação de tendência linear entre a redução da freqüência da resposta clínica e o aumento da dimensão das neoplasias cutâneas não-melanoma (pBACKGROUND: Photodynamic therapy is based on the association of a light source and photosensitizer in order to selectively destroy cells. OBJECTIVE: To evaluate the short and long-term effects, clinical response, and cosmetic outcome of the photodynamic therapy with 5-aminolaevulinic acid for non-melanoma skin cancer. METHODS: TThirty-four non-melanoma skin cancer - 19 Bowen’s diseases and 15 basal cell carcinomas, were submitted to a single 6-hour topical and occlusive application of 20% 5-aminolaevulinic acid, and were later exposed to 630 nm diode laser single session. RESULTS: Burning sensation during the session; erythema, edema and erosions in the first 72 hours; healing process after 4 weeks on average and excellent or good cosmetic results were observed. After 3 months, tumor

  1. Marriage or Family Therapy.

    Science.gov (United States)

    Haley, Jay

    1984-01-01

    Reviews the differences between family therapy and marriage counseling in terms of professional organization, theory, and practice. Suggests that training in marriage therapy does not appear adequate for family therapy. The goal of the therapy field should be more consensus in theory and a single profession of therapists. (JAC)

  2. Family Play Therapy.

    Science.gov (United States)

    Ariel, Shlomo

    This paper examines a case study of family play therapy in Israel. The unique contributions of play therapy are evaluated including the therapy's accessibility to young children, its richness and flexibility, its exposure of covert patterns, its wealth of therapeutic means, and its therapeutic economy. The systematization of the therapy attempts…

  3. Art Therapy Verses Psychotherapy

    Science.gov (United States)

    Del Giacco, Maureen

    2009-01-01

    The purpose of my paper is to identify the difference between psychotherapy and art therapy. Then to introduce a technique within the field of art therapy that is relevant to neuro-plasticity Del Giacco Neuro Art Therapy. The paper identifies the importance of the amygdala and the hippocampus within the role of art therapy. Supporting…

  4. Physical Therapy (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Physical Therapy KidsHealth > For Parents > Physical Therapy A A A en español Terapia física Physical Therapy Basics Doctors often recommend physical therapy (PT) for ...

  5. Marriage or Family Therapy.

    Science.gov (United States)

    Haley, Jay

    1984-01-01

    Reviews the differences between family therapy and marriage counseling in terms of professional organization, theory, and practice. Suggests that training in marriage therapy does not appear adequate for family therapy. The goal of the therapy field should be more consensus in theory and a single profession of therapists. (JAC)

  6. Peripheral neuropathy: pathogenic mechanisms and alternative therapies.

    Science.gov (United States)

    Head, Kathleen A

    2006-12-01

    Peripheral neuropathy (PN), associated with diabetes, neurotoxic chemotherapy, human immunodeficiency virus (HIV)/antiretroviral drugs, alcoholism, nutrient deficiencies, heavy metal toxicity, and other etiologies, results in significant morbidity. Conventional pain medications primarily mask symptoms and have significant side effects and addiction profiles. However, a widening body of research indicates alternative medicine may offer significant benefit to this patient population. Alpha-lipoic acid, acetyl-L-carnitine, benfotiamine, methylcobalamin, and topical capsaicin are among the most well-researched alternative options for the treatment of PN. Other potential nutrient or botanical therapies include vitamin E, glutathione, folate, pyridoxine, biotin, myo-inositol, omega-3 and -6 fatty acids, L-arginine, L-glutamine, taurine, N-acetylcysteine, zinc, magnesium, chromium, and St. John's wort. In the realm of physical medicine, acupuncture, magnetic therapy, and yoga have been found to provide benefit. New cutting-edge conventional therapies, including dual-action peptides, may also hold promise.

  7. Solid Lipid Nanoparticles Loaded with Retinoic Acid and Lauric Acid as an Alternative for Topical Treatment of Acne Vulgaris.

    Science.gov (United States)

    Silva, Elton Luiz; Carneiro, Guilherme; De Araújo, Lidiane Advíncula; Trindade, Mariana de Jesus Vaz; Yoshida, Maria Irene; Oréfice, Rodrigo Lambert; Farias, Luis de Macêdo; De Carvalho, Maria Auxiliadora Roque; Dos Santos, Simone Gonçalves; Goulart, Gisele Assis Castro; Alves, Ricardo José; Ferreira, Lucas Antônio Miranda

    2015-01-01

    Topical therapy is the first choice for the treatment of mild to moderate acne and all-trans retinoic acid is one of the most used drugs. The combination of retinoids and antimicrobials is an innovative approach for acne therapy. Recently, lauric acid, a saturated fatty acid, has shown strong antimicrobial activity against Propionibacterium acnes. However, topical application of retinoic acid is followed by high incidence of side-effects, including erythema and irritation. Solid lipid nanoparticles represent an alternative to overcome these side-effects. This work aims to develop solid lipid nanoparticles loaded with retinoic acid and lauric acid and evaluate their antibacterial activity. The influence of lipophilic stearylamine on the characteristics of solid lipid nanoparticles was investigated. Solid lipid nanoparticles were characterized for size, zeta potential, encapsulation efficiency, differential scanning calorimetry and X-ray diffraction. The in vitro inhibitory activity of retinoic acid-lauric acid-loaded solid lipid nanoparticles was evaluated against Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis. High encapsulation efficiency was obtained at initial time (94 ± 7% and 100 ± 4% for retinoic acid and lauric acid, respectively) and it was demonstrated that lauric acid-loaded-solid lipid nanoparticles provided the incorporation of retinoic acid. However, the presence of stearylamine is necessary to ensure stability of encapsulation. Moreover, retinoic acid-lauric acid-loaded solid lipid nanoparticles showed growth inhibitory activity against Staphylococcus epidermidis, Propionibacterium acnes and Staphylococcus aureus, representing an interesting alternative for the topical therapy of acne vulgaris.

  8. Folic acid

    Science.gov (United States)

    ... taking a specific nutritional supplement, containing vitamin B3 (nicotinamide), a compound isolated from grains (azelaic acid), zinc, ... lung cancer in most people. A type of skin cancer called melanoma. Limited research suggests that taking ...

  9. Folic Acid

    Science.gov (United States)

    ... B-complex vitamin needed by the body to manufacture red blood cells. A deficiency of this vitamin ... prepared from dried yeast, fruit, and fresh leafy green vegetables to increase the folic acid in your ...

  10. Screening of homocystinemia and H-type hypertension in health check-up populations and effect observation of folic acid intervention therapy%体检人群同型半胱氨酸血症与H型高血压的筛查及叶酸干预治疗效果观察

    Institute of Scientific and Technical Information of China (English)

    陈晓红; 廖家有; 王齐芳; 胡蓉; 谢东阳; 何华; 徐慧荣

    2015-01-01

    Objective To understand the level of plasma homocysteine (Hcy) in health check-up populations and to ob-serve the curative effect of folate intervention on hyperhomecysteinemia and enalapril and folic acid intervention on H-type hy-pertension. Methods 10 400 healthy individuals undergoing physical examination in the physical examination center of the First Affiliated Hospital of Ganan Medical College from January to December 2013 were selected as the research subjects. The Hcy level was detected and the simple hyperhomecysteinemia and H-type hypertension were screened and the intervention therapy was conducted. Among them,100 cases of simple hyperhomecysteinemia were selected and given the folic acid therapy;200 cases of H-type hypertension were divided into the two groups and respectively given the interventional therapy of enalapril combined with folic acid or enalapril folic acid (fixed compound) intervention therapy. Plasma Hcy was re-checked and sitting blood pressure was measured in 1,2,3 months of treatment. Results Among 10 400 cases of healthy examination population, high Hcy accounted for 23.08%(2 400/10 400),in which simple hyperhomecysteinemia was 8.78%(913/10 400),H-type hypertension was 14.30%(1 487/10 400). Plasma Hcy level in simple hyperhomecysteinemia patients was decreased after 1 ,2 and 3 months of folic acid intervention therapy,the differences were statistically significant(P0.05). Conclusion The higher proportion of simple hyperhomecysteinemia and H-type hypertension were screened out among the physical examina-tion population. It is suggested that the routine physical examination should pay attention to the Hcy level detection ,which has im-portant significance for screening hyperhomecysteinemia ,early finding H-type hypertension and conducting the early folic acid in-tervention therapy.%目的:了解体检人群同型半胱氨酸(Hcy)的水平,观察叶酸对高同型半胱氨酸血症及依那普利联合叶酸、依那普利叶

  11. Pyridoxine supplementation during isoniazid therapy.

    Science.gov (United States)

    Snider, D E

    1980-12-01

    Vitamin B6 (pyridoxine) supplementation during isoniazid (INH) therapy is necessary in some patients to prevent the development of peripheral neuropathy. In vivo pyridoxine is converted into coenzymes which play an essential role in the metabolism of protein, carbohydrates, fatty acids, and several other substances, including brain amines, INH apparently competitively inhibits the action of pyridoxine in these metabolic functions. The reported frequency of INH-induced neuropathy in various studies is reviewed and population groups at relatively high risk of developing this complication are identified. The routine use of pyridoxine supplementation to prevent peripheral neuropathy in high risk populations is recommended.

  12. OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction.

    Science.gov (United States)

    Rauch, Bernhard; Schiele, Rudolf; Schneider, Steffen; Diller, Frank; Victor, Norbert; Gohlke, Helmut; Gottwik, Martin; Steinbeck, Gerhard; Del Castillo, Ulrike; Sack, Rudolf; Worth, Heinrich; Katus, Hugo; Spitzer, Wilhelm; Sabin, Georg; Senges, Jochen

    2010-11-23

    There is no randomized, double-blind trial testing the prognostic effect of highly purified omega-3 fatty acids in addition to current guideline-adjusted treatment of acute myocardial infarction. OMEGA is a randomized, placebo-controlled, double-blind, multicenter trial testing the effects of omega-3-acid ethyl esters-90 (1 g/d for 1 year) on the rate of sudden cardiac death in survivors of acute myocardial infarction, if given in addition to current guideline-adjusted treatment. Secondary end points were total mortality and nonfatal clinical events. Patients (n=3851; female, 25.6%; mean age, 64.0 years) were randomized in 104 German centers 3 to 14 days after acute myocardial infarction from October 2003 until June 2007. Acute coronary angiography was performed in 93.8% and acute percutaneous coronary intervention in 77.8% of all patients. During a follow-up of 365 days, the event rates were (omega and control groups) as follows: sudden cardiac death, 1.5% and 1.5% (P=0.84); total mortality, 4.6% and 3.7% (P=0.18); major adverse cerebrovascular and cardiovascular events, 10.4% and 8.8% (P=0.1); and revascularization in survivors, 27.6% and 29.1% (P=0.34). Guideline-adjusted treatment of acute myocardial infarction results in a low rate of sudden cardiac death and other clinical events within 1 year of follow-up, which could not be shown to be further reduced by the application of omega-3 fatty acids. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251134.

  13. Non-viral gene delivery strategies for gene therapy: a "ménage à trois" among nucleic acids, materials, and the biological environment. Stimuli-responsive gene delivery vectors

    Science.gov (United States)

    Pezzoli, Daniele; Candiani, Gabriele

    2013-03-01

    Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription-translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors.

  14. Ibotenic acid and thioibotenic acid

    DEFF Research Database (Denmark)

    Hermit, Mette B; Greenwood, Jeremy R; Nielsen, Birgitte

    2004-01-01

    with the conformations preferred by the ligands upon docking to mGlu1 and models of the other mGlu subtypes, we propose that unlike other subtypes, group III mGlu receptor binding sites require a ligand conformation at an energy level which is prohibitively expensive for ibotenic acid, but not for thioibotenic acid....... These studies demonstrate how subtle differences in chemical structures can result in profound differences in pharmacological activity....

  15. Drug therapy during pregnancy.

    Science.gov (United States)

    Niebyl, J R

    1992-02-01

    A randomized prospective trial has shown that folic acid started before conception and continued for the first trimester reduces the risk of recurrence of neural tube defects by 72% in women with a previously affected child. Carbamazepine exposure in utero is associated with a 1% risk of spina bifida. Long-term follow-up of antenatal exposure to phenobarbital and carbamazepine in two groups of infants shows no neurologic differences between the two groups. Magnesium sulfate is more effective in prevention of recurrent eclamptic seizures than phenytoin. During pregnancy, the need for thyroxine increases in many women. Vitamin B6 and ginger are both effective for nausea and vomiting in early pregnancy. Low-dose aspirin does not change the course of preeclampsia when it is started after the diagnosis is made. Angiotensin-converting enzyme inhibitors cause significant disturbances of fetal and neonatal renal function. Prophylactic beta-adrenergic agents fail to prevent prematurity in twins. Oral tocolysis with magnesium chloride or ritodrine is no more effective than observation alone. The risk of primary pulmonary hypertension in the newborn after indomethacin tocolysis is increased with prolonged therapy. Lithium causes polyhydramnios from fetal diabetes insipidus in utero. Treatment of Ureaplasma urealyticum infection with erythromycin during pregnancy does not eliminate the organism from the lower genital tract and does not improve perinatal outcome.

  16. Progress of mechanism of ω-3 polyunsaturated fatty acid in sepsis therapy%ω-3多不饱和脂肪酸治疗脓毒症的机制研究进展

    Institute of Scientific and Technical Information of China (English)

    缪红军

    2015-01-01

    Inflammation,immune suppression and oxidative stress is the main pathogenesis of sepsis.In recent years,more study have found ω-3 polyunsaturated fatty acid(ω-3PUFA) can inhibit inflammation by some mechanisms namely,reducing metabolites from arachidonic acid(AA) by competing with it through a variety of ways,alteration of membrane lipid rafts,inhibition of nuclear receptor activation(specifically nuclear factor NF-κB)to modulate production of inflammatory mediators,and metabolism into novel pro-resolving and antiinflammatory mediators (resolvins and protectins).In addition,ω-3PUFA can reduce oxidative stress by improvement the antioxidant defense system,etc.Many clinical studies have demonstrated that ω-3PUF is effective in the for sepsis patients.The paper reviews the specific mechanism of ω-3PUFA treatment for sepsis.%炎症反应、免疫抑制、氧化应激等是脓毒症的主要致病机制.近年来研究发现,ω-3多不饱和脂肪酸(ω-3 polyunsaturated fatty acid,ω-3PUFA)可通过多种途径与花生四烯酸竞争,减少其代谢产物;通过改变细胞膜信号平台“脂筏”的性质、通过其代谢产物参与炎症的消退与组织修复,降低NF-κB的激活,抑制炎症反应.ω-3PUFA还能改善机体的抗氧化防御系统,减轻氧化应激.目前临床研究证实ω-3 PUFA能有效治疗脓毒症患者.该文就ω-3PUFA治疗脓毒症的具体机制作一综述.

  17. Acid Rain

    Science.gov (United States)

    Bricker, Owen P.; Rice, Karen C.; Dietrich, W.E.; Sposito, Garrison

    1997-01-01

    Acid deposition, or acid rain as it is more commonly referred to, has become a widely publicized environmental issue in the U.S. over the past decade. The term usually conjures up images of fish kills, dying forests, "dead" lakes, and damage to monuments and other historic artifacts. The primary cause of acid deposition is emission of S02 and NOx to the atmosphere during the combustion of fossil fuels. Oxidation of these compounds in the atmosphere forms strong acids - H2SO4 and HNO3 - which are returned to the Earth in rain, snow, fog, cloud water, and as dry deposition.Although acid deposition has only recently been recognized as an environmental problem in the U.S., it is not a new phenomenon (Cogbill & Likens 1974). As early as the middle of the 17th century in England, the deleterious effects of industrial emissions on plants, animals, and humans, and the atmospheric transport of pollutants between England and France had become issues of concern (Evelyn 1661, Graunt 1662). It is interesting that well over three hundred years ago in England, recommendations were made to move industry outside of towns and build higher chimneys to spread the pollution into "distant parts." Increasing the height of smokestacks has helped alleviate local problems, but has exacerbated others. In the U.S. the height of the tallest smokestack has more than doubled, and the average height of smokestacks has tripled since the 1950s (Patrick et al 1981). This trend occurred in most industrialized nations during the 20th century and has had the effect of transforming acid rain from a local urban problem into a problem of global scale.

  18. Music Therapy and Music Therapy Research. Response

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This response to Keynote by Prof. Even Ruud (N)"Music Education and Music Therapy seeks to define these two areas with specific focus on tools and methods for analysis of music as these methods are developed in music therapy. This includes that the music therapist, the music and the client create...

  19. Music Therapy and Music Therapy Research. Response

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This response to Keynote by Prof. Even Ruud (N)"Music Education and Music Therapy seeks to define these two areas with specific focus on tools and methods for analysis of music as these methods are developed in music therapy. This includes that the music therapist, the music and the client create...

  20. New Form of Hypertonic Solution for Nebulization Therapy

    Directory of Open Access Journals (Sweden)

    O. I. Simonova

    2016-01-01

    Full Text Available Mucolytic, expectorative and antitussive drugs are traditionally used in acute or chronic respiratory episodes affected by acute respiratory infections. Today, preference is given to drugs in a form of solutions for nebulization therapy. The article presents data on the new dosage form of 7% inhalation hypertonic solution in combination with hyaluronic acid used in mucostasis therapy for chronic respiratory diseases. The information on the properties and the favorable effect of hyaluronic acid is provided. We discuss the evidence base of inhalation of the hypertonic solution in combination with hyaluronic acid in cystic fibrosis.

  1. Complementary and Integrative Therapies

    Science.gov (United States)

    ... Art therapy and music therapy • Chiropractic medicine and massage • Guided imagery • Meditation and prayer • Qi gong • Reflexology • Reiki • Yoga Whole medical systems use many types ...

  2. Virtual particle therapy centre

    CERN Multimedia

    2015-01-01

    Particle therapy is an advanced technique of cancer radiation therapy, using protons or other ions to target the cancerous mass. This advanced technique requires a multi-disciplinary team working in a specialised centre. 3D animation: Nymus3D

  3. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  4. Gerson Therapy (PDQ)

    Science.gov (United States)

    ... therapy be conducted. Have any side effects or risks been reported from use of the Gerson therapy? Reports of three deaths that may be related to coffee enemas have been published. Taking too many enemas ...

  5. Physical Therapy Diagnosis

    National Research Council Canada - National Science Library

    Zimny, Nancy J; Goodman, Catherine C; Orest, Marianne; Delitto, Anthony; Snyder-Mackler, Lynn

    1995-01-01

    ...: Examples in Orthopedic Physical Therapy" (March 1995). I believe the article raised multiple issues that are important to address to move the discussion of diagnosis within the physical therapy profession forward...

  6. Targeted Cancer Therapies

    Science.gov (United States)

    ... changes, hair depigmentation) Problems with blood clotting and wound healing High blood pressure Gastrointestinal perforation (a rare side effect of some targeted therapies) Certain side effects of some targeted therapies have ...

  7. American Occupational Therapy Association

    Science.gov (United States)

    ... Manage Your Practice Evidence-Based Practice & Research Ethics Occupational Therapy Assistants Advocacy & Policy New Evaluation Codes Learn how ... Reimbursement Education & Careers OT is a Top Job Occupational therapy consistently ranks high as one of the top ...

  8. Hyperbaric oxygen therapy

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002375.htm Hyperbaric oxygen therapy To use the sharing features on this page, please enable JavaScript. Hyperbaric oxygen therapy uses a special pressure chamber to increase ...

  9. Hormone Replacement Therapy

    Science.gov (United States)

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  10. Photodynamic Therapy for Cancer

    Science.gov (United States)

    ... References Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nature Reviews Cancer 2003; 3(5):380–387. [PubMed Abstract] Wilson BC. Photodynamic therapy for cancer: principles. Canadian Journal of Gastroenterology 2002; ...

  11. Home Oxygen Therapy

    Science.gov (United States)

    ... Teenagers Living With Lung Disease Articles written by Respiratory Experts Home Oxygen Therapy More and more people are using oxygen therapy ... April 12, 2012 Revised: © 2017 American Association for Respiratory Care

  12. Photodynamic therapy for cancer

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000906.htm Photodynamic therapy for cancer To use the sharing features on ... type of light to kill cancer cells. How Photodynamic Therapy Works First, the doctors injects a medicine that ...

  13. Complementary Pancreatitis Therapies

    Science.gov (United States)

    ... medication, and improve quality of life.1,2 Massage Therapy Massage therapy involves touch and different techniques of stroking ... of the body or be a full-body massage. Massage can be performed through one’s clothing or ...

  14. Perfluorooctanoic acid

    NARCIS (Netherlands)

    de Voogt, P.; Wexler, P.

    2014-01-01

    Perfluorooctanoic acid (PFOA, 335-67-1) is used in fluoropolymer production and firefighting foams and persists in the environment. Human exposure to PFOA is mostly through the diet. PFOA primarily affects the liver and can cause developmental and reproductive toxic effects in test animals.

  15. Physical Therapy and Surgery

    OpenAIRE

    Valle-Onate, Rafael; Ward, Michael M.; Kerr, Gail S.

    2012-01-01

    Physical therapy and orthopedic surgery are important components in the treatment of ankylosing spondylitis (AS). Supervised physical therapy is more effective that individual or unsupervised exercise in improving symptoms, but controlled trials suggest than combined inpatient and outpatient therapy provides the greatest improvement. Recommendations for exercise are universal, but the best types and sequence of therapies are not known. Total hip replacement is the surgery most commonly perfor...

  16. Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer therapy.

    Science.gov (United States)

    McCarty, Mark F

    2013-10-01

    Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor whose elevated activity in many cancers helps them to survive under hypoxic conditions and enhances their capacity to grow invasively, establish metastases, and survive chemo- or radiotherapy. Optimal intracellular levels of ascorbate suppress the level and transcriptional activity of HIF-1under normoxic or mildly hypoxic conditions by supporting the activity of proly and asparagyl hydroxylases that target HIF-1alpha. High intracellular ascorbate can also work in various ways to down-regulate activation of NF-kappaB which, like HIF-1 is constitutively active in many cancers and promotes aggressive behavior - in part by promoting transcription of HIF-1alpha. Yet recent evidence suggests that, even in the context of adequate ascorbate nutrition, the intracellular ascorbate content of many aggressive cancers may be supoptimal for effective HIF-1 control. This likely reflects low expression or activity of the SVCT2 ascorbate transporter. The expression of SVCT2 in cancers has so far received little study; but the extracellular acidity characteristic of many tumors would be expected to reduce the activity of this transporter, which has a mildly alkaline pH optimum. Unfortunately, since SVCT2 has a high affinity for ascorbate, and its activity is nearly saturated at normal healthy serum levels of this vitamin, increased oral administration of ascorbate would be unlikely to have much impact on the intracellular ascorbate content of tumors. However, cancers in which HIF-1 is active express high levels of glucose transporters such as GLUT-1, and these transporters can promote influx of dehydroascorbic acid (DHA) via facilitated diffusion; once inside the cell, DHA is rapidly reduced to ascorbate, which effectively is "trapped" within the cell. Hence, episodic intravenous infusions of modest doses of DHA may have potential for optimizing the intracellular ascorbate content of cancers, potentially

  17. Musings on Adventure Therapy.

    Science.gov (United States)

    Alvarez, Antonio G.; Stauffer, Gary A.

    2001-01-01

    Critiques various definitions of adventure therapy, then suggests that adventure therapy is any intentional, facilitated use of adventure tools and techniques to guide personal change toward desired therapeutic goals. Reflects on the nature of adventure therapy through a discussion of the application of this definition and its implications for…

  18. Venous Thromboembolism Anticoagulation Therapy

    Institute of Scientific and Technical Information of China (English)

    刘泽霖

    2009-01-01

    @@ VTE of the main treatment for anticoagulant thera-py, anticoagulant therapy drug of choice for low molecu-lar weight heparin (LMWH) for the overwhelming major-ity of clinicians agree that long-term oral anticoagulant therapy is still Vit. K antagonist (mainly warfarin).

  19. Aquatic Therapy for Children

    Science.gov (United States)

    Kucher, Greta; Moore, Kelsey; Rodia, Rachel; Moser, Christy Szczech

    2015-01-01

    Aquatic therapy has long been highlighted in the literature as a potentially powerful therapeutic intervention. This review will highlight basic definitions of aquatic therapy, review salient research, and identify specific diagnoses that may benefit from aquatic therapy. Online resources, blogs, and books that occupational therapists may find…

  20. Aquatic Therapy for Children

    Science.gov (United States)

    Kucher, Greta; Moore, Kelsey; Rodia, Rachel; Moser, Christy Szczech

    2015-01-01

    Aquatic therapy has long been highlighted in the literature as a potentially powerful therapeutic intervention. This review will highlight basic definitions of aquatic therapy, review salient research, and identify specific diagnoses that may benefit from aquatic therapy. Online resources, blogs, and books that occupational therapists may find…

  1. Evaluation of Inter Therapy

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This article (revised conference lecture from the 10th World Congress of Music Therapy, Oxford July 2002)) emphasizes the evaluation of the training of Inter Therapy for music therapy students at the MA training at Aalborg University. The students take turns in being client and therapist within...

  2. American Music Therapy Association

    Science.gov (United States)

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login Quick Links Facts About Music Therapy Qualifications of ... with AMTA Sponsor AMTA Events Social Networking Support Music Therapy When you shop at AmazonSmile, Amazon will donate ...

  3. Cardiovascular Effects of Salvianolic Acid B

    OpenAIRE

    Jie Wang; Xingjiang Xiong; Bo Feng(Zhejiang Institute of Modern Physics, Zhejiang University, 38 Zheda Road, Hangzhou 310027, P.R. China)

    2013-01-01

    Salvianolic acid B (SAB, Sal B) is the representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge (Labiatae) which has been used widely and successfully in Asian countries for clinical therapy of various vascular disturbance-related diseases for hundreds of years. However, its exact cardioprotective components and the underlying mechanism for therapeutic basis are still poorly understood. This paper discussed and elucidated the underlying bio...

  4. Hyperammonemia Associated with Valproic Acid Concentrations

    Directory of Open Access Journals (Sweden)

    Marta Vázquez

    2014-01-01

    Full Text Available Valproic acid, a branched short-chain fatty acid, has numerous action mechanisms which turn it into a broad spectrum anticonvulsant drug and make its use possible in some other pathologies such as bipolar disorder. It is extensively metabolized in liver, representing β-oxidation in the mitochondria one of its main metabolic route (40%. Carnitine is responsible for its entry into the mitochondria as any other fatty acid. Long-term high-dose VPA therapy or acute VPA overdose induces carnitine depletion, resulting in high levels of ammonia in blood. As a high correlation between salivary valproic acid levels and plasma ultrafiltrate levels was found in humans, saliva becomes a promising monitoring fluid in order to study valproic acid pharmacokinetics and its toxic effect. Extended-release (twice daily formulations of valproic acid or carnitine supplementation are the proposed two therapeutic strategies in order to reverse hyperammonemia.

  5. Clinical Effect of 5-aminolevulinic Acid Photodynamic Therapy Combined with Carbon Dioxide Laser on Condyloma Acuminatum in Senile Patients%5-氨基酮戊酸光动力联合CO2激光治疗老年尖锐湿疣临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    李灿; 兰长贵; 梅晓锋; 陈伟; 赵静

    2015-01-01

    目的:探讨5-氨基酮戊酸光动力疗法(5-aminolevulinic acid photodynamic therapy ,ALA-PDT)联合CO2激光治疗老年尖锐湿疣的临床疗效。方法选择我院就诊的60例老年尖锐湿疣患者,随机分为治疗组和对照组各30人,对照组仅采用CO2激光去除疣体;治疗组用CO2激光去除疣体,用20%ALA溶液沿疣体周围2cm外敷创面,薄膜封包3小时后用光动力治疗仪距离患处15cm照射20分钟,每周1次,连续3周。治疗结束后两组患者均随访6个月。结果治疗组完成随访27例,对照组完成随访29例。治疗组治愈率为70.37%,对照组治愈率为37.93%,两组治愈率差异具有统计学意义(P<0.05)。结论5-氨基酮戊酸光动力联合CO2激光治疗老年尖锐湿疣治愈率高,复发率低。%Objective To discuss the clinical effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with car-bon dioxide laser on condyloma acuminatum in senile patients. Methods 60 senile out-patients with condyloma acuminatum were select-ed and divided randomly into 2 groups:treatment group and control group, 30 in each;carbon dioxide laser was applied in removing the warts of the patients in both groups while ALA-PDT was added to patients in treatment group:external application of 20%ALA liquid was made on the lesions and the round area within 2cm and the lesions were covered with occlusive film for 3 hours, and then were irra-diated by Photodynamic Therapeutic Apparatus with a distance of 15cm from the lesions for 20 minutes, once a week, 3 times in total;follow-up lasted from 6 months in both group. Results 27 patients in treatment group received follow-up while 29 in control group;the cure rate in treatment group was 70.37%while 37.93%in control group, the difference was of statistical significance (P<0.05). Conclu-sions 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with carbon dioxide laser is of high cure rate and low reoccur

  6. Newer and upcoming therapies for melasma

    Directory of Open Access Journals (Sweden)

    Rashmi Sarkar

    2012-01-01

    Full Text Available Melasma is one of the most common and distressing pigmentary disorders presenting to dermatology clinics. The precise cause of melasma remains unknown; however, there are many possible contributing factors. It is notably difficult to treat and has a tendency to relapse. The existing and most tried topical therapy is hydroquinone and the triple combination with tretinoin and corticosteroids, which is considered the gold standard for melasma. Besides that, azelaic acid, kojic acid, arbutin, ascorbic acid, glycolic acid and salicylic peels have also been tried with limited success. However, multiple novel topical agents are being investigated for their potential as hypopigmenting agents with unique mode of action. But, further trials are required to study their efficacy and safety before they can be further recommended. The article highlights these newer formulations and also briefly mentions about the newer chemical peels and the much hyped lasers in treating this difficult and frustrating condition.

  7. Hendee's radiation therapy physics

    CERN Document Server

    Pawlicki, Todd; Starkschall, George

    2016-01-01

    The publication of this fourth edition, more than ten years on from the publication of Radiation Therapy Physics third edition, provides a comprehensive and valuable update to the educational offerings in this field. Led by a new team of highly esteemed authors, building on Dr Hendee’s tradition, Hendee’s Radiation Therapy Physics offers a succinctly written, fully modernised update. Radiation physics has undergone many changes in the past ten years: intensity-modulated radiation therapy (IMRT) has become a routine method of radiation treatment delivery, digital imaging has replaced film-screen imaging for localization and verification, image-guided radiation therapy (IGRT) is frequently used, in many centers proton therapy has become a viable mode of radiation therapy, new approaches have been introduced to radiation therapy quality assurance and safety that focus more on process analysis rather than specific performance testing, and the explosion in patient-and machine-related data has necessitated an ...

  8. Radiation Therapy: Professions in Radiation Therapy

    Science.gov (United States)

    ... Resources Professions Site Index A-Z Professions in Radiation Therapy Radiation Oncologist Therapeutic Medical Physicist Radiation Therapist Dosimetrist Radiation Oncology Nurse Social Worker Dietitian Radiation Oncologist Radiation oncologists are physicians who oversee the ...

  9. Art Therapy: What Is Art Therapy?

    Science.gov (United States)

    ... manage behavior and addictions, develop social skills, improve reality orientation, reduce anxiety, and increase self-esteem. A goal in art therapy is to improve or restore a client’s functioning ...

  10. Radon therapy; Radon in der Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Spruck, Kaija [Technische Hochschule Mittelhessen, Giessen (Germany). Inst. fuer Medizinische Physik und Strahlenschutz

    2017-04-01

    Radon therapies are used since more than 100 years in human medicine. Today this method is controversially discussed due to the possible increase of ionizing radiation induced tumor risk. Although the exact mode of biological radiation effect on the cell level is still not known new studies show the efficiency of the radon therapy without side effect for instance for rheumatic/inflammatory or respiratory disorders.

  11. Hydroxycarboxylic acids and salts

    Energy Technology Data Exchange (ETDEWEB)

    Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N

    2015-02-24

    Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.

  12. Nanocarriers in gene therapy: a review.

    Science.gov (United States)

    Xu, Hongpan; Li, Zhiyang; Si, Jin

    2014-12-01

    With its rapid development in the past few decades, gene therapy has shown potential for use as a standard clinical intervention for the treatment of several conditions, including cancers, infectious diseases, cardiovascular disorders, inner ear disorders, dermatological, ophthalmologic, and neurological pathologies. Current gene therapy is not limited to the delivery of DNA only. Other therapeutic nucleic acid materials such as small interfering RNA, antisense oligonucleotides, or microRNA have also been included into the protocols of gene therapy. The correct choice of vector is a key factor in the success of gene therapy, where both viral and non-viral vectors are commonly used. Viral vectors are associated with some severe side effects (e.g., immunologenicity and carcinogenicity). They show poor target cell specificity, are unable to transfer large-sized genes, and are costly. Therefore, non-viral vectors, especially nanocarriers, have become a realistic alternative to viral vectors for achieving better efficacy in gene therapy. Different types of nanocarriers such as liposomes, metallic and polymeric nanoparticles, dendrimers, gelatins, and quantum dots/rods have been developed, and each shows distinct characteristics. Nevertheless, a variety of new challenges should be properly addressed for ensuring the success of nanocarriers in clinical applications. In this review article, we first discuss the advances and applications of nanocarriers in gene therapy, and then describe the drawbacks and existing challenges of the emerging gene delivery methods based on the use of nanomaterials.

  13. An overview of gene therapy in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Amit Bali

    2013-01-01

    Full Text Available Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction and expression, mediation of apoptosis and clinical response including pathological complete responses. The objective of this article is to provide an overview of the current available gene therapies for head and neck cancer.

  14. Light therapies for acne.

    Science.gov (United States)

    Barbaric, Jelena; Abbott, Rachel; Posadzki, Pawel; Car, Mate; Gunn, Laura H; Layton, Alison M; Majeed, Azeem; Car, Josip

    2016-09-27

    -assessed outcomes in the majority of studies. Attrition and reporting bias were low in over half of the studies and unclear or high in the rest. Two thirds of studies were industry-sponsored; study authors either reported conflict of interest, or such information was not declared, so we judged the risk of bias as unclear.Comparisons of most interventions for our first primary outcome 'Participant's global assessment of improvement' were not possible due to the variation in the interventions and the way the studies' outcomes were measured. We did not combine the effect estimates but rated the quality of the evidence as very low for the comparison of light therapies, including PDT to placebo, no treatment, topical treatment or other comparators for this outcome. One study which included 266 participants with moderate to severe acne showed little or no difference in effectiveness for this outcome between 20% aminolevulinic acid (ALA)-PDT (activated by blue light) versus vehicle plus blue light (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.72 to 1.04, low-quality evidence). A study (n = 180) of a comparison of ALA-PDT (activated by red light) concentrations showed 20% ALA was no more effective than 15% (RR 1.05, 95% CI 0.96 to 1.15) but better than 10% ALA (RR 1.22, 95% CI 1.05 to 1.42) and 5% ALA (RR 1.47, 95% CI 1.19 to 1.81). The number needed to treat for an additional beneficial outcome (NNTB) was 6 (95% CI 3 to 19) and 4 (95% CI 2 to 6) for the comparison of 20% ALA with 10% and 5% ALA, respectively.For our second primary outcome 'Investigator-assessed changes in lesion counts', we combined three RCTs, with 360 participants with moderate to severe acne and found methyl aminolevulinate (MAL) PDT (activated by red light) was no different to placebo cream plus red light with regard to change in inflamed lesions (ILs) (mean difference (MD) -2.85, 95% CI -7.51 to 1.81), percentage change in ILs (MD -10.09, 95% CI -20.25 to 0.06), change in non-inflamed lesions (NILs) (MD -2

  15. 病变内激素注射结合抑酸疗法治疗喉接触性肉芽肿的疗效分析%Analysis of the curative effect of intralesional steroid injection combined with acid-suppressive therapy for laryngeal contact granuloma

    Institute of Scientific and Technical Information of China (English)

    田师宇; 李进让; 郭鹏飞; 李可亮; 张昊

    2016-01-01

    Objective To study the efficacy of intralesional steroid injection combined with acidsuppressive therapy for laryngeal contact granuloma.Methods Eighty eight patients with laryngeal contact granuloma diagnosed from March 2010 to October 2014 were reviewed.Twenty-one patients took intralesional steroid injection combined with acid-suppressive therapy as experimental group (4 patients in initial treatment group,17 patients in non-initial treatment group),other 67 patients only received acid-suppressive therapy as control group.The clinical data of these patients was analyzed.Results In experimental group,15 patients were cured (71.43%) and the average cure time were (3.80 ± 0.43) months,total injection time was 2-6 times and the median was 3 times.In control group,50 patients were cured (74.63%) and the average cure time were (5.31 ±0.38) months.No any systemic and local complications were found in all the patients during the follow-up period of 6-42 months.The cure rate had no significant difference between the experimental group and control group,but the cure time in the former group was shorter than that in the latter group (Z =-2.093,P =0.036).In the experimental group,the initial treatment patients had no significant difference in cure rate and cure time compared with non initial patients (x2 =1.112,P =0.544;Z =O.000,P =1.000).Conclusion Intralesional steroid injection combined with acid-suppressive therapy can be recommended as a safe and effective alternative therapy for laryngeal contact granuloma,especially the refractory granuloma.%目的 评估并探讨病变内激素注射结合抑酸疗法对喉接触性肉芽肿的治疗效果.方法 回顾性分析2010年3月至2014年10月在海军总医院耳鼻咽喉头颈外科诊治的88例特发性喉接触性肉芽肿患者,采取病变内激素注射结合抑酸疗法的21例患者作为试验组(初治组患者4例,非初治组患者17例),同期将采取单纯抑酸疗法的67例患者作为对照组,

  16. [Physical therapy in osteoarthritis].

    Science.gov (United States)

    Gnjidić, Zoja

    2010-01-01

    Physical therapy has an important role in treating rheumatic diseases; its goal is to reduced pain, swelling and to keep joints mobile. The properly manage osteoarthritis is nonpharmacological and pharmacological modalities. Physical therapy applied as a remedy for osteoarthritis is a part of multimodal therapy. The basis for physical therapy management is determined by the recommendation of the physical therapeutic science and evidence-based medicine. When making a decision about application of different methods of treatment in physical therapy, it is important to correctly diagnose a structural transformation and functional problem. Systematic review of the scientific, evidence-based, international concensus recommendations for the management of the osteoarthritis published between 2000 and 2010 were identified high-quality evidence therapy practice that is efficient and effective in increasing movement capability function, and reduce pain, disability, medical intake and improved physical function for patients with osteoarthritis

  17. Unproven (questionable) cancer therapies.

    Science.gov (United States)

    Brigden, M L

    1995-11-01

    More than half of all cancer patients use some form of alternative treatment during the course of their illness. Alternative therapies are often started early in patients' illness, and their use is frequently not acknowledged to health care professionals. Some alternative therapies are harmful, and their promoters may be fraudulent. Persons who try alternative cancer therapies may not be poorly educated but may ultimately abandon conventional treatment. Recent attention has focused on aspects of questionable therapies that make these treatments attractive to patients and that may be perceived as being deficient in the practice of conventional health care professionals. Physicians with patients with cancer should always make sure that unproven therapies are discussed early in the therapeutic relationship. They should also attempt to be aware of alternative therapies that are in vogue in their particular geographic area.

  18. Drug therapy for diabetes.

    Science.gov (United States)

    Haas, L B

    1991-09-01

    Drug therapy with oral hypoglycemic agents and insulin are components of diabetes management regimens that also include diet, exercise/activity, monitoring, and education. Major concerns for practitioners using drug therapy are selection of the appropriate therapy for a particular patient, and drug interactions and side effects. Drug therapy is based on knowledge of the medications' pharmacokinetics; glucose goals, as determined by practitioners and patients; common sense; and strong participatory relationships between practitioners and patients and, if indicated, families. When using insulin, practitioners need to consider the differences between insulin therapy for insulin-dependent and non-insulin-dependent diabetes; how to initiate, adjust, and supplement insulin; situations that require variations in insulin therapy; and injection mechanics.

  19. Nuclear medicine therapy

    CERN Document Server

    Eary, Janet F

    2013-01-01

    One in three of the 30 million Americans who are hospitalized are diagnosed or treated with nuclear medicine techniques. This text provides a succinct overview and detailed set of procedures and considerations for patient therapy with unsealed radioactivity sources.  Serving as a complete literature reference for therapy with radiopharmaceuticals currently utilized in practice, this source covers the role of the physician in radionuclide therapy, and essential procedures and protocols required by health care personnel.

  20. Principles of gene therapy

    OpenAIRE

    Mammen Biju; Ramakrishnan T; Sudhakar Uma; Vijayalakshmi

    2007-01-01

    Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. This article reviews the fundamentals in gene therapy and its various modes of administration with an insight into the role of gene therapy in Periodontics an...

  1. Advances in Cancer Therapy

    OpenAIRE

    Jordan BF, Sonveaux P

    2011-01-01

    The book "Advances in Cancer Therapy" is a new addition to the Intech collection of books and aims at providing scientists and clinicians with a comprehensive overview of the state of current knowledge and latest research findings in the area of cancer therapy. For this purpose research articles, clinical investigations and review papers that are thought to improve the readers' understanding of cancer therapy developments and/or to keep them up to date with the most recent advances in this fi...

  2. Placental gene therapy

    OpenAIRE

    David, A. L.; Ashcroft, R

    2009-01-01

    Gene therapy uses genetic material as a drug delivery vehicle to express therapeutic proteins. Placental gene therapy may be useful for correction of two important obstetric conditions, foetal growth restriction and pre-eclampsia in which there is a failure of the physiological trophoblast remodelling of the uterine spiral arteries in early pregnancy. The patient in this scenario is the foetus. Placental gene therapy might be justifiable when: there is reasonable certainty that the foetus wil...

  3. Biological therapies for spondyloarthritis

    OpenAIRE

    Bruner, Vincenzo; Atteno, Mariangela; Spanò, Angelo; Scarpa, Raffaele; Peluso, Rosario

    2014-01-01

    Biological therapies and new imaging techniques have changed the therapeutic and diagnostic approach to spondyloarthritis. In patients with axial spondyloarthritis, tumor necrosis factor α (TNFα) inhibitor treatment is currently the only effective therapy in patients for whom conventional therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) has failed. TNFα inhibitor treatment is more effective in preventing articular damage in peripheral joints than in axial ones. It is important to tr...

  4. Cochlear Gene Therapy

    OpenAIRE

    2012-01-01

    The purpose of this review is to highlight recent advances in cochlear gene therapy over the past several years. Cochlear gene therapy has undergone tremendous advances over the past decade. Beginning with some groundbreaking work in 2005 documenting hair cell regeneration using virallymediated delivery of the mouse atonal 1 gene, gene therapy is now being explored as a possible treatment for a variety of causes of hearing loss.

  5. Unproven (questionable) cancer therapies.

    OpenAIRE

    Brigden, M.L.

    1995-01-01

    More than half of all cancer patients use some form of alternative treatment during the course of their illness. Alternative therapies are often started early in patients' illness, and their use is frequently not acknowledged to health care professionals. Some alternative therapies are harmful, and their promoters may be fraudulent. Persons who try alternative cancer therapies may not be poorly educated but may ultimately abandon conventional treatment. Recent attention has focused on aspects...

  6. Evaluation of Inter Therapy

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This article (revised conference lecture from the 10th World Congress of Music Therapy, Oxford July 2002)) emphasizes the evaluation of the training of Inter Therapy for music therapy students at the MA training at Aalborg University. The students take turns in being client and therapist within...... the same partner constellation. Through this training they learn as a therapeutic method to contain and incorporate experiences from being in the client role into managing the therapist role....

  7. Hydrofluoric acid poisoning

    Science.gov (United States)

    Fluorhydric acid ... stomach, or intestine have holes (perforations) from the acid. ... Hydrofluoric acid is especially dangerous. The most common accidents involving hydrofluoric acid cause severe burns on the skin ...

  8. 降尿酸治疗对痛风高尿酸血症患者IL-1β和 NALP3水平的影响%Influence of Uric Acid-Lowering Therapy on IL-1βand NALP3 Levels in Gout Patients with Hyperuricemia

    Institute of Scientific and Technical Information of China (English)

    罗来敏; 陈钦开; 杨小娟

    2016-01-01

    目的:观察黄嘌呤氧化酶抑制剂对痛风高尿酸血症患者体内炎症因子水平的影响。方法将72例痛风高尿酸血症患者按治疗方法的不同分为3组,分别给予非布司他40 mg·d-1、80 mg·d-1、别嘌呤醇300 mg·d-1治疗6个月;另选24例健康受试者作为对照组。所有受试者治疗前后进行血尿酸检测,采用 ELISA 法进行血清白介素-1β(IL-1β)和核苷酸结合寡聚化结构域样受体3(NALP3)水平检测。结果治疗前痛风治疗组血尿酸水平明显高于对照组,药物治疗6个月后血尿酸水平明显降低。治疗前痛风治疗组血清 IL-1β水平高于对照组,药物治疗后血清 IL-1β水平有所下降;治疗前痛风治疗组血清 NALP3水平低于对照组,药物治疗后血清 IL-1β水平有所上升。结论黄嘌呤氧化酶抑制剂能明显降低这类患者血尿酸水平,降尿酸治疗可能存在下调体内炎症反应的趋势。%ABSTRACT:Objective To observe the influence of xanthine oxidase inhibitors on the levels of inflammatory factors in gout patients with hyperuricemia.Methods Seventy-two gout patients with hyperuricemia were treated with febuxostat 40 mg·d-1 ,febuxostat 80 mg·d-1 or allopuri-nol 300 mg·d-1 for 6 months.In addition,24 healthy subjects were selected as the control group. Blood uric acid levels were detected before and after treatment.Furthermore,serum IL-1β and NALP3 levels were measured by ELISA.Results Before treatment,gout patients with hyperuri-cemia had higher levels of uric acid and IL-1βand lower levels of NALP3 than healthy subjects. However,levels of uric acid and IL-1βwere decreased and levels of NALP3 were increased in pa-tients after treatment for 6 months.Conclusion Xanthine oxidase inhibitors can significantly de-crease uric acid levels in gout patients.Uric acid-lowering therapy may show a trend of reducing inflammatory reactions.

  9. Medical Art Therapy

    Directory of Open Access Journals (Sweden)

    Birgul Aydin

    2012-03-01

    Full Text Available Art therapy is a form of expressive therapy that uses art materials. Art therapy combines traditional psychotherapeutic theories and techniques with an understanding of the psychological aspects of the creative process, especially the affective properties of the different art materials. Medical art therapy has been defined as the clinical application of art expression and imagery with individuals who are physically ill, experiencing physical trauma or undergoing invasive or aggressive medical procedures such as surgery or chemotherapy and is considered as a form of complementary or integrative medicine. Several studies have shown that patients with physical illness benefit from medical art therapy in different aspects. Unlike other therapies, art therapy can take the patients away from their illness for a while by means of creative activities during sessions, can make them forget the illness or lost abilities. Art therapy leads to re-experiencing normality and personal power even with short creative activity sessions. In this article definition, influence and necessity of medical art therapy are briefly reviewed.

  10. Physical Therapy and Surgery

    Science.gov (United States)

    Valle-Onate, Rafael; Ward, Michael M.; Kerr, Gail S.

    2012-01-01

    Physical therapy and orthopedic surgery are important components in the treatment of ankylosing spondylitis (AS). Supervised physical therapy is more effective that individual or unsupervised exercise in improving symptoms, but controlled trials suggest than combined inpatient and outpatient therapy provides the greatest improvement. Recommendations for exercise are universal, but the best types and sequence of therapies are not known. Total hip replacement is the surgery most commonly performed for AS, with good long-term implant survival. Heterotopic ossification may occur no more frequently after hip replacement in patients with AS than in patients with other diseases. Corrective spinal surgery is rarely performed and requires specialized centers and experienced surgeons. PMID:22543536

  11. Neutron Therapy Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Neutron Therapy Facility provides a moderate intensity, broad energy spectrum neutron beam that can be used for short term irradiations for radiobiology (cells)...

  12. Antiplatelet therapy and exodontia

    National Research Council Canada - National Science Library

    Schreuder, Willem H; Peacock, Zachary S

    2015-01-01

    .... The authors reviewed the literature, focusing on the indications and mechanisms of antiplatelet therapy and the perioperative management of patients taking these agents who require exodontia or other...

  13. [Morita therapy over history].

    Science.gov (United States)

    Usa, Shinichi

    2003-01-01

    At Sansei Hospital in Kyoto we performed Morita Therapy not only for Japanese clients but also foreign clients from several countries, like Germany, Switzerland, U.S.A., China, Korea, India and Indonesia. We could treat those foreign clients using Morita Therapy with good success although they came from various cultural backgrounds. One of the characteristic Approaches of Morita Therapy was that it avoided the conceptualization of self-consciousness and self image as a subjective fiction established by abstract and logical thinking. Secondary Morita Therapy moves clients to deal with activities in real life. These 2 approaches help clients not to be involved in symptom development or fixation mechanisms and break through self-centeredness. At the first stage of Morita Therapy, namely in the bed rest period clients can experience his psychic state as if he were a just born baby. The founder of Gestalt Therapy, Frederick S. Perls experienced by himself Morita Therapy. During bed rest therapy he behaved as if he were a baby. This behavior came out not from conscious abstract and logical thinking but from spontaneous "pre-conscious" state of mind. Morita called this "Jun-na-kokoro" (Pure mind). Morita knew that neurotic symptoms come out from those abstract and logical thinking which could lead to fixation of symptoms so that therapy principle might be the de-centralization of self and the pure mind experience which is found in our daily life and also in daily life of foreign people from various cultural backgrounds.

  14. [Cognitive behavior therapy].

    Science.gov (United States)

    Munezawa, Takeshi

    2009-08-01

    Insomnia is one of the most frequently encountered disorders in general clinical practices. At present, the most commonly used therapy for insomnia is pharmacotherapy. There are some problems in pharmacotherapy such as side effects. Therefore nonpharmacological therapy for insomnia is needed. The cognitive behavior therapy for insomnia (CBT-I) is a nonpharmacological therapy attracting attention most. CBT-I not only alleviates insomnia symptoms in patients but also enables them to reduce/discontinue the use of hypnotics. I reviewed a study about the effectiveness of CBT-I and commented the future directions of CBT-I.

  15. Writing Music Therapy

    Directory of Open Access Journals (Sweden)

    Mary Helena Rykov

    2011-03-01

    Full Text Available

    Communicating about music therapy is problematic because discursive language fails to convey the nonverbal, embodied essence of experience. I explore the emergence of this problem in the music therapy literature. I discuss the scholarship of phenomenological writing. I provide examples of nondiscursive music therapy writing. I introduce the genre of poetic inquiry.

    Poetry is the most musical form of language. Poetry and music, linked throughout history, share many characteristics. It makes sense that we use poetry to write about music therapy.

    Writing is a crucial skill for music therapy professionals who must produce various notes, proposals, and reports. Writing poetically is a diminished stance compared to discursive prose writing. It is understandable that representing music therapy in experimental, tentative, and creative texts is risky. I invite music therapists to aspire towards poetry when writing music therapy to better address nonverbal, embodied, music therapy essence. I address this invitation to all writers of music therapy: undergraduate and graduate students, clinicians, and researchers.

  16. Music Therapy with Adolescents

    Directory of Open Access Journals (Sweden)

    Jukko Tervo

    2005-03-01

    Full Text Available The therapeutic community described in this paper was situated at the University of Oulu Central Hospital Department of Psychiatry, Finland, during the years 1979-1989. The ward consisted of eight beds, four for boys and four for girls. The basic emphasis in the treatment was laid on psychoanalytic psychotherapy and music and art therapies suitable for the stage of adolescent development. Adolescent community therapy (psychoanalytic psychotherapy, music therapy, art therapy, special school etc. creates an environment which supports individual growth of the adolescent and youth culture. This, in turn, simultaneously supports psychotherapy.

  17. Bile acid signaling and biliary functions

    Directory of Open Access Journals (Sweden)

    Hannah Jones

    2015-03-01

    Full Text Available This review focuses on various components of bile acid signaling in relation to cholangiocytes. Their roles as targets for potential therapies for cholangiopathies are also explored. While many factors are involved in these complex signaling pathways, this review emphasizes the roles of transmembrane G protein coupled receptor (TGR5, farnesoid X receptor (FXR, ursodeoxycholic acid (UDCA and the bicarbonate umbrella. Following a general background on cholangiocytes and bile acids, we will expand the review and include sections that are most recently known (within 5–7 years regarding the field of bile acid signaling and cholangiocyte function. These findings all demonstrate that bile acids influence biliary functions which can, in turn, regulate the cholangiocyte response during pathological events.

  18. [Treatment of hypertriglyceridemia with omega-3 fatty acids].

    Science.gov (United States)

    Miyoshi, Toru; Ito, Hiroshi

    2013-09-01

    Omega-3 fatty acids such as eicosapentaenoic acid(EPA) and docosahexaenoic acid(DHA) have important biologic functions, including effects on membranes, eicosanoid metabolism, and gene transcription. Studies indicate that the use of EPA and DHA lowered triglyceride levels, which is accomplished by decreasing the production of hepatic triglycerides and increasing the clearance of plasma triglycerides. Recent clinical studies showed that intake of omega-3 fatty acids reduced cardiovascular events. In addition, combination therapy with omega-3 fatty acids and a statin is a safe and effective way to improve lipid levels and cardiovascular prognosis beyond the benefits provided by statin therapy alone. Our focus is to review the potential mechanisms by which these fatty acids reduce cardiovascular disease risk.

  19. Cognitive Behavioral Therapy and Motivational Enhancement Therapy.

    Science.gov (United States)

    Wu, Sarah S; Schoenfelder, Erin; Hsiao, Ray Chih-Jui

    2016-10-01

    Although cognitive behavioral therapy (CBT) is widely recognized as the preferred treatment of psychiatric disorders, less is known about the application of CBT to substance use disorders, particularly in adolescence. This article discusses how CBT conceptualizes substance use and how it is implemented as a treatment of adolescent substance abuse. The article draws on several manuals for CBT that implement it as a standalone treatment or in combination with motivational enhancement therapies. Also reviewed are several studies that examined the efficacy of CBT. Finally, the implications are discussed. Numerous starting resources are provided to help a clinician implement CBT.

  20. Hyaluronic acid for anticancer drug and nucleic acid delivery.

    Science.gov (United States)

    Dosio, Franco; Arpicco, Silvia; Stella, Barbara; Fattal, Elias

    2016-02-01

    Hyaluronic acid (HA) is widely used in anticancer drug delivery, since it is biocompatible, biodegradable, non-toxic, and non-immunogenic; moreover, HA receptors are overexpressed on many tumor cells. Exploiting this ligand-receptor interaction, the use of HA is now a rapidly-growing platform for targeting CD44-overexpressing cells, to improve anticancer therapies. The rationale underlying approaches, chemical strategies, and recent advances in the use of HA to design drug carriers for delivering anticancer agents, are reviewed. Comprehensive descriptions are given of HA-based drug conjugates, particulate carriers (micelles, liposomes, nanoparticles, microparticles), inorganic nanostructures, and hydrogels, with particular emphasis on reports of preclinical/clinical results.