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Sample records for 5-aminolevulinic acid treatment

  1. Optical spectroscopy by 5-aminolevulinic acid hexylester induced photodynamic treatment in rat bladder cancer

    NASA Astrophysics Data System (ADS)

    Larsen, Eivind L. P.; Randeberg, Lise L.; Gederaas, Odrun A.; Arum, Carl-Jørgen; Krokan, Hans E.; Hjelme, Dag R.; Svaasand, Lars O.

    2006-02-01

    Photodynamic therapy (PDT) is a treatment modality which has been shown to be effective for both malignant and non-malignant diseases. New photosensitizers such as 5-aminolevulinic acid hexylester (hALA) may increase the efficiency of PDT. Monitoring of the tissue response provides important information for optimizing factors such as drug and light dose for this treatment modality. Optical spectroscopy may be suited for this task. To test the efficacy of hALA induced PDT, a study on rats with a superficial bladder cancer model, in which a bladder cancer cell line (AY-27) is instilled, will be performed. Preliminary studies have included a PDT feasibility study on rats, fluorescence spectroscopy on AY-27 cell suspensions, and optical reflection and fluorescence spectroscopy in rat bladders in vivo. The results from the preliminary studies are promising, and the study on hALA induced PDT treatment of bladder cancer will be continued.

  2. Comparison of 5-Aminolevulinic Acid Photodynamic Therapy and Clobetasol Propionate in Treatment of Vulvar Lichen Sclerosus.

    PubMed

    Shi, Lei; Miao, Fei; Zhang, Ling-Lin; Zhang, Guo-Long; Wang, Pei-Ru; Ji, Jie; Wang, Xiao-Jie; Huang, Zheng; Wang, Hong-Wei; Wang, Xiu-Li

    2016-06-15

    The aim of this study was to evaluate the effectiveness of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) for the treatment of vulvar lichen sclerosus (VLS) and compare its effectiveness with that of clobetasol propionate. Four sessions of topical photodynamic therapy (PDT) were administered at 2-week intervals (n = 20). Clobetasol propionate (0.05%) was used daily for 8 weeks (n = 20). The rate of complete response in the PDT group (14/20) was double that of the clobetasol propionate group (7/20) (p < 0.05, 2 = 4.912). Horizontal visual analogue scores indicated that PDT was more effective than clobetasol propionate. Pain intensity numeric rating scale values for PDT were between 3.05 and 4.45. One month after the final session of PDT, only one patient relapsed and all 7 patients in clobetasol propionate group relapsed. ALA-PDT is a well-tolerated and effective option for the treatment of VLS. PMID:26775671

  3. 5-Aminolevulinic Acid Photodynamic Therapy combined with CO2 laser therapy in treatment of laryngeal papilloma: Case report.

    PubMed

    Zhang, Yunjie; Yang, Yuguang; Zou, Xianbiao; Huang, Zheng

    2016-06-01

    This article describes the case of 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT) via self-retaining laryngoscope under general anesthesia combined with CO2 Laser Therapy in the treatment of three patients with juvenile laryngeal papilloma. Laryngeal papilloma Clinically, it features rapid growth, multi-focus, frequent recurrence and possibility of spreading to the lower respiratory tract. ALA-PDT via self-retaining laryngoscope under general anesthesia combined with CO2 Laser Therapy is safe and effective for clearing laryngeal papilloma, laryngeal papilloma was fully removed from the three patients, with no recurrence during the 6-24 months of follow-up medical examination. 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT) via self-retaining laryngoscope under general anesthesia combined with CO2 Laser can be used for treating laryngeal papilloma. PMID:27045601

  4. Effect of 5-aminolevulinic acid on erythropoiesis: A preclinical in vitro characterization for the treatment of congenital sideroblastic anemia

    SciTech Connect

    Fujiwara, Tohru; Takahashi, Kiwamu; Okitsu, Yoko; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Ichinohasama, Ryo; Nakamura, Yukio; Nakajima, Motowo; Tanaka, Tohru; Harigae, Hideo

    2014-11-07

    Highlights: • Treatment with ALA induces erythroid differentiation of K562 cells. • Transportation of ALA into erythroid cells occurs predominantly via SLC36A1. • ALA restores defects in ALAS2 in human iPS cell-derived erythroblasts. • ALA may represent a novel therapeutic option for CSA caused by ALAS2 mutations. - Abstract: Congenital sideroblastic anemia (CSA) is a hereditary disorder characterized by microcytic anemia and bone marrow sideroblasts. The most common form of CSA is attributed to mutations in the X-linked gene 5-aminolevulinic acid synthase 2 (ALAS2). ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), a crucial precursor in heme synthesis. Therefore, ALA supplementation could be an effective therapeutic strategy to restore heme synthesis in CSA caused by ALAS2 defects. In a preclinical study, we examined the effects of ALA in human erythroid cells, including K562 cells and human induced pluripotent stem cell-derived erythroid progenitor (HiDEP) cells. ALA treatment resulted in significant dose-dependent accumulation of heme in the K562 cell line. Concomitantly, the treatment substantially induced erythroid differentiation as assessed using benzidine staining. Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed significant upregulation of heme-regulated genes, such as the globin genes [hemoglobin alpha (HBA) and hemoglobin gamma (HBG)] and the heme oxygenase 1 (HMOX1) gene, in K562 cells. Next, to investigate the mechanism by which ALA is transported into erythroid cells, quantitative RT-PCR analysis was performed on previously identified ALA transporters, including solute carrier family 15 (oligopeptide transporter), member (SLC15A) 1, SLC15A2, solute carrier family 36 (proton/amino acid symporter), member (SLC36A1), and solute carrier family 6 (neurotransmitter transporter), member 13 (SLC6A13). Our analysis revealed that SLC36A1 was abundantly

  5. Needle-free injection of 5-aminolevulinic acid in photodynamic therapy for the treatment of condylomata acuminata

    PubMed Central

    LI, XIULI; WANG, XIUXIU; GU, JUNYING; MA, YUE’E; LIU, ZHIYU; SHI, YULING

    2013-01-01

    The external application of 5-aminolevulinic acid (ALA) in photodynamic therapy (PDT) results in a shallow penetration depth in thick or extensive condylomata acuminata (CA) lesions, thus demonstrating a poor therapeutic effect for those patients. To compare the efficacy of needle-free injection with external application of ALA in PDT for the treatment of CA, 160 CA patients with thick or extensive warts received ALA-PDT by means of external application or needle-free injection of ALA, respectively. The complete response (CR) rate and recurrence rate in the two groups were analyzed. The CR rate after the first treatment in the needle-free injection group (68.8%) was significantly higher compared with that in the external application group (52.5%; P=0.035). The recurrence rates in the needle-free injection group and external application group were 4.1 and 15.4%, respectively (P=0.022). The needle-free injection of ALA increases the therapeutic effect of PDT for CA patients with thick or extensive lesions. It shortens the treatment time and reduces the recurrence rate, and has great potential in the treatment of CA. PMID:23935753

  6. Prospective study of topical 5-aminolevulinic acid photodynamic therapy for the treatment of severe adolescent acne in Chinese patients.

    PubMed

    Ma, Ying; Liu, Ye; Wang, Qianqian; Ren, Jie; Xiang, Leihong

    2015-05-01

    Acne vulgaris is one of the most common skin diseases in adolescents. In the present study, we aimed to evaluate the effectiveness and safety of topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) for the treatment of severe acne in Chinese adolescent patients. Twenty-one Chinese adolescent patients aged 12-18 years with Pillsbury III-IV severe facial acne were treated with three courses of ALA-PDT. A 5% ALA lotion was applied topically for 60 min followed by irradiation with light-emitting diode light at 633 nm with a light intensity of 75-80 mW/cm(2) and a light dose of 90-96 J/cm(2) . Clinical assessment was conducted before and after each treatment, and at each follow-up session. The total effective rates were 85.71%, 90.48%, and 95.23% after the three PDT sessions, and at the 4- and 8-week follow ups, respectively. ALA-PDT is an effective treatment for severe adolescent acne vulgaris, and is associated with mild and reversible side-effects. PMID:25772520

  7. Chitosan-based mucoadhesive films containing 5-aminolevulinic acid for buccal cancer's treatment.

    PubMed

    Costa, Irina dos Santos Miranda; Abranches, Renata Pereira; Garcia, Maria Teresa Junqueira; Pierre, Maria Bernadete Riemma

    2014-11-01

    Photodynamic therapy (PDT) is a relatively new method to treat various kinds of tumors, including those of the oral cavity. The topical 5-ALA-PDT treatment for tumors of the oral mucosa is preferred, since when administered systemically, there is a general photosensitization drawback in the patient. However, 5-ALA is a hydrophilic molecule and its penetration and retention is limited by topical route, including oral mucosa. We propose a topical delivery system of chitosan-based mucoadhesive film, aiming to promote greater retention of 5-ALA in tissue. The chitosan (CHT) films (4% w/w) were prepared using the solvent evaporation/casting technique. They were tested without 5-ALA resulting in permeability to water vapor (W.V.P=2.15-8.54 g mm/(h cm(2)Pa) swelling ∼300.0% (±10.5) at 4 h or 24 h and in vitro residence time >24 h for all tests. CHT films containing 10.0% (w/w) 5-ALA have resulted in average weight of 0.22 g and thickness of 0.608 mm as suitable characteristics for oral application. In the presence of CHT films both in vitro permeation and retention of 5-ALA (1.0% or 10.0%) were increased. However, 10.0% 5-ALA presented highest values of permeation and retention (∼4 and 17 times respectively, compared to propylene glycol vehicle). On the other hand, in vitro mucoadhesion of CHT films was decreased (18.2-fold and 3.1-fold) by 5-ALA addition (1.0% or 10.0% respectively). However, CHT film containing 10.0% of 5-ALA can be a potential delivery system for topical use in the treatment of tumors of the oral cavity using PDT because it favored the retention of 5-ALA in this tissue and has shown convenient mucoadhesion. PMID:25190225

  8. 5-Aminolevulinic Acid-based Photodynamic Intense Pulsed Light Therapy Shows Better Effects in the Treatment of Skin Photoaging in Asian Skin

    PubMed Central

    Xiang, Leihong Flora; Gold, Michael H.

    2010-01-01

    Objective: To investigate the effects of photodynamic intense pulsed light therapy on skin photoaging in Asian skin. Methods: This was a prospective, single-blinded, controlled, clinical trial with 40 patients enrolled. The enrolled patients applied 5% 5-aminolevulinic acid on the left side of the face while a placebo was applied on the right side of the face. After a one-hour incubation, the patients received intense pulsed light therapy. After four treatment cycles, the pH values, transepidermal water loss of the dermis of the forehead and canthus skin, as well as the moisture capacity of stratum corneum and the global score of photoaging were assessed. Results: The pH value of forehead and canthus skin, moisture capacity of stratum corneum, and the dermis of forehead and canthus skin of the photodynamic intense pulsed light therapy treated sides were significantly higher than those of the control sides in all of the patients. The photoaging score decreased after the therapy on both sides, with the photodynamic intense pulsed light therapy treated sides decreasing more than the control sides (P<0.01). Conclusion: 5-aminolevulinic acid photodynamic intense pulsed light therapy showed better effects in the treatment of skin photoaging compared to intense pulsed light therapy alone. PMID:20725543

  9. Microbial production and applications of 5-aminolevulinic acid.

    PubMed

    Liu, Shuli; Zhang, Guangming; Li, Xiangkun; Zhang, Jie

    2014-09-01

    5-Aminolevulinic acid (ALA), an important intermediate in tetrapyrrole biosynthesis in organisms, has been widely applied in many fields, such as medicine, agriculture, and the food industry, due to its biochemical characteristics. Research efforts supporting the microbial production of ALA have received increasing interest due to its dominant advantages over chemical synthesis, including higher yields, lesser pollutant emissions, and a lesser monetary cost. ALA synthesis using photosynthetic bacteria (PSB) is a promising approach in various microbial synthesis methods. In this review, recent advances on the microbial production of ALA with an emphasis on PSB are summarized, the key enzymes in the biosynthesis pathway (especially the relationship between key enzymes and key genes) are detailed, regulation strategies are described, and the significant influencing factors on the ALA biosynthesis and application of ALA are outlined. Furthermore, the eco-friendly perspective involving the combination of wastewater treatment and microbial production of ALA is conceived. PMID:25022665

  10. 5-aminolevulinic acid in photodynamic diagnosis and therapy of urological malignancies

    NASA Astrophysics Data System (ADS)

    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.

  11. 5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction.

    PubMed

    Fujino, Masayuki; Nishio, Yoshiaki; Ito, Hidenori; Tanaka, Tohru; Li, Xiao-Kang

    2016-08-01

    5-Aminolevulinic acid (5-ALA) is a naturally occurring amino acid and precursor of heme and protoporphyrin IX (PpIX). Exogenously administrated 5-ALA increases the accumulation of PpIX in tumor cells specifically due to the compromised metabolism of 5-ALA to heme in mitochondria. PpIX emits red fluorescence by the irradiation of blue light and the formation of reactive oxygen species and singlet oxygen. Thus, performing a photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-ALA have given rise to a new strategy for tumor diagnosis and therapy. In addition to the field of tumor therapy, 5-ALA has been implicated in the treatment of inflammatory disease, autoimmune disease and transplantation due to the anti-inflammation and immunoregulation properties that are elicited with the expression of heme oxygenase (HO)-1, an inducible enzyme that catalyzes the rate-limiting step in the oxidative degradation of heme to free iron, biliverdin and carbon monoxide (CO), in combination with sodium ferrous citrate (SFC), because an inhibitor of HO-1 abolishes the effects of 5-ALA. Furthermore, NF-E2-related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), and heme are involved in the HO-1 expression. Biliverdin and CO are also known to have anti-apoptotic, anti-inflammatory and immunoregulatory functions. We herein review the current use of 5-ALA in inflammatory diseases, transplantation medicine, and tumor therapy. PMID:26643355

  12. A Pilot Cost-Effectiveness Analysis of Treatments in Newly Diagnosed High-Grade Gliomas: The Example of 5-Aminolevulinic Acid Compared With White-Light Surgery

    PubMed Central

    Alves, Marta; Castel-Branco, Marta; Stummer, Walter

    2015-01-01

    BACKGROUND: High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA). OBJECTIVE: To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service. METHODS: We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, life-years, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratios are below €10 000 in all evaluated outcomes, being around €9100 per quality-adjusted life-year gained, €6700 per life-year gained, and €8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of €20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year. CONCLUSION: 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on

  13. Photodynamic inactivation of Klebsiella pneumoniae biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester.

    PubMed

    Liu, Chengcheng; Zhou, Yingli; Wang, Li; Han, Lei; Lei, Jin'e; Ishaq, Hafiz Muhammad; Nair, Sean P; Xu, Jiru

    2016-04-01

    The treatment of Klebsiella pneumoniae, particularly extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, is currently a great challenge. Photodynamic antimicrobial chemotherapy is a promising approach for killing antibiotic-resistant bacteria. The aim of this study was to evaluate the capacity of 5-aminolevulinic acid (5-ALA) and its derivative 5-ALA methyl ester (MAL) in the presence of white light to cause photodynamic inactivation (PDI) of K. pneumoniae planktonic and biofilm cells. In the presence of white light, 5-ALA and MAL inactivated planktonic cells in a concentration-dependent manner. Biofilms were also sensitive to 5-ALA and MAL-mediated PDI. The mechanisms by which 5-ALA and MAL caused PDI of ESBL-producing K. pneumonia were also investigated. Exposure of K. pneumonia to light in the presence of either 5-ALA or MAL induced cleavage of genomic DNA and the rapid release of intracellular biopolymers. Intensely denatured cytoplasmic contents and aggregated ribosomes were also detected by transmission electron microscopy. Scanning electron microscopy showed that PDI of biofilms caused aggregated bacteria to detach and that the bacterial cell envelope was damaged. This study provides insights into 5-ALA and MAL-mediated PDI of ESBL-producing K. pneumoniae. PMID:26886586

  14. The 5-aminolevulinic acid-induced porphyrin biosynthesis in benign and malignant cells of the skin.

    PubMed

    Lang, K; Bolsen, K; Stahl, W; Ruzicka, T; Sies, H; Lehmann, P; Fritsch, C

    2001-12-01

    In fluorescence diagnosis and photodynamic therapy of neoplastic tissues 5-aminolevulinic acid is used to synthesize endogenous porphyrins as photosensitizers. The efficacy of neoplastic tissues to fluorescence diagnosis and photodynamic therapy is thought to be dependent on the total level of intralesional formed porphyrins. The available profiles of porphyrin metabolites in normal and in neoplastic cell lines after administration of 5-aminolevulinic acid vary considerably. Thus, this is the first in-vitro study which compares the porphyrin biosynthesis in normal skin cells (HaCaT, fibroblasts) with melanoma cells (Bro, SKMel-23, SKMel-28). After incubation with 1 mM 5-aminolevulinic acid, kinetics of porphyrin levels and metabolites were determined in the cells and the corresponding supernatants. Exogenous 5-aminolevulinic acid induced porphyrin formation in all cells with maximum values after an incubation period of 16-36 h. Increase of porphyrin levels varied from 10- to 80-fold (SKMel-28>HaCaT>fibroblasts>SKMel-23>Bro) with minimum 1.5 times higher levels of porphyrins in the supernatants than in the cells. In cells and supernatants protoporphyrin and coproporphyrin were the predominantly formed porphyrin metabolites. Metastatic melanoma cells (SKMel-23, SKMel-28) accumulated much higher porphyrin levels than primary melanoma cells (Bro). In conclusion, by optimizing the treatment modalities, especially the light source, topical photodynamic therapy (PDT) could become a treatment alternative of melanoma metastases in progressive disease. PMID:11748002

  15. Photofrin and 5-aminolevulinic acid permeation through oral mucosa in vitro

    NASA Astrophysics Data System (ADS)

    Flock, Stephen T.; Alleman, Anthony; Lehman, Paul; Blevins, Steve; Stone, Angie; Fink, Louis; Dinehart, Scott; Stern, Scott J.

    1994-07-01

    Photofrin and 5-aminolevulinic acid are photosensitizers that show promise in the photodynamic treatment of cancer, port-wine stains, atherosclerosis and viral lesions. Photofrin is a mixture of porphyrins which, upon the absorption of light, become temporarily cytotoxic. One side-effect associated with the use of Photofrin is long-term cutaneous photosensitivity. It is possible that topical application of this photosensitizing dye will ameliorate such a side-effect. Another way to avoid the cutaneous photosensitivity in photodynamic therapy is to use 5- aminolevulinic acid, which is a porphyrin precursor that causes an increase in the synthesis and concentration of the photosensitizer protoporphyrin IX. 5-aminolevulinic acid is usually applied topically, and so minimizes cutaneous photosensitivity while maximizing the local protoporphyrin concentration. There are a host of disorders in oral mucosa that are potentially treatable by photodynamic therapy. However, since stratum corneum presents an impermeable barrier to many pharmaceuticals, it is not clear that topical application of the photosensitizer will result in a clinically relevant tissue concentration. We have therefore studied the permeation behavior of Photofrin and 5-aminolevulinic acid by applying them to the surface of ex vivo oral mucosa tissue positioned by a Franz diffusion cell. In order to increase the permeability of the photosensitizer across the stratum corneum, we studied the effects of four different drug carriers: phosphate buffered saline, dimethylsulfoxide, ethanol and Azone with isopropyl alcohol.

  16. Clinical efficacy of 5-aminolevulinic acid photodynamic therapy in the treatment of moderate to severe facial acne vulgaris

    PubMed Central

    CHEN, XIANGQI; SONG, HONGTAO; CHEN, SHENGPING; ZHANG, JING; NIU, GAOXIANG; LIU, XIANGNONG

    2015-01-01

    Acne vulgaris is considered as a therapeutic challenge in terms of managing ongoing symptoms and preventing scar formation. Although there are many available treatments for alleviating acne, therapies for resistant or moderate-to-severe forms have been limited to systemic agents that are accompanied by potentially severe side-effects. While, aminolevulinic acid (ALA) photodynamic therapy (PDT) has increasingly been used as a simple and safe therapeutic option of acne vulgaris, the clinical efficacy requires confirmation in further studies. The aim of this study was to investigate the efficacy and safety of 5-ALA-PDT in the treatment of moderate-to-severe facial acne vulgaris. A total of 50 patients with moderate-to-severe facial acne were enrolled in the study and randomly divided equally into a therapy group and a control group. In the therapy group, the patients were treated with 5% 5-ALA for 1.5 h, followed by three 20-min doses of infrared radiation once a week; in the control group, the patients were treated with three 20 min doses of infrared radiation without 5-ALA once a week. Both treatments lasted for 3 weeks. The clinical efficacy was determined by evaluating acne lesion counts at weeks 0, 2, 4 and 6. Total efficacy rate (TER) was the primary endpoint of the study, and was defined as the proportion of the patients whose treatment effectiveness evaluation was cured (≥90% of skin lesions improved) and excellent (60–89% improvement). Adverse effects were recorded throughout the study. The study was completed by 24 patients in the therapy group and 23 patients in the control group. The numbers of acne lesions significantly decreased. The TER of the therapy group was significantly higher than that of the control group at weeks 4 and 6. Adverse effects were observed in 12 patients of the therapy group and 2 patients of the control group. In the therapy group the most common adverse effect was a burning sensation (n=7), followed by transient

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Isolation and characterization of a new mutant of Saccharomyces cerevisiae with altered synthesis of 5-aminolevulinic acid.

    PubMed Central

    Carvajal, E; Panek, A D; Mattoon, J R

    1990-01-01

    A new gene, RHM1, required for normal production of 5-aminolevulinic acid by Saccharomyces cerevisiae, was identified by a novel screening method. Ethyl methanesulfonate treatment of a fluorescent porphyric strain bearing the pop3-1 mutation produced nonfluorescent or weakly fluorescent mutants with defects in early stages of tetrapyrrole biosynthesis. Class I mutants defective in synthesis of 5-aminolevulinate regained fluorescence when grown on medium supplemented with 5-aminolevulinate, whereas class II mutants altered in later biosynthetic steps did not. Among six recessive class I mutants, at least three complementation groups were found. One mutant contained an allele of HEM1, the structural gene for 5-aminolevulinate synthase, and two mutants contained alleles of the regulatory gene CYC4. The remaining mutants contained genes complementary to both hem1 and cyc4. Mutant strain DA3-RS3/68 contained mutant gene rhm1, which segregated independently of hem1 and cyc4 during meiosis. 5-Aminolevulinate synthase activity of the rhm1 mutant was 35 to 40% of that of the parental pop3-1 strain, whereas intracellular 5-aminolevulinate concentration was only 3 to 4% of the parental value. Transformation of an rhm1 strain with a multicopy plasmid containing the cloned HEM1 gene restored normal levels of 5-aminolevulinate synthase activity, but intracellular 5-aminolevulinate was increased to only 9 to 10% of normal. We concluded that RHM1 could control either targeting of 5-aminolevulinate synthase to the mitochondrial matrix or the activity of the enzyme in vivo. PMID:2188943

  19. Intraoperative 5-aminolevulinic acid-induced fluorescence in primary central nervous system lymphoma.

    PubMed

    Grossman, Rachel; Nossek, Erez; Shimony, Nir; Raz, Michal; Ram, Zvi

    2014-01-01

    The authors report a case of primary CNS lymphoma located in the floor of the fourth ventricle that showed intense fluorescence after preoperative administration of 5-aminolevulinic acid. The authors believe that this is the first demonstration of a 5-aminolevulinic acid-induced fluorescence pattern in primary CNS lymphoma. PMID:24138204

  20. Pleiotropic effects of 5-aminolevulinic acid in mouse brain.

    PubMed

    Lavandera, Jimena; Rodríguez, Jorge; Ruspini, Silvina; Meiss, Roberto; Zuccoli, Johanna Romina; Martínez, María Del Carmen; Gerez, Esther; Batlle, Alcira; Buzaleh, Ana María

    2016-08-01

    5-Aminolevulinic acid (ALA) seems to be responsible for the neuropsychiatric manifestations of acute intermittent porphyria (AIP). Our aim was to study the effect of ALA on the different metabolic pathways in the mouse brain to enhance our knowledge about the action of this heme precursor on the central nervous system. Heme metabolism, the cholinergic system, the defense enzyme system, and nitric oxide metabolism were evaluated in the encephalon of CF-1 mice receiving a single (40 mg/kg body mass) or multiple doses of ALA (40 mg/kg, every 48 h for 14 days). We subsequently found ALA accumulation in the encephalon of the mice. ALA also altered the brain cholinergic system. After one dose of ALA, a decrease in superoxide dismutase activity and a reduction in glutathione levels were detected, whereas malondialdehyde levels and catalase activity were increased. Heme oxygenase was also increased as an antioxidant response to protect the encephalon against injury. All nitric oxide synthase isoforms were induced by ALA, these changes were more significant for the inducible isoform in glial cells. In conclusion, ALA affected several metabolic pathways in mouse encephalon. Data indicate that a rapid response to oxidative stress was developed; however, with long-term intoxication, the redox balance was probably restored, thereby minimizing oxidative damage. PMID:27472495

  1. Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status

    NASA Astrophysics Data System (ADS)

    Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

    1995-03-01

    Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

  2. Review of dermatology use of 5-aminolevulinic acid photodynamic therapy in China from 1997 to 2013

    NASA Astrophysics Data System (ADS)

    Wang, Peiru; Zhang, Guolong; Wang, Xiuli

    2015-07-01

    The prodrug 5-aminolevulinic acid (ALA) and its ester derivatives have been used in photodynamic therapy (PDT) in dermatology worldwide. In China, ALA-PDT was first used to treat urethral condylomata acuminata and non-melanoma skin cancers in 1997. A powder formulation of ALA hydrochloride was approved by the Chinese Food and Drug Administration for the treatment of condylomata acuminata in 2007. Large successful experience of treating condylomatas was accumulated compared with Western countries. Meanwhile, numerous clinical studies as well as off-label use of ALAPDT have been carried out in China. To reflect the progress of ALA-PDT in China, several major Chinese and English databases were searched and published data were reviewed in this article.

  3. Dual pH-responsive 5-aminolevulinic acid pseudopolyrotaxane prodrug micelles for enhanced photodynamic therapy.

    PubMed

    Tong, Hongxin; Wang, Yin; Li, Huan; Jin, Qiao; Ji, Jian

    2016-03-11

    Novel 5-aminolevulinic acid (ALA) pseudopolyrotaxane prodrug micelles with dual pH-responsive properties were prepared by the host-guest interaction of α-cyclodextrin (α-CD) and poly(ethylene glycol) (PEG). The micelles exhibited pH dependent cellular uptake and pH-sensitive ALA release, enabling enhanced photodynamic therapy. PMID:26882232

  4. 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

    PubMed Central

    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. PMID:25140800

  5. Binding of /sup 14/C-5-aminolevulinic acid to a stromal protein from developing pea chloroplasts

    SciTech Connect

    Thayer, S.S.; Castelfranco, P.A.; Wilkinson, J.; Benson, G.

    1987-04-01

    /sup 14/-5-Aminolevulinic acid (/sup 14/C-ALA) binds to a stromal protein with an apparent molecular weight of 42-43 KD on LDS and non-denaturing gels. The reaction is rapid. Binding is inhibited by sulfhydryl reagents, mM concentrations of levulinic, dihydroxy heptanoic acids and gabaculine, 10 ..mu..M N-methylprotoporphyrin. Dicarboxilic acids, such as deltaKG, Glu, OAA, do not inhibit. Chloramphenicol, ATP, protoporphyrin, anoxia, light, darkness have no effect. The product, once formed, is stable to treatment with 5% conc. HCl in cold acetone. It can be chased in a second incubation with unlabeled ALA, but not with levulinic acid. No activity was detected in the subplastidic membrane fractions. Western blot analysis failed to reveal any homology between the labeled protein and either cytochrome for ALA dehydratase. This ALA-binding protein was not formed in chloroplasts isolated from fully expanded pea leaves. Therefore, it is deemed likely to participate in ALA metabolism during chloroplast development.

  6. Photodynamic Therapy (PDT) using intratumoral injection of the 5- aminolevulinic acid (5-ALA) for the treatment of eye cancer in cattle

    NASA Astrophysics Data System (ADS)

    Hage, Raduan; Mancilha, Geraldo; Zângaro, Renato A.; Munin, Egberto; Plapler, Hélio

    2007-02-01

    A six-year old Holstein cow with an eye cancer (ocular squamous cell carcinoma) involving the third eyelid and conjunctiva was submitted to photodynamic therapy using intratumoral 20% aminolevulinic acid (5-ALA - Aldrich Chemical Company, Milwaukee, USA) and a light emitting diode (LED - VET LED - MMOptics (R)) with wavelength between 600 and 700 nm, 2 cm diameter circular light beam, power of 150 mW, light dose of 50 J/cm2 as a source of irradiation. Fifteen days after the experimental procedure we observed about 50% tumor reduction and complete remission after 3 months. Relapse was not observed up to 12 months after the treatment. Although the study only includes one animal not allowing definite conclusions, it indicates that PDT represents a safe and technically feasible approach in the treatment of eye cancer in cattle.

  7. Off-label photodynamic therapy for recalcitrant facial flat warts using topical 5-aminolevulinic acid.

    PubMed

    Yang, Ya-Li; Sang, Junjun; Liao, Ning-Xin; Wei, Fang; Liao, Wanqin; Chen, Jiang-Han

    2016-07-01

    The facial flat wart (verruca plana) is one of the most common reasons for dermatology and primary care visits. Although there are many therapeutic modalities, no single therapy has been proven to be completely curative. Case reports and uncontrolled studies suggested that photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) can effectively treat recalcitrant facial flat warts. A total of 12 patients with recalcitrant facial flat warts were enrolled in the study. ALA gel (10 %) was applied topically to lesions and incubated for 3 h. The lesions were irradiated by an LED light of 630 ± 10 nm at dose levels of 60-100 mW/cm. Clinical assessment was conducted before and after every treatment for up to 24 weeks. Among the ten patients completing three sessions of ALA-PDT, five had complete lesions clearance, and the other five patients were significantly improved. At the 24-week follow-up, the average effective rate was 88.8 %, with no recurrences. No significant side effects were reported. A low-dose topical ALA-PDT regimen using 10 % ALA, 3 h incubation, and a red light source for three treatment sessions are suggested as the optimal scheme for the treatment of recalcitrant flat warts on the face in Chinese patients. Superior efficacy is found in elevated or active period lesions with mild side effects. PMID:27059226

  8. Clinical applications of 5-aminolevulinic acid-mediated fluorescence for gastric cancer

    PubMed Central

    Namikawa, Tsutomu; Yatabe, Tomoaki; Inoue, Keiji; Shuin, Taro; Hanazaki, Kazuhiro

    2015-01-01

    5-aminolevulinic acid (ALA) is a naturally occurring amino acid that is a protoporphyrin IX (PpIX) precursor and a next-generation photosensitive substance. After exogenous administration of ALA, PpIX specifically accumulates in cancer cells owing to the impaired metabolism of ALA to PpIX in mitochondria, which results in a red fluorescence following irradiation with blue light and the formation of singlet oxygen. Fluorescence navigation by photodynamic diagnosis (PDD) using ALA provides good visualization and detection of gastric cancer lesions and is a potentially valuable diagnostic tool for gastric cancer for evaluating both the surgical resection margins and extension of the lesion. Furthermore, PDD using ALA might be used to detect peritoneal metastases during preoperative staging laparoscopy, where it could provide useful information for the selection of a therapeutic approach. Another promising application for this modality is in the evaluation of lymph node metastases. Photodynamic therapy (PDT) using ALA to cause selective damage based on the accumulation of a photosensitizer in malignant tissue is expected to be a non-invasive endoscopic treatment for superficial early gastric cancer. ALA has the potential to be used not only as a diagnostic agent but also as a therapeutic drug, resulting in a new strategy for cancer diagnosis and therapy. Here, we review the current use of PDD and PDT in gastric cancer and evaluate its future potential beyond conventional modalities combined with a light energy upconverter, a light-emitting diode and near-infrared rays as light sources. PMID:26269666

  9. Photodynamic effects on nasopharyngeal carcinoma (NPC) cells with 5-aminolevulinic acid or its hexyl ester.

    PubMed

    Wu, R W K; Chu, E S M; Yow, C M N; Chen, J Y

    2006-10-01

    Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Hong Kong and southern China. To explore a new modality of NPC treatment, 5-aminolevulinic acid (ALA) or its hexyl ester (ALA-H) mediated photodynamic therapy (PDT) was studied in vitro. The results show that NPC cells are sensitive to both ALA and ALA-H mediated PDT. However, ALA-H PDT is much more effective at cell inactivation than ALA-PDT, due to a higher efficiency of ALA-H on producing endogenous protoporphyrin (PpIX) in cells. Both apoptosis and necrosis are involved in cell death, but apoptosis plays a major role under the short time incubation of drugs. ALA and ALA-H mediated PDT not only destroy the cells directly, but also inhibit the expression of matrix metalloproteinase-2 (MMP2) in cells, a maker for tumor metastasis. The ALA-H shows promising PDT results on NPC in vitro; therefore it is worth investigating further in vivo for NPC treatment. PMID:16442708

  10. Physicochemical characterisation of a novel thermogelling formulation for percutaneous penetration of 5-aminolevulinic acid.

    PubMed

    Grüning, Nadja; Müller-Goymann, Christel Charlotte

    2008-06-01

    The present contribution was dedicated to the development and characterisation of a semisolid formulation of 5-aminolevulinic acid (5-ALA), appropriate for the diagnosis and treatment of actinic keratosis in photodynamic therapy. To achieve sufficiently high concentrations of the polar substance within the living epithelium after topical application, the semisolid base was enriched with penetration enhancers. A semisolid liquid crystalline system for drug delivering was the formulation of choice. It was composed of isopropyl alcohol, dimethyl isosorbide, medium chain triglycerides, water, and Pluronic F 127 as a polyoxyethylene-polyoxypropylene surface-active block copolymer. Rheometrical investigations were performed in the oscillatory mode and showed a thermo reversible gelification behaviour of the formulation, which therefore was denoted Thermogel. Permeation studies through human stratum corneum revealed higher permeation coefficients for 5-ALA from the Thermogel than from different German Pharmacopoeia creams. For example a 7.5-fold increase in comparison with Basiscreme DAC, and a 19.5-fold increase compared to water containing hydrophilic ointment. With respect to Dolgit(R) Mikrogel, the permeation coefficient from the Thermogel was 6.4-fold higher. These results were in accordance with those of differential scanning calorimetry measurements. Thermogel disclosed the strongest interactions with stratum corneum lipids. PMID:17828744

  11. Role of 5-aminolevulinic acid-conjugated gold nanoparticles for photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Zhang, Zhenxi; Wang, Sijia; Xu, Hao; Wang, Bo; Yao, Cuiping

    2015-05-01

    There are three possible mechanisms for 5-aminolevulinic acid (5-ALA) conjugated gold nanoparticles (GNPs) through electrostatic bonding for photodynamic therapy (PDT) of cancer: GNPs delivery function, singlet oxygen generation (SOG) by GNPs irradiated by light, and surface resonance enhancement (SRE) of SOG. Figuring out the exact mechanism is important for further clinical treatment. 5-ALA-GNPs and human chronic myeloid leukemia K562 cells were used to study delivery function and SOG by GNPs. The SRE of SOG enabled by GNPs was explored by protoporphyrin IX (PpIX)-GNPs conjugate through electrostatic bonding. Cell experiments show that the GNPs can improve the efficiency of PDT, which is due to the vehicle effect of GNPs. PpIX-GNPs conjugate experiments demonstrated that SOG can be improved about 2.5 times over PpIX alone. The experiments and theoretical results show that the local field enhancement (LFE) via localized surface plasmon resonance (LSPR) of GNPs is the major role; the LFE was dependent on the irradiation wavelength and the GNP's size. The LFE increased with an increase of the GNP size (2R ≤50 nm). However, the LSPR function of the GNPs was not found in cell experiments. Our study shows that in 5-ALA-conjugated GNPs PDT, the delivery function of GNPs is the major role.

  12. The application of 5-aminolevulinic acid in the treatment of precancerous lesions, skin cancer, and a new approach to the control of therapy

    NASA Astrophysics Data System (ADS)

    Kulas, Zbigniew; Bereś-Pawlik, Elżbieta; Bieniek, Andrzej; Matusiak, Łukasz

    2009-02-01

    The aim of our work was to determine a therapeutic effect of photodynamic therapy (PDT). Twenty five patients with the Bowen's disease, actinic keratosis and basal cell carcinoma (superficial, nodular) were examined. They were treated with photosensitizer - aminolevulinic acid (metabolized in protoporphyrin IX), and the new red light source built of high-power diodes. A new method, based on numerical analysis of fluorescence imaging of tissues, was proposed as a way for controlling therapy.

  13. Evidence that isolated developing chloroplasts are capable of synthesizing chlorophyll b from 5-aminolevulinic acid

    SciTech Connect

    Huang, Laiqiang; Hoffman, N.E. )

    1990-09-01

    Developing chloroplasts isolated from cucumber (Cucumis sativus L. var Beit Alpha) cotyledons are capable of incorporating ({sup 14}C)5-aminolevulinic acid into chlorophyll (Chl) b and Chl a when incubated under photosynthetic illumination. Thin layer chromatography and high pressure liquid chromatography were employed to analyze the pigments. The specific radioactivity in Chl a was over three times higher than that found in Chl b. Both Chl a and b synthesizing activities in organello decayed rapidly at approximately the same rate. We conclude that concomitant synthesis of Chl a/b-binding apoprotein is not required for Chl b synthesis.

  14. Photodynamic therapy of urethral condylomata acuminata using topically 5-aminolevulinic acid

    NASA Astrophysics Data System (ADS)

    Wang, Xiuli; Wang, Hongwei; Wang, Haishan; Xu, Shizheng; Liao, Kanghuang; Hillemanns, Peter

    2005-07-01

    Background Electrocoagulation and laser evaporation for urethral condylomata acuminata have high recurrence rates and can be associated with urethral malformations. Objective To investigate the effect of photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) on urethral condylomata acuminata and to examine the histological changes in lesions of condylomata acuminata after ALA-PDT. Methods One hundred and sixty-four urethral condylomata patients were given topical ALA followed by intraurethral PDT through a cylindrical fiber. Among the cases, 16 penile and vulval condylomatous lesions in 11 patients were treated with topical ALA-PDT at same time. After the treatment, biopsy specimens were collected from the 16 penile and vulval lesions. The histological changes were then evaluated by light microscope and electron microscope. Results The complete response rate for urethral condylomata by topical ALA-PDT was 95.12% and the recurrence rate was 5.13% after 6 to 24 months follow-up. Keratinocytes in middle and upper layers of the epidermis with marked vacuolation and some necrocytosis were detected one and three hours after PDT. Necrosis in all layers of the epidermis was noted five hours after PDT by microscopy. In electron microscopy of kerationcytes, distinct ultrastructural abnormalities of mitochondrion, endoplasmic reticulum and membrane damage were observed. Apoptotic bodies were detected three hours after PDT and a large number of the keratinocytes exhibited necrosis five hours after PDT by electron microscope. Conclusions Results suggests that topical ALA-PDT is a simple, effective, relatively safe, less recurrent and comparatively well tolerated treatment for urethral condylomata acuminata. The mechanisms might be that ALA-PDT could trigger apoptotic process and necrosis in the HPV infected keratinocytes. Key words:

  15. Rapid stabilisation of atherosclerotic plaque with 5-aminolevulinic acid-mediated sonodynamic therapy.

    PubMed

    Li, Zhitao; Sun, Xin; Guo, Shuyuan; Wang, Liping; Wang, Tengyu; Peng, Chenghai; Wang, Wei; Tian, Zhen; Zhao, Ruibo; Cao, Wenwu; Tian, Ye

    2015-10-01

    5-Aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) effectively induces the apoptosis of atherogenic macrophages, but whether it can stabilise atherosclerotic plaque in vivo is unclear. Here, we used an animal model to evaluate the effects of ALA-SDT on plaque stabilisation. Sixty rabbits were induced atherosclerotic plaques in the femoral artery with a combination of silastic tube placement with atherogenic diet, and randomly assigned into control (n = 12) and SDT (n = 48) groups. In the SDT group, after intravenous injected with ALA (60 mg/kg) animals underwent the treatment of ultrasound with intensities of 0.75, 1.00, 1.50 and 2.00 W/cm(²) (n = 12 for each intensity). Seven days after the treatment, the plaque disruption assay was performed to test plaque stability. We found that ALA-SDT with ultrasound intensity of 1.5 W/cm(²) showed the strongest efficacy to stabilise plaques. Under this condition, the frequency of plaque disruption decreased by 88% (p<0.01), positive area of macrophages reduced by 94% (p<0.001) and percentage content of lipids dropped by 60% (p < 0.001), while percentage content of collagens increased by 127% (p<0.001). We also found that the plaque stabilisation by ALA-SDT was associated with increased macrophage apoptosis and apoptotic cell clearance. Moreover, ALA-SDT decreased the contents and activities of matrix metalloproteinase-2,9 and increased the levels of tissue inhibitors of matrix metalloproteinase-1,2 in plaques. Our studies demonstrate that ALA-SDT promotes plaque stabilisation by inducing macrophage elimination and inhibiting matrix degradation. This method might be a promising regimen for atherosclerosis therapy. PMID:26179778

  16. [Effect of 5-aminolevulinic acid on photosynthetic characteristics of tomato seedlings under NaCl stress].

    PubMed

    Zhao, Yan-Yan; Yan, Fei; Hu, Li-Pan; Zhou, Xiao-Ting; Zou, Zhi-Rong

    2014-10-01

    In this research, the possibility of exogenous application of 5-aminolevulinic acid (ALA) on photosynthetic characteristics of tomato seedlings under NaCl stress was investigated. Five leaves seedlings of tomato (Solanum lycopersicum cv. Jinpeng No. 1) were used as starting materials, applied with 50 mg · L(-1) ALA by foliage spray or 10 mg · L(-1) ALA by root soaking to study the changes in their photosynthesis and fluorescence parameters under 100 mmol · L(-1) NaCl. The result showed that, photosynthetic gas exchange parameters (net photosynthetic rate P,, stomata conductance g(s), intercellular CO2 concentration Ci, transpiration Tr) and chlorophyll fluorescence parameters (Fv'/Fm', Fm', ΦPS II, ETR, qP, Pc) were severely reduced under NaCl treatment and ALA application by foliage spray or root soaking with proper concentrations exerted positive influences on tomato seedlings under salt stress, while there were some differences between foliage spray and root soaking in the influence on chlorophyll content, photosynthesis and chlorophyll fluorescence. Both foliage spray with 50 mg · L(-1) ALA and root soaking with 10 mg L(-1) ALA significantly increased Pn, Ci, g(s) and Tr of tomato seedlings under NaCl stress, alleviated photosynthetic inhibition. Root application of ALA had a better effect on the chlorophyll content than foliage application. However, the photosynthetic parameters showed that foliage application of ALA had a better effect than root application, and both treatments had no difference in the influence on chlorophyll fluorescence parameters of tomato seedlings. It could be deduced that the regulating effect of ALA on enhancing salt tolerance of tomato seedlings is attributed to its effect on improving chlorophyll biosynthesis and metabolism, increasing stomatal conductance and reducing stomatal limitation, thus, enhancing the photosynthetic capacity and PS II photochemical efficiency of tomato leaves under NaCl stress. PMID:25796901

  17. Production of 5-aminolevulinic acid by cell free multi-enzyme catalysis.

    PubMed

    Meng, Qinglong; Zhang, Yanfei; Ju, Xiaozhi; Ma, Chunling; Ma, Hongwu; Chen, Jiuzhou; Zheng, Ping; Sun, Jibin; Zhu, Jun; Ma, Yanhe; Zhao, Xueming; Chen, Tao

    2016-05-20

    5-Aminolevulinic acid (ALA) is the precursor for the biosynthesis of tetrapyrroles and has broad agricultural and medical applications. Currently ALA is mainly produced by chemical synthesis and microbial fermentation. Cell free multi-enzyme catalysis is a promising method for producing high value chemicals. Here we reported our work on developing a cell free process for ALA production using thermostable enzymes. Cheap substrates (succinate and glycine) were used for ALA synthesis by two enzymes: 5-aminolevulinic acid synthase (ALAS) from Laceyella sacchari (LS-ALAS) and succinyl-CoA synthase (Suc) from Escherichia coli. ATP was regenerated by polyphosphate kinase (Ppk) using polyphosphate as the substrate. Succinate was added into the reaction system in a fed-batch mode to avoid its inhibition effect on Suc. After reaction for 160min, ALA concentration was increased to 5.4mM. This is the first reported work on developing the cell free process for ALA production. Through further process and enzyme optimization the cell free process could be an effective and economic way for ALA production. PMID:27012885

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

    NASA Astrophysics Data System (ADS)

    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.

  19. Recent advances in photodynamic diagnosis of gastric cancer using 5-aminolevulinic acid

    PubMed Central

    Koizumi, Noriaki; Harada, Yoshinori; Minamikawa, Takeo; Tanaka, Hideo; Otsuji, Eigo; Takamatsu, Tetsuro

    2016-01-01

    Photodynamic diagnosis based on 5-aminolevulinic acid-induced protoporphyrin IX has been clinically applied in many fields based upon its evidenced efficacy and adequate safety. In order to establish a personalized medicine approach for treating gastric cancer patients, rapid intraoperative detection of malignant lesions has become important. Feasibility of photodynamic diagnosis using 5-aminolevulinic acid for gastric cancer patients has been investigated, especially for the detection of peritoneal dissemination and lymph node metastasis. This method enables intraoperative real-time fluorescence detection of peritoneal dissemination, exhibiting higher sensitivity than white light observation without histopathological examination. The method also enables detection of metastatic foci within excised lymph nodes, exhibiting a diagnostic accuracy comparable to that of a current molecular diagnostics technique. Although several complicating issues still need to be resolved, such as the effect of tissue autofluorescence and the insufficient depth penetration of excitation light, this simple and rapid method has the potential to become a useful diagnostic tool for gastric cancer, as well as urinary bladder cancer and glioma. PMID:26811665

  20. A Formulation Study of 5-Aminolevulinic Encapsulated in DPPC Liposomes in Melanoma Treatment

    PubMed Central

    Lin, Ming-Wei; Huang, Yaw-Bin; Chen, Chun-Lin; Wu, Pao-Chu; Chou, Chien-Ying; Wu, Ping-Ching; Hung, Shih-Ya

    2016-01-01

    Photodynamic therapy (PDT) is a widely used technique for epithelial skin cancer treatment. 5-aminolevulinic acid (5-ALA) is a drug currently used for PDT and is a hydrophilic molecule at its physiological pH, and this limits its capacity to cross the stratum corneum of skin. Since skin penetration is a key factor in the efficacy of topical 5-ALA-mediated PDT, numerous strategies have been proposed to improve skin penetration. Yet this problem is still ongoing. The results of a previous study showed a low rate of 5-ALA encapsulated in liposomes (5.7%) that were 400 nm in size. In the present study, we used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes as vehicles and tested their delivery efficacy of 5-ALA-medicated PDT both in vitro and in vivo. Our data shows that 5-ALA encapsulated in 0.1 or 0.5% DPPC liposomes (5-ALA/DPPC) had a better encapsulated rate (15~16%) and were smaller in size (84~89 nm). We found the 5-ALA/DPPC formulation reduced cell viability, mitochondria membrane potential, and enhanced intracellular ROS accumulation as compared to 5-ALA alone in melanoma cells. Furthermore, the 5-ALA/DPPC formulation also had better skin penetration ability as compared to the 5-ALA in our ex vivo data by assaying 5-ALA converted into protoporphyrin IX (PpIX) in the skin of the mice that were experimented on. In melanoma xenograft models, 5-ALA/DPPC enhanced PpIX accumulation only in tumor tissue but not normal skin. In conclusion, we found DPPC liposomes to be good carriers for 5-ALA delivery and believe that they may prove useful in 5-ALA-mediated PDT in the future. PMID:27429584

  1. Novel multifunctional acyloxyalkyl ester prodrugs of 5-aminolevulinic acid display improved anticancer activity dependent on photoactivation

    NASA Astrophysics Data System (ADS)

    Berkovitch, G.; Nudelman, A.; Ehenberg, B.; Rephaeli, A.; Malik, Z.

    2009-06-01

    New approaches to PDT using multifunctional 5-aminolevulinic acid (ALA) based prodrugs activating mutual routes of toxicity are described. We investigated the mutual anti-cancer activity of ALA prodrugs which upon metabolic hydrolysis by unspecific esterases release ALA, formaldehyde or acetaldehye and the histone deacetylase inhibitor (HDACI) butyric acid. The most potent prodrug in this study was butyryloxyethyl 5-amino-4-oxopentanoate (AN-233) that stimulated a rapid biosynthesis of protoporphyrin IX (PpIX) in human glioblastoma U-251 cells and generated an efficient photodynamic destruction. AN-233 induced a considerable high level of intracellular ROS in the cells following light irradiation, reduction of mitochondrial activity, dissipation of the mitochondrial membrane potential resulting in necrotic and apoptotic cell death. The main advantage of AN-233 over ALA stems from its ability to induce photodamage at a significantly lower dose than ALA.

  2. 5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice

    PubMed Central

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

    2015-01-01

    Objective 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. Methods 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. Results 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). Conclusions 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. PMID:26161801

  3. To what extent will 5-aminolevulinic acid change the face of malignant glioma surgery?

    PubMed

    Díez Valle, Ricardo; Tejada Solis, Sonia

    2015-01-01

    Glioma surgery is an essential part of glioma management; however, fully achieving the goal of surgery has been uncommon. The goal of surgery is 'maximal safe resection' with the accepted target for maximal being complete resection of the contrast-enhancing tumor. This ideal result was obtained in less than 30% of cases in centers of excellence until a few years ago. The development of fluorescence-guided surgery using 5-aminolevulinic acid has initiated a radical change. Over the past 5 years, various groups have published rates of complete resection of the enhancing tumor that exceed 80%. In the coming years, as the use of the technology expands, complete resection should become a common, predictable result at many centers. Consequently, adjuvant therapies that benefit from resection could play a bigger role, resection could be incorporated as a variable in randomized trials and distant recurrence might become a more common problem. PMID:26118538

  4. 5-aminolevulinic acid guidance during awake craniotomy to maximise extent of safe resection of glioblastoma multiforme.

    PubMed

    Corns, Robert; Mukherjee, Soumya; Johansen, Anja; Sivakumar, Gnanamurthy

    2015-01-01

    Overall survival for patients with glioblastoma multiforme (GBM) has been consistently shown to improve when the surgeon achieves a gross total resection of the tumour. It has also been demonstrated that surgical adjuncts such as 5-aminolevulinic acid (5-ALA) fluorescence--which delineates malignant tumour tissue--normal brain tissue margin seen using violet-blue excitation under an operating microscope--helps achieve this. We describe the case of a patient with recurrent left frontal GBM encroaching on Broca's area (eloquent brain). Gross total resection of the tumour was achieved by combining two techniques, awake resection to prevent damage to eloquent brain and 5-ALA fluorescence guidance to maximise the extent of tumour resection.This technique led to gross total resection of all T1-enhancing tumour with the avoidance of neurological deficit. The authors recommend this technique in patients when awake surgery can be tolerated and gross total resection is the aim of surgery. PMID:26177997

  5. Fluorescence-guided resections and photodynamic therapy for malignant gliomas using 5-aminolevulinic acid

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Beck, Tobias; Beyer, Wolfgang; Pongratz, Thomas; Sroka, Ronald; Baumgartner, Reinhold; Stummer, Walter; Olzowy, Bernhard; Mehrkens, Jan H.; Tonn, Joerg C.; Reulen, Hans J.

    2005-04-01

    Oral application of 20 mg/kg bw of 5-aminolevulinic acid results in a highly specific accumulation of fluorescent and phototoxic Protoporphyrin IX in malignant glioma tissue. Surgical removal with fluorescence guidance is studied in a phase III clinical trial, adjuvant Photodynamic Therapy (PDT) to the surgical cavity is in phase II and for interstitial PDT of recurrent gliomas, a phase I/II study has started. Fluorescence guided resections have been shown to be safe and effective in augmenting neurosurgical removal of malignant gliomas in 52 consecutive patients. Intra-operative fluorescence spectroscopy showed statistically significant higher sensitizer accumulation in vital brain tumor versus the infiltration zone and in the infiltration zone versus adjacent normal brain, which contained very little PPIX. This is promisingly exploited for PDT - both to the surgical cavity by surface irradiation and for stereotactically guided interstitial irradiation.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Photodynamic diagnosis (PDD) of bladder cancer with intravesical 5-aminolevulinic-acid-induced fluorescence

    NASA Astrophysics Data System (ADS)

    Grimbergen, Matthijs C. M.; Jonges, T. G. N.; Lock, M. Tycho W.; van Swol, Christiaan F. P.; Boon, Tom A.; van Moorselaar, R. Jeroen A.

    2001-05-01

    Flat urothelial lesions as well as small papillary tumors are easily missed during transurethral resection (TUR). PDD is based on the detection of protoporphyrin-IX induced fluorescence after topical administration of 5- aminolevulinic acid (ALA). We report on our initial clinical results of 130 procedures in 98 patients. Two hours prior to TUR 1.5 g ALA dissolved in 50 ml 1.4% NaHCO3 solution was installed intravesically. For fluorescence excitation a blue light source (375-440 nm, Karl Storz) was used. In total 478 biopsies (2-9 per patient) were taken from fluorescent and nonfluorescent areas. Normal nonfluorescent bladder urothelium was blue, whereas cancer epithelium developed a brilliant red fluorescence. During white light cystoscopy, 143 bladder tumors were found. Sixty-three additional tumors were detected because of their positive fluorescence. The overall sensitivity of fluorescence cystoscopy (98%) was greater than that of white light cystoscopy (69%). Their specificities were 51% and 80% respectively.

  8. Metabolic engineering of Corynebacterium glutamicum for efficient production of 5-aminolevulinic acid.

    PubMed

    Feng, Lili; Zhang, Ya; Fu, Jing; Mao, Yufeng; Chen, Tao; Zhao, Xueming; Wang, Zhiwen

    2016-06-01

    5-Aminolevulinic acid (5-ALA) has recently attracted attention for its potential applications in the fields of medicine and agriculture. In this study, Corynebacterium glutamicum was firstly engineered for 5-ALA production via the C4 pathway. HemA encoding 5-aminolevulinic acid synthase from Rhodobacter sphaeroides was codon optimized and expressed in C. glutamicum ATCC13032, resulting in accumulation of 5-ALA. Deletion of all known genes responsible for the formation of acetate and lactate further enhanced production of 5-ALA. Overexpression of ppc gene encoding phoenolpyruvate carboxylase resulted in an accumulation of 5-ALA up to 2.06 ± 0.05 g/L. Furthermore, deletion of high-molecular-weight penicillin-binding proteins (HMW-PBPs) genes pbp1a, pbp1b, and pbp2b led to an increase in 5-ALA production of 13.53%, 29.47%, and 22.22%, respectively. Finally, 5-ALA production was enhanced to 3.14 ± 0.02 g/L in shake flask by heterologously expressing rhtA encoding threonine/homoserine exporter, and 86.77% of supplemented glycine was channeled toward 5-ALA production in shake flask. The engineered C. glutamicum ALA7 strain produced 7.53 g/L 5-ALA in a 5 L bioreactor. This study demonstrated the potential utility of C. glutamicum as a platform for metabolic production of 5-ALA. Change of cell permeability by metabolic engineering HMW-PBPs may provide a new strategy for biochemicals production in Corynebacterium glutamicum. Biotechnol. Bioeng. 2016;113: 1284-1293. © 2015 Wiley Periodicals, Inc. PMID:26616115

  9. Topical versus systemic 5-aminolevulinic acid administration for photodynamic therapy of the colon in B10.RBP mice

    NASA Astrophysics Data System (ADS)

    Gil, Maciej; Woszczynski, Marek; Regula, Jaroslaw; MacRobert, Alexander J.; Butruk, Eugeniusz; Bown, Stephen G.

    1999-07-01

    5-aminolevulinic acid (5-ALA) is an interesting photosensitizing substance for photodynamic therapy (PDT), successfully applied topically for urological malignancy. In gastroenterology it has proven efficacy for treatment of some GI neoplasms after systemic administration. This study was aimed at investigating the possibility of topical 5-ALA administration also for the PDT of gut cancer in a mice model. 5-ALA solution at different concentrations (5%, 1.5%, and 0.5%) was instilled in the colon of mice, which was later removed and examined by fluorescence microscopy. The results of fluorescence studies were compared with those obtained in a control group treated with 5-ALA given systematically. Satisfactory epithelial fluorescence levels and good selectivity between gut layers were obtained after intracolonic 5-ALA instillation. However, mean fluorescence intensity was higher after systemic drug applications. Our results suggest that 5-ALA may probably be used topically for the PDT of some gut neoplasms.

  10. Responses to hexyl 5-aminolevulinate-induced photodynamic treatment in rat bladder cancer model

    NASA Astrophysics Data System (ADS)

    Arum, Carl-Jørgen; Gederas, Odrun; Larsen, Eivind; Randeberg, Lise; Zhao, Chun-Mei

    2010-02-01

    OBJECTIVES: In this study, we evaluated histologically the effects of hexyl 5-aminolevulinateinduced photodynamic treatment in the AY-27 tumor cell induced rat bladder cancer model. MATERIAL & METHODS: The animals (fischer-344 female rats) were divided into 2 groups, half of which were orthotopically implanted with 400,000 syngeniec AY-27 urothelia1 rat bladder cancer cells and half sham implanted. 14 days post implantation 6 rats from each group were treated with hexyl 5-aminolevulinate-induced photodynamic treatment (8mM HAL and light fluence of 20 J/cm2). Additional groups of animals were only given HAL instillation, only light treatment, or no treatment. All animals were sacrificed 7 days after the PDT/only HAL/only light or no treatment. Each bladder was removed, embedded in paraffin and stained with hematoxylin, eosin, and saferin for histological evaluation at high magnification for features of tissue damage by a pathologist blinded to the sample source. RESULTS: In all animals that were AY-27 implanted and not given complete PDT treatment, viable tumors were found in the bladder mucosa and wall. In the animals treated with complete HAL-PDT only 3 of 6 animals had viable tumor. In the 3 animals with viable tumor it was significantly reduced in volume compared to the untreated animals. It was also noted that in the PDT treated animals there was a significantly increased inflammatory response (lymphocytic and mononuclear cell infiltration) in the peri-tumor area compared to implanted animals without complete HAL-PDT. CONCLUSION: Our results suggest that hexyl 5-aminolevulinate-induced photodynamic treatment in a rat bladder cancer model involves both direct effects on cell death (necrosis and apoptosis) and indirect effects to evoke the host immune-response, together contributing to tumor eradication.

  11. Physiological and metabolic effects of 5-aminolevulinic acid for mitigating salinity stress in creeping bentgrass.

    PubMed

    Yang, Zhimin; Chang, Zuoliang; Sun, Lihong; Yu, Jingjin; Huang, Bingru

    2014-01-01

    The objectives of this study were to determine whether foliar application of a chlorophyll precursor, 5-aminolevulinic acid (ALA), could mitigate salinity stress damages in perennial grass species by regulating photosynthetic activities, ion content, antioxidant metabolism, or metabolite accumulation. A salinity-sensitive perennial grass species, creeping bentgrass (Agrostis stolonifera), was irrigated daily with 200 mM NaCl for 28 d, which were foliar sprayed with water or ALA (0.5 mg L-1) weekly during the experiment in growth chamber. Foliar application of ALA was effective in mitigating physiological damage resulting from salinity stress, as manifested by increased turf quality, shoot growth rate, leaf relative water content, chlorophyll content, net photosynthetic rate, stomatal conductance and transpiration rate. Foliar application of ALA also alleviated membrane damages, as shown by lower membrane electrolyte leakage and lipid peroxidation, which was associated with increases in the activities of antioxidant enzymes. Leaf content of Na+ was reduced and the ratio of K+/Na+ was increased with ALA application under salinity stress. The positive effects of ALA for salinity tolerance were also associated with the accumulation of organic acids (α-ketoglutaric acid, succinic acid, and malic acid), amino acids (alanine, 5-oxoproline, aspartic acid, and γ -aminobutyric acid), and sugars (glucose, fructose, galactose, lyxose, allose, xylose, sucrose, and maltose). ALA-mitigation of physiological damages by salinity could be due to suppression of Na+ accumulation and enhanced physiological and metabolic activities related to photosynthesis, respiration, osmotic regulation, and antioxidant defense. PMID:25551443

  12. Physiological and Metabolic Effects of 5-Aminolevulinic Acid for Mitigating Salinity Stress in Creeping Bentgrass

    PubMed Central

    Yang, Zhimin; Chang, Zuoliang; Sun, Lihong; Yu, Jingjin; Huang, Bingru

    2014-01-01

    The objectives of this study were to determine whether foliar application of a chlorophyll precursor, 5-aminolevulinic acid (ALA), could mitigate salinity stress damages in perennial grass species by regulating photosynthetic activities, ion content, antioxidant metabolism, or metabolite accumulation. A salinity-sensitive perennial grass species, creeping bentgrass (Agrostis stolonifera), was irrigated daily with 200 mM NaCl for 28 d, which were foliar sprayed with water or ALA (0.5 mg L−1) weekly during the experiment in growth chamber. Foliar application of ALA was effective in mitigating physiological damage resulting from salinity stress, as manifested by increased turf quality, shoot growth rate, leaf relative water content, chlorophyll content, net photosynthetic rate, stomatal conductance and transpiration rate. Foliar application of ALA also alleviated membrane damages, as shown by lower membrane electrolyte leakage and lipid peroxidation, which was associated with increases in the activities of antioxidant enzymes. Leaf content of Na+ was reduced and the ratio of K+/Na+ was increased with ALA application under salinity stress. The positive effects of ALA for salinity tolerance were also associated with the accumulation of organic acids (α-ketoglutaric acid, succinic acid, and malic acid), amino acids (alanine, 5-oxoproline, aspartic acid, and γ -aminobutyric acid), and sugars (glucose, fructose, galactose, lyxose, allose, xylose, sucrose, and maltose). ALA-mitigation of physiological damages by salinity could be due to suppression of Na+ accumulation and enhanced physiological and metabolic activities related to photosynthesis, respiration, osmotic regulation, and antioxidant defense. PMID:25551443

  13. Regulation of the hemA gene during 5-aminolevulinic acid formation in Pseudomonas aeruginosa.

    PubMed Central

    Hungerer, C; Troup, B; Römling, U; Jahn, D

    1995-01-01

    The general tetrapyrrole precursor 5-aminolevulinic acid is formed in bacteria via two different biosynthetic pathways. Members of the alpha group of the proteobacteria use 5-aminolevulinic acid synthase for the condensation of succinyl-coenzyme A and glycine, while other bacteria utilize a two-step pathway from aminoacylated tRNA(Glu). The tRNA-dependent pathway, involving the enzymes glutamyl-tRNA reductase (encoded by hemA) and glutamate-1-semialdehyde-2,1-aminomutase (encoded by hemL), was demonstrated to be used by Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas stutzeri, Comamonas testosteroni, Azotobacter vinelandii, and Acinetobacter calcoaceticus. To study the regulation of the pathway, the glutamyl-tRNA reductase gene (hemA) from P. aeruginosa was cloned by complementation of an Escherichia coli hemA mutant. The hemA gene was mapped to the SpeI A fragment and the DpnIL fragment of the P. aeruginosa chromosome corresponding to min 24.1 to 26.8. The cloned hemA gene, coding for a protein of 423 amino acids with a calculated molecular mass of 46,234 Da, forms an operon with the gene for protein release factor 1 (prf1). This translational factor mediates the termination of the protein chain at the ribosome at amber and ochre codons. Since the cloned hemA gene did not possess one of the appropriate stop codons, an autoregulatory mechanism such as that postulated for the enterobacterial system was ruled out. Three open reading frames of unknown function transcribed in the opposite direction to the hemA gene were found. hemM/orf1 and orf2 were found to be homologous to open reading frames located in the 5' region of enterobacterial hemA genes. Utilization of both transcription start sites was changed in a P. aeruginosa mutant missing the oxygen regulator Anr (Fnr analog), indicating the involvement of the transcription factor in hemA expression. DNA sequences homologous to one half of an Anr binding site were detected at one of the determined

  14. Tunable phosphatase-sensitive stable prodrugs of 5-aminolevulinic acid for tumor fluorescence photodetection.

    PubMed

    Babič, Andrej; Herceg, Viktorija; Ateb, Imène; Allémann, Eric; Lange, Norbert

    2016-08-10

    5-Aminolevulinic acid (5-ALA) has been at the forefront of small molecule based fluorescence-guided tumor resection and photodynamic therapy. 5-ALA and two of its esters received marketing authorization but suffer from several major limitations, namely low stability and poor pharmacokinetic profile. Here, we present a new class of 5-ALA derivatives aiming at the stabilization of 5-ALA by incorporating a phosphatase sensitive group, with or without self-cleavable linker. Compared to 5-ALA hexyl ester (5-ALA-Hex), these compounds display an excellent stability under acidic, basic and physiological conditions. The activation and conversion into the 5-ALA is controlled and can be structure-tailored. The prodrugs display reduced acute toxicity compared to 5-ALA-Hex with superior dose response profiles of protoporphyrin IX synthesis and fluorescence intensity in human glioblastoma cells in vitro. Clinically relevant fluorescence kinetics in vivo shown in U87MG glioblastoma spheroid tumor model in chick embryos provide a solid basis for their further development and translation to clinical fluorescence guided tumor resection and photodynamic therapy. PMID:27235981

  15. Alternative Routes for the Synthesis of 5-Aminolevulinic Acid in Maize Leaves 1

    PubMed Central

    Harel, Eitan; Ne'Eman, Emma

    1983-01-01

    Intact plastids from greening maize (Zea mays L.) leaves converted [14C]glutamate and [14C]2-ketoglutarate (KG) to [14C]5-aminolevulinic acid (ALA). Glutamate appeared to be the immediate precursor of ALA, while KG was first converted to glutamate, as shown by the effect of various inhibitors of amino acid metabolism. Plastids from greening leaves contained markedly higher activity as compared with etioplasts or chloroplasts. The synthesis of ALA by intact plastids was light dependent. The enzyme system resides in the stroma of plastids or may be lightly bound to membranes. The solubilized system showed maximal activity around pH 7.9 and required Mg2+, ATP, and NADPH although dependence on the latter was not clear-cut. A relatively high level of activity could be extracted from etioplasts. Maximal activity was obtained from plastids of leaves which had been illuminated for 90 minutes, after which activity declined sharply. The enzyme system solubilized from plastids also catalyzed the conversion of putative glutamate 1-semialdehyde to ALA in a reaction which was not dependent on the addition of an amino donor. The system in maize greatly resembled the one which had been reported from barley. It is suggested that this system is the one responsible for the biosynthesis of ALA destined for chlorophyll formation. PMID:16663121

  16. Fluorescence photodetection of head and neck cancer following topical or systemic application of 5-aminolevulinic acid

    NASA Astrophysics Data System (ADS)

    Leunig, Andreas; Rick, Kai; Stepp, Herbert G.; Gutmann, Ralph; Goetz, Alwin E.; Baumgartner, Reinhold; Feyh, Jens

    1996-12-01

    The aim of photodynamic diagnosis is the complete visualization of all neoplastic lesions in a tumorous organ after topical or systemic application of a tumor selective photosensitizer. In this investigation we performed quantitative fluorescence measurements following topical and systemic application of 5-aminolevulinic acid to head and neck tumors. We investigated 15 patients with neoplastic lesions of the oral cavity and 5 patients with carcinoma of the larynx after rinsing a 0.4 percent-5-ALA solution or inhalation 5 percent-5-ALA. One patient was given 5-ALA systemically p.o. in a concentration of 10mg/kg b.w. Time course and type of porphyrin accumulation were analyzed in neoplastic and surrounding normal tissue by measuring emission spectra of ALA-induced protoporphyrin IX fluorescence at regular intervals for up to 3 hours following 15 minutes of continuous rinsing of a 0.4 percent- ALA-solution, 1 hour of continuous inhalation and 3 hours after p.o. application. After excitation with violet light of a high pressure xenon arc lamp, fluorescence images in the red spectral range from the tumor tissue and the corresponding macroscopic visible tumor were recorded with a CCD-camera. A quantitative analysis of the fluorescence contrast in neoplastic and surrounding tissue was performed using an optical multichannel analyzer.

  17. Effect of 5-aminolevulinic acid on kinetics of protoporphyrin IX production in CHO cells.

    PubMed

    Wołuń-Cholewa, M; Warchoł, W

    2004-01-01

    5-aminolevulinic acid (ALA) is utilized in a photodynamic therapy as a compound capable of augmenting intracellular pool of protoporphyrin IX (PpIX), which exhibits properties of a photosensitizer. The studies were aimed at monitoring accumulation of endogenous protoporphyrin IX in CHO cells under effect of various concentrations of ALA in culture medium and following removal of the compound from the culture medium. Cell content of PpIX was determined following incubation of the cells for 72 h in a culture medium containing different concentration of ALA. Moreover, the cells were preincubated for 2 h in ALA at various concentrations and separated from the compound by medium change and their PpIX content was monitored following incubation. PpIX content was defined by a fluorescent technique under the confocal microscope. In the course of continuous incubation of cells with ALA, biphasic alterations were noted in cellular PpIX concentration. Removal of ALA from the incubation medium resulted at first in a decrease in PpIX content in cells, which was followed by an evidently augmented accumulation of the compound in the cells. The results suggested that in the case of CHO cells, exogenous ALA was not an exclusive source of PpIX synthesis and that alterations in enzyme activities were responsible for production of PpIX. PMID:15253138

  18. Comparison of 5-aminolevulinic acid-encapsulated liposome versus ethosome for skin delivery for photodynamic therapy.

    PubMed

    Fang, Yi-Ping; Tsai, Yi-Hung; Wu, Pao-Chu; Huang, Yaw-Bin

    2008-05-22

    Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an alternative therapy for many non-melanoma skin cancers. The major limitation of this therapy, however, is the low permeability of ALA through the stratum corneum (SC) of the skin. The objective of the present work was to characterize ethosomes containing ALA and to enhance the skin production of protoporphyrin IX (PpIX), compared to traditional liposomes. Results showed that the average particle sizes of the ethosomes were less than those of liposomes. Moreover, the entrapment efficiency of ALA in the ethosome formulations was 8-66% depending on the surfactant added. The particle size of the ethosomes was still approximately <200 nm after 32 days of storage. An in vivo animal study observed the presence of PpIX in the skin by confocal laser scanning microscopy (CLSM). The results indicated that the penetration ability of ethosomes was greater than that of liposomes. The enhancements of all the formulations were ranging from 11- to 15-fold in contrast to that of control (ALA in an aqueous solution) in terms of PpIX intensity. In addition, colorimetry detected no erythema in the irradiated skin. The results demonstrated that the enhancement ratio of ethosome formulations did not significantly differ between the non-irradiated and irradiated groups except for PE/CH/SS, which may have been due to a photobleaching effect of the PDT-irradiation process. PMID:18325699

  19. Sonodynamic therapy using 5-aminolevulinic acid enhances the efficacy of bleomycin.

    PubMed

    Osaki, Tomohiro; Ono, Misato; Uto, Yoshihiro; Ishizuka, Masahiro; Tanaka, Tohru; Yamanaka, Nobuyasu; Kurahashi, Tsukasa; Azuma, Kazuo; Murahata, Yusuke; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Okamoto, Yoshiharu

    2016-04-01

    Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound and a sonosensitizer agent. We examined whether 5-aminolevulinic acid (5-ALA)-based SDT at 1 or 3 MHz could enhance the cytotoxicity of bleomycin (BLM) toward mouse mammary tumor cells both in vitro and in vivo. At 1 MHz, cell viability in the 5-ALA-based SDT group at 1, 2, and 3 W/cm(2) was 34.30%, 50.90%, and 60.16%, respectively. Cell viability in the 5-ALA-based SDT+BLM group at 1, 2, and 3 W/cm(2) was 0.09%, 0.32%, and 0.17%, respectively. In contrast, at 3 MHz, 5-ALA-based SDT+BLM did not show pronounced cytotoxicity. In the in vivo study, 5-ALA-based SDT+BLM was significantly more cytotoxic than 5-ALA-based SDT at 1 MHz and 3 MHz. These findings suggest that the mechanism of tumor shrinkage induced by 5-ALA-based SDT+BLM might involve not only direct cell killing, but also vascular shutdown. Thus, we show here that 5-ALA-based SDT enhances the efficacy of BLM both in vitro and in vivo. PMID:26799128

  20. Plasma protoporphyrin IX following administration of 5-aminolevulinic acid as a potential tumor marker

    PubMed Central

    OTA, URARA; FUKUHARA, HIDEO; ISHIZUKA, MASAHIRO; ABE, FUMINORI; KAWADA, CHIAKI; TAMURA, KENJI; TANAKA, TOHRU; INOUE, KEIJI; OGURA, SHUN-ICHIRO; SHUIN, TARO

    2015-01-01

    Exogenously administered 5-aminolevulinic acid (ALA) is metabolized to protoporphyrin IX (PpIX), which specifically accumulates in cancer cells and emits red fluorescence by blue light irradiation. These phenomena are applied for the intraoperative diagnosis of cancer. Based on the fact that accumulated PpIX in cancer cells is exported extracellularly via the ATP-binding cassette transporter G2, we hypothesized that the measurement of plasma PpIX concentrations could be applied as a tumor marker for cancer screening. In the present study, the use of plasma samples from bladder cancer patients were evaluated as a tumor marker. ALA, 1.0 g, was orally administered to bladder cancer patients and healthy adults. The plasma concentration of PpIX was measured using a high-performance liquid chromatography system. The plasma PpIX concentration following ALA administration was significantly higher in bladder cancer patients than that in the healthy adults, suggesting the effectiveness of plasma PpIX analysis following ALA administration for cancer screening. Additionally, 4 h after ALA administration, plasma PpIX showed high sensitivity (94.4%) and high specificity (80.0%). PMID:26171183

  1. Rhodobacter sphaeroides mutants which accumulate 5-aminolevulinic acid under aerobic and dark conditions.

    PubMed

    Nishikawa, S; Watanabe, K; Tanaka, T; Miyachi, N; Hotta, Y; Murooka, Y

    1999-01-01

    The photosynthetic bacterium Rhodobacter sphaeroides accumulates 5-aminolevulinic acid (ALA), which is a precursor in tetrapyrrole biosynthesis, under light illumination and upon addition of levulinic acid as an inhibitor of ALA dehydratase. To generate an industrial strain which produces ALA in the absence of light, we sequentially mutated R. sphaeroides CR-286 using N-methyl-N'-nitro-N-nitrosoguanidine (NTG). The mutant strains were screened by cultivating in the absence of light and assayed for ALA by the Ehrlich reaction in a 96-well microtiter plate. The mutant strain CR-386, derived from R. sphaeroides CR-286, was selected as a mutant that exhibited significant ALA accumulation. While CR-286 required light illumination for ALA production, CR-386 was able to accumulate 1.5 mM ALA in the presence of 50 mM glucose, 60 mM glycine, 15 mM levulinic acid and 1.0% (w/v) yeast extract under conditions of agitation in the absence of light. The mutant strain CR-450, derived from strain CR-386, was selected further as a mutant that exhibited significant ALA accumulation but no accumulation of aminoacetone, analogue of ALA. CR-450 accumulated 3.8 mM ALA under the same conditions. In the presence of 50 mM glucose, 60 mM glycine, 5 mM levulinic acid and 1.0% (w/v) yeast extract, the mutant strain CR-520, derived from strain CR-450, and strain CR-606, derived from strain CR-520, accumulated 8.1 mM and 11.2 mM ALA, respectively. In batch fermentation, the strain CR-606 accumulated 20 mM ALA over 18 h after the addition of glycine, levulinic acid, glucose and yeast extract. PMID:16232557

  2. 5-aminolevulinic acid for quantitative seek-and-treat of high-grade dysplasia in Barrett's esophagus cellular models

    NASA Astrophysics Data System (ADS)

    Yeh, Shu-Chi Allison; Ling, Celine S. N.; Andrews, David W.; Patterson, Michael S.; Diamond, Kevin R.; Hayward, Joseph E.; Armstrong, David; Fang, Qiyin

    2015-02-01

    High-grade dysplasia (HGD) in Barrett's esophagus (BE) poses increased risk for developing esophageal adenocarcinoma. To date, early detection and treatment of HGD regions are still challenging due to the sampling error from tissue biopsy and relocation error during the treatment after histopathological analysis. In this study, CP-A (metaplasia) and CP-B (HGD) cell lines were used to investigate the "seek-and-treat" potential using 5-aminolevulinic acid-induced protoporphyrin IX (PpIX). The photodynamic therapy photosensitizer then provides both a phototoxic effect and additional image contrast for automatic detection and real-time laser treatment. Complementary to our studies on automatic classification, this work focused on characterizing subcellular irradiation and the potential phototoxicity on both metaplasia and HGD. The treatment results showed that the HGD cells are less viable than metaplastic cells due to more PpIX production at earlier times. Also, due to mitochondrial localization of PpIX, a better killing effect was achieved by involving mitochondria or whole cells compared with just nucleus irradiation in the detected region. With the additional toxicity given by PpIX and potential morphological/textural differences for pattern recognition, this cellular platform serves as a platform to further investigate real-time "seek-and-treat" strategies in three-dimensional models for improving early detection and treatment of BE.

  3. Hydrokolloid occlusive dressings for photodynamic therapy (PDT) of cutaneous lesions with endogenous porphyrins induced by 5-aminolevulinic acid

    NASA Astrophysics Data System (ADS)

    Gahlen, Johannes; Stern, Josef; Herfarth, Christian

    1995-03-01

    Protoporphyrin (Pp IX) is the final intermediate product before haem and can be stimulated to a phototoxic reaction with light. The presence of 5-aminolevulinic acid can increase the intracellular biosynthesis of Pp IX in certain types of tumor cells. The photosensitizing concentrations of Pp IX make laser light induced fluorescence diagnostics (LIFD) and photodynamic therapy possible. A topical application of a 5-aminolevulinic acid solution requires a waterproof occlusive dressing for several hours. We developed a simple technique for a practical preparation for PDT using a hydrocolloid dressing. The normal surrounding skin can be spared. We present our first therapeutic experience with a case of cutaneous breast cancer in a 65-year-old female patient. Six hours after topical application of 10% isotonic 5- aminolevulinic acid under the hydrocolloid dressing PDT was performed (Ar-Dye Laser, 630 nm wavelength). Twenty four hours after PDT a superficial tumor necrosis could be observed with a maximum depth of tumor necrosis of 2 - 3 mm. The surrounding normal skin was without any inflammation.

  4. 5-Aminolevulinic acid production in engineered Corynebacterium glutamicum via C5 biosynthesis pathway.

    PubMed

    Ramzi, Ahmad Bazli; Hyeon, Jeong Eun; Kim, Seung Wook; Park, Chulhwan; Han, Sung Ok

    2015-12-01

    ALA (5-aminolevulinic acid) is an important intermediate in the synthesis of tetrapyrroles and the use of ALA has been gradually increasing in many fields, including medicine and agriculture. In this study, improved biological production of ALA in Corynebacterium glutamicum was achieved by overexpressing glutamate-initiated C5 pathway. For this purpose, copies of the glutamyl t-RNA reductase HemA from several bacteria were mutated by site-directed mutagenesis of which a HemA version from Salmonella typhimurium exhibited the highest ALA production. Cultivation of the HemA-expressing strain produced approximately 204 mg/L of ALA, while co-expression with HemL (glutamate-1-semialdehyde aminotransferase) increased ALA concentration to 457 mg/L, representing 11.6- and 25.9-fold increases over the control strain (17 mg/L of ALA). Further effects of metabolic perturbation were investigated, leading to penicillin addition that further improves ALA production to 584 mg/L. In an optimized flask fermentation, engineered C. glutamicum strains expressing the HemA and hemAL operon produced up to 1.1 and 2.2g/L ALA, respectively, under glutamate-producing conditions. The final yields represent 10.7- and 22.0-fold increases over the control strain (0.1g/L of ALA). From these findings, ALA biosynthesis from glucose was successfully demonstrated and this study is the first to report ALA overproduction in C. glutamicum via metabolic engineering. PMID:26453466

  5. 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence in Meningioma: Qualitative and Quantitative Measurements In Vivo

    PubMed Central

    Valdes, Pablo A.; Bekelis, Kimon; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E.; Erkmen, Kadir; Paulsen, Keith D.; Roberts, David W.

    2014-01-01

    BACKGROUND The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. OBJECTIVE To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. METHODS ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intra-operative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. RESULTS Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (CPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher CPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. CONCLUSION ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature. PMID:23887194

  6. Alleviation of salt-induced oxidative damage by 5-aminolevulinic acid in wheat seedlings

    NASA Astrophysics Data System (ADS)

    Genişel, Mucip; Erdal, Serkan

    2016-04-01

    The aim of this study was to elucidate how 5-aminolevulinic acid (ALA), the precursor of chlorophyll compounds, affects the defence mechanisms of wheat seedlings induced by salt stress. To determine the possible stimulative effects of ALA against salinity, 11-day old wheat seedlings were sprayed with ALA at two different concentrations (10 and 20 mg.l-1) and then stressed by exposure to salt (150 mM NaCl). The salt stress led to significant changes in the antioxidant activity. While guaiacol peroxidase activity decreased, the activities of superoxide dismutase, catalase, and ascorbate peroxidase markedly increased under salt stress. Compared to the salt stress alone, the application of ALA beforehand further increased the activity of these enzymes. This study is the first time the effects of ALA have been monitored with regard to protein content and the isoenzyme profiles of the antioxidant enzymes. Although the salt stress reduced both the soluble protein content and protein band intensities, pre-treating with ALA significantly mitigated these stress-induced reductions. The data for the isoenzyme profiles of the antioxidant enzymes paralleled that of the ALA-induced increases in antioxidant activity. As a consequence of the high antioxidant activity in the seedlings pre-treated with ALA, the stress-induced elevations in the reactive oxygen species, superoxide anion, and hydrogen peroxide contents and lipid peroxidation levels were markedly diminished. Taken together, this data demonstrated that pre-treating with ALA confers resistance to salt stress by modulating the protein synthesis and antioxidant activity in wheat seedlings.

  7. Development and ex vivo evaluation of 5-aminolevulinic acid-loaded niosomal formulations for topical photodynamic therapy.

    PubMed

    Bragagni, Marco; Scozzafava, Andrea; Mastrolorenzo, Antonio; Supuran, Claudiu T; Mura, Paola

    2015-10-15

    The objective of this study was the development of a niosomal formulation for improving skin permeation and penetration of 5-aminolevulinic acid (ALA) in the treatment of skin malignancies by photodynamic therapy (PDT). Different niosomal dispersions were prepared, using two different preparation methods. The effect of addition to a classic formulation, consisting in an equimolar Span 60-cholesterol mixture, of two different edge activators, dicethyl-phosphate (DCP) and sodium cholate (SC), and of the presence of ethanol on the vesicle properties and stability was evaluated. Selected formulations were loaded with the drug and evaluated for physicochemical and stability properties and encapsulation efficiency. Classic and elastic DCP-containing niosomes were the only formulations able to effectively incorporate the drug without instability problems. Ex vivo permeation and penetration studies through excised human skin showed that both the niosomal formulations were significantly more effective in improving ALA skin delivery than the simple aqueous drug solution commonly used in clinical practice, allowing, respectively, an increase of about 80 and 40% of the drug permeated amount and of about 100 and 50% of the drug retained into the skin. These results lead to consider the developed formulations potentially useful for improving ALA bioavailability and therapeutic effectiveness in skin malignancies treatment by topical PDT. PMID:26283280

  8. Formation of protoporphyrin IX in mouse skin after topical application of 5-aminolevulinic acid and its methyl esther

    NASA Astrophysics Data System (ADS)

    Sorensen, Roar; Juzenas, Petras; Iani, Vladimir; Moan, Johan

    1999-02-01

    Normal skin of nude mice (Balb/c) was treated topically with 5-aminolevulinic acid (ALA) and its methyl ester (ALA-Me) for 24 hours. Approximately 0.1 gram of freshly prepared cream was applied to a spot of 1 cm2 on the flank of the mice, which was then covered with a transparent dressing. The ALA induced protoporphyrin IX (PpIX) was studied by means of a noninvasive fiber-optic fluorescence probe connected to a luminescence spectrometer. The excitation wavelength was 407 nm, and the emission wavelength was 637 nm. For the first hour a slight lag in PpIX production was observed for the mice treated with ALA-Me compared to the mice treated with ALA. After approximately 12 hours the ALA and the ALA-Me treated mice showed the same PpIX fluorescence intensity. From 12 hours until 24 hours the PpIX fluorescence intensity decreased for both treatment modalities, even though ALA and ALA-Me were continuously present. At 24 hours ALA-Me-treated mice had less than half the amount of PpIX in their skin compared with ALA- treated mice.

  9. [Photodynamic diagnosis and therapy of neoplasms of the facial skin after topical administration of 5-aminolevulinic acid].

    PubMed

    Lang, S; Baumgartner, R; Struck, R; Leunig, A; Gutmann, R; Feyh, J

    1995-02-01

    Topical application of 5-aminolevulinic acid (5-ALA) is a useful instrument for photodynamic diagnosis and therapy of skin tumours. Diagnostic fluorescence imaging after laser light irradiation (410 nm) revealed a high, tumour-specific fluorescence even in tumour areas not apparent prior to this examination technique. This demonstrates the possibility of photodynamic diagnosis to detect skin tumours. In the therapeutic group 8 patients with 6 solar keratoses and 12 basal cell carcinomas underwent laser light irradiation using a wavelength of 635 nm (dosage 100 J/cm2) 6 hours after topical application of 5-ALA in W/O emulsion. 2-12 hours after laser application we observed reddened tumour tissue with mild oedema, subsequently followed by a crust and epithelised within 4-6 weeks. 2 months after PDT a complete response was observed for all solar keratoses and for 10 of 12 basal cell carcinomas. Photodynamic therapy following topical application of 5-ALA may be an alternative treatment modality for skin tumours. PMID:7710611

  10. 5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Inhibits RIPK1/RIPK3-Dependent Necroptosis in THP-1-Derived Foam Cells

    PubMed Central

    Tian, Fang; Yao, Jianting; Yan, Meng; Sun, Xin; Wang, Wei; Gao, Weiwei; Tian, Zhen; Guo, Shuyuan; Dong, Zengxiang; Li, Bicheng; Gao, Tielei; Shan, Peng; Liu, Bing; Wang, Haiyang; Cheng, Jiali; Gao, Qianping; Zhang, Zhiguo; Cao, Wenwu; Tian, Ye

    2016-01-01

    Necroptosis, or programmed necrosis, contributes to the formation of necrotic cores in atherosclerotic plaque in animal models. However, whether inhibition of necroptosis ameliorates atherosclerosis is largely unknown. In this study, we demonstrated that necroptosis occurred in clinical atherosclerotic samples, suggesting that it may also play an important role in human atherosclerosis. We established an in vitro necroptotic model in which necroptosis was induced in THP-1-derived foam cells by serum deprivation. With this model, we demonstrated that 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) inhibited necroptosis while promoting apoptosis. ALA-SDT activated the caspase-3 and caspase-8 pathways in foam cells, which is responsible for the switch from necroptosis to apoptosis. The inhibition of either caspase-8 or caspase-3 abolished the anti-necroptotic effect of ALA-SDT. In addition, we found that caspase-3 activation peaked 4 hours after ALA-SDT treatment, 2 hours earlier than maximal caspase-8activation. Taken together, our data indicate that ALA-SDT mediates the switch from necroptosis to apoptosis by activating the caspase-3 and caspase-8 pathways and may improve the prognosis of atherosclerosis. PMID:26911899

  11. 5-Aminolevulinic Acid-Protoporphyrin IX Fluorescence-Guided Surgery of High-Grade Gliomas: A Systematic Review.

    PubMed

    Guyotat, Jacques; Pallud, Johan; Armoiry, Xavier; Pavlov, Vladislav; Metellus, Philippe

    2016-01-01

    The current first-line treatment of malignant gliomas consists in surgical resection (if possible) as large as possible. The existing tools don't permit to identify the limits of tumor infiltration, which goes beyond the zone of contrast enhancement on MRI. The fluorescence-guided malignant gliomas surgery was started 15 years ago and had become a standard of care in many countries. The technique is based on fluorescent molecule revelation using the filters, positioned within the surgical microscope. The fluorophore, protoporphyrin IX (PpIX), is converted in tumoral cells from 5-aminolevulinic acid (5-ALA), given orally before surgery. Many studies have shown that the ratio of gross total resections was higher if the fluorescence technique was used. The fluorescence signal intensity is correlated to the cell density and the PpIX concentration. The current method has a very high specificity but still lower sensibility, particularly regarding the zones with poor tumoral infiltration. This book reviews the principles of the technique and the results (extent of resection and survival). PMID:26508406

  12. Intra-operative visualization of brain tumors with 5-aminolevulinic acid-induced fluorescence.

    PubMed

    Widhalm, Georg

    2014-01-01

    Precise histopathological diagnosis of brain tumors is essential for the correct patient management. Furthermore, complete resection of brain tumors is associated with an improved patient prognosis. However, histopathological undergrading and incomplete tumor removal are not uncommon, especially due to insufficient intra-operative visualization of brain tumor tissue. The fluorescent dye 5-aminolevulinic acid (5-ALA) is currently applied for fluorescence-guided resections of high-grade gliomas. The value of 5-ALA-induced protoporphyrin (PpIX) fluorescence for intra-operative visualization of other tumors than high-grade gliomas remains unclear. Within the frame of this thesis, we found a significantly higher rate of complete resections of our high-grade gliomas as compared to control cases by using the newly established 5-ALA fluorescence technology at our department. Additionally, we showed that MRI spectroscopy-based chemical shift imaging (CSI) is capable to identify intratumoral high-grade glioma areas (= anaplastic foci) during navigation guided resections to avoid histopathological undergrading. However, the accuracy of navigation systems with integrated pre-operative imaging data such as CSI declines during resections due to intra-operative brainshift. In two further studies, we found that 5-ALA induced PpIX fluorescence is capable as a novel intra-operative marker to detect anaplastic foci within initially suspected low-grade gliomas independent of brainshift. Finally, we showed that the application of 5-ALA is also of relevance in needle biopsies for intra-operative identification of representative brain tumor tissue. These data indicate that 5-ALA is not only of major importance for resection of high-grade gliomas, but also for intra-operative visualization of anaplastic foci as well as representative brain tumor tissue in needle biopsies unaffected by brainshift. Consequently, this new technique might become a novel standard in brain tumor surgery that

  13. In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria

    PubMed Central

    Suzuki, Shigeo; Hikosaka, Kenji; Balogun, Emmanuel O.; Komatsuya, Keisuke; Niikura, Mamoru; Kobayashi, Fumie; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo

    2015-01-01

    5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe2+) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. PMID:26324278

  14. Treating cutaneous squamous cell carcinoma using 5-aminolevulinic acid polylactic-co-glycolic acid nanoparticle-mediated photodynamic therapy in a mouse model

    PubMed Central

    Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Zhao, Feng; Luan, Hansen; Wang, Xiuli

    2015-01-01

    Background Squamous cell carcinoma (SCC) is a common skin cancer, and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted 5-aminolevulinic acid (ALA) delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Materials and methods Ultraviolet-induced cutaneous SCCs were established in hairless mice. ALA-loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NP-induced protoporphyrin IX fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results PLGA NPs enhanced protoporphyrin IX production in SCC. ALA PLGA NP-mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC. PMID:25609949

  15. Efficacy of a Complex of 5-Aminolevulinic Acid and Glycyl-Histidyl-Lysine Peptide on Hair Growth

    PubMed Central

    Sim, Hyun Bo; Jang, Yong Hyun; Lee, Seok-Jong; Kim, Do Won; Yim, Soon-Ho

    2016-01-01

    Background Pattern hair loss is a very common problem. Although effective therapeutics for the treatment of pattern hair loss have been used, novel therapeutic modalities are still required to enhance hair growth. Objective We investigated the efficacy and safety of a complex (ALAVAX) of 5-aminolevulinic acid (5-ALA) and glycyl-histidyl-lysine (GHK) peptide for the treatment of pattern hair loss. Methods Forty-five patients with male pattern hair loss were treated with ALAVAX 100 mg/ml (group A), ALAVAX 50 mg/ml (group B) or placebo (group C) once a day for 6 months. Total hair count, hair length, hair thickness, patient's assessment and adverse events were evaluated at month 1, 3, and 6. Results An increase in hair count for 6 months was 52.6 (p<0.05) in group A, 71.5 (p<0.05) in group B, and 9.6 in group C. The ratio of changes in hair count between group B (2.38) and group C (1.21) at 6 months showed a statistically significant difference (p<0.05). The proportion above good satisfaction was higher in group A (26.7%) than in the other groups (group B: 14.3%, group C: 7.1%). There was no statistically significant difference in hair length and hair thickness among 3 groups at 6 months. There was no adverse event in 3 groups. Conclusion Our study showed that a complex of 5-ALA and GHK peptide may be considered as one of the complementary agents for the treatment of male pattern hair loss. PMID:27489425

  16. Insulin-Like Growth Factor-2 Is Induced Following 5-Aminolevulinic Acid-Mediated Photodynamic Therapy in SW620 Human Colon Cancer Cell Line

    PubMed Central

    Woźniak, Marta; Duś-Szachniewicz, Kamila; Ziółkowski, Piotr

    2015-01-01

    The IGF system is a family of polypeptide growth factors, which plays a significant role in the development and growth of many cells. Dysregulation of insulin-like growth factors and their pathway components has been connected with essential tumor properties, such as tumor cell proliferation, antiapoptotic properties, invasive behavior and chemotherapy resistance. However, the effects of photodynamic therapy (PDT), one of the cancer treatment methods for the regulation of the IGF signaling pathway, are still unclear. The aim of this study was to investigate the expression of IGF-2 after 5-aminolevulinic acid (5-ALA)-mediated-PDT in SW620 human colorectal cancer cells with evaluation of cell proliferation and apoptosis and to determine the effects of PDT on the IGF-2 receptor (IGF-2R), IGF-2 binding protein-1 (IGF-2BP-1) and the proapoptotic protein, BAX. Cells were treated with 5-aminolevulinic acid and its methyl ester. Changes of the expression and concentration of IGF-2 before and after treatment were assayed by immunocytochemistry, Western blot and ELISA. We found that IGF-2 was significantly overexpressed in the SW620 cell line, while its receptor and binding protein-1 were not significantly changed. Within this study, we would like to suggest that IGF-2 contributes to the effects of PDT and that its expression will influence post-PDT efficacy. PMID:26445041

  17. Insulin-Like Growth Factor-2 Is Induced Following 5-Aminolevulinic Acid-Mediated Photodynamic Therapy in SW620 Human Colon Cancer Cell Line.

    PubMed

    Woźniak, Marta; Duś-Szachniewicz, Kamila; Ziółkowski, Piotr

    2015-01-01

    The IGF system is a family of polypeptide growth factors, which plays a significant role in the development and growth of many cells. Dysregulation of insulin-like growth factors and their pathway components has been connected with essential tumor properties, such as tumor cell proliferation, antiapoptotic properties, invasive behavior and chemotherapy resistance. However, the effects of photodynamic therapy (PDT), one of the cancer treatment methods for the regulation of the IGF signaling pathway, are still unclear. The aim of this study was to investigate the expression of IGF-2 after 5-aminolevulinic acid (5-ALA)-mediated-PDT in SW620 human colorectal cancer cells with evaluation of cell proliferation and apoptosis and to determine the effects of PDT on the IGF-2 receptor (IGF-2R), IGF-2 binding protein-1 (IGF-2BP-1) and the proapoptotic protein, BAX. Cells were treated with 5-aminolevulinic acid and its methyl ester. Changes of the expression and concentration of IGF-2 before and after treatment were assayed by immunocytochemistry, Western blot and ELISA. We found that IGF-2 was significantly overexpressed in the SW620 cell line, while its receptor and binding protein-1 were not significantly changed. Within this study, we would like to suggest that IGF-2 contributes to the effects of PDT and that its expression will influence post-PDT efficacy. PMID:26445041

  18. Nitric Oxide Mediates 5-Aminolevulinic Acid-Induced Antioxidant Defense in Leaves of Elymus nutans Griseb. Exposed to Chilling Stress

    PubMed Central

    Fu, Juanjuan; Chu, Xitong; Sun, Yongfang; Miao, Yanjun; Xu, Yuefei; Hu, Tianming

    2015-01-01

    Nitric oxide (NO) and 5-aminolevulinic acid (ALA) are both extremely important signalling molecules employed by plants to control many aspects of physiology. In the present study, the role of NO in ALA-induced antioxidant defense in leaves of two sources of Elymus nutans Griseb. (Damxung, DX and Zhengdao, ZD) was investigated. Chilling stress enhanced electrolyte leakage, accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2) and superoxide radical in two E. nutans, which were substantially alleviated by exogenous ALA and NO application. Pretreatment with NO scavenger PTIO or NOS inhibitor L-NNA alone and in combination with ALA induced enhancements in electrolyte leakage and the accumulation of MDA, H2O2 and superoxide radical in leaves of DX and ZD exposed to chilling stress, indicating that the inhibition of NO biosynthesis reduced the chilling resistance of E. nutans and the ALA-enhanced chilling resistance. Further analyses showed that ALA and NO enhanced antioxidant defense and activated plasma membrane (PM) H+-ATPase and decreased the accumulation of ROS induced by chilling stress. A pronounced increase in nitric oxide synthase (NOS) activity and NO release by exogenous ALA treatment was found in chilling-resistant DX plants exposed to chilling stress, while only a little increase was observed in chilling-sensitive ZD. Furthermore, inhibition of NO accumulation by PTIO or L-NNA blocked the protective effect of exogenous ALA, while both exogenous NO treatment and inhibition of endogenous NO accumulation did not induce ALA production. These results suggested that NO might be a downstream signal mediating ALA-induced chilling resistance in E. nutans. PMID:26151364

  19. Regulation of Cadmium-Induced Proteomic and Metabolic Changes by 5-Aminolevulinic Acid in Leaves of Brassica napus L.

    PubMed Central

    Ali, Basharat; Gill, Rafaqat A.; Yang, Su; Gill, Muhammad B.; Farooq, Muhammad A.; Liu, Dan; Daud, Muhammad K.; Ali, Shafaqat; Zhou, Weijun

    2015-01-01

    It is evident from previous reports that 5-aminolevulinic acid (ALA), like other known plant growth regulators, is effective in countering the injurious effects of heavy metal-stress in oilseed rape (Brassica napus L.). The present study was carried out to explore the capability of ALA to improve cadmium (Cd2+) tolerance in B. napus through physiological, molecular, and proteomic analytical approaches. Results showed that application of ALA helped the plants to adjust Cd2+-induced metabolic and photosynthetic fluorescence changes in the leaves of B. napus under Cd2+ stress. The data revealed that ALA treatment enhanced the gene expressions of antioxidant enzyme activities substantially and could increase the expression to a certain degree under Cd2+ stress conditions. In the present study, 34 protein spots were identified that differentially regulated due to Cd2+ and/or ALA treatments. Among them, 18 proteins were significantly regulated by ALA, including the proteins associated with stress related, carbohydrate metabolism, catalysis, dehydration of damaged protein, CO2 assimilation/photosynthesis and protein synthesis/regulation. From these 18 ALA-regulated proteins, 12 proteins were significantly down-regulated and 6 proteins were up-regulated. Interestingly, it was observed that ALA-induced the up-regulation of dihydrolipoyl dehydrogenase, light harvesting complex photo-system II subunit 6 and 30S ribosomal proteins in the presence of Cd2+ stress. In addition, it was also observed that ALA-induced the down-regulation in thioredoxin-like protein, 2, 3-bisphosphoglycerate, proteasome and thiamine thiazole synthase proteins under Cd2+ stress. Taken together, the present study sheds light on molecular mechanisms involved in ALA-induced Cd2+ tolerance in B. napus leaves and suggests a more active involvement of ALA in plant physiological processes than previously proposed. PMID:25909456

  20. 5-Aminolevulinic acid-mediated sonodynamic therapy reverses macrophage and dendritic cell passivity in murine melanoma xenografts.

    PubMed

    Wang, Shan; Hu, Zheng; Wang, Xiaolong; Gu, Chuanwen; Gao, Zhongxiuzi; Cao, Wenwu; Zheng, Jinhua

    2014-09-01

    Sonodynamic therapy (SDT) uses a combination of sonosensitizing drugs and low-intensity therapeutic ultrasound to cause apoptosis and autophagy of tumor cells. However, its effects on the tumor microenvironment, especially on the immune state, remain unknown. In this study, we investigated the transformation of macrophages and dendritic cells (DCs) in the tumor microenvironment during 5-aminolevulinic acid (5-ALA)-mediated SDT in mice transplanted with B16F10 melanomas. Tumor growth and mouse weight were measured. Hematoxylin-eosin staining was used to evaluate tumor morphology to quantify the anti-tumor efficacy of 5-ALA-mediated SDT. We investigated anti-tumor immunity in the tumor microenvironment by immunocytochemical staining of CD68, CD163, CD80, CD86, tumor necrosis factor α (TNF-α), interleukin 10 (IL-10) and interferon γ (IFN-γ). Tumor growth was restrained by 5-ALA-mediated SDT in B16F10 melanoma-bearing mice. CD68 levels increased and CD163 decreased, indicating that M2 macrophages were converted to the M1 phenotype in the tumor. The increase in CD80 and CD86 showed that DCs in the tumor microenvironment tend to mature after SDT treatment. The cytokines INF-γ, TNF-α and IL-10 significantly increased in SDT. Application of low-intensity therapeutic ultrasound alone also led to similar trends in our study, but combined treatment with 5-ALA yielded a change. The original stabilized immune state in the tumor microenvironment can be interrupted by low-intensity therapeutic ultrasound combined with 5-ALA, which enhanced the pro-inflammatory response and reversed the passive properties of macrophages and dendritic cells. PMID:25023114

  1. Involvement of Singlet Oxygen in 5-Aminolevulinic Acid-Induced Photodynamic Damage of Cucumber (Cucumis sativus L.) Chloroplasts 1

    PubMed Central

    Chakraborty, Niranjan; Tripathy, Baishnab Charan

    1992-01-01

    Cucumber (Cucumis sativus L., cv Poinsette) plants were sprayed with 20 millimolar 5-aminolevulinic acid and then incubated in the dark for 14 hours. The intact chloroplasts were isolated from the above plants in the dark and were exposed to weak light (250 micromoles per square meter per second). Within 30 minutes, photosystem II activity was reduced by 50%. The singlet oxygen (1O2) scavengers, histidine and sodium azide (NaN3) significantly protected against the damage caused to photosystem II. The hydroxyl radical scavenger formate failed to protect the thylakoid membranes. The production of 1O2 monitored as N,N-dimethyl p-nitrosoaniline bleaching increased as a function of light exposure time of treated chloroplasts and was abolished by the 1O2 quencher, NaN3. Membrane lipid peroxidation monitored as malondialdehyde production was also significantly reduced when chloroplasts were illuminated in the presence of NaN3 and histidine. Protochlorophyllide was the most abundant pigment accumulated in intact chloroplasts isolated from 5-aminolevulinic acid-treated plants and was probably acting as type II photosensitizer. PMID:16668650

  2. Comparative split-face study of 5-aminolevulinic acid photodynamic therapy with intense pulsed light for photorejuvenation of Asian skin.

    PubMed

    Kosaka, Sachiko; Yasumoto, Minako; Akilov, Oleg E; Hasan, Tayyaba; Kawana, Seiji

    2010-12-01

    Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) (ALA-PDT) using intense pulsed light (IPL) as a light source (IPL-ALA-PDT) has been used for photorejuvenation, but it is unclear if this protocol can be applied to darker skin types. We performed this study to assess our IPL-ALA-PDT protocol for photorejuvenation in Asian skin. To determine an appropriate dose, ALA ointment (0-20%) was applied to the upper arm of five healthy volunteers and the fluorescence intensity (FI) was measured using a spectrofluorometer. Non-linear regression analysis of FI 2 h after ALA application with global fitting gave a typical sigmoid dose-response curve with R² = 0.9705 and saturation after 5% ALA. The entire faces of 16 Japanese women with photodamage were then treated with IPL (500-670 and 870-1400 nm, 23-30 J/cm²) 2 h after application of 5% ALA to one side of the face. Three treatments were delivered at 4-week intervals with follow-up visits. Comparative analysis of photorejuvenation showed noticeable improvements on both sides of the face, although the reduction in the photoaging score from baseline did not differ significantly between the two sides in all subjects. Despite this finding, 75% of the patients felt that the IPL-ALA-PDT-treated side of the face showed greater improvement than the IPL-treated side. However, all IPL-ALA-PDT-treated sides showed adverse effects such as erythema and pain. Therefore, we conclude that the IPL-ALA-PDT protocol requires optimization for photorejuvenation in Asians. PMID:21083701

  3. Transport properties and association behaviour of the zwitterionic drug 5-aminolevulinic acid in water. A precision conductometric study.

    PubMed

    Merclin, Nadia; Beronius, Per

    2004-02-01

    The behavior of the hydrochloride salt of 5-aminolevulinic acid (ALA-HCl) with respect to transport properties and dissociation in aqueous solution at 25 degrees C has been studied using precision conductometry within the concentration range 0.24-5.17mM. The conductivity data are interpreted according to elaborated conductance theory. The carboxyl group appears to be, in practice, undissociated. The dissociation constant, K(a), of the NH(3)(+) form of the amino acid molecules is determined to 6.78x10(-5) (molarity scale); pK(a)=4.17. The limiting molar conductivity of the ALA-H(+) ion, lambda(0)=33.5cm(2)Omega(-1)mol(-1); electric mobility u=3.47x10(-4)cm(2)V(-1)s(-1), is close to the electric mobilites of the acetate and benzoic ions. PMID:14757508

  4. The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis.

    PubMed

    Sugiyama, Yuta; Hagiya, Yuichiro; Nakajima, Motowo; Ishizuka, Masahiro; Tanaka, Tohru; Ogura, Shun-Ichiro

    2014-03-01

    Our previous study demonstrated that 5-aminolevulinic acid (ALA) administered to mice stimulates oxidative phosphorylation by upregulation of the mitochondrial respiratory chain complex IV enzyme cytochrome c oxidase (COX). The present study investigated whether ALA disrupts the Warburg effect, which represents a shift in ATP generation from oxidative phosphorylation to glycolysis, protecting tumor cells against oxidative stress-mediated apoptosis. The human lung carcinoma cell line A549 exposed to ALA exhibited enhanced oxidative phosphorylation, which was indicated by an increase in COX protein expression and oxygen consumption. Furthermore, ALA suppressed glycolysis-mediated acidosis. This normalization of the ATP metabolic pathways significantly increased the generation of superoxide anion radical (O2•-) and the functional expression of active caspase-3, leading to caspase-dependent apoptosis. These data demonstrate that ALA inhibits the Warburg effect and induces cancer cell death. Use of this endogenous compound might constitute a novel approach to cancer therapy. PMID:24366173

  5. In Vitro Comparison of Hypericin and 5-Aminolevulinic Acid-Derived Protoporphyrin IX for Photodynamic Inactivation of Medulloblastoma Cells

    PubMed Central

    Ritz, Rainer; Scheidle, Christian; Noell, Susan; Roser, Florian; Schenk, Martin; Dietz, Klaus; Strauss, Wolfgang S. L.

    2012-01-01

    Background Hypericin (HYP) is a naturally occurring photosensitizer. Cellular uptake and photodynamic inactivation after incubation with this photosensitizer have neither been examined in medulloblastoma cells in vitro, nor compared with 5-aminolevulinic acid-derived protoporphyrin IX (5-ALA-derived PpIX). Methods In 3 medulloblastoma cell lines (D283 Med, Daoy, and D341 Med) the time- and concentration-dependent intracellular accumulation of HYP and 5-ALA-derived PpIX was analyzed by fluorescence microscopy (FM) and FACS. Photocytotoxicity was measured after illumination at 595 nm (HYP) and 635 nm (5-ALA-derived PpIX) in D283 Med cells and compared to U373 MG glioma cells. Results All medulloblastoma cell lines exhibited concentration- and time-dependent uptake of HYP. Incubation with HYP up to 10 µM resulted in a rapid increase in fluorescence intensity, which peaked between 2 and 4 hours. 5-ALA-derived PpIX accumulation increased in D283 Med cells by 22% over baseline after 5-ALA incubation up to 1.2 mM. Photocytotoxicity of 5-ALA-derived PpIX was higher in D283 Med medulloblastoma compared to U373MG glioma. The [lethal dose (light dose that is required to reduce cell survival to 50% of control)] of 5-ALA-derived PpIX was 3.8 J/cm2 in D283 Med cells versus 5.7 J/cm2 in U373MG glioma cells. Photocytotoxicity of HYP in D283 Med cells was determined at 2.5 µM after an incubation time of 2 h and an illumination wavelength of 595 nm. The value was 0.47 J/cm2. Conclusion By its 5-fold increase in fluorescence over autofluorescence levels HYP has excellent properties for tumor visualization in medulloblastomas. The high photocytotoxicity of HYP, compared to 5-ALA-derived PpIX, is convincingly demonstrated by its 8- to 13-fold lower . Therefore HYP might be a promising molecule for intraoperative visualization and photodynamic treatment of medulloblastomas. PMID:23251668

  6. Optimization of Biomass and 5-Aminolevulinic Acid Production by Rhodobacter sphaeroides ATCC17023 via Response Surface Methodology.

    PubMed

    Liu, Shuli; Zhang, Guangming; Li, Jianzheng; Li, Xiangkun; Zhang, Jie

    2016-06-01

    Microbial 5-aminolevulinic acid (ALA) produced from wastewater is considered as potential renewable energy. However, many hurdles are needed to be overcome such as the regulation of key influencing factors on ALA yield. Biomass and ALA production by Rhodobacter sphaeroides was optimized using response surface methodology. The culturing medium was artificial volatile fatty acids wastewater. Three additives were optimized, namely succinate and glycine that are precursors of ALA biosynthesis, and D-glucose that is an inhibitor of ALA dehydratase. The optimal conditions were achieved by analyzing the response surface plots. Statistical analysis showed that succinate at 8.56 mmol/L, glycine at 5.06 mmol/L, and D-glucose at 7.82 mmol/L were the best conditions. Under these optimal conditions, the highest biomass production and ALA yield of 3.55 g/L and 5.49 mg/g-biomass were achieved. Subsequent verification experiments at optimal values had the maximum biomass production of 3.41 ± 0.002 g/L and ALA yield of 5.78 ± 0.08 mg/g-biomass. PMID:26875086

  7. Influence of precursors and inhibitor on the production of extracellular 5-aminolevulinic acid and biomass by Rhodopseudomonas palustris KG31.

    PubMed

    Saikeur, Angkana; Choorit, Wanna; Prasertsan, Poonsuk; Kantachote, Duangporn; Sasaki, Ken

    2009-05-01

    5-Aminolevulinic acid (ALA) and the biomass of photosynthetic bacteria, Rhodopseudomonas palustris KG31, have very high potential for development and exploitation as bioherbicide and biofertilizer respectively. In this work, the effects of two precursors and an inhibitor of aminolevulinic dehydratase (ALAD) added to the VFA culture medium on the production of ALA and biomass were investigated. The experimental runs were carried out according to a Box-Behnken design. The precursors were added to the medium at the beginning of cultivation, while the inhibitor was added after 24 h. Statistical analysis indicated that levulinic acid (LA) has a positive effect on ALA production while glycine has a negative effect on biomass production. In order to enhance both ALA and biomass products, the most suitable medium was VFA medium supplemented with 3.0 mM glycine and 10 mM LA, giving ALA and biomass of 182.91 microM and 3.1 gDCW/l within 54 h. PMID:19420716

  8. Photobleaching-based method to individualize irradiation time during interstitial 5-aminolevulinic acid photodynamic therapy.

    PubMed

    Hennig, Georg; Stepp, Herbert; Johansson, Ann

    2011-09-01

    Interstitial photodynamic therapy (iPDT) is being investigated for the treatment of high-grade human brain malignancies. In recent clinical studies, fluorescence monitoring during iPDT of glioblastoma multiforme has revealed patient-specific accumulation of photosensitizer (aminolevulinic acid (ALA) induced protoporphyrin IX, PpIX) and its photobleaching kinetics. As photosensitizer degradation, also referred to as photobleaching, and tissue damage are caused by the same underlying processes, the photobleaching kinetics might provide a tool for real-time treatment supervision. Here, we show with computer simulations that varying optical properties have a strong influence on the irradiation time required to fully bleach the photosensitizer. We propose a method to potentially determine the time point during iPDT, when the photosensitizer within the target volume has been largely photobleached. Simulations show that it is possible to determine this time point by continuously monitoring the ratio of the fluorescence intensities at two time points during irradiation. We show that this method works for a large range of optical properties, different photobleaching rates and varying inter-fibre distances. In conclusion, the relative fluorescence method offers the potential to individualize irradiation times to consume the photosensitizer within the target tissue during iPDT. PMID:21864802

  9. Clearance of protoporphyrin IX from mouse skin after topical application of 5-aminolevulinic acid and its methyl ester

    NASA Astrophysics Data System (ADS)

    Juzenas, Petras; Sorensen, Roar; Iani, Vladimir; Moan, Johan

    1999-02-01

    The clearance of protoporphyrin IX (PpIX) from the skin of hairless BALB/c mice after topical application of 5- aminolevulinic acid (ALA) and its methyl ester (ALA-Me) was investigated. Creams containing 2 or 20% of ALA or ALA-Me were topically applied on spots of approximately 1 cm2 for 12 hours. The PpIX fluorescence was detected by the means of a Perkin Elmer LS50B luminescence spectrometer equipped with a fiber-optic probe. The emission spectrum was identical with that of cell-bound PpIX. After 12 hours application of ALA and ALA-Me similar amounts of PpIX were found. After creme removal the ALA-induced PpIX fluorescence decayed with a half-life of about 20 hours (20% ALA cream). The ALA-Me-induced PpIX was faster cleared from the skin than ALA-induced PpIX, and had a half-life of about 7 hours (20% ALA-Me cream).

  10. Rheological characterization and permeation behavior of poloxamer 407-based systems containing 5-aminolevulinic acid for potential application in photodynamic therapy.

    PubMed

    van Hemelrijck, Carlos; Müller-Goymann, Christel C

    2012-11-01

    Topical application of 5-aminolevulinic acid (ALA) in photodynamic therapy is of great interest because of avoiding systemic side effects with such an easy way of application. However, due to ALA's high polarity its dermal bioavailability is rather limited and thus, permeation enhancement of this active is of major interest in research. In a previous study, a semisolid poloxamer 407-based (POX), five-component system ("thermogel") was developed for permeation enhancement of ALA across isolated human stratum corneum. In the present study, five-component systems of systematically varied compositions were investigated both rheologically and in terms of permeation enhancement. The five-component systems contained water, a fixed combination of 1:1 of isopropyl alcohol (IPA) and dimethyl isosorbide (DMIS) and a fixed ratio of 4:1 of POX to propylene glycol dicaprylocaprate (MIG). Rheological characterization showed that complex viscosity depended on IPA/DMIS and POX/MIG content. The gelation temperature (GT) was strongly influenced by interactions between MIG, IPA and DMIS. Regarding permeation behavior, several systems showing better permeation fluxes than the original "thermogel" were identified. Surprisingly, permeation flux did not inversely correlate with the complex viscosity, showing that permeation behavior may depend on a variety of further physicochemical characteristics including individual composition and microstructure of the respective formulation. PMID:22898092

  11. Bi-functional prodrugs of 5-aminolevulinic acid and butyric acid increase erythropoiesis in anemic mice in an erythropoietin-independent manner.

    PubMed

    Rephaeli, Ada; Tarasenko, Nataly; Fibach, Eitan; Rozic, Gabriela; Lubin, Ido; Lipovetsky, Julia; Furman, Svetlana; Malik, Zvi; Nudelman, Abraham

    2016-08-25

    Anemia is a major cause of morbidity and mortality worldwide resulting from a wide variety of pathological conditions. In severe cases it is treated by blood transfusions or injection of erythroid stimulating agents, e.g., erythropoietin (Epo), which can be associated with serious adverse effects. Therefore, there is a need to develop new treatment modalities. We recently reported that treatment of erythroleukemic cells with the novel the bi-functional prodrugs of 5-aminolevulinic acid (ALA) and butyric acid (BA), AN233 and AN908, enhanced hemoglobin (Hb) synthesis to a substantially higher level than did ALA and BA individually or their mixture. Herein, we describe that these prodrugs when given orally to mice induced histone deacetylase inhibition in the kidneys, bone marrow and spleen, thus, indicating good penetrability to the tissues. In mice where anemia was chemically induced, treatment with the prodrugs increased the Hb, the number of red blood cells (RBCs) and the percentage of reticulocytes to normal levels. The prodrugs had no adverse effects even after repeated treatment at 100-200mg/kg for 50days. The lack of increased levels of Epo in the blood of mice that were treated with the prodrugs suggests that AN233 and AN908 affected the Hb and RBC levels in an Epo-independent manner. Taken together with our previous studies, we propose that the prodrugs increase globin expression by BA inhibition of histone deacetylase and elevation heme synthesis by ALA. These results support an Epo-independent approach for treating anemia with these prodrugs. PMID:27283485

  12. Expression of the Rhodobacter sphaeroides hemA and hemT genes, encoding two 5-aminolevulinic acid synthase isozymes.

    PubMed Central

    Neidle, E L; Kaplan, S

    1993-01-01

    The nucleotide sequences of the Rhodobacter sphaeroides hemA and hemT genes, encoding 5-aminolevulinic acid (ALA) synthase isozymes, were determined. ALA synthase catalyzes the condensation of glycine and succinyl coenzyme A, the first and rate-limiting step in tetrapyrrole biosynthesis. The hemA and hemT structural gene sequences were 65% identical to each other, and the deduced HemA and HemT polypeptide sequences were 53% identical, with an additional 16% of aligned amino acids being similar. HemA and HemT were homologous to all characterized ALA synthases, including two human ALA synthase isozymes. In addition, they were evolutionarily related to 7-keto-8-aminopelargonic acid synthetase (BioF) and 2-amino-3-ketobutyrate coenzyme A ligase (Kbl), enzymes which catalyze similar reactions. Two hemA transcripts were identified, both expressed under photosynthetic conditions at levels approximately three times higher than those found under aerobic conditions. A single transcriptional start point was identified for both transcripts, and a consensus sequence at this location indicated that an Fnr-like protein may be involved in the transcriptional regulation of hemA. Transcription of hemT was not detected in wild-type cells under the physiological growth conditions tested. In a mutant strain in which the hemA gene had been inactivated, however, hemT was expressed. In this mutant, hemT transcripts were characterized by Northern (RNA) hybridization, primer extension, and ribonuclease protection techniques. A small open reading frame of unknown function was identified upstream of, and transcribed in the same direction as, hemA. Images PMID:8468290

  13. Effect of continuous and multiple doses of 5-aminolevulinic acid on protoporphyrin IX concentrations in the rat uterus.

    PubMed

    Roy, B N; Van Vugt, D A; Weagle, G E; Pottier, R H; Reid, R L

    1997-11-01

    The objective of the present study was to determine if the concentration of protoporphyrin IX (PpIX) in the rat endometrium could be increased by administering 5-aminolevulinic acid (ALA) in multiple doses or by continuous infusion. The effect of pH, temperature and time in solution on the stability of ALA were also investigated. Estrogen-filled silastic capsules were implanted subcutaneously into ovary intact female rats (200-225 g) (n = 66). On the third day of hormonal priming, ALA (10 mg or 25 mg) dissolved in saline and adjusted to a pH of 5-5.5 was administered intrauterine either as a single bolus or as two injections 3 hours apart (n = 10). A fifth group of rats was infused with 25 mg ALA over a 12 hour period using an osmotic minipump (n = 6). In a second experiment, ALA (25 mg) was injected immediately after being dissolved in saline (pH 2) (n = 16) or after incubation at 37 degrees C for 12 hour (pH 2) (n = 7). PpIX was then extracted from the endometrium and myometrium using a 1:1 methanol/perchloric acid solution and quantified spectrofluorometrically. A dose-response relationship was observed between 10 and 25 mg of ALA and endometrial PpIX concentrations. However, no differences in endometrial PpIX concentrations were detected between rats administered ALA either as a single bolus or as two doses. Continuous infusion of 25 mg of ALA resulted in statistically lower endometrial PpIX concentrations compared to 25 mg ALA injected either as a single bolus or as two injections. Neither pH, temperature, nor time in solution affected ALA-induced PpIX accumulation. We conclude that the simplest way of achieving the highest PpIX concentration in the rat endometrium in vivo is to administer a bolus injection of 25 mg of ALA. PMID:9440319

  14. Fractionated PDT with 5-aminolevulinic acid: effective, cost effective, and patient friendly

    NASA Astrophysics Data System (ADS)

    de Vijlder, Hannah C.; Middelburg, Tom A.; de Bruijn, Henriette S.; Robinson, Dominic J.; Neumann, H. A. Martino; de Haas, Ellen R. M.

    2009-06-01

    PDT with ALA and MAL is established as a relatively effective treatment for non-melanoma skin cancer and premalignancies. PDT is often repeated, because a single treatment gives poor long term results. Preclinical studies showed that ALA-PDT applying a fractionated illumination scheme with a small first light fraction and a second larger light fraction separated by a dark interval of two hours resulted in a significant increase in efficacy. Whereas the efficacy was not enhanced by fractionating MAL-PDT, indicating that ALA-PDT mechanism is not the same as MAL-PDT mechanism. The increase in efficacy using fractionated PDT was confirmed clinically. A randomized comparative clinical study comparing fractionated ALA-PDT versus non-fractionated ALA-PDT in the treatment of superficial basal cell carcinoma showed a significant higher response rate in the lesions treated with fractionated ALA-PDT after a follow-up of one year ( p<0.002, log-rank test). The five year follow-up is studied at moment. So far the complete response in the group treated with fractionated ALA-PDT seems to be only a few percentages lower compared to the one year follow-up. Besides the gain in response rate, fractionated ALA PDT is cost effective. ALA gel is less expensive than the commercially available MAL (Metvix) and moreover fractionated ALA-PDT takes one treatment day, instead of two treatment days using the Metvix treatment protocol (two MAL-PDT treatments separated by one week), both reducing direct and indirect costs and the burden to the patient.

  15. Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

    2007-02-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time

  16. Outcomes after combined use of intraoperative MRI and 5-aminolevulinic acid in high-grade glioma surgery

    PubMed Central

    Schatlo, Bawarjan; Fandino, Javier; Smoll, Nicolas R.; Wetzel, Oliver; Remonda, Luca; Marbacher, Serge; Perrig, Wolfgang; Landolt, Hans; Fathi, Ali-Reza

    2015-01-01

    Background Previous studies have shown the individual benefits of 5-aminolevulinic acid (5-ALA) and intraoperative (i)MRI in enhancing survival for patients with high-grade glioma. In this retrospective study, we compare rates of progression-free and overall survival between patients who underwent surgical resection with the combination of 5-ALA and iMRI and a control group without iMRI. Methods In 200 consecutive patients with high-grade gliomas, we recorded age, sex, World Health Organization tumor grade, and pre- and postoperative Karnofsky performance status (good ≥80 and poor <80). A 0.15-Tesla magnet was used for iMRI; all patients operated on with iMRI received 5-ALA. Overall and progression-free survival rates were compared using multivariable regression analysis. Results Median overall survival was 13.8 months in the non-iMRI group and 17.9 months in the iMRI group (P = .043). However, on identifying confounding variables (ie, KPS and resection status) in this univariate analysis, we then adjusted for these confounders in multivariate analysis and eliminated this distinction in overall survival (hazard ratio: 1.23, P = .34, 95% CI: 0.81, 1.86). Although 5-ALA enhanced the achievement of gross total resection (odds ratio: 3.19, P = .01, 95% CI: 1.28, 7.93), it offered no effect on overall or progression-free survival when adjusted for resection status. Conclusions Gross total resection is the key surgical variable that influences progression and survival in patients with high-grade glioma and more likely when surgical adjuncts, such as iMRI in combination with 5-ALA, are used to enhance resection. PMID:25858636

  17. Clearance of protoporphyrin IX induced by 5-aminolevulinic acid from WiDr human colon carcinoma cells

    NASA Astrophysics Data System (ADS)

    Juzeniene, Asta; Kaliszewski, Miron; Bugaj, Andrzej; Moan, Johan

    2009-06-01

    5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is the most widely practiced form of PDT in dermatology. One of the advantages of ALA-PDT is that undesirable photosensitization lasts only for 24-48 h. In order to optimize ALA-PDT it is necessary to understand the mechanisms controlling intracellular PpIX clearance (efflux and transformation into heme) in order to decrease protoporphyrin IX (PpIX) clearance rates in the early stages of its production. The aim of this study was to investigate the factors controlling the clearance of intracellular PpIX. Fluorescence spectroscopy was used to study PpIX kinetics in WiDr cells initially treated with ALA. The clearance rate of PpIX in WiDr cells was faster after application of a low concentration of ALA (0.1 mM) than after application of high concentration of ALA (1 mM). PpIX was cleared faster from cells which initially were seeded at low densities than cells seeded at higher densities. The presence of the iron chelator deferoxamine reduced the clearance rate of PpIX, while the presence of ferrous sulfate acted oppositely. The decay rate of PpIX in WiDr cells was faster at higher temperature than at lower. The ferrochelatase activity at pH 7.2 was significantly greater than that at pH 6.7. ALA concentration, application time, cell density, temperature, pH, intracellular iron content, intracellular amount and localization of PpIX are factors controlling PpIX clearance.

  18. A LC–MS/MS method for the specific, sensitive, and simultaneous quantification of 5-aminolevulinic acid and porphobilinogen

    PubMed Central

    Zhang, Jinglan; Yasuda, Makiko; Desnick, Robert J.; Balwani, Manisha; Bishop, David; Yu, Chunli

    2012-01-01

    Accurate determinations of 5-aminolevulinic acid (ALA) and porphobilinogen (PBG) in physiologic fluids are required for the diagnosis and therapeutic monitoring of acute porphyrias. Current colorimetric methods are insensitive and over-estimate ALA and PBG due to poor specificity, while LC–MS/MS methods increase sensitivity, but have limited matrices. An LC–MS/MS method was developed to simultaneously determine ALA and PBG concentrations in fluids or tissues which were solid phase extracted, butanol derivatized, and quantitated by selective reaction monitoring using 13C5, 15N-ALA and 2,4-13C2-PBG internal standards. ALA was separated from interfering compounds on a reverse phase C8-column. For ALA and PBG, the matrix effects (87.3–105%) and process efficiencies (77.6–97.8% and 37.2–41.6%, respectively) were acceptable in plasma and urine matrices. The assay was highly sensitive for ALA and PBG (LLOQ = 0.05 µM with 25 µL urine or 100 µL plasma), and required ~4 h from extraction to results. ALA and PBG accuracy ranged from 88.2 to 110% (n = 10); intra- and inter-assay coefficients of variations were <10% for urine and plasma. In clinical applications, patients with mutation-confirmed acute porphyrias had normal to slightly increased urinary ALA and PBG levels when asymptomatic, and high levels during acute attacks, which decreased with hemin therapy. In AIP mice, baseline ALA and PBG levels in urine, plasma, and liver were increased after phenobarbital induction 28-/63-, 42-/266-, and 13-/316-fold, respectively. This LC–MS/MS method is rapid, specific, highly sensitive, accurate, and simultaneously measures ALA and PBG in urine, plasma, and tissues permitting porphyria clinical diagnoses, therapeutic monitoring, and research. PMID:21783436

  19. Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes

    NASA Astrophysics Data System (ADS)

    Millon, Stacy R.; Ostrander, Julie H.; Yazdanfar, Siavash; Brown, J. Quincy; Bender, Janelle E.; Rajeha, Anita; Ramanujam, Nirmala

    2010-01-01

    We describe the potential of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence as a source of contrast for margin detection in commonly diagnosed breast cancer subtypes. Fluorescence intensity of PpIX in untreated and ALA-treated normal mammary epithelial and breast cancer cell lines of varying estrogen receptor expression were quantitatively imaged with confocal microscopy. Percentage change in fluorescence intensity integrated over 610-700 nm (attributed to PpIX) of posttreated compared to pretreated cells showed statistically significant differences between four breast cancer and two normal mammary epithelial cell lines. However, a direct comparison of post-treatment PpIX fluorescence intensities showed no differences between breast cancer and normal mammary epithelial cell lines due to confounding effects by endogenous fluorescence from flavin adenine dinucleotide (FAD). Clinically, it is impractical to obtain pre- and post-treatment images. Thus, spectral imaging was demonstrated as a means to remove the effects of endogenous FAD fluorescence allowing for discrimination between post-treatment PpIX fluorescence of four breast cancer and two normal mammary epithelial cell lines. Fluorescence spectral imaging of ALA-treated breast cancer cells showed preferential PpIX accumulation regardless of malignant phenotype and suggests a useful contrast mechanism for discrimination of residual cancer at the surface of breast tumor margins.

  20. Synergism of herbicide toxicity by 5-aminolevulinic acid is related to physiological and ultra-structural disorders in crickweed (Malachium aquaticum L.).

    PubMed

    Xu, Ling; Zhang, Wenfang; Ali, Basharat; Islam, Faisal; Zhu, Jinwen; Zhou, Weijun

    2015-11-01

    Selection of effective herbicides to control weeds has been one of the major objectives of scientists. This study determines the differential tolerance or susceptibility of crickweed (Malachium aquaticum L.) to various concentration combinations of 5-aminolevulinic acid (ALA) (1, 10 and 100mg/L) and propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoate (ZJ0273) (100, 200, and 500mg/L). ALA was applied as pre- and post-treatment alone or in combination with ZJ0273. Results showed that ZJ0273 stress alone imposed negative effects on M. aquaticum seedling's growth, net photosynthetic rates and SPAD values, and the rate of decline was consistently increased with the increase in ZJ0273 concentration. The ZJ0273 treatment showed a gradual decrease in the activities of antioxidant enzymes peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX), and increase in the accumulation of malondialdehyde (MDA). Changes in chloroplast swelling, increased number of plastoglobuli, disruption of thylakoid, disintegrated mitochondria and turbid nucleoplasm were noticed. Moreover, SDS-PAGE analysis of total proteins revealed that herbicide stress in the leaves was associated with the decrease or disappearance of some protein bands. Further, two-dimensional gel electrophoresis (2-DE) results showed that proteins in different spots were classified into three types for M. aquaticum. These results indicate that the combined treatment of ALA and ZJ0273 synergizes the herbicide toxicity which is different from its independent effects on M. aquaticum and thus, could improve weed control efficacy. PMID:26615151

  1. Topical glycerol monooleate/propylene glycol formulations enhance 5-aminolevulinic acid in vitro skin delivery and in vivo protophorphyrin IX accumulation in hairless mouse skin.

    PubMed

    Steluti, Regilene; De Rosa, Fernanda Scarmato; Collett, John; Tedesco, Antônio Cláudio; Bentley, Maria Vitória Lopes Badra

    2005-08-01

    Photodynamic therapy (PDT), a potential therapy for cancer treatment, utilizes exogenously applied or endogenously formed photosensitizers, further activated by light in an appropriate wavelength and dose to induce cell death through free radical formation. 5-Aminolevulinic acid (5-ALA) is a pro-drug which can be converted to the effective photosensitizer, protoporphyrin IX (PpIX). However, the use of 5-ALA in PDT is limited by the low penetration capacity of this highly hydrophilic molecule into appropriate skin layers. In the present study, we propose to increase 5-ALA penetration by using formulations containing glycerol monooleate (GMO), an interesting and useful component of pharmaceutical formulations. Propylene glycol solutions containing different concentrations of GMO significantly increased the in vitro skin permeation/retention of 5-ALA in comparison to control solutions. In vivo studies also showed increased PpIX accumulation in mouse hairless skin, after the use of topical 5-ALA formulations containing GMO in a concentration-dependent manner. The results show that skin 5-ALA penetration and PpIX accumulation, important factors for the success of topical 5-ALA-PDT in skin cancer, are optimized by GMO/propylene glycol formulations. PMID:15996585

  2. eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy

    PubMed Central

    Fan, Zhichao; Cui, Xiaojun; Wei, Dan; Liu, Wei; Li, Buhong; He, Hao; Ye, Huamao; Zhu, Naishuo; Wei, Xunbin

    2016-01-01

    Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 106 M−1). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy. PMID:27150264

  3. eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Fan, Zhichao; Cui, Xiaojun; Wei, Dan; Liu, Wei; Li, Buhong; He, Hao; Ye, Huamao; Zhu, Naishuo; Wei, Xunbin

    2016-05-01

    Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 106 M‑1). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy.

  4. eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy.

    PubMed

    Fan, Zhichao; Cui, Xiaojun; Wei, Dan; Liu, Wei; Li, Buhong; He, Hao; Ye, Huamao; Zhu, Naishuo; Wei, Xunbin

    2016-01-01

    Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 10(6) M(-1)). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy. PMID:27150264

  5. Mitochondrial and endoplasmic reticulum stress-induced apoptotic pathways are activated by 5-aminolevulinic acid-based photodynamic therapy in HL60 leukemia cells.

    PubMed

    Grebenová, Dana; Kuzelová, Katerina; Smetana, Karel; Pluskalová, Michaela; Cajthamlová, Hana; Marinov, Iuri; Fuchs, Ota; Soucek, Josef; Jarolím, Petr; Hrkal, Zbynek

    2003-02-01

    We studied the mechanism of the cytotoxic effects of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT; induction with 1 mM ALA for 4 h followed by a blue light dose of 18 J/cm(2)) on the human promyelocytic leukemia cell line HL60 using biochemical and electron microscopy methods. The disruption of mitochondrial membrane potential, deltapsi(m), was paralleled by a decrease in ATP level, unmasking of the mitochondrial antigen 7A6, release of cytochrome c into the cytoplasm, activation of caspases 9 and 3 and cleavage of poly(ADP-ribose) polymerase (PARP). This was followed by DNA fragmentation. These data suggest that ALA-PDT activates the mitochondrial apoptotic pathway. The level of endoplasmic reticulum Ca(2+)-binding chaperones ERp57 and ERp72 and of anti-apoptotic proteins Bcl-2 and Bcl-x(L) was decreased whereas that of Ca(2+)-binding protein calmodulin and the stress protein HSP60 was elevated following ALA-PDT. Inhibition of the initiator caspase 9, execution caspase 3 and Ca(2+)-dependent protease m-calpain, did not prevent DNA fragmentation. We conclude that, in our in vitro model, ALA-based photodynamic treatment initiates several signaling processes in HL60 cells that lead to rapidly progressing apoptosis, which is followed by slow necrosis. Two apoptotic processes proceed in parallel, one representing the mitochondrial pathway, the other involving disruption of calcium homeostasis and activation of the endoplasmic reticulum stress-mediated pathway. PMID:12633980

  6. Safety and Efficacy of 5-Aminolevulinic Acid for High Grade Glioma in Usual Clinical Practice: A Prospective Cohort Study

    PubMed Central

    Teixidor, Pilar; Vidal, Xavier; Montané, Eva

    2016-01-01

    Background During the last decade, the use of 5-aminolevulinic acid (5-ALA) has been steadily increasing in neurosurgery. The study's main objectives were to prospectively evaluate the effectiveness and safety of 5-ALA when used in clinical practice setting on high-grade gliomas’ patients. Methods National, multicenter and prospective observational study. Inclusion criteria: authorized conditions of use of 5-ALA. Exclusion criteria: contraindication to 5-ALA, inoperable or partial resected tumors, pregnancy and children. Epidemiological, clinical, laboratory, radiological, and safety data were collected. Effectiveness was assessed using complete resection of the tumor, and progression-free and overall survival probabilities. Results Between May 2010 and September 2014, 85 patients treated with 5-ALA were included, and 77 were suitable for the effectiveness analysis. Complete resection was achieved in 41 patients (54%). Surgeons considered suboptimal the fluorescence of 5-ALA in 40% of the patients assessed. The median duration of follow-up was 12.3 months. The progression-free survival probability at 6 months was 58%. The median duration overall survival was 14.2 months. Progression tumor risk factors were grade of glioma, age and resection degree; and death risk factors were grade of glioma and gender. No severe adverse effects were reported. At one month after surgery, new or increased neurological morbidity was 6.5%. Hepatic enzymes were frequently increased within the first month after surgery; however, they subsequently normalized, and this was found to have no clinical significance. Conclusion In clinical practice, the 5-ALA showed a good safety profile, but the benefits related to 5-ALA have not been yet clearly shown. The improved differentiation expected by fluorescence between normal and tumor cerebral tissue was suboptimal in a relevant number of patients; in addition, the expected higher degree of resection was lower than in clinical trials as well as

  7. Perturbed porphyrin biosynthesis contributes to differential herbicidal symptoms in photodynamically stressed rice (Oryza sativa) treated with 5-aminolevulinic acid and oxyfluorfen.

    PubMed

    Phung, Thu-Ha; Jung, Sunyo

    2014-11-01

    This paper focuses on the molecular mechanism of deregulated porphyrin biosynthesis in rice plants under photodynamic stress imposed by an exogenous supply of 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). Plants treated with 5 mM ALA or 50 µM OF exhibited differential herbicidal symptoms as characterized by white and brown necrosis, respectively, with substantial increases in cellular leakage and malondialdehyde production. Protoporphyrin IX accumulated to higher levels after 1 day of ALA and OF treatment, whereas it decreased to the control level after 2 days of ALA treatment. Plants responded to OF by greatly decreasing the levels of Mg-protoporphyrin IX (MgProto IX), MgProto IX methyl ester, and protochlorophyllide to levels lower than control, whereas their levels drastically increased 1 day after ALA treatment and then disappeared 2 days after the treatment. Enzyme activity and transcript levels of HEMA1, GSA and ALAD for ALA synthesis greatly decreased in ALA- and OF-treated plants. Transcript levels of PPO1, CHLH, CHLI, and PORB genes involving Mg-porphyrin synthesis continuously decreased in ALA- and OF-treated plants, with greater decreases in ALA-treated plants. By contrast, up-regulation of FC2 and HO2 genes in Fe-porphyrin branch was noticeable in ALA and OF-treated plants 1 day and 2 days after the treatments, respectively. Decreased transcript levels of nuclear-encoded genes Lhcb1, Lhcb6, and RbcS were accompanied by disappearance of MgProto IX in ALA- and OF-treated plants after 2 days of the treatments. Under photodynamic stress imposed by ALA and OF, tight control of porphyrin biosynthesis prevents accumulation of toxic metabolic intermediates not only by down-regulation of their biosynthesis but also by photodynamic degradation. The up-regulation of FC2 and HO2 also appears to compensate for the photodynamic stress-induced damage. PMID:25454526

  8. Topical delivery of 5-aminolevulinic acid-encapsulated ethosomes in a hyperproliferative skin animal model using the CLSM technique to evaluate the penetration behavior.

    PubMed

    Fang, Yi-Ping; Huang, Yaw-Bin; Wu, Pao-Chu; Tsai, Yi-Hung

    2009-11-01

    Psoriasis, an inflammatory skin disease, exhibits recurring itching, soreness, and cracked and bleeding skin. Currently, the topical delivery of 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is an optional treatment for psoriasis which provides long-term therapeutic effects, is non-toxic and enjoys better compliance with patients. However, the precursor of ALA is hydrophilic, and thus its ability to penetrate the skin is limited. Also, little research has provided a platform to investigate the penetration behavior in disordered skin. We employed a highly potent ethosomal carrier (phosphatidylethanolamine; PE) to investigate the penetration behavior of ALA and the recovery of skin in a hyperproliferative murine model. We found that the application of ethosomes produced a significant increase in cumulative amounts of 5-26-fold in normal and hyperproliferative murine skin samples when compared to an ALA aqueous solution; and the ALA aqueous solution appeared less precise in terms of the penetration mode in hyperproliferative murine skin. After the ethosomes had been applied, the protoporphyrin IX (PpIX) intensity increased about 3.64-fold compared with that of the ALA aqueous solution, and the penetration depth reached 30-80 microm. The results demonstrated that the ethosomal carrier significantly improved the delivery of ALA and the formation of PpIX in both normal and hyperproliferative murine skin samples, and the expression level of tumor necrosis factor (TNF)-alpha was reduced after the ALA-ethosomes were applied to treat hyperproliferative murine skin. Furthermore, the results of present study encourage more investigations on the mechanism of the interaction with ethosomes and hyperproliferative murine skin. PMID:19660544

  9. Generation of reactive oxygen species from 5-aminolevulinic acid and Glutamate in cooperation with excited CdSe/ZnS QDs

    NASA Astrophysics Data System (ADS)

    Duong, Hong Dinh; Lee, Jee Won; Rhee, Jong Il

    2014-08-01

    CdSe/ZnS quantum dots (QDs) can be joined in the reductive pathway involving the electron transfer to an acceptor or in the oxidative pathway involving the hole transfer to a donor. They were exploited in the oxidation reactions of 5-aminolevulinic acid (ALA) and glutamate (GLU) for the generation of reactive oxygen species (ROS) such as hydroxyl radical (HO●) and superoxide anion (O2 ● -). Fast and highly efficient oxidation reactions of ALA to produce HO● and of GLU to produce O2 ●- were observed in the cooperation of mercaptopropionic acid (MPA)-capped CdSe/ZnS QDs under LED irradiation. Fluorescence spectroscopy and electron spin resonance (ESR) spectroscopy were used to evaluate the generation of different forms of ROS. Confocal fluorescent microscopic images of the size and morphology of HeLa cells confirmed the ROS generation from ALA or GLU in cooperation with CdSe/ZnS QDs under LED irradiation.

  10. Comparative study of two routes of administration of 5-aminolevulinic acid (oral and intratumoral via) and their effect on the accumulation of PpIX in tissues in murine model of breast cancer

    NASA Astrophysics Data System (ADS)

    González-Agüero, G.; Ramón-Gallegos, E.

    2012-10-01

    Protoporphyrin IX (PpIX) is a photosensitizer synthesized from 5-aminolevulinic acid (ALA) that has been used in photodynamic therapy (PDT) as a promising treatment for many types of cancer. In this work it was quantified the accumulation of PpIX in tumors and in different tissues of female mice (nu/nu) inoculated with breast cancer cells. Two routes of administration of ALA: gastric probe and intratumoral injection were used to find optimum time of accumulation and the via that induce the higher quantity of PpIX to improve the efficiency of PDT. The results show that the accumulation of PpIX using the intratumoral via is two times bigger than the oral via in tumors at 8 h of treatment. The concentrations obtained in the different tissues are not physiologically significant.

  11. Combination of 5-aminolevulinic acid and ferrous ion reduces plasma glucose and hemoglobin A1c levels in Zucker diabetic fatty rats.

    PubMed

    Hara, Takeshi; Koda, Aya; Nozawa, Naoko; Ota, Urara; Kondo, Hikaru; Nakagawa, Hitoshi; Kamiya, Atsuko; Miyashita, Kazutoshi; Itoh, Hiroshi; Nakajima, Motowo; Tanaka, Tohru

    2016-06-01

    Mitochondrial dysfunction is associated with type 2 diabetes mellitus (T2DM). 5-Aminolevulinic acid (ALA), a natural amino acid produced only in the mitochondria, is a precursor of heme. Cytochromes that contain heme play an important role in aerobic energy metabolism. Thus, ALA may help reduce T2DM-associated hyperglycemia. In this study, we investigated the effect of ALA combined with sodium ferrous citrate (SFC) on hyperglycemia in Zucker diabetic fatty (ZDF) rats. We found that the gavage administration of ALA combined with SFC (ALA/SFC) for 6 weeks reduced plasma glucose and hemoglobin A1c (HbA1c) levels in rats without affecting plasma insulin levels. The glucose-lowering effect depended on the amount of ALA/SFC administered per day. Furthermore, the glucose tolerance was also significantly improved by ALA/SFC administration. Although food intake was slightly reduced in the rats administered ALA/SFC, there was no effect on their body weight. Importantly, ALA/SFC administration induced heme oxygenase-1 (HO-1) expression in white adipose tissue and liver, and the induced expression levels of HO-1 correlated with the glucose-lowering effects of ALA/SFC. Taken together, these results suggest that ALA combined with ferrous ion is effective in reducing hyperglycemia of T2DM without affecting plasma insulin levels. HO-1 induction may be involved in the mechanisms underlying the glucose-lowering effect of ALA/SFC. PMID:27239432

  12. Interstitial photodynamic therapy of canine prostate with meso-tetra-(m-hydroxyphenyl) chlorin and 5-aminolevulinic acid: a preliminary study

    NASA Astrophysics Data System (ADS)

    Chang, Shi-Chung; Buonaccorsi, Giovanni A.; MacRobert, Alexander J.; Bown, Stephen G.

    1996-01-01

    Photodynamic therapy (PDT) is proved to have potential for managing various malignancies. We investigated tissue biodistribution and photodynamic effects on a canine model in vivo using second generation photosensitizers, meso-tetra(m-hydroxyphenyl)chlorin (mTHPC) and 5-aminolaevulinic acid (ALA) to evaluate the feasibility and possible future application of PDT on the prostate. Using fluorescence microscopy, the optimal sensitization time of the prostate was between 24 - 72 hours with mTHPC and, 3 hours with ALA. After optimum time of sensitization, prostates of mature beagle were treated with laser at various sites by placing fiber interstitially under the guidance of transrectal ultrasound. The light dose for each treatment site was 100 J (100 mW for 1,000 seconds at the wavelength of 650 and 630 nm, respectively). With mTHPC, single laser fiber was able to induce organ confined PDT lesion as large as 20 by 18 by 18 mm in size. However, the PDT lesion with ALA was negligible 3 days after treatment. Physical distress manifested as urinary retention, poor appetite and body weigh loss, was more prominent with increasing number of treatment sites as a result of extensive prostatic swelling and urethral damages. However, these problems usually alleviated spontaneously 7 to 10 days after PDT. The characteristic histological changes were hemorrhagic necrosis and glandular destruction with preservation of interlobular collagen fibers. Urethral damage seen at the early stage healed by regeneration of urothelium in 4 weeks. We conclude that interstitial PDT with mTHPC is technically possible to produce extensive glandular necrosis in the normal prostate which heals safely and does not change the prostatic architecture. ALA, although it seems promising for bladder tumors, is much less effective than mTHPC on the prostate. With mTHPC, it might have the potential for treating prostate cancers localized in the periphery of the gland.

  13. Wavelength-dependent in-vitro and in-vivo photodynamic effects after sensitization with 5-aminolevulinic acid induced protoporphyrin IX

    NASA Astrophysics Data System (ADS)

    Szeimies, Rolf-Markus; Abels, Christoph; Fritsch, Clemens; Steinbach, Pia; Baeumler, Wolfgang; Messmann, Helmut; Goetz, Alwin E.; Goerz, Guenter; Landthaler, Michael

    1996-01-01

    Photodynamic therapy (PDT) with topically applied 5-aminolevulinic acid (ALA) is of growing interest, in particular in dermatology. Due to the fact that PDT with intravenously administered Photofrin is the only clinically approved sensitizer so far and is performed at a wavelength of 630 nm, this wavelength is also used in most experimental and clinical trials with ALA. In this study influence of irradiation with coherent light from a tunable dye laser at different wavelengths ranging from 625 to 649 nm was investigated. In in vitro experiments HaCaT immortalized human keratinocytes were sensitized with 30 (mu) g/ml ALA for 24 hrs. By determination of cell viability with the MTT test, best cell-killing effects were observed following irradiation at 635 nm. In an in vivo setting using an amelanotic melanoma (A-Mel-3) grown subcutaneously in Syrian Golden hamsters, these results were confirmed: tumor growth determined by measuring tumor volume increase after 28 days was less pronounced in animals treated with 100 mg/kg ALA i.v. and irradiated 2.5 hrs. later at 635 nm, as compared to animals receiving an equal dose and irradiated at 630 nm. This observation in vitro is probably due to large amounts of photosensitizing protoporphyrin IX (PP) localized in cell membranes which is visualized by confocal laser scanning microscopy (CLSM) and determined by HPLC analysis. These results suggest that in ALA-PDT when a coherent light source is used probably better results are achieved irradiating at 635 nm.

  14. Characterization of a pseudo ternary phase diagram of poloxamer 407 systems for potential application of 5-aminolevulinic acid in photodynamic therapy.

    PubMed

    van Hemelrijck, Carlos; Müller-Goymann, Christel C

    2011-11-28

    A poloxamer 407 (POX) gel containing dimethyl isosorbide (DMIS), isopropyl alcohol (IPA), propylene glycol dicaprylocaprate (MIG) and water has been suggested in a previous study for permeation enhancement of 5-aminolevulinic acid (ALA) across isolated human stratum corneum. The purpose of this study was to characterize other formulations coming from the same pseudo ternary phase diagram as the "Thermogel" in order to find out which of them show appropriate characteristics to be used as a vehicle for ALA since it could be shown that variation of the ingredients' content had an influence on the permeation rate. A pseudo ternary phase diagram was developed with water, a fixed combination of 1:1 of IPA and DMIS and a fixed ratio of 4:1 POX to MIG. The systems were categorized according to their consistencies and ringing gel characteristics with special emphasis on appropriate formulations for dermal application. Polarizing microscopy enabled a clear differentiation between isotropic and anisotropic systems. Wide angle X-ray diffraction analyzes confirmed that anisotropy was due to crystalline POX. Furthermore both methods showed that IPA/DMIS was an inferior solvent mixture for POX related to water. PMID:21925581

  15. Differential antioxidant defense and detoxification mechanisms in photodynamically stressed rice plants treated with the deregulators of porphyrin biosynthesis, 5-aminolevulinic acid and oxyfluorfen.

    PubMed

    Phung, Thu-Ha; Jung, Sunyo

    2015-04-01

    This study focuses on differential molecular mechanisms of antioxidant and detoxification systems in rice plants under two different types of photodynamic stress imposed by porphyrin deregulators, 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). The ALA-treated plants with white necrosis exhibited a greater decrease in photochemical quantum efficiency, Fv/Fm, as well as a greater increase in activity of superoxide dismutase, compared to the OF-treated plants. By contrast, the brown necrosis in OF-treated plants resulted in not only more widely dispersed H2O2 production and greater increases in H2O2-decomposing enzymes, catalase and peroxidase, but also lower ascorbate redox state. In addition, ALA- and OF-treated plants markedly up-regulated transcript levels of genes involved in detoxification processes including transport and movement, cellular homeostasis, and xenobiotic conjugation, with prominent up-regulation of serine/threonine kinase and chaperone only in ALA-treated plants. Our results demonstrate that different photodynamic stress imposed by ALA and OF developed differential actions of antioxidant enzymes and detoxification. Particularly, detoxification system may play potential roles in plant protection against photodynamic stress imposed by porphyrin deregulators, thereby contributing to alleviation of photodynamic damage. PMID:25735982

  16. Heterologous expression of glutamyl-tRNA reductase gene in Rhodobacter sphaeroides O.U.001 to enhance 5-aminolevulinic acid production

    PubMed Central

    Kars, Gökhan; Alparslan, Ümmühan

    2014-01-01

    The pathways for synthesis of 5-aminolevulinic acid (5-ALA) use either succinyl-CoA and glycine (C-4 pathway), or glutamate (C-5 pathway). Although Rhodobacter sphaeroides synthesizes 5-ALA through the C-4 pathway, it also has the genes coding for the enzymes of the C-5 pathway, except for glutamyl-tRNA reductase. The glutamyl-tRNA reductase gene was cloned from Rhodospirillum rubrum and expressed in R. sphaeroides; thus, the C-5 pathway was enabled to function upon assembling all the required genes. Consequently, a new and unique bacterial strain producing more 5-ALA was developed. Biohydrogen was also produced in the same bioprocess within a biorefinery approach using sugar beet molasses as substrate. The amount of 5-ALA produced by the modified strain was 25.9 mg/g dry cell weight (DCW), whereas the wild-type strain produced 12.4 mg/g DCW. In addition, the amount of H2 generated by the modified and wild-type cells, respectively, was 0.92 L/L culture and 1.05 L/L culture. PMID:26740781

  17. Alleviation of Lead Toxicity by 5-Aminolevulinic Acid Is Related to Elevated Growth, Photosynthesis, and Suppressed Ultrastructural Damages in Oilseed Rape

    PubMed Central

    Tian, Tian; Qin, Yebo; Gill, Rafaqat A.; Ali, Shafaqat

    2014-01-01

    Lead (Pb) is a widely spread pollutant and leads to diverse morphological and structural changes in the plants. In this study, alleviating role of 5-aminolevulinic acid (ALA) in oilseed rape (Brassica napus L.) was investigated with or without foliar application of ALA (25 mg L−1) in hydroponic environment under different Pb levels (0, 100, and 400 µM). Outcomes stated that plant morphology and photosynthetic attributes were reduced under the application of Pb alone. However, ALA application significantly increased the plant growth and photosynthetic parameters under Pb toxicity. Moreover, ALA also lowered the Pb concentration in shoots and roots under Pb toxicity. The microscopic studies depicted that exogenously applied ALA ameliorated the Pb stress and significantly improved the cell ultrastructures. After application of ALA under Pb stress, mesophyll cell had well-developed nucleus and chloroplast having a number of starch granules. Moreover, micrographs illustrated that root tip cell contained well-developed nucleus, a number of mitochondria, and golgi bodies. These results proposed that under 15-day Pb-induced stress, ALA improved the plant growth, chlorophyll content, photosynthetic parameters, and ultrastructural modifications in leaf mesophyll and root tip cells of the B. napus plants. PMID:24683549

  18. 5-aminolevulinic acid-mediated photodynamic therapy of intraepithelial neoplasia and human papillomavirus of the uterine cervix--a new experimental approach.

    PubMed

    Wierrani, F; Kubin, A; Jindra, R; Henry, M; Gharehbaghi, K; Grin, W; Söltz-Szötz, J; Alth, G; Grünberger, W

    1999-01-01

    The aim of this study was to treat patients for ectocervical dysplasia [cervical intraepithelial neoplasia (CIN) grades 1 and 2] and associated human papilloma virus (HPV) infections with photodynamic therapy (PDT). In 20 patients, 5-aminolevulinic acid (5-ALA, 12% w/v) was applied topically with a cervical cap 8 h prior to illumination. A thermal light source (150 W halogen lamp) emitting a broadband red light (total energy: 100 J/cm2, fluence rate: 90 mW/cm2) was used for superficial illumination of the portio. In addition, an Nd:YAG pumped dye laser (652 nm) was used to illuminate the cervical canal (total energy: 50 J/cm2, fluence rate: 300 mW/cm2). Preliminary results of follow-ups at 1, 3, 6, and 9 months posttherapy showed a cytological improvement in the grading of the PAP smears in 19 patients and the eradication of cervical HPV in 80%. These results demonstrate that ectocervical dysplasia and associated HPV infections can be treated by PDT. PMID:10403907

  19. The role of 5-aminolevulinic acid in enhancing surgery for high-grade glioma, its current boundaries, and future perspectives: A systematic review.

    PubMed

    Mansouri, Alireza; Mansouri, Sheila; Hachem, Laureen D; Klironomos, George; Vogelbaum, Michael A; Bernstein, Mark; Zadeh, Gelareh

    2016-08-15

    5-Aminolevulinic acid (5-ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to assess the evidence regarding 5-ALA as a surgical adjunct. The MEDLINE, EMBASE, and CENTRAL databases were searched, using terms relevant to "5-ALA" and "high-grade gliomas." Included studies were based on adults aged ≥18 years who underwent surgical resection/biopsy. No language or date limitations were used. Forty-three studies (1830 patients) were identified. Thirty-six were coordinated by European countries, 2 were in the United States, and none were in Canada. One was randomized, 28 were prospective, and 14 were retrospective. Twenty-six studies assessed the utility of 5-ALA as a diagnostic tool, 24 assessed its influence on the extent of resection (EOR), 9 assessed survival, and 22 reported adverse events. 5-ALA had high sensitivity and positive predictive value, whereas its specificity increased with additional adjuncts. The EOR increased with 5-ALA, but only progression-free survival was significantly influenced. Reporting of adverse events was not systematic. The use of 5-ALA improved tumor visualization and thus enabled a greater EOR and perhaps increased survival. However, additional adjuncts may be necessary for maximizing the specificity of resection and patient safety. Additional parameters, such as patient quality of life and health economic analyses, would be informative. Thus, additional systematic collection of prospective evidence may be necessary for the global incorporation of this potentially valuable surgical adjunct into routine practice. Cancer 2016;122:2469-78. © 2016 American Cancer Society. PMID:27183272

  20. Histopathological implications of ventricle wall 5-aminolevulinic acid-induced fluorescence in the absence of tumor involvement on magnetic resonance images.

    PubMed

    Moon, Ju Hyung; Kim, Se Hoon; Shim, Jin-Kyoung; Roh, Tae-Hoon; Sung, Kyoung Su; Lee, Ji-Hyun; Park, Junseong; Choi, Junjeong; Kim, Eui-Hyun; Kim, Sun Ho; Kang, Seok-Gu; Chang, Jong Hee

    2016-08-01

    During 5-aminolevulinic acid (ALA)-guided glioblastoma multiforme (GBM) surgery, we encountered fluorescence in ventricular walls that lacked enhancement on magnetic resonance (MR) images and were free of macroscopic invasion of tumor cells. However, the meaning of ventricular wall fluorescence during 5-ALA-guided surgery is still unknown. The aim of this study was to investigate the relationship between intraoperative 5-ALA fluorescence and histopathological findings of ventricular walls free of enhancement on MR images. Nineteen patients with newly diagnosed GBM located near the lateral ventricle underwent 5‑ALA fluorescence‑guided surgery. During the surgery, the ventricle wall was opened and investigated with the aid of a surgical microscope equipped with optical filters to examine 5‑ALA fluorescence of the ventricular wall. Twenty‑five ventricular wall tissues that were apparently free of tumor involvement by MR imaging and macroscopic observation were obtained during surgery. Among the 19 cases with brightly fluorescing tumor masses, 11 patients (57.9%) exhibited 5‑ALA‑induced fluorescence in the ventricular wall. Of the 25 ventricular wall samples, 11 exhibited 5‑ALA‑induced fluorescence; upon pathologic examination, tumors were present in 5 samples (45.5%), but the remaining 6 (54.5%) were free of tumor cells. A pathologic examination revealed no tumor cells in the 14 samples that lacked 5‑ALA‑induced fluorescence. Our data suggest the possibility that glioma cells exhibiting 5‑ALA fluorescence are present in the ventricle wall, despite no signs of tumor involvement in MR images. Further investigation of non‑tumor cells from tissues with 5‑ALA fluorescence is needed to understand the nature of this unexpected ventricular wall fluorescence. PMID:27374931

  1. Impact of 5-aminolevulinic acid with iron supplementation on exercise efficiency and home-based walking training achievement in older women

    PubMed Central

    Masuki, Shizue; Morita, Atsumi; Kamijo, Yoshi-ichiro; Ikegawa, Shigeki; Kataoka, Yufuko; Ogawa, Yu; Sumiyoshi, Eri; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo

    2015-01-01

    A reduction in exercise efficiency with aging limits daily living activities. We examined whether 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) increased exercise efficiency and voluntary achievement of interval walking training (IWT) in older women. Ten women [65 ± 3(SD) yr] who had performed IWT for >12 mo and were currently performing IWT participated in this study. The study was conducted in a placebo-controlled, double-blind crossover design. All subjects underwent two trials for 7 days each in which they performed IWT with ALA+SFC (100 and 115 mg/day, respectively) or placebo supplement intake (CNT), intermittently with a 2-wk washout period. Before and after each trial, subjects underwent a graded cycling test at 27.0°C atmospheric temperature and 50% relative humidity, and oxygen consumption rate, carbon dioxide production rate, and lactate concentration in plasma were measured. Furthermore, for the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. We found that, in the ALA+SFC trial, oxygen consumption rate and carbon dioxide production rate during graded cycling decreased by 12% (P < 0.001) and 11% (P = 0.001) at every workload, respectively, accompanied by a 16% reduction in lactate concentration in plasma (P < 0.001), although all remained unchanged in the CNT trial (P > 0.2). All of the reductions were significantly greater in the ALA+SFC than the CNT trial (P < 0.05). Furthermore, the training days, impulse, and time at fast walking were 42% (P = 0.028), 102% (P = 0.027), and 69% (P = 0.039) higher during the ALA+SFC than the CNT intake period, respectively. Thus ALA+SFC supplementation augmented exercise efficiency and thereby improved IWT achievement in older women. PMID:26514619

  2. Impact of 5-aminolevulinic acid with iron supplementation on exercise efficiency and home-based walking training achievement in older women.

    PubMed

    Masuki, Shizue; Morita, Atsumi; Kamijo, Yoshi-ichiro; Ikegawa, Shigeki; Kataoka, Yufuko; Ogawa, Yu; Sumiyoshi, Eri; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo; Nose, Hiroshi

    2016-01-01

    A reduction in exercise efficiency with aging limits daily living activities. We examined whether 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) increased exercise efficiency and voluntary achievement of interval walking training (IWT) in older women. Ten women [65 ± 3(SD) yr] who had performed IWT for >12 mo and were currently performing IWT participated in this study. The study was conducted in a placebo-controlled, double-blind crossover design. All subjects underwent two trials for 7 days each in which they performed IWT with ALA+SFC (100 and 115 mg/day, respectively) or placebo supplement intake (CNT), intermittently with a 2-wk washout period. Before and after each trial, subjects underwent a graded cycling test at 27.0 °C atmospheric temperature and 50% relative humidity, and oxygen consumption rate, carbon dioxide production rate, and lactate concentration in plasma were measured. Furthermore, for the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. We found that, in the ALA+SFC trial, oxygen consumption rate and carbon dioxide production rate during graded cycling decreased by 12% (P < 0.001) and 11% (P = 0.001) at every workload, respectively, accompanied by a 16% reduction in lactate concentration in plasma (P < 0.001), although all remained unchanged in the CNT trial (P > 0.2). All of the reductions were significantly greater in the ALA+SFC than the CNT trial (P < 0.05). Furthermore, the training days, impulse, and time at fast walking were 42% (P = 0.028), 102% (P = 0.027), and 69% (P = 0.039) higher during the ALA+SFC than the CNT intake period, respectively. Thus ALA+SFC supplementation augmented exercise efficiency and thereby improved IWT achievement in older women. PMID:26514619

  3. Oil components modulate the skin delivery of 5-aminolevulinic acid and its ester prodrug from oil-in-water and water-in-oil nanoemulsions

    PubMed Central

    Zhang, Li-Wen; Al-Suwayeh, Saleh A; Hung, Chi-Feng; Chen, Chih-Chieh; Fang, Jia-You

    2011-01-01

    The study evaluated the potential of nanoemulsions for the topical delivery of 5-aminolevulinic acid (ALA) and methyl ALA (mALA). The drugs were incorporated in oil-in-water (O/W) and water-in-oil (W/O) formulations obtained by using soybean oil or squalene as the oil phase. The droplet size, zeta potential, and environmental polarity of the nanocarriers were assessed as physicochemical properties. The O/W and W/O emulsions showed diameters of 216–256 and 18–125 nm, which, respectively, were within the range of submicron- and nano-sized dispersions. In vitro diffusion experiments using Franz-type cells and porcine skin were performed. Nude mice were used, and skin fluorescence derived from protoporphyrin IX was documented by confocal laser scanning microscopy (CLSM). The loading of ALA or mALA into the emulsions resulted in slower release across cellulose membranes. The release rate and skin flux of topical drug application were adjusted by changing the type of nanocarrier, the soybean oil O/W systems showing the highest skin permeation. This formulation increased ALA flux via porcine skin to 180 nmol/cm2/h, which was 2.6-fold that of the aqueous control. The CLSM results showed that soybean oil systems promoted mALA permeation to deeper layers of the skin from ∼100 μm to ∼140 μm, which would be beneficial for treating subepidermal and subcutaneous lesions. Drug permeation from W/O systems did not surpass that from the aqueous solution. An in vivo dermal irritation test indicated that the emulsions were safe for topical administration of ALA and mALA. PMID:21556344

  4. Differential antioxidant defense and detoxification mechanisms in photodynamically stressed rice plants treated with the deregulators of porphyrin biosynthesis, 5-aminolevulinic acid and oxyfluorfen

    SciTech Connect

    Phung, Thu-Ha; Jung, Sunyo

    2015-04-03

    This study focuses on differential molecular mechanisms of antioxidant and detoxification systems in rice plants under two different types of photodynamic stress imposed by porphyrin deregulators, 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). The ALA-treated plants with white necrosis exhibited a greater decrease in photochemical quantum efficiency, F{sub v}/F{sub m}, as well as a greater increase in activity of superoxide dismutase, compared to the OF-treated plants. By contrast, the brown necrosis in OF-treated plants resulted in not only more widely dispersed H{sub 2}O{sub 2} production and greater increases in H{sub 2}O{sub 2}-decomposing enzymes, catalase and peroxidase, but also lower ascorbate redox state. In addition, ALA- and OF-treated plants markedly up-regulated transcript levels of genes involved in detoxification processes including transport and movement, cellular homeostasis, and xenobiotic conjugation, with prominent up-regulation of serine/threonine kinase and chaperone only in ALA-treated plants. Our results demonstrate that different photodynamic stress imposed by ALA and OF developed differential actions of antioxidant enzymes and detoxification. Particularly, detoxification system may play potential roles in plant protection against photodynamic stress imposed by porphyrin deregulators, thereby contributing to alleviation of photodynamic damage. - Highlights: • We employ two different types of photodynamic stress, white and brown necrosis. • We examine molecular mechanisms of antioxidative and detoxification systems. • ALA and OF develop differential actions of antioxidant and detoxification systems. • Coordinated mechanism of antioxidants and detoxification works against toxic ROS. • Detoxification system plays critical roles in protection against photodynamic stress.

  5. Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status

    NASA Astrophysics Data System (ADS)

    Marcus, Stuart L.; Sobel, Russel S.; Golub, Allyn L.; Carroll, Ronald L.; Lundahl, Scott L.; Shulman, D. Geoffrey

    1996-04-01

    Exogenous provision of ALA to many tissues results in the accumulation of sufficient quantities of the endogenous photosensitizer protoporphyrin IX, (PpIX), to produce a photodynamic effect. Therefore, ALA may be considered the only current PDT agent in clinical development which is a biochemical precursor of a photosensitizer. Topical ALA application, followed by exposure to activating light (ALA PDT), has been reported effective for the treatment of a variety of dermatologic diseases including cutaneous T-cell lymphoma, superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses, and is also being examined for treatment of acne and hirsutism. PpIX induced by ALA application also may serve as a fluorescence detection marker for photodiagnosis (PD) of malignant and pre- malignant conditions of the urinary bladder and other organs. Local internal application of ALA has also been used for selective endometrial ablation in animal model systems and is beginning to be examined in human clinical studies. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer, various gastrointestinal cancers, and the condition known as Barrett's esophagus. This brief paper reviews the current clinical and development status of ALA PDT.

  6. Enhancement of 5-aminolevulinic-acid-induced photodynamic therapy using light-dose fractionation and iron-chelating agents

    NASA Astrophysics Data System (ADS)

    Curnow, Alison; Postle-Hacon, Matthew J.; MacRobert, Alexander J.; Bown, Stephen G.

    1998-05-01

    Preliminary clinical studies of 5-aminolaevulinic acid (ALA) induced photodynamic therapy (PDT) with the maximum tolerated oral dose (60 mg/kg), currently appear to only produce limited amounts of necrosis. We have studied ways of increasing this effect without increasing the drug dose. In normal, female, Wistar rats we have found it possible to increase the area of necrosis produced in the colon substantially by simply interrupting the light dose (25 J, 635 nm, 100 mW) for a short period of time, while all other variables are kept constant. It is possible to cause up to four times more necrosis with a dose of 200 mg/kg ALA i.v. by introducing a single 150 second interval which splits the light dose into two fractions after 5 J has been delivered. We have found these parameters to be optimal for this dose. Likewise, in the same model, the effect of the iron chelating agent, CP94, was also investigated and we have found it possible to produce three times the area of necrosis with the simultaneous administration of 100 mg/kg CP94 i.v. and 50 mg/kg ALA i.v. We have therefore shown, that it is possible to significantly increase the effects of ALA induced PDT without increasing the administered dose of ALA by utilizing these techniques.

  7. 5-Aminolevulinic Acid Thins Pear Fruits by Inhibiting Pollen Tube Growth via Ca2+-ATPase-Mediated Ca2+ Efflux

    PubMed Central

    An, Yuyan; Li, Jie; Duan, Chunhui; Liu, Longbo; Sun, Yongping; Cao, Rongxiang; Wang, Liangju

    2016-01-01

    Chemical fruit thinning has become a popular practice in modern fruit orchards for achieving high quality fruits, reducing costs of hand thinning and promoting return bloom. However, most of the suggested chemical thinners are often concerned for their detrimental effects and environmental problems. 5-Aminolevulic acid (ALA) is a natural, nontoxic, biodegradable, and environment-friendly plant growth regulator. One of its outstanding roles is improving plant photosynthesis and fruit quality. Here, results showed that applying 100–200 mg/L ALA at full bloom stage significantly reduced pear fruit set. Both in vivo and in vitro studies showed that ALA significantly inhibited pollen germination and tube growth. ALA decreased not only cytosolic Ca2+ concentration ([Ca2+]cyt) but also “tip-focused” [Ca2+]cyt gradient, indicating that ALA inhibited pollen tube growth by down-regulating calcium signaling. ALA drastically enhanced pollen Ca2+-ATPase activity, suggesting that ALA-induced decrease of calcium signaling probably resulted from activating calcium pump. The significant negative correlations between Ca2+-ATPase activity and pollen germination or pollen tube length further demonstrated the critical role of calcium pump in ALA's negative effect on pollen germination. Taken together, our results suggest that ALA at low concentrations is a potential biochemical thinner, and it inhibits pollen germination and tube growth via Ca2+ efflux by activating Ca2+-ATPase, thereby thinning fruits by preventing fertilization. PMID:26904082

  8. Evaluating the efficacy and safety of a novel endoscopic fluorescence imaging modality using oral 5-aminolevulinic acid for colorectal tumors

    PubMed Central

    Tsuruki, Eriko So; Saito, Yutaka; Abe, Seiichiro; Takamaru, Hiroyuki; Yamada, Masayoshi; Sakamoto, Taku; Nakajima, Takeshi; Matsuda, Takahisa; Sekine, Shigeki; Taniguchi, Hirokazu

    2016-01-01

    Background and study aims: Five-aminolevulinic acid (5-ALA) is being increasingly used for photodynamic diagnosis and therapy of various types of tumors including brain, urologic, and other neoplasias. The use of 5-ALA to treat Barrett’s carcinomas has been documented, but its clinical effectiveness for diagnosis of gastrointestinal tumors, particularly early cancers, remains unknown. Patients and methods: The aim of our feasibility study was to evaluate the visibility of colorectal tumors using endoscopic fluorescence imaging (EFI) after oral administration of 5-ALA. The lesions identified by direct visualization and by the spectrums produced using EFI modality with 5-ALA were compared to the clinicopathologic features of resected specimens. Results: Twenty-three patients with a total of 27 known colorectal lesions were enrolled in the study. The median tumor size was 30 mm (range 10 – 75). Eleven of the lesions were flat or depressed lesions and 16 were sessile. Red fluorescence was observed in 22 out of 27 lesions. Red fluorescence was negative in 4 out of 11 flat or depressed lesions. In comparison with histopathologic findings, the rates of red fluorescence visibility were 62.5 % in low-grade intraepithelial neoplasia, 77.8 % in high-grade neoplasia, and 100 % in submucosal carcinoma. Red fluorescence visibility increased with the degree of dysplasia. There were no significant adverse events identified in this study. Conclusions: This feasibility study using EFI with 5-ALA demonstrated high visibility of superficial colorectal neoplasia. EFI with 5-ALA appears to be a novel, safe technique for improving real-time colorectal tumor imaging. PMID:26793782

  9. Tissue responses to hexyl 5-aminolevulinate-induced photodynamic treatment in syngeneic orthotopic rat bladder cancer model: possible pathways of action

    NASA Astrophysics Data System (ADS)

    Arum, Carl-Jørgen; Gederaas, Odrun A.; Larsen, Eivind L. P.; Randeberg, Lise L.; Hjelde, Astrid; Krokan, Hans E.; Svaasand, Lars O.; Chen, Duan; Zhao, Chun-Mei

    2011-02-01

    Orthotopic bladder cancer model in rats mimics human bladder cancer with respect to urothelial tumorigenesis and progression. Utilizing this model at pT1 (superficial stage), we analyze the tissue responses to hexyl 5-aminolevulinate-induced photodynamic therapy (HAL-PDT). In comparison to untreated rats, HAL-PDT causes little change in tumor-free rat bladder but induces inflammatory changes with increased lymphocytes and mononuclear cell infiltration in rat bladders with tumor. Immunohistochemistry reveals that HAL-PDT is without effect on proliferating cell nuclear antigen expression within the tumor and increases caspase-3 expression in both normal urothelium and the tumor. Transmission electron microscopy reveals severe mitochondrial damage, formations of apoptotic bodies, vacuoles, and lipofuscin bodies, but no microvillus-formed niches in HAL-PDT-treated bladder cancer rats. Bioinformatics analysis of the gene expression profile indicates an activation of T-cell receptor signaling pathway in bladder cancer rats without PDT. HAL-PDT increases the expression of CD3 and CD45RA in the tumor (determined by immunohistochemistry). We suggest that pathways of action of HAL-PDT may include, at least, activations of mitochondrial apoptosis and autophagy, breakdown of cancer stem cell niches, and importantly, enhancement of T-cell activation.

  10. Photodynamic therapy of human skin tumors using topical application of 5-aminolevulinic acid, dimethylsulfoxide (DMSO), and edetic acid disodium salt (EDTA)

    NASA Astrophysics Data System (ADS)

    Orenstein, Arie; Kostenich, Gennady; Tsur, H.; Roitman, Leonid; Ehrenberg, Benjamin; Malik, Zvi

    1995-01-01

    The results of photodynamic therapy (PDT) in 48 patients bearing basal cell carcinoma (BCC) and 7 patients with squamous cell carcinoma (SCC) of the skin are described. Five- aminolevulinic acid (5-ALA) was applied topically in two formulations. The first formulation contained 20% of 5-ALA in a base cream, and the second formulation (5-ALA composite cream), contained an additional 2% of dimethylsulfoxide (DMSO) and 2% of edetic acid disodium salt (EDTA). The creams were left on the skin for 2 - 5 hours. Production of protoporphyrin (PP) was measured in situ by a laser-induced fluorescence (LIF) method. The results of fluorescence measurement clearly indicate that PP accumulation in tumors induced by the 5-ALA composite cream was markedly higher than that induced by the 5-ALA cream. The tumors were light-irradiated (600 - 720 nm) after 4 - 5 hours of cream applications, using the light delivery system Versa-Light by a light dose of 100 J/cm2. The clinically superficial BCC tumors were highly responsive to PDT; the overall result in BCC patients was an 85.4% complete response. Histological examination showed an initial edematous reaction, followed by necrosis and complete disappearance of the tumor. The superficial SCC tumors showed a 100% complete response after PDT. The ulcerated nodular SCC showed partial responses.

  11. Evolutinoary Consideration on 5-Aminolevulinate Synthase in Nature

    NASA Astrophysics Data System (ADS)

    Oh-Hama, Tamiko

    1997-08-01

    5-Aminolevulinic acid (ALA), a universal precursor of tetrapyrrole compounds can be synthesized by two pathways: the C5 (glutamate) pathway and ALA synthase. From the phylogenetic distribution it is shown that distribution of ALA synthase is restricted to the α subclass of purple bacteria in prokaryotes, and further distributed to mitochondria of eukaryotes. The monophyletic origin of bacterial and eukaryotic ALA synthase is shown by sequence analysis of the enzyme. Evolution of ALA synthase in the α subclass of purple bacteria is discussed in relation to the energy-generating and biosynthetic devices in subclasses of this bacteria.

  12. The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors

    PubMed Central

    Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias

    2015-01-01

    BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased

  13. Daylight photodynamic therapy with 1.5% 3-butenyl 5-aminolevulinate gel as a convenient, effective and safe therapy in acne treatment: A double-blind randomized controlled trial.

    PubMed

    Kwon, Hyuck Hoon; Moon, Ki Rang; Park, Seon Yong; Yoon, Ji Young; Suh, Dae Hun; Lee, Jee Bum

    2016-05-01

    While daylight photodynamic therapy (PDT) is a simpler and more tolerable treatment procedure for both clinicians and patients, it has never been applied for acne treatment. In this study, we evaluated efficacy, safety and histological changes of facial acne after application of the novel variant of 5-aminolevulinate (ALA)-ester, 1.5% 3-butenyl ALA-bu gel, using daylight only as the potential visible light source. Forty-six acne patients were randomly assigned to either ALA-bu or vehicle application group in a double-blind fashion. Both groups applied the allocated gel to facial acne lesions every other day for 12 weeks. At the final 12 week, both inflammatory and non-inflammatory acne lesions had decreased significantly by 58.0% and 34.1% in the ALA-bu group, respectively. Only a few patients expressed mild adverse effects. In the histopathological analysis, attenuated inflammatory cell infiltrations were observed and immunostaining intensities for interleukin-8, interleukin-1β, matrix metalloproteinase-9 and phosphorylated nuclear factor-κB were reduced concomitantly. Changes of their mRNA expression demonstrated comparable patterns. In conclusion, this ambulatory PDT was effective, very well tolerated and convenient for treating inflammatory acne lesions. Experimental results correlated well with clinical results. This novel regimen would provide a viable option for acne therapy. PMID:26660491

  14. A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas.

    PubMed

    Lau, Darryl; Hervey-Jumper, Shawn L; Chang, Susan; Molinaro, Annette M; McDermott, Michael W; Phillips, Joanna J; Berger, Mitchel S

    2016-05-01

    OBJECT There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity. METHODS A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated. RESULTS A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating

  15. In situ assay for 5-aminolevulinate dehydratase and application to the study of a catabolite repression-resistant Saccharomyces cerevisiae mutant.

    PubMed

    Borralho, L M; Panek, A D; Malamud, D R; Sanders, H K; Mattoon, J R

    1983-10-01

    To facilitate the study of the effects of carbon catabolite repression and mutations on 5-aminolevulinate dehydratase (EC 4.2.1.24) from Saccharomyces cerevisiae, a sensitive in situ assay was developed, using cells permeabilized by five cycles of freezing and thawing. Enzymatic activity was measured by colorimetric determination of porphobilinogen with a modified Ehrlich reagent. For normal strains, porphobilinogen production was linear for 15 min, and the reaction rate was directly proportional to the permeabilized cell concentration up to 20 mg (dry weight) per ml. The reaction exhibited Michaelis-Menten-type kinetics, and an apparent Km of 2.6 mM was obtained for 5-aminolevulinic acid. This value is only slightly higher than the value of 1.8 mM obtained for the enzyme assayed in cell extracts. The in situ assay was used to assess catabolite repression-dependent changes in 5-aminolevulinate dehydratase during batch culture on glucose medium. In normal S. cerevisiae cells, the enzyme is strongly repressed as long as glucose is present in the medium. In contrast, a strain bearing the hex2-3 mutation exhibits derepressed levels of enzyme activity during growth on glucose. Synthesis of cytochromes by this strain is also resistant to catabolite repression. Similar studies employing a strain containing the glc1 mutation, which enhances porphyrin accumulation, did not reveal any significant phenotypic change in catabolite regulation of 5-aminolevulinate dehydratase. PMID:6352674

  16. Immunocytochemical studies on the localization of 5-aminolevulinate synthase in rat liver.

    PubMed

    Rohde, M; Srivastava, G; Rylatt, D B; Bundesen, P; Zamattia, J; Crane, D I; May, B K

    1990-08-01

    The localization of 5-aminolevulinate synthase (ALAS) in hepatocytes of untreated and porphyrinogenic drug-treated rats has been examined by an immunocytochemical approach using a monoclonal antibody and protein A-gold labeling. Gold particles representing antigenic sites for ALAS were observed in the mitochondria and cytoplasm of untreated and drug-treated cells. Quantitative analysis of the labeling density showed that levels of ALAS increased significantly in both of these cellular compartments following drug treatment. Evidence that the detected cytoplasmic form of ALAS represents the precursor of the enzyme was obtained from immunoblotting experiments. The direct detection of cytosolic ALAS in vivo rules out the possibility that enzyme activity previously detected in the cytosol fraction resulted from mitochondrial leakage during cell fractionation. The results indicate that the cytosolic accumulation of ALAS is not a consequence of the inability of mitochondria to accommodate more enzyme. However, the molecular basis for this cytosolic accumulation is not known. The studies also established that the mitochondrial enzyme is predominantly, if not exclusively, associated with the matrix side of the inner mitochondrial membrane. PMID:2369125

  17. Light regulation of chlorophyll biosynthesis at the level of 5-aminolevulinate formation in Arabidopsis.

    PubMed Central

    Ilag, L L; Kumar, A M; Söll, D

    1994-01-01

    5-Aminolevulinic acid (ALA) is the universal precursor of tetrapyrroles, such as chlorophyll and heme. The major control of chlorophyll biosynthesis is at the step of ALA formation. In the chloroplasts of plants, as in Escherichia coli, ALA is derived from the glutamate of Glu-tRNA via the two-step C5 pathway. The first enzyme, Glu-tRNA reductase, catalyzes the reduction of Glu-tRNA to glutamate 1-semialdehyde with the release of intact tRNA. The second enzyme, glutamate 1-semialdehyde 2,1-aminomutase, converts glutamate 1-semialdehyde to ALA. To further examine ALA formation in plants, we isolated Arabidopsis genes that encode the enzymes of the C5 pathway via functional complementation of mutations in the corresponding genes of E. coli. The Glu-tRNA reductase gene was designated HEMA and the glutamate 1-semialdehyde 2,1-aminomutase gene, GSA1. Each gene contains two short introns (149 and 241 nucleotides for HEMA, 153 and 86 nucleotides for GSA1). The deduced amino acid sequence of the HEMA protein predicts a protein of 60 kD with substantial similarity (30 to 47% identity) to sequences derived from the known hemA genes from microorganisms that make ALA by the C5 pathway. Purified Arabidopsis HEMA protein has Glu-tRNA reductase activity. The GSA1 gene encodes a 50-kD protein whose deduced amino acid sequence shows extensive homology (55 to 78% identity) with glutamate 1-semialdehyde 2,1-aminomutase proteins from other species. RNA gel blot analyses indicated that transcripts for both genes are found in root, leaf, stem, and flower tissues and that their levels are dramatically elevated by light. Thus, light may regulate ALA, and hence chlorophyll formation, by exerting coordinated transcriptional control over both enzymes of the C5 pathway. PMID:7908550

  18. High light inhibits chlorophyll biosynthesis at the level of 5-aminolevulinate synthesis during de-etiolation in cucumber (Cucumis sativus) cotyledons.

    PubMed

    Aarti, D; Tanaka, R; Ito, H; Tanaka, A

    2007-01-01

    Using the vascular plant Cucumis sativus (cucumber) as a model, we studied the effects of high (intense and excess) light upon chlorophyll biosynthesis during de-etiolation. When illuminated with high light (1500-1600 microE/m2/s), etiolated cucumber cotyledons failed to synthesize chlorophyll entirely. However, upon transfer to low light conditions (40-45 microE/m2/s), chlorophyll biosynthesis and subsequent accumulation resumed following an initial 2-12 h delay. Duration of high light treatment negatively correlated with chlorophyll biosynthetic activity. Specifically, we found that high light severely inhibited 5-aminolevulinic acid (ALA) synthesis. This effect partly could be because of the decrease in protein level of glutamyl-tRNA reductase (GluTR) observed. Protein level of glutamate-1-semialdehyde (GSA-AT) remained unchanged. It was also found that high light did not suppress HEMA 1 expression. Therefore, we speculated that this significant inhibition of ALA synthesis might have occurred mainly because of concomitant inactivation of GluTR and/or inhibition of complex formation between GluTR and GSA-AT. Our further observation that both methyl viologen and rose bengal similarly inhibit ALA synthesis under low light conditions suggested that reactive oxygen species (ROS) could be responsible for the inhibition of ALA synthesis in cotyledons exposed to high light conditions. PMID:16922603

  19. Evolution of cyclizing 5-aminolevulinate synthases in the biosynthesis of actinomycete secondary metabolites: outcomes for genetic screening techniques

    PubMed Central

    Petříčková, Kateřina; Chroňáková, Alica; Zelenka, Tomáš; Chrudimský, Tomáš; Pospíšil, Stanislav; Petříček, Miroslav; Krištůfek, Václav

    2015-01-01

    A combined approach, comprising PCR screening and genome mining, was used to unravel the diversity and phylogeny of genes encoding 5-aminolevulinic acid synthases (ALASs, hemA gene products) in streptomycetes-related strains. In actinomycetes, these genes were believed to be directly connected with the production of secondary metabolites carrying the C5N unit, 2-amino-3-hydroxycyclopent-2-enone, with biological activities making them attractive for future use in medicine and agriculture. Unlike “classical” primary metabolism ALAS, the C5N unit-forming cyclizing ALAS (cALAS) catalyses intramolecular cyclization of nascent 5-aminolevulinate. Specific amino acid sequence changes can be traced by comparison of “classical” ALASs against cALASs. PCR screening revealed 226 hemA gene-carrying strains from 1,500 tested, with 87% putatively encoding cALAS. Phylogenetic analysis of the hemA homologs revealed strain clustering according to putative type of metabolic product, which could be used to select producers of specific C5N compound classes. Supporting information was acquired through analysis of actinomycete genomic sequence data available in GenBank and further genetic or metabolic characterization of selected strains. Comparison of 16S rRNA taxonomic identification and BOX-PCR profiles provided evidence for numerous horizontal gene transfers of biosynthetic genes or gene clusters within actinomycete populations and even from non-actinomycete organisms. Our results underline the importance of environmental and evolutionary data in the design of efficient techniques for identification of novel producers. PMID:26300877

  20. Quantitative and qualitative 5-aminolevulinic acid–induced protoporphyrin IX fluorescence in skull base meningiomas

    PubMed Central

    Bekelis, Kimon; Valdés, Pablo A.; Erkmen, Kadir; Leblond, Frederic; Kim, Anthony; Wilson, Brian C.; Harris, Brent T.; Paulsen, Keith D.; Roberts, David W.

    2011-01-01

    Object Complete resection of skull base meningiomas provides patients with the best chance for a cure; however, surgery is frequently difficult given the proximity of lesions to vital structures, such as cranial nerves, major vessels, and venous sinuses. Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative assessment of protoporphyrin IX (PpIX) fluorescence following the exogenous administration of 5-aminolevulinic acid (ALA) has demonstrated utility in malignant glioma resection but limited use in meningiomas. Here the authors demonstrate the use of ALA-induced PpIX fluorescence guidance in resecting a skull base meningioma and elaborate on the advantages and disadvantages provided by both quantitative and qualitative fluorescence methodologies in skull base meningioma resection. Methods A 52-year-old patient with a sphenoid wing WHO Grade I meningioma underwent tumor resection as part of an institutional review board–approved prospective study of fluorescence-guided resection. A surgical microscope modified for fluorescence imaging was used for the qualitative assessment of visible fluorescence, and an intraoperative probe for in situ fluorescence detection was utilized for quantitative measurements of PpIX. The authors assessed the detection capabilities of both the qualitative and quantitative fluorescence approaches. Results The patient harboring a sphenoid wing meningioma with intraorbital extension underwent radical resection of the tumor with both visibly and nonvisibly fluorescent regions. The patient underwent a complete resection without any complications. Some areas of the tumor demonstrated visible fluorescence. The quantitative probe detected neoplastic tissue better than the qualitative modified surgical microscope. The intraoperative probe was particularly useful in areas that did not reveal visible fluorescence, and tissue from these areas was confirmed as tumor following histopathological

  1. [Activity of 5-aminolevulinate synthase in rat liver during degradation of cytochrome P-450 caused by administration of cadmium chloride].

    PubMed

    Kaliman, P A; Inshina, N N

    2003-01-01

    The 5-aminolevulinate synthase, tryptophan-2,3-dioxygenase activities and cytochrome P-450 content in the rat liver was studied in different terms after CdCl2 administration and after administration of metal salt against a background of 2-hours action of alpha-tocopherol. The lowering of activity of 5-aminolevulinate synthase in 2 h with the consequent increase of the enzyme activity in 6 h and 24 h was detected. The holoenzyme activity and heme saturation of tryptophan-2,3-dioxygenase increased 6 h after CdCl2 administration. The holoenzyme activity and the total activity of tryptophan-2,3-dioxygenase rised in 24 h. The level of cytochrome P-450 lowered. Preliminary administration of alpha-tocopherol prevented changes of studied parameters 24 h after CdCl2 administration. The relationship between decrease of cytochrome P-450 level and 5-aminolevulinate synthase activation are discussed. PMID:14577179

  2. Catalytically active alkaline molten globular enzyme: Effect of pH and temperature on the structural integrity of 5-aminolevulinate synthase.

    PubMed

    Stojanovski, Bosko M; Breydo, Leonid; Hunter, Gregory A; Uversky, Vladimir N; Ferreira, Gloria C

    2014-12-01

    5-Aminolevulinate synthase (ALAS), a pyridoxal-5'phosphate (PLP)-dependent enzyme, catalyzes the first step of heme biosynthesis in mammals. Circular dichroism (CD) and fluorescence spectroscopies were used to examine the effects of pH (1.0-3.0 and 7.5-10.5) and temperature (20 and 37°C) on the structural integrity of ALAS. The secondary structure, as deduced from far-UV CD, is mostly resilient to pH and temperature changes. Partial unfolding was observed at pH2.0, but further decreasing pH resulted in acid-induced refolding of the secondary structure to nearly native levels. The tertiary structure rigidity, monitored by near-UV CD, is lost under acidic and specific alkaline conditions (pH10.5 and pH9.5/37°C), where ALAS populates a molten globule state. As the enzyme becomes less structured with increased alkalinity, the chiral environment of the internal aldimine is also modified, with a shift from a 420nm to 330nm dichroic band. Under acidic conditions, the PLP cofactor dissociates from ALAS. Reaction with 8-anilino-1-naphthalenesulfonic acid corroborates increased exposure of hydrophobic clusters in the alkaline and acidic molten globules, although the reaction is more pronounced with the latter. Furthermore, quenching the intrinsic fluorescence of ALAS with acrylamide at pH1.0 and 9.5 yielded subtly different dynamic quenching constants. The alkaline molten globule state of ALAS is catalytically active (pH9.5/37°C), although the kcat value is significantly decreased. Finally, the binding of 5-aminolevulinate restricts conformational fluctuations in the alkaline molten globule. Overall, our findings prove how the structural plasticity of ALAS contributes to reaching a functional enzyme. PMID:25240868

  3. The Effect of Multiple Sequential Light Sources to Activate Aminolevulinic Acid in the Treatment of Actinic Keratoses: A Retrospective Study

    PubMed Central

    Goldman, Mitchel P.; Fabi, Sabrina G.; Guiha, Isabella

    2014-01-01

    There is a lack of research regarding the sequential use of multiple light sources for topical 5-aminolevulinic acid activation in photodynamic therapy for actinic keratosis. This study evaluated 5-aminolevulinic acid-photodynamic therapy for actinic keratosis using blue light combined with red light, pulsed dye laser, and/or intense pulsed light in a retrospective fashion. Field-directed 5-aminolevulinic acid-photodynamic therapy was performed with blue light only, blue light + pulsed dye laser, blue light + intense pulsed light, blue light + pulsed dye laser + intense pulsed light, or blue light + red light + pulsed dye laser + intense pulsed light for nonhyperkeratotic actinic keratoses of face, scalp, or upper trunk. Blue light + intense pulsed light + pulsed dye laser produced greater patient-reported improvement in actinic keratoses than blue light or blue light + intense pulsed light and greater subject-reported improvement in overall skin quality than blue light + intense pulsed light. The addition of red light led to no further benefit in either outcome measure. Photodynamic therapy with multiple, sequential laser and light sources led to greater patient-graded improvement in actinic keratoses than that with a single light source (blue light), without significant differences in post-treatment adverse events. However, the small, widely disparate number of patients between groups and follow-up times between patients, as well as retrospective assessments based on subjective patient recall, severely limit the significance of these findings. Nevertheless, the results raise interesting questions regarding the use of multiple light and laser sources for photodynamic therapy of actinic keratoses and warrant further research with a prospective, randomized, controlled study. PMID:25276272

  4. Erythroid 5-aminolevulinate synthase mediates the upregulation of membrane band 3 protein expression by iron.

    PubMed

    Huang, Qianchuan; Li, Jinying; Feng, Weihua; Xu, Yanqun; Huang, Zhenxia; Lv, Shuqing; Zhou, Hong; Gao, Lei

    2010-03-01

    Iron deficiency leads to abnormal expression and function of band 3 protein in erythrocytes, but the underlying mechanisms remain elusive. The mRNA of erythroid-specific 5-aminolevulinate synthase (eALAS) contains an iron response element and the eALAS protein is an important mediator of iron utilization by erythrocytes. In this study, we investigated the effect of short hairpin RNA (shRNA) mediated silencing of eALAS on the expression of band 3 protein induced by iron. By real-time RT-PCR and Western blot we showed that at mRNA and protein level iron-induced expression of band 3 protein was lower in eALAS-shRNA transfected K562 cells than in control cells. Of note, the lowest expression was detected in K562 cells cultured in iron deficiency condition (p < 0.01). Thus either iron deficiency or depletion of eALAS could suppress the expression of erythroid band 3 protein. These results demonstrated for the first time that iron and the iron-regulatory system regulate the expression of the erythrocyte membrane proteins. PMID:20087844

  5. 5-Aminolevulinate production by Escherichia coli containing the Rhodobacter sphaeroides hemA gene

    SciTech Connect

    Van Der Werf, M.J.; Zeikus, J.G. |

    1996-10-01

    The Rhodobacter sphaeroides hemA gene codes for 5-aminolevulinate (ALA) synthase. This enzyme catalyzes the pyridoxal phosphate-dependent condensation of succinyl coenzyme A and glycine-forming ALA. The R. sphaeroides hemA gene in the pUC18/19 vector system was transformed into Escherichia coli. The effects of both genetic and physiological factors on the expression of ALA synthase and the production of ALA were studied. ALA synthase activity levels were maximal when hemA had the same transcription direction as the lac promoter. The distance between the lac promoter and hemA affected the expression of ALA synthase on different growth substrates. The E. coli host strain used had an enormous effect on the ALA synthase activity level and on the production of ALA, with E. coli DH1 being best suited. The ALA synthase activity level was also dependent on the carbon source. Succinate, L-malate, fumarate, and L-aspartate gave the highest levels of ALA synthase activity, while the use of lactose as a carbon source resulted in a repression of ALA synthase. After growth on succinate, ALA synthase represented {approx}5% of total cellular protein. The ALA synthase activity level was also dependent on the pH of the medium, with maximal activity occurring at pH 6.5. ALA production by whole cells was limited by the availability of glycine, and the addition of 2 g of glycine per liter to the growth medium increased the production of ALA fivefold, to 2.25 mM. In recombinant E. coli extracts, up to 22 mM ALA was produced from succinate, glycine, and ATP. 58 refs., 4 figs., 7 tabs.

  6. Effects of light irradiation upon photodynamic therapy based on 5-aminolevulinic acid–gold nanoparticle conjugates in K562 cells via singlet oxygen generation

    PubMed Central

    Xu, Hao; Liu, Chen; Mei, Jiansheng; Yao, Cuiping; Wang, Sijia; Wang, Jing; Li, Zheng; Zhang, Zhenxi

    2012-01-01

    Purpose As a precursor of the potent photosensitizer protoporphyrin IX (PpIX), 5-aminolevulinic acid (5-ALA), was conjugated onto cationic gold nanoparticles (GNPs) to improve the efficacy of photodynamic therapy (PDT). Methods Cationic GNPs reduced by branched polyethyleneimine and 5-ALA were conjugated onto the cationic GNPs by creating an electrostatic interaction at physiological pH. The efficacy of ALA-GNP conjugates in PDT was investigated under irradiation with a mercury lamp (central wavelength of 395 nm) and three types of light-emitting diode arrays (central wavelengths of 399, 502, and 621 nm, respectively). The impacts of GNPs on PDT were then analyzed by measuring the intracellular PpIX levels in K562 cells and the singlet oxygen yield of PpIX under irradiation. Results The 2 mM ALA-GNP conjugates showed greater cytotoxicity against K562 cells than ALA alone. Light-emitting diode (505 nm) irradiation of the conjugates caused a level of K562 cell destruction similar to that with irradiation by a mercury lamp, although it had no adverse effects on drug-free control cells. These results may be attributed to the singlet oxygen yield of PpIX, which can be enhanced by GNPs. Conclusion Under irradiation with a suitable light source, ALA-GNP conjugates can effectively destroy K562 cells. The technique offers a new strategy of PDT. PMID:23055721

  7. Asn-150 of Murine Erythroid 5-Aminolevulinate Synthase Modulates the Catalytic Balance between the Rates of the Reversible Reaction.

    PubMed

    Stojanovski, Bosko M; Ferreira, Gloria C

    2015-12-25

    5-Aminolevulinate synthase (ALAS) catalyzes the first step in mammalian heme biosynthesis, the pyridoxal 5'-phosphate (PLP)-dependent and reversible reaction between glycine and succinyl-CoA to generate CoA, CO2, and 5-aminolevulinate (ALA). Apart from coordinating the positioning of succinyl-CoA, Rhodobacter capsulatus ALAS Asn-85 has a proposed role in regulating the opening of an active site channel. Here, we constructed a library of murine erythroid ALAS variants with substitutions at the position occupied by the analogous bacterial asparagine, screened for ALAS function, and characterized the catalytic properties of the N150H and N150F variants. Quinonoid intermediate formation occurred with a significantly reduced rate for either the N150H- or N150F-catalyzed condensation of glycine with succinyl-CoA during a single turnover. The introduced mutations caused modifications in the ALAS active site such that the resulting variants tipped the balance between the forward- and reverse-catalyzed reactions. Although wild-type ALAS catalyzes the conversion of ALA into the quinonoid intermediate at a rate 6.3-fold slower than the formation of the same quinonoid intermediate from glycine and succinyl-CoA, the N150F variant catalyzes the forward reaction at a mere 1.2-fold faster rate than that of the reverse reaction, and the N150H variant reverses the rate values with a 1.7-fold faster rate for the reverse reaction than that for the forward reaction. We conclude that the evolutionary selection of Asn-150 was significant for optimizing the forward enzymatic reaction at the expense of the reverse, thus ensuring that ALA is predominantly available for heme biosynthesis. PMID:26511319

  8. Human Erythroid 5-Aminolevulinate Synthase Mutations Associated with X-Linked Protoporphyria Disrupt the Conformational Equilibrium and Enhance Product Release.

    PubMed

    Fratz, Erica J; Clayton, Jerome; Hunter, Gregory A; Ducamp, Sarah; Breydo, Leonid; Uversky, Vladimir N; Deybach, Jean-Charles; Gouya, Laurent; Puy, Hervé; Ferreira, Gloria C

    2015-09-15

    Regulation of 5-aminolevulinate synthase (ALAS) is at the origin of balanced heme production in mammals. Mutations in the C-terminal region of human erythroid-specific ALAS (hALAS2) are associated with X-linked protoporphyria (XLPP), a disease characterized by extreme photosensitivity, with elevated blood concentrations of free protoporphyrin IX and zinc protoporphyrin. To investigate the molecular basis for this disease, recombinant hALAS2 and variants of the enzyme harboring the gain-of-function XLPP mutations were constructed, purified, and analyzed kinetically, spectroscopically, and thermodynamically. Enhanced activities of the XLPP variants resulted from increases in the rate at which the product 5-aminolevulinate (ALA) was released from the enzyme. Circular dichroism spectroscopy revealed that the XLPP mutations altered the microenvironment of the pyridoxal 5'-phosphate cofactor, which underwent further and specific alterations upon succinyl-CoA binding. Transient kinetic analyses of the variant-catalyzed reactions and protein fluorescence quenching upon binding of ALA to the XLPP variants demonstrated that the protein conformational transition step associated with product release was predominantly affected. Of relevance is the fact that XLPP could also be modeled in cell culture. We propose that (1) the XLPP mutations destabilize the succinyl-CoA-induced hALAS2 closed conformation and thus accelerate ALA release, (2) the extended C-terminus of wild-type mammalian ALAS2 provides a regulatory role that allows for allosteric modulation of activity, thereby controlling the rate of erythroid heme biosynthesis, and (3) this control is disrupted in XLPP, resulting in porphyrin accumulation. PMID:26300302

  9. Murine erythroid 5-aminolevulinate synthase: Truncation of a disordered N-terminal extension is not detrimental for catalysis.

    PubMed

    Stojanovski, Bosko M; Breydo, Leonid; Uversky, Vladimir N; Ferreira, Gloria C

    2016-05-01

    5-Aminolevulinate synthase (ALAS), a pyridoxal 5'-phosphate (PLP)-dependent homodimeric enzyme, catalyzes the initial step of heme biosynthesis in non-plant eukaryotes. The precursor form of the enzyme is translated in the cytosol, and upon mitochondrial import, the N-terminal targeting presequence is proteolytically cleaved to generate mature ALAS. In bone marrow-derived erythroid cells, a mitochondrial- and site-specific endoprotease of yet unknown primary structure, produces a protein shorter than mature erythroid ALAS (ALAS2) found in peripheral blood erythroid cells. This truncated ALAS2 lacks the presequence and the N-terminal sequence (corresponding to ~7 KDa molecular mass) present in ALAS2 from peripheral blood erythroid cells. How the truncation affects the structural topology and catalytic properties of ALAS2 is presently not known. To address this question, we created a recombinant, truncated, murine ALAS2 (ΔmALAS2) devoid of the cleavable N-terminal region and examined its catalytic and biophysical properties. The N-terminal truncation of mALAS2 did not significantly affect the organization of the secondary structure, but a subtle reduction in the rigidity of the tertiary structure was noted. Furthermore, thermal denaturation studies revealed a decrease of 4.3°C in the Tm value of ΔmALAS2, implicating lower thermal stability. While the kcat of ΔmALAS2 is slightly increased over that of the wild-type enzyme, the slowest step in the ΔmALAS2-catalyzed reaction remains dominated by ALA release. Importantly, intrinsic disorder algorithms imply that the N-terminal region of mALAS2 is highly disordered, and thus susceptible to proteolysis. We propose that the N-terminal truncation offers a cell-specific ALAS2 regulatory mechanism without hindering heme synthesis. PMID:26854603

  10. Recent advances in the prevention and treatment of skin cancer using photodynamic therapy

    PubMed Central

    Zhao, Baozhong; He, Yu-Ying

    2011-01-01

    Photodynamic therapy (PDT) is a noninvasive procedure that involves a photosensitizing drug and its subsequent activation by light to produce reactive oxygen species that specifically destroy target cells. Recently, PDT has been widely used in treating non-melanoma skin malignancies, the most common cancer in the USA, with superior cosmetic outcomes compared with conventional therapies. The topical ‘photosensitizers’ commonly used are 5-aminolevulinic acid (ALA) and its esterified derivative methyl 5-aminolevulinate, which are precursors of the endogenous photosensitizer protoporphyrin IX. After treatment with ALA or methyl 5-aminolevulinate, protoporphyrin IX preferentially accumulates in the lesion area of various skin diseases, which allows not only PDT treatment but also fluorescence diagnosis with ALA-induced porphyrins. Susceptible lesions include various forms of non-melanoma skin cancer such as actinic keratosis, basal cell carcinoma and squamous cell carcinoma. The most recent and promising developments in PDT include the discovery of new photosensitizers, the exploitation of new drug delivery systems and the combination of other modalities, which will all contribute to increasing PDT therapeutic efficacy and improving outcome. This article summarizes the main principles of PDT and its current clinical use in the management of non-melanoma skin cancers, as well as recent developments and possible future research directions. PMID:21080805

  11. Differential reduction in soluble and membrane-bound c-type cytochrome contents in a Paracoccus denitrificans mutant partially deficient in 5-aminolevulinate synthase activity.

    PubMed Central

    Page, M D; Ferguson, S J

    1994-01-01

    A mutant of Paracoccus denitrificans, DP104, unable to grow anaerobically with nitrate as the terminal electron acceptor or aerobically with methanol as the electron donor and staining negatively in the dimethylphenylene diamine oxidation (Nadi) test, was isolated by transposon Tn5::phoA mutagenesis. P. denitrificans DP104 grown aerobically with succinate or choline had very low levels (2 to 3% of the wild-type levels) of spectroscopically detectable soluble c-type cytochromes. In contrast, membrane cytochromes of the a, b, and c types were present at 50% of the levels found in the wild type. The apo form of cytochrome c550, at an approximately 1:1 molar ratio with the holo form, was found in the periplasm of DP104. The TnphoA element was shown to be inserted immediately upstream of the translational start of hemA, the gene coding for 5-aminolevulinate synthase, which was sequenced. Low-level expression of this gene, driven off an incidental promoter provided by TnphoA-cointegrated suicide vector DNA, is the basis of the phenotype which could be complemented by the addition of 5-aminolevulinate to growth media. Disruption of the hemA gene generated a P. denitrificans strain auxotrophic for 5-aminolevulinate, establishing that there is no hemA-independent pathway of heme synthesis in this organism. The differential deficiency in periplasmic c-type cytochromes relative to membrane cytochromes in DP104 is suggested to arise from unequal competition for the restricted supply of heme which results from the effects of the transposon insertion. Images PMID:7928952

  12. Differential accumulation and organ-specific metabolism of 5-aminolevulinic acid between cancer cells and normal epithelial and stromal cells

    NASA Astrophysics Data System (ADS)

    Krieg, Rene C.; Rauch, Joachim; Seidl, Juergen; Stepp, Herbert G.; Messmann, Helmut; Knuechel, Ruth

    2001-01-01

    To optimize conditions of photodynamic therapy (PDT) with ALA induced protoporphyrin IX (PPIX), topography of accumulation and metabolism of PPIX were analyzed in vitro. Adenocarcinoma cell lines, urothelial carcinoma cell lines, and a normal fibroblast cell line were cultured in plateau phase. ALA-induced PPIX accumulation, porphobilinogendeaminase-, ferrochelatase- activity, intracellular iron content, transferrin receptor expression and PPIX localization were determined using standard techniques. PBG activity as well as PPIX content were found higher in adenocarcinoma cells than in urothelial cells. Urothelial cell lines showed significant alterations in FC values in contrast to similar levels of FC in adenocarcinoma cell lines overall. Well differentiated cells showed higher iron content than lower differentiated cells. Transferrin receptor expression was found independent of PPIX content and intracellular iron content. In HT29, PPIX localizes mostly in the cell membrane, in SW480 and CaCo2 in mitochondria, and in urothelial cells mainly in cytosol. Data presented encourage the systematic and organ- related analysis of PPIX metabolism, since significant differences have been found between urothelial tumor cells and adenocarcinoma cells which may demand different strategies of therapy optimization and combination therapy regimens.

  13. The effects of visual fluorescence marking induced by 5-aminolevulinic acid for endoscopic diagnosis of urinary bladder cancer

    NASA Astrophysics Data System (ADS)

    Daniltchenko, Dmitri I.; Koenig, Frank; Schnorr, Dietmar; Valdman, Alexander; Al-Shukri, Salman; Loening, Stefan A.

    2003-10-01

    During cystoscopy procedure, fluorescence diagnostics induced by 5-ALA improves visual detection of the bladder cancer. Macroscopic ALA-fluorescence allows visualizing of small flat tumors, carcinoma in situ, true neoplasm margins and dysplasias of the bladder. Following ALA instillation, cystoscopy has been performed under both standard and blue light illumination. Totally, 153 biopsies have been carried out at 53 patients with suspicion of bladder cancer. The results were compared to ALA-fluorescence data. In 13% of the patients, bladder cancer and dysplasia were found out in addition, due to red fluorescence. The sensitivity and specificity of ALA-fluorescence technique aggregated 96% and 52% respectively. The sensitivity and specificity of 5-ALA-fluorescent detection exceeded standard endoscopy under white light on 20%. The new method does not exclude a false positive and a false negative fluorescent luminescence. The ALA-based fluorescence detection system enhances the diagnosis of malignant/dysplastic bladder lesions significantly.

  14. New method of acne disease fluorescent diagnostics in natural and fluorescent light and treatment control

    NASA Astrophysics Data System (ADS)

    Karimova, L. N.; Berezin, A. N.; Shevchik, S. A.; Kharnas, S. S.; Kusmin, S. G.; Loschenov, V. B.

    2005-08-01

    In the given research the new method of fluorescent diagnostics (FD) and photodynamic therapy (PDT) control of acne disease is submitted. Method is based on simultaneous diagnostics in natural and fluorescent light. PDT was based on using 5-ALA (5- aminolevulinic acid) preparation and 600-730 nanometers radiation. If the examined site of a skin possessed a high endogenous porphyrin fluorescence level, PDT was carried out without 5-ALA. For FD and treatment control a dot spectroscopy and the fluorescent imaging of the affected skin were used.

  15. Topical photodynamic therapy with 5-ALA in the treatment of arsenic-induced skin tumors

    NASA Astrophysics Data System (ADS)

    Karrer, Sigrid; Szeimies, Rolf-Markus; Landthaler, Michael

    1995-03-01

    A case of a 62-year-old woman suffering from psoriasis who was treated orally with arsenic 25 years ago is reported. The cumulative dose of arsenic trioxide was 800 mg. Since 10 years ago arsenic keratoses, basal cell carcinomas, Bowen's disease and invasive squamous cell carcinomas mainly on her hands and feet have developed, skin changes were clearly a sequence of arsenic therapy. Control of disease was poor, her right little finger had to be amputated. Topical photodynamic therapy with 5-aminolevulinic acid was performed on her right hand. Clinical and histological examinations 6 months after treatment showed an excellent cosmetic result with no signs of tumor residue.

  16. Treatment of Amino Acid Metabolism Disorders

    MedlinePlus

    ... Treatment of amino acid metabolism disorders Treatment of amino acid metabolism disorders E-mail to a friend Please ... this page It's been added to your dashboard . Amino acid metabolism disorders are rare health conditions that affect ...

  17. Short Communication Molecular cloning and expression pattern of the porcine 5-aminolevulinate synthase 1 (ALAS1) gene and its association with reproductive traits.

    PubMed

    Liu, L Q; Li, F E; Deng, C Y

    2016-01-01

    5-Aminolevulinate synthase 1 (ALAS1) is the first enzyme in the heme biosynthetic pathway and is upregulated in follicular tissue during the early stages of ovulation. In this study, we isolated the complete coding sequence of the porcine ALAS1 gene and its 2-9 intron sequence, identified a single nucleotide polymorphism (SNP; T/C) in intron 9, and developed a PCR-MspI-restriction fragment length polymorphism genotyping assay. Association of the SNP with litter size was assessed in two populations [purebred Large White and the experimental synthetic (DIV) line]. Statistical analysis demonstrated that for total number of piglets born (TNB) in all parities, pigs with the CC genotype had an additional 0.68 and 0.74 piglets compared to the TC and TT animals (P < 0.05) in the DIV line, respectively. Purebred Large White sows inheriting the CC and TC genotypes gave birth to an additional 0.96 and 0.70 piglets compared to the TT animals (P < 0.05) in all parities, respectively. In addition, for TNB in all parities, a significant additive effect of 0.48 ± 0.23 and 0.37 ± 0.17 piglets/ litter was detected in sows of both populations (P < 0.05), respectively. The highest levels of ALAS1 gene expression were observed in isolated ovarian granulosa cells 2 and 12 h after stimulation with pregnant mare serum gonadotropin human chorionic gonadotropin, which represents the time of follicular development and ovulation, respectively. Therefore, the ALAS1 gene was significantly associated with litter size in two populations and could be a useful molecular marker for the selection of increasing litter size in pigs. PMID:26910002

  18. Treatment of Fatty Acid Oxidation Disorders

    MedlinePlus

    ... of fatty acid oxidation disorders Treatment of fatty acid oxidation disorders E-mail to a friend Please ... page It's been added to your dashboard . Fatty acid oxidation disorders are rare health conditions that affect ...

  19. Performance, 5-aminolevulinic acid (ALA) yield and microbial population dynamics in a photobioreactor system treating soybean wastewater: Effect of hydraulic retention time (HRT) and organic loading rate (OLR).

    PubMed

    Liu, Shuli; Zhang, Guangming; Zhang, Jie; Li, Xiangkun; Li, Jianzheng

    2016-06-01

    Effects of hydraulic retention time (HRT) and influent organic loading rate (OLR) were investigated in a photobioreactor containing PNSB (Rhodobacter sphaeroides)-chemoheterotrophic bacteria to treat soybean wastewater. Pollutants removal, biomass production and ALA yield in different phases were investigated in together with functional microbial population dynamics. The results showed that proper HRT and OLR increased the photobioreactor performance including pollutants removal, biomass and ALA productions. 89.5% COD, 90.6% TN and 91.2% TP removals were achieved as well as the highest biomass production of 2655mg/L and ALA yield of 7.40mg/g-biomass under the optimal HRT of 60h and OLR of 2.48g/L/d. In addition, HRT and OLR have important impacts on PNSB and total bacteria dynamics. PMID:26818577

  20. Complementary use of optical coherence tomography and 5-aminolevulinic acid induced fluorescent spectroscopy for diagnosis of neoplastic processes in cervix and vulva

    NASA Astrophysics Data System (ADS)

    Sapozhnikova, Veronika V.; Shakhova, Natalia M.; Kamensky, Vladislav A.; Kuranov, Roman V.; Loshenov, Victor B.; Petrova, Svetlana A.

    2003-07-01

    A new approach to improving the diagnostic value of optical methods is suggested, which is based on a complementary investigation of different optical parameters of biotissues. The aim of this paper is comparative study of the feasibility of two optical methods - fluorescence spectroscopy and optical coherence tomography - for visualization of borders of neoplastic processes in the uterine cervix and vulva. Fluorescence spectroscopy is based on the detection of biochemical and optical coherence tomography on backscattering properties in norm and pathological changes of tissues. By means of these optical methods changes in biochemical and morphological properties of tissues were investigated. A parallel analysis of these two optical methods and histology from the center of tumors and their optical borders was made. Thirteen female patients with neoplastic changes in uterine cervix and vulva were enrolled in this study. The borders of the tumor determined by optical methods (fluorescence spectroscopy and optical coherence tomography) are coinciding with the biopsy proved ones. In addition, OCT and fluorescence borders of tumor in the uterine cervix and vulva exceeds colposcopically detectable borders, the averaging difference 2 mm. In future optical methods would considerably enhance diagnostic accuracy of conventional methods used in oncogynecology.

  1. Treatment options in acute porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria.

    PubMed

    Harper, Pauline; Wahlin, Staffan

    2007-12-01

    The porphyrias are a group of uncommon metabolic diseases caused by enzyme deficiencies within heme biosynthesis that lead to neurotoxic or phototoxic heme precursor accumulation. There are four acute porphyrias characterized by neuropsychiatric symptoms: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and 5-aminolevulinic acid dehydratase deficiency porphyria. Treatment includes elimination of any porphyrogenic factor and symptomatic treatment. Carbohydrate and intravenous heme administration constitute specific therapies in the disorders' acute phase. The mainstay treatment in the cutaneous porphyrias is avoidance of sunlight exposure. In porphyria cutanea tarda and the two acute porphyrias with skin manifestations, variegate porphyria and hereditary coproporphyria, care of the vulnerable skin is important. In porphyria cutanea tarda, specific treatment is accomplished by a series of phlebotomies and/or by low-dose chloroquine administration. In erythropoietic protoporphyria, light-protective beta-carotene is prescribed. PMID:18221605

  2. Photodynamic therapy (ALA-PDT) in the treatment of pathological states of the cornea

    NASA Astrophysics Data System (ADS)

    Switka-Wieclawska, Iwona; Kecik, Tadeusz; Kwasny, Miroslaw; Graczyk, Alfreda

    2003-10-01

    Each year an increasing amount of research is published on the use of photodynamic therapy in medicine. The most recent research has focused mostly on the use of photosensitizer called vertoporphyrin (Visudyne) is the treatment of subretinal neovascularization in age-related macular degeneration (AMD) or myopia, following a substantial amount of ophthalmology research mostly experimental on the application of the method in diagnosis and treatment of some eye tumors. In the Department of Ophthalmology of Polish Medical University in Warsaw, PDT was used as supplementary method in a selected group of patients with chronic virus ulcer of the cornea and keratopathies. During the treatment 5-aminolevulinic acid (5-ALA) was applied in ointment form as a photosensitizer activated with light wave of 633 nm. It appears, on the basis of the results obtained, that photodynamic therapy (ALA-PDT) may become in the future a valuable supplement to the methods being used at the present treating pathological states of the cornea.

  3. Effective treatment of d-penicillamine induced elastosis perforans serpiginosa with ALA-PDT.

    PubMed

    Wang, Duoqin; Liang, Jun; Xu, Jinhua; Chen, Lianjun

    2015-03-01

    A case of D-penicillamine(DPA) induced elastosis perforans serpiginosa(EPS) in a 32-year-old Chinese man was reported. The presentation lasted two years and was refractory to traditional medical treatment. He was then commenced on 7.6% 5-aminolevulinic acid (ALA) induced photodynamic therapy(PDT) by a LED light of 633 nm at dose levels of 130J/ cm2 for each session with total 3 sessions at one week interval. The patient was tolerated and responded well to this new approach for DPA-induced EPS without any adverse events. The etiology, pathophysiology, natural history, and treatment options for DPA-induced EPS are reviewed, and the authors suggest this method of treatment to be effective and safe for patients of DPA-induced EPS refractory to conventional therapy. PMID:25463318

  4. [Treatment of hydrofluoric acid burns].

    PubMed

    Thiele, B; Winter, U J; Mahrle, G; Steigleder, G K

    1986-01-31

    A chemical-plant worker sustained hydrofluoric acid burns during cleaning procedures. Intra-arterial perfusion and intralesional injections of calcium gluconate solution prevented progression of the burns into deeper tissue layers. PMID:3943470

  5. Successful treatment of oral verrucous hyperplasia with photodynamic therapy combined with cryotherapy--report of 3 cases.

    PubMed

    Chang, Yu-Chao; Yu, Chuan-Hang

    2014-06-01

    Our previous study showed successful treatment of a large oral verrucous hyperplasia (OVH) with topical 5-aminolevulinic acid-mediated photodynamic therapy combined with cryotherapy (ALA-PDT). In this case series, we extended this combined method for another three OVH lesions in three different patients. The clinical procedure was conducted as follows: the OVH lesions were irradiated with a 635-nm laser 1.5h after topical application of 20% ALA on the lesion for a total of 1000 s, which consisted of five 3-min and one 100-s irradiations separated by five 3-min rests. Cryogun cryotherapy was then performed on the lesion after ALA-PDT. The tumor was cleared after 1-6 treatments. No recurrence of the lesion was found after a follow-up period of 6-24 months. We suggest that our combined treatment protocol may be effective in treating OVH lesions. PMID:24561304

  6. Acid peptic diseases: pharmacological approach to treatment

    PubMed Central

    Mejia, Alex; Kraft, Walter K

    2011-01-01

    Acid peptic disorders are the result of distinctive, but overlapping pathogenic mechanisms leading to either excessive acid secretion or diminished mucosal defense. They are common entities present in daily clinical practice that, owing to their chronicity, represent a significant cost to healthcare. Key elements in the success of controlling these entities have been the development of potent and safe drugs based on physiological targets. The histamine-2 receptor antagonists revolutionized the treatment of acid peptic disorders owing to their safety and efficacy profile. The proton-pump inhibitors (PPIs) represent a further therapeutic advance due to more potent inhibition of acid secretion. Ample data from clinical trials and observational experience have confirmed the utility of these agents in the treatment of acid peptic diseases, with differential efficacy and safety characteristics between and within drug classes. Paradigms in their speed and duration of action have underscored the need for new chemical entities that, from a single dose, would provide reliable duration of acid control, particularly at night. Moreover, PPIs reduce, but do not eliminate, the risk of ulcers in patients taking NSAIDs, reflecting untargeted physiopathologic pathways and a breach in the ability to sustain an intragastric pH of more than 4. This review provides an assessment of the current understanding of the physiology of acid production, a discussion of medications targeting gastric acid production and a review of efficacy in specific acid peptic diseases, as well as current challenges and future directions in the treatment of acid-mediated diseases. PMID:21822447

  7. Treatment of broiler litter with organic acids.

    PubMed

    Ivanov, I E

    2001-04-01

    Experiments for treatment of contaminated broiler litter with citric, tartaric and salicylic acids were performed. At days 2 and 6 after the treatment, pH values (using a pH-meter), the ammonia concentrations (titration with 0.1 N HCl) and the microbial cells counts were determined in both experimental and control specimens of litter. The cost of acidification of litter was also determined. Our studies showed that the treatment of the contaminated litter with 5 per cent citric acid, 4 per cent tartaric acid and 1.5 per cent salicylic acid created an acid medium with pH under 5.0 and thus reduced the microbial counts to 2.2 x 10(3)colony forming units per gram manure litter. The treatment reduced the content of ammonia in the litter and in the air under the hygienic limits, i.e. 25-50 ppm. The cost of acidification of litter with these organic acids amounted to 0.1 $ per bird and 1.5 $ per 15 birds on one square metre in a growth period of 50 days. PMID:11356097

  8. Bacterial Cyanuric Acid Hydrolase for Water Treatment.

    PubMed

    Yeom, Sujin; Mutlu, Baris R; Aksan, Alptekin; Wackett, Lawrence P

    2015-10-01

    Di- and trichloroisocyanuric acids are widely used as water disinfection agents, but cyanuric acid accumulates with repeated additions and must be removed to maintain free hypochlorite for disinfection. This study describes the development of methods for using a cyanuric acid-degrading enzyme contained within nonliving cells that were encapsulated within a porous silica matrix. Initially, three different bacterial cyanuric acid hydrolases were compared: TrzD from Acidovorax citrulli strain 12227, AtzD from Pseudomonas sp. strain ADP, and CAH from Moorella thermoacetica ATCC 39073. Each enzyme was expressed recombinantly in Escherichia coli and tested for cyanuric acid hydrolase activity using freely suspended or encapsulated cell formats. Cyanuric acid hydrolase activities differed by only a 2-fold range when comparing across the different enzymes with a given format. A practical water filtration system is most likely to be used with nonviable cells, and all cells were rendered nonviable by heat treatment at 70°C for 1 h. Only the CAH enzyme from the thermophile M. thermoacetica retained significant activity under those conditions, and so it was tested in a flowthrough system simulating a bioreactive pool filter. Starting with a cyanuric acid concentration of 10,000 μM, more than 70% of the cyanuric acid was degraded in 24 h, it was completely removed in 72 h, and a respike of 10,000 μM cyanuric acid a week later showed identical biodegradation kinetics. An experiment conducted with water obtained from municipal swimming pools showed the efficacy of the process, although cyanuric acid degradation rates decreased by 50% in the presence of 4.5 ppm hypochlorite. In total, these experiments demonstrated significant robustness of cyanuric acid hydrolase and the silica bead materials in remediation. PMID:26187963

  9. Bacterial Cyanuric Acid Hydrolase for Water Treatment

    PubMed Central

    Yeom, Sujin; Mutlu, Baris R.; Aksan, Alptekin

    2015-01-01

    Di- and trichloroisocyanuric acids are widely used as water disinfection agents, but cyanuric acid accumulates with repeated additions and must be removed to maintain free hypochlorite for disinfection. This study describes the development of methods for using a cyanuric acid-degrading enzyme contained within nonliving cells that were encapsulated within a porous silica matrix. Initially, three different bacterial cyanuric acid hydrolases were compared: TrzD from Acidovorax citrulli strain 12227, AtzD from Pseudomonas sp. strain ADP, and CAH from Moorella thermoacetica ATCC 39073. Each enzyme was expressed recombinantly in Escherichia coli and tested for cyanuric acid hydrolase activity using freely suspended or encapsulated cell formats. Cyanuric acid hydrolase activities differed by only a 2-fold range when comparing across the different enzymes with a given format. A practical water filtration system is most likely to be used with nonviable cells, and all cells were rendered nonviable by heat treatment at 70°C for 1 h. Only the CAH enzyme from the thermophile M. thermoacetica retained significant activity under those conditions, and so it was tested in a flowthrough system simulating a bioreactive pool filter. Starting with a cyanuric acid concentration of 10,000 μM, more than 70% of the cyanuric acid was degraded in 24 h, it was completely removed in 72 h, and a respike of 10,000 μM cyanuric acid a week later showed identical biodegradation kinetics. An experiment conducted with water obtained from municipal swimming pools showed the efficacy of the process, although cyanuric acid degradation rates decreased by 50% in the presence of 4.5 ppm hypochlorite. In total, these experiments demonstrated significant robustness of cyanuric acid hydrolase and the silica bead materials in remediation. PMID:26187963

  10. Betulinic Acid for Cancer Treatment and Prevention

    PubMed Central

    Fulda, Simone

    2008-01-01

    Betulinic acid is a natural product with a range of biological effects, for example potent antitumor activity. This anticancer property is linked to its ability to induce apoptotic cell death in cancer cells by triggering the mitochondrial pathway of apoptosis. In contrast to the cytotoxicity of betulinic acid against a variety of cancer types, normal cells and tissue are relatively resistant to betulinic acid, pointing to a therapeutic window. Compounds that exert a direct action on mitochondria present promising experimental cancer therapeutics, since they may trigger cell death under circumstances in which standard chemotherapeutics fail. Thus, mitochondrion-targeted agents such as betulinic acid hold great promise as a novel therapeutic strategy in the treatment of human cancers. PMID:19325847

  11. ACID EXTRACTION TREATMENT SYSTEM FOR TREATMENT OF METAL CONTAMINATED SOILS

    EPA Science Inventory

    The Acid Extraction Treatment System (AETS) reduces the concentrations and/or leachability of heavy metals in contaminated soils so the soil can be returned to the site from which it originated. he objective of the project was to determine the effectiveness and commercial viabili...

  12. Multifunctional Nucleic Acids for Tumor Cell Treatment

    PubMed Central

    Pofahl, Monika; Wengel, Jesper

    2014-01-01

    We report on a multifunctional nucleic acid, termed AptamiR, composed of an aptamer domain and an antimiR domain. This composition mediates cell specific delivery of antimiR molecules for silencing of endogenous micro RNA. The introduced multifunctional molecule preserves cell targeting, anti-proliferative and antimiR function in one 37-nucleotide nucleic acid molecule. It inhibits cancer cell growth and induces gene expression that is pathologically damped by an oncomir. These findings will have a strong impact on future developments regarding aptamer- and antimiR-related applications for tumor targeting and treatment. PMID:24494617

  13. Current and new treatments of photodamaged skin.

    PubMed

    Shamban, Ava T

    2009-12-01

    Patients with photodamaged skin need guidance in selecting treatment plans that optimize outcomes, minimize downtime, and reduce adverse effects. The gold standard among cosmeceuticals is the topical retinoids, such as tretinoin. A topical formulation of folic acid and creatine appears to be a viable treatment option for the treatment of photodamaged skin. The use of specific topical cosmeceuticals in combination with nonablative photorejuvenation is recommended in choosing modalities that address the concerns of the patient. A combination of intense pulsed light (IPL), low-intensity diode light, and biostimulating drugs has been shown to provide results superior to those of IPL alone for photorejuvenation. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is the treatment of choice for type C photodamage. Low-strength 5-ALA (1 to 2%) applied several times, every 10 to 15 minutes, and incubated for 30 to 60 minutes with 550 to 630 nm, 530 to 1200 nm, or 570 to 1200 nm light activation improved hyperpigmented lesions, skin smoothing, and skin elasticity with high patient satisfaction. The use of 0.5% liposome-encapsulated 5-ALA spraying has been shown to be an alternative to 20% 5-ALA in a cream base in patients undergoing photorejuvenation. Adipose-derived stem cells and their derived secretory factors may have potential as treatments of photodamage. PMID:20024876

  14. Acid mine treatment with open limestone channels

    SciTech Connect

    Ziemkiewicz, P.F.; Brant, D.L.; Skousen, J.G.

    1996-12-31

    Acid mine drainage (AMD) is often associated with mining of pyritic coal and metal deposits. Typical AMD associated with coal mines in the eastern US can have acidity and iron concentrations ranging from the teens to the thousands of mg/l. Aluminum and manganese can be present in concentrations ranging from zero to the low hundreds of mg/l. Much attention has been devoted to developing inexpensive, limestone (LS)-based systems for treating AMID with little or no maintenance. However, LS tends to coat with metal hydroxides when exposed to AMID in an oxidized state, a process known as {open_quotes}armoring{close_quotes}. It is generally assumed that once armored, LS ceases to neutralize acid. Another problem is that the hydroxides tend to settle into plug the pore spaces in LS beds forcing water to move around rather than through the LS. While both are caused by the precipitation of metal hydroxides, armoring and plugging are two different problems. Plugging of LS pores can be avoided by maintaining a high flushing rate through the LS bed. Armoring, however, occurs regardless of water velocity. This study investigated the influence of armoring on LS solubility and the implications of armoring and plugging on the construction of open (oxidizing) LS channels for treating AMD. We evaluated the AMID treatment performance of armored and unarmored LS in oxidizing environments both in laboratory and field studies.

  15. Dealumination of zeolite {beta} via dicarboxylic acid treatment

    SciTech Connect

    Apelian, M.R.; Fung, A.S.; Kennedy, G.J.; Degnan, T.F.

    1996-10-10

    It is demonstrated that zeolite {beta} and zeolite {beta} containing catalysts can be dealuminated to very low acidity levels using a novel oxalic acid treatment without reducing zeolite integrity. The effect of the oxalic acid treatment has been studied over a wide range of treatment conditions for both silica-bound and unbound zeolite {beta} catalysts. Greater than 90% dealumination is observed with a concomitant reduction in n-hexane-cracking activity as measured by the alpha ({alpha}) test. Removal of framework aluminum occurs via a two-step hyrolysis/chelation mechanism, with the oxalic acid acting both as an acid and as a chelating agent. Framework aluminum removal is accompanied by the formation of internal silanol groups. Water soluble aluminum oxalates are present in the extracted solutions. Silanol groups are annealed with extended oxalic acid treatment. Oxalic acid treatment results in a unique contraction of the zeolite {beta} lattice structure not observed for mineral acid treated or steamed zeolite {beta} catalysts. 15 refs., 11 figs., 5 tabs.

  16. Improved diagnosis and therapy of superficial transitional cell carcinoma (TCC) of the urinary bladder by 5-aminolevulinic-acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence: a prospective study in 100 patients

    NASA Astrophysics Data System (ADS)

    Kuntz, Rainer M.; Ruecker, Frank

    2001-05-01

    The prognosis of superficial bladder cancer is strongly related to a high recurrence rate and the presence of concomitant plane tumor lesions such as severe dysplasia or carcinoma in situ. They are frequently overlooked on white light cystoscopy. Furthermore, the traditional transurethral tumor resection of superficial bladder tumor is frequently incomplete. This prospective study aimed to evaluate whether or not 5-ALA induced PPIX fluorescence cystoscopy could increase the detection of superficial bladder tumors and/or plane carcinoma in situ invisible on white light cystoscopy. 100 patients with superficial TCC of the urinary bladder underwent cystoscopy under white light and under blue fluorescence light. 2 hours (1-4 hours) prior to cystoscopy 50 ml 3 percent 5-ALA-solution were intravesically instilled into the empty bladder. All lesions visible on white light cystoscopy were compared with fluorescence findings and, vice versa, all fluorescence findings were compared with white light cystoscopy findings. All lesions visible under white light, and all lesions only visible under 5-ALA induced fluorescence were resected/biopsied and histologically examined.

  17. Acid mine water aeration and treatment system

    DOEpatents

    Ackman, Terry E.; Place, John M.

    1987-01-01

    An in-line system is provided for treating acid mine drainage which basically comprises the combination of a jet pump (or pumps) and a static mixer. The jet pump entrains air into the acid waste water using a Venturi effect so as to provide aeration of the waste water while further aeration is provided by the helical vanes of the static mixer. A neutralizing agent is injected into the suction chamber of the jet pump and the static mixer is formed by plural sections offset by 90 degrees.

  18. Increase of α1-acid glycoprotein after treatment with amitriptyline

    PubMed Central

    Baumann, P.; Tinguely, D.; Schöpf, J.

    1982-01-01

    Sixteen primary depressive patients were treated for 3 weeks with amitriptyline 150 mg daily. In thirteen patients the plasma level of α1-acid glycoprotein (AAG) significantly increased after the treatment but the albumin levels did not change. PMID:7104160

  19. 15. INTERIOR MIDDLE BAY DETAIL VIEW, FACING WEST. ACID TREATMENT, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. INTERIOR MIDDLE BAY DETAIL VIEW, FACING WEST. ACID TREATMENT, CUTTING EQUIPMENT, LOCKERS ABANDONED ON SITE. TRACKS FOR MOVEMENT OF MATERIALS VISIBLE HANGING FROM CEILING. - NASA Industrial Plant, Missile Research Laboratory, 12214 Lakewood Boulevard, Downey, Los Angeles County, CA

  20. 300 Area waste acid treatment system closure plan. Revision 1

    SciTech Connect

    1996-03-01

    This section provides a description of the Hanford Site, identifies the proposed method of 300 Area Waste Acid Treatment System (WATS) closure, and briefly summarizes the contents of each chapter of this plan.

  1. Fluorescence Guided PDT for Optimization of Skin Cancer Treatment

    NASA Astrophysics Data System (ADS)

    Blanco, Kate; Moriyama, Lilian; Inada, Natalia; Kurachi, Cristina; Salvio, Ana; Leite, Everson; Menezes, Priscila; Bagnato, Vanderlei

    2015-04-01

    The photodynamic therapy (PDT) is an alternative technique that can be indicated for superficial basal cell carcinoma (sBCC), Bowen’s disease and actinic keratosis with high efficiency. The objective of this study is to present the importance of fluorescence imaging for PDT guidance and monitoring in real time. Confirming that the lesion is well prepared and the photosensitizer shows a homogenous distribution, the outcome after few PDT sessions will be positive and the recurrence should be lower. Our proposition in this study is use the widefield fluorescence imaging to evaluate the PDT protocol in situ and in real time for each lesion. This evaluation procedure is performed in two steps: first with the monitoring of the production of protoporphyrin IX (PpIX) induced by methyl aminolevulinate (MAL), an derivative of 5-aminolevulinic acid (ALA) and second with the detection of PpIX photobleaching after illumination. The fluorescence images provide information correlated with distinct clinical features and with the treatment outcome. Eight BCC lesions are presented and discussed in this study. Different fluorescence patterns of PpIX production and photobleaching could be correlated with the treatment response. The presented results show the potential of using widefield fluorescence imaging as a guidance tool to customized PDT.

  2. 300 Area waste acid treatment system closure plan

    SciTech Connect

    LUKE, S.N.

    1999-05-17

    The Hanford Facility Dangerous Waste Permit Application is considered to be a single application organized into a General Information Portion (document number DOERL-91-28) and a Unit-Specific Portion. The scope of the Unit-Specific Portion includes closure plan documentation submitted for individual, treatment, storage, and/or disposal units undergoing closure, such as the 300 Area Waste Acid Treatment System. Documentation contained in the General Information Portion is broader in nature and could be used by multiple treatment, storage, and/or disposal units (e.g., the glossary provided in the General Information Portion). Whenever appropriate, 300 Area Waste Acid Treatment System documentation makes cross-reference to the General Information Portion, rather than duplicating text. This 300 Area Waste Acid Treatment System Closure Plan (Revision 2) includes a Hanford Facility Dangerous Waste Permit Application, Part A, Form 3. Information provided in this closure plan is current as of April 1999.

  3. Photodynamic therapy with 5-aminoolevulinic acid-induced porphyrins and DMSO/EDTA for basal cell carcinoma

    NASA Astrophysics Data System (ADS)

    Warloe, Trond; Peng, Qian; Heyerdahl, Helen; Moan, Johan; Steen, Harald B.; Giercksky, Karl-Erik

    1995-03-01

    Seven hundred sixty three basal cell carcinomas (BCCs) in 122 patients were treated by photodynamic therapy by 5-aminolevulinic acid (ALA) in cream topically applied, either alone, in combination with dimethyl sulphoxide (DMSO) and ethylenediaminetetraacetic acid disodium salt (EDTA), or with DMSO as a pretreatment. After 3 hours cream exposure 40 - 200 Joules/cm2 of 630 nm laser light was given. Fluorescence imaging of biopsies showed highly improved ALA penetration depth and doubled ALA-induced porphyrin production using DMSO/EDTA. Treatment response was recorded after 3 months. After a single treatment 90% of 393 superficial lesions responded completely, independent of using DMSO/EDTA. In 363 nodulo-ulcerative lesions the complete response rate increased from 67% to above 90% with DMSO/EDTA for lesions less than 2 mm thickness and from 34% to about 50% for lesions thicker than 2 mm. Recurrence rate observed during a follow-up period longer than 12 months was 2 - 5%. PDT of superficial thin BCCs with ALA-induced porphyrins and DMSO/EDTA equals surgery and radiotherapy with respect to cure rate and recurrence. Cosmetic results of ALA-based PDT seemed to be better than those after other therapies. In patients with the nevoid BCC syndrome the complete response rate after PDT was far lower.

  4. Topical application of ALA PDT for the treatment of moderate to severe acne vulgaris

    NASA Astrophysics Data System (ADS)

    Wang, Xiu-Li; Wang, Hong-Wei; Zhang, Ling-Lin; Su, Lina; Guo, Ming-Xia; Huang, Zheng

    2009-06-01

    Objectives: To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)- medicated photodynamic therapy (ALA PDT) for the treatment of moderate to severe acne vulgaris. Methods: Sixteen Chinese patients with moderate to severe facial acne were treated with 1-3 courses of ALA PDT. ALA cream (3%) was freshly prepared and applied to acne lesions for 3-4 h. The lesions were irradiated by a 635 nm diode laser at dose levels of 60 - 80 J/cm2 at 100 mW/cm2. Clinical assessments were conducted before and after treatment up to 3 months. Results: All patents showed response to ALA PDT. Complete clearance was seen in 10 patients (62.5%) and partial clearance in 6 patients (37.5%). One case showed recurrence after complete clearance at 2 months and another two showed recurrence after complete clearance at 3 months. However, the number of new lesions were significantly reduced. Adverse effects were minimal. Conclusions: The results of this preliminary clinical study is encouraging. ALA PDT is a simple, safe and useful therapeutic option for the treatment of moderate to severe acne. Further studies to evaluate the treatment with a larger number of patients and for a longer period of follow-up are needed.

  5. Photodynamic Therapy with Ablative Carbon Dioxide Fractional Laser in Treatment of Actinic Keratosis

    PubMed Central

    Jang, Yong Hyun; Lee, Dong Jun; Shin, Jaeyoung; Kang, Hee Young; Lee, Eun-So

    2013-01-01

    Background Recently, photodynamic therapy (PDT) has been shown to be an effective first-line treatment for actinic keratosis (AK). However, a major limitation of PDT is the long incubation time required to allow penetration of the photosensitizer. Objective The aim of this study was to assess if pretreatment with an ablative carbon dioxide (CO2) fractional laser can reduce the incubation time of the photosensitizer. Methods Initially, 29 patients with a total of 34 AK lesions were treated with an ablative CO2 fractional laser at Ajou University Hospital between January and December 2010. Immediately after the laser treatment, topical 20% 5-aminolevulinic acid or methyl-aminolevulinate was applied to the AK lesions and incubated for 70 to 90 minutes. Then, the treated areas were illuminated with a red light source. Improvement was clinically or histologically assessed eight weeks after the treatment. Results In spite of the short incubation time, 24 lesions (70.6%) showed a complete response (CR) within three sessions of PDT (10 lesions a clinical CR and 14 lesions a clinical/histological CR). There were no significant side effects associated with the combination of ablative CO2 fractional laser and PDT. Conclusion Ablative CO2 fractional laser may be considered an additional treatment option for reducing the incubation time of the photosensitizer in PDT. PMID:24371387

  6. Atypical femoral fracture following zoledronic acid treatment.

    PubMed

    Ataoğlu, Baybars; Kaptan, Ahmet Yiğit; Eren, Toygun Kağan; Yapar, Ali Ekber; Berkay, Ahmet Fırat

    2016-04-01

    A 68-year-old female patient admitted to our clinic with right anterior thigh pain ongoing for six months and which increased in last two months. The patient had no trauma history. The patient had been followed-up for 15 years because of osteoporosis and administrated alendronate and ibandronate treatment for 10 years. Patient had three shots of zoledronate once a year during the last three years. Her pain was increasing when she was walking. Physical examination revealed pain in her right thigh. Radiogram showed thickened lateral cortex of the subtrochanteric area. Magnetic resonance imaging also showed thickening and edema of the same area. These images were correlated with atypical fracture in right femoral subthrochanteric zone. Dual energy X-ray absorptiometry revealed that T score was -3.3 in lumbar region and -2.5 in femoral neck. Zoledronate treatment was ended. Prophylactic surgical fixation was performed with titanium elastic nails. PMID:26874637

  7. Hydrothermal acid treatment for sugar extraction from Golenkinia sp.

    PubMed

    Choi, Sun-A; Choi, Won-Il; Lee, Jin-Suk; Kim, Seung Wook; Lee, Gye-An; Yun, Jihyun; Park, Ji-Yeon

    2015-08-01

    In this study, hydrothermal acid treatment for efficient recovery of sugar from Golenkinia sp. was investigated. The initial glucose and XMG (xylose, mannose, and galactose) contents of a prepared Golenkinia sp. solution (40g/L) were 15.05 and 5.24g/L, respectively. The microalgal cell walls were hydrolyzed, for sugar recovery, by enzymatic saccharification and/or hydrothermal acid treatment. Among the various hydrothermal acid treatment conditions, the most optimal were the 2.0% H2SO4 concentration at 150°C for 15min, under which the glucose- and XMG-extraction yields were 71.7% and 64.9%, respectively. By pH 4.8, 50°C enzymatic hydrolysis after optimal hydrothermal acid treatment, the glucose- and XMG-extraction yields were additionally increased by 8.3% and 0.8%, respectively. After hydrothermal acid treatment, the combination with the enzymatic hydrolysis process improved the total sugar yield of Golenkinia sp. to 75.4%. PMID:25976916

  8. Comparison of three light doses in the photodynamic treatment of actinic keratosis using mathematical modeling

    NASA Astrophysics Data System (ADS)

    Vignion-Dewalle, Anne-Sophie; Betrouni, Nacim; Tylcz, Jean-Baptiste; Vermandel, Maximilien; Mortier, Laurent; Mordon, Serge

    2015-05-01

    Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for cancer therapy. Although high efficacy is demonstrated for PDT using standardized protocols in nonhyperkeratotic actinic keratoses, alternative light doses expected to increase efficiency, to reduce adverse effects or to expand the use of PDT, are still being evaluated and refined. We propose a comparison of the three most common light doses in the treatment of actinic keratosis with 5-aminolevulinic acid PDT through mathematical modeling. The proposed model is based on an iterative procedure that involves determination of the local fluence rate, updating of the local optical properties, and estimation of the local damage induced by the therapy. This model was applied on a simplified skin sample model including an actinic keratosis lesion, with three different light doses (red light dose, 37 J/cm2, 75 mW/cm2, 500 s blue light dose, 10 J/cm2, 10 mW/cm2, 1000 s and daylight dose, 9000 s). Results analysis shows that the three studied light doses, although all efficient, lead to variable local damage. Defining reference damage enables the nonoptimal parameters for the current light doses to be refined and the treatment to be more suitable.

  9. Aminolevulinic acid (ALA)-assisted photodynamic diagnosis of subclinical and latent HPV infection of external genital region.

    PubMed

    Wang, Hong-Wei; Wang, Xiu-Li; Zhang, Ling-Lin; Guo, Ming-Xia; Huang, Zheng

    2008-12-01

    The relatively high recurrence rate of genital warts can be attributed to the unsuccessful elimination of viruses in areas of subclinical and latent infection. Therefore, the identification and treatment of the subclinical and latent infection is a key to reduce the recurrence. The goal of this study is to investigate the usefulness of 5-aminolevulinic acid (ALA)-assisted in situ fluorescence diagnosis of subclinical lesion and latent HPV infection. A total of 30 patients with histologically confirmed genital warts (condylomata acuminata) were subjected to topical application of ALA, acetic acid test, histopathologic examination and HPV DNA subtyping. Topical application of ALA was performed by applying 20% ALA cream to the lesion plus 2-cm margin for 2h followed by fluorescence examination. Correlations between histopathologic examination, aceto-whitening test, HPV DNA subtyping and fluorescence were examined. All warty lesions and subclinical lesions (n=25) showed red fluorescence and harbored HPV DNA (HPV6 or 11). Latent HPV infections at 0.5-2 cm away from the warty lesion also showed red fluorescence. Nonspecific fluorescence was associated with mucosa, inflammatory infiltration and erosive lesion. ALA-assisted photodynamic diagnosis could be employed for the detection of the lesion and subclinical lesion of genital warts. It is also useful in detecting latent HPV infection. PMID:19356665

  10. Theobromine Inhibits Uric Acid Crystallization. A Potential Application in the Treatment of Uric Acid Nephrolithiasis

    PubMed Central

    Grases, Felix; Rodriguez, Adrian; Costa-Bauza, Antonia

    2014-01-01

    Purpose To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis. Materials and Methods The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system. Results The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments. Conclusions Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis. PMID:25333633

  11. Regulation of ion homeostasis by aminolevulinic acid in salt-stressed wheat seedlings

    NASA Astrophysics Data System (ADS)

    Türk, Hülya; Genişel, Mucip; Erdal, Serkan

    2016-04-01

    Salinity is regarded as a worldwide agricultural threat, as it seriously limits plant development and productivity. Salt stress reduces water uptake in plants by disrupting the osmotic balance of soil solution. In addition, it creates a damaged metabolic process by causing ion imbalance in cells. In this study, we aim to examine the negative effects of 5-aminolevulinic acid (ALA) (20 mg/l) on the ion balance in wheat seedling leaves exposed to salt stress (150 mM). Sodium is known to be highly toxic for plant cells at high concentrations, and is significantly increased by salt stress. However, it can be reduced by combined application of ALA and salt, compared to salt application alone. On the other hand, while the K+/Na+ ratio was reduced by salt stress, ALA application changed this ratio in favor of K+. Manganese, iron, and copper were also able to reduce stress. However, ALA pre-treatment resulted in mineral level increments. Conversely, the stress-induced rise in magnesium, potassium, calcium, phosphorus, zinc, and molybdenum were further improved by ALA application. These data clearly show that ALA has an important regulatory effect of ion balance in wheat leaves.

  12. Surgery combined with topical photodynamic therapy for the treatment of squamous cell carcinoma of the lip.

    PubMed

    Wang, Yuanyuan; Yang, Yadong; Yang, Yunchuan; Lu, Yuangang

    2016-06-01

    Due to the unique location of the squamous cell carcinoma (SCC) of the lip, using a single method such as extended resection or radiotherapy probably causes morphological and functional defects. So we used surgery combined with topical photodynamic therapy (PDT) to treat SCC of the lip. Under local anesthesia with 5% lidocaine, the hyperplastic and ulcerative SCC of the lip were curetted and assisted by topical PDTs after surgery. The 20% 5-aminolevulinic acid cream was used as a photosensitizer and applied evenly to the surface of the tumor lesion for 4h. Then the lesion site was irradiated with a 635-nm laser at 120J/cm(2). A total of five PDTs were performed postoperatively at an interval of 2 weeks. Photos were taken before and after every PDT to compare the skin lesions, treatment effects, and side effects. A long-term follow-up was undertaken to observe tumor recurrence. After surgery combined with five topical PDTs, the SCC of the lip disappeared without the compromised morphology of the lip, significant side effects, or tumor recurrence in one-year follow-up. Surgery combined with topical PDT can reduce the excision size of tumors and play a positive role in the treatment of tumors of special locations. PMID:27102062

  13. LIME TREATMENT LAGOONS TECHNOLOGY FOR TREATING ACID MINE DRAINAGE

    EPA Science Inventory

    Active and inactive mines can produce runoff and drainage that are among the most environmentally damaging processes affecting land in the United States. Acid mine drainage (AMD) from mining sites across the country requires treatment because of high metal concentrations that exc...

  14. DEVELOPMENT OF SRB TREATMENT SYSTEMS FOR ACID MINE DRAINAGE

    EPA Science Inventory

    Over the past decade, significant advances have been made in the development of sulfate- reducing bacteria (SRB) technology to treat acid mine drainage (AMD), Bench-scale testing, field demonstrations, and engineered applications of SRBs for the treatment of AMD will be presented...

  15. Loss-of-Function Ferrochelatase and Gain-of-Function Erythroid-Specific 5-Aminolevulinate Synthase Mutations Causing Erythropoietic Protoporphyria and X-Linked Protoporphyria in North American Patients Reveal Novel Mutations and a High Prevalence of X-Linked Protoporphyria

    PubMed Central

    Balwani, Manisha; Doheny, Dana; Bishop, David F; Nazarenko, Irina; Yasuda, Makiko; Dailey, Harry A; Anderson, Karl E; Bissell, D Montgomery; Bloomer, Joseph; Bonkovsky, Herbert L; Phillips, John D; Liu, Lawrence; Desnick, Robert J

    2013-01-01

    Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inborn errors of heme biosynthesis with the same phenotype but resulting from autosomal recessive loss-of-function mutations in the ferrochelatase (FECH) gene and gain-of-function mutations in the X-linked erythroid-specific 5-aminolevulinate synthase (ALAS2) gene, respectively. The EPP phenotype is characterized by acute, painful, cutaneous photosensitivity and elevated erythrocyte protoporphyrin levels. We report the FECH and ALAS2 mutations in 155 unrelated North American patients with the EPP phenotype. FECH sequencing and dosage analyses identified 140 patients with EPP: 134 with one loss-of-function allele and the common IVS3-48T>C low expression allele, three with two loss-of-function mutations and three with one loss-of-function mutation and two low expression alleles. There were 48 previously reported and 23 novel FECH mutations. The remaining 15 probands had ALAS2 gain-of-function mutations causing XLP: 13 with the previously reported deletion, c.1706_1709delAGTG, and two with novel mutations, c.1734delG and c.1642C>T(p.Q548X). Notably, XLP represented ~10% of EPP phenotype patients in North America, two to five times more than in Western Europe. XLP males had twofold higher erythrocyte protoporphyrin levels than EPP patients, predisposing to more severe photosensitivity and liver disease. Identification of XLP patients permits accurate diagnosis and counseling of at-risk relatives and asymptomatic heterozygotes. PMID:23364466

  16. Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review

    PubMed Central

    Li, Jian-yuan; Cao, Hong-yan; Cheng, Gen-hong; Sun, Ming-yu

    2014-01-01

    Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra). GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions. PMID:24963489

  17. Treatment of hydrofluoric acid exposure to the eye

    PubMed Central

    Atley, Katherine; Ridyard, Edward

    2015-01-01

    AIM To review the current evidence of the treatment of hydrofluoric acid (HF) exposure to the human cornea. METHODS A comprehensive manual search of the literature was conducted through the Ovid interface to assess the mechanism and efficacy of each irrigator through a variety of clinical cases and experimental studies. RESULTS Ocular exposure to HF is extremely damaging to the eye and swift recognition and decontamination with an appropriate agent forms the basis of treatment. Although there are various decontamination solutions that have efficacy against the corrosive action of HF, irrigation with Hexafluorine proved to be the most safe and effective treatment for the eye. CONCLUSION In conclusion emergency departments could benefit from the availability of Hexafluorine for the treatment of HF ocular burns in patients. PMID:25709926

  18. Acetylsalicylic acid treatment improves differentiation and immunomodulation of SHED.

    PubMed

    Liu, Y; Chen, C; Liu, S; Liu, D; Xu, X; Chen, X; Shi, S

    2015-01-01

    Stem cells from exfoliated deciduous teeth (SHED) possess multipotent differentiation and immunomodulatory properties. They have been used for orofacial bone regeneration and autoimmune disease treatment. In this study, we show that acetylsalicylic acid (ASA) treatment is able to significantly improve SHED-mediated osteogenic differentiation and immunomodulation. Mechanistically, ASA treatment upregulates the telomerase reverse transcriptase (TERT)/Wnt/β-catenin cascade, leading to improvement of SHED-mediated bone regeneration, and also upregulates TERT/FASL signaling, leading to improvement of SHED-mediated T-cell apoptosis and ameliorating disease phenotypes in dextran sodium sulfate-induced colitis mice. These data indicate that ASA treatment is a practical approach to improving SHED-based cell therapy. PMID:25394850

  19. Removal of coagulant aluminum from water treatment residuals by acid.

    PubMed

    Okuda, Tetsuji; Nishijima, Wataru; Sugimoto, Mayo; Saka, Naoyuki; Nakai, Satoshi; Tanabe, Kazuyasu; Ito, Junki; Takenaka, Kenji; Okada, Mitsumasa

    2014-09-01

    Sediment sludge during coagulation and sedimentation in drinking water treatment is called "water treatment residuals (WTR)". Polyaluminum chloride (PAC) is mainly used as a coagulant in Japan. The recycling of WTR has been desired; one method for its reuse is as plowed soil. However, WTR reuse in this way is inhibited by the aluminum from the added PAC, because of its high adsorption capacity for phosphate and other fertilizer components. The removal of such aluminum from WTR would therefore be advantageous for its reuse as plowed soil; this research clarified the effect of acid washing on aluminum removal from WTR and on plant growth in the treated soil. The percentage of aluminum removal from raw WTR by sulphuric acid solution was around 90% at pH 3, the percentage decreasing to 40% in the case of a sun-dried sample. The maximum phosphate adsorption capacity was decreased and the available phosphorus was increased by acid washing, with 90% of aluminum removal. The enhancement of Japanese mustard spinach growth and the increased in plant uptake of phosphates following acid washing were observed. PMID:24835954

  20. Lactic acid fermentation within a cascading approach for biowaste treatment.

    PubMed

    Probst, Maraike; Walde, Janette; Pümpel, Thomas; Wagner, Andreas Otto; Schneider, Irene; Insam, Heribert

    2015-04-01

    Limited availability of resources and increased amounts of waste coupled with an ever-increasing demand for raw materials are typical characteristics of our times. As such, there is an urgent need to accordingly update waste treatment technology. The aim of this study was to determine whether a separate treatment of the liquid and the solid fraction of biowaste could enhance overall efficiency. Liquid fractions obtained from two different separation procedures were fermented at a pH of 5 and uncontrolled pH conditions for 72 h. The fermentation conditions leading to highest lactic acid productivity and yield were evaluated. The substrates gained by both separation procedures showed efficient lactic acid production up to <25 g L(-1). The pH control increased lactic acid concentration by about 27 %. Furthermore, quantitative real-time PCR analyses revealed stronger Lactobacilli growth in these fermentations. As identified via Illumina sequencing Lactobacillus delbrueckii and its closest relatives seemed to drive the fermentation independent of the substrate. These results could help to improve today's resourcing concept by providing a separate treatment of the liquid and solid biowaste fraction. PMID:25652656

  1. Cathepsin K in treatment monitoring following intravenous zoledronic acid

    PubMed Central

    JAHN, OLIVER; WEX, THOMAS; KLOSE, SILKE; KROPF, SIEGFRIED; ADOLF, DANIELA; PIATEK, STEFAN

    2014-01-01

    Cathepsin K (CatK) is mainly expressed by osteoclasts and plays an important role in bone resorption. As CatK is expressed and secreted by osteoclasts during active bone resorption, it may be a useful and specific biochemical marker of osteoclastic activity. Therefore, CatK serum levels were studied for monitoring the treatment of females with postmenopausal osteoporosis by zoledronic acid. The serum CatK levels were determined in nine postmenopausal females before and after 3, 6 and 12 months of treatment. The levels were significantly reduced after 3 and 6 months (P<0.05), whereas they returned to baseline after 1 year. Taken together, the serum level of CatK may be suitable for monitoring anti-osteoporotic therapy in association with treatment response. PMID:25279169

  2. Emerging Technology Summary. ACID EXTRACTION TREATMENT SYSTEM FOR TREATMENT OF METAL CONTAMINATED SOILS

    EPA Science Inventory

    The Acid Extraction Treatment System (AETS) is intended to reduce the concentrations and/or teachability of heavy metals in contaminated soils so the soil can be returned to the site from which it originated. The objective of the project was to determine the effectiveness and com...

  3. Evaluation of water treatment sludge for ameliorating acid mine waste.

    PubMed

    Van Rensburg, L; Morgenthal, T L

    2003-01-01

    This study investigated the liming effect of water treatment sludge on acid mine spoils. The study was conducted with sludge from a water purification plant along the Vaal River catchments in South Africa. The optimum application rate for liming acid spoils and the speed and depth with which the sludge reacted with the mine waste were investigated. Chemical analysis indicated that the sludge is suitable as a liming agent because of its alkaline pH (8.08), high bicarbonate concentration (183.03 mg L(-1)), and low salinity (electrical conductivity = 76 mS m(-1)). The high cation exchange capacity of 15.47 cmol(c) kg(-1) and elevated nitrate concentration (73.16 mg L(-1)) also increase its value as an ameliorative material. The soluble concentrations for manganese, aluminum, lead, and selenium were high at a pH of 5 although only selenium (0.83 mg L(-1)) warranted some concern. According to experimental results, the application of 10 Mg ha(-1) of sludge to acid gold tailings increased the leach water pH from 4.5 to more than 7.5 and also increased the medium pH from 2.4 to 7.5. The addition of sludge further reduced the solubility of iron, manganese, copper, and zinc in the ameliorated gold tailings, but increased the electrical conductivity. The liming tempo was highest in the coal discard profile that had a coarse particle size distribution and took the longest to move through the gold tailings that had a fine particle size distribution. Results from this study indicate that the water treatment sludge investigated is suitable as a liming agent for rehabilitation of acid mine waste. PMID:14535306

  4. Preclinical Development of a Subcutaneous ALAS1 RNAi Therapeutic for Treatment of Hepatic Porphyrias Using Circulating RNA Quantification.

    PubMed

    Chan, Amy; Liebow, Abigail; Yasuda, Makiko; Gan, Lin; Racie, Tim; Maier, Martin; Kuchimanchi, Satya; Foster, Don; Milstein, Stuart; Charisse, Klaus; Sehgal, Alfica; Manoharan, Muthiah; Meyers, Rachel; Fitzgerald, Kevin; Simon, Amy; Desnick, Robert J; Querbes, William

    2015-01-01

    The acute hepatic porphyrias are caused by inherited enzymatic deficiencies in the heme biosynthesis pathway. Induction of the first enzyme 5-aminolevulinic acid synthase 1 (ALAS1) by triggers such as fasting or drug exposure can lead to accumulation of neurotoxic heme intermediates that cause disease symptoms. We have demonstrated that hepatic ALAS1 silencing using siRNA in a lipid nanoparticle effectively prevents and treats induced attacks in a mouse model of acute intermittent porphyria. Herein, we report the development of ALN-AS1, an investigational GalNAc-conjugated RNAi therapeutic targeting ALAS1. One challenge in advancing ALN-AS1 to patients is the inability to detect liver ALAS1 mRNA in the absence of liver biopsies. We here describe a less invasive circulating extracellular RNA detection assay to monitor RNAi drug activity in serum and urine. A striking correlation in ALAS1 mRNA was observed across liver, serum, and urine in both rodents and nonhuman primates (NHPs) following treatment with ALN-AS1. Moreover, in donor-matched human urine and serum, we demonstrate a notable correspondence in ALAS1 levels, minimal interday assay variability, low interpatient variability from serial sample collections, and the ability to distinguish between healthy volunteers and porphyria patients with induced ALAS1 levels. The collective data highlight the potential utility of this assay in the clinical development of ALN-AS1, and in broadening our understanding of acute hepatic porphyrias disease pathophysiology. PMID:26528940

  5. Preclinical Development of a Subcutaneous ALAS1 RNAi Therapeutic for Treatment of Hepatic Porphyrias Using Circulating RNA Quantification

    PubMed Central

    Chan, Amy; Liebow, Abigail; Yasuda, Makiko; Gan, Lin; Racie, Tim; Maier, Martin; Kuchimanchi, Satya; Foster, Don; Milstein, Stuart; Charisse, Klaus; Sehgal, Alfica; Manoharan, Muthiah; Meyers, Rachel; Fitzgerald, Kevin; Simon, Amy; Desnick, Robert J; Querbes, William

    2015-01-01

    The acute hepatic porphyrias are caused by inherited enzymatic deficiencies in the heme biosynthesis pathway. Induction of the first enzyme 5-aminolevulinic acid synthase 1 (ALAS1) by triggers such as fasting or drug exposure can lead to accumulation of neurotoxic heme intermediates that cause disease symptoms. We have demonstrated that hepatic ALAS1 silencing using siRNA in a lipid nanoparticle effectively prevents and treats induced attacks in a mouse model of acute intermittent porphyria. Herein, we report the development of ALN-AS1, an investigational GalNAc-conjugated RNAi therapeutic targeting ALAS1. One challenge in advancing ALN-AS1 to patients is the inability to detect liver ALAS1 mRNA in the absence of liver biopsies. We here describe a less invasive circulating extracellular RNA detection assay to monitor RNAi drug activity in serum and urine. A striking correlation in ALAS1 mRNA was observed across liver, serum, and urine in both rodents and nonhuman primates (NHPs) following treatment with ALN-AS1. Moreover, in donor-matched human urine and serum, we demonstrate a notable correspondence in ALAS1 levels, minimal interday assay variability, low interpatient variability from serial sample collections, and the ability to distinguish between healthy volunteers and porphyria patients with induced ALAS1 levels. The collective data highlight the potential utility of this assay in the clinical development of ALN-AS1, and in broadening our understanding of acute hepatic porphyrias disease pathophysiology. PMID:26528940

  6. [PREPARATIONS OF PAMIDRONOVIC ACID IN COMPLEX TREATMENT ON OSTEOGENESIS IMPERFECTA].

    PubMed

    Zyma, A M; Guk, Yu M; Magomedov, O M; Gayko, O G; Kincha-Polishchuk, T A

    2015-07-01

    Modern view of drug therapy in the complex treatment of orthopedic manifestations of osteogenesis imperfecta (OI) was submitted. Developed and tested system of drug correction of structural and functional state of bone tissue (BT) using drugs pamidronovic acid, depending on osteoporosis severity and type of disease. Such therapy is appropriate to apply both independently and in conjunction with surgery to correct deformations of long bones of the lower extremities. Effectiveness and feasibility of the proposed methods of drug therapy was proved, most patients resume features walking and support. PMID:26591224

  7. Treatment of vinasse from tequila production using polyglutamic acid.

    PubMed

    Carvajal-Zarrabal, Octavio; Nolasco-Hipólito, Cirilo; Barradas-Dermitz, Dulce Ma; Hayward-Jones, Patricia M; Aguilar-Uscanga, Ma Guadalupe; Bujang, Kopli

    2012-03-01

    Vinasse, the wastewater from ethanol distillation, is characterised by high levels of organic and inorganic matter, high exit process temperature (ca. 90°C) and low pH (3.0-4.5). In this study, the treatment of tequila vinasse was achieved by a flocculation-coagulation process using poly-γ-glutamic acid (PGA). Results showed that the use of PGA (250-300 ppm) combined with sodium hypochlorite and sand filtration managed to remove about 70% of the turbidity and reduced chemical oxygen demand (COD) by 79.5% with the extra benefit of colour removal. PGA showed its best flocculating activity at pH 2.5-3.5 and a temperature of 30-55°C. Such a treatment may be a solution for small tequila companies for which other solutions to deal with their vinasse may not be economically affordable. PMID:21600690

  8. Current issues regarding treatment of mitochondrial fatty acid oxidation disorders.

    PubMed

    Spiekerkoetter, Ute; Bastin, Jean; Gillingham, Melanie; Morris, Andrew; Wijburg, Frits; Wilcken, Bridget

    2010-10-01

    Treatment recommendations in mitochondrial fatty acid oxidation (FAO) defects are diverse. With implementation of newborn screening and identification of asymptomatic patients, it is necessary to define whom to treat and how strictly. We here discuss critical questions that are currently under debate. For some asymptomatic long-chain defects, long-chain fat restriction plays a minor role, and a normal diet may be introduced. For patients presenting only with myopathic symptoms, e.g., during exercise, treatment may be adapted to energy demand. As a consequence, patients with exercise-induced myopathy may be able to return to normal activity when provided with medium-chain triglycerides (MCT) prior to exercise. There is no need to limit participation in sports. Progression of retinopathy in disorders of the mitochondrial trifunctional protein complex is closely associated with hydroxyacylcarnitine accumulation. A strict low-fat diet with MCT supplementation is recommended to slow or prevent progression of chorioretinopathy. Additional docosahexanoic acid does not prevent the decline in retinal function but does promote nonspecific improvement in visual acuity and is recommended. There is no evidence that L-carnitine supplementation is beneficial. Thus, supplementation with L-carnitine in a newborn identified by screening with either a medium-chain or long-chain defect is not supported. With respect to the use of the odd-chain medium-chain triglyceride triheptanoin in myopathic phenotypes, randomized trials are needed to establish whether triheptanoin is more effective than even-chain MCT. With increasing pathophysiological knowledge, new treatment options have been identified and are being clinically evaluated. These include the use of bezafibrates in myopathic long-chain defects. PMID:20830526

  9. Topical tranexamic acid as a promising treatment for melasma

    PubMed Central

    Ebrahimi, Bahareh; Naeini, Farahnaz Fatemi

    2014-01-01

    Background: In recent times, tranexamic acid (TA) is claimed to have whitening effects especially for ultraviolet-induced hyperpigmentation including melasma. The aim of our study was to evaluate the efficacy and safety of topical solution of TA and compare it with combined solution of hydroquinone and dexamethasone as the gold standard treatment of melasma in Iranian women. Materials and Methods: This was a double-blind split-face trial of 12 weeks which was conducted in Isfahan, Iran. Fifty Iranian melasma patients applied topical solution of 3% TA on one side of the face, and topical solution of 3% hydroquinone + 0.01% dexamethasone on the other side two times a day. The Melasma Area and Severity Index (MASI) and the side effects were evaluated at baseline and every 4 weeks before and after photographs to be compared by a dermatologist were taken. The patient satisfaction was documented at week 12. Results: A repeated measurement analysis was used to evaluate the changes in the MASI score before and after treatments. A significant decreasing trend was observed in the MASI score of both groups with no significant difference between them during the study (P < 0.05). No differences were seen in patients’ and investigator's satisfaction of melasma improvement between two groups (P < 0.05). However, the side effects of hydroquinone + dexamethasone were significantly prominent compared with TA (P = 0.01). Conclusion: This study's results introduce the topical TA as an effective and safe medication for the treatment of melasma. PMID:25422661

  10. Aristolochic acid nephropathy: epidemiology, clinical presentation, and treatment.

    PubMed

    Luciano, Randy L; Perazella, Mark A

    2015-01-01

    Aristolochic acid (AA) is a compound extracted from the Aristolochia species of herbs. It has been used for centuries as a remedy for various illnesses and diseases. However, in the early 1990s in the setting of a weight loss herbal remedy, AA exposure was associated with a syndrome of kidney injury, termed aristolochic acid nephropathy (AAN). This entity is marked by elevated serum creatinine, significant anemia, and histopathologic changes demonstrating a hypocellular interstitial infiltrate with severe fibrosis. Progression towards end-stage renal disease (ESRD) is rapid, with most patients having chronic kidney disease for less than 2 years. In addition, AAN is associated with a 40-45 % prevalence of urothelial carcinomas. Treatment of AAN is limited to glucocorticoids that have been shown to delay progression in non-randomized trials. As most patients progress to ESRD, need for renal replacement therapy, as either dialysis or kidney transplant, usually ensues. However, given the high malignant potential, care must be taken to minimize future development of upper urinary tract cancers by performing prophylactic bilateral nephroureterectomies and aggressive cancer surveillance. PMID:25446374

  11. Maleic acid treatment of biologically detoxified corn stover liquor.

    PubMed

    Kim, Daehwan; Ximenes, Eduardo A; Nichols, Nancy N; Cao, Guangli; Frazer, Sarah E; Ladisch, Michael R

    2016-09-01

    Elimination of microbial and enzyme inhibitors from pretreated lignocellulose is critical for effective cellulose conversion and yeast fermentation of liquid hot water (LHW) pretreated corn stover. In this study, xylan oligomers were hydrolyzed using either maleic acid or hemicellulases, and other soluble inhibitors were eliminated by biological detoxification. Corn stover at 20% (w/v) solids was LHW pretreated LHW (severity factor: 4.3). The 20% solids (w/v) pretreated corn stover derived liquor was recovered and biologically detoxified using the fungus Coniochaeta ligniaria NRRL30616. After maleic acid treatment, and using 5 filter paper units of cellulase/g glucan (8.3mg protein/g glucan), 73% higher cellulose conversion from corn stover was obtained for biodetoxified samples compared to undetoxified samples. This corresponded to 87% cellulose to glucose conversion. Ethanol production by yeast of pretreated corn stover solids hydrolysate was 1.4 times higher than undetoxified samples, with a reduction of 3h in the fermentation lag phase. PMID:27262718

  12. Treatment of carpal tunnel syndrome with alpha-lipoic acid.

    PubMed

    Di Geronimo, G; Caccese, A Fonzone; Caruso, L; Soldati, A; Passaretti, U

    2009-01-01

    Carpal Tunnel Syndrome (CTS) is the most common peripheral mononeuropathy; its symptoms and functional limitations significantly penalize the daily activities and quality of life of many people. While surgery is reserved to most severe cases, the earlier stages of disease may be controlled by a pharmacological treatment aimed to "neuroprotection", i.e. to limiting and correcting the nerve damage. Our study was aimed to compare the efficacy of a fixed association of alpha-lipoic acid (ALA) 600 mg/die and gamma-linolenic acid (GLA) 360 mg/die, and a multivitamin B preparation (Vit B6 150 mg, Vit B1 100 mg, Vit B12 500 microg daily) for 90 days in 112 subjects with moderately severe CTS. Demographic, case-history and treatment efficacy data were collected; the Boston questionnaire was administered and the patients were evaluated by Hi-Ob scale and electro-myography. A significant reduction in both symptoms scores and functional impairment (Boston questionnaire) was observed in ALA/GLA group, while the multivitamin group experienced a slight improvement of symptoms and a deterioration of functional scores. Electromyography showed a statistically significant improvement with ALA/GLA, but not with the multivitamin product. The Hi-Ob scale showed significant efficacy of ALA/GLA in improving symptoms and functional impairment, while in the multivitamin group the improvement was significant, but less marked than in the ALA/GLA group. In conclusion, the fixed association of ALA and GLA proved to be a useful tool and may be proposed for controlling symptoms and improving the evolution of CTS, especially in the earlier stages of disease. PMID:19499849

  13. Solid Lipid Nanoparticles Loaded with Retinoic Acid and Lauric Acid as an Alternative for Topical Treatment of Acne Vulgaris.

    PubMed

    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. PMID:26328443

  14. Enhancement of cell viability after treatment with polyunsaturated fatty acids.

    PubMed

    Bartl, J; Walitza, S; Grünblatt, E

    2014-01-24

    Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent in children and adolescents and both environmental and genetic factors play major roles. Polyunsaturated fatty acids (PUFAs) are postulated to contribute to the development of the infant brain and an imbalance in these may increase the risk of ADHD. In recent clinical studies, supplementation with PUFAs improved symptoms of ADHD in some cases. Similarly, some beneficial effects were observed with PUFA treatment in neuronal cell cultures. Therefore, in this study, we hypothesized that a specific PUFA combination (available on the market as Equazen™ [Vifor Pharma, Switzerland]) along with iron, zinc, or vitamin B5 (vitB5) would produce an additive beneficial effect on the viability of rat pheochromocytoma-12 dopaminergic cells. The specific PUFA combination alone, as well as added to each of the three nutrients, was tested in a dose-response manner. The specific PUFAs significantly improved cell viability, starting at very low doses (100pM) from 60h up to 90h; while the combined treatment with vitB5 and minerals did not provide additional benefit. Our results confirmed the beneficial effect of the specific PUFAs on neuronal cell viability; although supplementation with minerals and vitB5 did not enhance this effect. PMID:24269370

  15. Towards energy positive wastewater treatment by sludge treatment using free nitrous acid.

    PubMed

    Wang, Qilin; Hao, Xiaodi; Yuan, Zhiguo

    2016-02-01

    Free nitrous acid (FNA i.e. HNO2) was revealed to be effective in enhancing biodegradability of secondary sludge. Also, nitrite-oxidizing bacteria were found to be more susceptible to FNA than ammonium-oxidizing bacteria. Based on these findings, a novel FNA-based sludge treatment technology is proposed to enhance energy recovery from wastewater/sludge. Energy analysis indicated that the FNA-based technology would make wastewater treatment become an energy generating process (yielding energy at 4 kWh/PE/y; kWh/PE/y: kilowatt hours per population equivalent per year), rather than being a large energy consumer that it is today (consuming energy at 24 kWh/PE/y). Importantly, FNA required for the sludge treatment could be produced as a by-product of wastewater treatment. This proposed FNA-based technology is economically and environmentally attractive, and can be easily implemented in any wastewater treatment plants. It only involves the installation of a simple sludge mixing tank. This article presents the concept of the FNA-based technology. PMID:26539712

  16. A Sustainable Approach for Acid Rock Drainage Treatment using Clinoptilolite

    NASA Astrophysics Data System (ADS)

    Li, L. Y.; Xu, W.; Grace, J. R.

    2009-04-01

    Problems related to acid rock drainage (ARD) occur along many highways of British Columbia. The ARD problem at Pennask Creek along Highway 97C in the Thompson-Okanagan region is an ideal site for pilot study to investigate a possible remediation solution. The highway was opened in 1991. An ARD problem was identified in 1997. Both sides of Highway 97C are producing acidified runoff from both cut rock surface and a fractured ditch. This runoff eventually enters Pennask Creek, the largest spawning source of rainbow trout in British Columbia. The current remediation technique using limestone for ARD treatment appears to be unnecessarily expensive, to generate additional solid waste and to not be optimally effective. A soil mineral natural zeolite - clinoptilolite - which is inexpensive and locally available, has a high metal adsorption capacity and a significant buffering capacity. Moreover, the clinoptilolite materials could be back-flushed and reused on site. An earlier batch adsorption study from our laboratory demonstrated that clinoptilolite has a high adsorption capacity for Cu, Zn, Al, with adsorption concentrations 131, 158 and 215 mg/kg clinoptilolite, respectively, from ARD of pH 3.3. Removal of metals from the loaded clinoptilolite by back-flushing was found to depend on the pH, with an optimum pH range for extraction of 2.5 to 4.0 for a contact time of one hour. The rank of desorption effectiveness was EDTA > NaCl > NaNO3 > NaOAC > NaHCO3 > Na2CO3 > NaOH > Ca(OH)2. A novel process involving cyclic adsorption on clinoptilolite followed by regeneration of the sorbent by desorption is examined for the removal of heavy metals from acid rock drainage. Experimental results show that the adsorption of zinc and copper depends on the pH and on external mass transfer. Desorption is assisted by adding NaCl to the water. A slurry bubble column was able to significantly reduce the time required for both adsorption and desorption in batch tests. XRD analysis indicated

  17. Ozonolysis mechanism of lignin model compounds and microbial treatment of organic acids produced.

    PubMed

    Nakamura, Y; Daidai, M; Kobayashi, F

    2004-01-01

    Treatment methods comprising ozonolysis and microbial treatment of lignin discharged from the pulp manufacture industries were investigated by using a sulfite pulp wastewater and a lignin model compound, i.e. sodium lignosulfonate. Dynamic behaviors for the formations of intermediate derivatives such as muconic acid, maleic acid, and oxalic acid produced from the ozonolysis of sulfite pulp wastewater were observed from data of UV absorption at 280 nm by a spectrophotometer and at 210 nm by high performance liquid chromatography. The microorganisms that were isolated by the enrichment culture method were used to degrade the organic acids such as oxalic acid and acetic acid. Time courses of biological degradation of these organic acids indicated diauxic growth, which was found in a culture with mixed substrates. In the treatment of sodium lignosulfonate, the ozonolysis and microbial treatment using activated sludge converted sodium lignosulfonate into carbon dioxide and water almost completely. PMID:15461411

  18. Combination ALA-PDT and Ablative Fractional Er:YAG Laser (2,940 nm) on the Treatment of Severe Acne

    PubMed Central

    Yin, Rui; Lin, Lin; Xiao, Yan; Hao, Fei; Hamblin, Michael R.

    2014-01-01

    Background Scarring is a very common complication of severe acne and is difficult to treat by conventional methods. 5-Aminolevulinic acid (ALA) photodynamic therapy (PDT) is a novel treatment for improving acne lesions. Fractional laser resurfacing is a promising treatment for scar treatment because of its unique ability to stimulate the wound healing response and its depth of penetration. Objective To evaluate the efficacy of combination therapies of ALA-PDT and ablative fractional Er:YAG laser (2,940 nm) for scarring lesions in severe acne patients. Methods A prospective, single-arm, pilot study. Forty subjects with severe acne were treated with 15% ALA-PDT for four times at 10-day intervals. They then received ablative fractional Er:YAG laser treatment five times at 4-week intervals. Three independent investigators evaluated subject outcomes at 1, 3, 6, and 12 months post-treatment (primary outcome); patients also provided self-assessments of improvement (secondary outcome). Results Significant reductions in acne score (P<0.01) were obtained at follow-up visits after 1, 3, 6, and 12 months. After 6 month, the lesions showed overall improvement in all of subjects (good to excellent in acne inflammatory lesions), 80% overall improvement in acne scars. After 12 months, most of subjects had improved hypertrophic/atrophic scars (good to excellent in 85%) and no one had recurrent acne inflammatory lesions. Patient self-evaluation also revealed good to excellent improvements (on average) in acne lesions and scarring, with significant improvements in self-esteem after 6 months post-treatment. Conclusions PDT can control the inflammation and improve the severity of acne lesions. Fractional resurfacing is a promising new treatment modality for scars by stimulating wound healing and remodeling. The combination therapy is a promising option for severe acne to prevent and improve car formation. PMID:24391075

  19. Use of Optical Fiber Imported Intra-Tissue Photodynamic Therapy for Treatment of Moderate to Severe Acne Vulgaris

    PubMed Central

    Wang, Qian; Yuan, Dan; Liu, Wei; Chen, Jin; Lin, Xinyu; Cheng, Shi; Li, Fumin; Duan, Xiling

    2016-01-01

    Background To treat moderate to severe acne vulgaris, we developed an optical fiber imported intra-tissue photodynamic therapy: the optical fiber irradiation 5-aminolevulinic acid photodynamic therapy (OFI-ALA-PDT). The aim of this study was to compare the treatment effect and tolerability of OFI-ALA-PDT versus traditional ALA-PDT in the treatment of moderate to severe acne vulgaris. Material/Methods 60 patients with facial acne enrolled into this study were randomly divided into an OFI-ALA-PDT group and a traditional ALA-PDT group, with 30 patients in each group. The difference between these 2 groups was the red light irradiation methods used. In the OFI-ALA-PDT group we used intra-tissue irradiation (import the red light directly into the target lesion with optical fiber) for 5 min, while the traditional ALA-PDT group received whole-face irradiation for 20 min. All patients received 1 irradiation every 7 to 10 days for a total of 6 irradiations. Treatment effects and adverse reactions were recorded after the 4th and 6th irradiation, and at 4, 8, 16 weeks after the entire treatment. Results After the 4th irradiation, significantly different effective rates were observed in these groups (90.0% for the OFI-ALA-PDT group and 66.7% for the control group). However, no significant difference in effective rate was recorded in the later observations. There were 182 adverse reactions in the OFI-ALA-PDT group and 497 in the control group, which showed a significant difference (P<0.05). Conclusions OFI-ALA-PDT showed improved treatment effective rate in the early stage of irradiation, and it had fewer adverse reactions. PMID:26839152

  20. Delta 4-3-oxosteroid 5 beta-reductase deficiency: failure of ursodeoxycholic acid treatment and response to chenodeoxycholic acid plus cholic acid.

    PubMed Central

    Clayton, P T; Mills, K A; Johnson, A W; Barabino, A; Marazzi, M G

    1996-01-01

    BACKGROUND--In some infants with liver disease, 3-oxo-delta 4 bile acids are the major bile acids in urine, a phenomenon attributed to reduced activity of the delta 4-3-oxosteroid 5 beta-reductase required for synthesis of chenodeoxycholic acid and cholic acid. These patients form a heterogeneous group. Many have a known cause of hepatic dysfunction and plasma concentrations of chenodeoxycholic acid and cholic acid that are actually greater than those of the 3-oxo-delta 4 bile acids. It is unlikely that these patients have a primary genetic deficiency of the 5 beta-reductase enzyme. AIMS--To document the bile acid profile, clinical phenotype, and response to treatment of an infant with cholestasis, increased plasma concentrations of 3-oxo-delta 4 bile acids, low plasma concentrations of chenodeoxycholic acid and cholic acid, and no other identifiable cause of liver disease. PATIENTS--This infant was compared with normal infants and infants with cholestasis of known cause. METHODS--Analysis of bile acids by liquid secondary ionisation mass spectrometry and gas chromatography-mass spectrometry. RESULTS--The plasma bile acid profile of the patient was unique. She had chronic cholestatic liver disease associated with malabsorption of vitamins D and E and a normal gamma-glutamyltranspeptidase when the transaminases were increased. The liver disease failed to improve with ursodeoxycholic acid but responded to a combination of chenodeoxycholic acid and cholic acid. CONCLUSION--Treatment of primary 5 beta-reductase deficiency requires the use of bile acids that inhibit cholesterol 7 alpha-hydroxylase. PMID:8707100

  1. Photochemical internalization for the treatment of malignant gliomas

    NASA Astrophysics Data System (ADS)

    Madsen, Steen J.; Kharkhuu, Khishigzaya; Berg, Kristian; Hirschberg, Henry

    2007-02-01

    Photochemical internalization (PCI) is a technique to improve the utilization of macromolecules (e.g. chemotherapeutic agents) in cancer therapy in a site-specific manner. The concept is based on the use of specially designed photosensitizers which localize preferentially in the membranes of endocytic vesicles. Upon exposure to light the photosensitizers induce the formation of reactive oxygen species such as singlet molecular oxygen. The photooxidation of the endocytic membranes leads to the release of the contents of the vesicles into the cytosol. In this way, macromolecules encapsulated by the vesicles will reach the cytosol and exert their biological activity instead of being degraded by lysosomal hydrolases. The utility of PCI for the treatment of malignant gliomas was investigated in vitro using an F98 rat glioma cell line. The cytotoxicity of 5-aminolevulinic acid (ALA) based PCI of bleomycin was compared to: (1) ALA-PDT, and (2) bleomycin. In all cases, monolayers were incubated in ALA, bleomycin, or ALA + bleomycin for 4 hours and were subsequently exposed to 635 nm light. Toxicity was evaluated using colony formation assays. F98 rat glioma cells in monolayer were found to be susceptible to the effects of both ALA-PDT and bleomycin. ALA-PDT was found to be particularly effective when light was delivered at a low irradiance of 5 mW cm -2. In this case, a radiant exposure of 20 J cm -2 resulted in only 4% survival. Bleomycin was found to be toxic at relatively low concentrations, incubation of F98 cells in 10 μg ml -1 for 4 hours resulted in 1% survival. The PCI effect was found to be negligible for the parameters investigated in the F98 cell line suggesting that: (1) the incubation time was sub-optimal and/or (2) ALA was inappropriate for this application.

  2. Treatment of rheumatoid arthritis with prostaglandin E1 precursors cis-linoleic acid and gamma-linolenic acid.

    PubMed

    Hansen, T M; Lerche, A; Kassis, V; Lorenzen, I; Søndergaard, J

    1983-01-01

    20 patients with active rheumatoid arthritis were treated for 12 weeks with the prostaglandin E1 precursors cis-linoleic acid and gamma-linolenic acid in the form of primrose evening oil (Efamol) and the co-factors zinc, ascorbic acid, niacin, and pyridoxin (Efavit). There was a slight fall in skin reactivity to UV light during the treatment, but no effect on plasma or urine concentrations of PGE1, cAMP or cGMP. There was no effect of the treatment on ESR, P-fibrinogen, number of tender joints, number of swollen joints, the duration of morning stiffness, or on the patient's estimation of pain. PMID:6304871

  3. Effects of acid treatment duration and sulfuric acid molarity on purification of multi-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Mortazavi, Seyedeh; Novinrooz, Abdul; Reyhani, Ali; Mirershadi, Soghra

    2010-12-01

    Multi-walled carbon nanotubes were synthesized using a Fe-Ni bimetallic catalyst supported by MgO using thermal chemical vapor deposition. Purification processes to remove unwanted carbon structures and other metallic impurities were carried out by boiling in sulfuric acid solution. Various analytical techniques such as TGA/DSC, Raman spectroscopy, SEM, HRTEM and EDAX were employed to investigate the morphology, graphitization and quality of the carbon nanotubes. The obtained results reveal the molarity of sulfuric acid and immersed time of the carbon nanotubes in the acid solution is very effective at purifying multi-walled carbon nanotubes. It was also found that 5 M concentration of boiling sulfuric acid for a 3 h treatment duration led to the highest removal of the impurities with the least destructive effect. Moreover, it was observed that acid treatment results in decreasing of CNTs' diameter.

  4. Effects of acid treatment duration and sulfuric acid molarity on purification of multi-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Mortazavi, Seyedeh Z.; Novinrooz, Abdul J.; Reyhani, Ali; Mirershadi, Soghra

    2010-12-01

    Multi-walled carbon nanotubes were synthesized using a Fe-Ni bimetallic catalyst supported by MgO using thermal chemical vapor deposition. Purification processes to remove unwanted carbon structures and other metallic impurities were carried out by boiling in sulfuric acid solution. Various analytical techniques such as TGA/DSC, Raman spectroscopy, SEM, HRTEM and EDAX were employed to investigate the morphology, graphitization and quality of the carbon nanotubes. The obtained results reveal the molarity of sulfuric acid and immersed time of the carbon nanotubes in the acid solution is very effective at purifying multi-walled carbon nanotubes. It was also found that 5 M concentration of boiling sulfuric acid for a 3 h treatment duration led to the highest removal of the impurities with the least destructive effect. Moreover, it was observed that acid treatment results in decreasing of CNTs’ diameter.

  5. Bile acid conjugation in early stage cholestatic liver disease before and during treatment with ursodeoxycholic acid.

    PubMed

    Fracchia, M; Setchell, K D; Crosignani, A; Podda, M; O'Connell, N; Ferraris, R; Hofmann, A F; Galatola, G

    1996-04-30

    The efficiency of bile acid conjugation before and during therapy with 600 mg/day of ursodeoxycholic acid was measured in seven adult patients with early chronic cholestatic liver disease (6 with primary biliary cirrhosis; 1 with primary sclerosing cholangitis). Duodenal bile samples were obtained by aspiration and the proportion of unconjugated bile acids was determined using lipophilic anion exchange chromatography to separate bile acid classes, followed by analysis of individual bile acids by gas chromatography-mass spectrometry. The proportion of conjugated bile acids was determined by high-performance liquid chromatography. Use of a (99m)Tc-HIDA recovery marker permitted the absolute mass of unconjugated bile acids in the gallbladder to be calculated. Unconjugated bile acids comprised 0.4% of total biliary bile acids before and 0.2% during ursodeoxycholic acid therapy, indicating highly efficient conjugation of bile acids. During therapy, percentage unconjugated ursodeoxycholic acid significantly increased from (mean +/- S.D.) 13 +/- 13% to 54 +/- 12%; P < 0.002. When the unconjugated and conjugated fractions of bile acids were compared, there was an enrichment in unconjugated fraction for cholic acid and ursodeoxycholic acid and a depletion for chenodeoxycholic acid both in basal condition and during ursodeoxycholic acid therapy, suggesting that hydrophilic bile acids were conjugated less efficiently. During therapy, the conjugation efficiency significantly increased for cholic acid and ursodeoxycholic acid. The pretreatment mass of total unconjugated bile acids in the gallbladder was (mean +/- S.D.) 4.4 +/- 3.2 mumol, and was not significantly changed by ursodeoxycholic acid therapy (6.2 +/- 3.5 mumol). However, ursodeoxycholic acid therapy caused a significant increase in the mass of unconjugated ursodeoxycholic acid. It is concluded that endogenous bile acids and exogenous ursodeoxycholic acid when given at the usual dose are efficiently conjugated in

  6. Hydrothermal-acid treatment for effectual extraction of eicosapentaenoic acid (EPA)-abundant lipids from Nannochloropsis salina.

    PubMed

    Lee, Ilgyu; Han, Jong-In

    2015-09-01

    Hydrothermal acid treatment, was adopted to extract eicosapentaenoic acid (EPA) from wet biomass of Nannochloropsis salina. It was found that sulfuric acid-based treatment increased EPA yield from 11.8 to 58.1 mg/g cell in a way that was nearly proportional to its concentration. Nitric acid exhibited the same pattern at low concentrations, but unlike sulfuric acid its effectiveness unexpectedly dropped from 0.5% to 2.0%. The optimal and minimal conditions for hydrothermal acid pretreatment were determined using a statistical approach; its maximum EPA yield (predicted: 43.69 mg/g cell; experimental: 43.93 mg/g cell) was established at a condition of 1.27% of sulfuric acid, 113.34 °C of temperature, and 36.71 min of reaction time. Our work demonstrated that the acid-catalyzed cell disruption, accompanied by heat, can be one potentially promising option for ω-3 fatty acids extraction. PMID:25966023

  7. Efficacy of 15% Trichloroacetic Acid and 50% Glycolic Acid Peel in the Treatment of Frictional Melanosis: A Comparative Study

    PubMed Central

    Sacchidanand, S; Shetty, Ashvith B; Leelavathy, B

    2015-01-01

    Background: Frictional dermal melanosis is aesthetically displeasing. Various modalities ranging from depigmenting agents to lasers have been tried but it continues to be a difficult problem to treat. Objective: To study and compare the efficacy of 15% trichloroacetic acid (TCA) and 50% glycolic acid in the treatment of frictional melanosis of the forearm. Materials and Methods: 40 patients of frictional melanosis of the forearm were included in the study. Patients were randomly divided into two equal groups A and B. Pre-peel priming was carried out with 12% glycolic acid and sunscreen for 2 weeks. Group A was treated with trichloroacetic acid (TCA-15%) peel and Group B with glycolic acid (GA-50%) peel. Four peels were done one every 15 days. Clinical photographs were taken to assess the response. Response to therapy was evaluated by both objective and subjective methods. The patients were followed up for 3 months after the last peel to note any relapse. Results: Both TCA and glycolic acid peels were effective in frictional melanosis. TCA showed better response compared to glycolic acid at the end of the treatment, both by subjective and objective methods. However, this difference was not statistically significant (P > 0.05). No permanent side effects were seen in any of the treated patients and the improvement was sustained without any relapse at 3 months. Conclusion: Chemical peeling with both tricholoroacetic acid (15%) and glycolic acid (50%) is safe and effective for the treatment of frictional dermal melanosis. Tricholoroacetic acid was found to be marginally superior to glycolic acid. PMID:25949021

  8. Case Report: Valproic Acid and Risperidone Treatment Leading to Development of Hyperammonemia and Mania

    ERIC Educational Resources Information Center

    Carlson, Teri; Reynolds, Charles A.; Caplan, Rochelle

    2007-01-01

    This case report describes two children who developed hyperammonemia together with frank manic behavior during treatment with a combination of valproic acid and risperidone. One child had been maintained on valproic acid for years and risperidone was added. In the second case, valproic acid was introduced to a child who had been treated with…

  9. Treatment and prevention systems for acid mine drainage and halogenated contaminants

    SciTech Connect

    Jin, Song; Fallgren, Paul H.; Morris, Jeffrey M.

    2012-01-31

    Embodiments include treatments for acid mine drainage generation sources (10 perhaps by injection of at least one substrate (11) and biologically constructing a protective biofilm (13) on acid mine drainage generation source materials (14). Further embodiments include treatments for degradation of contaminated water environments (17) with substrates such as returned milk and the like.

  10. SU-E-T-381: Radio-Dynamic Therapy (RDT) for the Treatment of Late-Stage Cancers

    SciTech Connect

    Ma, C; Chen, L; Price, R; Zhang, Q; Zeng, J; Xu, K; Sun, Q

    2014-06-01

    Purpose: Photo-dynamic therapy (PDT) is an effective treatment modality because of the preferential absorption of photosensitizing agent in tumor cells than in surrounding normal tissues. A limitation of PDT for cancer therapy is the finite penetration of laser light to activate the targeting agent in deep-seated tumors. Radio-dynamic therapy (RDT) is designed to overcome this problem by the combination of high-energy (up to 45MV) photon beams and photo/radio-sensitizers. This work investigates the feasibility of PDT for late-stage cancer patients who are no longer respond to conventional therapies available. Methods: The high-energy photon beams are generated using a LA45 RaceTrack Microtron (Top Grade Medical, Beijing, China). The targeting agent investigated is 5- aminolevulinic acid (5-ALA). Both in vitro cell lines and in vivo animal models have been used to investigate the mechanisms of RDT and its therapeutic effects and normal tissue toxicities. Oral 5-ALA (30-60 mg/kg) was administered 4-6 hours before the radiation treatment and the total radiation dose varied between 0.1-4.0Gy in 1-4 fractions. Clinical trials are initiated in China for late-stage cancer patients targeting both primary tumors utilizing localized therapies such as 3DCRT/IMRT and metastases using TBI. Results: There is clear correlation between the cell death and the 5-ALA concentration/radiation dose. The therapeutic effect of RDT is demonstrated using an animal model where the volume of parotid tumors for the RT only group continued to grow after 3Gy irradiation while the RDT group showed a complete response with the same radiation dose. The preliminary clinical results showed encouraging clinical outcome. Conclusion: RDT is a novel treatment technique that may be developed into an effective cancer treatment modality. Further studies on the mechanisms of RDT and its potential clinical applications are warranted.

  11. Preclinical in vitro and in vivo studies to examine the potential use of photodynamic therapy in the treatment of osteomyelitis

    NASA Astrophysics Data System (ADS)

    Bisland, Stuart K.; Chien, Claudia; Wilson, Brian C.; Burch, Shane

    2005-04-01

    Osteomyelitis can lead to severe morbidity and even death resulting from an acute or chronic inflammation of the bone and contiguous structures due to fungal or bacterial infection. Incidence approximates 1 in 1,000 neonates and 1 in 5,000 children in the United States annually and increases up to 0.36% and 16% in adults with diabetes or sickle cell anaemia, respectively. Current regiments of treatment include antibiotics and/or surgery. However, the increasing number of antibiotic resistant pathogens suggests that alternate strategies are required. We are investigating photodynamic therapy (PDT) as one such alternate treatment for osteomyelitis using a bioluminescent strain of biofilm-producing staphylococcus aureus (SA) grown onto kirschner wires (K-wire). SA-coated K-wires were exposed to methylene blue (MB) or 5-aminolevulinic acid (ALA)-mediated PDT either in vitro or following implant into the tibial medullary cavity of Sprague-Dawley rats. The progression of SA biofilm was monitored non-invasively using bioluminescence and expressed as a percentage of the signal for each sample immediately prior to treatment. SA infections were subject to PDT 10 days post inoculation. Treatment comprised administration of ALA (300 mg/Kg) intraperitoneally followed 4 hr later by light (635 +/- 10 nm; 38 or 75 J/cm2) delivered transcutaneously via an optical fiber placed onto the tibia. In vitro, MB and ALA displayed similar cell kill with >= 4log10 cell kill. In vivo, ALA-mediated PDT inhibited biofilm implants in bone. These results confirm that MB or ALA-mediated PDT have potential to treat SA cultures grown in vitro or in vivo using an animal model of osteomyelitis.

  12. Ascorbic acid: Chemistry, biology and the treatment of cancer☆

    PubMed Central

    Du, Juan; Cullen, Joseph J.; Buettner, Garry R.

    2013-01-01

    Since the discovery of vitamin C, the number of its known biological functions is continually expanding. Both the names ascorbic acid and vitamin C reflect its antiscorbutic properties due to its role in the synthesis of collagen in connective tissues. Ascorbate acts as an electron-donor keeping iron in the ferrous state thereby maintaining the full activity of collagen hydroxylases; parallel reactions with a variety of dioxygenases affect the expression of a wide array of genes, for example via the HIF system, as well as via the epigenetic landscape of cells and tissues. In fact, all known physiological and biochemical functions of ascorbate are due to its action as an electron donor. The ability to donate one or two electrons makes AscH− an excellent reducing agent and antioxidant. Ascorbate readily undergoes pH-dependent autoxidation producing hydrogen peroxide (H2O2). In the presence of catalytic metals this oxidation is accelerated. In this review, we show that the chemical and biochemical nature of ascorbate contribute to its antioxidant as well as its prooxidant properties. Recent pharmacokinetic data indicate that intravenous (i.v.) administration of ascorbate bypasses the tight control of the gut producing highly elevated plasma levels; ascorbate at very high levels can act as prodrug to deliver a significant flux of H2O2 to tumors. This new knowledge has rekindled interest and spurred new research into the clinical potential of pharmacological ascorbate. Knowledge and understanding of the mechanisms of action of pharmacological ascorbate bring a rationale to its use to treat disease especially the use of i.v. delivery of pharmacological ascorbate as an adjuvant in the treatment of cancer. PMID:22728050

  13. Plasma-chemical waste treatment of acid gases

    SciTech Connect

    Harkness, J.B.L.; Doctor, R.D.; Daniels, E.J.

    1993-09-01

    The research to date has shown that a H{sub 2}S waste-treatment process based on plasma-chemical dissociation technology is compatible with refinery and high-carbon-oxide acid-gas streams. The minor amounts of impurities produced in the plasma-chemical reactor should be treatable by an internal catalytic reduction step. Furthermore, the plasma-chemical technology appears to be more efficient and more economical than the current technology. The principal key to achieving high conversions with relatively low energies of dissociation is the concept of the high-velocity, cyclonic-flow pattern in the plasma reaction zone coupled with the recycling of unconverted hydrogen sulfide. Future work will include testing the effects of components that might be carried over to the plasma reactor by ``upset`` conditions in the amine purification system of a plant and testing the plasma-chemical process on other industrial wastes streams that contain potentially valuable chemical reagents. The strategy for the commercialization of this technology is to form a Cooperative Research and Development Agreement with the Institute of Hydrogen Energy and Plasma Technology of the Russian Scientific Center/Kurchatov Institute and with an American start-up company to develop an ``American`` version of the process and to build a commercial-scale demonstration unit in the United States. The timetable proposed would involve building a ``field test`` facility which would test the plasma-chemical reactor and sulfur recovery unit operations on an industrial hydrogen sulfide waste s at a scale large enough to obtain the energy and material balance data required for a final analysis of the commercial potential of this technology. The field test would then be followed by construction of a commercial demonstration unit in two to three years. The commercial demonstration unit would be a fully integrated plant consisting of one commercial-scale module.

  14. Preferential Treatment: Interaction Between Amino Acids and Minerals

    NASA Astrophysics Data System (ADS)

    Crapster-Pregont, E. J.; Cleaves, H. J.; Hazen, R. M.

    2008-12-01

    Amino acids are the building blocks of proteins and are important for some models of the origin of life. Polymerization of amino acids from dilute solution is unlikely without a scaffold or catalyst. The surfaces of early Earth minerals are the most likely candidates for this role. The surface adsorption behavior of 12 amino acids (L-alanine, L-serine, L-aspartic acid, L-proline, L- phenylalanine, L-valine, L-arginine, d-amino valeric acid, glycine, L-lysine, L-isoleucine, and B-alanine) on 21 minerals (quartz, calcite, enstatite, illite, olivine, pyrrhotite, pyrite, alkali basalt, albite, analcime, chlorite, barite, hydroxyl apatite, hematite, magnetite, aluminum hydroxide, kaolin, silica gel, corundum, rutile, and montmorillonite) was determined via batch adsorption experiments. Absorption was determined for concentrations between 10-4M and 10-6M in the presence of 0.1M NaCl, and between pH values of 3 and 9 at 25 degrees C. The equilibrated solutions were centrifuged, filtered, derivatized using a fluorescent amino group tag (dansyl-chloride) and analyzed by HPLC. Adsorption was standardized using BET surface area measurements for each mineral to give the number of mols of each amino acid adsorbed per square meter for each mineral. The results indicate an enormous difference in the adsorption of amino acids between minerals, along with major differences in the adsorption of individual amino acids on the same mineral surface. There is also a change in the absorbance of amino acids as the pH changes. Many previous studies of amino acid concentration and catalysis by minerals have used clay minerals because of their high surface areas, however, this data suggests that the surfaces of minerals such as calcite, quartz and pyrite have even higher affinities for amino acids. The results suggest mineral surfaces that could be optimal locations for the polymerization of molecules linked to the origin of life.

  15. Treatment of Irradiated Mice with High-Dose Ascorbic Acid Reduced Lethality

    PubMed Central

    Sato, Tomohito; Kinoshita, Manabu; Yamamoto, Tetsuo; Ito, Masataka; Nishida, Takafumi; Takeuchi, Masaru; Saitoh, Daizoh; Seki, Shuhji; Mukai, Yasuo

    2015-01-01

    Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI) followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg) up to 24 h (1, 6, 12, or 24 h) after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total) also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure. PMID:25651298

  16. PASSIVE TREATMENT OF ACID ROCK DRAINAGE FROM A SUBSURFACE MINE

    EPA Science Inventory

    Acidic, metal-contaminated drainages are a critical problem facing many areas of the world. Acid rock drainage results when metal sulfide minerals, particularly pyrite, are oxidized by exposure to oxygen and water. The deleterious effects of these drainages on receiving streams a...

  17. Tolerability and Efficacy of Retinoic Acid Given after Full-face Peel Treatment of Photodamaged Skin

    PubMed Central

    Hu, Judy Y.; Biron, Julie A.; Yatskayer, Margarita; Dahl, Amanda; Oresajo, Christian

    2011-01-01

    Objective: All-trans retinoic acid is a well-established topical treatment of photodamaged skin. This study assessed the tolerance and efficacy of all-trans retinoic acid after full-face treatment with a chemical peel. Design: This was a split-face, randomized study. One side of each face was treated with peel and the other side with peel and all-trans retinoic acid (3%). Four treatments were given during the 10-week study period. Setting: Physician office. Participants: Fifteen female subjects 39 to 55 years of age. Measurements: Results were evaluated at Baseline; Weeks 4, 7, and 10; and at a 13-week follow-up visit by dermal grading of visual symptoms of irritation, subjective experiences of irritation, clinical grading of skin condition, and self-assessment questionnaires. Results: Both peel and peel plus all-trans retinoic acid treatments achieved significant improvement in fine lines, radiance, roughness, skin tone clarity, skin tone evenness, and hyperpigmentation appearance. Improvement in wrinkles and firmness was not observed in the peel plus all-trans retinoic acid arm, while pore appearance failed to improve in either treatment arm. Improvement in overall facial appearance was greater in the peel alone arm. Peel alone and the addition of all-trans retinoic acid did not cause dryness, edema, or peeling, and the frequency of peel-induced erythema did not increase with the addition of all-trans retinoic acid. Subject-perceived improvements with the peel treatment did not differ significantly from subject-perceived improvements of the peel plus all-trans retinoic acid treatment. Adverse events requiring intervention or discontinuing treatment were not observed in either treatment arm. Conclusion: The addition of all-trans retinoic acid after peel treatment does not significantly enhance peel-induced improvement in photoaging parameters, peel-induced adverse effects, and subject-perceived improvements. PMID:22010055

  18. Effects of Acid Treatment on Dental Zirconia: An In Vitro Study

    PubMed Central

    Xie, Haifeng; Shen, Shuping; Qian, Mengke; Zhang, Feimin; Chen, Chen; Tay, Franklin R.

    2015-01-01

    The aim of this study was to evaluate the effects of hydrofluoric (HF) acid, acetic acid, and citric acid treatments on the physical properties and structure of yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) at ambient temperature. In total, 110 bar-shaped zirconia specimens were randomly assigned to 11 groups. The specimens in the control group (C) received no surface treatment, while those in the Cage group were hydrothermally aged at 134°C and 0.2 MPa for 20 h. Ten specimens each were immersed at ambient temperature in 5% and 40% HF acid for 2 h (40HF0), 1 day (5HF1, 40HF1), and 5 days (5HF5, 40HF5), while 10 each were immersed at ambient temperature in 10% acetic acid and 20% citric acid for 7 (AC7, CI7) and 14 days (AC14, CI14). X-ray diffraction (XRD) was used to quantitatively estimate the monoclinic phase. Furthermore, flexural strength, surface roughness, and surface Vickers hardness were measured after treatment. Scanning electron microscopy (SEM) was used to characterize the surface morphology. The Cage group specimens exhibited an increased monoclinic phase and flexural strength. Furthermore, 40% HF acid immersion decreased the flexural strength and surface hardness and deteriorated the surface finish, while 5% HF acid immersion only decreased the surface hardness. All the HF acid-immersed specimens showed an etched surface texture on SEM observations, while the other groups did not. These findings suggest that the treatment of Y-TZP with 40% HF acid at ambient temperature causes potential damage, while treatment with 5% HF acid, acetic acid, and citric acid is safe. PMID:26301413

  19. Pre-clinical in vitro and in vivo studies to examine the potential use of photodynamic therapy in the treatment of osteomyelitis.

    PubMed

    Bisland, Stuart K; Chien, Claudia; Wilson, Brian C; Burch, Shane

    2006-01-01

    Osteomyelitis can lead to severe morbidity and even death resulting from an acute or chronic inflammation of the bone and contiguous structures due to fungal or bacterial infection. Incidence approximates 1 in 1000 neonates and 1 in 5000 children in the United States annually and increases up to 0.36% and 16% in adults with diabetes or sickle cell anaemia, respectively. Current regimens of treatment include antibiotics and/or surgery. However, the increasing number of antibiotic resistant pathogens suggests that alternate strategies are required. We are investigating photodynamic therapy (PDT) as one such alternate treatment for osteomyelitis using a bioluminescent strain of biofilm-producing staphylococcus aureus (S. aureus) grown onto kirschner wires (K-wire). S. aureus-coated K-wires were exposed to methylene blue (MB) or 5-aminolevulinic acid (ALA)-mediated PDT either in vitro or following implant into the tibial medullary cavity of Sprague-Dawley rats. The progression of S. aureus biofilm was monitored non-invasively using bioluminescence and expressed as a percentage of the signal for each sample immediately prior to treatment. S. aureus infections were subject to PDT 10 days post inoculation. Treatment comprised administration of ALA (300 mg kg(-1)) intraperitoneally followed 4 h later by light (635 +/- 10 nm; 75 J cm(-2)) delivered transcutaneously via an optical fiber placed onto the tibia and resulted in significant delay in bacterial growth. In vitro, MB and ALA displayed similar cell kill with > or =4 log(10) cell kill. In vivo, ALA-mediated PDT inhibited biofilm implants in bone. These results confirm that MB or ALA-mediated PDT have potential to treat S. aureus cultures grown in vitro or in vivo using an animal model of osteomyelitis. PMID:16395425

  20. Treatment of gas streams for removal of acid gases

    SciTech Connect

    Nieh, E.C.Y.

    1987-09-29

    A method is described for the purification of a stream of gas comprising a normally gaseous hydrocarbon or synthesis gas contaminated with acid gases which comprises the steps of: countercurrently contacting the gas stream in an absorption zone with a treating agent to remove a substantial portion of the acid contaminants from the hydrocarbon gas stream by absorption into the treating agent, discharging an at least partially purified hydrocarbon gas stream from the absorption zone, and discharging the treating agent enriched with absorbed acid gas components from the absorption zone. The treating agent consists essentially of an aqueous solution of from about 40 to about 60 wt. % of N-methyldiethanolamine and from about 5 to about 15 wt. % of N,N-diethyl hydroxylamine.

  1. Acid pre-treatment method for in situ ore leaching

    DOEpatents

    Mallon, R.G.; Braun, R.L.

    1975-10-28

    An acid leaching method is described for the recovery of a desired element from a subterranean rubblized body of primary ore containing the element and also having associated therewith a carbonate mineral wherein the rubblized ore body is flooded with an aqueous acidic solution in order to release carbon dioxide from the associated carbonate mineral. After a substantial portion of the available carbon dioxide is released and removed from the ore body, as by venting to the atmosphere, an oxidizing gas is introduced into the flooded, rubblized ore to oxidize the ore and form an acid leach solution effective in the presence of the dissolved oxidizing gas to dissolve the ore and cause the desired element to go into solution. The leach solution is then circulated to the surface where the metal values are recovered therefrom.

  2. Obeticholic acid for the treatment of primary biliary cirrhosis.

    PubMed

    Trivedi, Palak J; Hirschfield, Gideon M; Gershwin, M Eric

    2016-01-01

    Primary biliary cirrhosis (PBC) is characterized by progressive nonsuppurative destruction of small bile ducts, resulting in intrahepatic cholestasis, fibrosis and ultimately end-stage liver disease. Timely intervention with ursodeoxycholic acid is associated with excellent survival, although approximately one-third of all patients fail to achieve biochemical response, signifying a critical need for additional therapeutic strategies. Obeticholic acid (OCA) is a potent ligand of the nuclear hormone receptor farnesoid X receptor (FXR). Activation of FXR inhibits bile acid synthesis and protects against toxic accumulation in models of cholestasis and facilitates hepatic regeneration in preclinical studies. Data from recent Phase II and III controlled trials suggest a therapeutic impact of OCA in PBC biochemical nonresponders, as evidenced by change in proven laboratory surrogates of long-term outcome. Dose-dependent pruritus is a common adverse effect, but may be overcome through dose-titration. Longer term studies are needed with focus on safety and long-term clinical efficacy. PMID:26549695

  3. Use of an Amino Acid Mixture in Treatment of Phenylketonuria

    PubMed Central

    Bentovim, A.; Clayton, Barbara E.; Francis, Dorothy E. M.; Shepherd, Jean; Wolff, O. H.

    1970-01-01

    Twelve children with phenylketonuria diagnosed and treated from the first few weeks of life were grouped into pairs. Before the trial all of them were receiving a commercial preparation containing a protein hydrolysate low in phenylalanine (Cymogran, Allen and Hanburys Ltd.) as a substitute for natural protein. One of each pair was given an amino acid mixture instead of Cymogran for about 6 months. Use of the mixture involved considerable modification of the diet, and in particular the inclusion of greater amounts of phenylalanine-free foods. All six accepted the new mixture without difficulty, food problems were greatly reduced, parents welcomed the new preparation, and the quality of family life improved. Normal growth was maintained and with a mixture of l amino acids the plasma and urinary amino acid levels were normal. Further studies are needed before the mixture can be recommended for children under 20 months of age. PMID:5477678

  4. Plasma amino acid and serum unesterified fatty acid deficits and the effect of nutritional support in chemotherapy treatment.

    PubMed

    Ching, N; Grossi, C; Jham, G; Angers, J; Zurawinsky, H; Ching, C Y; Nealon, T F

    1984-06-01

    The deficits in plasma amino acids and serum unesterified fatty acids of cancer patients undergoing chemotherapy and/or radiation therapy were studied to delineate the special requirements of the patients and efficacy of our nutritional therapy. Seven general surgery patients and 13 patients treated by the Head-Neck Service had baseline levels measured as part of their nutritional evaluation prior to surgical treatment of their cancers. Fifteen chemotherapy outpatients maintained on their regular diets had fasting levels analyzed. Twenty-six patients who were admitted for their therapy had their intake of the regular hospital diet supplemented with a low-residue enteral diet formula (Vivonex High Nitrogen Diet); parenteral nutrition was used only if their oral intake was totally inadequate. Baseline and sequential measurements were made of plasma amino acid and serum unesterified fatty acid levels by gas liquid chromatographic techniques. Before operation the patients had normal levels of amino acids except for a significant deficiency of threonine and glycine observed in patients with head-neck tumors. Outpatients with and without hepatic metastases had significantly depressed levels of the essential amino acids valine, leucine, threonine, and methionine and the nonessential amino acids serine, glycine, and proline. The baseline levels of the patients admitted for treatment had similar deficiencies except for more evidence of lysine deficiency. Patients supported with total parenteral nutrition had rapid elevation of the amino acid levels. The patients whose intake was supplemented with the oral diets had improvement in their amino acid levels, but the deficiency in the leucine and threonine fractions persisted up to 4 weeks of therapy. Although the lysine levels were normal when first analyzed, significant differences developed in the patients without hepatic metastases after the start of chemotherapy with return to normal only after chemotherapy was discontinued

  5. LIMESTONE-LIME TREATMENT OF ACID MINE DRAINAGE - FULL SCALE

    EPA Science Inventory

    The nation-wide problems related to acidic discharges from coal mining operations are well documented in both popular and technical literature. Neutralization is and will continue to be a necessary short-term measure in numerous instances, while long-range programs are being deve...

  6. Maleic acid treatment of biologically detoxified corn stover liquor

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elimination of microbial and/or enzyme inhibitors from pretreated lignocellulose is critical for effective cellulose conversion and yeast fermentation of liquid hot-water (LHW) pretreated corn stover. In this study, xylan oligomers were hydrolyzed using either maleic acid or hemicellulases. Other so...

  7. Treatment of Natural Peanut Butter with Phytic Acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peanut butter may be less allergenic if allergens in the butter exist as insoluble complexes that are not absorbed by the body. We determined that such complexes form in natural peanut butter that is treated with phytic acid. Commercial natural peanut butter (non-hydrogenated, creamy, oil-based, and...

  8. Could peracetic acid be an alternative treatment in aquaculture?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid (PAA) is an antimicrobial disinfectant used in agriculture, food processing and medical facilities. It has recently been tested as a means to control infestations of Ichthyophthirius multifiliis and Saprolegnia parasitica. Free-swimming theronts of I. multifiliis can be eliminated u...

  9. MODULAR FIELD-BIOREACTOR FOR ACID MINE DRAINAGE TREATMENT

    EPA Science Inventory

    The presentation focuses on the improvements to engineered features of a passive technology that has been used for remediation of acid rock drainage (ARD). This passive remedial technology, a sulfate-reducing bacteria (SRB) bioreactor, takes advantage of the ability of SRB that,...

  10. Dynamic peracetic acid (PAA) exposure, a treatment strategy against ectoparasites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The search for alternative therapeutic agents is a difficult and laborious task. The use of peracetic acid (PAA) has recently been evaluated as an alternative compound for disinfection (Gustavino et al., 2005). In addition to having a broad antimicrobial spectrum, PAA does not contribute to the form...

  11. Operational Lessons Leaned During bioreactor Demonstrations for Acid Rock Drainage Treatment

    EPA Science Inventory

    The U.S. Environmental Protection Agency's Mine Waste Technology Program (MWTP) has emphasized the development of biologically-based treatment technologies for acid rock drainage (ARD). Progressively evolving technology demonstrations have resulted in significant advances in sulf...

  12. Operational Lessons Learned During Bioreactor Demonstrations for Acid Rock Drainage Treatment

    EPA Science Inventory

    The U.S. Environmental Protection Agency’s Mine Waste Technology Program (MWTP) has emphasized the development of biologically-based treatment technologies for acid rock drainage (ARD). Progressively evolving technology demonstrations have resulted in significant advances in sul...

  13. Imiquimod immunotherapy and ALA photodynamic therapy combination for the treatment of genital bowenoid papulosis

    NASA Astrophysics Data System (ADS)

    Wang, Xiu-Li; Wang, Hong-Wei; Guo, Ming-Xia; Huang, Zheng

    2007-02-01

    To investigate the feasibility and efficacy of combination of imiquimod immunotherapy and 5- aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) for the treatment of genital bowenoid papulosis (BP). A total of twenty seven BP patients were randomized into two groups: (I) fifteen patients (12 male and 3 female, age 22-56 years old) were treated with topical application of 5% imiquimod cream (three times a week) and ALA-PDT (100 J/cm2 at 100 mW/cm2, once a week) for 1-4 times in one week interval. (II) Twelve patients (6 male and 6 female, age 29-58 years old) were treated with CO II laser vaporization as a control. Patients were followed up for 3 to 12 months. Results: In combined therapy group, 60% (9/15) patients showed complete remission and only one recurred (11.1%) during follow up. Local side effects included mild erythema, edema, erosion and burning and/or stinging sensation. No systemic side effect was found. In CO II laser vaporization group, 83.3% (10/12) patients showed complete remission. However, recurrence occurred in 6 patients (60.0%). Local side effects included mild to moderate edema, erosion, ulceration, delayed healing, prolonged pain and scarring. The difference of recurrence rate between two groups was statistically significant (P < 0.05). Topical application of imiquimod cream and ALA-PDT is safe, effective and associated with low recurrence and less side effect. Its true clinical value needs to be further investigated by a long-term follow-up of large scale trial.

  14. Effect of oxalic acid treatment on sediment arsenic concentrations and lability under reducing conditions.

    PubMed

    Sun, Jing; Bostick, Benjamin C; Mailloux, Brian J; Ross, James M; Chillrud, Steven N

    2016-07-01

    Oxalic acid enhances arsenic (As) mobilization by dissolving As host minerals and competing for sorption sites. Oxalic acid amendments thus could potentially improve the efficiency of widely used pump-and-treat (P&T) remediation. This study investigates the effectiveness of oxalic acid on As mobilization from contaminated sediments with different As input sources and redox conditions, and examines whether residual sediment As after oxalic acid treatment can still be reductively mobilized. Batch extraction, column, and microcosm experiments were performed in the laboratory using sediments from the Dover Municipal Landfill and the Vineland Chemical Company Superfund sites. Oxalic acid mobilized As from both Dover and Vineland sediments, although the efficiency rates were different. The residual As in both Dover and Vineland sediments after oxalic acid treatment was less vulnerable to microbial reduction than before the treatment. Oxalic acid could thus improve the efficiency of P&T. X-ray absorption spectroscopy analysis indicated that the Vineland sediment samples still contained reactive Fe(III) minerals after oxalic acid treatment, and thus released more As into solution under reducing conditions than the treated Dover samples. Therefore, the efficacy of enhanced P&T must consider sediment Fe mineralogy when evaluating its overall potential for remediating groundwater As. PMID:26970042

  15. Well-test analysis following a closed-fracture acidizing treatment

    SciTech Connect

    Daneshi, T. ); Soliman, M.Y.; Hunt, J.L. )

    1990-12-01

    A model representing fluid flow in a reservoir treated with closed-fracture acidizing (CFA) is presented. The model is characterized by a low-conductivity fracture (representing the closed fracture) and highly conductive wormholes (owing to acid flow). Application of the model to pressure-transient data analysis following a CFA treatment is presented through a field example.

  16. PERIODS OF VERTEBRAL COLUMN SENSITIVITY TO BORIC ACID TREATMENT IN CD-1 MICE IN UTERO

    EPA Science Inventory

    Periods of vertebral column sensitivity to boric acid treatment in CD-1 mice in utero.

    Cherrington JW, Chernoff N.

    Department of Toxicology, North Carolina State University, Raleigh, NC 27695, USA. jana_cherrington@hotmail.com

    Boric acid (BA) has many uses as...

  17. Bioremediation of acid mine drainage coupled with domestic wastewater treatment.

    PubMed

    Sánchez-Andrea, Irene; Triana, David; Sanz, Jose L

    2012-01-01

    Acid mine drainage (AMD) - characterized by high acidity and elevated sulfate and metal concentrations - represents a big environmental concern. Biological sulfate reduction has become an alternative to the classical physicochemical methods. In this study, domestic wastewater (DW) was tested as a cost-effective carbon-source for the remediation of AMD. Sediments from Tinto River, an extreme acidic environment with an elevated concentration of metals, were used as inoculum. Three anaerobic bioreactors with different microbial supports were fed with a 1:10 (v:v) mixture of synthetic AMD:DW. Around 50% of the organic matter present in the DW co-precipitated with the metals from the AMD previous to feeding the reactor. Therefore, the reactors had to be supplemented with an extra carbon-source (acetate) to achieve higher S elimination. Elevated removal efficiencies of chemical oxygen demand (COD) (>88%), sulfate (>75%), Fe (>85%) and other dissolved metals (>99% except for Mn) were achieved. Bacterial communities were examined through denaturing gradient gel electrophoresis and scanning electron microscopy. Higher biodiversity was found in the bioreactors compared with that of the inoculum. Dominant species belong to two metabolic groups: fermentative (Clostridium spp., Delftia spp., Paludibacter spp. and Pelotomaculum spp.) and sulfate-reducing bacteria (Desulfomonile spp., Desulfovibrio spp., Desulfosporosinus spp. and Desulfotomaculum spp.). PMID:23032774

  18. Resistant starch improvement of rice starches under a combination of acid and heat-moisture treatments.

    PubMed

    Hung, Pham Van; Vien, Ngo Lam; Lan Phi, Nguyen Thi

    2016-01-15

    The effects of a combination of acid and heat-moisture treatment on formation of resistant starch (RS) and characteristics of high-amylose, normal and waxy rice starches were investigated in this study. The degrees of polymerization of the rice starches treated with citric acid, lactic acid or acetic acid were significantly reduced as compared to the native starches. The RS contents of acid and heat-moisture treated rice starches were in a range of 30.1-39.0%, significantly higher than those of native rice starches (6.3-10.2%) and those of heat-moisture treated rice starches (18.5-23.9%). The acid and heat-moisture treatments reduced swelling power and viscosity, but increased solubility of the starches, while the crystalline structure did not change. Among the organic acids used, citric acid had the most impact on starch characteristics and RS formation, followed by lactic acid and acetic acid. The results are useful in production of RS for functional food application. PMID:26258703

  19. Oxidative acid treatment and characterization of new biocarbon from sustainable Miscanthus biomass.

    PubMed

    Anstey, Andrew; Vivekanandhan, Singaravelu; Rodriguez-Uribe, Arturo; Misra, Manjusri; Mohanty, Amar Kumar

    2016-04-15

    Oxidative acid treatments of biochar produced from Miscanthus were performed in this study using nitric acid, sulfuric acid, and a mixture of both. The structural and morphological changes of the acid-treated biochar were investigated using Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Raman spectroscopy, organic elemental analysis and energy-dispersive X-ray spectroscopy (EDS). Improved surface functionality of the treated biochars was observed in their respective FT-IR spectra through the presence of nitro and carboxylic acid functional groups. SEM-EDS and elemental analysis revealed a large increase in the oxygen to carbon ratio in the biochar, which was evidence of chemical oxidation from the acid treatment. Further, TGA study showed the reduced thermal stability of acid-treated biochar over 200°C due to the increased oxygen content. Acid treatments also influenced the graphitic structure of the biochar, as observed in the Raman spectra. The results suggest that biochar can be successfully functionalized for composite applications and provide a sustainable alternative to petroleum-based carbon additives. PMID:26820927

  20. TREATMENT OF ACID MINE DRAINAGE USING FISHBONE APATITE IITM

    SciTech Connect

    Neal A. Yancey

    2006-10-01

    ABSTRACT. In 2000, a reactive barrier was installed on the East Fork of Ninemile Creek near Wallace, Idaho to treat acid mine discharge. The barrier was filled with fishbone derived Apatite IITM to remove the contaminants of concern (Zn, Pb, and Cd) and raise the pH of the acidic mine discharge. Metal removal has been achieved by a combination of chemical, biological, and physical precipitation. Flow for the water ranges from 5 to 35 gallons per minute. The water is successfully being treated, but the system experienced varying degrees of plugging. In 2002, gravel was mixed with the Apatite IITM to help control plugging. In 2003 the Idaho National Laboratory was ask to provide technical support to the Coeur d’Alene Basin Commission to help identify a remedy to the plugging issue. Air sparging was employed to treat the plugging issues. Plastic packing rings were added in the fall of 2005, which have increased the void space in the media and increased flows during the 10 months of operation since the improvements were made.

  1. Anthranilic Acid: A Potential Biomarker and Treatment Target for Schizophrenia

    PubMed Central

    Oxenkrug, Gregory; van der Hart, Marieke; Roeser, Julien; Summergrad, Paul

    2016-01-01

    Dysregulation of Trp-Kyn pathway is the most recent hypothesis of mechanisms of schizophrenia. In particular, over-production of kynurenic acid (KYNA), one of the three immediate downstream metabolites of kynurenine (Kyn) along tryptophan (Trp): Kyn pathway, has been considered as a new target for therapeutic intervention in schizophrenia. Up-regulation of KYNA formation was suggested to occur at the expense of down-regulated production of 3-hydroxyKyn (3-HK), the second immediate downstream metabolite of Kyn. We were interested to assess the third immediate downstream Kyn metabolite, anthranilic acid (AA). Serum AA concentrations were evaluated in schizophrenia patients and control subjects by HPLC-mass spectrometry method. We found 2-fold increase of AA and 3-fold decrease of 3-HK concentrations in serum of schizophrenia patients. Up regulated formation of AA might contribute to mechanisms of schizophrenia considering experimental evidences of AA augmentation of autoimmune processes in rat and mice; clinical findings of AA elevation in rheumatoid arthritis and type 1 diabetes, autoimmune diseases diametrical to schizophrenia; and involvement of autoimmunity in development of schizophrenia. Present data warrant further studies of AA as biological marker in, at least, a subgroup (associated with autoimmune mechanisms) of schizophrenia patients and as a new target for therapeutic intervention. PMID:27042691

  2. Treatment of mining acidic leachates with indigenous limestone, Zimapan Mexico.

    PubMed

    Labastida, I; Armienta, M A; Lara-Castro, R H; Aguayo, A; Cruz, O; Ceniceros, N

    2013-11-15

    An experimental study to evaluate the potential of using indigenous limestones in a passive system to treat acid mine drainage, at a mining zone of Mexico was carried out. Chemical and mineralogical characteristics of four types of native rocks (KIT1, KIT2, KSS, QZ) showed distinct CaCO3 contents. Synthetic aqueous leachates from an old tailings impoundment had a pH of 2.18, 34 mg/L As, 705 mg/L Fetotal, and 3975 mg/L SO4(2-). To evaluate dissolution behavior of rocks, kinetic batch experiments with an acid Fe-rich solution were performed. Decaying kinetic constants adjusting H(+) concentration to a first order exponential process were: KIT1 (k = 2.89), KIT2 (k = 0.89) and KSS (k = 0.47). Infrared spectrum and XRD of precipitates showed schwertmannite formation. To determine As and heavy metals (Fe, Cd, Zn, Al) removal from the synthetic leachates, batch experiments using KIT1 were developed. Arsenic decreased from 34.00 mg/L to 0.04 mg/L, Fe and Al were totally removed, and concentrations of Zn and Cd decreased 88% and 91% respectively. Analyses by IR and SEM-EDS indicate that co-precipitation with Fe-Hydroxides formed upon leachate interaction with limestone is the main As removal process. Chamosite, identified by XRD may participate in the removal of Al, SiO2 and a fraction of Fe. PMID:22819958

  3. Sodium bicarbonate treatment extends life of formerly acid lake

    SciTech Connect

    Not Available

    1988-02-01

    For the second time, researchers have used a familiar home remedy to restore the balance of a once acid lake. On September 29, Wolf Pond, in New York's Adirondack State Park, was treated with sodium bicarbonate to adjust alkalinity and keep pH at normal levels at least into the 1990's. Since it was first treated with bicarbonate in 1984, Wolf Pond has recovered and stabilized enough to sustain fish life once again. Repeated dosing is necessary because acid rain and runoff gradually deplete alkalinity in the lake over a period of years. Wolf Pond was selected for study because it has very little outflow and its major source of replenishment is rain. As the 1986 study explained, sodium bicarbonate was chosen for this application because it provides four advantages: (1) it is very soluble; (2) it cannot raise pH above 8.5; (3) it is easy to handle and apply; and (4) it is safe enough to be a common ingredient of many pharmaceuticals and foods.

  4. SITE PROGRAM EVALUATION OF INNOVATIVE ACID MINE DRAINAGE TREATMENT TECHNOLOGIES AT THE LEVIATHAN MINE SITE, CA

    EPA Science Inventory

    The EPA SITE Program is conducting a detailed sampling and evaluation of several innovative acid mine drainage treatment technologies at the Leviathan Mine Superfund site in California. Technologies include BiPhasic Lime Treatment Plant, an alkaline lagoon, and an innovative bio...

  5. Production of γ-Amino Butyric Acid in Tea Leaves wit Treatment of Lactic Acid Bacteria

    NASA Astrophysics Data System (ADS)

    Watanabe, Yuko; Hayakawa, Kiyoshi; Ueno, Hiroshi

    Lactic acid bacteria was searched for producing termented tea that contained a lot of γ-amino butyric acid(GABA). Also examined were the growth condition, GABA production and changes in catechin contents in the tea leaves. Lactobacillus brevis L12 was found to be suitable for the production of fermented tea since it gave as much GABA as gabaron tea when tea leaves being suspended with water at 10% and incubated for 4 days at 25°C. The amount of GABA produced was more than calculated based upon the content of glutamic acid in tea leaves. It is probable to assume that glutamate derived from glutamine and theanine is converted into GABA.

  6. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    SciTech Connect

    Van Beneden, Katrien; Geers, Caroline; Pauwels, Marina; Mannaerts, Inge; Wissing, Karl M.; Van den Branden, Christiane; Grunsven, Leo A. van

    2013-09-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  7. Comprehensive Treatment of Periorbital Region with Hyaluronic Acid

    PubMed Central

    Rocha, Camila Roos Mariano Da; Bastos, Julien Toni De; Silva, Priscila Mara Chaves e

    2015-01-01

    The periorbital subunit is one of the first facial regions to show signs of aging, primarily due to volume depletion of the soft tissue and bony resorption. Surgical and office-based nonsurgical procedures form an important basis for periorbital rejuvenation. It is important to make a detailed clinical evaluation of the patient to indicate the most appropriate procedure to be performed. With the objective of showing a nonsurgical procedure for the rejuvenation of the periorbital area, the authors describe a technique of applying fillers in the upper and lower periorbital regions, paying attention to the anatomy of this facial region and the type of product to be used besides the expected results of the procedure and its possible adverse effects and complications. The nonsurgical rejuvenation of the periorbicular region with hyaluronic acid is a new and innovative technique. In the opinion of the authors, it is a great aesthetic impact area and consequently brings high satisfaction to patients. PMID:26155325

  8. Comprehensive Treatment of Periorbital Region with Hyaluronic Acid.

    PubMed

    Bravo, Bruna Souza Felix; Rocha, Camila Roos Mariano Da; Bastos, Julien Toni De; Silva, Priscila Mara Chaves E

    2015-06-01

    The periorbital subunit is one of the first facial regions to show signs of aging, primarily due to volume depletion of the soft tissue and bony resorption. Surgical and office-based nonsurgical procedures form an important basis for periorbital rejuvenation. It is important to make a detailed clinical evaluation of the patient to indicate the most appropriate procedure to be performed. With the objective of showing a nonsurgical procedure for the rejuvenation of the periorbital area, the authors describe a technique of applying fillers in the upper and lower periorbital regions, paying attention to the anatomy of this facial region and the type of product to be used besides the expected results of the procedure and its possible adverse effects and complications. The nonsurgical rejuvenation of the periorbicular region with hyaluronic acid is a new and innovative technique. In the opinion of the authors, it is a great aesthetic impact area and consequently brings high satisfaction to patients. PMID:26155325

  9. Inhibition of breast cancer cell proliferation in repeated and non-repeated treatment with zoledronic acid

    PubMed Central

    2012-01-01

    Background Zoledronic acid is used to treat bone metastases and has been shown to reduce skeletal-related events and exert antitumor activity. The present in vitro study investigates the mechanism of action of Zoledronic Acid on breast cancer cell lines with different hormonal and HER2 patterns. Furthermore, we investigated the efficacy of repeated versus non-repeated treatments. Methods The study was performed on 4 breast cancer cell lines (BRC-230, SkBr3, MCF-7 and MDA-MB-231). Non-repeated treatment (single exposure of 168 hrs’ duration) with zoledronic acid was compared with repeated treatment (separate exposures, each of 48 hrs’ duration, for a total of 168 hrs) at different dosages. A dose–response profile was generated using sulforhodamine B assay. Apoptosis was evaluated by TUNEL assay and biomolecular characteristics were analyzed by western blot. Results Zoledronic acid produced a dose-dependent inhibition of proliferation in all cell lines. Anti-proliferative activity was enhanced with the repeated treatment, proving to be statistically significant in the triple-negative lines. In these lines repeated treatment showed a cytocidal effect, with apoptotic cell death caused by caspase 3, 8 and 9 activation and decreased RAS and pMAPK expression. Apoptosis was not observed in estrogen receptor-positive line: p21 overexpression suggested a slowing down of cell cycle. A decrease in RAS and pMAPK expression was seen in HER2-overexpressing line after treatment. Conclusions The study suggests that zoledronic acid has an antitumor activity in breast cancer cell lines. Its mechanism of action involves the decrease of RAS and RHO, as in osteoclasts. Repeated treatment enhances antitumor activity compared to non-repeated treatment. Repeated treatment has a killing effect on triple-negative lines due to apoptosis activation. Further research is warranted especially in the treatment of triple-negative breast cancer. PMID:23173568

  10. Evaluation of intravenous magnesium sulfate for the treatment of hydrofluoric acid burns.

    PubMed

    Cox, R D; Osgood, K A

    1994-01-01

    Hydrofluoric acid exposures to the skin can produce severe, progressive burns. Medical treatment of these burns is aimed at neutralizing the free fluoride ion, which is felt to be responsible for burn progression. Both calcium and magnesium will form complexes with free fluoride and have been used as topical or intradermal treatments in the past. This study evaluated the efficacy of intravenous magnesium sulfate for the treatment of hydrofluoric acid burns and compared this treatment to controls and burns treated with intradermal calcium gluconate in a rabbit model. Both treatments demonstrated a reduction in burn area over time, wound depth, healing time and final scar area compared to controls. The intravenous magnesium treatment showed trends toward improved outcome compared to the intradermal calcium treatment in all parameters evaluated, but these differences did not reach statistical significance. This investigation found intravenous magnesium to be an effective method for treating hydrofluoric acid burns. Intravenous magnesium may have significant utility for treating hydrofluoric acid burns that are not amenable to current therapies. PMID:8145352

  11. Photodynamic therapy using hemagglutinating virus of Japan envelope (HVJ-E): a novel therapeutic approach for the treatment of hormone antagonistic prostate cancer

    NASA Astrophysics Data System (ADS)

    Inai, Mizuho; Yamauchi, Masaya; Honda, Norihiro; Hazama, Hisanao; Tachikawa, Shoji; Nakamura, Hiroyuki; Nishida, Tomoki; Yasuda, Hidehiro; Kaneda, Yasufumi; Awazu, Kunio

    2015-03-01

    Traditional treatment options for prostate cancer are insufficient to cure advanced drug-resistant prostate cancer. Thus, as an alternative form of cancer therapy, photodynamic therapy (PDT) has become the main subject of intense investigation as a possible treatment modality. In this study, ultraviolet-inactivated viral vector, called hemagglutinating virus of Japan envelope (HVJ-E) was utilized to establish an effective delivery system for photosensitizer. Lipidated protoporphyrin IX (PpIX lipid) was inserted in HVJ-E by centrifugation to create a new drug delivering system that allows selective accumulation of photosensitizers in cancer cells. To study in vitro drug release mechanism of porphyrus envelope, the ultra-high voltage electron microscope tomography was applied. Next, to evaluate the photodynamic efficiency of porphyrus envelope for hormone antagonistic prostate cancer cells (PC-3), uptake of porphyrus envelope derived PpIX lipid and PpIX induced from exogenously administered precursor of 5-aminolevulinic acid hydrochloride (5-ALA) were compared by measuring fluorescence intensity of PpIX. Finally, to evaluate the efficacy of porphyrus envelope-PDT, laser light at a wavelength of 405 nm was irradiated to PC-3 cells. As a result, incorporation of porphyrus envelope-derived PpIX lipid occurred via membrane fusion, giving the highest fluorescence intensity when compared to 5-ALA-induced PpIX. Also, results from PDT experiment revealed the 28.6 × 103-fold and 206-fold increase in therapeutic efficacy when compared to those of PDT using 5-ALA induced PpIX and PpIX lipid, respectively. Our findings suggest how porphyrus envelope can induce efficient accumulation of PpIX lipid, which can enhance the therapeutic efficacy of PDT against hormone antagonistic prostate cancer.

  12. Photodynamic treatment (ALA-PDT) suppresses the expression of the oncogenic Bcr-Abl kinase and affects the cytoskeleton organization in K562 cells.

    PubMed

    Pluskalová, Michaela; Peslová, Gabriela; Grebenová, Dana; Halada, Petr; Hrkal, Zbynek

    2006-06-01

    K562 is the chronic myelogenous leukemia (CML)-derived cell line that expresses high levels of chimeric oncoprotein Bcr-Abl. The deregulated (permanent) kinase activity of Bcr-Abl leads to continuous proliferation of K562 cells and their resistance to the apoptosis promotion by conventional drugs. The photodynamic treatment (PDT) based on the application of 5-aminolevulinic acid (ALA) and irradiation with blue light (ALA-PDT) resulted in the suppression of K562 cells proliferation. It was followed by a necrosis-like cell death [K. Kuzelová, D. Grebenová, M. Pluskalová, I. Marinov, Z. Hrkal, J. Photochem. Photobiol. B 73 (2004) 67-78]. ALA-PDT led to the perturbation of the Hsp90/p23 multichaperone complex of which the Bcr-Abl is the client protein. Bcr-Abl protein was suppressed whereas the bcr-abl mRNA level was not affected. Further on, we observed several changes in the cytoskeleton organization. We detected ALA-PDT-mediated disruption of filamental actin structure using FITC-Phalloidin staining. In connection with this we uncovered certain cytoskeleton organizing proteins involved in the cell response to the treatment. Among these proteins, Septin2, which plays a role in maintaining actin bundles, was suppressed. Another one, PDZ-LIM domain protein 1 (CLP36) was altered. This protein acts as an adaptor molecule for LIM-kinase which phosphorylates and thus inactivates cofilin. Cofilin was indeed dephosphorylated and could thus be activated and operate as an actin-depolymerizing factor. We propose the scheme of molecular response of K562 cells to ALA-PDT. PMID:16495075

  13. Effects of Boronizing Treatment on Corrosion Resistance of 65Mn Steel in two Acid Mediums

    NASA Astrophysics Data System (ADS)

    Wang, Hongyu; Zhao, Yufeng; Yuan, Xiaoming; Chen, Kangmin; Xu, Ruihua

    To explore the soil workability of rotary blade suitable for large tilling depth (over 20 cm) manufactured through boronizing treatment, this work focuses on the corrosion behavior of 65Mn steel after boronizing treatment in two acid mediums, i.e. the strong acidic medium that hydrochloric solution and the weak acidic that fertilizer-containing soil, and the comparison with existing technology of general rotary blade (lonnealing after overall quenching). The result shows that the corrosion resistance in the two acid mediums of 65Mn steel after boronizing treatment is remarkably improved. After 168 hours' corrosion in the hydrochloric acid solution, the weight loss of boronizing-status sample is only 27.9% of that of lonnealing-status sample. Moreover, there is no obvious weight loss in boronizing-status sample after 168 hours' corrosion in the fertilizer-containing soil, while the weight of lonnealing-status sample is lighter than the original weight after about 150 hours' corrosion. The improvement of the corrosion resistance lies in the significant reduction of the anodization speed in strong acid medium and the effective prevention of phosphorization reaction in weak acidic medium.

  14. Modeling and optimizing the design of matrix treatments in carbonate reservoirs with self-diverting acid systems

    NASA Astrophysics Data System (ADS)

    Bulgakova, G. T.; Kharisov, R. Ya; Sharifullin, A. R.; Pestrikov, A. V.

    2015-01-01

    Application of a self-diverting-acid based on viscoelastic surfactant (SDVA) is a promising technology for improving the efficacy of acid treatment in oil and gas-bearing carbonate reservoirs. In this study, we present a mathematical model for assessing SDVA flow and reaction with carbonate rock using the SDVA rheological characteristics. The model calculates the technological parameters for acidizing operations and the prediction of well productivity after acid treatment, in addition to technical and economic optimization of the acidizing process by modeling different acid treatment options with varying volumes, injection rates, process fluids stages and initial economic scenarios.

  15. Biomimetic Deposition of Hydroxyapatite by Mixed Acid Treatment of Titanium Surfaces.

    PubMed

    Zhao, J M; Park, W U; Hwang, K H; Lee, J K; Yoon, S Y

    2015-03-01

    A simple chemical method was established for inducing bioactivity of Ti metal. In the present study, two kinds of mixed acid solutions were used to treat Ti specimens to induce Ca-P formation. Following a strong mixed acid activation process, Ca-P coatings successfully formed on the Ti surfaces in the simulated body fluid. Strong mixed acid etching was used to increase the roughness of the metal surface, because the porous and rough surfaces allow better adhesion between Ca-P coatings and substrate. Nano-scale modification of titanium surfaces can alter cellular and tissue responses, which may benefit osseointegration and dental implant therapy. Some specimens were treated with a 5 M NaOH aqueous solution, and then heat treated at 600 °C in order to form an amorphous sodium titanate layer on their surface. This treated titanium metal is believed to form a dense and uniform bone-like apatite layer on its surface in a simulated body fluid (SBF). This study proved that mixed acid treatment is not only important for surface passivation but is also another bioactive treatment for titanium surfaces, an alternative to alkali treatment. In addition, mixed acid treatment uses a lower temperature and shorter time period than alkali treatment. PMID:26413704

  16. Palladium nanoparticles synthesized by reducing species generated during a successive acidic/alkaline treatment of sucrose

    NASA Astrophysics Data System (ADS)

    Amornkitbamrung, Lunjakorn; Pienpinijtham, Prompong; Thammacharoen, Chuchaat; Ekgasit, Sanong

    2014-03-01

    Uniform spherical palladium nanoparticles with an average particle size of 4.3 ± 0.5 nm were successfully synthesized by reducing H2PdCl4 with intermediates in situ generated during a successive acidic/alkaline treatment of sucrose. A successive acidic/alkaline treatment plays an important role on converting the non-reducing sucrose into efficient reducing species containing aldehyde functionality. The Benedict's test corroborates the development and vanishing of the in situ generated reducing species upon prolonged degradation. An increase in alkalinity drastically improves the reduction efficiency. ATR FT-IR spectroscopy indicated spontaneous development of carboxylate after the alkaline treatment. Under the employed condition, small organic species with carbonyl groups (aldehyde, acid, and acid salt) were generated through the sucrose degradation before being oxidized to carbonate after an hour of the treatment. Sucrose was completely decomposed into carbonate after a 24-h successive acidic/alkaline treatment. The synthesized palladium nanoparticles express a good catalytic activity in the decolorization process of Congo red by sodium borohydride.

  17. Influence of nitric acid treatment in different media on X-ray structural parameters of coal

    SciTech Connect

    Sudip Maity; Ashim Choudhury

    2008-11-15

    The treatment of coal with nitric acid in aqueous and non-aqueous media introduces changes in the chemical and spatial structure of the organic mass. Four coals of different rank have been treated with nitric acid in aqueous and glacial acetic acid media for assessing the changes in the structural parameters by the X-ray diffraction (XRD) technique. Slow-scan XRD has been performed for the raw and treated coals, and X-ray structural parameters (d002, Lc, and Nc) and aromaticity (fa) have been determined by profile-fitting software. Considerable variation of the structural parameters has been observed with respect to the raw coals. The d002 values have decreased in aqueous medium but increased in acetic acid medium; however, Lc, Nc, and fa values have increased in aqueous medium but decreased in acetic acid medium. It is also observed that considerable oxidation takes place during nitric acid treatment in aqueous medium, but nitration is the predominant phenomenon in acetic acid medium. Disordering of the coal structure increases in acetic acid medium, but a reverse trend is observed in the aqueous medium. As a result, structurally modified coals (SMCs) are derived as new coal-derived substances. 15 refs., 6 figs., 3 tabs.

  18. Update on marine omega-3 fatty acids: management of dyslipidemia and current omega-3 treatment options.

    PubMed

    Weintraub, Howard

    2013-10-01

    Low-density lipoprotein cholesterol (LDL-C) is currently the primary target in the management of dyslipidemia, and statins are first-line pharmacologic interventions. Adjunct therapy such as niacins, fibrates, bile acid sequestrants, or cholesterol absorption inhibitors may be considered to help reduce cardiovascular risk. This review discusses the need for alternative adjunct treatment options and the potential place for omega-3 fatty acids as such. The cardiovascular benefits of fish consumption are attributed to the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and a variety of omega-3 fatty acid products are available with varied amounts of EPA and DHA. The product types include prescription drugs, food supplements, and medical foods sourced from fish, krill, algal and plant oils or purified from these oils. Two prescription omega-3 fatty acids are currently available, omega-3 fatty acid ethyl esters (contains both EPA and DHA ethyl esters), and icosapent ethyl (IPE; contains high-purity EPA ethyl ester). A pharmaceutical containing free fatty acid forms of omega-3 is currently in development. Omega-3 fatty acid formulations containing EPA and DHA have been shown to increase LDL-C levels while IPE has been shown to lower triglyceride levels without raising LDL-C levels, alone or in combination with statin therapy. In addition, recent studies have not been able to demonstrate reduced cardiovascular risk following treatment with fibrates, niacins, cholesterol absorption inhibitors, or omega-3 fatty acid formulations containing both EPA and DHA in statin-treated patients; thus, there remains a need for further cardiovascular outcomes studies for adjunct therapy. PMID:24075771

  19. Alleviation of postharvest chilling injury of tomato fruit by salicylic acid treatment.

    PubMed

    Aghdam, Morteza Soleimani; Asghari, Mohammadreza; Khorsandi, Orojali; Mohayeji, Mehdi

    2014-10-01

    Tomato fruit at the mature green stage were treated with salicylic acid at different concentration (0, 1 and 2 mM) and analyzed for chilling injury (CI), electrolyte leakage (EL), malondialdehyde (MDA) and proline contents and phospholipase D (PLD) and lipoxygenase (LOX) activities during cold storage. PLD and LOX activities were significantly reduced by salicylic acid treatment. Compared with the control fruit, salicylic acid treatment alleviated chilling injury, reduced electrolyte leakage, malondialdehyde content and increased proline content. Our result suggest that the reduce activity of PLD and LOX, by salicylic acid may be a chilling tolerance strategy in tomato fruit. Inhibition of PLD and LOX activity during low temperature storage could ameliorate chilling injury and oxidation damage and enhance membrane integrity in tomato fruit. PMID:25328231

  20. Formic acid-based treatments for control of Varroa destructor in a Mediterranean area.

    PubMed

    Satta, Alberto; Floris, Ignazio; Eguaras, Martin; Cabras, Paolo; Garau, Vincenzo Luigi; Melis, Marinella

    2005-04-01

    Two formic acid autumnal treatments, gel packets (BeeVar formulation) and impregnated paperwick (Liebig-Dispenser), were tested in apiary to evaluate their effectiveness against Varroa destructor Anderson & Trueman and their residues in honey in a Mediterranean region (Sardinia, Italy). Both treatments were efficient in the apiary control of the varroosis, with values of percentage of mite mortality ranging between 93.6 and 100%, without statistical differences between them. The more gradual release of formic acid from the gel application allowed a longer action (2 wk for each treatment) compared with the Liebig-Dispenser (approximately 3d for each treatment). The rate of daily evaporation ranged between approximately 5 and 9 g/d from BeeVar and approximately 26 and 35 g/d from the Liebig-Dispenser, in the first and second treatment, respectively. The total amount of formic acid administered per hive during all the treatment period was approximately 200 g for either treatment. A significantly higher adult bee mortality was recorded in the Liebig-Dispenser-treated hives compared with the BeeVar-treated group. On the contrary, BeeVar treatment produced an interruption of brood reared, whereas the extension of the sealed brood area of the Liebig-Dispenser-treated hives was not significantly different from that of the control hives. Neither queen mortality nor robbing activity was observed due to the treatments. Formic acid residues in honey collected in the nest were 3,855 +/- 2,061 and 3,030 +/- 1,624 mg/kg for the BeeVar- and the Liebig-Dispenser-treated hives, respectively. After 21 d from the end of the treatment, the residues fell to 1,261 +/- 1,054 and 794 +/- 518 mg/kg for the honey sampled from the BeeVar and Liebig-Dispenser groups, respectively. PMID:15889712

  1. Recent Advances in Delivery of Drug-Nucleic Acid Combinations for Cancer Treatment

    PubMed Central

    Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

    2013-01-01

    Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. PMID:23624358

  2. Photo-Fenton-like treatment of K-acid: assessment of treatability, toxicity and oxidation products.

    PubMed

    Olmez-Hanci, Tugba; Arslan-Alaton, Idil; Gelegen, Ozlem

    2014-01-01

    Photo-Fenton-like treatment of the commercially important naphthalene sulphonate K-acid (2-naphthylamine-3,6,8-trisulphonic acid) was investigated using UV-C, UV-A and visible light irradiation. Changes in toxicity patterns were followed by the Vibrio fischeri bioassay. Rapid and complete degradation of K-acid accompanied with nearly complete oxidation and mineralization rates (>90%) were achieved for all studied irradiation types. On the other hand, detoxification was rather limited and did not change significantly during photo-Fenton-like treatment. Several oxidation products could be identified via liquid chromatograph-mass spectrometer analyses, such as desulphonated and hydroxylated naphthalene derivatives, quinones, and ring-opening as well as dimerization products. Photo-Fenton-like treatment of K-acid with UV-C, UV-A and visible light irradiation occurred through a series of hydroxylation and desulphonation reactions, followed by ring cleavage. A common degradation pathway for photo-Fenton-like treatment of K-acid using different irradiation types was proposed. PMID:25259495

  3. Safety and tolerability of gamma-hydroxybutyric acid in the treatment of alcohol-dependent patients.

    PubMed

    Beghè, F; Carpanini, M T

    2000-04-01

    Gamma-hydroxybutyric acid (GHB) has been in clinical use in Italy since 1991 for treatment of alcohol dependence. Results of phase III and phase IV studies have shown that the drug is effective and well tolerated in the treatment of alcohol withdrawal syndrome and in reducing alcohol consumption and alcohol craving. Pharmacosurveillance indicates that abuse of gamma-hydroxybutyric acid is a limited phenomenon in clinical settings when the drug is dispensed under strict medical surveillance and entrusted to a referring familiar member of the patient. PMID:10869863

  4. Treatment recommendations in long-chain fatty acid oxidation defects: consensus from a workshop.

    PubMed

    Spiekerkoetter, U; Lindner, M; Santer, R; Grotzke, M; Baumgartner, M R; Boehles, H; Das, A; Haase, C; Hennermann, J B; Karall, D; de Klerk, H; Knerr, I; Koch, H G; Plecko, B; Röschinger, W; Schwab, K O; Scheible, D; Wijburg, F A; Zschocke, J; Mayatepek, E; Wendel, U

    2009-08-01

    Published data on treatment of fatty acid oxidation defects are scarce. Treatment recommendations have been developed on the basis of observations in 75 patients with long-chain fatty acid oxidation defects from 18 metabolic centres in Central Europe. Recommendations are based on expert practice and are suggested to be the basis for further multicentre prospective studies and the development of approved treatment guidelines. Considering that disease complications and prognosis differ between different disorders of long-chain fatty acid oxidation and also depend on the severity of the underlying enzyme deficiency, treatment recommendations have to be disease-specific and depend on individual disease severity. Disorders of the mitochondrial trifunctional protein are associated with the most severe clinical picture and require a strict fat-reduced and fat-modified (medium-chain triglyceride-supplemented) diet. Many patients still suffer acute life-threatening events or long-term neuropathic symptoms despite adequate treatment, and newborn screening has not significantly changed the prognosis for these severe phenotypes. Very long-chain acyl-CoA dehydrogenase deficiency recognized in neonatal screening, in contrast, frequently has a less severe disease course and dietary restrictions in many patients may be loosened. On the basis of the collected data, recommendations are given with regard to the fat and carbohydrate content of the diet, the maximal length of fasting periods and the use of l-carnitine in long-chain fatty acid oxidation defects. PMID:19452263

  5. Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid?

    PubMed Central

    Ross, Brian M; Seguin, Jennifer; Sieswerda, Lee E

    2007-01-01

    Background A growing number of observational and epidemiological studies have suggested that mental illness, in particular mood disorders, is associated with reduced dietary intake and/or cellular abundance of omega-3 polyunsaturated fatty acids (PUFA). This has prompted researchers to test the efficacy of omega-3 PUFA in a range of different psychiatric disorders. We have critically reviewed the double blind placebo controlled clinical trials published prior to April 2007 to determine whether omega-3 PUFA are likely to be efficacious in these disorders. Results Most trials involved a small number of participants but were largely well designed. Omega-3 PUFA were well tolerated by both children and adults with mild gastrointestinal effects being the only consistently reported adverse event. For schizophrenia and borderline personality disorder we found little evidence of a robust clinically relevant effect. In the case of attention deficit hyperactivity disorder and related disorders, most trials showed at most small benefits over placebo. A limited meta-analysis of these trials suggested that benefits of omega-3 PUFA supplementation may be greater in a classroom setting than at home. Some evidence indicates that omega-3 PUFA may reduce symptoms of anxiety although the data is preliminary and inconclusive. The most convincing evidence for beneficial effects of omega-3 PUFA is to be found in mood disorders. A meta-analysis of trials involving patients with major depressive disorder and bipolar disorder provided evidence that omega-3 PUFA supplementation reduces symptoms of depression. Furthermore, meta-regression analysis suggests that supplementation with eicosapentaenoic acid may be more beneficial in mood disorders than with docosahexaenoic acid, although several confounding factors prevented a definitive conclusion being made regarding which species of omega-3 PUFA is most beneficial. The mechanisms underlying the apparent efficacy of omega-3 PUFA in mood

  6. Quality and antioxidant properties on sweet cherries as affected by preharvest salicylic and acetylsalicylic acids treatments.

    PubMed

    Giménez, María José; Valverde, Juan Miguel; Valero, Daniel; Guillén, Fabián; Martínez-Romero, Domingo; Serrano, María; Castillo, Salvador

    2014-10-01

    The effects of salicylic acid (SA) or acetylsalicylic acid (ASA) treatments during on-tree cherry growth and ripening on fruit quality attributes, especially those related with the content on bioactive compounds and antioxidant activity were analysed in this research. For this purpose, two sweet cherry cultivars, 'Sweet Heart' and 'Sweet Late', were used and SA or ASA treatments, at 0.5, 1.0 and 2.0mM concentrations, were applied at three key points of fruit development (pit hardening, initial colour changes and onset of ripening). These treatments increased fruit weight and ameliorated quality attributes at commercial harvest, and led to cherries with higher concentration in total phenolics and in total anthocyanins, as well as higher antioxidant activity, in both hydrophilic and lipophilic fractions. Thus, preharvest treatments with SA or ASA could be promising tools to improve sweet cherry quality and health beneficial effects for consumers. PMID:24799232

  7. Effect of Putrescine Treatment on Chilling Injury, Fatty Acid Composition and Antioxidant System in Kiwifruit.

    PubMed

    Yang, Qingzhen; Wang, Feng; Rao, Jingping

    2016-01-01

    We investigated the effects of different concentrations (0, 1, 2 and 4 mM) of putrescine on chilling injury, fruit quality, ethylene production rate, fatty acid composition and the antioxidant system of cold-stored kiwifruit (Actinidia chinensis Planch. var. chinensis 'Hongyang'). We achieved a significant decrease in ethylene production, maintained fruit quality and alleviated chilling injury during storage via treatment with 2 mM putrescine. Furthermore, putrescine treatment inhibited increases in superoxide anion production rate and H2O2 concentration, while maintaining higher membrane lipid unsaturation as well as increased activities of superoxide dismutase and catalase. In addition, putrescine treatment enhanced the activities of antioxidant enzymes related to the ascorbate-glutathione cycle while causing higher levels of ascorbic acid and reduced glutathione. Our results suggest that induced tolerance against chilling injury via putrescine treatment in cold-stored kiwifruit may be due to enhanced antioxidant activity, increased unsaturation of membrane lipids, and inhibited ethylene production. PMID:27607076

  8. The effects of different thermal treatments and organic acid levels on nutrient digestibility in broilers.

    PubMed

    Goodarzi Boroojeni, F; Mader, A; Knorr, F; Ruhnke, I; Röhe, I; Hafeez, A; Männer, K; Zentek, J

    2014-05-01

    Poultry feed is a potential vector for pathogens. Heat processing and organic acid treatments may decontaminate feed and can affect bird performance as well as feed digestibility. The present study was performed to investigate the effect of different thermal treatments including pelleting (P), long-term conditioning at 85°C for 3 min (L), or expanding at 110°C (E110) and 130°C for 3 to 5 s (E130) without or with 0.75 and 1.5% organic acid supplementation (63.75% formic acid, 25.00% propionic acid, and 11.25% water) on performance, nutrient digestibility, and organ weights of broilers. In total, 960 one-day-old broiler chicks were randomly assigned to 8 replicates using a 3 × 4 factorial arrangement. Performance variables were determined, and the relative organ weights and ileal and total amino acid (AA) digestibilities were measured at d 35. The organic acid inclusion linearly improved feed efficiency in the first week (P ≤ 0.05). The acid inclusion levels and thermal treatments had no significant effect on the performance variables at later intervals of the growing period of the birds. The L group showed the lowest ileal AA and CP digestibility. The inclusion of organic acids had a quadratic effect on total and ileal digestibility of isoleucine (P ≤ 0.05), whereas it had no significant effect on the ileal digestibility of other AA and nutrients. The relative weights of the jejunum and small intestine were significantly higher in the E130 group compared with P and L (P ≤ 0.05). In conclusion, our study demonstrated that long-term heat conditioning can decrease ileal nutrient digestibility, whereas pelleting and expansion, independently of organic acid addition, seemed to have no negative impact on broiler performance and nutrient digestibilities. Moreover, adding a blend of organic acids to broiler diets had neither positive nor negative effects on nutrient digestibility and final broiler performance. This indicates the feasibility of short-term thermal

  9. Hydrolysis of Miscanthus for bioethanol production using dilute acid presoaking combined with wet explosion pre-treatment and enzymatic treatment.

    PubMed

    Sørensen, Annette; Teller, Philip J; Hilstrøm, Troels; Ahring, Birgitte K

    2008-09-01

    Miscanthus is a high yielding bioenergy crop. In this study we used acid presoaking, wet explosion, and enzymatic hydrolysis to evaluate the combination of the different pre-treatment methods for bioethanol production with Miscanthus. Acid presoaking is primarily carried out in order to remove xylose prior to wet explosion. The acid presoaking extracted 63.2% xylose and 5.2% glucose. Direct enzymatic hydrolysis of the presoaked biomass was found to give only low sugar yields of 24-26% glucose. Wet explosion is a pre-treatment method that combines wet-oxidation and steam explosion. The effect of wet explosion on non-presoaked and presoaked Miscanthus was investigated using both atmospheric air and hydrogen peroxide as the oxidizing agent. All wet explosion pre-treatments showed to have a disrupting effect on the lignocellulosic biomass, making the sugars accessible for enzymatic hydrolysis. The combination of presoaking, wet explosion, and enzymatic hydrolysis was found to give the highest sugar yields. The use of atmospheric air gave the highest xylose yield (94.9% xylose, 61.3% glucose), while hydrogen peroxide gave the highest glucose yield (82.4% xylose, 63.7% glucose). PMID:18164954

  10. Effects of Acid Vapor, Basic Vapor and Heat Treatments on the Properties of Langmuir-Blodgett Films of Divalent Metal Salts of Fatty Acids

    NASA Astrophysics Data System (ADS)

    Saito, Mitsuyoshi; Sugi, Michio; Ikegami, Keiichi; Yoneyama, Mitsuru; Iizima, Sigeru

    1986-06-01

    When LB films are exposed to the atmosphere vaporized from acid at room temperature, the X-ray diffraction peaks attributed to the lamellar structure disappear and new peaks appear depending on the metal ion species of the salt, whereas such noticeable change is not observed by basic vapor treatment and heat treatment. Diffraction patterns for LB films of free fatty acids are not influenced by these three treatments.

  11. Effects of cyanobacterial extracellular products and gibberellic acid on salinity tolerance in Oryza sativa L

    PubMed Central

    Rodríguez, AA; Stella, AM; Storni, MM; Zulpa, G; Zaccaro, MC

    2006-01-01

    Salt stress is one of the most serious factors limiting the productivity of rice, the staple diet in many countries. Gibberellic acid has been reported to reduce NaCl-induced growth inhibition in some plants including rice. Most paddy soils have a natural population of Cyanobacteria, prokaryotic photosynthethic microorganisms, which synthesize and liberate plant growth regulators such as gibberellins that could exert a natural beneficial effect on salt stressed rice plants. The aim of this work was to evaluate the effect of the cyanobacterium Scytonema hofmanni extracellular products on the growth of rice seedlings inhibited by NaCl and to compare it with the effect of the gibberellic acid in the same stress condition. Growth (length and weight of the seedlings) and biochemical parameters (5-aminolevulinate dehydratase activity, total free porphyrin and pigments content) were evaluated. Salt exposure negatively affected all parameters measured, with the exception of chlorophyll. Chlrorophyll concentrations nearly doubled upon exposure to high salt. Gibberellic acid counteracted the effect of salt on the length and dry weight of the shoot, and on carotenoid and chlorophyll b contents. Extracellular products nullified the salt effect on shoot dry weight and carotenoid content; partially counteracted the effect on shoot length (from 54% to 38% decrease), root dry weight (from 59% to 41% decrease) and total free porphyrin (from 31 to 13% decrease); reduced by 35% the salt increase of chlorophyll a; had no effect on root length and chlorophyll b. Gibberellic acid and extracellular products increased 5-aminolevulinate dehydratase activity over the control without salt. When coincident with high salinity, exposure to either EP or GA3, resulted in a reversal of shoot-related responses to salt stress. We propose that Scytonema hofmanni extracellular products may counteract altered hormone homeostasis of rice seedlings under salt stress by producing gibberellin-like plant

  12. Increased expression of mitochondrial benzodiazepine receptors following low-level light treatment facilitates enhanced protoporphyrin IX production in glioma-derived cells in vitro

    NASA Astrophysics Data System (ADS)

    Bisland, S. K.; Hassanali, N. S.; Johnson, C.; Wilson, B. C.

    2007-02-01

    This study investigates whether low level light treatment (LLLT) can enhance the expression of Peripheral-type mitochondrial benzodiazepine receptors (PBRs) on the glioma-derived tumour cell line, CNS-1, and by doing so promote the synthesis of protoporphyrin IX (PpIX) and increase the photodynamic therapy (PDT)-induced cell kill using 5-aminolevulinic acid (ALA). The endogenous photosensitizer, (PpIX) and related metabolites including coproporphyrin III are known to traffic via the PBRs on the outer mitochondrial membrane on their passage into or out of the mitochondria. Astrocyte-derived cells within the brain express PBRs, while neurons express the central-type of benzodiazepine receptor. CNS-1 cells were exposed to a range of differing low-level light protocols immediately prior to PDT. LLLT involved using broad-spectrum light or monochromatic laser light specific to 635 or 905 nm wavelength. Cells (5μ10 5) were exposed to a range of LLLT doses (0, 1 or 5 J/cm2) using a fixed intensity of 10 mW/cm2 and subsequently harvested for cell viability, immunofluorescence or western blot analysis of PBR expression. The amount of PpIX within the cells was determined using chemical extraction techniques. Results confirm the induction of PBR following LLLT is dependent on the dose and wavelength of light used. Broadspectrum light provided the greatest cell kill following PDT, although LLLT with 635 nm or 905 nm also increased cell kill as compared to PDT alone. All LLLT regimens increased PBR expression compared to controls with corresponding increases in PpIX production. These data suggest that by selectively increasing PBR expression in tumour cells, LLLT may facilitate enhanced cell kill using ALA-PDT without damaging surrounding normal brain.

  13. Lactic acid and trisodium phosphate treatment of lamb breast to reduce bacterial contamination.

    PubMed

    Ramirez, A J; Acuff, G R; Lucia, L M; Savell, J W

    2001-09-01

    Lactic acid and trisodium phosphate (TSP) were evaluated for the ability to reduce Escherichia coli and aerobic plate counts (APCs) on lamb breasts that were inoculated with a lamb fecal paste. A 90-s water rinse was applied followed by either a 9-s (55 degrees C) 2% lactic acid spray, a 60-s (55 degrees C) 12% TSP dip, or a combined treatment of both lactic acid and TSP treatments. Lactic acid reduced E. coli and APCs by 1.6 log10/cm2, and TSP caused a 1.8-log10/cm2 reduction in E. coli and a 0.7-log10/cm2 reduction in APCs. Combined reductions by the lactic acid spray followed by the TSP dip were 1.8 and 1.5 log10/cm2 for E. coli and APCs, respectively. Lactic acid and trisodium phosphate, used alone or in combination, were effective in reducing numbers of E. coli and could be useful as pathogen intervention steps in lamb slaughter processing. PMID:11563525

  14. Total volatile fatty acid concentrations are unreliable estimators of treatment effects on ruminal fermentation in vivo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Volatile fatty acid concentrations ([VFA], mM) have long been used to assess impact of dietary treatments on ruminal fermentation in vivo. However, discrepancies in statistical results between VFA and VFA pool size (VFAmol), possibly related to ruminal digesta liquid amount (LIQ, kg), suggest issues...

  15. COMPOST-FREE BIOREACTOR TREATMENT OF ACID ROCK DRAINAGE LEVIATHAN MINE, CALIFORNIA INNOVATIVE TECHNOLOGY EVALUATION REPORT

    EPA Science Inventory

    As part of the Superfund Innovative Technology Evaluation (SITE) program, an evaluation of the compost-free bioreactor treatment of acid rock drainage (ARD) from the Aspen Seep was conducted at the Leviathan Mine Superfund site located in a remote, high altitude area of Alpine Co...

  16. COMPOST-FREE BIOLOGICAL TREATMENT OF ACID ROCK DRAINAGE, TECHNICAL EVALUATION BULLETIN

    EPA Science Inventory

    As part of the Superfund Innovative Technology Evaluation (SITE) program, an evaluation of the compost-free bioreactor treatment of acid rock drainage (ARD) from the Aspen Seep was conducted at the Leviathan Mine Superfund site located in a remote, high altitude area of Alpine Co...

  17. COMPOST-FREE BIOREACTOR TREATMENT OF ACID ROCK DRAINAGE - TECHNOLOGY CAPSULE

    EPA Science Inventory

    As part of the Superfund Innovative Technology Evaluation (SITE) program, an evaluation of the compost-free bioreactor treatment of acid rock drainage (ARD) from the Aspen Seep was conducted at the Leviathan Mine Superfund site located in a remote, high altitude area of Alpine Co...

  18. LIME TREATMENT LAGOONS TECHNOLOGY FOR TREATING ACID MINE DRAINAGE FROM TWO MINING SITES

    EPA Science Inventory

    Runoff and drainage from active and inactive mines are someof the most environmentally damaging land uses i the US. Acid Mine drainage (AMD) from mining sites across the country requires treatment because of high metal concentrations that exceed regulatory standards for safe disc...

  19. Degradation of Poly(L-Lactic acid) and Biocomposites in various Alkaline and Temperature Treatments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ribbons of poly(lactic acid) (PLA) and PLA containing 10 or 25 % Osage orange (OO) biocomposites of various sized heartwood particles were exposed to soil conditions either outdoors or in a greenhouse. No appreciable degradation was evident even after 200 days treatments. An artificial alkaline de...

  20. Sanitizing with peracetic acid (PAA)- An alternative treatment to use in aquaculture ...?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Because of the lack of approved treatments for fish disease, disinfectants were tested to treat fish pathogens. One of these substances is peracetic acid (PAA). PAA is an agent used for disinfection in aquaculture, but it must be investigated thoroughly in order to mitigate diseases without harmful ...

  1. Evaluation of continuous 4 day exposure to peracetic acid as a treatment for Ichthyophthirius multifiliis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The parasitic ciliate Ichthyophthirius multifiliis infests all species of freshwater fish and can cause severe economic losses in fish breeding. The most effective treatment, malachite green, has been banned in Europe and North America for use in food-fish production. Peracetic acid (PAA) was foun...

  2. SO2 gas adsorption by modified kaolin clays: influence of previous heating and time acid treatments.

    PubMed

    Volzone, Cristina; Ortiga, Jose

    2011-10-01

    Modified kaolin clays were used as adsorbents for SO(2) gas adsorptions. The clays were heated up to 900 °C previous to acid treatments with 0.5 N sulfuric acid solutions at boiling temperature during different times up to 1440 min. Equilibrium adsorption at 25 °C and 0.1 MPa was carried out by using a volumetric apparatus. The samples were characterized by chemical analysis, X-ray diffraction and infrared analysis. The heating of the clays followed by acid treatment improved the adsorption capacity of the kaolin clays. The presence of amorphous silica and hydroxyl in the final products improved SO(2) adsorption capacity. Better properties for SO(2) adsorption were found in kaolin rich in not well ordered kaolinite clay mineral. PMID:21696883

  3. Responses of soil buffering capacity to acid treatment in three typical subtropical forests.

    PubMed

    Jiang, Jun; Wang, Ying-Ping; Yu, Mengxiao; Li, Kun; Shao, Yijing; Yan, Junhua

    2016-09-01

    Elevated anthropogenic acid deposition can significantly affect forest ecosystem functioning by changing soil pH, nutrient balance, and chemical leaching and so on. These effects generally differ among different forests, and the dominant mechanisms for those observed responses often vary, depending on climate, soil conditions and vegetation types. Using soil monoliths (0-40cm) from pine forest (pioneer), coniferous and broadleaved mixed forest (transitional) and broadleaved forest (mature) in southern China, we conducted a leaching experiment with acid treatments at different pH levels (control: pH≈4.5; pH=3.5; pH=2.5). We found that pH3.5 treatment significantly reduced dissolved organic carbon (DOC) concentrations in leachate from the pioneer forest soil. pH2.5 treatment significantly increased concentrations of NO3(-), SO4(2-), Ca(2+), Mg(2+), Al(3+), Fe(3+) and DOC in leachate from the pioneer forest soil, and also concentrations of NO3(-), SO4(2-), Mg(2+), Al(3+), Fe(3+) and DOC in leachate from the transitional forest soil. All acid treatments had no significant effects on concentrations of these chemicals in leachate from the mature forest soil. The responses can be explained by the changes in soil pH, acid neutralizing capacity (ANC) and concentrations of Al and Fe. Our results showed that acid buffering capacity of the pioneer or transitional forest soil was lower than that of the mature forest soil. Therefore preserving mature forests in southern China is important for reducing the adverse impacts of high acid deposition on stream water quality at present and into the future. PMID:27185346

  4. Electrochemical treatment of acidic aqueous ferrous sulfate and copper sulfate as models for acid mine drainage.

    PubMed

    Bunce, N J; Chartrand, M; Keech, P

    2001-12-01

    Acid mine drainage (AMD) is a serious environmental problem in the mining industry. The present work describes electrolytic reduction of solutions of synthetic AMD, comprising FeSO4/H2SO4 and CuSO4/H2SO4, in flow-through cells whose anode and cathode compartments were separated using ion exchange membranes. In the case of FeSO4/H2SO4 at constant flow rate, the pH of the effluent from the catholyte increased progressively with current at a variety of cathodes, due to electrolytic reduction of H+ ions to elemental hydrogen. Near-quantitative removal of iron was achieved by sparging air into the catholyte effluent, thereby precipitating iron outside the electrochemical cell, and avoiding fouling of the electrodes. The anode reaction was the oxidation of water to O2, a proton-releasing process. Using cation exchange membranes and sodium sulfate as the supporting electrolyte in the anode compartment, the efficiency of the process was compromised at high currents by transport of H+ competitively with Na+ from the anode to the cathode compartments. Higher efficiencies were obtained when anion exchange membranes were used, and in this case no additional supporting electrolyte other than dilute H2SO4 was needed, the net reaction being the electrochemically driven transfer of the elements of H2SO4 from the cathode to the anode compartments. Current efficiencies approximately 50% were achieved, the loss of efficiency being accounted for by ohmic heating of the solutions. In the case of CuSO4/H2SO4 and anion exchange membranes at high currents, reduction of Cu2+ and H+ ions and transport of SO4(2-) ions out of the catholyte caused unacceptably high potentials to be generated. PMID:11763043

  5. The effects of essential fatty acids preparation in the treatment of intrauterine growth retardation.

    PubMed

    Zhang, L

    1997-10-01

    A treatment of intravenous infusion of glucose, amino acids, and emulsion enriched in essential fatty acids (EFAs), linoleic, and linolenic acids were given to 30 pregnant women with intrauterine growth retardation (IUGR) and 28 non-EFAs treated cases as controls. There was a marked gain in fetal biparietal diameter (BPD) and in the estimated weight of the treated group over the control group. The mean birth weight was significantly different in the two groups. Fetal BPD increased much more in patients treated with EFAs at 28-34 gestational weeks than those at 34 1/7-37 weeks, which indicates that early initiate complement of n-3 and n-6 fatty acids to IUGR mothers may correct pregnancy-induced EFAs deficiency and maternal-fetal malnutrition, which demonstrates a fetal catch-up of growth in the brain and the whole body. PMID:9394162

  6. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease

    PubMed Central

    Porez, Geoffrey; Prawitt, Janne; Gross, Barbara; Staels, Bart

    2012-01-01

    Dyslipidemia is an important risk factor for cardiovascular disease (CVD) and atherosclerosis. When dyslipidemia coincides with other metabolic disorders such as obesity, hypertension, and glucose intolerance, defined as the metabolic syndrome (MS), individuals present an elevated risk to develop type 2 diabetes (T2D) as well as CVD. Because the MS epidemic represents a growing public health problem worldwide, the development of therapies remains a major challenge. Alterations of bile acid pool regulation in T2D have revealed a link between bile acid and metabolic homeostasis. The bile acid receptors farnesoid X receptor (FXR) and TGR5 both regulate lipid, glucose, and energy metabolism, rendering them potential pharmacological targets for MS therapy. This review discusses the mechanisms of metabolic regulation by FXR and TGR5 and the utility relevance of natural and synthetic modulators of FXR and TGR5 activity, including bile acid sequestrants, in the treatment of the MS. PMID:22550135

  7. The sonodegradation of caffeic acid under ultrasound treatment: relation to stability.

    PubMed

    Sun, Yujing; Qiao, Liping; Ye, Xingqian; Liu, Donghong; Zhang, Xianzhong; Huang, Haizhi

    2013-01-01

    The degradation of caffeic acid under ultrasound treatment in a model system was investigated. The type of solvent and temperature were important factors in determining the outcome of the degradation reactions. Liquid height, ultrasonic intensity and duty cycle only affected degradation rate, but did not change the nature of the degradation. The degradation rate of caffeic acid decreased with increasing temperature. Degradation kinetics of caffeic acid under ultrasound fitted a zero-order reaction from -5 to 25 °C. Caffeic acid underwent decomposition and oligomerization reactions under ultrasound. The degradation products were tentatively identified by FT-IR and HPLC-UV-ESIMS to include the corresponding decarboxylation products and their dimers. PMID:23292325

  8. Mechanism of chlorogenic acid treatment on femoral head necrosis and its protection of osteoblasts

    PubMed Central

    ZHANG, MINGJUAN; HU, XIANDA

    2016-01-01

    The aim of the present study was to investigate the therapeutic effect of chlorogenic acid on hormonal femoral head necrosis and its protection of osteoblasts. The study established a femoral head necrosis model in Wistar rats using Escherichia coli endotoxin and prednisolone acetate. The rats were divided into five groups and were treated with different concentrations of chlorogenic acid (1, 10 and 20 mg/kg). The main detected indicators were the blood rheology, bone mineral density, and the hydroxyproline and hexosamine (HOM) contents. At a cellular level, osteoblasts were cultured and treated by drug-containing serum. Subsequently, cell proliferation and the osteoblast cycle were measured using flow cytometry, and the protein expression levels of Bax and B-cell lymphoma 2 (Bcl-2) were detected using western blotting. Chlorogenic acid at a concentration of 20 mg/kg (high-dose) enhanced the bone mineral density of the femoral head and femoral neck following ischemia. Simultaneously, blood flow following the injection of prednisolone acetate was significantly improved, and the HOM contents of the high-dose chlorogenic acid group were significantly different. The results from the flow cytometry analysis indicated that chlorogenic acid can efficiently ameliorate hormone-induced necrosis. The osteoblasts were isolated and cultured. The MTT colorimetric assay showed that chlorogenic acid at different densities can increase the proliferation capabilities of osteoblasts and accelerate the transition process of G0/G1 phase to S phase, as well as enhance mitosis and the regeneration of osteoblasts. Western blotting detection indicated that chlorogenic acid may prohibit the decrease of Bcl-2 and the increase of Bax during apoptosis, thereby inhibiting osteoblast apoptosis and preventing the deterioration of femoral head necrosis. In conclusion, chlorogenic acid at the density of 20 mg/kg is effective in the treatment of hormonal femoral head necrosis, which may be

  9. Effects of Fatty Acid Treatments on the Dexamethasone-Induced Intramuscular Lipid Accumulation in Chickens

    PubMed Central

    Wang, Xiao juan; Wei, Dai lin; Song, Zhi gang; Jiao, Hong chao; Lin, Hai

    2012-01-01

    Background Glucocorticoid has an important effect on lipid metabolism in muscles, and the type of fatty acid likely affects mitochondrial utilization. Therefore, we hypothesize that the different fatty acid types treatment may affect the glucocorticoid induction of intramuscular lipid accumulation. Methodology/Principal Findings The effect of dexamethasone (DEX) on fatty acid metabolism and storage in skeletal muscle of broiler chickens (Gallus gallus domesticus) was investigated with and without fatty acid treatments. Male Arbor Acres chickens (31 d old) were treated with either palmitic acid (PA) or oleic acid (OA) for 7 days, followed by DEX administration for 3 days (35–37 d old). The DEX-induced lipid uptake and oxidation imbalance, which was estimated by increased fatty acid transport protein 1 (FATP1) expression and decreased carnitine palmitoyl transferase 1 activity, contributed to skeletal muscle lipid accumulation. More sensitive than glycolytic muscle, the oxidative muscle in DEX-treated chickens showed a decrease in the AMP to ATP ratio, a decrease in AMP-activated protein kinase (AMPK) alpha phosphorylation and its activity, as well as an increase in the phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal p70S6 kinase, without Akt activation. DEX-stimulated lipid deposition was augmented by PA, but alleviated by OA, in response to pathways that were regulated differently, including AMPK, mTOR and FATP1. Conclusions DEX-induced intramuscular lipid accumulation was aggravated by SFA but alleviated by unsaturated fatty acid. The suppressed AMPK and augmented mTOR signaling pathways were involved in glucocortcoid-mediated enhanced intramuscular fat accumulation. PMID:22623960

  10. Proteomic analysis of the molecular response of Raji cells to maslinic acid treatment.

    PubMed

    Yap, W H; Khoo, K S; Lim, S H; Yeo, C C; Lim, Y M

    2012-01-15

    Maslinic acid, a natural pentacyclic triterpene has been shown to inhibit growth and induce apoptosis in some tumour cell lines. We studied the molecular response of Raji cells towards maslinic acid treatment. A proteomics approach was employed to identify the target proteins. Seventeen differentially expressed proteins including those involved in DNA replication, microtubule filament assembly, nucleo-cytoplasmic trafficking, cell signaling, energy metabolism and cytoskeletal organization were identified by MALDI TOF-TOF MS. The down-regulation of stathmin, Ran GTPase activating protein-1 (RanBP1), and microtubule associated protein RP/EB family member 1 (EB1) were confirmed by Western blotting. The study of the effect of maslinic acid on Raji cell cycle regulation showed that it induced a G1 cell cycle arrest. The differential proteomic changes in maslinic acid-treated Raji cells demonstrated that it also inhibited expression of dUTPase and stathmin which are known to induce early S and G2 cell cycle arrests. The mechanism of maslinic acid-induced cell cycle arrest may be mediated by inhibiting cyclin D1 expression and enhancing the levels of cell cycle-dependent kinase (CDK) inhibitor p21 protein. Maslinic acid suppressed nuclear factor-kappa B (NF-κB) activity which is known to stimulate expression of anti-apoptotic and cell cycle regulatory gene products. These results suggest that maslinic acid affects multiple signaling molecules and inhibits fundamental pathways regulating cell growth and survival in Raji cells. PMID:21893403

  11. Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells

    SciTech Connect

    Luo, Yi Rana, Payal; Will, Yvonne

    2012-06-01

    Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting that fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients. -- Highlights: ► Palmitic acid and cyclosporine (CsA) synergistically increased cytotoxicity. ► The impairment of mitochondrial functions may contribute to the enhanced toxicity. ► Inhibition of JNK activity attenuated

  12. Cerebrospinal fluid levels of phenylacetic acid in mental illness: behavioral associations and response to neuroleptic treatment.

    PubMed

    Sharma, R P; Faull, K; Javaid, J I; Davis, J M

    1995-05-01

    Cerebrospinal fluid levels of phenylacetic acid (CSF PAA) were obtained from normal controls and from drug-free psychiatric inpatients (schizophrenia, major depression, mania, and schizoaffective disorder). Post-treatment CSF PAA levels were obtained from 16 patients after 4 weeks of neuroleptic treatment. Phenylacetic acid levels were higher in women and were significantly correlated with age. There were no differences in CSF PAA levels between the various diagnostic groups and no difference between the paranoid and the nonparanoid subtypes of schizophrenia. CSF PAA was significantly correlated with several measures of psychopathology, especially the Brief Psychiatric Rating Scale hostility/suspiciousness factor. Neuroleptic treatment did not result in significant PAA changes. These findings are discussed in light of the amphetamine-like role ascribed to phenylethylamine, the precursor of PAA. PMID:7639084

  13. UV Spectra of Amino Acid Immobilized at Nanoparticles Formation through Nanosphere Lithography (NSL) by Plasma Treatment

    SciTech Connect

    Mohamad, Farizan; Agam, Mohd Arif; Nur, Hadi

    2011-05-25

    The modifying of nanospheres structures by plasma treatments to the fabricated nanoparticles arrays by Nanosphere Lithography (NSL) techniques to create Periodic Particles Arrays (PPAs) with different size, shape and orientation. Spectra of amino acid that immobilized to the nanoparticles arrays under Ultra Violet (UV) spectrums were studied. The PPAs with different sizes, shapes and orientation were fabricated by plasma treatment of 5 sec, 7 sec and 10 sec to the Polystyrene Nanosphere (PSN). Plasma treatment will effect to the PSN including etching part of the PSN to produce a much bigger channel to the single layer template of the PSN. Metal was deposited at interstitial sites between of the polymer balls and later removed by dissolving them in organic solvent, leaving a hexagonal pattern of metal structures at the interstitial sites. The nanoparticles immobilized with the standard amino acid, which later investigated under UV spectrums. The spectrums shows the possibilities use as biosensor devices.

  14. [Comparison between penicillin and amoxicillin-clavulanic acid for the treatment of recurrent tonsillopharyngitis in childhood].

    PubMed

    Asensi, F; López-Hontangas, J L; Otero, M; Santos, M; Román, J; Pérez-Tamarit, D

    1999-09-01

    Fifty-one children aged 2-14 years with recurrent tonsillopharyngitis, presenting dysphagia, fever and lymphadenitis, with more than two similar episodes in the last three years and showing a beta-hemolytic group A streptococci in the pharyngeal smear, were studied. They underwent random treatment for ten days with phenoxymethylpenicillin (40-60 mg/kg/day) (n = 28) or amoxicillin-clavulanic acid (20-40 mg/kg/day) (n = 23) taken orally three times a day. Clinical and bacteriological tests were carried out at 10 days and 2, 6 and 12 months post-treatment. The clinical and bacteriological results showed the superiority of the amoxicillin-clavulanic acid treatment both in the short term (disappearance of symptoms) and in the long term (decrease in recurrence). These results support the idea that betalactamases produced by the pharyngeal flora play an important role in the failures of penicillin. PMID:10878510

  15. Recovery of Acid Production in Streptococcus mutans Biofilms after Short-Term Fluoride Treatment.

    PubMed

    Dang, Minh-Huy; Jung, Ji-Eun; Lee, Dae-Woo; Song, Kwang-Yeob; Jeon, Jae-Gyu

    2016-01-01

    Fluoride is commonly used as an ingredient of topical oral hygiene measures. Despite the anti-acidogenic activities of fluoride against cariogenic biofilms, the recovery of the biofilms from fluoride damage is unclear. Herein, we investigated the recovery of acid production in Streptococcus mutans biofilms after short-term or during periodic 1-min fluoride treatments. For this study, 46-hour-old S. mutans biofilms were treated with fluoride (0-2,000 ppm F-) for 1-8 min and then incubated in saliva for 0-100 min. The 74-hour-old biofilms were also periodically treated with the fluoride concentration during biofilm formation (1 min/treatment). Changes in acidogenicity and viability were determined via pH drop and colony-forming unit assays, respectively. In this study, acid production after a 1-min fluoride treatment was recovered as saliva incubation time increased, which followed a linear pattern of concentration dependence (R = 0.99, R2 = 0.98). The recovery pattern was in a biphasic pattern, with an initial rapid rate followed by a second slow recovery. Furthermore, recovery from fluoride damage was retarded in a concentration-dependent manner as treatment time increased. In periodic 1-min fluoride treatments, acid production in the biofilms was not diminished during the non-fluoride treatment period; however, it was reduced in a concentration-dependent manner during the fluoride treatment period. The viability of the biofilm cells did not change, even at high fluoride concentrations. Collectively, our results suggest that brief fluoride treatment does not sustain anti-acidogenic activity against S. mutans in biofilms since the damage is recoverable with time. PMID:27355469

  16. Impact of treatment processes on the removal of perfluoroalkyl acids from the drinking water production chain.

    PubMed

    Eschauzier, Christian; Beerendonk, Erwin; Scholte-Veenendaal, Petra; De Voogt, Pim

    2012-02-01

    The behavior of polyfluoralkyl acids (PFAAs) from intake (raw source water) to finished drinking water was assessed by taking samples from influent and effluent of the several treatment steps used in a drinking water production chain. These consisted of intake, coagulation, rapid sand filtration, dune passage, aeration, rapid sand filtration, ozonation, pellet softening, granular activated carbon (GAC) filtration, slow sand filtration, and finished drinking water. In the intake water taken from the Lek canal (a tributary of the river Rhine), the most abundant PFAA were PFBA (perfluorobutanoic acid), PFBS (perfluorobutane sulfonate), PFOS (perfluorooctane sulfonate), and PFOA (perfluorooctanoic acid). During treatment, longer chain PFAA such as PFNA (perfluorononanoic acid) and PFOS were readily removed by the GAC treatment step and their GAC effluent concentrations were reduced to levels below the limits of quantitation (LOQ) (0.23 and 0.24 ng/L for PFOS and PFNA, respectively). However, more hydrophilic shorter chain PFAA (especially PFBA and PFBS) were not removed by GAC and their concentrations remained constant through treatment. A decreasing removal capacity of the GAC was observed with increasing carbon loading and with decreasing carbon chain length of the PFAAs. This study shows that none of the treatment steps, including softening processes, are effective for PFAA removal, except for GAC filtration. GAC can effectively remove certain PFAA from the drinking water cycle.The enrichment of branched PFOS and PFOA isomers relative to non branched isomers during GAC filtration was observed during treatment. The finished water contained 26 and 19 ng/L of PFBA and PFBS. Other PFAAs were present in concentrations below 4.2 ng/L The concentrations of PFAA observed in finished waters are no reason for concern for human health as margins to existing guidelines are sufficiently large. PMID:22201258

  17. Caffeic acid-coated multifunctional magnetic nanoparticles for the treatment and bimodal imaging of tumours.

    PubMed

    Lee, Jun; Kim, Kyoung Sub; Na, Kun

    2016-07-01

    Accurate theragnosis of tumour is essential for improving the life rate of tumour patients. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used as both diagnostic and therapeutic agents. However, their application is often limited because of a lack of water solubility, lack of cancer treatment efficacy, and ineffective targeting of tumour cells. In this report, a double ligand (caffeic acid-polyethylene glycol-folic acid; FA-PEG-CA, caffeic acid-polyethylene glycol-pheophorbide-a; PheoA-PEG-CA) coated iron oxide nanoparticle has been fabricated that overcomes the limitations of conventional SPION. Photosensitizer and tumour targeting ligands were coated on SPION using a ligand-substitution method. We confirmed the successful substitution of oleic acid ligands with FA-PEG-CA and PheoA-PEG-CA ligands by FT-IR spectroscopy. The caffeic acid coated iron oxide nanoparticles (CAMNPs) also demonstrated high water solubility in an aqueous environment and folate-mediated active tumour targeting. The water solubility of CAMNPs was evaluated by DLS measurement and TEM images. The cytotoxicity of CAMNPs increased two-fold in MDA-MB-231 cells at a laser irradiation condition. The fabricated CAMNPs retained their ability to function as both MRI diagnostic and tumour-selective therapeutic agents. These results suggest that these efficient characteristics of CAMNPs can be incorporated into applications, thus enhancing the efficacy of clinical cancer treatment. PMID:27107705

  18. Amino Acid PET – An Imaging Option to Identify Treatment Response, Posttherapeutic Effects, and Tumor Recurrence?

    PubMed Central

    Galldiks, Norbert; Langen, Karl-Josef

    2016-01-01

    Routine diagnostics and treatment monitoring in patients with primary and secondary brain tumors is usually based on contrast-enhanced standard MRI. However, the capacity of standard MRI to differentiate neoplastic tissue from non-specific posttreatment effects may be limited particularly after therapeutic interventions such as radio- and/or chemotherapy or newer treatment options, e.g., immune therapy. Metabolic imaging using PET may provide relevant additional information on tumor metabolism, which allows a more accurate diagnosis especially in clinically equivocal situations, particularly when radiolabeled amino acids are used. Amino acid PET allows a sensitive monitoring of a response to various treatment options, the early detection of tumor recurrence, and an improved differentiation of tumor recurrence from posttherapeutic effects. In the past, this method had only limited availability due to the use of PET tracers with a short half-life, e.g., C-11. In recent years, however, novel amino acid PET tracers labeled with positron emitters with a longer half-life (F-18) have been developed and clinically validated, which allow a more efficient and cost-effective application. These developments and the well-documented diagnostic performance of PET using radiolabeled amino acids suggest that its application continues to spread and that this technique may be available as a routine diagnostic tool for several indications in the field of neuro-oncology. PMID:27516754

  19. A study to determine the efficacy of treatments for hydrofluoric acid burns.

    PubMed

    Seyb, S T; Noordhoek, L; Botens, S; Mani, M M

    1995-01-01

    Hydrofluoric acid burns are characterized by progressive tissue destruction and severe pain. Fluoride ion chelators, such as salts of calcium and magnesium, have been used to treat these burns. This study was designed to compare the efficacy of several treatment methods that involve the use of these salts. Standard hydrofluoric acid burns were produced on the shaved hindquarters of rats. After being rinsed with water, the chemical burns were treated by one of seven experimental methods. The progress of the chemical burn damage was observed for 1 week by measuring the surface areas of the burns. Calcium gluconate burn jelly, 20% calcium gluconate in water, and 50% aqueous dimethyl sulfoxide did not significantly slow the spread of the burn area. However, subcutaneous injections of calcium gluconate or magnesium sulfate and topical applications of calcium gluconate in a solution of dimethyl sulfoxide significantly slowed the progress of the burns during the first 24 hours and enhanced tissue recovery for the remainder of the observation period. These results indicate that subcutaneous injections of magnesium or calcium salts appear to be more effective than conventional topical applications in the treatment of hydrofluoric acid burns. More significantly, topically applied calcium gluconate combined with a penetration enhancer, such as dimethyl sulfoxide, is as effective as injection treatments in reducing damage caused by hydrofluoric acid. PMID:7673304

  20. [Use of alpha-lipoic acid and omega-3 in postpartum pain treatment].

    PubMed

    Costantino, D; Guaraldi, C; Costantino, M; Bounous, V E

    2015-10-01

    Postpartum pain is a frequent condition that negatively affects women's quality of life, interferring with everyday life. Analgesic drugs and surgery are often contraindicated in pregnancy and during breast feeding. This review of the literature aims to evaluate the rational of the association of lipoic acid and omega-3 employ in the management of postpartum pain. Lipoic acid is a cofactor essential in mitochondrial metabolism with antioxidant and anti-inflammatory activity. Lipoic acid has been shown to be effective in neuropatic pain treatment in patients with sciatica, carpal tunnel syndrome and diabetic neuropathy. Omega-3 are known for their anti-inflammatory and neurotrophic activity. The peripheral and central activity of both substances allows to act on neuroinflammation mechanisms thus reducing cronicization of pain and also determining a potential improvement of women's emotional status. The preliminary data here presented confirm the positive effect of this association on the treatment of postpartum perineal pain. The supplementation of lipoic acid in association with omega-3 seems effective and safe for the treatment of chronic postpartum pain, allowing a pathogenetic approach to neuroinflammation, thus reducing the consumption of analgesic drugs, often contraindicated during breast-feeding. PMID:26491825

  1. Detection and treatment of omega-3 fatty acid deficiency in psychiatric practice: Rationale and implementation.

    PubMed

    Messamore, Erik; McNamara, Robert K

    2016-01-01

    A body of translational evidence has implicated dietary deficiency in long-chain omega-3 (LCn-3) fatty acids, including eicosapenaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and potentially etiology of different psychiatric disorders. Case-control studies have consistently observed low erythrocyte (red blood cell) EPA and/or DHA levels in patients with major depressive disorder, bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder. Low erythrocyte EPA + DHA biostatus can be treated with fish oil-based formulations containing preformed EPA + DHA, and extant evidence suggests that fish oil supplementation is safe and well-tolerated and may have therapeutic benefits. These and other data provide a rationale for screening for and treating LCn-3 fatty acid deficiency in patients with psychiatric illness. To this end, we have implemented a pilot program that routinely measures blood fatty acid levels in psychiatric patients entering a residential inpatient clinic. To date over 130 blood samples, primarily from patients with treatment-refractory mood or anxiety disorders, have been collected and analyzed. Our initial results indicate that the majority (75 %) of patients exhibit whole blood EPA + DHA levels at ≤ 4 percent of total fatty acid composition, a rate that is significantly higher than general population norms (25 %). In a sub-set of cases, corrective treatment with fish oil-based products has resulted in improvements in psychiatric symptoms without notable side effects. In view of the urgent need for improvements in conventional treatment algorithms, these preliminary findings provide important support for expanding this approach in routine psychiatric practice. PMID:26860589

  2. Effect of formic acid or formaldehyde treatment of alfalfa silage on nutrient utilization by dairy cows.

    PubMed

    Nagel, S A; Broderick, G A

    1992-01-01

    Third-cutting alfalfa with 37% DM was ensiled untreated or treated with either 2.8 g of formic acid/100 g of DM or .31 g of formaldehyde/100 g of DM and fed to lactating dairy cows in two experiments. Silage treated with formic acid had the lowest pH and concentrations of NPN, NH3, and total free AA. Both treatments decreased rumen in vitro protein degradability but did not affect in vitro rumen plus pepsin digestibility. In trial 1, part 1, 22 Holstein cows received a standard diet for 18 d postpartum and then were fed for 6 wk one of three diets containing 98% alfalfa silage DM. Although DMI was comparable, yields of milk, SCM, fat, protein, lactose, and SNF were higher when treated silages were fed. Plasma concentrations of branched-chain, essential, and total AA increased when formic acid-treated silage was fed. Rumen pH and concentrations of NH3 and VFA were similar for all diets. Rumen escape protein, estimated using 15N as a microbial protein marker, was increased more by formic acid than by formaldehyde treatment. In trial 1, part 2, supplementation with 4.8% fish meal increased concentration of milk protein and yields of milk, protein, lactose, and SNF. Milk urea concentration was higher on the untreated silage diet. Total tract apparent DM and N digestibilities were not affected by silage treatment, although fish meal decreased apparent DM digestibility. In trial 2, 80:20 alfalfa silage:ground corn diets were fed to 12 midlactation cows in a 3 x 3 Latin square study. Milk production was unaffected, but milk protein concentration and DMI were higher when treated silages were fed. Feeding treated silages increased plasma concentrations of branched-chain AA, essential AA, and total AA. Formaldehyde and especially formic acid treatment effectively improved utilization of nutrients in alfalfa silage by lactating dairy cows. PMID:1541728

  3. Efficacy of omega-3 fatty acids in the treatment of borderline personality disorder: a study of the association with valproic acid.

    PubMed

    Bellino, Silvio; Bozzatello, Paola; Rocca, Giuseppe; Bogetto, Filippo

    2014-02-01

    Omega-3 fatty acids have received increasing interest due to their effects in stabilizing plasmatic membranes and regulating cell signaling. The efficacy of omega-3 fatty acids in psychiatric disorders, in particular mood disorders, has been studied. There have been two trials on eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) in the treatment of borderline personality disorder (BPD). The present 12-week controlled trial aimed to assess the efficacy of the association of EPA and DHA with valproic acid, compared to single valproic acid, in 43 consecutive BPD outpatients. Participants were evaluated at baseline and after 12 weeks with: Clinical Global Impression - Severity (CGI-S), Hamilton Scales for depression and anxiety (HAM-D, HAM-A), Social and Occupational Functioning Assessment Scale (SOFAS), borderline personality disorder severity index (BPDSI), Barratt Impulsiveness Scale - version 11 (BIS-11), Modified Overt Aggression Scale (MOAS), Self-Harm Inventory (SHI) and Dosage Record Treatment Emergent Symptom Scale (DOTES). PMID:24196948

  4. Infantile Refsum Disease: Influence of Dietary Treatment on Plasma Phytanic Acid Levels.

    PubMed

    Sá, Maria João Nabais; Rocha, Júlio C; Almeida, Manuela F; Carmona, Carla; Martins, Esmeralda; Miranda, Vasco; Coutinho, Miguel; Ferreira, Rita; Pacheco, Sara; Laranjeira, Francisco; Ribeiro, Isaura; Fortuna, Ana Maria; Lacerda, Lúcia

    2016-01-01

    Infantile Refsum disease (IRD) is one of the less severe of Zellweger spectrum disorders (ZSDs), a group of peroxisomal biogenesis disorders resulting from a generalized peroxisomal function impairment. Increased plasma levels of very long chain fatty acids (VLCFA) and phytanic acid are biomarkers used in IRD diagnosis. Furthermore, an increased plasma level of phytanic acid is known to be associated with neurologic damage. Treatment of IRD is symptomatic and multidisciplinary.The authors report a 3-year-old child, born from consanguineous parents, who presented with developmental delay, retinitis pigmentosa, sensorineural deafness and craniofacial dysmorphisms. While the relative level of plasma C26:0 was slightly increased, other VLCFA were normal. Thus, a detailed characterization of the phenotype was essential to point to a ZSD. Repeatedly increased levels of plasma VLCFA, along with phytanic acid and pristanic acid, deficient dihydroxyacetone phosphate acyltransferase activity in fibroblasts and identification of the homozygous pathogenic mutation c.2528G>A (p.Gly843Asp) in the PEX1 gene, confirmed this diagnosis. Nutritional advice and follow-up was proposed aiming phytanic acid dietary intake reduction. During dietary treatment, plasma levels of phytanic acid decreased to normal, and the patient's development evaluation showed slow progressive acquisition of new competences.This case report highlights the relevance of considering a ZSD in any child with developmental delay who manifests hearing and visual impairment and of performing a systematic biochemical investigation, when plasma VLCFA are mildly increased. During dietary intervention, a biochemical improvement was observed, and the long-term clinical effect of this approach needs to be evaluated. PMID:26303611

  5. The effects of acid treatment and calcium ions on the solubility of concanavalin A

    NASA Technical Reports Server (NTRS)

    Cacioppo, Elizabeth; Pusey, Marc L.

    1992-01-01

    The effects of acid treatment (which removes Mn and Ca ions) and Ca(2+) ions on the solubility of jack-bean-meal concanavalin A were investigated using two techniques: the sitting drop technique and the microcolumn technique. It was found that the solubility of concanavalin A varied with the protein preparation procedures and with measurement techniques. Addition of Ca(2+) resulted in greatly lowered solubilities compared with the acid treated protein. The sitting drop solubilities for the recalcified protein agreed better with those reported by Mikol and Giege (1989) than with solubilities determined from column data.

  6. Effect of ultrasonic treatments on nanoparticle preparation of acid-hydrolyzed waxy maize starch.

    PubMed

    Kim, Hee-Young; Han, Jung-Ah; Kweon, Dong-Keon; Park, Jong-Dae; Lim, Seung-Taik

    2013-04-01

    Waxy maize starch was dispersed (14.7% solids) in an aqueous sulfuric acid solution (3.16M), and hydrolyzed by stirring for up to 7 days at 40°C with ultrasonic treatments at different vibration amplitudes (20 and 40%) and durations (30 and 60min/day). The amount of starch nanoparticles in the hydrolyzates isolated after 7 days, measured by a dynamic light scattering detector, was raised from 20% to 70% by an ultrasonic treatment (20% amplitude, 30min). The aggregation of nanoparticles possibly occurring during the hydrolysis was effectively prevented by the ultrasonication. Alternatively, ultrasonic treatments were applied to the re-dispersed suspension of the large microparticles of starch hydrolyzates (2 days) precipitated by a mild centrifugation (500rpm, 10min). By an ultrasonic treatment at 60% vibration amplitude for 3min, the microparticles could be completely transformed to nanoparticles. The inherent crystalline structure of waxy maize starch (A-type in X-ray diffraction) remained after the ultrasonic treatments during acid hydrolysis, but it was disrupted by the ultrasonic treatments for the re-dispersed microparticles. PMID:23499099

  7. Exogenous γ-aminobutyric acid treatment affects citrate and amino acid accumulation to improve fruit quality and storage performance of postharvest citrus fruit.

    PubMed

    Sheng, Ling; Shen, Dandan; Luo, Yi; Sun, Xiaohua; Wang, Jinqiu; Luo, Tao; Zeng, Yunliu; Xu, Juan; Deng, Xiuxin; Cheng, Yunjiang

    2017-02-01

    The loss of organic acids during postharvest storage is one of the major factors that reduces the fruit quality and economic value of citrus. Citrate is the most important organic acid in citrus fruits. Molecular evidence has proved that γ-aminobutyric acid (GABA) shunt plays a key role in citrate metabolism. Here, we investigated the effects of exogenous GABA treatment on citrate metabolism and storage quality of postharvest citrus fruit. The content of citrate was significantly increased, which was primarily attributed to the inhibition of the expression of glutamate decarboxylase (GAD). Amino acids, including glutamate, alanine, serine, aspartate and proline, were also increased. Moreover, GABA treatment decreased the fruit rot rate. The activities of antioxidant enzymes and the content of energy source ATP were affected by the treatment. Our results indicate that GABA treatment is a very effective approach for postharvest quality maintenance and improvement of storage performance in citrus production. PMID:27596402

  8. Treatment of olive mill wastewater by chemical processes: effect of acid cracking pretreatment.

    PubMed

    Hande Gursoy-Haksevenler, B; Arslan-Alaton, Idil

    2014-01-01

    The effect of acid cracking (pH 2.0; T 70 °C) and filtration as a pretreatment step on the chemical treatability of olive mill wastewater (chemical oxygen demand (COD) 150,000 m/L; total organic carbon (TOC) 36,000 mg/L; oil-grease 8,200 mg/L; total phenols 3,800 mg/L) was investigated. FeCl3 coagulation, Ca(OH)2 precipitation, electrocoagulation using stainless steel electrodes and the Fenton's reagent were applied as chemical treatment methods. Removal performances were examined in terms of COD, TOC, oil-grease, total phenols, colour, suspended solids and acute toxicity with the photobacterium Vibrio fischeri. Significant oil-grease (95%) and suspended solids (96%) accompanied with 58% COD, 43% TOC, 39% total phenols and 80% colour removals were obtained by acid cracking-filtration pretreatment. Among the investigated chemical treatment processes, electrocoagulation and the Fenton's reagent were found more effective after pretreatment, especially in terms of total phenols removal. Total phenols removal increased from 39 to 72% when pretreatment was applied, while no significant additional (≈10-15%) COD and TOC removals were obtained when acid cracking was coupled with chemical treatment. The acute toxicity of the original olive mill wastewater sample increased considerably after pretreatment from 75 to 89% (measured for the 10-fold diluted wastewater sample). An operating cost analysis was also performed for the selected chemical treatment processes. PMID:24718336

  9. Alkali Treatment of Acidic Solution from Hanford K Basin Sludge Dissolution

    SciTech Connect

    AA Bessonov; AB Yusov; AM Fedoseev; AV Gelis; AY Garnov; CH Delegard; GM Plavnik; LN Astafurova; MS Grigoriev; NA Budantseva; NN Krot; SI Nikitenko; TP Puraeva; VP Perminov; VP Shilov

    1998-12-22

    Nitric acid solutions will be created from the dissolution of Hanford K Basin sludge. These acidic dissolver solutions must be made alkaline by treatment with NaOH solution before they are disposed to ~ the Tank Waste Remediation System on the Hanford Site. During the alkali treatments, sodium diuranate, hydroxides of iron and aluminum, and radioelements (uranium, plutonium, and americium) will precipitate from the dissolver solution. Laboratory tests, discussed here, were pefiormed to provide information on these precipitates and their precipitation behavior that is important in designing the engineering flowsheet for the treatment process. Specifically, experiments were conducted to determine the optimum precipitation conditions; the completeness of uranium, plutonium, and americium precipitation; the rate of sedimentation; and the physico-chemical characteristics of the solids formed by alkali treatment of simulated acidic dissolver solutions. These experiments also determined the redistribution of uranium, plutonium, and americium flom the sodium di~ate and iron and al&inurn hydroxide precipitates upon contact with carbonate- and EDTA-bearing simulated waste solutions. Note: EDTA is the tetrasodium salt of ethylenediaminetetraacetate.

  10. A clinical pilot study of lignin--ascorbic acid combination treatment of herpes simplex virus.

    PubMed

    Lopez, Blanca Silvia Gonzalez; Yamamoto, Masaji; Utsumi, Katsuaki; Aratsu, Chiaki; Sakagami, Hiroshi

    2009-01-01

    Antiviral drugs as well as natural remedies have been used to reduce symptoms and the rate of recurrences of herpes simplex virus type 1 (HSV-1) infection, a common disease. To evaluate anti-HSV-1 activity of a pine cone lignin and ascorbic acid treatment, a clinical pilot study was carried out. Forty-eight healthy patients of both genders between 4 and 61 years old (mean: 31+/-16 years), with active lesions of HSV-1, took part in the study. According to the HSV-1 stage at the presentation, the patients were classified into the prodromic (16 patients), erythema (11 patients), papule edema (1 patient), vesicle/pustule (13 patients) and ulcer stages (7 patients). One mg of lignin-ascorbic acid tablet or solution was orally administered three times daily for a month. Clinical evaluations were made daily the first week and at least three times a week during the second week after the onset and every six months during the subsequent year to identify recurrence episodes. The patients who began the lignin-ascorbic acid treatment within the first 48 hours of symptom onset did not develop HSV-1 characteristic lesions, whereas those patients who began the treatment later experienced a shorter duration of cold sore lesions and a decrease in the symptoms compared with previous episodes. The majority of the patients reported the reduction in the severity of symptoms and the reduction in the recurrence episodes after the lignin-ascorbic acid treatment compared with previous episodes, suggesting its possible applicability for the prevention and treatment of HSV-1 infection. PMID:20023248

  11. The vertical transmission of salmonellas and formic acid treatment of chicken feed. A possible strategy for control.

    PubMed Central

    Humphrey, T. J.; Lanning, D. G.

    1988-01-01

    The treatment of feed given to laying hens with 0.5% formic acid reduced significantly the isolation rate of salmonellas and was associated with a reduction in the incidence of infection in newly hatched chicks. These improvements were not sustained until slaughter, however, as growing birds acquired salmonellas, probably from feed which was not acid treated. The data indicate that formic acid treatment of chicken food could have important benefits for the public health. PMID:3338506

  12. Re-treatment of relapsed Paget's disease of bone with zoledronic acid: results from an open-label study.

    PubMed

    Reid, Ian R; Brown, Jacques P; Levitt, Naomi; Román Ivorra, José A; Bachiller-Corral, Javier; Ross, Ian L; Su, Guoqin; Antunez-Flores, Oscar; Aftring, R Paul

    2013-01-01

    Six patients from the phase 3 trials of zoledronic acid in Paget's disease, who had received zoledronic acid initially and had subsequently relapsed, were entered into an open re-treatment study. Following re-treatment, each patient reached similar absolute nadirs of serum alkaline phosphatase to those recorded after their first dose. No significant adverse events were reported. It is concluded that, while re-treatment of Paget's disease with zoledronic acid is rarely needed, it is safe and effective, with no evidence of treatment resistance based on this small cohort. PMID:24422139

  13. Improvement in electrochemical capacitance of activated carbon from scrap tires by nitric acid treatment

    NASA Astrophysics Data System (ADS)

    Han, Yan; Zhao, Ping-Ping; Dong, Xiao-Ting; Zhang, Cui; Liu, Shuang-Xi

    2014-12-01

    Activated carbon (AC) obtained from the industrial pyrolytic tire char is treated by concentrated nitric acid (AC-HNO3) and then used as the electrode material for supercapacitors. Surface properties and electrochemical capacitances of AC and ACHNO3 are studied. It is found that the morphology and the porous texture for AC and AC-HNO3 have little difference, while the oxygen content increases and functional groups change after the acid treatment. Electrochemical results demonstrate that the AC-HNO3 electrode displays higher specific capacitance, better stability and cycling performance, and lower equivalent series resistance, indicating that AC obtained from the industrial pyrolytic tire char treated by concentrated nitric acid is applicable for supercapacitors.

  14. Geochemistry of rare earth elements in a passive treatment system built for acid mine drainage remediation.

    PubMed

    Prudêncio, Maria Isabel; Valente, Teresa; Marques, Rosa; Sequeira Braga, Maria Amália; Pamplona, Jorge

    2015-11-01

    Rare earth elements (REE) were used to assess attenuation processes in a passive system for acid mine drainage treatment (Jales, Portugal). Hydrochemical parameters and REE contents in water, soils and sediments were obtained along the treatment system, after summer and winter. A decrease of REE contents in the water resulting from the interaction with limestone after summer occurs; in the wetlands REE are significantly released by the soil particles to the water. After winter, a higher water dynamics favors the AMD treatment effectiveness and performance since REE contents decrease along the system; La and Ce are preferentially sequestered by ochre sludge but released to the water in the wetlands, influencing the REE pattern of the creek water. Thus, REE fractionation occurs in the passive treatment systems and can be used as tracer to follow up and understand the geochemical processes that promote the remediation of AMD. PMID:26247412

  15. Effects of heat treatment on chitosan nanocomposite film reinforced with nanocrystalline cellulose and tannic acid.

    PubMed

    Rubentheren, V; Ward, Thomas A; Chee, Ching Yern; Nair, Praveena; Salami, Erfan; Fearday, Christopher

    2016-04-20

    This article presents an analysis of the influence of heat treatment on chitosan nanocomposite film. A series of samples comprising: pure chitosan film, chitosan film embedded with nanocrystalline cellulose (NCC), chitosan film crosslinked with tannic acid and chitosan film with a blend of NCC and tannic acid were heat treated using a convection oven. Fourier-transform-infrared spectroscopy (FTIR) and X-ray diffraction test (XRD) shows the changes in chemical interaction of the heat treated films. The heat treated films show significant improvements in moisture absorption. Tensile strength and Young's Modulus were increased up to 7MPa and 259MPa, respectively when the samples were subjected to heat treatment. For the NCC particles, a transmission electron microscope (TEM) was used to inspect the structural properties of cellulose particle in suspension form. PMID:26876845

  16. Topical treatments for hydrofluoric acid dermal burns. Further assessment of efficacy using an experimental piq model.

    PubMed

    Dunn, B J; MacKinnon, M A; Knowlden, N F; Billmaier, D J; Derelanko, M J; Rusch, G M; Naas, D J; Dahlgren, R R

    1996-05-01

    Several topical treatments for hydrofluoric acid dermal burns (Zephiran, calcium acetate and magnesium hydroxide antacid soaks, and calcium gluconate gel) were assessed for efficacy in a pig model. Gross appearance and histopathology of treated and untreated burn sites were evaluated. For superficial burns, Zephiran was most effective; calcium acetate, magnesium hydroxide antacid, and calcium gluconate gel were less effective. For deep burns, gross observations showed that calcium acetate and Zephiran were most efficacious, whereas histopathology indicated comparable efficacy of Zephiran, calcium acetate, and calcium gluconate gel for all skin layers. Magnesium hydroxide antacid demonstrated efficacy only for the subdermis. The clinically beneficial effects of both Zephiran and calcium gluconate gel were affirmed. Although results suggest that calcium acetate and magnesium-containing antacids may be beneficial for human hydrofluoric acid dermal burns, these are not established clinical treatments. PMID:8733642

  17. Decontamination and inspection plan for phase 2 closure of the 300-Area waste acid treatment system

    SciTech Connect

    Hays, C.B.

    1998-02-06

    This decontamination and inspection plan (DIP) describes decontamination and verification activities in support of Phase 2 closure of the 300 Area Waste Acid Treatment System (WATS). Phase 2, the second phase of three proposed phases of closure for WATS, provides for closure of all WATS portions of the 334-A Building and some, but not all, WATS portions of the 333 and 303-F Buildings. Closure of the entire unit will not occur until all three closure phases have been completed. The DIP also describes the designation and management-process for waste and debris generated during Phase 2 closure activities. Information regarding the decontamination and verification methods for Phase 1 closure can be found in Decontamination and Inspection Plan, for Phase 1 closure of the 300 Area Waste Acid Treatment System, 21 WHC-SD-ENV-AP-001. Information regarding Phase 3 closure will be provided in later documents.

  18. Influence of Fenofibrate Treatment on Triacylglycerides, Diacylglycerides and Fatty Acids in Fructose Fed Rats

    PubMed Central

    Kopf, Thomas; Schaefer, Hans-Ludwig; Troetzmueller, Martin; Koefeler, Harald; Broenstrup, Mark; Konovalova, Tatiana; Schmitz, Gerd

    2014-01-01

    Fenofibrate (FF) lowers plasma triglycerides via PPARα activation. Here, we analyzed lipidomic changes upon FF treatment of fructose fed rats. Three groups with 6 animals each were defined as control, fructose-fed and fructose-fed/FF treated. Male Wistar Unilever Rats were subjected to 10% fructose-feeding for 20 days. On day 14, fenofibrate treatment (100 mg/kg p.o.) was initiated and maintained for 7 days. Lipid species in serum were analyzed using mass spectrometry (ESI-MS/MS; LC-FT-MS, GC-MS) on days 0, 14 and 20 in all three groups. In addition, lipid levels in liver and intestine were determined. Short-chain TAGs increased in serum and liver upon fructose-feeding, while almost all TAG-species decreased under FF treatment. Long-chain unsaturated DAG-levels (36:1, 36:2, 36:4, 38:3, 38:4, 38:5) increased upon FF treatment in rat liver and decreased in rat serum. FAs, especially short-chain FAs (12:0, 14:0, 16:0) increased during fructose-challenge. VLDL secretion increased upon fructose-feeding and together with FA-levels decreased to control levels during FF treatment. Fructose challenge of de novo fatty acid synthesis through fatty acid synthase (FAS) may enhance the release of FAs ≤16:0 chain length, a process reversed by FF-mediated PPARα-activation. PMID:25198467

  19. Passive treatment of acid mine drainage with high metal concentrations using dispersed alkaline substrate.

    PubMed

    Rötting, Tobias S; Thomas, Robert C; Ayora, Carlos; Carrera, Jesús

    2008-01-01

    Passive treatment systems based on the dissolution of coarse calcite grains are widely used to remediate acid mine drainage (AMD). Unfortunately, they tolerate only low metal concentrations or acidity loads, because they are prone to passivation (loss of reactivity due to coating) and/or clogging (loss of permeability) by precipitates. To overcome these problems, a dispersed alkaline substrate (DAS) composed of a fine-grained alkaline reagent (calcite sand) mixed with a coarse inert matrix (wood chips) was developed. The small grains provide a large reactive surface and dissolve almost completely before the growing layer of precipitates passivates the substrate, whereas the dispersion of nuclei for precipitation on the inert surfaces retards clogging. Chemical and hydraulic performance of DAS was investigated in two laboratory columns fed at different flow rates with natural AMD of pH 2.3 to 3.5 and inflow net acidity 1350 to 2300 mg/L as CaCO(3). The DAS columns removed 900 to 1600 mg/L net acidity, 3 to 4.5 times more than conventional passive treatment systems. Regardless of the flow rate employed, Al, Fe(III), Cu, and Pb were virtually eliminated. Minor Zn, Ni, and Cd were removed at low flow rates. High acidity removal is possible because these metals accumulate intentionally in DAS, and their precipitation promotes further calcite dissolution. During 15 mo, DAS operated without clogging at 120 g acidity/m(2).d, four times the loading rate recommended for conventional passive systems; DAS may therefore be capable of treating AMD at sites where influent chemistry precludes the use of other passive systems. PMID:18689735

  20. Core acid treatment influence on well reservoir properties in Kazan oil-gas condensate field

    NASA Astrophysics Data System (ADS)

    Janishevskii, A.; Ezhova, A.

    2015-11-01

    The research involves investigation of the influence of hydrochloric acid (HCI-12%) and mud acid (mixture: HCl - 10% and HF - 3%) treatment on the Upper-Jurassic reservoir properties in Kazan oil-gas condensate field wells. The sample collection included three lots of core cylinders from one and the same depth (all in all 42). Two lots of core cylinders were distributed as following: first lot - reservoir properties were determined, and, then thin sections were cut off from cylinder faces; second lot- core cylinders were exposed to hydrochloric acid treatment, then, after flushing the reservoir properties were determined, and thin sections were prepared. Based on the quantitative petrographic rock analysis, involvin 42 thin sections, the following factors were determined: granulometric mineral composition, cement content, intergranular contacts and pore space structure. According to the comparative analysis of initial samples, the following was determined: content decrease of feldspar, clay and mica fragments, mica, clay and carbonate cement; increase of pore spaces while in the investigated samples- on exposure of rocks to acids effective porosity and permeability value range is ambiguous.

  1. The influence of acid treatments over vermiculite based material as adsorbent for cationic textile dyestuffs.

    PubMed

    Stawiński, Wojciech; Freitas, Olga; Chmielarz, Lucjan; Węgrzyn, Agnieszka; Komędera, Kamila; Błachowski, Artur; Figueiredo, Sónia

    2016-06-01

    The influence of different acid treatments over vermiculite was evaluated. Equilibrium, kinetic and column studies have been conducted. The results showed that vermiculite first treated with nitric acid and then with citric acid has higher adsorption capacity, presenting maximum adsorption capacities in column experiments: for Astrazon Red (AR), 100.8 ± 0.8 mg g(-1) and 54 ± 1 mg g(-1) for modified and raw material, respectively; for Methylene Blue (MB) 150 ± 4 mg g(-1) and 55 ± 2 mg g(-1) for modified and raw material, respectively. Materials characterization by X-ray diffraction, UV-vis-diffuse reflectance spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy, X-ray fluorescence, N2 adsorption and CEC determination, has been performed. The results suggest the existence of exchange of interlayer cations, leaching of metals from vermiculite's sheets and formation of an amorphous phase in the material. Adsorption follows pseudo 2(nd) order model kinetics for both dyestuffs and equilibrium occurs accordingly to Langmuir's model for AR and Freundlich's model for MB. In column systems Yan's model is the best fit. The enhanced properties of acid treated vermiculite offer new perspectives for the use of this adsorbent in wastewater treatment. PMID:27015571

  2. Recovery of calcium carbonate from steelmaking slag and utilization for acid mine drainage pre-treatment.

    PubMed

    Mulopo, J; Mashego, M; Zvimba, J N

    2012-01-01

    The conversion of steelmaking slag (a waste product of the steelmaking process) to calcium carbonate (CaCO(3)) was tested using hydrochloric acid, ammonium hydroxide and carbon dioxide via a pH-swing process. Batch reactors were used to assess the technical feasibility of calcium carbonate recovery and its use for pre-treatment of acid mine drainage (AMD) from coal mines. The effects of key process parameters, such as the amount of acid (HCl/calcium molar ratio), the pH and the CO(2) flow rate were considered. It was observed that calcium extraction from steelmaking slag significantly increased with an increase in the amount of hydrochloric acid. The CO(2) flow rate also had a positive effect on the carbonation reaction rate but did not affect the morphology of the calcium carbonate produced for values less than 2 L/min. The CaCO(3) recovered from the bench scale batch reactor demonstrated effective neutralization ability during AMD pre-treatment compared with the commercial laboratory grade CaCO(3). PMID:22643421

  3. The potential role of boswellic acids in cancer prevention and treatment.

    PubMed

    Roy, Nand Kishor; Deka, Anindita; Bordoloi, Devivasha; Mishra, Srishti; Kumar, Alan Prem; Sethi, Gautam; Kunnumakkara, Ajaikumar B

    2016-07-10

    Despite the extensive research carried out in the field of cancer therapeutics, cancer is one of the most dreadful diseases in the world with no definitive treatment to date. The key attributes responsible for this are the various limiting factors associated with conventional chemotherapeutics that primarily include adverse side-effects and development of chemoresistance. Hence, there is an utter need to find compounds that are highly safe and efficacious for the prevention and treatment of cancer. Boswellic acid, a group of pentacyclic compounds, seems to be promising enough due to its inherent anti-cancerous properties. Considering this perspective, the present review highlights the established studies related to the anti-cancer potential of boswellic acid against different cancer types. The molecular mechanisms underlying the targets of boswellic acid that are accountable for its potent anti-cancer effect are also discussed. Overall, this review projects the pieces of evidence that reveal the potential of boswellic acid as a suitable candidate that can be appropriately developed and designed into a promising anti-cancer drug. PMID:27091399

  4. Local utilization of metacresolsulfonic acid combined with streptomycin in the treatment of actinomycosis.

    PubMed

    Silva, L A F; Fioravanti, M C S; Oliveira, K S; Atayde, I B; Andrade, M A; Jayme, V S; Rabelo, R E; Romani, A F; Araújo, E G

    2004-10-01

    The effectiveness of combining metacresolsufonic acid with streptomycin in the treatment of actinomycosis, diagnosed either clinically or in the laboratory, was evaluated in 12 bovines and 2 equines. Eighty-seven percent of treated animals were considered clinically cured and did not show any signs of relapse after a six-month follow-up period. Therapeutic diagnosis by clinical observation was the procedure of choice when it was not possible to obtain laboratory diagnosis. PMID:15604505

  5. Controlled trial of oligopeptide versus amino acid diet in treatment of active Crohn's disease.

    PubMed Central

    Mansfield, J C; Giaffer, M H; Holdsworth, C D

    1995-01-01

    Elemental diets are effective in inducing remission in active Crohn's disease, but how they exert this therapeutic effect is unclear. In a previous study a whole protein containing diet proved less effective than one in which food antigens were excluded, suggesting that exclusion of food antigens from the gut was a possible mechanism. This study was designed to test whether an oligopeptide diet of hydrolysed proteins was as effective as an amino acid based diet. These diets were equally antigen free but with different nitrogen sources. Forty four patients with active Crohn's disease were randomised in a controlled trial of amino acid versus oligopeptide diet. The feeds were given by nasogastric tube in equicaloric quantities and were the sole form of nutrition. Treatment was continued for four weeks although failure to improve by day 10 resulted in withdrawal. Quantitative leucocyte scintigraphy was used to investigate the effect of diet treatment on gut inflammation. Clinical and nutritional responses to treatment were also measured. Sixteen patients entered remission (including withdrawal of corticosteroids), six patients could not tolerate the nasogastric tube, and 22 patients failed to respond. The two diets were equally effective. Patients who responded had a rapid drop in clinical index of disease activity and a major reduction in the bowel uptake of leucocytes on scintigraphy. The oligopeptide and amino acid based enteral feeds were equally effective at inducing remission in active Crohn's disease. With both diets clinical improvement was accompanied by a reduction in intestinal inflammation. Images Figure 3 PMID:7890238

  6. Use of Fusidic Acid for Desquamative Gingivitis Treatment: 1-Year Follow-Up.

    PubMed

    Leite, Fábio Renato Manzolli; Nascimento, Gustavo Giacomelli; Demarco, Flávio Fernando; Waechter, Janine; Etges, Adriana

    2015-01-01

    This study evaluated retrospectively the effect of fusidic acid on the management of desquamative gingivitis (DG). The study population consisted of 15 patients with DG. Patients were requested to make topical application of 2% fusidic acid ointment 4 times a day for 6 weeks. Clinical assessments were recorded at baseline, at 6 weeks and 12 months after beginning the therapy. Patients' examination involved lesion size area, pain score and impact on daily activities. All patients presented lesions in maxilla; in 9 patients (60.0%) lesions were predominately at the anterior region and 6 (40.0%) at the posterior region of maxilla. Treatment significantly (p < 0.05) reduced the pain intensity (from 5.4 ± 1.12 to 1.16 ± 0.97) and its periodicity (from 53.33% with pain > 3 x/week to 13.33%), and the lesion size in 72.47% (± 4.12) immediately after 6 weeks of treatment. Improvements were sustained for 12 months compared to baseline (p < 0.001). It also reduced the impact of disease in daily activities (eating and oral hygiene performance), and improved the emotional condition of patients, who reported better social relationships and habits. Topical application of fusidic acid may be a possible alternative local palliative therapy for desquamative gingivitis treatment. PMID:26312984

  7. Regulating acidity, porosity, and morphology of hierarchical SAPO-11 zeolite by aging treatment.

    PubMed

    Liu, Yuxiang; Xu, Lu; Lv, Yuchao; Liu, Xinmei

    2016-10-01

    A facile method to modify pore structure, acidic character, and morphology of SAPO-11 molecular sieve was proposed. Aging treatment (e.g., microwave irradiation or lyophilization) is introduced in the preparation of dry gel. It regulates the kinetics of zeolitic nucleation and growth. X-ray diffraction, scanning electron microscopy, N2-adsorption, temperature programmed desorption, laser particle analyzer, and (29)Si MAS NMR were employed to investigate the effects of aging treatments on SAPO-11 products. The experimental results indicate that depolymerization reaction of silicon species is enhanced aged by microwave irradiation with a higher temperature (90°C). Ratio of SM 3 to SM 2 substituting mode increases producing more strong Brønsted acid sites. Lyophilization technology, as another aging method, was employed to control the morphology of SAPO-11. Nano-sized hierarchical SAPO-11 molecular sieve (200nm in length) is obtained with an oriented growth. Activity of hydroisomerization catalysts is regulated by aging treatment. Cracking reaction attributes to a high conversion nearly 87wt% for M90. The hydroisomerization reaction is enhanced for M40 due to a large proportion of moderate acid sites. PMID:27362909

  8. Foraging at wastewater treatment works affects brown adipose tissue fatty acid profiles in banana bats

    PubMed Central

    Hill, Kate; van Aswegen, Sunet; Schoeman, M. Corrie; Claassens, Sarina; Jansen van Rensburg, Peet; Naidoo, Samantha; Vosloo, Dalene

    2016-01-01

    ABSTRACT In this study we tested the hypothesis that the decrease in habitat quality at wastewater treatment works (WWTW), such as limited prey diversity and exposure to the toxic cocktail of pollutants, affect fatty acid profiles of interscapular brown adipose tissue (iBrAT) in bats. Further, the antioxidant capacity of oxidative tissues such as pectoral and cardiac muscle may not be adequate to protect those tissues against reactive molecules resulting from polyunsaturated fatty acid auto-oxidation in the WWTW bats. Bats were sampled at two urban WWTW, and two unpolluted reference sites in KwaZulu-Natal, South Africa. Brown adipose tissue (BrAT) mass was lower in WWTW bats than in reference site bats. We found lower levels of saturated phospholipid fatty acids and higher levels of mono- and polyunsaturated fatty acids in WWTW bats than in reference site bats, while C18 desaturation and n-6 to n-3 ratios were higher in the WWTW bats. This was not associated with high lipid peroxidation levels in pectoral and cardiac muscle. Combined, these results indicate that WWTW bats rely on iBrAT as an energy source, and opportunistic foraging on abundant, pollutant-tolerant prey may change fatty acid profiles in their tissue, with possible effects on mitochondrial functioning, torpor and energy usage. PMID:26740572

  9. Chemical stability of acid rock drainage treatment sludge and implications for sludge management

    SciTech Connect

    Danny M. McDonald; John A. Webb; Jeff Taylor

    2006-03-15

    To assess the chemical stability of sludges generated by neutralizing acid rock drainage (ARD) with alkaline reagents, synthetic ARD was treated with hydrated lime (batch and high-density sludge process), limestone, and two proprietary reagents (KB-1 and Bauxsol). The amorphous metal hydroxide sludge produced was leached using deionized water, U.S. EPA methods (toxicity characteristic leaching procedure, synthetic precipitation leaching procedure), and the new strong acid leach test (SALT), which leaches the sludge with a series of sulfuric acid extractant solutions; the pH decreases by {approximately} 1 pH unit with each test, until the final pH is {approximately}2. Sludges precipitated by all reagents had very similar leachabilities except for KB-1 and Bauxsol, which released more aluminum. SALT showed that lowering the pH of the leaching solution mobilized more metals from the sludges. Iron, aluminum, copper, and zinc began to leach at pH 2.5-3, {approximately}4.5, {approximately}5.5, and 6-6.5, respectively. The leachability of ARD treatment sludges is determined by the final pH of the leachate. A higher neutralization potential (e.g., a greater content of unreacted neutralizing agent) makes sludges inherently more chemically stable. Thus, when ARD or any acidic metalliferous wastewater is treated, a choice must be made between efficient reagent use and resistance to acid attack. 26 refs., 5 figs., 2 tabs.

  10. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    PubMed

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it. PMID:26634573

  11. Chemical stability of acid rock drainage treatment sludge and implications for sludge management.

    PubMed

    McDonald, Danny M; Webb, John A; Taylor, Jeff

    2006-03-15

    To assess the chemical stability of sludges generated by neutralizing acid rock drainage (ARD) with alkaline reagents, synthetic ARD was treated with hydrated lime (batch and high-density sludge process), limestone, and two proprietary reagents (KB-1 and Bauxsol). The amorphous metal hydroxide sludge produced was leached using deionized water, U.S. EPA methods (toxicity characteristic leaching procedure, synthetic precipitation leaching procedure), and the new strong acid leach test (SALT), which leaches the sludge with a series of sulfuric acid extractant solutions; the pH decreases by approximately 1 pH unit with each test, until the final pH is approximately 2. Sludges precipitated by all reagents had very similar leachabilities except for KB-1 and Bauxsol, which released more aluminum. SALT showed that lowering the pH of the leaching solution mobilized more metals from the sludges. Iron, aluminum, copper, and zinc began to leach at pH 2.5-3, approximately 4.5, approximately 5.5, and 6-6.5, respectively. The leachability of ARD treatment sludges is determined by the final pH of the leachate. A higher neutralization potential (e.g., a greater content of unreacted neutralizing agent) makes sludges inherently more chemically stable. Thus, when ARD or any acidic metalliferous wastewater is treated, a choice must be made between efficient reagent use and resistance to acid attack. PMID:16570625

  12. The effect of limestone treatments on the rate of acid generation from pyritic mine gangue.

    PubMed

    Burt, R A; Caruccio, F T

    1986-09-01

    Surface water enters the Haile Gold Mine, Lancaster County, South Carolina by means of a small stream and is ponded behind a dam and in an abandoned pit. This water is affected by acidic drainage. In spite of the large exposures of potentially acid producing pyritic rock, the flux of acid to the water is relatively low. Nevertheless, the resulting pH values of the mine water are low (around 3.5) due to negligible buffering capacity. In view of the observed low release of acidity, the potential for acid drainage abatement by limestone ameliorants appears feasible.This study investigated the effects of limestone treatment on acid generation rates of the Haile mine pyritic rocks through a series of leaching experiments. Below a critical alkalinity threshold value, solutions of dissolved limestone were found consistently to accelerate the rate of pyrite oxidation by varying degrees. The oxidation rates were further accelerated by admixing solid limestone with the pyritic rock. However, after a period of about a month, the pyrite oxidation rate of the admixed samples declined to a level lower than that of untreated pyrite. Leachates produced by the pyrite and limestone mixtures contained little if any iron. Further, in the mixtures, an alteration of the pyrite surface was apparent.The observed behaviour of the treated pyrite appears to be related to the immersion of the pyrite grains within a high alkalinity/high pH environment. The high pH increases the rate of oxidation of ferrous iron which results in a higher concentration of ferric iron at the pyrite surface. This, in turn, increases the rate of pyrite oxidation. Above a threshold alkalinity value, the precipitation of hydrous iron oxides at the pyrite surface eventually outpaces acid generation and coats the pyrite surface, retarding the rate of pyrite oxidation. PMID:24214013

  13. Geophysical mapping and subsurface injection for treatment of post-reclamation acid drainage

    SciTech Connect

    Plocus, V.G.; Rastogi, V.

    1997-12-31

    Post-reclamation acid discharge has haunted abandoned mine lands reclamation programs and the mining industry reclamation efforts. Many mine sites have been reclaimed, as mandated by regulations, but continue to generate acid. Such sites represent perpetual treatment problems for operators and, in the case of bond forfeitures or abandoned mine reclamation projects, they represent sources of perpetual surface and groundwater degradation. Post-reclamation discharge occurs when the Thiobacillus ferrooxidans bacteria, not destroyed prior to soil cover in the reclamation process, continue to thrive, even in a supposedly anaerobic environment. A post-reclamation remediation system utilizing subsurface injection of sodium hydroxide and an anionic surfactant offers a two phase integrated technologies approach. In Phase 1, the site is characterized by geophysical mapping with (1) electromagnetic terrain conductivity meters to determine locations of subsurface aquifers, and (2) proton processing magnetometers to delineate zones of pyritic oxidation in the subsurface environment. Infiltrometers are also used to determine permeability which influences pressure requirements and distance between wells. Site conditions and water analyses help quantify requirements for injection of sodium hydroxide and bactericide. Phase 2 involves drilling two sets of injection wells; the first into the acidified water table for injection of 20% sodium hydroxide solution to neutralize existing acid water, and the second into the acid producing material for injection of a 20% sodium hydroxide solution to neutralize existing acid salts, followed by a 2% solution of bactericide. The sodium hydroxide is injected to neutralize existing acid which prevents future acid generation. Results from a site in Pennsylvania, USA, which was treated in this manner are reported.

  14. Effect of quarantine treatments on the carbohydrate and organic acid content of mangoes (cv. Tommy Atkins)

    NASA Astrophysics Data System (ADS)

    Cruz, J. N.; Soares, C. A.; Fabbri, A. D. T.; Cordenunsi, B. R.; Sabato, S. F.

    2012-08-01

    Brazil is one of the largest mango producers and the third largest mango exporter worldwide. Irradiation treatment and its commercial feasibility have been studied in our country to make it possible to develop new markets and, consequently, to compete with the major exporters of mangoes, Mexico and India. This work was designed to compare irradiation treatment with the hot water dip treatment in mangoes cv. Tommy Atkins for export and to verify that the main attributes for acceptance, color and texture, as well as carbohydrate and organic acid contents, were maintained. In this study, the fruit was divided into groups: control, hot water dip-treated (46 °C for 90 min), and irradiation-treated at doses of 0.4 kGy and 1.0 kGy. The fruit was stored at low temperature (11 °C±2) for 14 days and then at room temperature (23 °C±2) until the end of the study. The results indicated that the fruit given a dose of 1.0 kGy remained in a less advanced stage of ripening (stage 3) throughout the storage period, but experienced a greater loss of texture in the beginning of the experiment. It was noted that only the control group had higher levels of citric acid and succinic acid on the last day of the experiment. There were no significant differences in the total sugar content between any treatment groups. Gamma radiation can be used as a quarantine treatment and does not interfere negatively with the quality attributes of mangoes.

  15. Bioassessment of a combined chemical-biological treatment for synthetic acid mine drainage.

    PubMed

    Pagnanelli, F; De Michelis, I; Di Muzio, S; Ferella, F; Vegliò, F

    2008-11-30

    In this work, ecotoxicological characteristics of synthetic samples of acid mine drainage (AMD) before and after a combined chemical-biological treatment were investigated by using Lepidium sativum and Daphnia magna. AMD treatment was performed in a two-column apparatus consisting of chemical precipitation by limestone and biological refinement by sulphate reducing bacteria. Synthetic samples of AMD before treatment were toxic for both L. sativum (germination index, G, lower than 10%) and D. magna (100% immobility) due to acid pH and presence of copper and zinc. Chemical treatment (raising pH to 5-6 and eliminating copper) generated effluents with reduced toxicity for L. sativum (G=33%), while 100% immobility was still observed for D. magna. Dynamic trends of toxicity for the first and fifth outputs of the biological column denoted a gradual improvement leading to hormesis for Lepidium (after the initial release of organic excess), while a constant residual toxicity remained for Daphnia (probably due to H(2)S produced by sulphate reducing bacteria). PMID:18394799

  16. Treatment of Myositis Ossificans with acetic acid phonophoresis: a case series

    PubMed Central

    Bagnulo, Angela; Gringmuth, Robert

    2014-01-01

    Objective To create awareness of myositis ossificans (MO) as a potential complication of muscle contusion by presenting its clinical presentation and diagnostic features. An effective method of treatment is offered for those patients who develop traumatic MO. Management: Patients in this case series developed traumatic MO, confirmed on diagnostic ultrasound. Patients participated in a treatment regimen consisting of phonophoresis of acetic acid with ultrasound. Outcome: In all cases, a trial of phonophoresis therapy significantly decreased patient signs, symptoms and the size of the calcification on diagnostic ultrasound in most at a 4-week post diagnosis mark. Discussion: Due to the potential damage to the muscle and its function, that surgical excision carries; safe effective methods of conservative treatment for MO are crucial. MO deserves more attention in the literature due to its common presentation in athletes. PMID:25550659

  17. Activated sludge as substrate for sulfate-reducing bacteria in acid mine drainage treatment

    SciTech Connect

    Al-Ani, W.A.G.; Henry, J.G.; Prasad, D.

    1996-11-01

    Acid mine drainage (AMD), characterized by high concentrations of sulfates and heavy metals and low pH, presents a potential hazard to the environment.Several treatment processes (chemical precipitation, ion exchange, reverse osmosis, electrodialysis and electrolytic recovery) are available, but these are often too expensive. Biological treatment of AMD, mediated by sulfate-reducing bacteria (SRB), seems promising. The objective of this study was to use activated sludge as a carbon source for the SRB and determine the most effective COD/sulfate ratio and hydraulic retention time (HRT) for reducing sulfate. Such information would be useful for the application of the proposed two-stage system to AMD treatment. Since the aim of this study was to obtain sulfate reduction and to avoid methane production, it was decided to operate the digesters initially at low COD/SO{sub 4}{sup 2{minus}} ratios of 1.0, 1.5, and 2.0.

  18. [Experience in using glutamic acid electrophoresis in the early treatment of craniocerebral injuries].

    PubMed

    Naĭdin, V L; Karaseva, T A; Salazkina, S I; Zhukov, P V; Krotkova, O A

    1982-01-01

    Endonasal electrophoresis with alpha-glutamic acid was used in 76 patients with severe craniocerebral injury. The result was good in 24 (38%) and satisfactory in 40 (55%) patients. Thus, a positive result of treatment was obtained in 88% of cases, which was confirmed by electrophysiological and neuropsychological studies. The method produced the greatest effect on the patients' psychic status: 74% of all disorders of higher psychic functions, mainly memory, were restored on the average by the end of treatment. Good tolerance of electrophoresis and its efficacy in the early period after severe injury, i. e. in the first month, were established. Contraindications for treatment were defined more precisely. Since the method is simple and does not call for special conditions, it may be widely used in any medical establishment equipped with galvanization apparatuses. PMID:6121438

  19. Topical diclofenac/hyaluronic acid gel in the treatment of solar keratoses.

    PubMed

    McEwan, L E; Smith, J G

    1997-11-01

    A randomized double-blind controlled trial of 130 patients was performed to study the efficacy and tolerability of topical 3% diclofenac in 2.5% hyaluronic acid (HA) gel (active) versus gel containing 2.5% HA alone (control) in the treatment of solar keratoses. Patients were asked to apply trial gel to the target lesion twice a day and also sunscreen once a day for 24 weeks. The complete response rates were 29% for the active gel and 17% for the control gel. The difference was not statistically significant (P = 0.14). A high percentage of patients in both groups experienced a partial response to treatment (38% active, 45% control) but there was no significant difference in the spectrum of response between the two treatments (P = 0.18). Local adverse reactions occurred significantly more frequently in patients using the active gel (29% compared to 5% using control gel, P = 0.0002). PMID:9431711

  20. Co-treatment of acid mine drainage with municipal wastewater: performance evaluation.

    PubMed

    Hughes, Theresa A; Gray, Nicholas F

    2013-11-01

    Co-treatment of acid mine drainage (AMD) with municipal wastewater (MWW) using the activated sludge process is a novel treatment technology offering potential savings over alternative systems in materials, proprietary chemicals and energy inputs. The impacts of AMD on laboratory-scale activated sludge units (plug-flow and sequencing batch reactors) treating synthetic MWW were investigated. Synthetic AMD containing Al, Cu, Fe, Mn, Pb, Zn and SO4 at a range of concentrations and pH values was formulated to simulate three possible co-treatment processes, i.e., (1) adding raw AMD to the activated sludge aeration tank, (2) pre-treating AMD prior to adding to the aeration tank by mixing with digested sludge and (3) pre-treating AMD by mixing with screened MWW. Continuous AMD loading to the activated sludge reactors during co-treatment did not cause a significant decrease in chemical oxygen demand (COD), 5-day biochemical oxygen demand, or total organic carbon removal; average COD removal rates ranged from 87-93%. Enhanced phosphate removal was observed in reactors loaded with Fe- and Al-rich AMD, with final effluent TP concentrations<2 mg/L. Removal rates for dissolved Al, Cu, Fe and Pb were 52-84%, 47-61%, 74-86% and 100%, respectively, in both systems. Manganese and Zn removal were strongly linked to acidity; removal from net-acidic AMD was <10% for both metals, whereas removal from circum-neutral AMD averaged 93-95% for Mn and 58-90% for Zn. Pre-mixing with screened MWW was the best process option in terms of AMD neutralization and metal removal. However, significant MWW alkalinity was consumed, suggesting an alkali supplement may be necessary. PMID:23161500

  1. Analysis of free amino acids in green coffee beans. II. Changes of the amino acid content in arabica coffees in connection with post-harvest model treatment.

    PubMed

    Arnold, U; Ludwig, E

    1996-10-01

    To investigate amino acid changes in green coffee beans in the post-harvest period, amino acid concentrations were determined in green beans and after modelled drying, fermentation and storage. After the drying at alternating temperatures up to maximally 40 degrees C, considerable changes in the concentrations of individual amino acids were identified. At the beginning of the storage period, significant changes in concentration were found to a minor extent. Under the condition of drying, it was mainly the concentration of glutamic acid that changed considerably. There was an increase in all the samples by 500 mg/kg dry matter on average, which corresponds to an increase of about 50% of the original value. In contrast, the concentration of aspartic acid in most of the samples decreased clearly due to drying. For the predominant part of the coffee samples, there was a significant increase in the hydrophobic amino acids Val, Phe, Ile and Leu. Changes of the quantities of other amino acids were non-uniform and only insignificant. Constant drying at 80 degrees C for most of the amino acids brought about only minor concentration changes compared to those values obtained at 40 degrees C. Modelled fermentation had no significant effect on the concentrations of the individual amino acids. After a 4-week storage of dried beans, amino acid concentrations did not change further. It is very possible that different post-harvest treatment parameters may influence the amount of aroma precursor compounds in the coffee beans. PMID:9123976

  2. Enhanced charge transport in highly conducting PEDOT-PSS films after acid treatment

    NASA Astrophysics Data System (ADS)

    Shiva, V. Akshaya; Bhatia, Ravi; Menon, Reghu

    The high electrical conductivity, good stability, high strength, flexibility and good transparency of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS), make it useful for many applications including polymeric anodes for organic photovoltaics, light-emitting diodes, flexible electrodes, supercapacitors, electrochromic devices, field-effect transistors and antistatic-coatings. However, the electrical conductivity of PEDOT-PSS has to be increased significantly for replacement of indium tin oxide (ITO) as the transparent electrode in optoelectronic devices. The as prepared (pristine) PEDOT-PSS film prepared from the PEDOT-PSS aqueous solution usually has conductivity below 1Scm-1, remarkably lower than ITO. Significant conductivity enhancement has been observed on transparent and conductive PEDOT-PSS films after a treatment with inorganic acids. Our study investigates the charge transport in pristine and H2SO4, HNO3, HCl treated PEDOT-PSS films. We have treated the films with various concentrations of acids to probe the effect of the acid treatment on the conduction mechanism. The study includes the measurement of dc and electric field dependent conductivity of films in the temperature range of 4.2K-300K. We have also performed magneto-resistance measurements in the range of 0-5T. An enhancement by a factor of~103 has been observed in the room temperature conductivity. The detailed magneto-transport studies explain the various mechanisms for the conductivity enhancement observed.

  3. In Vivo Treatment of Propionibacterium acnes Infection with Liposomal Lauric Acids

    PubMed Central

    Pornpattananangkul, Dissaya; Fu, Victoria; Thamphiwatana, Soracha; Zhang, Li; Chen, Michael; Vecchio, James; Gao, Weiwei; Huang, Chun-Ming; Zhang, Liangfang

    2013-01-01

    Propionibacterium acnes (P. acnes) is a Gram-positive bacterium strongly associated with acne infection. While many antimicrobial agents have been used in clinic to treat acne infection by targeting P. acnes, these existing anti-acne agents usually produce considerable side effects. Herein, we report the development and evaluation of liposomal lauric acids (LipoLA) as a new, effective and safe therapeutic agent for the treatment of acne infection. By incorporating lauric acids into the lipid bilayer of liposomes, we observed that the resulting LipoLA readily fused with bacterial membranes, causing effective killing of P. acnes by disrupting bacterial membrane structures. Using a mouse ear model, we demonstrated that the bactericidal property of LipoLA against P. acne was well preserved at physiological conditions. Topically applying LipoLA in a gel form onto the infectious sites led to eradication of P. acnes bacteria in vivo. Further skin toxicity studies showed that LipoLA did not induce acute toxicity to normal mouse skin tissues, while benzoyl peroxide and salicylic acid, the two most popular over-the-counter acne medications, generated moderate to severe skin irritation within 24 h. These results suggest that LipoLA hold a high therapeutic potential for the treatment of acne infection and other P. acnes related diseases. PMID:23495239

  4. Enhanced Blood Compatibility of Metallocene Polyethylene Subjected to Hydrochloric Acid Treatment for Cardiovascular Implants

    PubMed Central

    Jaganathan, Saravana Kumar; Mohandas, Hemanth; Sivakumar, Gunalan; Kasi, Palaniappan; Sudheer, Theertha; Avineri Veetil, Sruthi; Murugesan, Selvakumar; Supriyanto, Eko

    2014-01-01

    Blood compatibility of metallocene polyethylene (mPE) was investigated after modifying the surface using hydrochloric acid. Contact angle of the mPE exposed to HCl poses a decrease in its value which indicates increasing wettability and better blood compatibility. Surface of mPE analyzed by using FTIR revealed no significant changes in its functional groups after treatment. Furthermore, scanning electron microscope images supported the increasing wettability through the modifications like pit formations and etching on the acid rendered surface. To evaluate the effect of acid treatment on the coagulation cascade, prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. Both PT and APTT were delayed significantly (P < 0.05) after 60 min exposure implying improved blood compatibility of the surfaces. Hemolysis assay of the treated surface showed a remarkable decrease in the percentage of lysis of red blood cells when compared with untreated surface. Moreover, platelet adhesion assay demonstrated that HCl exposed surfaces deter the attachment of platelets and thereby reduce the chances of activation of blood coagulation cascade. These results confirmed the enhanced blood compatibility of mPE after HCl exposure which can be utilized for cardiovascular implants like artificial vascular prostheses, implants, and various blood contacting devices. PMID:24955370

  5. Acid mine drainage treatment using by-products from quicklime manufacturing as neutralization chemicals.

    PubMed

    Tolonen, Emma-Tuulia; Sarpola, Arja; Hu, Tao; Rämö, Jaakko; Lassi, Ulla

    2014-12-01

    The aim of this research was to investigate whether by-products from quicklime manufacturing could be used instead of commercial quicklime (CaO) or hydrated lime (Ca(OH)2), which are traditionally used as neutralization chemicals in acid mine drainage treatment. Four by-products were studied and the results were compared with quicklime and hydrated lime. The studied by-products were partly burnt lime stored outdoors, partly burnt lime stored in a silo, kiln dust and a mixture of partly burnt lime stored outdoors and dolomite. Present application options for these by-products are limited and they are largely considered waste. Chemical precipitation experiments were performed with the jar test. All the studied by-products removed over 99% of Al, As, Cd, Co, Cu, Fe, Mn, Ni, Zn and approximately 60% of sulphate from acid mine drainage. However, the neutralization capacity of the by-products and thus the amount of by-product needed as well as the amount of sludge produced varied. The results indicated that two out of the four studied by-products could be used as an alternative to quicklime or hydrated lime for acid mine drainage treatment. PMID:25193795

  6. In situ hypochlorous acid generation for the treatment of distillery spentwash

    SciTech Connect

    Vijayaraghavan, K.; Ramanujam, T.K.; Balasubramanian, N.

    1999-06-01

    Distillery spentwash constitutes a high organic load along with a high acid strength and color, which presents significant disposal or treatment problems. Treatment of high-strength organic waste can normally be achieved only by anaerobic processes, which are time-consuming and subject to environmental stress. Aerobic processes though faster are not economical for high-strength wastes because the aeration cost is prohibitive. High-strength organic waste like distillery spentwash can be effectively treated by electrolysis in the presence of sodium chloride. Because the graphite anode and stainless steel cathode zones were kept unseparated, chlorine produced during electrolysis forms hypochlorous acid. The hypochlorous acid thus formed oxidizes the organic matter present in the wastewater. The COD removal from the spentwash was found to be 99% for an initial COD concentration of 15,000 mg/l at the end of 240 min of electrolysis. The energy requirements were found to be 36 and 27 W{center_dot}h/l for treating 20 l of spentwash at 2.5 and 3% sodium chloride concentration, respectively. The observed energy difference is due to improved conductivity of the electrolyte.

  7. Medical treatment of biliary duct stones: effect of ursodeoxycholic acid administration.

    PubMed Central

    Salvioli, G; Salati, R; Lugli, R; Zanni, C

    1983-01-01

    Twenty-eight patients with radiolucent biliary duct stones without cholangitis and jaundice were randomly allocated into two treatment groups receiving ursodeoxycholic acid 12 mg/kg (group A) or placebo (group B) in three daily doses for 24 months. In group A stones disappeared completely in seven patients and partially in one; placebo administration had no effect on stone size and three patients of group B (only one of group A) went to surgery for complications. Ursodeoxycholic acid treatment did not adversely affect liver function tests, and alkaline phosphatase decreased. Abdominal and biliary colics also became less frequent in the first six months of therapy in group A, but not in the placebo group. The bile was supersaturated with cholesterol in both groups, but decreased significantly only in patients receiving ursodeoxycholic acid even though the lithogenic index remained high. Cholesterol saturation of bile does not seem to be the only factor determining the dissolution of biliary duct stones which sometimes contain cholesterol as the main component. PMID:6345281

  8. Jaw osteonecrosis management around a dental implant inserted 2 years before starting treatment with zoledronic acid

    PubMed Central

    Marín-Fernández, Ana-Belén; García Medina, Blas; Aguilar-Salvatierra, Antonio; Jiménez-Burkhardt, Alberto

    2015-01-01

    Bisphosphonates (BP) are a type of drug known to inhibit bone resorption through complex interventions. Their primary mechanism of action is aimed at the cellular level, inhibiting osteoclast activity and so bone resorption. BPs are widely used, with many patients receiving continuous treatment for years. But it is well known that these drugs can produce osteonecrosis of the jaw (ONJ). Zoledronic acid (ZA) is an intravenous BP used in the treatment and prophylaxis of bone disease in patients with malignant tumors with bone implication. ZA is the most potent BP in clinical development. This report describes the case of a 62-year-old woman with breast cancer antecedents which relapsed, who had received a maxillary dental implant two years before the start of therapy with zoledronic acid. She later developed osteonecrosis of the jaw (ONJ), which began in the peri-implant area, and was treated for stage 3 ONJ by sub-total maxillectomy. Key words:Bisphosphonates, zoledronic acid, osteonecrosis of the jaw, peri-implantitis, maxillectomy. PMID:26330946

  9. Antioxidative Peptides Derived from Enzyme Hydrolysis of Bone Collagen after Microwave Assisted Acid Pre-Treatment and Nitrogen Protection

    PubMed Central

    Lin, Yun-Jian; Le, Guo-Wei; Wang, Jie-Yun; Li, Ya-Xin; Shi, Yong-Hui; Sun, Jin

    2010-01-01

    This study focused on the preparation method of antioxidant peptides by enzymatic hydrolysis of bone collagen after microwave assisted acid pre-treatment and nitrogen protection. Phosphoric acid showed the highest ability of hydrolysis among the four other acids tested (hydrochloric acid, sulfuric acid and/or citric acid). The highest degree of hydrolysis (DH) was 9.5% using 4 mol/L phosphoric acid with a ratio of 1:6 under a microwave intensity of 510 W for 240 s. Neutral proteinase gave higher DH among the four protease tested (Acid protease, neutral protease, Alcalase and papain), with an optimum condition of: (1) ratio of enzyme and substrate, 4760 U/g; (2) concentration of substrate, 4%; (3) reaction temperature, 55 °C and (4) pH 7.0. At 4 h, DH increased significantly (P < 0.01) under nitrogen protection compared with normal microwave assisted acid pre-treatment hydrolysis conditions. The antioxidant ability of the hydrolysate increased and reached its maximum value at 3 h; however DH decreased dramatically after 3 h. Microwave assisted acid pre-treatment and nitrogen protection could be a quick preparatory method for hydrolyzing bone collagen. PMID:21151439

  10. Nalidixic acid and pivmecillinam for treatment of acute lower urinary tract infections.

    PubMed

    Hovelius, B; Mårdh, P A; Nygaard-Pedersen, L; Wathne, B

    1985-11-01

    Women, 15-45 years of age, with symptoms of lower urinary tract infection (UTI) were randomly treated with nalidixic acid (1 g X 3) or pivmecillinam (200-400 mg X 3) for three or seven days, respectively. Therapeutic failure, relapse, or reinfection occurred among 18% of 82 women, even though the isolated strains of gram-negative rods in these patients were susceptible in vitro to the antibiotics used. Therapeutic failure, i.e. no effect or at best only a minor effect on the symptoms, was registered in 10 of 13 cases of UTI caused by Staphylococcus saprophyticus and treated with nalidixic acid, which was consistent with the high minimum inhibitory concentrations (MIC) (128-512 micrograms/ml) of this antibiotic. S. saprophyticus was isolated in 9 of 12 patients during treatment with nalidixic acid. On the other hand, pivmecillinam therapy was clinically effective in 16 of 18 patients with UTI caused by S. saprophyticus, even though the MIC of mecillinam to these strains was considerably higher (8-64 micrograms/ml) than that vis-à-vis gram-negative rods. Thus the clinical effect of pivmecillinam was significantly better than that of nalidixic acid in cases of UTI caused by S. saprophyticus. The organism was not isolated from 14 patients receiving pivmecillinam therapy. PMID:4081404

  11. Novel Retinoic Acid Receptor Alpha Agonists for Treatment of Kidney Disease

    PubMed Central

    Liu, Ruijie; Li, Zhengzhe; Chen, Yibang; Evans, Todd; Chuang, Peter; Das, Bhaskar; He, John Cijiang

    2011-01-01

    Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA) attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs): RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1) in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN). Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN. PMID:22125642

  12. The Unexpected Uses of Urso- and Tauroursodeoxycholic Acid in the Treatment of Non-liver Diseases

    PubMed Central

    Vang, Sheila; Longley, Katie

    2014-01-01

    Tauroursodeoxycholic acid (TUDCA) is the taurine conjugate of ursodeoxycholic acid (UDCA), a US Food and Drug Administration–approved hydrophilic bile acid for the treatment of certain cholestatic liver diseases. There is a growing body of research on the mechanism(s) of TUDCA and its potential therapeutic effect on a wide variety of non-liver diseases. Both UDCA and TUDCA are potent inhibitors of apoptosis, in part by interfering with the upstream mitochondrial pathway of cell death, inhibiting oxygen-radical production, reducing endoplasmic reticulum (ER) stress, and stabilizing the unfolded protein response (UPR). Several studies have demonstrated that TUDCA serves as an anti-apoptotic agent for a number of neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease. In addition, TUDCA plays an important role in protecting against cell death in certain retinal disorders, such as retinitis pigmentosa. It has been shown to reduce ER stress associated with elevated glucose levels in diabetes by inhibiting caspase activation, up-regulating the UPR, and inhibiting reactive oxygen species. Obesity, stroke, acute myocardial infarction, spinal cord injury, and a long list of acute and chronic non-liver diseases associated with apoptosis are all potential therapeutic targets for T/UDCA. A growing number of pre-clinical and clinical studies underscore the potential benefit of this simple, naturally occurring bile acid, which has been used in Chinese medicine for more than 3000 years. PMID:24891994

  13. Decontamination of polluted water by treatment with a crude humic acid blend

    SciTech Connect

    Yates, L.M. III; Wandruszka, R. von )

    1999-06-15

    The use of humic acid for contaminant extraction from environmental matrices is an attractive concept because of the natural origin of the material and its low pollution potential. The problem of availability and the need for alkaline extraction were circumvented by the use of an unrefined leonardite humic acid (LHA) material used as received. This mined product has a high humic acid content, is inexpensive, and is available in bulk. LHA, applied without alkaline extraction, was used in the decontamination of water containing organic and inorganic test pollutants. The former included pyrene, difenzoquat, and rhodamine B base, while the latter were comprised of Pb[sup 2+], Zn[sup 2+], Ni[sup 2+], Cu[sup 2+], Sr[sup 2+], Cd[sup 2+], As[sup 3+], Ag[sup +], and Mg[sup 2+]. Simulated acidic waste solutions were treated by both batch precipitation and column extraction, with the pollutants applied singly and as mixtures. In the precipitation procedure, commercial lime was used as the coagulant, and virtually complete removal of the metals was achieved. Pyrene and difenzoquat were also removed, but rhodamine B base was not. With LHA column elution, all three organic compounds were fully extracted from waste solutions, including those containing mixed contaminants. Removal of metals by column treatment gave encouraging results, with Pb[sup 2+], Cu[sup 2+], and Sr[sup 2+] being extracted most effectively.

  14. The relevance of salicylic acid in the treatment of plaque psoriasis with dithranol creams.

    PubMed

    de Mare, S; Calis, N; den Hartog, G; van Erp, P E; van de Kerkhof, P C

    1988-01-01

    The relevance of salicylic acid in dithranol creams was evaluated in a double-blind study. Patients with chronic plaque psoriasis were treated using a short-contact schedule for dithranol on an outpatient basis. A left-right comparison was carried out between sites treated with either dithranol with 2% salicylic acid (D + S) or dithranol in the same base without salicylic acid (D-S). Clinical results were evaluated once a week using the psoriasis area severity index. In order to quantify the improvement, flow cytometric measurements were done using the monoclonal antibody Ks8.12, recognizing keratin 16 in normal and lesional epidermis. Simultaneously, relative DNA content was quantified which previously was described as a useful method to monitor a therapeutic effect. Both PASI scores and Ks8.12 binding decreased after 6 weeks treatment with D + S and D-S. However, percentages of cells in SG2M phases did not show a significant change. No significant difference was observed between sites treated with either D + S or D-S. Therefore we conclude that the addition of salicylic acid in a concentration of 2% does not enhance the efficacy of dithranol creams and we confirm that Ks8.12 is a useful quantitative marker for therapeutic efficacy. PMID:2483115

  15. Idiopathic bile acid malabsorption--a review of clinical presentation, diagnosis, and response to treatment.

    PubMed Central

    Williams, A J; Merrick, M V; Eastwood, M A

    1991-01-01

    Between 1982 and 1989, the seven day retention of 75SeHCAT was measured in 181 patients with chronic diarrhoea that remained unexplained after full investigation. Altogether 121 of the 181 had a seven day 75SeHCAT retention greater than or equal to 15% and thus had no evidence of abnormal bile acid turnover. Twenty one had a seven day 75SeHCAT retention greater than or equal to 10% but less than 15%. Their clinical features were typical of the irritable bowel syndrome, and none of eight treated with cholestyramine showed symptomatic improvement. Sixteen patients had a seven day retention greater than or equal to 5% and less than 10%, six of whom had improved symptoms after treatment with bile acid chelating agents. The remaining 23 patients had a 75SeHCAT retention of less than 5% at seven days and responded to bile acid chelators. This group had a characteristic illness with intermittent watery diarrhoea, but no constitutional upset. It was not possible to distinguish the patients with bile acid malabsorption exclusively on the basis of the clinical symptoms and investigations, other than 75SeHCAT retention. We conclude that the measurement of 75SeHCAT retention is useful, appropriate, and necessary in patients with unexplained chronic diarrhoea. PMID:1916479

  16. Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment.

    PubMed

    Königs, Anja; Kiliaan, Amanda J

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. The classical treatment of ADHD where stimulant medication is used has revealed severe side effects and intolerance. Consequently, the demand to search for alternative treatment has increased rapidly. When comparing levels of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in ADHD patients with those in age-matching controls, lower levels are found in ADHD patients' blood. ω-3 PUFAs are essential nutrients and necessary for a proper brain function and development. Additionally, there are strong indications that ω-3 PUFA supplements could have beneficial effects on ADHD. However, the results of ω-3 PUFA supplementation studies show a high variability. Therefore, we reviewed recent studies published between 2000 and 2015 to identify effective treatment combinations, the quality of design, and safety and tolerability of ω-3-containing food supplements. We searched the databases MEDLINE, PubMed, and Web of Science with keywords such as "ADHD" and "ω-3/6 PUFA" and identified 25 studies that met the inclusion and exclusion criteria. The results of these ω-3 PUFA studies are contradictory but, overall, show evidence for a successful treatment of ADHD symptoms. Tolerability of the given supplements was high, and only mild side effects were reported. In conclusion, there is evidence that a ω-3 PUFA treatment has a positive effect on ADHD. It should be added that treatment could be more effective in patients with mild forms of ADHD. Moreover, the dosage of stimulant medication could be reduced when used in combination with ω-3 PUFA supplements. Further studies are necessary to investigate underlying mechanisms that can lead to a reduction of ADHD symptoms due to ω-3 PUFA treatments and also to determine the optimal concentrations of ω-3 PUFAs, whether used as single treatment or in combination with other medication. PMID:27555775

  17. Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment

    PubMed Central

    Königs, Anja; Kiliaan, Amanda J

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. The classical treatment of ADHD where stimulant medication is used has revealed severe side effects and intolerance. Consequently, the demand to search for alternative treatment has increased rapidly. When comparing levels of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in ADHD patients with those in age-matching controls, lower levels are found in ADHD patients’ blood. ω-3 PUFAs are essential nutrients and necessary for a proper brain function and development. Additionally, there are strong indications that ω-3 PUFA supplements could have beneficial effects on ADHD. However, the results of ω-3 PUFA supplementation studies show a high variability. Therefore, we reviewed recent studies published between 2000 and 2015 to identify effective treatment combinations, the quality of design, and safety and tolerability of ω-3-containing food supplements. We searched the databases MEDLINE, PubMed, and Web of Science with keywords such as “ADHD” and “ω-3/6 PUFA” and identified 25 studies that met the inclusion and exclusion criteria. The results of these ω-3 PUFA studies are contradictory but, overall, show evidence for a successful treatment of ADHD symptoms. Tolerability of the given supplements was high, and only mild side effects were reported. In conclusion, there is evidence that a ω-3 PUFA treatment has a positive effect on ADHD. It should be added that treatment could be more effective in patients with mild forms of ADHD. Moreover, the dosage of stimulant medication could be reduced when used in combination with ω-3 PUFA supplements. Further studies are necessary to investigate underlying mechanisms that can lead to a reduction of ADHD symptoms due to ω-3 PUFA treatments and also to determine the optimal concentrations of ω-3 PUFAs, whether used as single treatment or in combination with other medication. PMID:27555775

  18. Efficacy of Cefpodoxime with Clavulanic Acid in the Treatment of Recurrent Pyoderma in Dogs

    PubMed Central

    Sudhakara Reddy, B.; Nalini Kumari, K.; Vaikunta Rao, V.; Rayulu, V. C.

    2014-01-01

    In the present study on recurrent pyoderma, dogs with a history of more than three episodes of skin infections in a period of one year were selected. The associated conditions and (or) underlying factors revealed upon thorough investigation were demodicosis, Malassezia dermatitis, flea infestation, hypothyroidism, keratinization disorder (seborrhea), combination of Malassezia dermatitis and tick infestation, and a combination of scabies and tick infestation. Therapy was given with cefpodoxime with clavulanic acid along with appropriate simultaneous medication for the underlying associated conditions. In all the cases response to therapy was excellent. Improvement was noticed by 9 to 19 days and 17 to 21 days in recurrent superficial and deep pyoderma, respectively. In one dog, relapse occurred by 45 days due to the associated condition of hypothyroidism which was confirmed through laboratory findings. Cefpodoxime with clavulanic acid proved to be an effective, safe, and convenient antibiotic for the treatment of recurrent pyoderma in dogs without any side effects. PMID:24977045

  19. Efficacy of cefpodoxime with clavulanic Acid in the treatment of recurrent pyoderma in dogs.

    PubMed

    Sudhakara Reddy, B; Nalini Kumari, K; Vaikunta Rao, V; Rayulu, V C

    2014-01-01

    In the present study on recurrent pyoderma, dogs with a history of more than three episodes of skin infections in a period of one year were selected. The associated conditions and (or) underlying factors revealed upon thorough investigation were demodicosis, Malassezia dermatitis, flea infestation, hypothyroidism, keratinization disorder (seborrhea), combination of Malassezia dermatitis and tick infestation, and a combination of scabies and tick infestation. Therapy was given with cefpodoxime with clavulanic acid along with appropriate simultaneous medication for the underlying associated conditions. In all the cases response to therapy was excellent. Improvement was noticed by 9 to 19 days and 17 to 21 days in recurrent superficial and deep pyoderma, respectively. In one dog, relapse occurred by 45 days due to the associated condition of hypothyroidism which was confirmed through laboratory findings. Cefpodoxime with clavulanic acid proved to be an effective, safe, and convenient antibiotic for the treatment of recurrent pyoderma in dogs without any side effects. PMID:24977045

  20. Evaluation of the Magnesium Hydroxide Treatment Process for Stabilizing PFP Plutonium/Nitric Acid Solutions

    SciTech Connect

    Gerber, Mark A.; Schmidt, Andrew J.; Delegard, Calvin H.; Silvers, Kurt L.; Baker, Aaron B.; Gano, Susan R.; Thornton, Brenda M.

    2000-09-28

    This document summarizes an evaluation of the magnesium hydroxide [Mg(OH)2] process to be used at the Hanford Plutonium Finishing Plant (PFP) for stabilizing plutonium/nitric acid solutions to meet the goal of stabilizing the plutonium in an oxide form suitable for storage under DOE-STD-3013-99. During the treatment process, nitric acid solutions bearing plutonium nitrate are neutralized with Mg(OH)2 in an air sparge reactor. The resulting slurry, containing plutonium hydroxide, is filtered and calcined. The process evaluation included a literature review and extensive laboratory- and bench-scale testing. The testing was conducted using cerium as a surrogate for plutonium to identify and quantify the effects of key processing variables on processing time (primarily neutralization and filtration time) and calcined product properties.

  1. Triheptanoin - a medium chain triglyceride with odd chain fatty acids: a new anaplerotic anticonvulsant treatment?

    PubMed Central

    Borges, Karin; Sonnewald, Ursula

    2012-01-01

    The triglyceride of heptanoate (C7 fatty acid), triheptanoin, is a tasteless oil used to treat rare metabolic disorders in USA and France. Heptanoate is metabolized by β-oxidation to provide propionyl-CoA, which after carboxylation can produce succinyl-CoA, resulting in anaplerosis – the refilling of the tricarboxylic acid cycle. Heptanoate is also metabolized by the liver to the “C5 ketones”, β-ketopentanoate and/or β-hydroxypentanoate, which are released into the blood and thought to enter the brain via monocarboxylate transporters. Oral triheptanoin has recently been discovered to be reproducibly anticonvulsant in acute and chronic mouse seizures models. However, current knowledge on alterations of brain metabolism after triheptanoin administration and anaplerosis via propionyl-CoA carboxylation in the brain is limited. This review outlines triheptanoin’s unique anticonvulsant profile and its clinical potential for the treatment of medically refractory epilepsy. Anaplerosis as a therapeutic approach for the treatment of epilepsy is discussed. More research is needed to elucidate the anticonvulsant mechanism of triheptanoin and to reveal its clinical potential for the treatment of epilepsy and other disorders of the brain. PMID:21855298

  2. Ferulic acid chronic treatment exerts antidepressant-like effect: role of antioxidant defense system.

    PubMed

    Lenzi, Juliana; Rodrigues, Andre Felipe; Rós, Adriana de Sousa; de Castro, Amanda Blanski; de Castro, Bianca Blanski; de Lima, Daniela Delwing; Magro, Débora Delwing Dal; Zeni, Ana Lúcia Bertarello

    2015-12-01

    Oxidative stress has been claimed a place in pathophysiology of depression; however, the details of the neurobiology of this condition remains incompletely understood. Recently, treatments employing antioxidants have been thoroughly researched. Ferulic acid (FA) is a phenolic compound with antioxidant and antidepressant-like effects. Herein, we investigated the involvement of the antioxidant activity of chronic oral FA treatment in its antidepressant-like effect using the tail suspension test (TST) and the forced swimming test (FST) in mice. The modulation of antioxidant system in blood, hippocampus and cerebral cortex was assessed after stress induction through TST and FST. Our results show that FA at the dose of 1 mg/kg has antidepressant-like effect without affecting locomotor activity. The stress induced by despair tests was able to decrease significantly the activities of superoxide dismutase (SOD) in the blood, catalase (CAT) in the blood and cerebral cortex and glutathione peroxidase (GSH-Px) in the cerebral cortex. Thiobarbituric acid-reactive substances (TBA-RS) levels were increased significantly in the cerebral cortex. Furthermore, the results show that FA was capable to increase SOD, CAT and GSH-Px activities and decrease TBA-RS levels in the blood, hippocampus and cerebral cortex. These findings demonstrated that FA treatment in low doses is capable to exert antidepressant-like effect with the involvement of the antioxidant defense system modulation. PMID:26340979

  3. Copper-Sulfate Pentahydrate as a Product of the Waste Sulfuric Acid Solution Treatment

    NASA Astrophysics Data System (ADS)

    Marković, Radmila; Stevanović, Jasmina; Avramović, Ljiljana; Nedeljković, Dragutin; Jugović, Branimir; Stajić-Trošić, Jasna; Gvozdenović, Milica

    2012-12-01

    The aim of this study is synthesis of copper-sulfate pentahydrate from the waste sulfuric acid solution-mother liquor generated during the regeneration process of copper bleed solution. Copper is removed from the mother liquor solution in the process of the electrolytic treatment using the insoluble lead anodes alloyed with 6 mass pct of antimony on the industrial-scale equipment. As the result of the decopperization process, copper is removed in the form of the cathode sludge and is precipitated at the bottom of the electrolytic cell. By this procedure, the content of copper could be reduced to the 20 mass pct of the initial value. Chemical characterization of the sludge has shown that it contains about 90 mass pct of copper. During the decopperization process, the very strong poison, arsine, can be formed, and the process is in that case terminated. The copper leaching degree of 82 mass pct is obtained using H2SO4 aqueous solution with the oxygen addition during the cathode sludge chemical treatment at 80 °C ± 5 °C. Obtained copper salt satisfies the requirements of the Serbian Standard for Pesticide, SRPS H.P1. 058. Therefore, the treatment of waste sulfuric acid solutions is of great economic and environmental interest.

  4. Application of acidic thermal treatment for one- and two-stage anaerobic digestion of sewage sludge.

    PubMed

    Takashima, M; Tanaka, Y

    2010-01-01

    The effectiveness of acidic thermal treatment (ATT) was examined in a 106-day continuous experiment, when applied to one- or two-stage anaerobic digestion of sewage sludge (4.3% TS). The ATT was performed at 170 °C and pH 5 for 1 hour (sulfuric acid for lowering pH). The one-stage process was mesophilic at 20 days hydraulic retention time (HRT), and incorporated the ATT as pre-treatment. The two-stage process consisted of a thermophilic digester at 5 days HRT and a mesophilic digester at 15 days HRT, and incorporated the ATT as interstage-treatment. On average, VSS reduction was 48.7% for the one-stage control, 65.8% for the one-stage ATT, 52.7% for the two-stage control and 67.6% for the two-stage ATT. Therefore, VSS reduction was increased by 15-17%, when the ATT was combined in both one- and two-stage processes. In addition, the dewaterability of digested sludge was remarkably improved, and phosphate release was enhanced. On the other hand, total methane production did not differ significantly, and color generation was noted in the digested sludge solutions with the ATT. In conclusion, the anaerobic digestion with ATT can be an attractive alternative for sludge reduction, handling, and phosphorus recovery. PMID:21099053

  5. Triheptanoin--a medium chain triglyceride with odd chain fatty acids: a new anaplerotic anticonvulsant treatment?

    PubMed

    Borges, Karin; Sonnewald, Ursula

    2012-07-01

    The triglyceride of heptanoate (C7 fatty acid), triheptanoin, is a tasteless oil used to treat rare metabolic disorders in USA and France. Heptanoate is metabolized by β-oxidation to provide propionyl-CoA, which after carboxylation can produce succinyl-CoA, resulting in anaplerosis - the refilling of the tricarboxylic acid cycle. Heptanoate is also metabolized by the liver to the C5 ketones, β-ketopentanoate and/or β-hydroxypentanoate, which are released into the blood and thought to enter the brain via monocarboxylate transporters. Oral triheptanoin has recently been discovered to be reproducibly anticonvulsant in acute and chronic mouse seizures models. However, current knowledge on alterations of brain metabolism after triheptanoin administration and anaplerosis via propionyl-CoA carboxylation in the brain is limited. This review outlines triheptanoin's unique anticonvulsant profile and its clinical potential for the treatment of medically refractory epilepsy. Anaplerosis as a therapeutic approach for the treatment of epilepsy is discussed. More research is needed to elucidate the anticonvulsant mechanism of triheptanoin and to reveal its clinical potential for the treatment of epilepsy and other disorders of the brain. PMID:21855298

  6. Effectiveness of coagulation and acid precipitation processes for the pre-treatment of diluted black liquor.

    PubMed

    Garg, Anurag; Mishra, I M; Chand, S

    2010-08-15

    The effectiveness of coagulation (using aluminium-based chemicals and ferrous sulfate) and acid precipitation (using H(2)SO(4)) processes for the pre-treatment of diluted black liquor obtained from a pulp and paper mill is reported. Commercial alum was found to be the most economical among all the aluminium and ferrous salts used as a coagulant. A maximum removal of chemical oxygen demand (COD) (ca. 63%) and colour reduction (ca. 90%) from the wastewater (COD = 7000 mg l(-1)) at pH 5.0 was obtained with alum. During the acid precipitation process, at pH < 5.0, significant COD reductions (up to 64%) were observed. Solid residue obtained from the alum treatment at a temperature of 95 degrees C showed much better (3 times) settling rate than that for the residue obtained after treatment with the same coagulant at a temperature of 25 degrees C. The settling curves had three parts, namely, hindered, transition and compression zones. Tory plots were used to determine the critical height of suspension-supernatant interface that is used in the design of a clarifier-thickener unit. High heating values and large biomass fraction of the solid residues can encourage the fuel users to use this waste derived sludge as a potential renewable energy source. PMID:20430523

  7. Treatment of renal uric acid stone by extracorporeal shock wave lithotripsy combined with sodium bicarbonate: 2 case reports

    PubMed Central

    Li, Hao-Yong; Lian, Pei-Yu; Zhou, Zhi-Yan; Song, Peng; Yan, Yi; Liu, Ji-Hong

    2015-01-01

    Uric acid stone is the most comment radiolucent renal stone with high recurrence rate, which would further cause acute upper urinary tract obstruction and kidney failure. Here we report two cases of renal uric acid stone from December 2012 to April 2013. One 43-year-old male patient suffered from chronic uric acid nephrolithiasis caused by the long-term indwelling of bilateral double-J stent. Another 69-year-old patient was also diagnosed with uric acid nephrolithiasis at the right kidney. Both patients were first treated with extracorporeal shock wave lithotripsy (ESWL), followed by 1.5% sodium bicarbonate dissolution therapy. After a week of the treatment, the uric acid stones in both patients were completely dissolved without retrograde infection. In summary, the use of ESWL and sodium bicarbonate dissolution therapy as a combined modality is a safe, effective, inexpensive treatment for uric acid nephrolithiasis. PMID:26550383

  8. Microbiological monitoring of acid mine drainage treatment systems and aquatic surroundings using real-time PCR.

    PubMed

    Han, J S; Kim, C G

    2009-01-01

    In general, acid mine drainage (AMD) causes low pH and high metal concentrations in mining areas and surroundings. The aim of this research was to achieve microbiological monitoring for AMD and to assess whether mine water outflows have any ecological effects on the aqueous ecosystem receiving effluents from different types of treatment system. The water quality of aquatic sample was analyzed and the molecular biological diversity of the samples was assessed using 16S rRNA methods, which were implemented to determine which bacteria existed throughout various unit processes for different AMD treatment systems and their receiving water environments. Acidiphilium cryptum, a heterotrophic acidophile, was found at the AMD sites, and Rhodoferax ferrireducens, which can reduce iron using insoluble Fe(III) as an electron acceptor, was detected at many AMD treatment facilities and downstream of the treatment processes. Subsequently, quantitative real-time PCR was conducted on specific genes of selected bacteria. Surprisingly, obvious trends were observed in the relative abundance of the various bacteria that corresponded to the water quality analytical results. The copy number of Desulfosporosinus orientus, a sulfate reducing bacteria, was also observed to decrease in response to decreases in metals according to the downstream flow of the AMD treatment system. PMID:19494446

  9. Effect of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother-placenta-foetus trio during cholestasis of pregnancy

    PubMed Central

    Estiú, Maria C; Monte, Maria J; Rivas, Laura; Moirón, Maria; Gomez-Rodriguez, Laura; Rodriguez-Bravo, Tomas; Marin, Jose JG; Macias, Rocio IR

    2015-01-01

    Aim Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and elevated bile acid concentrations in maternal serum. This is accompanied by an enhanced risk of intra-uterine and perinatal complications. High concentrations of sulphated progesterone metabolites (PMS) have been suggested to be involved in the multifactorial aetiopathogenesis of ICP. The aim of this study was to investigate further the mechanism accounting for the beneficial effect of oral administration of ursodeoxycholic acid (UDCA), which is the standard treatment, regarding bile acid and PMS homeostasis in the mother-placenta-foetus trio. Method Using HPLC-MS/MS bile acids and PMS were determined in maternal and foetal serum and placenta. The expression of ABC proteins in placenta was determined by real time quantitative PCR (RT-QPCR) and immunofluorescence. Results In ICP, markedly increased concentrations of bile acids (tauroconjugates > glycoconjugates >> unconjugated), progesterone and PMS in placenta and maternal serum were accompanied by enhanced concentrations in foetal serum of bile acids, but not of PMS. UDCA treatment reduced bile acid accumulation in the mother-placenta-foetus trio, but had no significant effect on progesterone and PMS concentrations. ABCG2 mRNA abundance was increased in placentas from ICP patients vs. controls and remained stable following UDCA treatment, despite an apparent further increase in ABCG2. Conclusion UDCA administration partially reduces ICP-induced bile acid accumulation in mothers and foetuses despite the lack of effect on concentrations of progesterone and PMS in maternal serum. Up-regulation of placental ABCG2 may play an important role in protecting the foetus from high concentrations of bile acids and PMS during ICP. PMID:25099365

  10. Modification and improvement of proton-exchange membrane fuel cells via treatment using peracetic acid

    NASA Astrophysics Data System (ADS)

    Xu, Zhiqiang; Qi, Zhigang; Kaufman, Arthur

    Electrodes and catalyst-coated membranes (CCMs) were treated using peracetic acid. After such a treatment, the properties and performance of these electrodes and CCMs were changed in several aspects. First, their catalytic activity was increased compared to the untreated counterparts. Second, their ability to hold water within the catalyst layers was increased so that the cathode did not need to be humidified. Third, if the cathode was humidified together with the anode, some of the electrodes were more readily to be flooded than the untreated counterparts.

  11. Combined heat treatment and acid hydrolysis of cassava grate waste (CGW) biomass for ethanol production

    SciTech Connect

    Agu, R.C.; Amadife, A.E.; Ude, C.M.; Onyia, A.; Ogu, E.O.; Okafor, M.; Ezejiofor, E.

    1997-12-31

    The effect of combined heat treatment and acid hydrolysis (various concentrations) on cassava grate waste (CGW) biomass for ethanol production was investigated. At high concentrations of H{sub 2}SO{sub 4} (1--5 M), hydrolysis of the CGW biomass was achieved but with excessive charring or dehydration reaction. At lower acid concentrations, hydrolysis of CGW biomass was also achieved with 0.3--0.5 M H{sub 2}SO{sub 4}, while partial hydrolysis was obtained below 0.3 M H{sub 2}SO{sub 4} (the lowest acid concentration that hydrolyzed CGW biomass) at 120 C and 1 atm pressure for 30 min. A 60% process efficiency was achieved with 0.3 M H{sub 2}SO{sub 4} in hydrolyzing the cellulose and lignin materials present in the CGW biomass. High acid concentration is therefore not required for CGW biomass hydrolysis. The low acid concentration required for CGW biomass hydrolysis, as well as the minimal cost required for detoxification of CGW biomass because of low hydrogen cyanide content of CGW biomass would seem to make this process very economical. From three liters of the CGW biomass hydrolysate obtained from hydrolysis with 0.3M H{sub 2}SO{sub 4}, ethanol yield was 3.5 (v/v%) after yeast fermentation. However, although the process resulted in gainful utilization of CGW biomass, additional costs would be required to effectively dispose new by-products generated from CGW biomass processing.

  12. Survival mechanism of Escherichia coli O157:H7 against combined treatment with acetic acid and sodium chloride.

    PubMed

    Lee, Sun-Young; Kang, Dong-Hyun

    2016-05-01

    The combination of salt and acid is commonly used in the production of many foods, including pickles and fermented foods. However, in our previous studies, the addition of salt significantly reduced the inhibitory effect of acetic acid on Escherichia coli O157:H7 in laboratory media and pickled cucumbers. Therefore, this study was conducted to determine the mechanism by which salt confers resistance against acetic acid in E. coli O157:H7. The addition of high concentrations (up to 9% or 15% [w/v]) of salt increased the resistance of E. coli O157:H7 to acetic acid treatment. Combined treatment with acetic acid and salt showed varying results among different bacterial strains (an antagonistic effect for E. coli O157:H7 and Shigella and a synergistic effect for Listeria monocytogenes and Staphylococcus aureus). The addition of salt increased the cytoplasmic pH of E. coli O157:H7, but decreased the cytoplasmic pH of L. monocytogenes and S. aureus on treatment with acetic acid. Therefore, the addition of salt increases the acid resistance of E. coli O157:H7 possibly by increasing its acid resistance response and consequently preventing the acidification of its cytoplasm by organic acids. PMID:26742620

  13. Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice

    PubMed Central

    Bocco, B.M.; Fernandes, G.W.; Lorena, F.B.; Cysneiros, R.M.; Christoffolete, M.A.; Grecco, S.S.; Lancellotti, C.L.; Romoff, P.; Lago, J.H.G.; Bianco, A.C.; Ribeiro, M.O.

    2016-01-01

    Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model. PMID:26840707

  14. Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice.

    PubMed

    Bocco, B M; Fernandes, G W; Lorena, F B; Cysneiros, R M; Christoffolete, M A; Grecco, S S; Lancellotti, C L; Romoff, P; Lago, J H G; Bianco, A C; Ribeiro, M O

    2016-03-01

    Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model. PMID:26840707

  15. Retinoic acid metabolism blocking agents (RAMBAs): a new paradigm in the treatment of hyperkeratotic disorders.

    PubMed

    Verfaille, Christel J; Borgers, Marcel; van Steensel, Maurice A M

    2008-05-01

    Synthetic vitamin A derivatives, retinoids,have long been the mainstay of treatment for several disorders of keratinization, notably the ichthyoses and severe acne. Some forms of psoriasis also respond well. Their considerable power comes at a price. They have dose-limiting side effects and can be highly teratogenic, limiting their use in women of childbearing age.Thus, retinoids are used less often than their potential would warrant. However, the recent development of compounds that block the catabolism of endogenous vitamin A, called Retinioic Acid Metabolism Blocking Agents or RAMBAs, offers new possibilities. With these drugs, retinoid effects with less side effects and a reduction of the post-treatment teratogenicity period due to their favourable pharmacokinetic profile might be expected. In this review, we discuss how retinoids work, how they are metabolized and how RAMBAs influence this process. We also review the presently available data from clinical trials with RAMBAs. PMID:17941881

  16. A national discharge load of perfluoroalkyl acids derived from industrial wastewater treatment plants in Korea.

    PubMed

    Kim, Hee-Young; Seok, Hyun-Woo; Kwon, Hye-Ok; Choi, Sung-Deuk; Seok, Kwang-Seol; Oh, Jeong Eun

    2016-09-01

    Levels of 11 perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were measured in wastewater (influent and effluent) and sludge samples collected from 25 industrial wastewater treatment plants (I-WWTPs) in five industrial sectors (chemicals, electronics, metals, paper, and textiles) in South Korea. The highest ∑11PFAAs concentrations were detected in the influent and effluent from the paper (median: 411ng/L) and textile (median: 106ng/L) industries, and PFOA and PFOS were the predominant PFAAs (49-66%) in wastewater. Exceptionally high levels of PFAAs were detected in the sludge associated with the electronics (median: 91.0ng/g) and chemical (median: 81.5ng/g) industries with PFOS being the predominant PFAA. The discharge loads of 11 PFAAs from I-WWTP were calculated that total discharge loads for the five industries were 0.146ton/yr. The textile industry had the highest discharge load with 0.055ton/yr (PFOA: 0.039ton/yr, PFOS: 0.010ton/yr). Municipal wastewater contributed more to the overall discharge of PFAAs (0.489ton/yr) due to the very small industrial wastewater discharge compared to municipal wastewater discharge, but the contribution of PFAAs from I-WWTPs cannot be ignored. PMID:27152994

  17. Three targets of branched-chain amino acid supplementation in the treatment of liver disease.

    PubMed

    Holecek, Milan

    2010-05-01

    The article explains the pathogenesis of disturbances in branched-chain amino acid (BCAA; valine, leucine, and isoleucine) and protein metabolism in various forms of hepatic injury and it is suggested that the main cause of decrease in plasma BCAA concentration in liver cirrhosis is hyperammonemia. Three possible targets of BCAA supplementation in hepatic disease are suggested: (1) hepatic encephalopathy, (2) liver regeneration, and (3) hepatic cachexia. The BCAA may ameliorate hepatic encephalopathy by promoting ammonia detoxification, correction of the plasma amino acid imbalance, and by reduced brain influx of aromatic amino acids. The influence of BCAA supplementation on hepatic encephalopathy could be more effective in chronic hepatic injury with hyperammonemia and low concentrations of BCAA in blood than in acute hepatic illness, where hyperaminoacidemia frequently develops. The favorable effect of BCAA on liver regeneration and nutritional state of the body is related to their stimulatory effect on protein synthesis, secretion of hepatocyte growth factor, glutamine production and inhibitory effect on proteolysis. Presumably the beneficial effect of BCAA on hepatic cachexia is significant in compensated liver disease with decreased plasma BCAA concentrations, whereas it is less pronounced in hepatic diseases with inflammatory complications and enhanced protein turnover. It is concluded that specific benefits associated with BCAA supplementation depend significantly on the type of liver disease and on the presence of inflammatory reaction. An important task for clinical research is to identify groups of patients for whom BCAA treatment can significantly improve the health-related quality of life and the prognosis of hepatic disease. PMID:20071143

  18. Neuroprotective effects of lactation against kainic acid treatment in the dorsal hippocampus of the rat.

    PubMed

    Vanoye-Carlo, América; Morales, Teresa; Ramos, Eugenia; Mendoza-Rodríguez, Adriana; Cerbón, Marco

    2008-01-01

    Marked hippocampal changes in response to excitatory amino acid agonists occur during pregnancy (e.g. decreased frequency in spontaneous recurrent seizures in rats with KA lesions of the hippocampus) and lactation (e.g. reduced c-Fos expression in response to N-methyl-d,l-aspartic acid but not to kainic acid). In this study, the possibility that lactation protects against the excitotoxic damage induced by KA in hippocampal areas was explored. We compared cell damage induced 24 h after a single systemic administration of KA (5 or 7.5 mg/kg bw) in regions CA1, CA3, and CA4 of the dorsal hippocampus of rats in the final week of lactation to that in diestrus phase. To determine cellular damage in a rostro-caudal segment of the dorsal hippocampus, we used NISSL and Fluorojade staining, immunohistochemistry for active caspase-3 and TUNEL, and we observed that the KA treatment provoked a significant loss of neurons in diestrus rats, principally in the pyramidal cells of CA1 region. In contrast, in lactating rats, pyramidal neurons from CA1, CA3, and CA4 in the dorsal hippocampus were significantly protected against KA-induced neuronal damage, indicating that lactation may be a natural model of neuroprotection. PMID:17963758

  19. Combined anticalcification treatment of bovine pericardium with decellularization and hyaluronic acid derivative.

    PubMed

    Zhu, Deyi; Jin, Liqiang; Wang, Xuemei; Xu, Li; Liu, Tianqi

    2014-01-01

    The objective of this work was to evaluate the effect of decellularization and hyaluronic acid derivative on the improvement of anticalcification of glutaraldehyde fixed bovine pericardium (GFBP) using a rat subcutaneous implantation model A cell extraction process was employed to remove the cells and cellular components from bovine pericardium (BP), leaving a framework of largely insoluble collagen. Then acellular BP was cross-linked by glutaraldehyde solution and treated with hyaluronic acid derivative (HA-ADH) which was obtained by coupling adipic dihydrazide (ADH) on-COOH of hyaluronic acid (HA). The results of in vivo calcification tests showed that the calcium content was decreased dramatically by decellularization alone (from 28.07 ± 18.87 to 2.44 ± 0.55 μg Ca/mg dry tissue after 8 weeks' implantation), and even less concentration was shown by the combination of HA derivative treatment and decellularization (GFaBP-HA group) (0.25 ± 0.08 μg Ca/mg dry tissue after 8 weeks' implantation). In addition, GFaBP-HA group not only presented a lower degree of calcification, but also showed lower ratios of Ca/P molar, which corresponded to amorphous calcium phosphates. The obtained results indicated that GFaBP-HA was a potential candidate for the manufacture of anticalcification bioprostheses. PMID:24211959

  20. New developments in the treatment of hyperammonemia: emerging use of carglumic acid

    PubMed Central

    Daniotti, Marta; la Marca, Giancarlo; Fiorini, Patrizio; Filippi, Luca

    2011-01-01

    Hyperammonemia is a true neonatal emergency with high toxicity for the central nervous system and developmental delay. The causes of neonatal hyperammonemia are genetic defects of urea cycle enzymes, organic acidemias, lysinuric protein intolerance, hyperammonemia–hyperornithinemia– homocitrullinemia syndrome, transient hyperammonemia of the newborn, and congenital hyperinsulinism with hyperammonemia. In some of these conditions the high blood ammonia levels are due to the reduction of N-acetylglutamate, an essential cofactor necessary for the function of the urea cycle, or to the reduction of carbamoyl-phosphate synthase-I activity. In these cases, N-carbamylglutamate (carglumic acid) can be administered together with the conventional therapy. Carglumic acid is an analog of N-acetylglutamate that has a direct action on carbamoyl-phosphate synthase-I. Its effects are reactivation of the urea cycle and reduction of plasma ammonia levels. As a consequence it improves the traditional treatment, avoiding the need of hemodialysis and peritoneal dialysis. In this review we evaluate the possible field of application of carglumic acid and its effectiveness and safety. PMID:21403788

  1. Enzyme-entrapped mesoporous silica for treatment of uric acid disorders.

    PubMed

    Muthukoori, Shanthini; Narayanan, Naagarajan; Chandra, Manuguri Sesha Sarath; Sethuraman, Swaminathan; Krishnan, Uma Maheswari

    2013-05-01

    Gout is an abnormality in the body resulting in the accumulation of uric acid mainly in joints. Dissolution of uric acid crystals into soluble allantoin by the enzyme uricase might provide a better alternative for the treatment of gout. This work aims to investigate the feasibility of a transdermal patch loaded with uricase for better patient compliance. Mesoporous silica (SBA-15) was chosen as the matrix for immobilisation of uricase. Highly oriented mesoporous SBA-15 was synthesized, characterized and uricase was physisorbed in the mesoporous material. The percentage adsorption and release of enzyme in borate buffer was monitored. The release followed linear kinetics and greater than 80% enzyme activity was retained indicating the potential of this system as an effective enzyme immobilization matrix. The enzyme permeability was studied with Wistar rat skin and human cadaver skin. It was found that in case of untreated rat skin 10% of enzyme permeated through skin in 100 h. The permeation increased by adding permeation enhancer (combination of oleic acid in propylene glycol (OA in PG)). The permeation enhancement was studied under two concentrations of OA in PG (1%, 5%) in both rat and human cadaver skin and it was found that 1% OA in PG showed better result in rat skin and 5% OA in PG showed good results in human cadaver skin. PMID:23802423

  2. Limited Effect of Chronic Valproic Acid Treatment in a Mouse Model of Machado-Joseph Disease

    PubMed Central

    Esteves, Sofia; Duarte-Silva, Sara; Naia, Luana; Neves-Carvalho, Andreia; Teixeira-Castro, Andreia; Rego, Ana Cristina; Silva-Fernandes, Anabela; Maciel, Patrícia

    2015-01-01

    Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeutics. PMID:26505994

  3. Oil sands thickened froth treatment tailings exhibit acid rock drainage potential during evaporative drying.

    PubMed

    Kuznetsov, Petr; Kuznetsova, Alsu; Foght, Julia M; Siddique, Tariq

    2015-02-01

    Bitumen extraction from oil sands ores after surface mining produces different tailings waste streams: 'froth treatment tailings' are enriched in pyrite relative to other streams. Tailings treatment can include addition of organic polymers to produce thickened tailings (TT). TT may be further de-watered by deposition into geotechnical cells for evaporative drying to increase shear strength prior to reclamation. To examine the acid rock drainage (ARD) potential of TT, we performed predictive analyses and laboratory experiments on material from field trials of two types of thickened froth treatment tailings (TT1 and TT2). Acid-base accounting (ABA) of initial samples showed that both TT1 and TT2 initially had net acid-producing potential, with ABA values of -141 and -230 t CaCO₃ equiv. 1000 t(-1) of TT, respectively. In long-term kinetic experiments, duplicate ~2-kg samples of TT were incubated in shallow trays and intermittently irrigated under air flow for 459 days to simulate evaporative field drying. Leachates collected from both TT samples initially had pH~6.8 that began decreasing after ~50 days (TT2) or ~250 days (TT1), stabilizing at pH~2. Correspondingly, the redox potential of leachates increased from 100-200 mV to 500-580 mV and electrical conductivity increased from 2-5 dS m(-1) to 26 dS m(-1), indicating dissolution of minerals during ARD. The rapid onset and prolonged ARD observed with TT2 is attributed to its greater pyrite (13.4%) and lower carbonate (1.4%) contents versus the slower onset of ARD in TT1 (initially 6.0% pyrite and 2.5% carbonates). 16S rRNA gene pyrosequencing analysis revealed rapid shift in microbial community when conditions became strongly acidic (pH~2) favoring the enrichment of Acidithiobacillus and Sulfobacillus bacteria in TT. This is the first report showing ARD potential of TT and the results have significant implications for effective management of pyrite-enriched oil sands tailings streams/deposits. PMID:25306090

  4. Immunomodulation with eicosapentaenoic acid supports the treatment of autoimmune small-vessel vasculitis

    PubMed Central

    Hirahashi, Junichi; Kawahata, Kimito; Arita, Makoto; Iwamoto, Ryo; Hishikawa, Keiichi; Honda, Mie; Hamasaki, Yoshifumi; Tanaka, Mototsugu; Okubo, Koshu; Kurosawa, Miho; Takase, Osamu; Nakakuki, Masanori; Saiga, Kan; Suzuki, Kazuo; Kawachi, Shoji; Tojo, Akihiro; Seki, George; Marumo, Takeshi; Hayashi, Matsuhiko; Fujita, Toshiro

    2014-01-01

    Small-vessel vasculitis is a life-threatening autoimmune disease that is frequently associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Conventional immunotherapy including steroids and cyclophosphamide can cause serious adverse events, limiting the efficacy and safety of treatment. Eicosapentaenoic acid (EPA), a key component of fish oil, is an omega-3 polyunsaturated fatty acid widely known to be cardioprotective and beneficial for vascular function. We report two elderly patients with systemic ANCA-associated vasculitis (AAV) in whom the administration of EPA in concert with steroids safely induced and maintained remission, without the use of additioal immunosuppressants. To explore the mechanisms by which EPA enhances the treatment of AAV, we employed SCG/Kj mice as a spontaneous murine model of AAV. Dietary enrichment with EPA significantly delayed the onset of crescentic glomerulonephritis and prolonged the overall survival. EPA-derived anti-inflammatory lipid mediators and their precursors were present in the kidney, plasma, spleen, and lungs in the EPA-treated mice. Furthermore, a decrease in ANCA production and CD4/CD8-double negative T cells, and an increase in Foxp3+ regulatory T cells in the lymph nodes of the kidney were observed in the EPA-treated mice. These clinical and experimental observations suggest that EPA can safely support and augment conventional therapy for treating autoimmune small-vessel vasculitis. PMID:25230773

  5. Parallel electrochemical treatment system and application for identifying acid-stable oxygen evolution electrocatalysts.

    PubMed

    Jones, Ryan J R; Shinde, Aniketa; Guevarra, Dan; Xiang, Chengxiang; Haber, Joel A; Jin, Jian; Gregoire, John M

    2015-02-01

    Many energy technologies require electrochemical stability or preactivation of functional materials. Due to the long experiment duration required for either electrochemical preactivation or evaluation of operational stability, parallel screening is required to enable high throughput experimentation. Imposing operational electrochemical conditions to a library of materials in parallel creates several opportunities for experimental artifacts. We discuss the electrochemical engineering principles and operational parameters that mitigate artifacts in the parallel electrochemical treatment system. We also demonstrate the effects of resistive losses within the planar working electrode through a combination of finite element modeling and illustrative experiments. Operation of the parallel-plate, membrane-separated electrochemical treatment system is demonstrated by exposing a composition library of mixed-metal oxides to oxygen evolution conditions in 1 M sulfuric acid for 2 h. This application is particularly important because the electrolysis and photoelectrolysis of water are promising future energy technologies inhibited by the lack of highly active, acid-stable catalysts containing only earth abundant elements. PMID:25561243

  6. Intra-Arterial Calcium Gluconate Treatment After Hydrofluoric Acid Burn of the Hand

    SciTech Connect

    Thomas, D. Jaeger, U.; Sagoschen, I.; Lamberti, C.; Wilhelm, K.

    2009-01-15

    Hydrofluoric acid (HF) is a colorless corrosive acid used in different industrial branches. Exposure to HF typically results from spills, and most often the hand or fingers are involved. Tissue damage through cutaneous HF exposure occurs through corrosive burns due to the free hydrogen ions and through skin penetration of the fluoride ions, causing a depletion of calcium in the deep tissue layers, ultimately leading to cell death and tissue necrosis. Treatment of HF burns consists of thoroughly flushing the exposed area with water and applying calcium gluconate gel to the skin. If topical treatment does not suffice, subcutaneous injections, as well as intravascular-both intravenous and intra-arterial-calcium gluconate therapy, have been advocated. We report for the first time a case of HF burn of the hand and digits associated with vasospasm. Pain and vasospasm were successfully treated by repeated intra-arterial calcium gluconate injection. We conclude that intra-arterial calcium gluconate injection is a successful and well-tolerated therapy for HF burn associated with Raynaud's syndrome. Intra-arterial injection allows for well-controlled delivery of therapy as well as assessment of the vascular status.

  7. Inhaled hyaluronic acid as ancillary treatment in children with bacterial acute rhinopharyngitis.

    PubMed

    Varricchio, A; Capasso, M; Avvisati, F; Varricchio, A M; De Lucia, A; Brunese, F P; Ciprandi, G

    2014-01-01

    Acute rhinopharyngitis (ARP) is the most common upper respiratory infection in children and represents a social problem for both the pharmaco-economic impact and a burden for the family. Topical antibiotic therapy is usually effective in bacterial ARP, but ancillary treatment might improve its efficacy. Hyaluronic acid (HA) is a promising molecule that has been recently proposed in upper respiratory disorders. Therefore, the purpose of this study was to evaluate the effects of ancillary HA treatment in children with bacterial ARP. Globally, 51 children (27 males, mean age 5.9 ± 2.1 years) with bacterial ARP were enrolled in the study. At baseline, children were randomly assigned to the treatment with: 125 mg of thiamphenicol diluted in 4 mL of saline isotonic solution twice daily (group A) or with 125 mg of thiamphenicol plus 4 ml of sodium hyaluronate 0.2% plus xylitol 5% (Aluneb, Sakura Italia) twice daily (group B) administered by the nasal device Rinowash (Airliquide Medical System, Italy) and connected to an aerosol nebulizer with pneumatic compressor (1.5 bar per 5 L/min) Nebula (Airliquide Medical System, Italy), for 10 days. sVAS, nasopharyngeal spotting, neutrophils and bacteria were assessed at baseline and after the treatment. Both treatments induced significant reduction of symptom perception, spotting, neutrophil and bacteria count. However, thiamphenicol plus HA was able to significantly induce a greater effect on sVAS (p=0.006), neutrophil count (p=0.01), and bacteria count (p=0.0003) than thiamphenicol alone. In conclusion, this study provides the first evidence that intranasal HA, as ancillary treatment, may be able to improve topical antibiotic efficacy in children with bacterial ARP. PMID:25316142

  8. A combined CaO/electrochemical treatment of the acid mine drainage from the "Robule" Lake.

    PubMed

    Orescanin, Visnja; Kollar, Robert

    2012-01-01

    The purpose of this work was development and application of the purification system suitable for the treatment of the acid mine drainage (AMD) accumulated in the "Robule" Lake, which represents the part of the Bor copper mining and smelting complex, Serbia. The study was undertaken in order to minimize adverse effect on the environment caused by the discharge of untreated AMD, which was characterized with low pH value (2.63) and high concentration of heavy metals (up to 610 mg/L) and sulfates (up to 12,000 mg/L). The treatment of the effluent included pretreatment/pH adjustment with CaO followed by electrocoagulation using iron and aluminum electrode sets. Following the final treatment, the decrease in the concentration of heavy metals ranged from 40 up to 61000 times depending on the metal and its initial concentration. The parameters, color and turbidity were removed completely in the pretreatment step, while the removal efficiencies for other considered parameters were as follows: EC = 55.48%, SO(4) (2-) = 70.83%, Hg = 98.36%, Pb = 97.50%, V = 98.43%, Cr = 99.86%, Mn = 97.96%, Fe = 100.00%, Co = 99.96%, Ni = 99.78%, Cu = 99.99% and Zn = 99.94%. Because the concentrations of heavy metals in the electrochemically treated AMD (ranging from 0.001 to 0.336 mg/L) are very low, the negative impact of this effluent on the aquatic life and humans is not expected. The sludge generated during the treatment of AMD is suitable for reuse for at least two purposes (pretreatment of AMD and covering of the flotation waste heap). From the presented results, it could be concluded that electrochemical treatment is a suitable approach for the treatment of AMD. PMID:22506711

  9. Geochemical modelling of EGS fracture stimulation applying weak and strong acid treatments

    NASA Astrophysics Data System (ADS)

    Sigfusson, Bergur; Sif Pind Aradottir, Edda

    2015-04-01

    Engineered Geothermal systems (EGS) provide geothermal power by tapping into the Earth's deep geothermal resources that are otherwise not exploitable due to lack of water and fractures, location or rock type. EGS technologies have the potential to cost effectively produce large amounts of electricity almost anywhere in the world. The EGS technology creates permeability in the rock by hydro-fracturing the reservoir with cold water pumped into the first well (the injection well) at a high pressure. The second well (the production well) intersects the stimulated fracture system and returns the hot water to the surface where electricity can be generated. A significant technological hurdle is ensuring effective connection between the wells and the fracture system and to control the deep-rooted fractures (can exceed 5 000 m depth). A large area for heat transfer and sufficient mass flow needs to be ensured between wells without creating fast flowing paths in the fracture network. Maintaining flow through the fracture system can cause considerable energy penalty to the overall process. Therefore, chemical methods to maintain fractures and prevent scaling can be necessary to prevent excessive pressure build up in the re-injection wells of EGS systems. The effect of different acid treatments on the porosity development of selected rock types was simulated with the aid of the Petrasim interface to the Toughreact simulation code. The thermodynamic and kinetic database of Aradottir et al. (2014) was expanded to include new minerals and the most important fluoride bearing species involved in mineral reactions during acid stimulation of geothermal systems. A series of simulations with injection waters containing fluoric acid, hydrochloric acid and CO2 or mixtures thereof were then carried out and porosity development in the fracture system monitored. The periodic injection of weak acid mixtures into EGS systems may be cost effective in some isolated cases to prevent pressure

  10. The effect of dilute acid pre-treatment process in bioethanol production from durian (Durio zibethinus) seeds waste

    NASA Astrophysics Data System (ADS)

    Ghazali, K. A.; Salleh, S. F.; Riayatsyah, T. M. I.; Aditiya, H. B.; Mahlia, T. M. I.

    2016-03-01

    Lignocellulosic biomass is one of the promising feedstocks for bioethanol production. The process starts from pre-treatment, hydrolysis, fermentation, distillation and finally obtaining the final product, ethanol. The efficiency of enzymatic hydrolysis of cellulosic biomass depends heavily on the effectiveness of the pre-treatment step which main function is to break the lignin structure of the biomass. This work aims to investigate the effects of dilute acid pre-treatment on the enzymatic hydrolysis of durian seeds waste to glucose and the subsequent bioethanol fermentation process. The yield of glucose from dilute acid pre-treated sample using 0.6% H2SO4 and 5% substrate concentration shows significant value of 23.4951 g/L. Combination of dilute acid pre-treatment and enzymatic hydrolysis using 150U of enzyme able to yield 50.0944 g/L of glucose content higher compared to normal pre-treated sample of 8.1093 g/L. Dilute acid pre-treatment sample also shows stable and efficient yeast activity during fermentation process with lowest glucose content at 2.9636 g/L compared to 14.7583g/L for normal pre-treated sample. Based on the result, it can be concluded that dilute acid pre-treatment increase the yield of ethanol from bioethanol production process.

  11. The chemistry of conventional and alternative treatment systems for the neutralization of acid mine drainage.

    PubMed

    Kalin, Margarete; Fyson, Andrew; Wheeler, William N

    2006-08-01

    The oxidation of pyritic mining waste is a self-perpetuating corrosive process which generates acid mine drainage (AMD) effluent for centuries or longer. The chemical neutralization of these complex, buffered effluents result in unstable, metal-laden sludges, which require disposal to minimize long-term environmental consequences. A variety of passive treatment systems for AMD, developed in the past two decades, combine limestone and organic substrates in constructed wetlands. These systems work well initially but over the longer term fail due to clogging with and the depletion of available organic carbon. However, some ecologically engineered systems, which exploit the activities of acid reducing microbes in the sediment, rely on photosynthesis in the water column as a source of organic matter. The primary productivity in the water column, which also generates some alkalinity, provides electron donors for the microbial reduction processes in the sediment. In its consideration of 'passive' systems, the literature has placed undue emphasis on sulphate reduction; thermodynamical iron reduction is equally important as is the need to prevent iron oxidation. Secondary precipitates of iron play a significant role in sediment-driven biomineralization processes, which affect the anaerobic degradation of organic matter and the stability of the resulting metal sulfides. One such passive system, which utilized a floating root mass as a source of organic carbon, is described. An extensive review of the literature and the chemical and biogeochemical reactions of AMD treatment systems, lead to the conclusion, that sediment based ecological systems offer the greatest potential for the sustainable treatment of AMD. PMID:16375949

  12. Treatment of flaxseed to reduce biohydrogenation of a-linolenic acid by ruminal microbes in sheep and cattle and increase n-3 fatty acid concentrations in red meat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our study determined if flaxseed treated with a formaldehyde-free process increased n-3 fatty acid (FA) levels in ruminant muscle. Twenty-four lambs (initial BW 43.8 ± 4.4 kg) were randomly divided into 4 groups for a 90-d trial. One treatment group (FLX) was fed 136 g/d of non-treated ground flaxse...

  13. Effects of ultrasonic treatment during acid hydrolysis on the yield, particle size and structure of cellulose nanocrystals.

    PubMed

    Guo, Juan; Guo, Xuxia; Wang, Siqun; Yin, Yafang

    2016-01-01

    Ultrasonic treatment is useful for the isolation of cellulose nanocrystals (CNCs). However, the effects of ultrasonic treatment on the structure and properties of CNCs have not been fully understood. We statistically analyzed the variations in yields and dimensions of CNCs prepared using acid hydrolysis, with or without ultrasonic treatment, and illustrated these variations by investigating the CNC structures. The results demonstrated that ultrasonic treatment promoted an increase in yields only for short hydrolysis times, while resulting in CNCs with shorter lengths and narrower dimension distributions. Furthermore, a prolonged acid attack under ultrasonic treatment caused a partial dissociation of cellulose hydrogen bond networks in the CNCs, ultimately resulting in the delamination and disorder of the cellulose crystalline structure, thus leading to a decrease in the width and thickness of the CNCs. This work provides more insights into the mechanisms of ultrasonic treatment on the structure and properties of CNCs. PMID:26453875

  14. Fucosylated Glycans in α1-Acid Glycoprotein for Monitoring Treatment Outcomes and Prognosis of Cancer Patients

    PubMed Central

    Yazawa, Shin; Takahashi, Ryo; Yokobori, Takehiko; Sano, Rie; Mogi, Akira; Saniabadi, Abby R.; Kuwano, Hiroyuki; Asao, Takayuki

    2016-01-01

    One standard treatment option for advanced-stage cancer is surgical resection of malignant tumors following by adjuvant chemotherapy and chemoradiotherapy. Additionally, neoadjuvant chemotherapy may be applied if required. During the time course of treatments, patients are generally followed by computed tomography (CT) surveillance, and by tumor marker diagnosis. However, currently, early evidence of recurrence and/or metastasis of tumors with a clinically relevant biomarker remains a major therapeutic challenge. In particular, there has been no validated biomarker for predicting treatment outcomes in therapeutic settings. Recently, we have looked at glycoforms of serum α1-acid glycoprotein (AGP) by using a crossed affinoimmunoelectrophoresis with two lectins and an anti-AGP antibody. The primary glycan structures of AGP were also analyzed by a mass spectrometer and a novel software in a large number of patients with various cancers. Accordingly, the relative abundance of α1,3fucosylated glycans in AGP (FUCAGP) was found to be significantly high in cancer patients as compared with the healthy controls. Further, strikingly elevated levels of FUCAGP were found in patients with poor prognosis but not in patients with good prognosis. In the current study, levels of FUCAGP in serum samples from various cancer patients were analyzed and 17 patients including 13 who had undergone chemotherapy were followed for several years post operation. FUCAGP level determined diligently by using a mass spectrometer was found to change along with disease prognosis as well as with responses to treatments, in particular, to various chemotherapies. Therefore, FUCAGP levels measured during following-up of the patients after operation appeared to be clinically relevant biomarker of treatment intervention. PMID:27295180

  15. THE USE OF COAL COMBUSTION BY-PRODUCTS FOR IN SITU TREATMENT OF ACID MINE DRAINAGE

    SciTech Connect

    Geoffrey A. Canty; Jess W. Everett

    2004-09-30

    In 1994 a demonstration project was undertaken to investigate the effectiveness of using CCBs for the in situ treatment of acidic mine water. Actual injection of alkaline material was performed in 1997 with initial positive results; however, the amount of alkalinity added to the system was limited and resulted in short duration treatment. In 1999, a CBRC grant was awarded to further investigate the effectiveness of alkaline injection technology (AIT). Funds were released in fall 2001. In December 2001, 2500 tons of fluidized bed combustion (FBC) ash were injected into the wells used in the 1997 injection project. Post injection monitoring continued for 24 months. During this period the mine chemistry had gone through a series of chemical changes that manifested as stages or ''treatment phases.'' The mine system appeared to be in the midst of reestablishing equilibrium with the partial pressure of mine headspace. Alkalinity and pH appeared to be gradually increasing during this transition. As of December 2003, the pH and alkalinity were roughly 7.3 and 65 ppm, respectively. Metal concentrations were significantly lower than pre-injection levels, but iron and manganese concentrations appeared to be gradually increasing (roughly 30 ppm and 1.25 ppm, respectively). Aluminum, nickel, and zinc were less than pre-injection concentrations and did not appear to be increasing (roughly

  16. Recovery of reducing sugars and volatile fatty acids from cornstalk at different hydrothermal treatment severity.

    PubMed

    Zhu, Zhangbing; Liu, Zhidan; Zhang, Yuanhui; Li, Baoming; Lu, Haifeng; Duan, Na; Si, Buchun; Shen, Ruixia; Lu, Jianwen

    2016-01-01

    This study focused on the degradation of cornstalk and recovery of reducing sugars and volatile fatty acids (VFAs) at different hydrothermal treatment severity (HTS) (4.17-8.28, 190-320°C). The highest recovery of reducing sugars and VFAs reached 92.39% of aqueous products, equal to 34.79% based on dry biomass (HTS, 6.31). GC-MS and HPLC identified that the aqueous contained furfural (0.35-2.88 g/L) and 5-hydroxymethyl furfural (0-0.85 g/L) besides reducing sugars and VFAs. Hemicellulose and cellulose were completely degraded at a HTS of 5.70 and 7.60, respectively. SEM analysis showed that cornstalk was gradually changed from rigid and highly ordered fibrils to molten and grainy structure as HTS increased. FT-IR and TGA revealed the significant changes of organic groups for cornstalk before and after hydrothermal treatment at different HTS. Hydrothermal treatment might be promising for providing feedstocks suitable for biohythane production. PMID:26316401

  17. Probiotic lactic acid bacteria and their potential in the prevention and treatment of allergic diseases

    PubMed Central

    Wróblewska, Paula; Adamczuk, Piotr; Silny, Wojciech

    2014-01-01

    Allergy is one of the most important and very common health problems worldwide. To reduce the proportion of people suffering from allergy, alternative methods of prevention and treatment are sought. The aim of this paper is to present the possibilities of probiotics in the prevention and treatment of allergic diseases. Probiotics are live microorganisms belonging mainly to the lactic acid bacteria. They modify the microflora of the human digestive system, especially the intestinal microflora. Prophylactic administration of probiotics in the early stages of life (naturally in breast milk or milk substitute synthetic compounds) is very important because intestinal microflora plays a huge role in the development of the immune system. Prevention of allergies as early as in the prenatal and postnatal periods provides huge opportunities for inhibiting the growing problem of allergy in emerging and highly developed societies. Effects of probiotic therapy depend on many factors such as the species of the microorganism used, the dose size and characteristics of the bacteria such as viability and capacity of adhesion to the intestinal walls. Authors of several studies showed beneficial effects of probiotics in the perinatal period, infancy, and also in adults in the prevention of atopic dermatitis or allergic rhinitis. Probiotics, due to their immunomodulatory properties and safety of use are a good, natural alternative for the prevention and treatment of many diseases including allergies. It is therefore important to explore the knowledge about their use and to carry out further clinical trials. PMID:26155109

  18. The status of the passive treatment systems for acid mine drainage in South Korea

    NASA Astrophysics Data System (ADS)

    Ji, Sangwoo; Kim, Sunjoon; Ko, Juin

    2008-09-01

    This study was performed to investigate the operating status, evaluate the problems, and discuss possible improvement methods of passive treatment systems for acid mine drainage (AMD) in South Korea. Thirty-five passive treatment systems in 29 mines have been constructed from 1996 to 2002 using successive alkalinity producing systems (SAPS) as the main treatment process. We investigated 29 systems (two for metal mines), 19 of which revealed various problems. Overflows of drainage from SAPS, wetland, or oxidation ponds were caused by the flow rate exceeding the capacities of the facilities or by the reduced permeability of the organic substance layer. Leakages occurred at various parts of the systems. In some cases, clogged and broken pipes at the mouths of the mine adits made the whole system unusable. Some systems showed very low efficiencies without apparent leakage or overflow. Even though the systems showed fairly good efficiencies in metal removal ratios (mainly iron) and pH control; sulfate removal rates were very poor except in three systems, which may indicate very poor sulfate reductions with sulfate reducing bacteria (SRB) as a means.

  19. Role of Hyaluronic Acid Treatment in the Prevention of Keloid Scarring

    PubMed Central

    Hoffmann, Andrea; Hoing, Jessica Lynn; Newman, Mackenzie; Simman, Richard

    2013-01-01

    Background Keloids are benign dermal scars characterized by enhanced growth factor signaling, hyperproliferation activity and reduced extracellular matrix (ECM) deposition of hyaluronic acid. Our hypothesis is that high molecular weight HA can be used to replenish HA deposition in keloids thereby normalizing the keloid fibroblast phenotype. Methods One normal (NF1) fibroblast culture and five keloid (KF1, KF2, KF3, KF4, KF5) fibroblast cultures were analyzed for changes in hyperproliferation, growth factor production and extracellular matrix deposition following 72 hour treatment with or without 10 μg/ml HA. Results Proliferation activity decreased significantly in KF3 following HA treatment. Pro-collagen I expression in KF2 was decreased following HA treatment in association with changes in fiber arrangement to more parallel collagen bundles. In addition, HA demonstrated a downregulation on TGF-b1 growth factor expression in KF3 and KF4 and a decrease in active TGF-b1 release in KF2 and KF5 using ELISA. Conclusion Our data demonstrates that HA has the potential to normalize keloid fibroblast characteristic features such as hyperproliferation, growth factor production and ECM deposition depending on the specific genotype of the keloid fibroblast cell line. This study suggests that high molecular weight HA can be used to replenish HA deposition in keloid fibroblasts thereby decreasing fibrosis and ultimately decreasing keloid manifestation. PMID:24936445

  20. Photoluminescence Enhancement and Structure Repairing of Monolayer MoSe2 by Hydrohalic Acid Treatment.

    PubMed

    Han, Hau-Vei; Lu, Ang-Yu; Lu, Li-Syuan; Huang, Jing-Kai; Li, Henan; Hsu, Chang-Lung; Lin, Yung-Chang; Chiu, Ming-Hui; Suenaga, Kazu; Chu, Chih-Wei; Kuo, Hao-Chung; Chang, Wen-Hao; Li, Lain-Jong; Shi, Yumeng

    2016-01-26

    Atomically thin two-dimensional transition-metal dichalcogenides (TMDCs) have attracted much attention recently due to their unique electronic and optical properties for future optoelectronic devices. The chemical vapor deposition (CVD) method is able to generate TMDCs layers with a scalable size and a controllable thickness. However, the TMDC monolayers grown by CVD may incorporate structural defects, and it is fundamentally important to understand the relation between photoluminescence and structural defects. In this report, point defects (Se vacancies) and oxidized Se defects in CVD-grown MoSe2 monolayers are identified by transmission electron microscopy and X-ray photoelectron spectroscopy. These defects can significantly trap free charge carriers and localize excitons, leading to the smearing of free band-to-band exciton emission. Here, we report that the simple hydrohalic acid treatment (such as HBr) is able to efficiently suppress the trap-state emission and promote the neutral exciton and trion emission in defective MoSe2 monolayers through the p-doping process, where the overall photoluminescence intensity at room temperature can be enhanced by a factor of 30. We show that HBr treatment is able to activate distinctive trion and free exciton emissions even from highly defective MoSe2 layers. Our results suggest that the HBr treatment not only reduces the n-doping in MoSe2 but also reduces the structural defects. The results provide further insights of the control and tailoring the exciton emission from CVD-grown monolayer TMDCs. PMID:26716765

  1. Dual effects of slightly acidic electrolyzed water (SAEW) treatment on the accumulation of γ-aminobutyric acid (GABA) and rutin in germinated buckwheat.

    PubMed

    Hao, Jianxiong; Wu, Tongjiao; Li, Huiying; Wang, Wei; Liu, Haijie

    2016-06-15

    In the present study, the dual effects of slightly acidic electrolyzed water (SAEW) treatment on γ-aminobutyric acid (GABA) and rutin accumulation of germinated buckwheat were evaluated during germination. The results showed that SAEW treatment (pH 5.83, ACC of 20.3 mg/L) could promote the accumulation of GABA and rutin in germinated buckwheat. The GABA and rutin contents of SAEW-germinated buckwheat reached 143.20 and 739.9 mg/100 g respectively, which is significantly higher than those of control (P<0.05). Moreover, SAEW treatment could increase the activity of glutamic acid decarboxylase (GAD) and phenylalanine ammonialyase (PAL) and thus result in the GABA and rutin accumulation of germinated buckwheat. The results suggested that SAEW treatment could promote the rutin accumulation of germinated buckwheat by influencing phenylpropanoid secondary metabolic pathway instead of the inhibition of rutin degrading enzyme (RDE) activity. In addition, SAEW treatment had no adverse impact on the sprouts growth and could reduce the microbial populations of germinated buckwheat during germination. PMID:26868552

  2. [EXPERIENCE OF USE OF BLEMAREN® IN THE TREATMENT OF PATIENTS IN URIC ACID AND CALCIUM OXALATE UROLITHIASIS].

    PubMed

    Konstantinova, O V; Yanenko, E K

    2015-01-01

    154 patients with urolithiasis were under outpatient observation for 2-8 years. Among them there were 76 women and 78 men aged 21-66 years, of which 46 patients with uric acid urolithiasis, and 88--with calcium oxalate urolithiasis. Treatment of patients was carried out systematically, depending on their condition. Indications for the application of Blemaren® included the presence of uric acid stones, uric acid and/or oxalate crystalluria. The duration of treatment was 6.1 months. The dosage of the drug varied from 6 to 18 g per day and was selected individually, depending on the purpose of the appointment of Blemaren®. Reduction of the urine pH to 6.2- 6.8-7.2 was the criterion for properly selected dose. To dissolve uric acid stones in the presence of hyperuricemia and/or hyperuricuria, Blemaren® was administered in combination with allopurinol at a dose of 0.1 g 3-4 times a day. Besides pharmacotherapy, treatment included diet therapy. It was found that the morning urine pH in urate urolithiasis is sustainable and has a range of 5.0-6.0, in 80.4% of cases--range of 5.0-5.5. In calcium oxalate urolithiasis this parameter is also stable and has a range of 5.0-6.7, in 82.9% of cases--range of 5.5-6.0. Optimal urine pH to eliminate uric acid and oxalate crystalluria in patients with uric acid and calcium oxalate urolithiasis is the interval of 6.2-6.4. It was shown that Blemaren® is a highly effective agent for treatment and prevention of uric acid and calcium oxalate crystalluria in calcium oxalate and uric acid urolithiasis. Further, its effectiveness in dissolving of uric acid stones in the absence of an infectious inflammatory process is 82.3%. PMID:26859932

  3. Effect of ultrasonic pre-treatment on low temperature acid hydrolysis of oil palm empty fruit bunch.

    PubMed

    Yunus, Robiah; Salleh, Shanti Faridah; Abdullah, Nurhafizah; Biak, Dyg Radiah Awg

    2010-12-01

    Various pre-treatment techniques change the physical and chemical structure of the lignocellulosic biomass and improve hydrolysis rates. The effect of ultrasonic pre-treatment on oil palm empty fruit bunch (OPEFB) fibre prior to acid hydrolysis has been evaluated. The main objective of this study was to determine if ultrasonic pre-treatment could function as a pre-treatment method for the acid hydrolysis of OPEFB fibre at a low temperature and pressure. Hydrolysis at a low temperature was studied using 2% sulphuric acid; 1:25 solid liquid ratio and 100 degrees C operating temperature. A maximum xylose yield of 58% was achieved when the OPEFB fibre was ultrasonicated at 90% amplitude for 45min. In the absence of ultrasonic pre-treatment only 22% of xylose was obtained. However, no substantial increase of xylose formation was observed for acid hydrolysis at higher temperatures of 120 and 140 degrees C on ultrasonicated OPEFB fibre. The samples were then analysed using a scanning electron microscope (SEM) to describe the morphological changes of the OPEFB fibre. The SEM observations show interesting morphological changes within the OPEFB fibre for different acid hydrolysis conditions. PMID:20719502

  4. Surface profile changes of scuffed bearing surfaces. [before and after acid treatment

    NASA Technical Reports Server (NTRS)

    Lauer, J. L.; Fung, S. S.; Jones, W. R., Jr.

    1982-01-01

    A phase locked interference microscope capable of resolving depth differences to 30 A and planar displacements of 6000 A was constructed for the examination of the profiles of bearing surfaces without physical contact. This instrument was used to determine surface chemical reactivity by applying a drop of dilute alcoholic hydrochloric acid and measuring the profile of the solid surface before and after application of this probe. Scuffed bearing surfaces reacted much faster than unscuffed ones, but bearing surfaces which had been previously exposed to lubricants containing an organic chloride reacted much more slowly. In a separate series of experiments, a number of stainless steel plates were heated in a nitrogen atmosphere to different temperatures and their reactivity examined later at room temperature. The change of surface contour as a result of the probe reaction followed an Arrhenius type relation with respect to heat treatment temperature. This result could have implications on the scuffing mechanism.

  5. Acid ceramidase and the treatment of ceramide diseases: The expanding role of enzyme replacement therapy.

    PubMed

    Schuchman, Edward H

    2016-09-01

    Ceramides are a diverse group of sphingolipids that play important roles in many biological processes. Acid ceramidase (AC) is one key enzyme that regulates ceramide metabolism. Early research on AC focused on the fact that it is the enzyme deficient in the rare genetic disorder, Farber Lipogranulomatosis. Recent research has revealed that deficiency of the same enzyme is responsible for a rare form of spinal muscular atrophy associated with myoclonic epilepsy (SMA-PME). Due to their diverse role in biology, accumulation of ceramides also has been implicated in the pathobiology of many other common diseases, including infectious lung diseases, diabetes, cancers and others. This has revealed the potential of AC as a therapy for many of these diseases. This review will focus on the biology of AC and the potential role of this enzyme in the treatment of human disease. PMID:27155573

  6. A new amino acid mixture permits new approaches to the treatment of phenylketonuria.

    PubMed

    Buist, N R; Prince, A P; Huntington, K L; Tuerck, J M; Waggoner, D D

    1994-12-01

    A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance. PMID:7766965

  7. Farnesoid X Receptor Agonists and Other Bile Acid Signaling Strategies for Treatment of Liver Disease.

    PubMed

    Halilbasic, Emina; Fuchs, Claudia; Traussnigg, Stefan; Trauner, Michael

    2016-01-01

    The intracellular nuclear receptor farnesoid X receptor (FXR) and the transmembrane G protein-coupled receptor 5 (TGR5) respond to bile acids (BAs) by activating transcriptional networks and/or signaling cascades. These cascades affect the expression of a great number of target genes relevant for BA, cholesterol, lipid and carbohydrate metabolism, as well as genes involved in inflammation, fibrosis and carcinogenesis. FXR activation in the liver tissue and beyond, such as the gut-liver axis, kidney and adipose tissue, plays a role in metabolic diseases. These BA receptors activators hold promise to become a new class of drugs to be used in the treatment of chronic liver disease, hepatocellular cancer and extrahepatic inflammatory and metabolic diseases. This review discusses the relevant BA receptors, the new drugs that target BA transport and signaling and their possible applications. PMID:27332721

  8. Methylsulfonylmethane and boswellic acids versus glucosamine sulfate in the treatment of knee arthritis: Randomized trial.

    PubMed

    Notarnicola, Angela; Maccagnano, Giuseppe; Moretti, Lorenzo; Pesce, Vito; Tafuri, Silvio; Fiore, Alessandra; Moretti, Biagio

    2016-03-01

    Until now glucosamine sulfate (GS) has been the most widely used supplement and has been shown to be efficacious in the treatment of osteoarthritis (OA). Methylsulfonylmethane (MSM) and boswellic acids (BA) are new effective supplements for the management of inflammation and joint degeneration, according to previous experimental studies. The aim of our study is to test the effectiveness of association of MSM and BA in comparison with GS in knee arthritis.In this prospective randomized clinical trial, MEBAGA (Methylsulfonylmethane and Boswellic Acids versus Glucosamine sulfate in the treatment of knee Arthritis), 120 participants affected by arthritis of the knee were randomly assigned to an experimental group (MB group) or a control group (GS group) treated for 60 days with 5 g of MSM and 7.2 mg of BA or with 1500 mg of GS daily, respectively. At the 2-month (T1) and 6-months (T2) follow-up , the efficacy of these two nutraceuticals was assessed using the visual analog pain scale (VAS) and the Lequesne Index (LI) for joint function, along with the use of anti-inflammatory drugs (non-steroidal anti-inflammatory drugs and anti-cyclooxygenase-2).The repeated measures ANOVA analysis shows that for VAS, LI, and the use of anti-inflammatory drugs scores there are improvements due to the time in the two groups (respectively, F=26.0; P<0.0001; F=4.15; P=0.02; F=3.38; P=0.04), with a tendency to better values for the MB group at T2.On the basis of these preliminary data, we could support the efficacy of the MSM in association with BA in the treatment of OA. These results are consistent with the anti-inflammatory and chondroprotective effects previously occurred in experimental studies. This new combination of integration (MSM and BS) has presented good results and satisfactory in comparison with GS, until now the cornerstone of the treatment of arthritis in according to guidelines. PMID:26684635

  9. Amino acids labelled with 11C as indicator of the effect of dietary treatment of hyperammonaemia.

    PubMed

    Hardell, L I; Stålnacke, C G; Lundqvist, H; Malmborg, P; Långström, B

    1984-01-01

    Short-lived radioactive carbon, 11C, (T 1/2 = 20 min) was incorporated into an essential amino acid [11C-methyl] -L-methionine, to form a true biological amino acid tracer with external detectability. This was tested in a study of the physiological tracer dynamics in a hyperammonaemic patient before and after a change in the dietary treatment. The protein intake was unchanged between the two investigations but the energy intake was increased from 53 to 63 kcal/kg BW/day. The tracer radioactivity was given per os. In the second investigation a relative decrease of radioactivity in the low molecular weight fraction of blood plasma was seen. Also the external measurements indicated a higher hepatic retention of radioactivity in the second investigation but no increased excretion of tracer. This may reflect an increased ability of the liver to utilize the incoming methionine from the vena porta. The hyperammonaemia remained over the second investigation but seven months later the ammonia content in the blood was almost normalized and the patient had also gained 3 kg in weight. The correlation between changes in tracer dynamics and changes in therapeutical effect of the diet is not further verified in this experiment but the investigation indicates the value of further studies in this topic using 11C-labelled amino acids also including the use of the newly introduced positron tomographic technique. It may be possible to develop this type of nuclide technique further to achieve a clinically useful method of optimizing therapeutic regiments in this type of metabolic disease. PMID:6393522

  10. Flaxseed treatments to reduce biohydrogenation of alpha-linolenic acid by rumen microbes in cattle.

    PubMed

    Kronberg, S L; Scholljegerdes, E J; Barceló-Coblijn, G; Murphy, E J

    2007-12-01

    Enrichment of beef muscle with n-3 fatty acids (FA) is one means to introduce these FA into the diet, but ruminal biohydrogenation limits their bioavailability. To address this problem, we evaluated the ability of condensed tannin (quebracho), in the presence or absence of casein, to protect 18:3n-3 in flaxseed from hydrogenation by ruminal microbes in cattle using an in vitro fermentation approach coupled with evaluation in cattle in vivo. Treated and untreated flaxseed was incubated with bovine rumen fluid for 0 and 24 h. With tannin treated flaxseed, hydrogenation of 18:3n-3 was limited to only 13% over 24 h compared to 43% for untreated flaxseed, while addition of casein to the tannin added no additional protection. To determine if a similar level of protection would occur in vivo, we used two groups of five steers fed either a grain-based or forage-based diet. Five steers were given a grain-based diet during the trial and were fed either ground flaxseed or tannin treated flaxseed for 15 days prior to blood collection for plasma lipid fatty acid analysis. The forage fed steers followed the same regimen. Ingestion of tannin-treated flaxseed did not increase 18:3n-3 and 20:5n-3 in plasma neutral lipids as compared to non-treated flaxseed. Thus, we demonstrated that treating ground flaxseed with quebracho tannin is not useful for increasing 18:3n-3 in the neutral lipid of bovine blood plasma, and suggest caution when interpreting results from in vitro trials that test potential treatments for protecting fatty acids from hydrogenation by ruminal microbes. PMID:17985170

  11. Optimized Protocol To Analyze Changes in the Lipidome of Xenografts after Treatment with 2-Hydroxyoleic Acid.

    PubMed

    Fernández, Roberto; Garate, Jone; Lage, Sergio; Terés, Silvia; Higuera, Mónica; Bestard-Escalas, Joan; Martin, M Laura; López, Daniel H; Guardiola-Serrano, Francisca; Escribá, Pablo V; Barceló-Coblijn, Gwendolyn; Fernández, José A

    2016-01-01

    Xenografts are a popular model for the study of the action of new antitumor drugs. However, xenografts are highly heterogeneous structures, and therefore it is sometimes difficult to evaluate the effects of the compounds on tumor metabolism. In this context, imaging mass spectrometry (IMS) may yield the required information, due to its inherent characteristics of sensitivity and spatial resolution. To the best of our knowledge, there is still no clear analysis protocol to properly evaluate the changes between samples due to the treatment. Here we present a protocol for the evaluation of the effect of 2-hydroxyoleic acid (2-OHOA), an antitumor compound, on xenografts lipidome based on IMS. Direct treated/control comparison did not show conclusive results. As we will demonstrate, a more sophisticated protocol was required to evaluate these changes including the following: (1) identification of different areas in the xenograft, (2) classification of these areas (necrotic/viable) to compare similar types of tissues, (3) suppression of the effect of the variation of adduct formation between samples, and (4) normalization of the variables using the standard deviation to eliminate the excessive impact of the stronger peaks in the statistical analysis. In this way, the 36 lipid species that experienced the largest changes between treated and control were identified. Furthermore, incorporation of 2-hydroxyoleic acid to a sphinganine base was also confirmed by MS/MS. Comparison of the changes observed here with previous results obtained with different techniques demonstrates the validity of the protocol. PMID:26607740

  12. Nanoliposomal irinotecan plus fluorouracil and folinic acid: a new treatment option in metastatic pancreatic cancer.

    PubMed

    Ur Rehman, Sana Saif; Lim, Kian; Wang-Gillam, Andrea

    2016-05-01

    Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease with half of patients diagnosed in the metastatic setting. Until recently, patients after progression on front-line gemcitabine-based regimen had no standard second-line option, although flouropyrimidine-based regimens were frequently used in this setting. Encapsulation of chemotherapeutics in liposomal formulation is an effective way of prolonging drug deposition thereby enhancing cytotoxic efficacy. In a large phase III randomized trial on metastatic PDAC patients who progressed after gemcitabine-based chemotherapy, a novel nanoliposome-encapsulated irinotecan (PEP02, MM-398, nal-IRI, Onivyde, Merrimack, Boston, US) plus fluorouracil and folinic acid demonstrated a significant survival advantage compared to fluorouracil and folinic acid alone. This pivotal study led to the recent FDA approval of nanoliposomal irinotecan in patients with metastatic PDAC. In this article, we will review the literature regarding existing treatment options for metastatic PDAC, focusing specifically on nanoliposomal irinotecan in the clinical setting and its future implication. PMID:27043737

  13. Chronic retinoic acid treatment suppresses adult hippocampal neurogenesis, in close correlation with depressive-like behavior.

    PubMed

    Hu, Pu; Wang, Yu; Liu, Ji; Meng, Fan-Tao; Qi, Xin-Rui; Chen, Lin; van Dam, Anne-Marie; Joëls, Marian; Lucassen, Paul J; Zhou, Jiang-Ning

    2016-07-01

    Clinical studies have highlighted an association between retinoid treatment and depressive symptoms. As we had shown before that chronic application of all-trans retinoic acid (RA) potently activated the hypothalamus-pituitary-adrenal (HPA) stress axis, we here questioned whether RA also induced changes in adult hippocampal neurogenesis, a form of structural plasticity sensitive to stress and implicated in aspects of depression and hippocampal function. RA was applied intracerebroventricularly (i.c.v.) to adult rats for 19 days after which animals were subjected to tests for depressive-like behavior (sucrose preference) and spatial learning and memory (water maze) performance. On day 27, adult hippocampal neurogenesis and astrogliosis was quantified using BrdU (newborn cell survival), PCNA (proliferation), doublecortin (DCX; neuronal differentiation), and GFAP (astrocytes) as markers. RA was found to increase retinoic acid receptor-α (RAR-α) protein expression in the hippocampus, suggesting an activation of RA-induced signaling mechanisms. RA further potently suppressed cell proliferation, newborn cell survival as well as neurogenesis, but not astrogliosis. These structural plasticity changes were significantly correlated with scores for anhedonia, a core symptom of depression, but not with water maze performance. Our results suggest that RA-induced impairments in hippocampal neurogenesis correlate with depression-like symptoms but not with spatial learning and memory in this design. Thus, manipulations aimed to enhance neurogenesis may help ameliorate emotional aspects of RA-associated mood disorders. © 2016 Wiley Periodicals, Inc. PMID:26860546

  14. Retinoic acid metabolism blocking agents (RAMBAs) for treatment of cancer and dermatological diseases.

    PubMed

    Njar, Vincent C O; Gediya, Lalji; Purushottamachar, Puranik; Chopra, Pankaj; Vasaitis, Tadas Sean; Khandelwal, Aakanksha; Mehta, Jhalak; Huynh, Carlic; Belosay, Aashvini; Patel, Jyoti

    2006-07-01

    The naturally occurring retinoids and their synthetic analogs play a key role in differentiation, proliferation, and apoptosis, and their use/potential in oncology, dermatology and a variety of diseases are well documented. This review focuses on the role of all-trans-retinoic acid (ATRA), the principal endogenous metabolite of vitamin A (retinol) and its metabolism in oncology and dermatology. ATRA has been used successfully in differentiated therapy of acute promyelocytic leukemia, skin cancer, Kaposi's sarcoma, and cutaneous T-cell lymphoma, and also in the treatment of acne and psoriasis. However, its usefulness is limited by the rapid emergence of acquired ATRA resistance involving multifactoral mechanisms. A key mechanism of resistance involves ATRA-induced catabolism of ATRA. Thus, a novel strategy to overcome the limitation associated with exogenous ATRA therapy has been to modulate and/or increase the levels of endogenous ATRA by inhibiting the cytochrome P450-dependent ATRA-4-hydroxylase enzymes (particularly CYP26s) responsible for ATRA metabolism. These inhibitors are also referred to as retinoic acid metabolism blocking agents (RAMBAs). This review highlights development in the design, synthesis, and evaluation of RAMBAs. Major emphasis is given to liarozole, the most studied and only RAMBA in clinical use and also the new RAMBAs in development and with clinical potential. PMID:16530416

  15. Preparation of metal-resistant immobilized sulfate reducing bacteria beads for acid mine drainage treatment.

    PubMed

    Zhang, Mingliang; Wang, Haixia; Han, Xuemei

    2016-07-01

    Novel immobilized sulfate-reducing bacteria (SRB) beads were prepared for the treatment of synthetic acid mine drainage (AMD) containing high concentrations of Fe, Cu, Cd and Zn using up-flow anaerobic packed-bed bioreactor. The tolerance of immobilized SRB beads to heavy metals was significantly enhanced compared with that of suspended SRB. High removal efficiencies of sulfate (61-88%) and heavy metals (>99.9%) as well as slightly alkaline effluent pH (7.3-7.8) were achieved when the bioreactor was fed with acidic influent (pH 2.7) containing high concentrations of multiple metals (Fe 469 mg/L, Cu 88 mg/L, Cd 92 mg/L and Zn 128 mg/L), which showed that the bioreactor filled with immobilized SRB beads had tolerance to AMD containing high concentrations of heavy metals. Partially decomposed maize straw was a carbon source and stabilizing agent in the initial phase of bioreactor operation but later had to be supplemented by a soluble carbon source such as sodium lactate. The microbial community in the bioreactor was characterized by denaturing gradient gel electrophoresis (DGGE) and sequencing of partial 16S rDNA genes. Synergistic interaction between SRB (Desulfovibrio desulfuricans) and co-existing fermentative bacteria could be the key factor for the utilization of complex organic substrate (maize straw) as carbon and nutrients source for sulfate reduction. PMID:27058913

  16. Role of Docosahexaenoic Acid Treatment in Improving Liver Histology in Pediatric Nonalcoholic Fatty Liver Disease

    PubMed Central

    Alisi, Anna; De Vito, Rita; Franchitto, Antonio; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio

    2014-01-01

    Introduction Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of liver-related morbidity and mortality in children. Recently, we have reported the effects of docosahexaenoic acid (DHA), the major dietary long-chain polyunsaturated fatty acids, in children with NAFLD. DHA exerts a potent anti-inflammatory activity through the G protein-coupled receptor (GPR)120. Our aim was to investigate in pediatric NAFLD the mechanisms underlying the effects of DHA administration on histo-pathological aspects, GPR120 expression, hepatic progenitor cell activation and macrophage pool. Patients and Methods 20 children with untreated NAFLD were included. Children were treated with DHA for 18 months. Liver biopsies before and after the treatment were analyzed. Hepatic progenitor cell activation, macrophage pool and GPR120 expression were evaluated and correlated with clinical and histo-pathological parameters. Results GPR120 was expressed by hepatocytes, liver macrophages, and hepatic progenitor cells. After DHA treatment, the following modifications were present: i) the improvement of histo-pathological parameters such as NAFLD activity score, ballooning, and steatosis; ii) the reduction of hepatic progenitor cell activation in correlation with histo-pathological parameters; iii) the reduction of the number of inflammatory macrophages; iv) the increase of GPR120 expression in hepatocytes; v) the reduction of serine-311-phosphorylated nuclear factor kappa B (NF-κB) nuclear translocation in hepatocytes and macrophages in correlation with serum inflammatory cytokines. Conclusions DHA could modulate hepatic progenitor cell activation, hepatocyte survival and macrophage polarization through the interaction with GPR120 and NF-κB repression. In this scenario, the modulation of GPR120 exploits a novel crucial role in the regulation of the cell-to-cell cross-talk that drives inflammatory response, hepatic progenitor cell activation and hepatocyte survival. PMID

  17. DEVELOPMENT AND VALIDATION OF AN ACID MINE DRAINAGE TREATMENT PROCESS FOR SOURCE WATER

    SciTech Connect

    Lane, Ann

    2015-12-31

    Throughout Northern Appalachia and surrounding regions, hundreds of abandoned mine sites exist which frequently are the source of Acid Mine Drainage (AMD). AMD typically contains metal ions in solution with sulfate ions which have been leached from the mine. These large volumes of water, if treated to a minimum standard, may be of use in Hydraulic Fracturing (HF) or other industrial processes. This project’s focus is to evaluate an AMD water treatment technology for the purpose of providing treated AMD as an alternative source of water for HF operations. The HydroFlex™ technology allows the conversion of a previous environmental liability into an asset while reducing stress on potable water sources. The technology achieves greater than 95% water recovery, while removing sulfate to concentrations below 100 mg/L and common metals (e.g., iron and aluminum) below 1 mg/L. The project is intended to demonstrate the capability of the process to provide AMD as alternative source water for HF operations. The second budget period of the project has been completed during which Battelle conducted two individual test campaigns in the field. The first test campaign demonstrated the ability of the HydroFlex system to remove sulfate to levels below 100 mg/L, meeting the requirements indicated by industry stakeholders for use of the treated AMD as source water. The second test campaign consisted of a series of focused confirmatory tests aimed at gathering additional data to refine the economic projections for the process. Throughout the project, regular communications were held with a group of project stakeholders to ensure alignment of the project objectives with industry requirements. Finally, the process byproduct generated by the HydroFlex process was evaluated for the treatment of produced water against commercial treatment chemicals. It was found that the process byproduct achieved similar results for produced water treatment as the chemicals currently in use. Further

  18. Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis.

    PubMed

    Rosenstein, Elliot D; Kushner, Laura J; Kramer, Neil; Kazandjian, Gregory

    2003-03-01

    The anti-inflammatory effects of both n-3 and n-6 polyunsaturated fatty acids (PUFA) have been demonstrated in vitro and in many disease states, in particular in the treatment of rheumatoid arthritis. The benefit of n-3 PUFA supplementation has been documented in animal models of periodontal inflammation and a trend towards reduced inflammation has been seen in human experimental gingivitis. The purpose of this study was to examine the potential anti-inflammatory effects of PUFA supplementation, by administration of fish oil as a source of the n-3 PUFA, eicosapentaenoic acid, and borage oil as a source of the n-6 PUFA, gamma-linolenic acid (GLA), to adults with periodontitis. Thirty adult human subjects with periodontitis were administered either fish oil 3000 mg daily; borage oil 3000 mg daily; fish oil 1500 and borage oil 1500 mg daily, or placebo. The modified gingival index, the plaque index (PI), periodontal probing depths and beta-glucuronidase levels in gingival crevicular fluid were measured at baseline and after 12 weeks of treatment. Improvement in gingival inflammation was observed in subjects treated with borage oil (P<0.016), with a trend apparent in subjects treated with fish oil or a combination of PUFA. There was no statistically significant improvement in PI, although a trend was apparent in those receiving borage oil. Improvement in probing depth was seen in those subjects treated with either fish oil alone or borage oil alone, but statistical significance was only seen for the comparison of borage oil and placebo (P<0.044). No change was seen in gingival crevicular fluid (GCF) beta-glucuronidase levels. The use of borage oil supplementation, a source of the n-6 PUFA, GLA, can have beneficial effects on periodontal inflammation. n-6 PUFA supplementation seemed to offer more impressive results than either n-3 PUFA supplementation or the combination of lower doses of the two supplements. Additional studies will be necessary to more fully assess the

  19. Fluorine distribution during thermal treatment of sulfuric acid leaching products of complex beryllium raw materials at JSC UMP

    NASA Astrophysics Data System (ADS)

    Borsuk, A. N.; Zherin, I. I.; Amelina, G. N.; Pivovarov, I.

    2016-06-01

    X-ray diffraction, infrared spectroscopy, thermogravimetry and mass spectrometry were employed to study the behavior and distribution of fluorine in sulfuric acid treatment of the melt of beryl-bertrandite-phenakite-fluorite concentrates with alkali fluxes. It was established that fluorine in a solid phase is predominantly present in the form of sodium and calcium fluorosilicates and in a gaseous phase it is evolved in the form of silicon tetrafluoride and fluorosulfonic acid.

  20. Bile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders.

    PubMed

    Fiorucci, Stefano; Distrutti, Eleonora

    2015-11-01

    The composition of the bile acid pool is a function of the microbial metabolism of bile acids in the intestine. Perturbations of the microbiota shape the bile acid pool and modulate the activity of bile acid-activated receptors (BARs) even beyond the gastrointestinal tract, triggering various metabolic axes and altering host metabolism. Bile acids, in turn, can also regulate the composition of the gut microbiome at the highest taxonomic levels. Primary bile acids from the host are preferential ligands for the farnesoid X receptor (FXR), while secondary bile acids from the microbiota are ligands for G-protein-coupled bile acid receptor 1 (GPBAR1). In this review, we examine the role of bile acid signaling in the regulation of intestinal microbiota and how changes in bile acid composition affect human metabolism. Bile acids may offer novel therapeutic modalities in inflammation, obesity, and diabetes. PMID:26481828

  1. Facile, room-temperature pre-treatment of rice husks with tetrabutylphosphonium hydroxide: Enhanced enzymatic and acid hydrolysis yields.

    PubMed

    Lau, B B Y; Luis, E T; Hossain, M M; Hart, W E S; Cencia-Lay, B; Black, J J; To, T Q; Aldous, L

    2015-12-01

    Aqueous solutions of tetrabutylphosphonium hydroxide have been evaluated as pretreatment media for rice husks, prior to sulphuric acid hydrolysis or cellulase enzymatic hydrolysis. Varying the water:tetrabutylphosphonium hydroxide ratio varied the rate of delignification, as well as silica, lignin and cellulose solubility. Pre-treatment with 60wt% hydroxide dissolved the rice husk and the regenerated material was thus heavily disrupted. Sulphuric acid hydrolysis of 60wt%-treated samples yielded the highest amount of glucose per gram of rice husk. Solutions with good lignin and silica solubility but only moderate to negligible cellulose solubility (10-40wt% hydroxide) were equally effective as pre-treatment media for both acid and enzymatic hydrolysis. However, pre-treatment with 60wt% hydroxide solutions was incompatible with downstream enzymatic hydrolysis. This was due to significant incorporation of phosphonium species in the regenerated biomass, which significantly inhibited the activity of the cellulase enzymes. PMID:26342336

  2. [Measurement of bile acid N-acetylglucosaminides in serum and urine of patients with chronic liver diseases during ursodeoxycholic acid treatment].

    PubMed

    Kimura, A; Nakamura, K; Makino, I

    1995-03-01

    Bile acid N-acetylglucosaminide (GlcNAc) was investigated in serum and urine of patients with chronic liver diseases during ursodeoxycholic acid (UDCA) treatment by HPLC. Bile acid N-acetylglucosaminide was not detected other than primary biliary cirrhosis in serum and urine. All of these N-acetyglucosaminide was ursodeoxycholic acid N-acetylglucosaminide (GlcNAc-UDCA). GlcNAc-UDCA excretion was 17.3 +/- 5.7 mg/day in PBC stage I, 12.1 +/- 5.4 mg/day in stage II, 39.1 +/- 20.8 mg/day in stage III. Among the GlcNAc fraction GlcNAc-UDCA-gly occupied greatest part followed by GlcNAc-UDCA-tau and non-amidated Glc-NAc-UDCA. GlcNAc-UDCA was 50.1% of total urinary bile acids excretion in PBC stage I, 32.5% in stage II, 20.5% in stage III. However, GlcNAc-UDCA was less than 2.5% of total serum bile acids in every stage. These results indicate that N-acetylglucosamine conjugation is one of the major pathway of UDCA in patient with primary biliary cirrhosis. PMID:7731091

  3. Application of acid-activated Bauxsol for wastewater treatment with high phosphate concentration: Characterization, adsorption optimization, and desorption behaviors.

    PubMed

    Ye, Jie; Cong, Xiangna; Zhang, Panyue; Zeng, Guangming; Hoffmann, Erhard; Liu, Yang; Wu, Yan; Zhang, Haibo; Fang, Wei; Hahn, Hermann H

    2016-02-01

    Acid-activated Bauxsol was applied to treat wastewater with high phosphate concentration in a batch adsorption system in this paper. The effect of acid activation on the change of Bauxsol structure was systematically investigated. The mineralogical inhomogeneity and intensity of Bauxsol decreased after acid activation, and FeCl3·2H2O and Al(OH)3 became the dominant phases of acid-activated Bauxsol adsorption. Moreover, the BET surface area and total pore volume of Bauxsol increased after acid activation. Interaction of initial solution pH and adsorption temperature on phosphate adsorption onto acid-activated Bauxsol was investigated by using response surface methodology with central composite design. The maximum phosphate adsorption capacity of 192.94 mg g(-1) was achieved with an initial solution pH of 4.19 and an adsorption temperature of 52.18 °C, which increased by 7.61 times compared with that of Bauxsol (22.40 mg g(-1)), and was higher than other adsorbents. Furthermore, the desorption studies demonstrated that the acid-activated Bauxsol was successfully regenerated with 0.5 mol L(-1) HCl solution. The adsorption capacity and desorption efficiency of acid-activated Bauxsol maintained at 80.48% and 93.02% in the fifth adsorption-desorption cycle, respectively, suggesting that the acid-activated Bauxsol could be repeatedly used in wastewater treatment with high phosphate concentration. PMID:26606195

  4. Passive treatment of acid mine drainage in down-flow limestone systems

    SciTech Connect

    Watzlaf, G.R.

    1997-12-31

    Passive down-flow systems, consisting of compost and/or limestone layers, may be well suited for treatment of acidic mine drainage containing ferric iron and/or aluminum. Two columns were constructed and operated in the laboratory. The first column simulated a downward, vertical-flow anaerobic wetland, also referred to as successive alkalinity-producing systems (SAPS), and has received mine drainage for 97 weeks. The 0.16-m diameter column was vertically oriented and (from bottom to top) consisted of a 0.30-m thick layer of limestone, a 0.76-m thick layer of spent mushroom compost, and 0.91 m of free standing water. Water flowed vertically downward through the system. A second column, filled with only limestone, received water from the same source as the first column. This limestone column contained a 1.06-m thick layer of limestone and 0.91 m of free standing water and has received water for 55 weeks. Actual acid mine drainage (pH = 3.1, acidity = 200 mg/L (as CaCO{sub 3}), SO{sub 4}{sup 2-} = 600 mg/L, Total Fe = 10 mg/L, Mn = 14 mg/L, and Al = 18 mg/L) was collected every two weeks from a nearby abandoned deep mine and applied to these columns at a rate of 3.8 mL/min. For the compost/limestone column, effluent pH remained above 6.2 (6.2-7.9); however, pH at a depth of 0.38 m in the compost (halfway) dropped to < 4 after 28 weeks (net acidic). At the bottom of the compost pH remained > 4.5 for all 97 weeks. Alkalinity was generated by a combination of limestone dissolution and sulfate reduction. Over the 97 week period, the column generated an average of 330 mg/L of alkalinity, mostly due to limestone dissolution. Bacterial sulfate reduction displayed an ever decreasing trend, initially accounting for more than 200 mg/L of alkalinity and after 40 weeks only accounting for about 50 mg/L.

  5. Novel treatment of acute promyelocytic leukemia: As₂O₃, retinoic acid and retinoid pharmacology.

    PubMed

    Zhu, George; Mische, Sarah E; Seigneres, Beatrice

    2013-01-01

    Acute promyelocytic leukemia(APL), a specific characteristic of t(15;17) chromosome translocation, represents 5% to 15% of cases of acute nonlymphocytic leukemia. An alternative approach is to consider retinoic acid(all-trans RA, ATRA or 13-cis RA or 9-cis RA) plus chemotherapy or RA plus As₂O₃ regimens as now novel therapy. Molecular gene analyses are conclusive in vivo evidence that oncogenic PML/RARa plays a crucial role in APL leukemogenesis. As a novel approach to APL treatment, one possible the action of RA, A consense sequence (5'-TCAGGTCATGACCTGA-3') has been postulated for the thyroid hormone (TRE) and retinoic acid responsive element (RARE) containing half palindromes, which located in the promoter region of target genes. High dose (100-fold) of RA-RARE-PML/RARa complex in intracellular localization appears to relieve repressor from DNA binding, including corepressors N-CoR, SMRT and HDACs, release PML/RARa- mediated transcriptional repression, and release histone deacetylase activity from PMLRARa. The resulting PML/RARa oncoprotein proteolytic degradation through the autophagy-lysosome pathway and the ubiquitin SUMO-proteasome system (UPS), as well as caspase 3 (cleavage site Asp522 within a-helics region of PML component of the fusion protein) or neutrophil elastase, or lysosomal protease enzyme induction. PML protein relocalizes into the wild-type nuclear body (PML-NB) configuration or/and wild-type RARa upregulated. An effect to relieve the blockade (inhibition) of PML/RARA-mediated RA dependent promyelocytic differentiation, and retinoic acid in APL therapy (see Figure in the full text, George Zhu, 1991). Here, like v-erbA, PML/RARa is a (strong) transcriptional repressor of the RA receptor (RAR) complex, and PML/RARa fusion receptor gene act as conditional oncogenic receptor (translocated chimeric retinoic acid a signaling) or oncogenic PML/RARa may participate in leukemogenesis of APL through blocking RA-mediated promyelocytic differentiation

  6. Review article: alginate-raft formulations in the treatment of heartburn and acid reflux.

    PubMed

    Mandel, K G; Daggy, B P; Brodie, D A; Jacoby, H I

    2000-06-01

    Alginate-based raft-forming formulations have been marketed word-wide for over 30 years under various brand names, including Gaviscon. They are used for the symptomatic treatment of heartburn and oesophagitis, and appear to act by a unique mechanism which differs from that of traditional antacids. In the presence of gastric acid, alginates precipitate, forming a gel. Alginate-based raft-forming formulations usually contain sodium or potassium bicarbonate; in the presence of gastric acid, the bicarbonate is converted to carbon dioxide which becomes entrapped within the gel precipitate, converting it into a foam which floats on the surface of the gastric contents, much like a raft on water. Both in vitro and in vivo studies have demonstrated that alginate-based rafts can entrap carbon dioxide, as well as antacid components contained in some formulations, thus providing a relatively pH-neutral barrier. Several studies have demonstrated that the alginate raft can preferentially move into the oesophagus in place, or ahead, of acidic gastric contents during episodes of gastro-oesophageal reflux; some studies further suggest that the raft can act as a physical barrier to reduce reflux episodes. Although some alginate-based formulations also contain antacid components which can provide significant acid neutralization capacity, the efficacy of these formulations to reduce heartburn symptoms does not appear to be totally dependent on the neutralization of bulk gastric contents. The strength of the alginate raft is dependant on several factors, including the amount of carbon dioxide generated and entrapped in the raft, the molecular properties of the alginate, and the presence of aluminium or calcium in the antacid components of the formulation. Raft formation occurs rapidly, often within a few seconds of dosing; hence alginate-containing antacids are comparable to traditional antacids for speed of onset of relief. Since the raft can be retained in the stomach for several

  7. Treatment Options for GERD or Acid Reflux Disease: A Review of the Research for Adults

    MedlinePlus

    ... consider when choosing a treatment: The benefits and risks of each treatment. The cost of each treatment. Which treatment best fits your likes, dislikes, and values. What are the costs of treatment? The cost ...

  8. Process control, energy recovery and cost savings in acetic acid wastewater treatment.

    PubMed

    Vaiopoulou, E; Melidis, P; Aivasidis, A

    2011-02-28

    An anaerobic fixed bed loop (AFBL) reactor was applied for treatment of acetic acid (HAc) wastewater. Two pH process control concepts were investigated; auxostatic and chemostatic control. In the auxostatic pH control, feed pump is interrupted when pH falls below a certain pH value in the bioreactor, which results in reactor operation at maximum load. Chemostatic control assures alkaline conditions by setting a certain pH value in the influent, preventing initial reactor acidification. The AFBL reactor treated HAc wastewater at low hydraulic residence time (HRT) (10-12 h), performed at high space time loads (40-45 kg COD/m(3) d) and high space time yield (30-35 kg COD/m(3) d) to achieve high COD (Chemical Oxygen Demand) removal (80%). Material and cost savings were accomplished by utilizing the microbial potential for wastewater neutralization during anaerobic treatment along with application of favourable pH-auxostatic control. NaOH requirement for neutralization was reduced by 75% and HRT was increased up to 20 h. Energy was recovered by applying costless CO(2) contained in the biogas for neutralization of alkaline wastewater. Biogas was enriched in methane by 4 times. This actually brings in more energy profits, since biogas extra heating for CO(2) content during biogas combustion is minimized and usage of other acidifying agents is omitted. PMID:21168957

  9. Treatment of the aged hand with injectable poly-l-lactic acid.

    PubMed

    Rendon, Marta I; Cardona, Lina M; Pinzon-Plazas, Mariana

    2010-12-01

    We report the use of injectable poly-l-lactic acid (PLLA) for volume restoration in a 45-year-old white female who was concerned about the appearance of her hands. The patient expressed a desire for long-term restoration, and selected injectable PLLA because of its known 2-year duration of effect, although she was informed that injectable PLLA is not FDA-approved for use in the hands. After reconstitution with 8 ml of diluent plus lidocaine, 0.1-0.2-ml aliquots of injectable PLLA were injected into selected sites, up to 5 ml per hand. The patient underwent three identical treatments, followed by postinjection use of moisturizing cream and massage; improvement in appearance was noted by the patient between the second and third treatments. Correction was maintained for at least 18 months, with no adverse events. We have also briefly reviewed the literature on the use of injectable PLLA for volume restoration in the hand. PMID:21142738

  10. Retinoic acid treatment of fibroblasts causes a rapid decrease in ( sup 3 H)inositol uptake

    SciTech Connect

    Sinha, R.; Creek, K.E.; Silverman-Jones, C.; de Luca, L.M. )

    1989-04-01

    NIH 3T3 fibroblasts treated with all-trans-retinoic acid (RA) showed a dramatic decrease in the uptake of ({sup 3}H)inositol compared to solvent-treated controls. The onset of RA-induced inhibition of ({sup 3}H)inositol uptake was rapid with a 10-15% decrease occurring after 2-3 h of RA exposure and 60-70% reduction after 16 h of RA treatment. A progressive dose-dependent decrease in inositol uptake was found as the concentration of RA increased from 10{sup {minus}8} to 10{sup {minus}5} M and the effect was fully reversible within 48 h after RA removal. RA inhibition of inositol uptake was also observed in 3T3-Swiss and Balb/3T3 cells but not in two virally transformed 3T3 cell lines. Phlorizin, amiloride, and monensin inhibited inositol uptake by 66, 74, and 58%, respectively, and this inhibition was additive when the cells were treated with RA as well as these inhibitors. A decreased incorporation of ({sup 3}H)inositol into polyphosphoinositides was also observed in RA-treated cells but not to the same extent as for ({sup 3}H)inositol uptake. In conclusion, RA treatment of 3T3 fibroblasts decreases the uptake of ({sup 3}H)inositol by up to 70% within 8 to 10 h at near physiological concentrations in a reversible and specific manner.

  11. Wine wastes as carbon source for biological treatment of acid mine drainage.

    PubMed

    Costa, M C; Santos, E S; Barros, R J; Pires, C; Martins, M

    2009-05-01

    Possible use of wine wastes containing ethanol as carbon and energy source for sulphate-reducing bacteria (SRB) growth and activity in the treatment of acid mine drainage (AMD) is studied for the first time. The experiments were performed using anaerobic down-flow packed bed reactors in semi-continuous systems. The performance of two bioreactors fed with wine wastes or ethanol as carbon sources is compared in terms of sulphate reduction, metals removal and neutralization. The results show that efficient neutralization and high sulphate removal (>90%) were attained with the use of wine wastes as substrate allowing the production of effluents with concentrations below the required local legislation for irrigation waters. This is only possible provided that the AMD and wine wastes are contacted with calcite tailing, a waste material that neutralizes and provides buffer capacity to the medium. The removal of metals using wine wastes as carbon source was 61-91% for Fe and 97% for both Zn and Cu. The lower removal of iron, when wine waste is used instead of ethanol, may be due to the presence of iron-chelating compounds in the waste, which prevent the formation of iron sulphide, and partial unavailability of sulphide because of re-oxidation to elemental sulphur. However, that did not affect significantly the quality of the effluent for irrigation. This work demonstrates that wine wastes are a potential alternative to traditional SRB substrates. This finding has direct implication to sustainable operation of SRB bioreactors for AMD treatment. PMID:19201010

  12. Treatment of acid mine drainage with anaerobic solid-substrate reactors

    SciTech Connect

    Drury, W.J.

    1999-10-01

    Anaerobic solid-substrate reactors were used in a laboratory study of acid mine drainage treatment. Parallel systems were run continuously for 23 months, both containing a solid substrate of 2:1 (weight) cow manure and sawdust. One system had cheese whey added with the mine drainage to provide an additional electron donor source to simulate sulfate-reducing bacteria activity. Effluent pH from the reactor with whey addition was relatively constant at 6.5. Effluent pH from the reactor without whey addition dropped over time from 6.7 to approximately 5.5. Whey addition increased effluent alkalinity [550 to 700 mg/L as calcium carbonate (CaCO{sub 3}) versus 50 to 300 mg/L as CaCO{sub 3}] and sulfate removal (98 to 80% versus 60 to 40%). Sulfate removal rate with whey addition decreased over time from 250 to 120 mmol/m{sup 3}{center{underscore}dot}d, whereas it decreased from 250 to 40 mmol/m{sup 3}{center{underscore}dot}d without whey addition. Whey addition increased removal of dissolved iron, dissolved manganese, and dissolved zinc in the second part of the experiment. Copper and cadmium removals were greater than 99%, and arsenic removal was 84% without whey addition and 89% with whey addition. Effluent sulfide concentrations were approximately 1 order of magnitude greater with whey addition. A 63-day period of excessive loading permanently decreased treatment efficiency without whey addition.

  13. Withdrawal of valproic acid treatment during pregnancy and seizure outcome: Observations from EURAP.

    PubMed

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio; Craig, John; Lindhout, Dick; Perucca, Emilio; Sabers, Anne; Thomas, Sanjeev V; Vajda, Frank

    2016-08-01

    Based on data from the EURAP observational International registry of antiepileptic drugs (AEDs) and pregnancy, we assessed changes in seizure control and subsequent AED changes in women who underwent attempts to withdraw valproic acid (VPA) during the first trimester of pregnancy. Applying Bayesian statistics, we compared seizure control in pregnancies where VPA was withdrawn (withdrawal group, n = 93), switched to another AED (switch group, n = 38), or maintained (maintained-therapy group, n = 1,588) during the first trimester. The probability of primarily or secondarily generalized tonic-clonic seizures (GTCS) was lower in the maintained-therapy group compared with the other two groups, both in the first trimester and for the entire duration of pregnancy. GTCS were twice as common during pregnancy in the withdrawal (33%) and switch groups (29%) compared with the maintained-treatment group (16%). Limitations in the data and study design do not allow to establish a cause-effect relationship between treatment changes and seizure outcome, but these observations provide a signal that withdrawal of, or switch from, VPA during the first trimester could lead to loss of seizure control, and highlight the need for a specifically designed prospective observational study. PMID:27319360

  14. Delivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tuberculosis treatment.

    PubMed

    Silva, João P; Gonçalves, Carine; Costa, César; Sousa, Jeremy; Silva-Gomes, Rita; Castro, António G; Pedrosa, Jorge; Appelberg, Rui; Gama, F Miguel

    2016-08-10

    Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, recently joined HIV/AIDS on the top rank of deadliest infectious diseases. Low patient compliance due to the expensive, long-lasting and multi-drug standard therapies often results in treatment failure and emergence of multi-drug resistant strains. In this scope, antimicrobial peptides (AMPs) arise as promising candidates for TB treatment. Here we describe the ability of the exogenous AMP LLKKK18 to efficiently kill mycobacteria. The peptide's potential was boosted by loading into self-assembling Hyaluronic Acid (HA) nanogels. These provide increased stability, reduced cytotoxicity and degradability, while potentiating peptide targeting to main sites of infection. The nanogels were effectively internalized by macrophages and the peptide presence and co-localization with mycobacteria within host cells was confirmed. This resulted in a significant reduction of the mycobacterial load in macrophages infected in vitro with the opportunistic M. avium or the pathogenic M. tuberculosis, an effect accompanied by lowered pro-inflammatory cytokine levels (IL-6 and TNF-α). Remarkably, intra-tracheal administration of peptide-loaded nanogels significantly reduced infection levels in mice infected with M. avium or M. tuberculosis, after just 5 or 10 every other day administrations. Considering the reported low probability of resistance acquisition, these findings suggest a great potential of LLKKK18-loaded nanogels for TB therapeutics. PMID:27261333

  15. Heavy metal removal from sewage sludge ash by thermochemical treatment with gaseous hydrochloric acid.

    PubMed

    Vogel, Christian; Adam, Christian

    2011-09-01

    Sewage sludge ash (SSA) is a suitable raw material for fertilizers due to its high phosphorus (P) content. However, heavy metals must be removed before agricultural application and P should be transferred into a bioavailable form. The utilization of gaseous hydrochloric acid for thermochemical heavy metal removal from SSA at approximately 1000 °C was investigated and compared to the utilization of alkaline earth metal chlorides. The heavy metal removal efficiency increased as expected with higher gas concentration, longer retention time and higher temperature. Equivalent heavy metal removal efficiency were achieved with these different Cl-donors under comparable conditions (150 g Cl/kg SSA, 1000 °C). In contrast, the bioavailability of the P-bearing compounds present in the SSA after thermal treatment with gaseous HCl was not as good as the bioavailability of the P-bearing compounds formed by the utilization of magnesium chloride. This disadvantage was overcome by mixing MgCO(3) as an Mg-donor to the SSA before thermochemical treatment with the gaseous Cl-donor. A test series under systematic variation of the operational parameters showed that copper removal is more depending on the retention time than the removal of zinc. Zn-removal was declined by a decreasing ratio of the partial pressures of ZnCl(2) and water. PMID:21819089

  16. Influence of pH-control in phosphoric acid treatment of titanium oxide and their powder properties

    SciTech Connect

    Onoda, Hiroaki Matsukura, Aki

    2015-06-15

    Highlights: • The photocatalytic activity was suppressed by phosphoric acid treatment. • The obtained pigment had small particles with sub-micrometer size. • By phosphoric acid treatment, the smoothness of samples improved. - Abstract: Titanium oxide that has the photocatalytic activity is used as a white pigment for cosmetics. A certain degree of sebum on the skin is decomposed by the ultraviolet radiation in sunlight. In this work, titanium oxide was shaken with phosphoric acid at various pH to synthesize a novel white pigment for cosmetics. Their chemical composition, powder properties, photocatalytic activity, color phase, and smoothness were studied. The obtained materials indicated XRD peaks of titanium oxide, however, these peak intensity became weak by phosphoric acid treatment. These samples without heating and heated at 100 °C included the small particles with sub-micrometer size. The photocatalytic activity of the obtained powders became weak by phosphoric acid treatment at pH 4 and 5 to protect the sebum on the skin.

  17. The effects of acid treatment on the thermoelectric power of multiwalled carbon nanotubes synthesized by chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Hewitt, Corey A.; Carroll, David L.

    2013-08-01

    Acid treatment of carbon nanotubes is a post synthesis processing step used to clean carbon nanotubes. We show that exposure of the nanotubes to oxygen rich reagents including nitric and sulfuric acid results in an increase of the thermoelectric power. Improving dispersion through the use of the surfactant triton-x results in a further increase in TEP of up to 21%. Additionally, refluxing in an oxygen rich acidic solution results in improved dispersion and an increased TEP. These results indicate that improved dispersion of the nanotubes by either sonication or reflux leads to increased oxygenation and thermopower.

  18. Effect of seed treatment with organic acids on the control of common bunt (Tilletia tritici and T. laevis) in wheat.

    PubMed

    Saidi, B; Azmeh, F; Mamluk, O F; Sikora, R A

    2001-01-01

    Common bunt caused by Tilletia tritici and T. laevis is an important disease, causes considerable losses in wheat yield on a world wild. The disease reduces yields, complicates harvesting and lowers the quality of the grain. It occurs more frequently and causes greater damage on winter wheat than on spring wheat. Grain standards designate wheat that has an unmistakable odor of smut or that contains smut balls, portions of balls, or spores of smut in excess of a quantity equal to 14 balls of average size in 250 g of wheat as "light smutty". Samples containing an excess of 30 balls, or their equivalent, in 250 g of wheat are graded as "smutty". Grain in these grades brings lower prices. Using commercial acetic acid and lactic acid, the pathogen was successfully controlled, but the treatment negatively affected seed germination and seedling vitality. Using dilutions of acetic acid and lactic acid, significant control of the pathogen also was achieved with acetic acid without causing phytotoxicity. Dilutions of lactic acid also gave good control, but showed some phytotoxicity. Using 30-50 ml/kg of vinegar, which is a natural source of acetic acid, proved to be one of the most effective alternatives for control of common bunt on wheat. The treatment had no negative effects on seed germination nor on seedling vitality. PMID:12425040

  19. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    SciTech Connect

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun Chung, Won-Yoon

    2014-03-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  20. Docetaxel-loaded polyglutamic acid-PEG nanocapsules for the treatment of metastatic cancer.

    PubMed

    Borrajo, Erea; Abellan-Pose, Raquel; Soto, Atenea; Garcia-Fuentes, Marcos; Csaba, Noemi; Alonso, Maria J; Vidal, Anxo

    2016-09-28

    The design of nanomedicines with suitable physicochemical characteristics for the lymphatic targeting of drugs is critical in order to reach the lymph nodes, where metastatic cells often accumulate. Based on the known effect of particle size and surface hydrophilicity on the capacity of nanocarriers to reach the lymph nodes, here we report the formation and characterization of 100nm polyglutamic acid-polyethylene glycol (PGA-PEG) nanocapsules together with the assessment of their potential for the treatment of cancer with lymphatic metastatic spread. To this purpose, we first studied the biodistribution of fluorescently labeled PGA-PEG nanocapsules (100nm), following, either intravenous or subcutaneous administration. The results confirmed the accumulation of nanocapsules in the lymphatic system, especially upon subcutaneous administration. Next, we evaluated the efficacy and toxicity of the docetaxel-loaded nanocapsules in an orthotopic lung cancer model that metastasizes to the lymph nodes. As expected from the rational design, DCX-loaded PGA-PEG nanocapsules exhibited a greatly enhanced antitumoral efficacy and a reduced toxicity when compared with the commercial formulation Taxotere®. Furthermore, the administration of DCX-loaded PGA-PEG nanocapsules resulted in the practical elimination of the metastatic load in the mediastinal lymph nodes, whereas the treatment with the commercial formulation had a minor effect. Overall, these findings underscore the potential of PGA-PEG nanocapsules for the delivery of anticancer drugs to both, the tumor tissue and the metastatic lymph nodes. Therefore, they represent a promising therapy for the treatment of lung metastatic cancer. PMID:27476608

  1. A novel model of in vitro osteocytogenesis induced by retinoic acid treatment.

    PubMed

    Mattinzoli, D; Messa, P; Corbelli, A; Ikehata, M; Zennaro, C; Armelloni, S; Li, M; Giardino, L; Rastaldi, M P

    2012-01-01

    Despite recent research which more and more stresses the importance of osteocytes in regulating bone and systemic mineral metabolism, current molecular and functional knowledge of osteocyte properties are still incomplete, mostly due to limited availability of in vitro models. Osteocytes are terminally differentiated dendritic cells, and therefore are not easy to obtain and maintain in primary cultures. As an alternative, osteocyte differentiation can be induced by progressive osteoblast embedding in mineralised extracellular matrix. In this model, which is suitable for reproduction of bone development, the presence of calcified matrix prevents several cell biological methods from being used. Therefore, the osteocyte-like MLO-Y4 cell line continues to be the most widely used cellular system. Here we show that treatment of primary osteoblasts or MC3T3-E1 cells with retinoic acid generates a homogeneous population of ramified cells with osteocyte features, as confirmed by morphological and molecular analyses. The first morphological changes are detectable in primary cells after 2 days of treatment, and in the cell line after 4 days of treatment. Differentiation is complete in 5 and 10 days, respectively, with progressive development of dendrites, loss of the ability to produce extracellular matrix, down-regulation of osteoblast markers, and up-regulation of osteocyte-specific molecules, most notably among them sclerostin. Compared to other published protocols, our method has a number of advantages. It is easy to perform and does not require special instrumentation, it is highly reproducible, and rapidly generates a mature osteocyte population in the complete absence of extracellular matrix, allowing the use of these cells for unlimited biological applications. PMID:23160992

  2. Expression and subcellular localization of thymosin beta15 following kainic acid treatment in rat brain

    SciTech Connect

    Kim, Young Woong; Kim, Younghwa; Kim, Eun Hae; Koh, Doyle; Sun, Woong Kim, Hyun

    2008-07-11

    Thymosin {beta}15 (T{beta}15) is a pleiotropic factor which exerts multiple roles in the development of nervous system and brain diseases. In this study, we found that the expressions of T{beta}15 mRNA and protein were substantially increased in several brain regions including hippocampal formation and cerebral cortex, following kainic acid (KA)-evoked seizures in rat. Interestingly, a subset of cortex neurons exhibited nuclear T{beta}15 immunoreactivity upon KA treatment. Furthermore, translocation of T{beta}15 from cytosol to nuclei was observed in cultured neurons or HeLa cells during staurosporine (STS)-induced apoptosis, which was also verified by time-lapse imaging of YFP-tagged T{beta}15. It appeared that localization of T{beta}15 is restricted to the cytosol in normal condition by its G-actin-interacting domain, because site-directed mutagenesis of this region resulted in the nuclear localization of T{beta}15 in the absence of STS treatment. To explore the role of nuclear T{beta}15, we enforced T{beta}15 to localize in the nuclei by fusion of T{beta}15 with nuclear localization signal (NLS-T{beta}15). However, overexpression of NLS-T{beta}15 did not alter the viability of cells in response to STS treatment. Collectively, these results suggest that nuclear localization of T{beta}15 is a controlled process during KA or STS stimulation, although its functional significance is yet to be clarified.

  3. Seed treatment with beta-aminobutyric acid protects Pennisetum glaucum systemically from Sclerospora graminicola.

    PubMed

    Shailasree, S; Sarosh, B R; Vasanthi, N S; Shetty, H S

    2001-08-01

    beta-Aminobutyric acid (BABA) treatment of pearl millet [Pennisetum glaucum (L) R Br] seeds influenced seedling vigour and protected the seedlings from downy mildew disease caused by the oomycetous biotropic fungus Sclerospora graminicola (Sacc) Schroet. Of the different concentrations of BABA tested, viz 25, 50, 75 and 100 mM, seeds treated with 50 mM for 6 h resulted in the maximum of 1428 seedling vigour and showed 23% disease incidence in comparison with the control which recorded a seedling vigour of 1260 and 98% disease incidence i.e. 75% protection from disease. Seeds treated with BABA when challenged for downy mildew disease using zoospores of S graminicola required 48 h after inducer treatment to develop maximum resistance. Durability of induced resistance was also tested in plants raised from seeds treated with the inducer and identified as resistant, by second challenge inoculation with the downy mildew pathogen at tillers and inflorescence axes. Reduced disease incidence of only 10 and 12% in these plants, compared with 71 and 76% disease in control plants inoculated at the tillers and inflorescence axes, respectively, suggested that resistance induced in seeds with BABA remained operative through vegetative and reproductive growth of pearl millet plants. Induction of resistance by seed treatment with BABA enhanced vegetative growth, viz height, fresh weight, leaf area and tillering, and reproductive growth, viz early flowering, number of productive ear heads and 1000 seed weight. Studies on induction of resistance in different cultivars of pearl millet with varying resistance reaction to downy mildew indicated that the protection offered by BABA is independent of the nature of cultivars used and not dependent on their constitutive resistance. PMID:11517726

  4. Development of anti-scale poly(aspartic acid-citric acid) dual polymer systems for water treatment.

    PubMed

    Nayunigari, Mithil Kumar; Gupta, Sanjay Kumar; Kokkarachedu, Varaprasad; Kanny, K; Bux, F

    2014-01-01

    The formation of calcium sulphate and calcium carbonate scale poses major problems in heat exchangers and water cooling systems, thereby affecting the performance of these types of equipment. In order to inhibit these scale formations, new types of biodegradable water soluble single polymer and dual poly(aspartic acid-citric acid) polymers were developed and tested. The effectiveness of single polymer and four different compositions of poly aspartic acid and citric acid dual polymer systems as scale inhibitors were evaluated. Details of the synthesis, thermal stability, scale inhibition and the morphological characterization of single and dual polymers are presented in this scientific paper. It was found that the calcium sulphate scale inhibition rate was in the range 76.06-91.45%, while the calcium carbonate scale inhibition rate observed was in the range 23.37-30.0% at 65-70 °C. The finding suggests that the water soluble dual polymers are very effective in sulphate scale inhibition in comparison of calcium carbonate scale inhibition. PMID:25189837

  5. Serum Collagen Type II Cleavage Epitope and Serum Hyaluronic Acid as Biomarkers for Treatment Monitoring of Dogs with Hip Osteoarthritis

    PubMed Central

    Vilar, José M.; Rubio, Mónica; Spinella, Giuseppe; Cuervo, Belén; Sopena, Joaquín; Cugat, Ramón; Garcia-Balletbó, Montserrat; Dominguez, Juan M.; Granados, Maria; Tvarijonaviciute, Asta; Ceron, José J.; Carrillo, José M.

    2016-01-01

    The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs. PMID:26886592

  6. Reversible modification of structure and properties of cellulose nanofibril-based multilayered thin films induced by postassembly acid treatment.

    PubMed

    Azzam, Firas; Moreau, Céline; Cousin, Fabrice; Menelle, Alain; Bizot, Hervé; Cathala, Bernard

    2015-03-10

    A postassembly acid-treatment consisting of an immersion in 5 mM HCl solution was applied to carboxylated cellulose nanofibrils (CNF)-poly(allylamine) hydrochloride (PAH) multilayered thin films. Our results show that the treatment did not affect the overall thickness of the films without any loss of the components. However, a modification of the surface morphology was observed, as well as the swelling behavior. The process was perfectly reversible since the original structure was recovered when the thin films were rinsed by ultrapure water. Moreover, a more pronounced antireflective character was detected for the treated films. The origin of these reversible modifications was discussed. Notably, the scattering length density (SLD) profiles of the films before and after treatment support the idea of a structural reorganization of the components within the film driven by the change of their charge densities induced by the acid treatment. PMID:25706711

  7. Alkyl polyglucose enhancing propionic acid enriched short-chain fatty acids production during anaerobic treatment of waste activated sludge and mechanisms.

    PubMed

    Luo, Jingyang; Feng, Leiyu; Chen, Yinguang; Sun, Han; Shen, Qiuting; Li, Xiang; Chen, Hong

    2015-04-15

    Adding alkyl polyglucose (APG) into an anaerobic treatment system of waste activated sludge (WAS) was reported to remarkably improve the production of short-chain fatty acids (SCFAs), especially propionic acid via simultaneously accelerating solubilization and hydrolysis, enhancing acidification, inhibiting methanogenesis and balancing carbon to nitrogen (C/N) ratio of substrate. Not only the production of SCFAs, especially propionic acid, was significantly improved by APG, but also the feasible operation time was shortened. The SCFAs yield at 0.3 g APG per gram of total suspended solids (TSS) within 4 d was 2988 ± 60 mg chemical oxygen demand (COD) per liter, much higher than that those from sole WAS or sole WAS plus sole APG. The corresponding yield of propionic acid was 1312 ± 25 mg COD/L, 7.9-fold of sole WAS. Mechanism investigation showed that during anaerobic treatment of WAS in the presence of APG both the solubilization and hydrolysis were accelerated and the acidification was enhanced, while the methanogenesis was inhibited. Moreover, the activities of key enzymes involved in WAS hydrolysis and acidification were improved through the adjustment of C/N ratio of substrates with APG. The abundance of microorganisms responsible for organic compounds hydrolysis and SCFAs production was also observed to be greatly enhanced with APG via 454 high-throughput pyrosequencing analysis. PMID:25697695

  8. Minodronic acid ameliorates vertebral bone strength by increasing bone mineral density in 9-month treatment of ovariectomized cynomolgus monkeys.

    PubMed

    Tanaka, Makoto; Mori, Hiroshi; Kawabata, Kazuhito; Mashiba, Tasuku

    2016-07-01

    The effect of treatment for 9months with minodronic acid, a nitrogen-containing bisphosphonate, on vertebral mechanical strength was examined in ovariectomized (OVX) cynomolgus monkeys. Forty skeletally mature female monkeys were randomized into four OVX groups and one sham group (n=8) based on lumbar bone mineral density (BMD). OVX animals were treated orally with 15 and 150μg/kg QD of minodronic acid or 500μg/kg QD alendronate as a reference drug. Measurements of bone turnover markers and lumbar BMD were conducted at 0, 4 and 8months. Measurements of bone mechanical strength and minodronic acid concentration in vertebral bodies were also performed. OVX resulted in a decrease in lumbar BMD and an increase in bone turnover markers at 4 and 8months, compared to the sham group, and the ultimate load on the lumbar vertebra was decreased in OVX animals. Minodronic acid and alendronate prevented the OVX-induced increase in bone turnover markers and decrease in lumbar BMD. Minodronic acid at 150μg/kg increased the ultimate load on lumbar vertebra compared to untreated OVX animals. Regression analysis revealed that the ultimate load was correlated with lumbar BMD and bone mineral content (BMC), and most strongly with the increase in lumbar BMD and BMC over 8months. In a separate analysis within the sham-OVX controls and minodronic acid and alendronate treatment groups, the ultimate loads were also correlated with BMD and BMC. The load-BMD (BMC) correlation in the minodronic acid group showed a trend for a shift to a higher load from the basal relationship in the sham-OVX controls. These results indicate that treatment with minodronic acid for 9months increases vertebral mechanical strength in OVX monkeys, mainly by increasing BMD and BMC. PMID:27155564

  9. L-arginine conjugates of bile acids-a possible treatment for non-alcoholic fatty liver disease

    PubMed Central

    2014-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is a continuum of diseases that include simple steatosis and non-alcoholic steatohepatitis (NASH) ultimately leading to cirrhosis, hepatocellular carcinoma and end stage liver failure. Currently there is no approved treatment for NASH. It is known that bile acids not only have physiological roles in lipid digestion but also have strong hormonal properties. We have synthesized a novel chenodeoxycholyl-arginine ethyl ester conjugate (CDCArg) for the treatment of NAFLD. Methods Chemical synthesis of CDCArg was performed. Experiments for prevention and treatment of NAFLD were carried out on C57BL/6 J male mice that were treated with high fat diet (HFD, 60% calories from fat). CDCArg or cholic acid bile acids were admixture into the diets. Food consumption, weight gain, liver histology, intraperitoneal glucose tolerance test, biochemical analysis and blood parameters were assessed at the end of the experiment after 5 weeks of diet (prevention study) or after 14 weeks of diet (treatment study). In the treatment study CDCArg was admixture into the diet at weeks 10–14. Results In comparison to HFD treated mice, mice treated with HFD supplemented with CDCArg, showed reduced liver steatosis, reduced body weight and decreased testicular fat and liver tissue mass. Blood glucose, cholesterol, insulin and leptin levels were also lower in this group. No evidence of toxicity of CDCArg was recorded. In fact, liver injury, as evaluated using plasma hepatic enzyme levels, was low in mice treated with HFD and CDCArg when compared to mice treated with HFD and cholic acid. Conclusion CDCArg supplementation protected the liver against HFD-induced NAFLD without any toxic effects. These results indicate that basic amino acids e.g., L-arginine and bile acids conjugates may be a potential therapy for NAFLD. PMID:24750587

  10. Lipoic acid as a novel treatment for Alzheimer's disease and related dementias.

    PubMed

    Holmquist, Lina; Stuchbury, Grant; Berbaum, Katrin; Muscat, Sonja; Young, Simon; Hager, Klaus; Engel, Jürgen; Münch, Gerald

    2007-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that destroys patient memory and cognition, communication ability with the social environment and the ability to carry out daily activities. Despite extensive research into the pathogenesis of AD, a neuroprotective treatment - particularly for the early stages of disease - remains unavailable for clinical use. In this review, we advance the suggestion that lipoic acid (LA) may fulfil this therapeutic need. A naturally occurring precursor of an essential cofactor for mitochondrial enzymes, including pyruvate dehydrogenase (PDH) and alpha-ketoglutarate dehydrogenase (KGDH), LA has been shown to have a variety of properties which can interfere with pathogenic principles of AD. For example, LA increases acetylcholine (ACh) production by activation of choline acetyltransferase and increases glucose uptake, thus supplying more acetyl-CoA for the production of ACh. LA chelates redox-active transition metals, thus inhibiting the formation of hydroxyl radicals and also scavenges reactive oxygen species (ROS), thereby increasing the levels of reduced glutathione. Via the same mechanisms, downregulation redox-sensitive inflammatory processes is also achieved. Furthermore, LA can scavenge lipid peroxidation products such as hydroxynonenal and acrolein. The reduced form of LA, dihydrolipoic acid (DHLA), is the active compound responsible for most of these beneficial effects. R-alpha-LA can be applied instead of DHLA, as it is reduced by mitochondrial lipoamide dehydrogenase, a part of the PDH complex. In this review, the properties of LA are explored with particular emphasis on how this agent, particularly the R-alpha-enantiomer, may be effective to treat AD and related dementias. PMID:16989905

  11. Trace metal mobilization from oil sands froth treatment thickened tailings exhibiting acid rock drainage.

    PubMed

    Kuznetsova, Alsu; Kuznetsov, Petr; Foght, Julia M; Siddique, Tariq

    2016-11-15

    Froth treatment thickened tailings (TT) are a waste product of bitumen extraction from surface-mined oil sands ores. When incubated in a laboratory under simulated moist oxic environmental conditions for ~450d, two different types of TT (TT1 and TT2) exhibited the potential to generate acid rock drainage (ARD) by producing acid leachate after 250 and 50d, respectively. We report here the release of toxic metals from TT via ARD, which could pose an environmental threat if oil sands TT deposits are not properly managed. Trace metal concentrations in leachate samples collected periodically revealed that Mn and Sr were released immediately even before the onset of ARD. Spikes in Co and Ni concentrations were observed both pre-ARD and during active ARD, particularly in TT1. For most elements measured (Fe, Cr, V, As, Cu, Pb, Zn, Cd, and Se), leaching was associated with ARD production. Though equivalent acidification (pH2) was achieved in leachate from both TT types, greater metal release was observed from TT2 where concentrations reached 10,000ppb for Ni, 5000ppb for Co, 3000ppb for As, 2000ppb for V, and 1000ppb for Cr. Generally, metal concentrations decreased in leachate with time during ARD and became negligible by the end of incubation (~450d) despite appreciable metals remaining in the leached TT. These results suggest that using TT for land reclamation purposes or surface deposition for volume reduction may unfavorably impact the environment, and warrants application of appropriate strategies for management of pyrite-enriched oil sands tailings streams. PMID:27443453

  12. Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment

    PubMed Central

    2013-01-01

    Background New alternatives for the treatment of Tuberculosis (TB) are urgently needed and medicinal plants represent a potential option. Chamaedora tepejilote and Lantana hispida are medicinal plants from Mexico and their hexanic extracts have shown antimycobacterial activity. Bioguided investigation of these extracts showed that the active compounds were ursolic acid (UA) and oleanolic acid (OA). Methods The activity of UA and OA against Mycobacterium tuberculosis H37Rv, four monoresistant strains, and two drug-resistant clinical isolates were determined by MABA test. The intracellular activity of UA and OA against M. tuberculosis H37Rv and a MDR clinical isolate were evaluated in a macrophage cell line. Finally, the antitubercular activity of UA and OA was tested in BALB/c mice infected with M. tuberculosis H37Rv or a MDR strain, by determining pulmonary bacilli loads, tissue damage by automated histomorphometry, and expression of IFN-γ, TNF-α, and iNOS by quantitative RT-PCR. Results The in vitro assay showed that the UA/OA mixture has synergistic activity. The intracellular activity of these compounds against M. tuberculosis H37Rv and a MDR clinical isolate in a macrophage cell line showed that both compounds, alone and in combination, were active against intracellular mycobacteria even at low doses. Moreover, when both compounds were used to treat BALB/c mice with TB induced by H37Rv or MDR bacilli, a significant reduction of bacterial loads and pneumonia were observed compared to the control. Interestingly, animals treated with UA and OA showed a higher expression of IFN-γ and TNF-α in their lungs, than control animals. Conclusion UA and OA showed antimicrobial activity plus an immune-stimulatory effect that permitted the control of experimental pulmonary TB. PMID:24098949

  13. Passive treatment of acid mine drainage in systems containing compost and limestone: Laboratory and field results

    SciTech Connect

    Watzlaf, G.R.; Pappas, D.M.

    1996-12-31

    Passive, down-flow systems, consisting of compost and limestone layers, termed successive alkalinity producing systems (SAPS), may be well suited for treatment of mine drainage containing ferric iron and/or aluminum. A column, simulating a SAPS, has been operated in the laboratory for 52 weeks. The 0.16-m diameter column consisted of a 0.30-m thick layer of limestone, a 0.76-m thick layer of spent mushroom compost thick layer of limestone, a 0.76-m thick layer of spent mushroom compost and 0.91 m of free standing water. Actual AMD (pH = 3.02, acidity = 218 mg/L (as CaCO{sub 3}), SO{sub 4} = 600 mg/L, Fe = 16.0 mg/L, Mn = 12.1 mg/L, and Al = 17.1 mg/L) was applied to the column at a rate of 3.8 mL/min. Effluent pH has remained above 6.2 (6.2-7.9) in the column system. A SAPS located in Jefferson County, PA has been monitored for the past 4.5 years. The SAPS has an approximate area of 1000 m{sup 2} and contains a 0.4-m thick layer of limestone, a 0.2-m thick layer of spent mushroom compost, and 1.5 m of free standing water. Mine water (acidity = 335 mg/L (as CaCO{sub 3}), SO{sub 4} = 1270 mg/L, Fe = 246 mg/L, Mn = 38.4 mg/L, and Al = <0.2 mg/L) flowed into the SAPS at a rate of 140 L/min. Water samples from the field and laboratory systems have been collected at strategic locations on a regular basis and analyzed for pH, alkalinity, acidity, Fe{sup 2+}, total Fe, Mn, Al, SO{sub 4}, Ca, Mg, Na, Co, Ni, and Zn. Alkalinity has been generated in both field and laboratory systems by a combination of limestone dissolution and sulfate reduction. The column generated an average of 378 mg/L of alkalinity; 74% due to limestone dissolution and 26% due to bacterial reduction of sulfate. The field SAPS generated an average of 231 mg/L of alkalinity and exhibited seasonal trends.

  14. Total volatile fatty acid concentrations are unreliable estimators of treatment effects on ruminal fermentation in vivo.

    PubMed

    Hall, M B; Nennich, T D; Doane, P H; Brink, G E

    2015-06-01

    Volatile fatty acid concentrations ([VFA], mM) have long been used to assess the effect of dietary treatments on ruminal fermentation in vivo. However, discrepancies in statistical results between [VFA] and VFA pool size (VFAmol) possibly related to ruminal digesta liquid amount (LIQ, kg) indicate potential issues with the use of [VFA]. We investigated relationships among [VFA], VFAmol, and LIQ measured 2 h postfeeding using individual lactating cow data (n=175) from 7 separate feeding studies. Regression analyses were performed using mixed models with "study" as a discrete random variable. The mean across studies and average range of values within studies, respectively, were 151 and 75 for [VFA], 11.2 and 9.8 for VFAmol, 73.3 and 41.0 for LIQ, and 289 and 83 mmol/kg for rumen fluid osmolality. Liquid amount changed with VFAmol (3.76 VFAmol+31.2; average within-study R2=0.69), but the relationship was weak between [VFA] and LIQ (0.524 LIQ+112.8; average within-study R2=0.12). The relationship between LIQ and VFAmol was likely a function of the osmotic gradient between rumen liquid and blood. The VFA are a major ruminal solute; VFAmol amounts can affect water flux in the rumen as similar tonicities of rumen fluid and blood are maintained. This also has a damping effect on ruminal solute concentration, creating the weak relationship between [VFA] and LIQ. Within studies, similar [VFA] were found in LIQ differing by 30 kg or more. The difference between minimum and maximum LIQ within cow within study was 12.7 kg (standard deviation=7.1), so inclusion of "cow" in analyses did not correct for the variation in LIQ. To allow valid comparisons of experimental treatments, responses must be on an equivalent basis; concentrations in different LIQ are not on an equivalent basis and so are not valid to use for comparing treatment effects. The [VFA] changed with VFAmol (5.80 VFAmol+86.3; average within-study R2=0.56). However, the ratio of [VFA] to VFAmol ranged from 9.0 to 24

  15. Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease

    PubMed Central

    Di Minno, Matteo Nicola Dario; Russolillo, Anna; Lupoli, Roberta; Ambrosino, Pasquale; Di Minno, Alessandro; Tarantino, Giovanni

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major independent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as a potential treatment of NAFLD have been described. n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors (hypertension, hyperlipidemia, endothelial dysfunction and atherosclerosis) by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor (PPAR) α, PPARγ, sterol regulatory element-binding protein-1, carbohydrate responsive element-binding protein], impacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules (tumor necrosis factor-α and interleukin-6) and of oxygen reactive species. Further strengthening the results of the in vitro studies, both animal models and human intervention trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory parameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well-designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources (fish oil, flaxseeds, olive

  16. Expression of Adipose MicroRNAs Is Sensitive to Dietary Conjugated Linoleic Acid Treatment in Mice

    PubMed Central

    Parra, Pilar; Serra, Francisca; Palou, Andreu

    2010-01-01

    Background Investigation of microRNAs (miRNAs) in obesity, their genetic targets and influence by dietary modulators is of great interest because it may potentially identify novel pathways involved in this complex metabolic disorder and influence future therapeutic approaches. This study aimed to determine whether miRNAs expression may be influenced by conjugated linoleic acid (CLA), currently used to induce fat loss. Methodology/Principal Findings We determined retroperitoneal adipose tissue (rWAT) expression of five miRNAs related to adipocyte differentiation (miRNA-143) and lipid metabolism (miRNA-103 and -107) and altered in obesity (miRNA-221 and -222), using the TaqMan®MicroRNA Assay (Applied-Biosystems). In the first experiment, mice were fed with a standard fat diet and orally treated with sunflower oil (control group) and 3 or 10 mg CLA/day for 37 days. In the second experiment, mice were fed with a high fat diet for 65 days. For the first 30 days, mice received the same doses of CLA described above and, from that time onwards, animals received a double dose. Results showed that expression of selected miRNAs was modified in response to CLA treatment and metabolic status. Interestingly, a strong correlation was observed between miR-103 and -107 expression, as well as miR-221 and -222 in both experiments. Moreover, changes in miRNAs expression correlated with several adipocyte gene expressions: miR-103 and -107 correlated with genes involved in fatty acid