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Sample records for 5-aminolevulinic acid 5-ala

  1. 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.

  2. 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

  3. Mechanism for enhanced 5-aminolevulinic acid fluorescence in isocitrate dehydrogenase 1 mutant malignant gliomas

    PubMed Central

    Kim, Ji Young; Kim, Sung Kwon; Kim, Seung-Ki; Park, Sung-Hye; Kim, Hyeonjin; Lee, Se-Hoon; Choi, Seung Hong; Park, Sunghyouk; Park, Chul-Kee

    2015-01-01

    Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has become the main treatment modality in malignant gliomas. However unlike glioblastomas, there are inconsistent result about fluorescence status in WHO grade III gliomas. Here, we show that mutational status of IDH1 is linked to 5-ALA fluorescence. Using genetically engineered malignant glioma cells harboring wild type (U87MG-IDH1WT) or mutant (U87MG-IDH1R132H) IDH1, we demonstrated a lag in 5-ALA metabolism and accumulation of protoporphyrin IX (PpIX) in U87MG-IDH1R132H cells. Next, we used liquid chromatography–mass spectrometry (LC-MS) to screen for tricarboxylic acid (TCA) cycle-related metabolite changes caused by 5-ALA exposure. We observed low baseline levels of NADPH, an essential cofactor for the rate-limiting step of heme degradation, in U87MG-IDH1R132H cells. High levels of NADPH are required to metabolize excessive 5-ALA, giving a plausible reason for the temporarily enhanced 5-ALA fluorescence in mutant IDH1 cells. This hypothesis was supported by the results of metabolic screening in human malignant glioma samples. In conclusion, we have discovered a relationship between enhanced 5-ALA fluorescence and IDH1 mutations in WHO grade III gliomas. Low levels of NADPH in tumors with mutated IDH1 is responsible for the enhanced fluorescence. PMID:26008980

  4. Clinical utility of 5-aminolevulinic acid HCl to better visualize and more completely remove gliomas

    PubMed Central

    Halani, Sameer H; Adamson, D Cory

    2016-01-01

    Surgical resection is typically the first line of treatment for gliomas. However, the neurosurgeon faces a major challenge in achieving maximal resection in high-grade gliomas as these infiltrative tumors make it difficult to discern tumor margins from normal brain with conventional white-light microscopy alone. To aid in resection of these infiltrative tumors, fluorescence-guided surgery has gained much popularity in intraoperative visualization of malignant gliomas, with 5-aminolevulinic acid (5-ALA) leading the way. First introduced in an article in Neurosurgery, 5-ALA has since become a safe, effective, and inexpensive method to visualize and improve resection of gliomas. This has undoubtedly led to improvements in the clinical course of patients as demonstrated by the increased overall and progression-free survival in patients with such devastating disease. This literature review aims to discuss the major studies and trials demonstrating the clinical utility of 5-ALA and its ability to aid in complete resection of malignant gliomas.

  5. Effects of 5-aminolevulinic acid on a murine model of diet-induced obesity

    PubMed Central

    Koganei, Megumi; Saitou, Yuri; Tsuchiya, Kyoko; Abe, Fuminori; Tanaka, Toru; Horinouchi, Izumi; Izumi, Yoshiya; Yamaji, Taketo; Takahashi, Takeshi

    2015-01-01

    The effects of 5-aminolevulinic acid (5-ALA) on obesity were investigated using a murine model (diet-induced obese mice). Diet-induced obese mice were divided into 4 groups: a control group (C group), which was fed a high-fat diet; a low-5-ALA dose (10 mg/kg/day) group (10A group); a moderate-5-ALA dose (30 mg/kg/day) group (30A group); and a high-5-ALA dose (100 mg/kg/day) group (100A group). 5-ALA was administered by mixing the high fat diet for 8 weeks. Body weight increases in the 30A and 100A groups were significantly smaller compared with those of the C group. Body fat measurements by X-ray computed tomography indicated that the 100A group showed a tendency toward low visceral fat quantities during the final week of the study. Visceral fat weights in the 30A and 100A groups were slightly low. The levels of serum alanine aminotransferase (ALT) and total cholesterol (TC) in the 10A group was slightly low, whereas the 30A and 100A groups showed significantly lower ALT and TC values. Liver lipid concentration showed a dose-dependent decrease with ALA. Thus, in this diet-induced obese murine model, administration of 5-ALA had a significantly beneficial impact on the visceral fat, serum ALT and TC, and liver lipid concentration. PMID:26388673

  6. Risk factors for developing oral 5-aminolevulinic acid-induced side effects in patients undergoing fluorescence guided resection.

    PubMed

    Chung, Ivan Wong Hin; Eljamel, Sam

    2013-12-01

    Oral 5 aminolevulinic acid (5-ALA) is used to assist surgical resection of malignant tumours in the brain and other locations. Hypotension and alteration of liver functions have been reported as potential adverse effects. This study was designed to assess the incidence and contributing factors that cause 5-ALA induced side effects in a cohort of 90 patients. Hypotension occurred in 11% of patients irrespective of 5-ALA dose. The only contributing factor was the presence of cardiovascular disease and antihypertensive drug therapy with an odd ratio of 17.7. Liver function were disturbed in 2% in patients who received 20mg or less/kg body weight compared to 4% in those who received a dose of >20mg/kg 5-ALA. The liver dysfunction was minor and was not clinically significant. We concluded that 5-ALA induced side effects were minimal and hypotension more likely to occur in patients receiving antihypertensive drug therapy.

  7. 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

  8. 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.

  9. Clinical utility of 5-aminolevulinic acid HCl to better visualize and more completely remove gliomas.

    PubMed

    Halani, Sameer H; Adamson, D Cory

    2016-01-01

    Surgical resection is typically the first line of treatment for gliomas. However, the neurosurgeon faces a major challenge in achieving maximal resection in high-grade gliomas as these infiltrative tumors make it difficult to discern tumor margins from normal brain with conventional white-light microscopy alone. To aid in resection of these infiltrative tumors, fluorescence-guided surgery has gained much popularity in intraoperative visualization of malignant gliomas, with 5-aminolevulinic acid (5-ALA) leading the way. First introduced in an article in Neurosurgery, 5-ALA has since become a safe, effective, and inexpensive method to visualize and improve resection of gliomas. This has undoubtedly led to improvements in the clinical course of patients as demonstrated by the increased overall and progression-free survival in patients with such devastating disease. This literature review aims to discuss the major studies and trials demonstrating the clinical utility of 5-ALA and its ability to aid in complete resection of malignant gliomas. PMID:27672334

  10. Clinical utility of 5-aminolevulinic acid HCl to better visualize and more completely remove gliomas

    PubMed Central

    Halani, Sameer H; Adamson, D Cory

    2016-01-01

    Surgical resection is typically the first line of treatment for gliomas. However, the neurosurgeon faces a major challenge in achieving maximal resection in high-grade gliomas as these infiltrative tumors make it difficult to discern tumor margins from normal brain with conventional white-light microscopy alone. To aid in resection of these infiltrative tumors, fluorescence-guided surgery has gained much popularity in intraoperative visualization of malignant gliomas, with 5-aminolevulinic acid (5-ALA) leading the way. First introduced in an article in Neurosurgery, 5-ALA has since become a safe, effective, and inexpensive method to visualize and improve resection of gliomas. This has undoubtedly led to improvements in the clinical course of patients as demonstrated by the increased overall and progression-free survival in patients with such devastating disease. This literature review aims to discuss the major studies and trials demonstrating the clinical utility of 5-ALA and its ability to aid in complete resection of malignant gliomas. PMID:27672334

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

    PubMed

    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. 5-aminolevulinic acid and neuronavigation in high-grade glioma surgery: results of a combined approach.

    PubMed

    Panciani, Pier Paolo; Fontanella, Marco; Garbossa, Diego; Agnoletti, Alessandro; Ducati, Alessandro; Lanotte, Michele

    2012-02-01

    In high-grade glioma surgery, several techniques are used to achieve the maximum cytoreductive treatment preserving neurological functions. However, the effectiveness of all the methods used alone is reduced by specific limitations of each. We assessed the reliability of a multimodal strategy based on 5-aminolevulinic acid (5-ALA) and neuronavigation. We prospectively studied 18 patients with suspected, non eloquent-area malignant gliomas amenable for complete resection. Conventional illumination was used until the excision appeared complete. The cavity was then systematically inspected in violet-blue light to identify any residual tumour. Multiple biopsies of both fluorescent and non-fluorescent tissue were performed in all cases. Each specimen was labelled according to the sampling location (inside or outside the boundary set by the neuronavigator). The samples were analysed by a neuropathologist blinded to the intraoperative classification. We reviewed the results of both methods, either singly or in combination. Individual analysis showed higher 5-ALA reliability compared to neuronavigation. However, several false-negative fluorescent specimens were detected. With the combined use of fluorescence and neuroimaging, only 1 sample (negative for both 5-ALA and navigation) was tumoral tissue. In our experience, the combined approach showed the best sensitivity and it is recommended in cases of lesions involving non-eloquent areas.

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

    NASA Astrophysics Data System (ADS)

    Pottier, Roy H.; Kennedy, James C.

    1996-01-01

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

  14. 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.

  15. Therapeutic effects of topical 5-aminolevulinic acid photodynamic therapy

    PubMed Central

    Hu, Yin-E; Dai, Shu-Fang; Wang, Bin; Qu, Wei; Gao, Jun-Ling

    2016-01-01

    Objective: To evaluate the therapeutic effects of combined 5-aminolevulinic acid (ALA) and photodynamic therapy (PDT) on genital warts and the safety. Methods: One hundred ten patients with genital warts who were treated in our hospital from June 2013 to October 2014 were selected. The warts and affected parts were disinfected with benzalkonium bromide solution, and the warts were covered with absorbent cotton that had already been added freshly prepared 20% ALA solution, packaged and fixed. Then they were wet-dressed in dark, into which ALA solution was added according to the proportion of 5:3:2 every 30 minutes for three consecutive hours. Afterwards, the warts were illuminated by using photodynamic laser apparatus. The clinical outcomes, adverse reactions and recurrence rates were observed. Results: Genital warts were relieved in 107 out of the 110 cases (cure rate: 97.3%). Male patients had significantly better treatment outcomes at the urethral orifice than those in other affected parts. In the 107 patients, the cure rate of male patients was 98.8%, and they were cured after being treated four times. In contrast, female patients, who were cured after 5 times of treatment, had the cure rate of 91.7%. Their cure rates were similar (χ2=0, P>0.05), but the males were cured after significantly fewer times of treatment than the females (t=-7.432, P<0.05). Five patients suffered from mild tingling or burning sensation upon dressing at the urethral orifice, and the others were all free from systemic adverse reactions. After illumination, a small portion of the patients had mildly red, swelling, painful affected parts, with mild edema that almost disappeared within three days. Three patients relapsed at the urethral orifice and were then cured after further treatment. Conclusion: ALA-PDT can treat genital warts safely with high cure rate and low recurrence rate, particularly working for those of males at the urethral orifice. PMID:27648048

  16. Therapeutic effects of topical 5-aminolevulinic acid photodynamic therapy

    PubMed Central

    Hu, Yin-E; Dai, Shu-Fang; Wang, Bin; Qu, Wei; Gao, Jun-Ling

    2016-01-01

    Objective: To evaluate the therapeutic effects of combined 5-aminolevulinic acid (ALA) and photodynamic therapy (PDT) on genital warts and the safety. Methods: One hundred ten patients with genital warts who were treated in our hospital from June 2013 to October 2014 were selected. The warts and affected parts were disinfected with benzalkonium bromide solution, and the warts were covered with absorbent cotton that had already been added freshly prepared 20% ALA solution, packaged and fixed. Then they were wet-dressed in dark, into which ALA solution was added according to the proportion of 5:3:2 every 30 minutes for three consecutive hours. Afterwards, the warts were illuminated by using photodynamic laser apparatus. The clinical outcomes, adverse reactions and recurrence rates were observed. Results: Genital warts were relieved in 107 out of the 110 cases (cure rate: 97.3%). Male patients had significantly better treatment outcomes at the urethral orifice than those in other affected parts. In the 107 patients, the cure rate of male patients was 98.8%, and they were cured after being treated four times. In contrast, female patients, who were cured after 5 times of treatment, had the cure rate of 91.7%. Their cure rates were similar (χ2=0, P>0.05), but the males were cured after significantly fewer times of treatment than the females (t=-7.432, P<0.05). Five patients suffered from mild tingling or burning sensation upon dressing at the urethral orifice, and the others were all free from systemic adverse reactions. After illumination, a small portion of the patients had mildly red, swelling, painful affected parts, with mild edema that almost disappeared within three days. Three patients relapsed at the urethral orifice and were then cured after further treatment. Conclusion: ALA-PDT can treat genital warts safely with high cure rate and low recurrence rate, particularly working for those of males at the urethral orifice.

  17. 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.

  18. The Safety and Tolerability of 5-Aminolevulinic Acid Phosphate with Sodium Ferrous Citrate in Patients with Type 2 Diabetes Mellitus in Bahrain

    PubMed Central

    Al-Saber, Feryal; Aldosari, Waleed; Alselaiti, Mariam; Khalfan, Hesham; Kaladari, Ahmed; Khan, Ghulam; Harb, George; Rehani, Riyadh; Kudo, Sizuka; Koda, Aya; Tanaka, Tohru

    2016-01-01

    Type 2 diabetes mellitus is prevalent especially in Gulf countries and poses serious long-term risks to patients. A multifaceted treatment approach can include nutritional supplements with antioxidant properties such as 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC). This prospective, randomized, single-blind, placebo-controlled, dose escalating pilot clinical trial assessed the safety of 5-ALA with SFC at doses up to 200 mg 5-ALA/229.42 mg SFC per day in patients living in Bahrain with type 2 diabetes mellitus that was uncontrolled despite the use of one or more antidiabetic drugs. Fifty-three patients (n = 53) from 3 sites at one center were enrolled by Dr. Feryal (Site #01), Dr. Hesham (Site #02), and Dr. Waleed (Site #03) (n = 35, 5-ALA-SFC; n = 18, placebo). There was no significant difference in incidence of adverse events reported, and the most frequent events reported were gastrointestinal in nature, consistent with the known safety profile of 5-ALA in patients with diabetes. No significant changes in laboratory values and no difference in hypoglycemia between patients receiving 5-ALA and placebo were noted. Overall, the current results support that use of 5-ALA-SFC up to 200 mg per day taken as 2 divided doses is safe in patients taking concomitant oral antidiabetic medications and may offer benefits in the diabetic population. This trial is registered with ClinicalTrials.gov NCT02481141. PMID:27738640

  19. 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

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

    PubMed

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

    2003-04-29

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

  1. 5-Aminolevulinic acid combined with ferrous iron induces carbon monoxide generation in mouse kidneys and protects from renal ischemia-reperfusion injury.

    PubMed

    Hou, Jiangang; Cai, Songjie; Kitajima, Yuya; Fujino, Masayuki; Ito, Hidenori; Takahashi, Kiwamu; Abe, Fuminori; Tanaka, Tohru; Ding, Qiang; Li, Xiao-Kang

    2013-10-15

    Renal ischemia reperfusion injury (IRI) is a major factor responsible for acute renal failure. An intermediate in heme synthesis, 5-aminolevulinic acid (5-ALA) is fundamental in aerobic energy metabolism. Heme oxygenase (HO)-1 cleaves heme to form biliverdin, carbon monoxide (CO), and iron (Fe(2+)), which is used with 5-ALA. In the present study, we investigated the role of 5-ALA in the attenuation of acute renal IRI using a mouse model. Male Balb/c mice received 30 mg/kg 5-ALA with Fe(2+) 48, 24, and 2 h before IRI and were subsequently subjected to bilateral renal pedicle occlusion for 45 min. The endogenous CO concentration of the kidneys from the mice administered 5-ALA/Fe(2+) increased significantly, and the peak concentrations of serum creatinine and blood urea nitrogen decreased. 5-ALA/Fe(2+) treatments significantly decreased the tubular damage and number of apoptotic cells. IRI-induced renal thiobarbituric acid-reactive substance levels were also significantly decreased in the 5-ALA/Fe(2+) group. Furthermore, mRNA expression of HO-1, TNF-α, and interferon-γ was significantly increased after IRI. Levels of HO-1 were increased and levels of TNF-α and interferon-γ were decreased in the 5-ALA/Fe(2+)-pretreated renal parenchyma after IRI. F4/80 staining showed reduced macrophage infiltration, and TUNEL staining revealed that there were fewer interstitial apoptotic cells. These findings suggest that 5-ALA/Fe(2+) can protect the kidneys against IRI by reducing macrophage infiltration and decreasing renal cell apoptosis via the generation of CO.

  2. Mechanism of rat osteosarcoma cell apoptosis induced by a combination of low-intensity ultrasound and 5-aminolevulinic acid in vitro.

    PubMed

    Li, Y N; Zhou, Q; Yang, B; Hu, Z; Wang, J H; Li, Q S; Cao, W W

    2015-01-01

    We investigated the killing effect of low-intensity ultrasound combined with 5-aminolevulinic acid (5-ALA) on the rat osteosarcoma cell line UMR-106. Logarithmic-phase UMR-106 cells were divided into a control group, ultrasound group and 5-ALA group. The cell apoptotic rate, production of reactive oxygen species, and the change in mitochondrial membrane potential were analyzed by flow cytometry; ultrastructural changes were observed by transmission electron microscopy. Using low-intensity ultrasound at 1.0 MHz and 2.0 W/cm(2) plus 5-ALA at a concentration of 2 mM, the apoptotic rate of the sonodynamic therapy group was 27.2 ± 3.4% which was significantly higher than that of the control group, ultrasound group, and 5-ALA group (P < 0.05). The production of reactive oxygen species was 32.6 ± 2.2% and the decrease in mitochondrial membrane potential was 39.5 ± 2.5%. The 33342 staining showed nuclear condensation and fragmentation in the ultrasound group and 5-ALA group. Structural changes in the cell membrane, mitochondria, Golgi apparatus, and other organelles observed by transmission electron microscopy included formation of apoptotic bodies. The killing effect of low-intensity ultrasound combined with 5-ALA on UMR-106 cells was significant. Cell apoptosis played a vital role in the killing effect, and the mitochondria pathway contributed to the apoptosis of UMR-106 cells. PMID:26345893

  3. Blood interference in fiber-optical based fluorescence guided resection of glioma using 5-aminolevulinic acid

    NASA Astrophysics Data System (ADS)

    Haj-Hosseini, Neda; Lowndes, Shannely; Salerud, Göran; Wårdell, Karin

    2011-03-01

    Fluorescence guidance in brain tumor resection is performed intra-operatively where bleeding is included. When using fiber-optical probes, the transmission of light to and from the tissue is totally or partially blocked if a small amount of blood appears in front of the probe. Sometimes even after rinsing with saline, the remnant blood cells on the optical probe head, disturb the measurements. In such a case, the corresponding spectrum cannot be reliably quantified and is therefore discarded. The optimal case would be to calculate and take out the blood effect systematically from the collected signals. However, the first step is to study the pattern of blood interference in the fluorescence spectrum. In this study, a fiber-optical based fluorescence spectroscopy system with a laser excitation light of 405 nm (1.4 J/cm2) was used during fluorescence guided brain tumor resection using 5-aminolevulinic acid (5-ALA). The blood interference pattern in the fluorescence spectrum collected from the brain was studied in two patients. The operation situation was modeled in the laboratory by placing blood drops from the finger tip on the skin of forearm and the data was compared to the brain in vivo measurements. Additionally, a theoretical model was developed to simulate the blood interference pattern on the skin autofluorescence. The blood affects the collected fluorescence intensity and leaves traces of oxy and deoxy-hemoglobin absorption peaks. According to the developed theoretical model, the autofluorescence signal is considered to be totally blocked by an approximately 500 μm thick blood layer.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. A New Strategy for Production of 5-Aminolevulinic Acid in Recombinant Corynebacterium glutamicum with High Yield

    PubMed Central

    Yang, Peng; Liu, Wenjing; Cheng, Xuelian; Wang, Jing; Qi, Qingsheng

    2016-01-01

    ABSTRACT 5-Aminolevulinic acid (ALA), a nonprotein amino acid involved in tetrapyrrole synthesis, has been widely applied in agriculture, medicine, and food production. Many engineered metabolic pathways have been constructed; however, the production yields are still low. In this study, several 5-aminolevulinic acid synthases (ALASs) from different sources were evaluated and compared with respect to their ALA production capacities in an engineered Corynebacterium glutamicum CgS1 strain that can accumulate succinyl-coenzyme A (CoA). A codon-optimized ALAS from Rhodobacter capsulatus SB1003 displayed the best potential. Recombinant strain CgS1/pEC-SB produced 7.6 g/liter ALA using a mineral salt medium in a fed-batch fermentation mode. Employing two-stage fermentation, 12.46 g/liter ALA was produced within 17 h, with a productivity of 0.73 g/liter/h, in recombinant C. glutamicum. Through overexpression of the heterologous nonspecific ALA exporter RhtA from Escherichia coli, the titer was further increased to 14.7 g/liter. This indicated that strain CgS1/pEC-SB-rhtA holds attractive industrial application potential for the future. IMPORTANCE In this study, a two-stage fermentation strategy was used for production of the value-added nonprotein amino acid 5-aminolevulinic acid from glucose and glycine in a generally recognized as safe (GRAS) host, Corynebacterium glutamicum. The ALA titer represented the highest in the literature, to our knowledge. This high production capacity, combined with the potential easy downstream processes, made the recombinant strain an attractive candidate for industrial use in the future. PMID:26921424

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Dexamethasone alone and in combination with desipramine, phenytoin, valproic acid or levetiracetam interferes with 5-ALA-mediated PpIX production and cellular retention in glioblastoma cells.

    PubMed

    Lawrence, Johnathan E; Steele, Christopher J; Rovin, Richard A; Belton, Robert J; Winn, Robert J

    2016-03-01

    Extent of resection of glioblastoma (GBM) correlates with overall survival. Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) can improve the extent of resection. Unfortunately not all patients given 5-ALA accumulate sufficient quantities of protoporphyrin IX (PpIX) for successful FGR. In this study, we investigated the effects of dexamethasone, desipramine, phenytoin, valproic acid, and levetiracetam on the production and accumulation of PpIX in U87MG cells. All of these drugs, except levetiracetam, reduce the total amount of PpIX produced by GBM cells (p < 0.05). When dexamethasone is mixed with another drug (desipramine, phenytoin, valproic acid or levetiracetam) the amount of PpIX produced is further decreased (p < 0.01). However, when cells are analyzed for PpIX cellular retention, dexamethasone accumulated significantly more PpIX than the vehicle control (p < 0.05). Cellular retention of PpIX was not different from controls in cells treated with dexamethasone plus desipramine, valproic acid or levetiracetam, but was significantly less for dexamethasone plus phenytoin (p < 0.01). These data suggest that medications given before and during surgery may interfere with PpIX accumulation in malignant cells. At this time, levetiracetam appears to be the best medication in its class (anticonvulsants) for patients undergoing 5-ALA-mediated FGR.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. Transcriptomic analysis for elucidating the physiological effects of 5-aminolevulinic acid accumulation on Corynebacterium glutamicum.

    PubMed

    Yu, Xiaoli; Jin, Haiying; Cheng, Xuelian; Wang, Qian; Qi, Qingsheng

    2016-11-01

    5-Aminolevulinic acid (ALA), the committed intermediate of the heme biosynthetic pathway, attracts close attention among researchers because of its potential applications to cancer treatment and agriculture. Overexpression of heterologous hemA and hemL, which encode glutamyl-tRNA reductase and glutamate-1-semialdehyde aminotransferase, respectively, in Corynebacterium glutamicum produces ALA, although whether ALA accumulation causes unintended effects on the host is unknown. Here we used an integrated systems approach to compare global transcriptional changes induced by the expression of hemA and hemL. Metabolic pathway such as glycolysis was inhibited, but tricarboxylic acid cycle, pentose phosphate pathway, and respiratory metabolism were stimulated. Moreover, the transcriptional levels of certain genes involved in heme biosynthesis were up-regulated, and the data implicate the two-component system (TCS) HrrSA was involved in the regulation of heme synthesis. With these understandings, it is proposed that ALA accumulation stimulates heme synthesis pathway and respiratory metabolism. Our study illuminates the physiological effects of overexpressing hemA and hemL on the phenotype of C. glutamicum and contributes important insights into the regulatory mechanisms of the heme biosynthetic pathways. PMID:27664748

  5. 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

  6. Rational design of 5-aminolevulinic acid derivatives aimed at improving photodynamic therapy.

    PubMed

    Casas, Adriana; Batlle, Alcira

    2002-07-01

    5-aminolevulinic acid (ALA) is the first intermediate in heme biosynthesis and is therefore a precursor of protoporphyrin IX (PpIX). PpIX is used as an endogenous photosensitizer in photodynamic therapy (PDT). Several chemical modifications have been made, both on the amino and carboxyl groups of ALA to induce higher PpIX production and photosensitisation. Esterification of ALA with aliphatic lineal and cyclic alcohols was found to reduce the amount of ALA required for photosensitization. Esterification by aliphatic alcohols with carbohydrate chains equal or lower than C4 leads to porphyrin accumulation lower than ALA, whereas equal or longer than C6 chains leads to greater synthesis of porphyrin. A branch point in the alcohol located next to the site of ester cleavage limits access of the esters to the esterase active site, resulting in lower PpIX production. ALA esters of the polyethylenglycol family can induce high levels of PpIX, with some selectivity for endothelial cells toward tumor cells. On the basis of the differential expression of some aminopeptidases in tumor vasculature when compared to normal vasculature, some ALA-pseudopeptides were synthesized. In a rational design of ALA derivatives, the transport mechanism of these aminoacids into the cell is central. Due to the similar characteristics between ALA and GABA transport, a novel approach for designing new ALA derivatives which could penetrate more easily into tumoral cells, would be to take into account the structures of the inhibitors of GABA transport. PMID:12678731

  7. 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

  8. Optimization of the heme biosynthesis pathway for the production of 5-aminolevulinic acid in Escherichia coli

    PubMed Central

    Zhang, Junli; Kang, Zhen; Chen, Jian; Du, Guocheng

    2015-01-01

    5-Aminolevulinic acid (ALA), the committed intermediate of the heme biosynthesis pathway, shows significant promise for cancer treatment. Here, we identified that in addition to hemA and hemL, hemB, hemD, hemF, hemG and hemH are also the major regulatory targets of the heme biosynthesis pathway. Interestingly, up-regulation of hemD and hemF benefited ALA accumulation whereas overexpression of hemB, hemG and hemH diminished ALA accumulation. Accordingly, by combinatorial overexpression of the hemA, hemL, hemD and hemF with different copy-number plasmids, the titer of ALA was improved to 3.25 g l−1. Furthermore, in combination with transcriptional and enzymatic analysis, we demonstrated that ALA dehydratase (HemB) encoded by hemB is feedback inhibited by the downstream intermediate protoporphyrinogen IX. This work has great potential to be scaled-up for microbial production of ALA and provides new important insights into the regulatory mechanism of the heme biosynthesis pathway. PMID:25716896

  9. Effectiveness of 5-aminolevulinic acid photodynamic therapy in the treatment of hidradenitis suppurativa: a report of 5 cases.

    PubMed

    Andino Navarrete, R; Hasson Nisis, A; Parra Cares, J

    2014-01-01

    Hidradenitis suppurativa has been described as a chronic, recurrent, and disabling inflammatory disease involving the entire hair follicle. Several treatments, including photodynamic therapy, have been used, but the results have been inconsistent and recurrence is high. In this prospective study, we evaluated disease severity, quality of life, and treatment tolerance in 5 patients with moderate to severe hidradenitis suppurativa treated with photodynamic therapy using 5-aminolevulinic acid and a 635-nm light source. Treatment effectiveness was evaluated using the Sartorius severity score, the Dermatology Life Quality Index, and a visual analog scale for pain and disease activity. Significant improvements were observed with all 3 instruments and the effects remained visible at 8 weeks. Our results suggest that photodynamic therapy with 5-aminolevulinic acid and a light wavelength of 635 nm could reduce disease severity and improve quality of life in patients with difficult-to-treat hidradenitis suppurativa.

  10. 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.

  11. 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.

  12. 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:

  13. [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

  14. [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.

  15. 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

  16. Quantification of topically delivered 5-aminolevulinic acid by lontophoresis across ex vivo human stratum corneum.

    PubMed

    Boddé, Harry E; Roemelé, Peter E H; Star, Willem M

    2002-04-01

    Iontophoretic transport of the prodrug 5-aminolevulinic acid (ALA), which is used for photodynamic therapy (PDT), across human stratum corneum (SC) was studied quantitatively in vitro. The experiments were carried out in a three-compartment iontophoresis cell consisting of two electrode chambers equipped with Ag-AgCl electrodes, each separated from a central acceptor chamber by a sheet of SC, supported by a dialysis membrane, to mimic the side-by-side configuration normally used in vivo. Acceptor fluid samples were collected every hour for a period of 30 h in a fraction collector and analyzed by high-performance liquid chromatography-fluorometry after derivatization of the ALA. The iontophoretic ALA flux was studied as a function of the applied current density and the ALA concentration in the donor solution (1, 2.5 or 10% ALA). Depending on the ALA concentration in the donor cell, iontophoresis enhances the flux from close to the detection limit of 0.23 nmol cm(-2) h(-1) at zero current density (passive diffusion) to several hundred or thousand nanomoles per square centimeter per hour at current densities ranging from 100 to 1000 microA cm(-2). For example, interpolating our data we find that with an ALA concentration of 2% in the donor chamber, a current density of 0.255 mA cm(-2) transports 0.065 micromol cm(-2) ALA across the SC in 10 min (conditions of Rhodes et al. (1997), J. Invest. Dermatol. 108, 87-91). For passive diffusion we find that a 5 h topical application of 20% ALA results in the transport of 0.05 micromol cm(-2). Thus, the amount of ALA that passively diffuses through the SC in several hours, leading to therapeutic levels of protoporphyrin IX (PpIX) in the epidermis, can be delivered by iontophoresis in 10 min or less. However, because the formation of sufficient PpIX also requires several hours and also because the SC overlying skin lesions such as basal cell carcinoma (BCC) is not intact, the clinical benefit of topical ALA delivery by

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

    PubMed

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

    2015-08-01

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

  18. 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

  19. 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

  20. 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.

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

    PubMed Central

    Ko, Dong-Yeob; Kim, Ki-Ho

    2014-01-01

    Background Few studies have compared the efficacy, cosmetic outcomes, and adverse events between 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and methyl aminolevulinate-PDT (MAL-PDT) for actinic keratoses (AKs) in Asian ethnic populations with dark-skin. Objective We retrospectively compared the long-term efficacy, recurrence rates, cosmetic outcomes, and safety of ALA-PDT versus MAL-PDT for facial AKs in Koreans. Methods A total of 222 facial AKs in 58 patients were included in this study. A total of 153 lesions (29 patients) were treated with 5-ALA, and 69 lesions (29 patients) with MAL. ALA and MAL creams were applied for 6 hours and 3 hours, respectively; the lesions were then illuminated with a halogen lamp at 150 J/cm2 for ALA-PDT and a diode lamp at 37 J/cm2 for MAL-PDT. Results The complete response rates of ALA-PDT and MAL-PDT were 56.9% and 50.7%, respectively, with no significant difference at 12 months after treatment. No significant difference in recurrence rates was observed between the 2 PDT modalities at either 6 or 12 months after treatment. There was no significant difference in the cosmetic outcomes between the 2 treatment modalities at 12 months after PDT. However, ALA-PDT caused significantly more painful than MAL-PDT (p=0.005). The adverse events were mild to moderate, transient, and self-limiting for both modalities. Conclusion MAL-PDT was similar to ALA-PDT in terms of long-term efficacy, recurrence rates, cosmetic outcomes, and adverse events; however, it was a significantly less painful procedure than ALA-PDT in our study. PMID:24966631

  2. Optimization of Influencing Factors on Biomass Accumulation and 5-Aminolevulinic Acid (ALA) Yield in Rhodobacter sphaeroides Wastewater Treatment.

    PubMed

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

    2015-11-01

    This study aimed to optimize four factors affecting biomass accumulation and 5-aminolevulinic acid (ALA) yield together with pollutants removal in Rhodobacter sphaeroides wastewater treatment. Results showed that it was feasible to produce biomass and ALA in R. sphaeroides wastewater treatment. Microaerobic, 1,000-3,000 lux, and pH 7.0 were optimal conditions for the highest ALA yield of 4.5 ± 0.5 mg/g-biomass. Under these conditions, COD removal and biomass production rate were 93.3 ± 0.9% and 31.8 ± 0.5 mg/l/h, respectively. In addition, trace elements Fe(2+), Mg(2+), Ni(2+), and Zn(2+) further improved the ALA yield, COD removal, and biomass production rate. Specifically, the highest ALA yield (12.5 ± 0.6 mg/g-biomass) was achieved with Fe(2+) addition.

  3. 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

  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

    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.

  5. 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

  6. Latest results of 5-ALA-based fluorescence diagnosis and other medical disciplines

    NASA Astrophysics Data System (ADS)

    Baumgartner, Reinhold

    1999-02-01

    Preclinical and clinical studies on 5-aminolevulinic acid (5- ALA) induced Protoporphyrin IX (PPIX) are performed in various departments now following promising clinical results for the detection of bladder cancer in urology. This paper provides an overview on the progress of 5-ALA assisted fluorescence diagnosis in urology, pulmonology, neurosurgery, gynecology and ENT coordinated by the Laser Research Laboratory of the Ludwig-Maximilians-University in Munich. 5-ALA can be applied either topically or systematically to induce an intracellular accumulation of fluorescing PPIX. With appropriate dosage of 5-ALA, malignant tissue can be stained selectively, and irradiation with violet light excites a bright red fluorescence of the tumor visible with naked eyes. Optical properties of the tissue tend to hamper the precise identification and demarcation of suspect areas in fluorescence images. Multicolor remission and fluorescence imaging, therefore, should improve tumor localization in future.

  7. Basic principles of fluorescence detection with use of 5-ALA

    NASA Astrophysics Data System (ADS)

    Baumgartner, Reinhold; Stepp, Herbert G.

    2000-06-01

    5-Aminolevulinic acid (5-ALA) has been proven to induce selective accumulation of flourescent Protoporphyrin IX (PPIX) in many types of malignant tissue. According to the target to treatment different routes of topical and systemical application of 5-ALA can be chosen. They include techniques like inhalation, installation and rinsing. For fluorescence detection a lamp based system have been developed in the laser-Forschungslabor in Munich together with Storz company. By skillful balancing of excitation filter centered around 400 nm and the observation filter with transmission above 450 nm images with high color contrast can be obtained. The universal application of the D-LIGHT could be demonstrated in different clinical disciplines like urology, neurosurgery, ENT clinic, gynecology and others.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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).

  13. Photosensitizer fluorescence and singlet oxygen luminescence as dosimetric predictors of topical 5-aminolevulinic acid photodynamic therapy induced clinical erythema

    PubMed Central

    Mallidi, Srivalleesha; Anbil, Sriram; Lee, Seonkyung; Manstein, Dieter; Elrington, Stefan; Kositratna, Garuna; Schoenfeld, David; Pogue, Brian; Davis, Steven J.; Hasan, Tayyaba

    2014-01-01

    Abstract. The need for patient-specific photodynamic therapy (PDT) in dermatologic and oncologic applications has triggered several studies that explore the utility of surrogate parameters as predictive reporters of treatment outcome. Although photosensitizer (PS) fluorescence, a widely used parameter, can be viewed as emission from several fluorescent states of the PS (e.g., minimally aggregated and monomeric), we suggest that singlet oxygen luminescence (SOL) indicates only the active PS component responsible for the PDT. Here, the ability of discrete PS fluorescence-based metrics (absolute and percent PS photobleaching and PS re-accumulation post-PDT) to predict the clinical phototoxic response (erythema) resulting from 5-aminolevulinic acid PDT was compared with discrete SOL (DSOL)-based metrics (DSOL counts pre-PDT and change in DSOL counts pre/post-PDT) in healthy human skin. Receiver operating characteristic curve (ROC) analyses demonstrated that absolute fluorescence photobleaching metric (AFPM) exhibited the highest area under the curve (AUC) of all tested parameters, including DSOL based metrics. The combination of dose-metrics did not yield better AUC than AFPM alone. Although sophisticated real-time SOL measurements may improve the clinical utility of SOL-based dosimetry, discrete PS fluorescence-based metrics are easy to implement, and our results suggest that AFPM may sufficiently predict the PDT outcomes and identify treatment nonresponders with high specificity in clinical contexts. PMID:24503639

  14. Improvement of systemic 5-aminolevulinic acid-based photodynamic therapy in vivo using light fractionation with a 75-minute interval.

    PubMed

    de Bruijn, H S; van der Veen, N; Robinson, D J; Star, W M

    1999-02-15

    We have studied different single and fractionated illumination schemes after systemic administration of 5-aminolevulinic acid (ALA) to Improve the response of nodular tumors to ALA-mediated photodynamic therapy. Tumors transplanted on the thigh of female WAG/Rij rats were transdermally illuminated with red light (633 nm) after systemic ALA administration (200 mg/kg). The effectiveness of each treatment scheme was determined from the tumor volume doubling time. A single illumination (100 J/cm2 at 100 mW/cm2, 2.5 h after ALA administration) yielded a doubling time of 6.6+/-1.2 days. This was significantly different from the untreated control (doubling time, 1.7+/-0.1 days). The only treatment scheme that yielded a significant improvement compared to all other schemes studied was illumination at both 1 and 2.5 h after ALA administration (both 100 J/cm2 at 100 mW/cm2) and resulted in a tumor volume doubling time of 18.9+/-2.9 days. A possible mechanism to explain this phenomenon is that the protoporphyrin IX formed after administration of ALA is photodegraded by the first illumination. In the 75-min interval, new porphyrin is formed enhancing the effect of the second illumination. PMID:10029082

  15. Topical photodynamic therapy with 5-aminolevulinic acid in the treatment of actinic keratoses: a first clinical study

    NASA Astrophysics Data System (ADS)

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

    1996-01-01

    In this first clinical study performed according to GCP- (good clinical practice) guidelines, efficacy, and tolerability of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) were tested in the treatment of actinic keratoses. Ten patients (6 f, 4 m) with 36 lesions (19 located on hands and arms, 17 on the head) received ALA-PDT once. Five to six hours after occlusive application of ALA (water-in-oil-emulsion containing 10% ALA) irradiation was performed with an incoherent light source. Up to 3 months after treatment patients were monitored. A score evaluating infiltration and keratosis of treated actinic keratoses allowed us to estimate therapeutic efficacy. Compared to the initial score (100%) significantly lower score-sums were observed at the 28 day follow-up at both localizations (head: 15%; hand: 67%). Complete remission (score sum 0) resulted in 71% of actinic keratoses localized on the head. Except for slight pain and burning sensations during and after irradiation there were no notable side effects. This study proved good efficacy and tolerability of topical PDT in the treatment of actinic keratoses. Whether PDT is able to compete with established treatment modalities remains to be shown in further studies.

  16. 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

  17. 5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Inhibits RIPK1/RIPK3-Dependent Necroptosis in THP-1-Derived Foam Cells.

    PubMed

    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

  18. 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

  19. 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.

  20. 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.

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

    PubMed

    Melnick, Stuart

    2005-01-01

    Photodynamic therapy with short-contact 5-aminolevulinic acid (Levulan Kerastick, Dusa Pharmaceuticals, Inc.) and activation by intense pulsed light in an initial treatment and blue light in 3 subsequent treatments has resulted in significant improvement in severity of acne, reduction in the number of lesions, improvement in skin texture, and smoothing of scar edges in an Asian patient with severe (class 4) facial cystic acne and scarring. PMID:16302560

  2. 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

  3. 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

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

    PubMed

    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.

  5. 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

  6. 5-Aminolevulinic acid ameliorates cadmium-induced morphological, biochemical, and ultrastructural changes in seedlings of oilseed rape.

    PubMed

    Ali, Basharat; Huang, C R; Qi, Z Y; Ali, Shafaqat; Daud, M K; Geng, X X; Liu, H B; Zhou, W J

    2013-10-01

    Due to its prolific growth, oilseed rape (Brassica napus L.) can be grown successfully for phytoremediation of cadmium (Cd)-contaminated soils. Nowadays, use of plant growth regulators against heavy metals stress is one of the major objectives of researchers. The present study evaluates the ameliorate effects of 5-aminolevulinic acid (ALA, 0, 0.4, 2, and 10 mg/l) on the growth of oilseed rape (B. napus L. cv. ZS 758) seedlings under Cd stress (0, 100, and 500 μM). Results have shown that Cd stress hampered the seedling growth by decreasing the radical and hypocotyls length, shoot and root biomass, chlorophyll content, and antioxidants enzymes. On the other hand, Cd stress increased the level of malondialdehyde (MDA) and production of H2O2 and accumulation of Cd in the shoots. The microscopic study of leaf mesophyll cells showed that toxicity of Cd totally destroyed the whole cell structure, and accumulation of Cd also appeared in micrographs. Application of ALA at lower dosage (2 mg/l) enhanced the seedling growth and biomass. The results showed that 2 mg/l ALA significantly improved chlorophyll content under Cd stress and decreased the level of Cd contents in shoots. Application of ALA reduced the MDA and H2O2 levels in the cotyledons. The antioxidants enzymes (ascorbate peroxidase, peroxidase, catalase, glutathione reductase, and superoxide dismutase) enhanced their activities significantly with the application of 2 mg/l ALA under Cd stress. This study also indicated that higher dosage of ALA (10 mg/l) imposed the negative effect on the growth of oilseed rape. Microscopic study showed that application of ALA alleviated the toxic effects of Cd in the mesophyll cell and improved the cell structure. Use of 2 mg/l ALA under 500 μM Cd was found to be more effective, and under this dosage, cell structure was clear, with obvious cell wall and cell membrane as well as a big nucleus, which was found with well-developed two or more nucleoli. Chloroplast was almost round

  7. 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

  8. Simplified and optimized multispectral imaging for 5-ALA-based fluorescence diagnosis of malignant lesions

    PubMed Central

    Minamikawa, Takeo; Matsuo, Hisataka; Kato, Yoshiyuki; Harada, Yoshinori; Otsuji, Eigo; Yanagisawa, Akio; Tanaka, Hideo; Takamatsu, Tetsuro

    2016-01-01

    5-aminolevulinic acid (5-ALA)-based fluorescence diagnosis is now clinically applied for accurate and ultrarapid diagnosis of malignant lesions such as lymph node metastasis during surgery. 5-ALA-based diagnosis evaluates fluorescence intensity of a fluorescent metabolite of 5-ALA, protoporphyrin IX (PPIX); however, the fluorescence of PPIX is often affected by autofluorescence of tissue chromophores, such as collagen and flavins. In this study, we demonstrated PPIX fluorescence estimation with autofluorescence elimination for 5-ALA-based fluorescence diagnosis of malignant lesions by simplified and optimized multispectral imaging. We computationally optimized observation wavelength regions for the estimation of PPIX fluorescence in terms of minimizing prediction error of PPIX fluorescence intensity in the presence of typical chromophores, collagen and flavins. By using the fluorescence intensities of the optimized wavelength regions, we verified quantitative detection of PPIX fluorescence by using chemical mixtures of PPIX, flavins, and collagen. Furthermore, we demonstrated detection capability by using metastatic and non-metastatic lymph nodes of colorectal cancer patients. These results suggest the potential and usefulness of the background-free estimation method of PPIX fluorescence for 5-ALA-based fluorescence diagnosis of malignant lesions, and we expect this method to be beneficial for intraoperative and rapid cancer diagnosis. PMID:27149301

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

    PubMed

    Baglo, Yan; Gabrielsen, Mari; Sylte, Ingebrigt; Gederaas, Odrun A

    2013-01-01

    Photodynamic therapy (PDT) is a safe and effective method currently used in the treatment of skin cancer. In ALA-based PDT, 5-aminolevulinic acid (ALA), or ALA esters, are used as pro-drugs to induce the formation of the potent photosensitizer protoporphyrin IX (PpIX). Activation of PpIX by light causes the formation of reactive oxygen species (ROS) and toxic responses. Studies have indicated that ALA and its methyl ester (MAL) are taken up into the cells via γ-butyric acid (GABA) transporters (GATs). Uptake via GATs into peripheral sensory nerve endings may also account for one of the few adverse side effects of ALA-based PDT, namely pain. In the present study, homology models of the four human GAT subtypes were constructed using three x-ray crystal structures of the homologous leucine transporter (LeuT) as templates. Binding of the native substrate GABA and the possible substrates ALA and MAL was investigated by molecular docking of the ligands into the central putative substrate binding sites in the outward-occluded GAT models. Electrostatic potentials (ESPs) of the putative substrate translocation pathway of each subtype were calculated using the outward-open and inward-open homology models. Our results suggested that ALA is a substrate of all four GATs and that MAL is a substrate of GAT-2, GAT-3 and BGT-1. The ESP calculations indicated that differences likely exist in the entry pathway of the transporters (i.e. in outward-open conformations). Such differences may be exploited for development of inhibitors that selectively target specific GAT subtypes and the homology models may hence provide tools for design of therapeutic inhibitors that can be used to reduce ALA-induced pain. PMID:23762315

  11. Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: a comparison of two light sources.

    PubMed

    Soler, A M; Angell-Petersen, E; Warloe, T; Tausjø, J; Steen, H B; Moan, J; Giercksky, K E

    2000-06-01

    The aim of this prospective randomized study was to compare the clinical and cosmetic outcome of superficial basal cell carcinomas (BCC), using either laser or broadband halogen light, in photodynamic therapy with topical 5-aminolevulinic acid (ALA). A total of 83 patients with 245 superficial BCC were included in the study. Standard treatment involved 15 min of local pretreatment with 99% dimethylsulfoxide (DMSO) before topical application of 20% ALA with DMSO (2%) and ethylendiaminetetraacetic acid (2%) as cofactors for 3 h before light exposure with either laser or a broadband lamp (BL). A complete response was achieved in 95 lesions (86%) in the laser group and 110 lesions (82%) in the BL group 6 months after treatment. Of these, 80 lesions (84%) in the laser group and 101 lesions (92%) in the lamp group were independently evaluated to have an excellent or good cosmetic post-treatment score. No serious adverse events were reported. This study shows that there is no statistical significant difference in cure the rate (P = 0.49) and the cosmetic outcome (P = 0.075) with topical application of a modified ALA-cream between light exposure from a simple BL with continuous spectrum (570-740 nm) or from a red-light laser (monochromatic 630 nm). Cost and safety are further elements in favor of the BL in this setting.

  12. Treatment of moderate to severe inflammatory acne vulgaris: photodynamic therapy with 5-aminolevulinic acid and a novel advanced fluorescence technology pulsed light source.

    PubMed

    Gold, Michael H; Biron, Julie A; Boring, Molly; Bridges, Tancy M; Bradshaw, Virginia L

    2007-03-01

    The use of photodynamic therapy (PDT) with 20% 5-aminolevulinic acid (ALA) for the treatment of acne vulgaris has been explored. This study evaluates the safety and efficacy of a new Advanced Fluorescence Technology (AFT) pulsed light source (420-950 nm) for photoactivation in ALA PDT for the treatment of moderate to severe inflammatory facial acne vulgaris. Nineteen subjects received 4 ALA PDT treatments with the AFT pulsed light source. Treatments were spaced 2 weeks apart. ALA was incubated for 15 to 30 minutes. At the end of the fourth treatment, the total reductions in inflammatory and noninflammatory lesion counts were 54.5% and 37.5%, respectively. Median Global Severity Scores suggest a trend toward reduction after several treatments. Investigator and subject assessments show moderate to marked improvement in most patients. The new AFT pulsed light source with ALA PDT appears to be a safe and effective modality for the treatment of moderate to severe inflammatory acne vulgaris.

  13. Complete resolution of a squamous cell carcinoma of the skin using intralesional 5-aminolevulinic acid photodynamic therapy intralesional PDT for SCC.

    PubMed

    Sotiriou, Eleni; Apalla, Zoi; Ioannides, Demetris

    2010-10-01

    We present an 82-year-old female patient with a 2-year history of an infiltrative squamous cell carcinoma (SCC) on her right cheek. The patient was treated with one intralesional photodynamic therapy (PDT) session using 10% 5-aminolevulinic acid solution. We used red light by a non-coherent light source at a light dose of 100 J/cm² and a fluency rate of 100 mW/cm². Complete clinical and histological response was achieved 3 months after the treatment procedure. Cosmetic outcome was evaluated as fair. The patient remains disease free with the absence of any clinical sign of recurrence 16 months after PDT. Long-term follow-up is needed for assessment of recurrences. Optimization of the therapeutic protocol, as well as justification of our results in larger studies are needed in order to elicit safe conclusions.

  14. 5-ALA Fluorescence in Native Pituitary Adenoma Cell Lines: Resection Control and Basis for Photodynamic Therapy (PDT)?

    PubMed Central

    Poeschke, Stephan; Greve, Burkhard; Prevedello, Daniel; Santacroce, Antonio; Stummer, Walter; Senner, Volker

    2016-01-01

    Objective: Pituitary adenomas (PA), especially invasive ones, are often not completely resectable. Usage of 5-aminolevulinic acid (5-ALA) for fluorescence guided surgery could improve the rate of total resection and, additionally, open the doors for photodynamic therapy (PDT) in case of unresectable or partially resected PAs. The aim of this study was to investigate the uptake of 5-ALA and the effect of 5-ALA based PDT in cell lines. Methods: GH3 and AtT-20 cell lines were incubated with different concentrations of 5-ALA, protoporphyrin IX (PPIX) fluorescence was measured by flow cytometry and fluorescencespectrometry. WST-1 assays were performed to determine the surviving fraction of cells after PDT. PPIX fluorescence intensities and PDT effect of the pituitary adenoma cells were compared to U373MG, a well-known glioblastoma cell line. Results: Both cell lines showed a 5-ALA dependent intracellular PPIX fluorescence. Significant differences after 24hrs of incubation were observed in AtT-20 cells in comparison to GH3. Regardless of the incubation or metabolism time, there was a proliferation inhibiting effect after PDT, with no statistical significance. Conclusion: Since GH3 cells showed a heterogenous uptake of 5-ALA in the flow cytometry profile, but not constantly high concentrations they might have a 5-ALA efflux mechanism, which still needs to be determined. In the case of AtT-20, the cells might need a longer time for the uptake due to their size or slow metabolism. We showed that the different cell lines have different uptake and metabolism mechanisms, which needs to be further investigated. The general uptake of 5-ALA allows the possibility of resection control and PDT for pituitary adenomas. But, the role of PDT for unresectable pituitary adenomas deserves further investigations. PMID:27583461

  15. Alleviation of lead toxicity by 5-aminolevulinic acid is related to elevated growth, photosynthesis, and suppressed ultrastructural damages in oilseed rape.

    PubMed

    Tian, Tian; Ali, Basharat; Qin, Yebo; Malik, Zaffar; Gill, Rafaqat A; Ali, Shafaqat; Zhou, Weijun

    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.

  16. Inhibition of MAPK signaling pathways enhances cell death induced by 5-Aminolevulinic acid-photodynamic therapy in skin squamous carcinoma cells.

    PubMed

    Ge, Xinhong; Liu, Jianping; Shi, Zhiyun; Jing, Li; Yu, Nan; Zhang, Xiujuan; Jiao, Yaning; Wang, Yili; Li, P Andy

    2016-04-01

    Combination of a photosensitizer, 5-aminolevulinic acid (ALA), with photodynamic therapy (PDT) has been widely used to treat skin squamous cell carcinoma (SCC). However, a portion of SCC patients do not respond well to PDT. The molecular reason for this resistance is not clear. We hypothesize that mitogen-activated phosphorylation kinase (MAPK) plays a key role in mediating SCC resistance to PDT. To determine whether inhibition of MAPK signaling enhances the anti-tumor effect of ALA-PDT in SCC. The human squamous carcinoma cell line, SCL-1, was either untreated or treated with various combinations of ALA, PDT light source and inhibitors of MAPK signaling components. ALA-PDT treatment significantly decreased cell viability, increased the percentage of annexin-V positive cells and resulted in formation of apoptotic bodies. ALA-PDT treated cells showed increased levels of p-MEK, p-ERK1/2, p-p38, p-Elk-1, p-JNK and p-c-Jun. Addition of inhibitors for ERK1/2 (PD98059), p38 (SB203580) and JNK (SP60125) reversed the changes and led to a more dramatic decrease in SCL-1 cell viability than seen with ALA-PDT alone. Inhibition of the MAPK pathway enhances the cytotoxic effect of ALA-PDT on SCL-1.

  17. 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.

  18. 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.

  19. 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

  20. Inhibition of MAPK signaling pathways enhances cell death induced by 5-Aminolevulinic acid-photodynamic therapy in skin squamous carcinoma cells.

    PubMed

    Ge, Xinhong; Liu, Jianping; Shi, Zhiyun; Jing, Li; Yu, Nan; Zhang, Xiujuan; Jiao, Yaning; Wang, Yili; Li, P Andy

    2016-04-01

    Combination of a photosensitizer, 5-aminolevulinic acid (ALA), with photodynamic therapy (PDT) has been widely used to treat skin squamous cell carcinoma (SCC). However, a portion of SCC patients do not respond well to PDT. The molecular reason for this resistance is not clear. We hypothesize that mitogen-activated phosphorylation kinase (MAPK) plays a key role in mediating SCC resistance to PDT. To determine whether inhibition of MAPK signaling enhances the anti-tumor effect of ALA-PDT in SCC. The human squamous carcinoma cell line, SCL-1, was either untreated or treated with various combinations of ALA, PDT light source and inhibitors of MAPK signaling components. ALA-PDT treatment significantly decreased cell viability, increased the percentage of annexin-V positive cells and resulted in formation of apoptotic bodies. ALA-PDT treated cells showed increased levels of p-MEK, p-ERK1/2, p-p38, p-Elk-1, p-JNK and p-c-Jun. Addition of inhibitors for ERK1/2 (PD98059), p38 (SB203580) and JNK (SP60125) reversed the changes and led to a more dramatic decrease in SCL-1 cell viability than seen with ALA-PDT alone. Inhibition of the MAPK pathway enhances the cytotoxic effect of ALA-PDT on SCL-1. PMID:27032574

  1. 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

  2. 5-Aminolevulinic Acid Thins Pear Fruits by Inhibiting Pollen Tube Growth via Ca(2+)-ATPase-Mediated Ca(2+) Efflux.

    PubMed

    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 Ca(2+) concentration ([Ca(2+)]cyt) but also "tip-focused" [Ca(2+)]cyt gradient, indicating that ALA inhibited pollen tube growth by down-regulating calcium signaling. ALA drastically enhanced pollen Ca(2+)-ATPase activity, suggesting that ALA-induced decrease of calcium signaling probably resulted from activating calcium pump. The significant negative correlations between Ca(2+)-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 Ca(2+) efflux by activating Ca(2+)-ATPase, thereby thinning fruits by preventing fertilization.

  3. 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

  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. Effects of exogenous 5-aminolevulinic acid on photosynthesis, stomatal conductance, transpiration rate, and PIP gene expression of tomato seedlings subject to salinity stress.

    PubMed

    Zhao, Y Y; Yan, F; Hu, L P; Zhou, X T; Zou, Z R; Cui, L R

    2015-01-01

    The effects of exogenous 5-aminolevulinic acid (ALA) on photosynthesis, plant growth, and the expression of two aquaporin genes in tomato seedlings under control and salinity conditions were investigated. Exogenous ALA application significantly improved net photosynthetic rate (Pn), total chlorophyll content, and plant biomass accumulation of tomato seedlings under salinity stress. As revealed by real-time PCR analyses, after treatment with ALA alone, expression of both LePIP1 and LePIP2 in the two tomato cultivars was up-regulated at 2 h and subsequently decreased to normal levels. Under salinity stress, transcript levels of LePIP1 in both leaves and roots of salt-sensitive cultivars (cv. Zhongza No.9) increased significantly and were considerably higher than in cultivars exposed to ALA alone. In contrast, the expression levels of LePIP1 and LePIP2 in cvs. Jinpeng No.1 cultivars were slightly lower under salinity stress than under ALA treatment. In addition, transcript levels of both LePIP1 and LePIP2 in the roots of Jinpeng No. 1 cultivars were considerably lower than those in the roots of Zhongza No. 9 cultivars under salinity stress, regardless of ALA supplementation, implying that Jinpeng No. 1 cultivars had a better capacity to maintain membrane intrinsic protein stability. Further, ALA application distinctly counteracted the up- or down-regulation of LePIP1 and LePIP2 in both cultivars under salinity stress, in accordance with the improvements instomatal conductance, transpiration rate, and Pn of tomato leaves. The results presented here indicate that ALA controls aquaporin expression, thus, presumably ALA regulates water homeostasis and enhances salt tolerance of tomato seedlings. PMID:26125845

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 5-Aminolevulinic Acid Protects against Cisplatin-Induced Nephrotoxicity without Compromising the Anticancer Efficiency of Cisplatin in Rats In Vitro and In Vivo

    PubMed Central

    Matsumoto, Tatsuki; Ishihara, Masayuki; Hamada, Kazu; Shimamura, Yoshiko; Ogata, Koji; Inoue, Kosuke; Taniguchi, Yoshinori; Horino, Taro; Karashima, Takashi; Tamura, Kenji; Fukuhara, Hideo; Fujimoto, Shimpei; Tsuda, Masayuki; Shuin, Taro

    2013-01-01

    Background/Aims Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP)-based chemotherapy. 5-Aminolevulinic acid (ALA) is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI). Method We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E). We divided four groups of rats: control, CDDP only, CDDP + ALA(post);(ALA 10 mg/kg + Fe in drinking water) after CDDP, CDDP + ALA(pre & post). Result CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX) IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO)-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP. Conclusion These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy. PMID:24324635

  11. Effects of exogenous 5-aminolevulinic acid on photosynthesis, stomatal conductance, transpiration rate, and PIP gene expression of tomato seedlings subject to salinity stress.

    PubMed

    Zhao, Y Y; Yan, F; Hu, L P; Zhou, X T; Zou, Z R; Cui, L R

    2015-06-11

    The effects of exogenous 5-aminolevulinic acid (ALA) on photosynthesis, plant growth, and the expression of two aquaporin genes in tomato seedlings under control and salinity conditions were investigated. Exogenous ALA application significantly improved net photosynthetic rate (Pn), total chlorophyll content, and plant biomass accumulation of tomato seedlings under salinity stress. As revealed by real-time PCR analyses, after treatment with ALA alone, expression of both LePIP1 and LePIP2 in the two tomato cultivars was up-regulated at 2 h and subsequently decreased to normal levels. Under salinity stress, transcript levels of LePIP1 in both leaves and roots of salt-sensitive cultivars (cv. Zhongza No.9) increased significantly and were considerably higher than in cultivars exposed to ALA alone. In contrast, the expression levels of LePIP1 and LePIP2 in cvs. Jinpeng No.1 cultivars were slightly lower under salinity stress than under ALA treatment. In addition, transcript levels of both LePIP1 and LePIP2 in the roots of Jinpeng No. 1 cultivars were considerably lower than those in the roots of Zhongza No. 9 cultivars under salinity stress, regardless of ALA supplementation, implying that Jinpeng No. 1 cultivars had a better capacity to maintain membrane intrinsic protein stability. Further, ALA application distinctly counteracted the up- or down-regulation of LePIP1 and LePIP2 in both cultivars under salinity stress, in accordance with the improvements instomatal conductance, transpiration rate, and Pn of tomato leaves. The results presented here indicate that ALA controls aquaporin expression, thus, presumably ALA regulates water homeostasis and enhances salt tolerance of tomato seedlings.

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

    PubMed

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

    2015-12-01

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

  14. Whole bladder wall photodynamic therapy using 5-ALA: an experimental study in pigs

    NASA Astrophysics Data System (ADS)

    van Staveren, Hugo J.; Beek, Johan F.; Verlaan, Cess W.; Edixhoven, Annie; Saarnak, Anne E.; Sterenborg, Dick; de Reijke, Theo M.; de la Riviere, Guy B.; Thomsen, Sharon L.; van Gemert, Martin J. C.; Star, Willem M.

    1996-01-01

    The agent 5-aminolevulinic acid (5-ALA) can be an alternative drug in whole bladder wall (WBW) photodynamic therapy (PDT), as its good tumor selectivity and the short time skin photosensitivity after systemic administration are advantageous for clinical use. To determine the maximum drug and light doses for reversible normal tissue damage, a pre-clinical study was performed using an in vivo normal piglet bladder model. First, the kinetics of PpIX production in 2 pigs was determined in vitro after oral administration of 75 and 150 mg/kg ALA respectively. The concentration of PpIX in plasma, and erythrocytes was determined by reversed phase high-performance liquid chromatography (HPLC) and the maximum was reached at approximately equals 5 hours after the administration of ALA. This provided a guideline for the optimum interval between ALA administration and light application. Next, various ALA doses were either administered orally or instilled in the bladder and different light doses were applied. Bladder biopsies were taken at regular intervals and normal tissue damage was investigated histologically. Reversible tissue damage was obtained using 60 mg/kg of 5-ALA in combination with a light dose of 100 J cm-2 (non-scattered plus scattered 630 nm wavelength light) in the case of oral administration. In the case of intravesical instillation, a drug dose of 2.5 gram and a light dose of 100 J cm-2 are still too high to obtain reversible tissue damage.

  15. Study of the efficacy of 5 ALA-mediated photodynamic therapy on human larynx squamous cell carcinoma (Hep2c) cell line

    NASA Astrophysics Data System (ADS)

    Khursid, A.; Atif, M.; Firdous, S.; Zaidi, S. S. Z.; Salman, R.; Ikram, M.

    2010-07-01

    5-aminolevulanic acid (ALA), a precursor of Protoporphyrin IX, was evaluated as an inducer of photodamage on Hep2c, human larynx squamous cell carcinoma, cell line. Porphyrins are used as active cytotoxic antitumor agents in photodynamic therapy (PDT). The present study evaluates the effects of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) using human larynx cells as experimental model. Hep2c cell line was irradiated with red light (a diode laser, λ = 635 nm). The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the cellular viability of Hep2c cells were studied. The optimal uptake of photosensitizer ALA in Hep-2c cells was investigated by means of spectrometric measurement. Cells viability was determined by means of neutral red assay (NR). It was observed that sensitizer or light doses have no significant effect on cells viability when studied independently. The spectrometric measurements showed that the maximal cellular uptake of 5-ALA occurred after 7 h in vitro incubation. The photocytotoxic assay showed that light dose of 85 J/cm2 gives effective PDT outcome for Hep2c cell line incubated with 55 μg/ml of 5-ALA with a conclusion that Hep2c cell line is sensitive to ALA-mediated PDT.

  16. Endoscopy imaging of 5-ALA-induced PPIX fluorescence for detecting early neoplasms in the oral cavity

    NASA Astrophysics Data System (ADS)

    Zheng, Wei; Olivo, Malini; Sivanandan, Ranjiv; Karuman, Philip; Lim, Tuan-Kay; Soo, K. C.

    2001-10-01

    A digitized fluorescence endoscopy imaging system combined with 5-Aminolevulinic Acid (5-ALA) induced Protoporphyrin IX (PPIX) has been developed for the detection of neoplasms in oral cavity. It mainly consists of the illumination console, fluorescence detection unit, computer system for image acquisition, processing and analysis, and online image display system as well. The developed system can produce both the digital and video fluorescence images in real time, and can be used to quantify fluorescence images acquired. Preliminary results from the Head and Neck clinic show that high sensitivity and high specificity can be achieved. Furthermore, applying the intensity ratios at two different wavelength regions, the developed system shows the capability of differentiating between different histopathological stages of oral lesions, suggesting a significant potential for realizing the non-invasive optical biopsy for early cancer diagnosis.

  17. 5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Promotes Phenotypic Switching from Dedifferentiated to Differentiated Phenotype via Reactive Oxygen Species and p38 Mitogen-Activated Protein Kinase in Vascular Smooth Muscle Cells.

    PubMed

    Dan, Juhua; Sun, Xin; Li, Wanlu; Zhang, Yun; Li, Xuesong; Xu, Haobo; Li, Zhitao; Tian, Zhen; Guo, Shuyuan; Yao, Jianting; Gao, Weidong; Tian, Ye

    2015-06-01

    Sonodynamic therapy (SDT) has been found to inhibit in-stent restenosis in animal models. However, the mechanism is not fully elucidated. Here, we investigated the effects of 5-aminolevulinic acid (ALA)-mediated SDT (ALA-SDT) on vascular smooth muscle cells (VSMCs), a cause of restenosis, with a focus on SDT-induced phenotypic switching. Serum-induced dedifferentiated VSMCs were cultured with ALA (1 mm, 24 h) and exposed to ultrasound (0.8 W/cm(2)) for 5 min. Results indicated that ALA-SDT inhibited the migration and proliferation of VSMCs and enhanced the expression of differentiated phenotypic markers in VSMCs. Additionally, ALA-SDT increased intracellular reactive oxygen species accumulation and phosphorylated p38 mitogen-activated protein kinase in VSMCs. Inhibition of reactive oxygen species elevation or p38 mitogen-activated protein kinase activity abolished the expression of smooth muscle 22α (SM22α) in VSMCs induced by ALA-SDT. Taken together, these results suggest that ALA-SDT promotes transformation of the VSMC phenotype from the dedifferentiated to differentiated status via reactive oxygen species and activated p38 mitogen-activated protein kinase.

  18. Inhibitory Effect of Gabaculine on 5-Aminolevulinate Dehydratase Activity in Radish Seedlings 1

    PubMed Central

    Tchuinmogne, Simo J.; Huault, Claude; Aoues, Abdelkader; Balangé, Alain P.

    1989-01-01

    We have compared the activity of 5-aminolevulinate dehydratase (5-ALAD) with the amount of protein detected by specific antibodies in rocket immunoelectrophoresis. Parallel kinetic evolutions of enzymic activity and amount of antigen were observed in radish (Raphanus sativus L.) cotyledons, both in complete darkness or under standard far red light involving phytochrome. However, the treatment of seedlings with gabaculine leads to an important decrease in enzymic activity, while the specific protein content is maintained. This inhibition is not overcome by the addition of glutamic acid, but by 5-aminolevulinic acid which points to a specific control of 5-ALAD activity by its substrate. As there is no discrepancy between the enzymic activity and the amount of antigen during the time course development of seedlings, this could confirm a coordinate cellular control between 5-aminolevulinic acid formation and 5-ALAD protein synthesis, both being amplified by the action of phytochrome. PMID:16666925

  19. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2009-12-01

    5-aminolevulanic acid (ALA), belonging among the promising second generation of sensitizers, was evaluated as an inducer of photodamage on HeLa (human cervical adenocarcinoma) cell line. A diode laser (635 nm) was used as a source for initiation of the photodynamic effect. We studied the influence of different incubation times, various concentrations of sensitizer, different irradiation doses and various combinations of sensitizer and light doses on the photodamage of HeLa cells. Viability of cells was determined by means of neutral red assay. The quantitative cellular uptake of ALA sensitizer was done by spectrophotometric measurements. No prominent cytotoxic or phototoxic effects on HeLa were observed due to sensitizer or light doses when studied independently of each other. However phototoxicity evoked by laser irradiated sensitizer was detected in HeLa cell line.

  1. Phototoxic effects of zinc oxide nanowires (ZnO NWs) complexed with 5-ALA in RD cell line

    NASA Astrophysics Data System (ADS)

    Fakhar-e-Alam, M.; Ali, S. M. U.; Ibupoto, Z. H.; Atif, M.; Willander, M.

    2011-12-01

    In this current study, we have manifested the photosensitizing effects of zinc oxide nanowires (ZnO NWs) in dark as well as under ultra violet light exposure with 240 nm of UV region, using human muscle cancer (Rhybdomyosarcoma cells, RD) as in vitro experimental model. We have fabricated ZnO-NWs on the tip of borosilicate glass capillaries (0.5 μm diameter) and were conjugated using 5-aminolevulinic acid (ALA) for the efficient intracellular drug delivery. When ZnO NWs were applied on tumor localizing drugs with non ionizing illumination, then excited drug liberates reactive oxygen species (ROS), effecting mitochondria and nucleus resulting in cell necrosis within few minutes. During investigations, we observed that when ZnO-NWs grown on intracellular tip was excited by using 240 nm of UV light, as a resultant 625 nm of emitted red light were used as appetizer in the presence of 5-ALA for chemical reaction, which produces singlet oxygen, responsible for cell necrosis. Morphological changes of necrosed cells were examined under microscopy. Moreover, Viability of controlled and treated RD cells with optimum dose of light (UV-Visible) has been assessed by MTT assay as well as reactive oxygen species (ROS) detection.

  2. Fluorescence-Guided Resection of Malignant Glioma with 5-ALA.

    PubMed

    Kaneko, Sadahiro; Kaneko, Sadao

    2016-01-01

    Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD). Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX) accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD. PMID:27429612

  3. Fluorescence-Guided Resection of Malignant Glioma with 5-ALA

    PubMed Central

    Kaneko, Sadahiro

    2016-01-01

    Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD). Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX) accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD. PMID:27429612

  4. 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.

  5. Characterization of 5-aminolevulinate synthase from Agrobacterium radiobacter, screening new inhibitors for 5-aminolevulinate dehydratase from Escherichia coli and their potential use for high 5-aminolevulinate production.

    PubMed

    Lin, Jianping; Fu, Weiqi; Cen, Peilin

    2009-04-01

    The hemA gene encoding 5-aminolevulinate synthase (ALAS) from Agrobacterium radiobacter zju-0121 showed 92.6% homology with that from A. radiobacter ATCC4718 and contained several rare codons. To enhance the expression of this gene, Escherichia coli Rosetta(DE3), which is a rare codon optimizer strain, was used as the host to construct an efficient recombinant strain. And the encoded protein was over-expressed as fusion protein and was purified by affinity purification on Ni-NTA agarose and by gel filtration chromatography on Sephadex G-25 Medium resin. The recombinant protein was partly characterized, and D-glucose, D-fructose, D-xylose, D-mannose, L-arabinose, D-galactose, lactose, sucrose and maltose were detected to have no distinct inhibition on this recombinant ALAS. Meanwhile, 20mM D-glucose or D-xylose inhibited about 20% activity of ALA dehydratase (ALAD) from Escherichia coli Rosetta(DE3). Combining D-xylose as a new inhibitor for ALAD with D-glucose in fed-batch culture and based on the optimal culture system using Rosetta(DE3)/pET28a-hemA, the yield of ALA achieved was 7.3g/l (56 mM) under the appropriate conditions in the fermenter.

  6. Neurotransmitter transporter family including SLC6A6 and SLC6A13 contributes to the 5-aminolevulinic acid (ALA)-induced accumulation of protoporphyrin IX and photodamage, through uptake of ALA by cancerous cells.

    PubMed

    Tran, Tai Tien; Mu, Anfeng; Adachi, Yuka; Adachi, Yasushi; Taketani, Shigeru

    2014-01-01

    δ-Aminolevulinic acid (ALA)-induced protoporphyrin accumulation is widely used in the treatment of cancer, as photodynamic therapy (PDT). To clarify the mechanisms of ALA uptake by tumor cells, we have examined the ALA-induced accumulation of protoporphyrin by the treatment of colon cancer DLD-1 and epithelial cancer HeLa cells with γ-aminobutyric acid (GABA)-related compounds. When the cells were treated with GABA, taurine and β-alanine, the level of protoporphyrin was decreased, suggesting that plasma membrane transporters involved in the transport of neurotransmitters contribute to the uptake of ALA. By transfection with neurotransmitter transporters SLC6A6, SLC6A8 and SLC6A13 cDNA, the ALA- and ALA methylester-dependent accumulation of protoporphyrin markedly increased in HEK293T cells, dependent on an increase in the uptake of ALA. When ALA-treated cells were exposed to white light, the extent of photodamage increased in SLC6A6- and SLC6A13-expressing cells. Conversely, knockdown of SLC6A6 or SLC6A13 with siRNAs in DLD-1 and HeLa cells decreased the ALA-induced accumulation. The expression of SLC6A6 and SLC6A13 was found in some cancer cell lines. Immunohistochemical studies revealed that the presence of these transporters was elevated in colon cancerous cells. These results indicated that neurotransmitter transporters including SLC6A6 and SLC6A13 mediate the uptake of ALA and can play roles in the enhancement of ALA-induced accumulation of protoporphyrin in cancerous cells.

  7. 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.

  8. Application of 5-ALA for differential diagnostics of stomach diseases

    NASA Astrophysics Data System (ADS)

    Okhotnikova, Natalja L.; Dadvany, Sergey A.; Kuszin, Michail I.; Kharnas, Sergey S.; Zavodnov, Victor Y.; Sklyanskaya, Olga A.; Loschenov, Victor B.; Volkova, Anna I.; Agafonov, Valery V.

    2001-01-01

    59 patients with stomach diseases including gastric cancer or polyp, gastritis, esofagus disease were investigated. Before gastroscopy all patients were given 5-ALA in doses 5mg, 10mg and 20mg per 1kg of body weight orally. Fluorescence diagnostics which estimates concentration of ALA-induced PPIX in regular and alternated tissues of gastric mucosa were carried out in 2-4 hours. Using of 5-ALA has shown high diagnostic effectiveness for differential diagnostics of stomach diseases. This technique has proved 10 diagnosis of cancer and revealed 15 malignant stomach diseases including 4 cancer in situ for patients with preliminary diagnosis of gastric ulcer. It also revealed 5 patients with enhanced fluorescence for which aimed biopsy has shown high degree of inflammation process. The latter were assigned as a risk group.

  9. 5-ALA-assisted photodynamic therapy in canine prostates

    NASA Astrophysics Data System (ADS)

    Sroka, Ronald; Muschter, Rolf; Knuechel, Ruth; Steinbach, Pia; Perlmutter, Aaron P.; Martin, Thomas; Baumgartner, Reinhold

    1996-05-01

    Photodynamic therapy (PDT) and interstitial thermotherapy are well known treatment modalities in urology. The approach of this study is to combine both to achieve a selective treatment procedure for benign prostatic hyperplasia (BPH) and prostate carcinoma. Measurements of thy in-vivo pharmacokinetics of 5-ALA induced porphyrins by means of fiber assisted ratiofluorometry showed a maximum fluorescence intensity at time intervals of 3 - 4 h post administration. Fluorescence microscopy at that time showed bright fluorescence in epithelial cells while in the stroma fluorescence could not be observed. Interstitial PDT using a 635-nm dye laser with an irradiation of 50 J/cm2 resulted in a nonthermic hemorrhagic lesion. The lesion size did not change significantly when an irradiation of 100 J/cm2 was used. The usefulness of PDT for treating BPH as well as prostate carcinoma has to be proven in further studies.

  10. Comparison of the beluga whale (Delphinapterus leucas) expressed genes for 5-aminolevulinate synthase with those in other vertebrates.

    PubMed

    Kreiling, J A; Duncan, R; Faggart, M A; Cornell, N W

    1999-06-01

    The cDNA and inferred amino acid sequences were determined for beluga whale (Delphinapterus leucas) erythroid (E) and housekeeping (H) forms of 5-aminolevulinate synthase (ALS), and they were compared with known sequences for five other vertebrates with particular attention to regulatory features. The cDNAs for whale ALS-E and -H encode, respectively, proteins of 582 and 640 amino acids. Sequence alignments suggest that the whale ALS-H, like those for rat and chicken, has an N-terminal mitochondrial targeting sequence of 56 amino acids. There is a high degree of amino acid conservation between the beluga whale proteins and those of other vertebrates, including regulatory elements and functional residues that have been defined in other ALSs. Both whale proteins contain three heme regulatory motifs suggesting that mitochondrial uptake may be regulated by heme. The ALS-E mRNA contains an iron responsive element in its 5'-untranslated region indicating that its expression may be post-transcriptionally regulated by cellular iron. This extensive structural similarity and the presence of the same regulatory elements found in other ALSs indicate that regulation of ALS in beluga whale is similar to that in other vertebrates.

  11. 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.

  12. 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.

  13. 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

  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. Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate

    NASA Astrophysics Data System (ADS)

    Warren, Christine B.; Lohser, Sara; Wene, Lauren C.; Pogue, Brian W.; Bailin, Philip L.; Maytin, Edward V.

    2010-09-01

    Topical 5-aminolevulinic acid (ALA) is widely used in photodynamic therapy (PDT) of actinic keratoses (AK), a type of premalignant skin lesion. However, the optimal time between ALA application and exposure to light has not been carefully investigated. Our objective is to study the kinetics of protoporphyrin IX (PpIX) accumulation in AK after short contact ALA and relate this to erythemal responses. Using a noninvasive dosimeter, PpIX fluorescence measurements (5 replicates) were taken at 20-min intervals for 2 h following ALA application, in 63 AK in 20 patients. Data were analyzed for maximal fluorescent signal obtained, kinetic slope, and changes in erythema. Our results show that PpIX accumulation was linear over time, becoming statistically higher than background in 48% of all lesions by 20 min, 92% of lesions by 1 h, and 100% of lesions by 2 h. PpIX accumulation was roughly correlated with changes in lesional erythema post-PDT. We conclude that significant amounts of PpIX are produced in all AK lesions by 2 h. The linear kinetics of accumulation suggest that shorter ALA application times may be efficacious in many patients. Noninvasive fluorescence monitoring of PpIX may be useful to delineate areas of high PpIX accumulation within precancerous areas of the skin.

  16. Delineating Normal from Diseased Brain by Aminolevulinic Acid-Induced Fluorescence

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert; Stummer, Walter

    5-Aminolevulinic acid (5-ALA) as a precursor of protoporphyrin IX (PpIX) has been established as an orally applied drug to guide surgical resection of malignant brain tumors by exciting the red fluorescence of PpIX. The accumulation of PpIX in glioblastoma multiforme (GBM) is highly selective and provides excellent contrast to normal brain when using surgical microscopes with appropriately filtered light sources and cameras. The positive predictive value of fluorescent tissue is very high, enabling safe gross total resection of GBM and other brain tumors and improving prognosis of patients. Compared to other intraoperative techniques that have been developed with the aim of increasing the rate of safe gross total resections of malignant gliomas, PpIX fluorescence is considerably simpler, more cost effective, and comparably reliable. We present the basics of 5-ALA-based fluorescence-guided resection, and discuss the clinical results obtained for GBM and the experience with the fluorescence staining of other primary brain tumors and metastases as well as the results for spinal cord tumors. The phototoxicity of PpIX, increasingly used for photodynamic therapy of brain tumors, is mentioned briefly in this chapter.

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

    PubMed Central

    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.

    2015-01-01

    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 accelerations 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 ALA binding to the XLPP variants demonstrated that the protein conformational transition step associated with product release was predominantly affected. Of relevance, 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

  18. 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.

  19. Quantitative fluorescence using 5-aminolevulinic acid–induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

    PubMed Central

    Valdés, Pablo A.; Jacobs, Valerie; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Paulsen, Keith D.; Roberts, David W.

    2015-01-01

    OBJECT Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)–induced PpIX fluorescence in a series of patients with LGG. METHODS Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 μg/kg of ALA approximately 3 hours prior to surgery under an institutional review board–approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were

  20. 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.

  1. Red versus blue light illumination in hexyl 5-aminolevulinate photodynamic therapy: the influence of light color and irradiance on the treatment outcome in vitro.

    PubMed

    Helander, Linda; Krokan, Hans E; Johnsson, Anders; Gederaas, Odrun A; Plaetzer, Kristjan

    2014-08-01

    Hexyl 5-aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinate, a key intermediate in biosynthesis of the photosensitizer protoporphyrin IX (PpIX). The photodynamic efficacy and cell death mode after red versus blue light illumination of HAL-induced PpIX have been examined and compared using five different cancer cell lines. LED arrays emitting at 410 and 624 nm served as homogenous and adjustable light sources. Our results show that the response after HAL-PDT is cell line specific, both regarding the shape of the dose-survival curve, the overall dose required for efficient cell killing, and the relative amount of apoptosis. The ratio between 410 and 624 nm in absorption coefficient correlates well with the difference in cell killing at the same wavelengths. In general, the PDT efficacy was several folds higher for blue light as compared with red light, as expected. However, HAL-PDT₆₂₄ induced more apoptosis than HAL-PDT₄₁₀ and illumination with low irradiance resulted in more apoptosis than high irradiance at the same lethal dose. This indicates differences in death modes after low and high irradiance after similar total light doses. From a treatment perspective, these differences may be important.

  2. Red versus blue light illumination in hexyl 5-aminolevulinate photodynamic therapy: the influence of light color and irradiance on the treatment outcome in vitro

    NASA Astrophysics Data System (ADS)

    Helander, Linda; Krokan, Hans E.; Johnsson, Anders; Gederaas, Odrun A.; Plaetzer, Kristjan

    2014-08-01

    Hexyl 5-aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinate, a key intermediate in biosynthesis of the photosensitizer protoporphyrin IX (PpIX). The photodynamic efficacy and cell death mode after red versus blue light illumination of HAL-induced PpIX have been examined and compared using five different cancer cell lines. LED arrays emitting at 410 and 624 nm served as homogenous and adjustable light sources. Our results show that the response after HAL-PDT is cell line specific, both regarding the shape of the dose-survival curve, the overall dose required for efficient cell killing, and the relative amount of apoptosis. The ratio between 410 and 624 nm in absorption coefficient correlates well with the difference in cell killing at the same wavelengths. In general, the PDT efficacy was several folds higher for blue light as compared with red light, as expected. However, HAL-PDT624 induced more apoptosis than HAL-PDT410 and illumination with low irradiance resulted in more apoptosis than high irradiance at the same lethal dose. This indicates differences in death modes after low and high irradiance after similar total light doses. From a treatment perspective, these differences may be important.

  3. Expression of a hemA gene from Agrobacterium radiobacter in a rare codon optimizing Escherichia coli for improving 5-aminolevulinate production.

    PubMed

    Fu, Weiqi; Lin, Jianping; Cen, Peilin

    2010-01-01

    The 5-aminolevulinate (ALA) synthase gene (hemA) from Agrobacterium radiobacter zju-0121, which was cloned previously in our laboratory, contains several rare codons. To enhance the expression of this gene, Escherichia coli Rosetta(DE3), which is a rare codon optimizer strain, was picked out as the host to construct an efficient recombinant strain. Cell extracts of the recombinant E. coli were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under the appropriate conditions. The results indicated that the activity of ALA synthase expressed in Rosetta(DE3)/pET-28a(+)-hemA was about 20% higher than that in E. coli BL21(DE3). Then the effects of precursors (glycine and succinate) and glucose, which is an inhibitor for ALA dehydratase as well as the carbon sources for cell growth, on the production of 5-aminolevulinate were investigated. Based on an optimal fed-batch culture system described in our previous work, up to 6.5 g/l (50 mM) ALA was produced in a 15-l fermenter.

  4. 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.

  5. 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

  6. Mechanisms of 5-aminolevulic acid ester uptake in mammalian cells

    PubMed Central

    Rodriguez, Lorena; Batlle, Alcira; Di Venosa, Gabriela; Battah, Sinan; Dobbin, Paul; MacRobert, Alexander J; Casas, Adriana

    2006-01-01

    The porphyrin precursor 5-aminolevulinic acid (ALA) is being widely used in photodynamic therapy of cancer. Improvement in ALA delivery has been sought through the use of ALA derivatives, in particular the esterification of ALA with aliphatic alcohols, which in certain cases can improve cellular penetration and selectivity. ALA uptake systems appear to be distinctive for each cell type. The LM3 mammary adenocarcinoma cell line takes ALA up by BETA transporters. In this work, we investigated ALA derivative transport systems through the inhibition of radiolabelled ALA uptake in the LM3 cells. We also performed inhibition studies of γ-aminobutyric acid (GABA) uptake. The more lipohilic ALA derivatives hexyl-ALA and undecanoyl-ALA inhibit ALA uptake, whereas methyl-ALA, R, S-ALA-2-(hydroxymethyl)tetrahydropyranyl ester and the dendron aminomethane tris methyl 5-ALA does not inhibit ALA uptake. A similar pattern was found for GABA, except that the dendron inhibited GABA uptake. However, hexyl-ALA and undecanoyl-ALA are not taken up by BETA transporters, but by simple diffusion, although they still inhibit ALA uptake by binding to the cell membrane. These results show that different modifications to the ALA molecule lead to different uptake mechanisms. Whereas ALA is taken up by BETA transporters, none of the ALA derivatives shares the same mechanism. Knowledge of the mechanisms of ALA derivatives entry into the cells is essential to understand and improve ALA-mediated PDT and to the design of new ALA derivatives that may be taken up at a higher rate than ALA. PMID:16432502

  7. 5-aminolevulinic acid induced protoporphyrin IX as a fluorescence marker for quantitative image analysis of high-grade dysplasia in Barrett's esophagus cellular models

    NASA Astrophysics Data System (ADS)

    Yeh, Shu-Chi Allison; Sahli, Samir; Andrews, David W.; Patterson, Michael S.; Armstrong, David; Provias, John; Fang, Qiyin

    2015-03-01

    Early detection and treatment of high-grade dysplasia (HGD) in Barrett's esophagus may reduce the risk of developing esophageal adenocarcinoma. Confocal endomicroscopy (CLE) has shown advantages over routine white-light endoscopic surveillance with biopsy for histological examination; however, CLE is compromised by insufficient contrast and by intra- and interobserver variation. An FDA-approved PDT photosensitizer was used here to reveal morphological and textural features similar to those found in histological analysis. Support vector machines were trained using the aforementioned features to obtain an automatic and robust detection of HGD. Our results showed 95% sensitivity and 87% specificity using the optimal feature combination and demonstrated the potential for extension to a three-dimensional cell model.

  8. Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas

    PubMed Central

    Montcel, Bruno; Mahieu-Williame, Laurent; Armoiry, Xavier; Meyronet, David; Guyotat, Jacques

    2013-01-01

    5-ALA-induced protoporphyrin IX (PpIX) fluorescence enables to guiding in intra-operative surgical glioma resection. However at present, it has yet to be shown that this method is able to identify infiltrative component of glioma. In extracted tumor tissues we measured a two-peaked emission in low grade gliomas and in the infiltrative component of glioblastomas due to multiple photochemical states of PpIX. The second emission peak appearing at 620 nm (shifted by 14 nm from the main peak at 634 nm) limits the sensibility of current methods to measured PpIX concentration. We propose new measured parameters, by taking into consideration the two-peaked emission, to overcome these limitations in sensitivity. These parameters clearly distinguish the solid component of glioblastomas from low grade gliomas and infiltrative component of glioblastomas. PMID:23577290

  9. 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.

  10. Dietary linoleic acid requirements in the presence of α-linolenic acid are lower than the historical 2 % of energy intake value, study in rats.

    PubMed

    Choque, Benjamin; Catheline, Daniel; Delplanque, Bernadette; Guesnet, Philippe; Legrand, Philippe

    2015-04-14

    Previous studies on rats and human subjects have established that the linoleic acid (LA) requirement is 2 % of the total energy intake (en%), but is obtained in the absence of α-linolenic acid (ALA) and consequently appear to be overestimated. This raises questions since a recent study including ALA has suggested to divide the historical value by four. However, this recent study has remained inconclusive because the animals used were not totally LA-deficient animals. For the first time, the present study was especially designed using physiological and biochemical markers and performed in two steps: (1) to achieve a specific n-6 fatty acid deficiency model using growing male rats fed either a 0 en% from LA/0 en% from ALA (0LA/0ALA), 0LA/0·5ALA or 2LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet; and (2) to refine the required level of LA in the presence of ALA using rats fed either a 0LA/0ALA, 0·5LA/0·5ALA, 1LA/0·5ALA, 1·5LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet. The first step shows that the best LA deficiency model was obtained using rats fed the 0LA/0ALA diet, born from female rats fed the 0LA/0·5ALA diet. The second step demonstrates that in growing rats, LA deficiency was corrected with an intake of 1-1·5 en% from LA and 0·5 en% from ALA. These data suggest that the requirements in humans should be revisited, considering the presence of ALA to set up the recommendation for LA.

  11. 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

  12. LCAA, a Novel Factor Required for Magnesium Protoporphyrin Monomethylester Cyclase Accumulation and Feedback Control of Aminolevulinic Acid Biosynthesis in Tobacco1[W][OA

    PubMed Central

    Albus, Christin Anne; Salinas, Annabel; Czarnecki, Olaf; Kahlau, Sabine; Rothbart, Maxi; Thiele, Wolfram; Lein, Wolfgang; Bock, Ralph; Grimm, Bernhard; Schöttler, Mark Aurel

    2012-01-01

    Low Chlorophyll Accumulation A (LCAA) antisense plants were obtained from a screen for genes whose partial down-regulation results in a strong chlorophyll deficiency in tobacco (Nicotiana tabacum). The LCAA mutants are affected in a plastid-localized protein of unknown function, which is conserved in cyanobacteria and all photosynthetic eukaryotes. They suffer from drastically reduced light-harvesting complex (LHC) contents, while the accumulation of all other photosynthetic complexes per leaf area is less affected. As the disturbed accumulation of LHC proteins could be either attributable to a defect in LHC biogenesis itself or to a bottleneck in chlorophyll biosynthesis, chlorophyll synthesis rates and chlorophyll synthesis intermediates were measured. LCAA antisense plants accumulate magnesium (Mg) protoporphyrin monomethylester and contain reduced protochlorophyllide levels and a reduced content of CHL27, a subunit of the Mg protoporphyrin monomethylester cyclase. Bimolecular fluorescence complementation assays confirm a direct interaction between LCAA and CHL27. 5-Aminolevulinic acid synthesis rates are increased and correlate with an increased content of glutamyl-transfer RNA reductase. We suggest that LCAA encodes an additional subunit of the Mg protoporphyrin monomethylester cyclase, is required for the stability of CHL27, and contributes to feedback-control of 5-aminolevulinic acid biosynthesis, the rate-limiting step of chlorophyll biosynthesis. PMID:23085838

  13. Human glioblastoma stem-like cells accumulate protoporphyrin IX when subjected to exogenous 5-aminolaevulinic acid, rendering them sensitive to photodynamic treatment.

    PubMed

    Schimanski, Adrian; Ebbert, Lara; Sabel, Michael C; Finocchiaro, Gaetano; Lamszus, Katrin; Ewelt, Christian; Etminan, Nima; Fischer, Johannes C; Sorg, Rüdiger V

    2016-10-01

    Glioblastoma (GBM) is the most frequent and lethal primary brain tumor in adults. Despite multimodal therapy combining resection, radio- and alkylating chemotherapy, disease recurrence is universal and prognosis of patients is poor. Glioblastoma stem-like cells (GSC), which can be grown as neurospheres from primary tumors in vitro, appear to be resistant to the established therapies and are suspected to be the driving force for disease recurrence. Thus, efficacy of emerging therapies may depend on targeting GSC. 5-aminolaevulinic acid-mediated photodynamic therapy (5-ALA/PDT) is a promising therapeutic approach in GBM. It utilizes the selective accumulation of the photosensitizer protoporphyrin IX (PPIX) in GBM cells after application of 5-ALA. When exposed to laser light of 635nm wavelength, PPIX initiates a photochemical reaction resulting in the generation of reactive oxygen species, which kill the tumor cells. Whether GSC accumulate PPIX and are sensitive to 5-ALA/PDT is currently unknown. Therefore, human GSC were derived from primary tumors and grown as neurospheres under serum free conditions. When subjected to exogenous 5-ALA, a dose- and time-dependent accumulation of PPIX in GSC was observed by flow cytometry, which varied between individual GSC preparations. Subsequent exposure to laser light of 635nm wavelength substantially killed GSC, whereas treatment with 5-ALA or exposure to laser light only had no effect. LD50 values differed between GSC preparations, but were negatively correlated with PPIX accumulation in GSC. In summary, we report for the first time that glioblastoma stem-like cells accumulate PPIX when subjected to 5-aminolaevulinic acid and are sensitive to 5-aminolaevulinc acid based photodynamic therapy. PMID:27588717

  14. Dairy fat blends high in α-linolenic acid are superior to n-3 fatty-acid-enriched palm oil blends for increasing DHA levels in the brains of young rats.

    PubMed

    Du, Qin; Martin, Jean-Charles; Agnani, Genevieve; Pages, Nicole; Leruyet, Pascale; Carayon, Pierre; Delplanque, Bernadette

    2012-12-01

    Achieving an appropriate docosahexaenoic acid (DHA) status in the neonatal brain is an important goal of neonatal nutrition. We evaluated how different dietary fat matrices improved DHA content in the brains of both male and female rats. Forty rats of each gender were born from dams fed over gestation and lactation with a low α-linolenic acid (ALA) diet (0.4% of fatty acids) and subjected for 6 weeks after weaning to a palm oil blend-based diet (10% by weight) that provided either 1.5% ALA or 1.5% ALA and 0.12% DHA with 0.4% arachidonic acid or to an anhydrous dairy fat blend that provided 1.5% or 2.3% ALA. Fatty acids in the plasma, red blood cells (RBCs) and whole brain were determined by gas chromatography. The 1.5% ALA dairy fat was superior to both the 1.5% ALA palm oil blends for increasing brain DHA (14.4% increase, P<.05), and the 2.3% ALA dairy blend exhibited a further increase that could be ascribed to both an ALA increase and n-6/n-3 ratio decrease. Females had significantly higher brain DHA due to a gender-to-diet interaction, with dairy fats attenuating the gender effect. Brain DHA was predicted with a better accuracy by some plasma and RBC fatty acids when used in combination (R(2) of 0.6) than when used individually (R(2)=0.47 for RBC n-3 docosapentaenoic acid at best). In conclusion, dairy fat blends enriched with ALA appear to be an interesting strategy for achieving optimal DHA levels in the brain of postweaning rats. Human applications are worth considering.

  15. 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

  16. Semi-automated Volumetric and Morphological Assessment of Glioblastoma Resection with Fluorescence-Guided Surgery

    PubMed Central

    Cordova, J. Scott; Gurbani, Saumya S.; Holder, Chad A.; Olson, Jeffrey J.; Schreibmann, Eduard; Shi, Ran; Guo, Ying; Shu, Hui-Kuo G.; Shim, Hyunsuk; Hadjipanayis, Costas G.

    2016-01-01

    Purpose Glioblastoma (GBM) neurosurgical resection relies on contrast-enhanced MRI-based neuronavigation. However, it is well-known that infiltrating tumor extends beyond contrast enhancement. Fluorescence-guided surgery (FGS) using 5-aminolevulinic acid (5-ALA) was evaluated to improve extent of resection (EOR) of GBMs. Pre-operative morphological tumor metrics were also assessed. Procedures Thirty patients from a Phase II trial evaluating 5-ALA FGS in newly diagnosed GBM were assessed. Tumors were segmented pre-operatively to assess morphological features as well as post-operatively to evaluate EOR and residual tumor volume (RTV). Results Median EOR and RTV were 94.3% and 0.821 cm3, respectively. Pre-operative surface area to volume ratio and RTV were significantly associated with overall survival, even when controlling for the known survival confounders. Conclusions This study supports claims that 5-ALA FGS is helpful at decreasing tumor burden and prolonging survival in GBM. Moreover, morphological indices are shown to impact both resection and patient survival. PMID:26463215

  17. Fluorescence diagnostics in oncological gynecology

    NASA Astrophysics Data System (ADS)

    Belyaeva, Ludmila A.; Adamyan, Leila V.; Kozachenko, Vladimir P.; Stratonnikov, Alexander A.; Stranadko, Eugene F.; Loschenov, Victor B.

    2003-10-01

    The method of fluorescent diagnostics (FD) of tumors is a promising tool that may allow to increase sensitivity of tumor detection especially at initial stages. One of the most promising photosensitizers today is 5-aminolevulinic acid (5-ALA) that, actually, is not photosensitizer itself but precursor of protoporphyrin IX (PpIX). This paper deals with cancer diagnostics in gynecology by means of ALA-induced Pp IX laser-fluorescence spectroscopy. The tissue fluorescence spectra in vivo were studied in patients with various pathologies of ovaries, uterine and vulva after 5-aminolevulinic acid administration. It was shown that different pathologies varies in accumulation of Pp IX. Coefficient of fluorescence kf for normal tissue is not high, but exceptions are endometrium and mucous membrane of uterine tubes. Benign tumors of uterus and ovary have low values of kf, but polyps of endometrium exhibit high kf. Optical express-biopsy is important for diagnosis of ovarian cancer and micrometastatic spread. Coefficients of diagnostic contrast were determined for cancer of endometrium, cervical cancer, vulvar cancer.

  18. 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.

  19. Tumoricidal effects of nanomaterials in HeLa cell line

    NASA Astrophysics Data System (ADS)

    Fakhar-E-Alam, M.; Kishwar, S.; Khan, Y.; Siddique, M.; Atif, M.; Nur, O.; Willander, M.

    2011-11-01

    The current study exhibits the cellular response of HeLa (cervical cancer) cells to metal oxides ultrafine nanomaterials e.g. manganese dioxide nanowires (MnO2 NRs), iron oxide nanoparticles (Fe2O3 NPs) and zinc oxide nanorods (ZnO NRs) as bare and as conjugated with photosensitizers. For cytotoxic evaluations, the cellular morphology, (MTT) assay, reactive oxygen species (ROS) production were used for cases with and without photo sensitizer as well illuminated with UV-visible laser exposed conditions. Three different photosensitizers were tested. These are 5-aminolevulinic acid (5-ALA), Photofrin® and protopor phyrin dimethyl ester (PPDME). Significant loss in cell viability was noted with 100-500 μg/ml in bare and conjugated forms of the metal oxides used. The effect was insignificant with lower concentrations (0.05-50 μg/ml). While notable anticancer effect of 5-ALA under 30 J/cm2 of diode laser irradiation was noted as compared to other photo sensitizer. By increasing the UV irradiation time of labeled cells, generation of ROS was observed, indicating the possibility of achieving efficient photodynamic therapy (PDT).

  20. Colloidal gold nanorings for improved photodynamic therapy through field-enhanced generation of reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Hu, Yue; Yang, Yamin; Wang, Hongjun; Du, Henry

    2013-02-01

    Au nanostructures that exhibit strong localized surface plasmon resonance (SPR) have excellent potential for photo-medicine, among a host of other applications. Here, we report the synthesis and use of colloidal gold nanorings (GNRs) with potential for enhanced photodynamic therapy of cancer. The GNRs were fabricated via galvanic replacement reaction of sacrificial Co nanoparticles in gold salt solution with low molecular weight (Mw = 2,500) poly(vinylpyrrolidone) (PVP) as a stabilizing agent. The size and the opening of the GNRs were controlled by the size of the starting Co particles and the concentration of the gold salt. UV-Vis absorption measurements indicated the tunability of the SPR of the GNRs from 560 nm to 780 nm. MTT assay showed that GNRs were non-toxic and biocompatible when incubated with breast cancer cells as well as the healthy counterpart cells. GNRs conjugated with 5-aminolevulinic acid (5-ALA) photosensitizer precursor led to elevated formation of reactive oxygen species and improved efficacy of photodynamic therapy of breast cancer cells under light irradiation compared to 5-ALA alone. These results can be attributed to significantly enhance localized electromagnetic field of the GNRs.

  1. Study on salt tolerance with YHem1 transgenic canola (Brassica napus).

    PubMed

    Sun, Xin-E; Feng, Xin-Xin; Li, Cui; Zhang, Zhi-Ping; Wang, Liang-Ju

    2015-06-01

    5-Aminolevulinic acid (5-ALA) has been suggested for improving plant salt tolerance via exogenous application. In this study, we used a transgenic canola (Brassica napus), which contained a constituted gene YHem1 and biosynthesized more 5-ALA, to study salt stress responses. In a long-term pot experiment, the transgenic plants produced higher yield under 200 mmol L(-1) NaCl treatment than the wild type (WT). In a short-term experiment, the YHem1 transformation accelerated endogenous 5-ALA metabolism, leading to more chlorophyll accumulation, higher diurnal photosynthetic rates and upregulated expression of the gene encoding Rubisco small subunit. Furthermore, the activities of antioxidant enzymes, including superoxide dismutase, guaiacol peroxidase, catalase and ascorbate peroxidase, were significantly higher in the transgenic plants than the WT, while the levels of O2 ·(-) and malondialdehyde were lower than the latter. Additionally, the Na(+) content was higher in the transgenic leaves than that in the WT under salinity, but K(+) and Cl(-) were significantly lower. The levels of N, P, Cu, and S in the transgenic plants were also significantly lower than those in the WT, but the Fe content was significantly improved. As the leaf Fe content was decreased by salinity, it was suggested that the stronger salt tolerance of the transgenic plants was related to the higher Fe acquisition. Lastly, YHem1 transformation improved the leaf proline content, but salinity decreased rather than increased it. The content of free amino acids and soluble sugars was similarly decreased as salinity increased, but it was higher in the transgenic plants than that in the WT.

  2. Study on salt tolerance with YHem1 transgenic canola (Brassica napus).

    PubMed

    Sun, Xin-E; Feng, Xin-Xin; Li, Cui; Zhang, Zhi-Ping; Wang, Liang-Ju

    2015-06-01

    5-Aminolevulinic acid (5-ALA) has been suggested for improving plant salt tolerance via exogenous application. In this study, we used a transgenic canola (Brassica napus), which contained a constituted gene YHem1 and biosynthesized more 5-ALA, to study salt stress responses. In a long-term pot experiment, the transgenic plants produced higher yield under 200 mmol L(-1) NaCl treatment than the wild type (WT). In a short-term experiment, the YHem1 transformation accelerated endogenous 5-ALA metabolism, leading to more chlorophyll accumulation, higher diurnal photosynthetic rates and upregulated expression of the gene encoding Rubisco small subunit. Furthermore, the activities of antioxidant enzymes, including superoxide dismutase, guaiacol peroxidase, catalase and ascorbate peroxidase, were significantly higher in the transgenic plants than the WT, while the levels of O2 ·(-) and malondialdehyde were lower than the latter. Additionally, the Na(+) content was higher in the transgenic leaves than that in the WT under salinity, but K(+) and Cl(-) were significantly lower. The levels of N, P, Cu, and S in the transgenic plants were also significantly lower than those in the WT, but the Fe content was significantly improved. As the leaf Fe content was decreased by salinity, it was suggested that the stronger salt tolerance of the transgenic plants was related to the higher Fe acquisition. Lastly, YHem1 transformation improved the leaf proline content, but salinity decreased rather than increased it. The content of free amino acids and soluble sugars was similarly decreased as salinity increased, but it was higher in the transgenic plants than that in the WT. PMID:25220348

  3. Fluorescence imaging and spectroscopy of ALA-induced protoporphyrin IX preferentially accumulated in tumor tissue

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Baumgartner, Reinhold; Beyer, Wolfgang; Knuechel, Ruth; Koerner, T. O.; Kriegmair, M.; Rick, Kai; Steinbach, Pia; Hofstetter, Alfons G.

    1995-12-01

    In a clinical pilot study performed on 104 patients suffering from bladder cancer it could be shown that intravesical instillation of a solution of 5-aminolevulinic acid (5-ALA) induces a tumorselective accumulation of Protoporphyrin IX (PPIX). Malignant lesions could be detected with a sensitivity of 97% and a specificity of 67%. The Kr+-laser as excitation light source could successfully be replaced by a filtered short arc Xe-lamp. Its emission wavelength band (375 nm - 440 nm) leads to an efficiency of 58% for PPIX- excitation compared to the laser. Two-hundred-sixty mW of output power at the distal end of a slightly modified cystoscope could be obtained. This is sufficient for recording fluorescence images with a target integrating color CCD-camera. Red fluorescence and blue remitted light are displayed simultaneously. Standard white light observation is possible with the same instrumentation. Pharmacokinetic measurements were performed on 18 patients after different routes of 5-ALA application (oral, inhalation and intravesical instillation). PPIX-fluorescence measurements were made on the skin and on the blood plasma. Pharmacokinetic of 5-ALA could be performed on blood plasma. Endoscopical florescence spectroscopy showed the high fluorescence contrast between tumor and normal tissue with a mean value of 10.7. Forthcoming clinical multicenter studies require an objective measure of the fluorescence intensity. Monte Carlo computer simulations showed that artifacts due to observation geometry and varying absorption can largely be reduced by ratioing fluorescence (red channel of camera) to remission (blue channel). Real time image ratioing provides false color images with a reliable fluorescence information.

  4. Role of ALA sensitivity in HepG2 cell in the presence of diode laser

    NASA Astrophysics Data System (ADS)

    Fakhar-E-Alam, M.; Atif, M.; Alsalhi, M. S.; Siddique, M.; Kishwar, S.; Qadir, M. I.; Willander, M.

    2011-05-01

    5-aminolevulinic acid (ALA) being an amazing second generation photosensitizer was studied as photodamaging drug on hepatocellular carcinoma (HepG2) cells. The mentioned photosensitizer is converted to PpIX in HepG2 cells in vitro, inducing haem in the cell causing generation of singlet oxygen leading to cell apoptosis. Cell uptake of 5-ALA was evaluated with different concentrations (ranging from 0-800 μg/ml) for 0-49 h incubation period. ALA administered in HepG2 cells is converted into Protoporphyrin IX (PpIX) which has a short half life and constitute a good hematoporphyrin derivative (HPD). Cytotoxicity of ALA in dark and cellular viability without ALA in the presence of light was studied, showing minimal toxic effects in dark with no photodamaging effect on mentioned cells in absence of ALA were observed. The optimal uptake of photosensitizer (5-ALA) in HepG2 cells was investigated by means of spectrophotometeric measurements, cellular viability was determined by means of neutral red assay (NRA). It was observed that with different concentrations (0-800 μg/ml) of ALA or light doses (0-160 J/cm2), there were no significant effect on cellular viability when studied independently. The novel of photocytotoxic study indicates that light dose of 120 J/cm2 produces convincing Photodynamic therapy (PDT) results for HepG2 cells incubated with 262 μg/ml of 5-ALA deducting that HepG2 cell line is sensitive to ALA mediated PDT. Finally morphological changes in HePG2 cells were determined before and after ALA-mediated PDT by confocal microscopy.

  5. Fluorescence image-guided photodynamic therapy of cancer cells using a scanning fiber endoscope

    NASA Astrophysics Data System (ADS)

    Woldetensae, Mikias H.; Kirshenbaum, Mark R.; Kramer, Greg M.; Zhang, Liang; Seibel, Eric J.

    2013-03-01

    A scanning fiber endoscope (SFE) and the cancer biomarker 5-aminolevulinic acid (5-ALA) were used to fluorescently detect and destroy superficial cancerous lesions, while experimenting with different dosimetry levels for concurrent or sequential imaging and laser therapy. The 1.6-mm diameter SFE was used to fluorescently image a confluent monolayer of A549 human lung cancer cells from culture, previously administered with 5 mM solution of 5-ALA for 4 hours. Twenty hours after therapy, cell cultures were stained to distinguish between living and dead cells using a laser scanning confocal microscope. To determine relative dosimetry for photodynamic therapy (PDT), 405-nm laser illumination was varied from 1 to 5 minutes with power varying from 5 to 18 mW, chosen to compare equal amounts of energy delivered to the cell culture. The SFE produced 500-line images of fluorescence at 15 Hz using the red detection channel centered at 635 nm. The results show that PDT of A549 cancer cell monolayers using 405nm light for imaging and 5-ALAinduced PpIX therapy was possible using the same SFE system. Increased duration and power of laser illumination produced an increased area of cell death upon live/dead staining. The ultrathin and flexible SFE was able to direct PDT using wide-field fluorescence imaging of a monolayer of cultured cancer cells after uptaking 5-ALA. The correlation between light intensity and duration of PDT was measured. Increased length of exposure and decreased light intensity yields larger areas of cell death than decreased length of exposure with increased light intensity.

  6. 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.

  7. 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.

  8. 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.

  9. Amino acids of ricin and its polypeptides.

    PubMed

    Chakravartula, Srinivas V S; Guttarla, Nagaraj

    2008-02-15

    Ricin and its corresponding polypeptides (A & B chain) were purified from castor seed. The molecular weight of ricin subunits were 29,000 and 28,000 daltons. The amino acids in ricin determined were Asp45 The22 Ser40 Glu53 Cys4 Gly96 His5 Ile21 Leu33 Lys20 Met4 Phe13 Pro37 Tyr11 Ala45 Val23 Arg20 indicating that ricin contains approximately 516 amino acid residues. The amino acids of the two subunits of ricin A and B chains were Asp23 The12 Ser21 Glu29 Cys2 Gly48 His3 Ile12, Leu17 Lys10 Met2 Phe6 Pro17 Tyr7 Ala35 Val13 Arg13 while in B chain the amino acids were Asp22 The10 Ser19 Glu25 Cys2 Gly47 His1 Ile10, Leu15 Lys11 Met1 Phe7 Pro6 Tyr5 Ala32Val11 Arg10. The total helical content of ricin came around 53.6% which is a new observation. PMID:18266157

  10. 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.

  11. Brown but not white adipose cells synthesize omega-3 docosahexaenoic acid in culture.

    PubMed

    Qin, Xia; Park, Hui Gyu; Zhang, Ji Yao; Lawrence, Peter; Liu, Guowen; Subramanian, Nivetha; Kothapalli, Kumar S D; Brenna, J Thomas

    2016-01-01

    Adipose tissue is a complex endocrine organ which coordinates several crucial biological functions including fatty acid metabolism, glucose metabolism, energy homeostasis, and immune function. Brown adipose tissue (BAT) is most abundant in young infants during the brain growth spurt when demands for omega-3 docosahexaenoic acid (DHA, 22:6n-3) is greatest for brain structure. Our aim was to characterize relative biosynthesis of omega-3 long chain polyunsaturated fatty acids (LCPUFA) from precursors in cultured white (WAT) and brown (BAT) cells and study relevant gene expression. Mouse WAT and BAT cells were grown in regular DMEM media to confluence, and differentiation was induced. At days 0 and 8 cells were treated with albumin bound d5-18:3n-3 (d5-ALA) and analyzed 24h later. d5-ALA increased cellular eicosapentaenoic acid (EPA, 20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) in undifferentiated BAT cells, whereas differentiated BAT cells accumulated 20:4n-3, EPA and DPA. DHA as a fraction of total omega-3 LCPUFA was greatest in differentiated BAT cells compared to undifferentiated cells. Undifferentiated WAT cells accumulated EPA, whereas differentiated cells accumulated DPA. WAT accumulated trace newly synthesized DHA. Zic1 a classical brown marker and Prdm16 a key driver of brown fat cell fate are expressed only in BAT cells. Ppargc1a is 15 fold higher in differentiated BAT cells. We conclude that in differentiated adipose cells accumulating fat, BAT cells but not WAT cells synthesize DHA, supporting the hypothesis that BAT is a net producer of DHA.

  12. 5-Aminolevolinic acid mitigates the cadmium-induced changes in Brassica napus as revealed by the biochemical and ultra-structural evaluation of roots.

    PubMed

    Ali, Basharat; Tao, Qiaojing; Zhou, Yuanfei; Gill, Rafaqat A; Ali, Shafaqat; Rafiq, Muhammad T; Xu, Ling; Zhou, Weijun

    2013-06-01

    In the present study, the ameliorating effects of 5-aminolevulinic acid (ALA) under cadmium (Cd) stress conditions were studied with special emphasis on root morphology and ultra-structure in oilseed rape. For this purpose, plants were treated hydroponically at three different Cd levels (0, 100, 500μM) and foliar spray of ALA with three concentrations (0, 12.5, 25mg/l) simultaneously. The results showed that foliar application of ALA improved the plant growth, root morphology and reduced the reactive oxygen species and malondialdehyde contents in roots under Cd stress conditions. The higher concentration of Cd (500μM) decreased the activities of antioxidants enzymes like catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and glutathione reductase (GR) and also reduced the oxidized glutathione and total glutathione contents in roots. Application of ALA at 25mg/l dosage significantly enhanced the antioxidant activities e.g. APX, SOD, POD, and GSH contents under Cd stress. The microscopic micrographs showed that application of exogenous ALA improved the cell structure under Cd toxicity. A whole cell with developed nucleus, nuclear membrane, smooth cell wall, continuous endoplasmic reticulum, and well shaped mitochondria was observed under the combine application of ALA and Cd. These results suggest that, application of ALA helped the plants to improve root growth, root antioxidant enzymes, and ultra-structural changes in root tip cells under fifteen days Cd-induced stress. PMID:23490193

  13. Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia

    PubMed Central

    Dufay, J. Noelia; Steele, Shelby L.; Gaston, Daniel; Nasrallah, Gheyath K.; Coombs, Andrew J.; Liwski, Robert S.; Fernandez, Conrad V.; Berman, Jason N.; McMaster, Christopher R.

    2016-01-01

    Sideroblastic anemias are acquired or inherited anemias that result in a decreased ability to synthesize hemoglobin in red blood cells and result in the presence of iron deposits in the mitochondria of red blood cell precursors. A common subtype of congenital sideroblastic anemia is due to autosomal recessive mutations in the SLC25A38 gene. The current treatment for SLC25A38 congenital sideroblastic anemia is chronic blood transfusion coupled with iron chelation. The function of SLC25A38 is not known. Here we report that the SLC25A38 protein, and its yeast homolog Hem25, are mitochondrial glycine transporters required for the initiation of heme synthesis. To do so, we took advantage of the fact that mitochondrial glycine has several roles beyond the synthesis of heme, including the synthesis of folate derivatives through the glycine cleavage system. The data were consistent with Hem25 not being the sole mitochondrial glycine importer, and we identify a second SLC25 family member Ymc1, as a potential secondary mitochondrial glycine importer. Based on these findings, we observed that high levels of exogenous glycine, or 5-aminolevulinic acid (5-Ala) a metabolite downstream of Hem25 in heme biosynthetic pathway, were able to restore heme levels to normal in yeast cells lacking Hem25 function. While neither glycine nor 5-Ala could ameliorate SLC25A38 congenital sideroblastic anemia in a zebrafish model, we determined that the addition of folate with glycine was able to restore hemoglobin levels. This difference is likely due to the fact that yeast can synthesize folate, whereas in zebrafish folate is an essential vitamin that must be obtained exogenously. Given the tolerability of glycine and folate in humans, this study points to a potential novel treatment for SLC25A38 congenital sideroblastic anemia. PMID:26821380

  14. Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia.

    PubMed

    Fernández-Murray, J Pedro; Prykhozhij, Sergey V; Dufay, J Noelia; Steele, Shelby L; Gaston, Daniel; Nasrallah, Gheyath K; Coombs, Andrew J; Liwski, Robert S; Fernandez, Conrad V; Berman, Jason N; McMaster, Christopher R

    2016-01-01

    Sideroblastic anemias are acquired or inherited anemias that result in a decreased ability to synthesize hemoglobin in red blood cells and result in the presence of iron deposits in the mitochondria of red blood cell precursors. A common subtype of congenital sideroblastic anemia is due to autosomal recessive mutations in the SLC25A38 gene. The current treatment for SLC25A38 congenital sideroblastic anemia is chronic blood transfusion coupled with iron chelation. The function of SLC25A38 is not known. Here we report that the SLC25A38 protein, and its yeast homolog Hem25, are mitochondrial glycine transporters required for the initiation of heme synthesis. To do so, we took advantage of the fact that mitochondrial glycine has several roles beyond the synthesis of heme, including the synthesis of folate derivatives through the glycine cleavage system. The data were consistent with Hem25 not being the sole mitochondrial glycine importer, and we identify a second SLC25 family member Ymc1, as a potential secondary mitochondrial glycine importer. Based on these findings, we observed that high levels of exogenous glycine, or 5-aminolevulinic acid (5-Ala) a metabolite downstream of Hem25 in heme biosynthetic pathway, were able to restore heme levels to normal in yeast cells lacking Hem25 function. While neither glycine nor 5-Ala could ameliorate SLC25A38 congenital sideroblastic anemia in a zebrafish model, we determined that the addition of folate with glycine was able to restore hemoglobin levels. This difference is likely due to the fact that yeast can synthesize folate, whereas in zebrafish folate is an essential vitamin that must be obtained exogenously. Given the tolerability of glycine and folate in humans, this study points to a potential novel treatment for SLC25A38 congenital sideroblastic anemia.

  15. Vitamin D as a potential enhancer of aminolevulinate-based photodynamic therapy for nonmelanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Anand, Sanjay; Atanaskova, Natasha; Wilson, Clara

    2010-02-01

    Vitamin D3 (Vit D3) is a hormone essential for normal bone and cardiovascular health, and may participate in preventing nonmelanoma skin cancers (NMSC). Calcitriol (1,25 dihydroxyD3) is the active form of the hormone. We showed previously that calcitriol is a potent inducer of protoporphyrin IX (PpIX) in skin keratinocytes grown in organotypic cultures. Here, we investigated the ability of Vit D3 to enhance PpIX levels within skin tumors in vivo. Squamous tumors, generated by chemical carcinogenesis in mice, were pretreated for 3 days with topical calcitriol. Then 5-aminolevulinic acid (5-ALA) was applied topically, and PpIX levels were measured by noninvasive fluorimetry and in biopsied tissue. Calcitriol pretreatment resulted in a 3 to 4-fold elevation of PpIX in tumors, relative to no pretreatmen, providing significantly more photosensitizer available for tumor destruction. For deep tumors, topical calcitriol may not penetrate sufficiently. Therefore we explored whether systemic Vit D3, given short-term (3 days), might elevate PpIX within NMSC in a deep tumor model (subcutaneously-implanted A431 human squamous carcinoma cells). Defined amounts of calcitriol were injected into the mice for 3 d, followed by systemic 5-ALA, tissue biopsy, and confocal microscopic measurement of PpIX in frozen tissues. PpIX was clearly elevated after systemically delivered calcitriol. More work is needed, but if the amount of calcitriol required to elevate PpIX levels proves to be small, then the approach may ultimately prove attractive. Since most Americans are currently Vitamin D deficient, a small increase in calcitriol might be possible without risk of hypercalcemia.

  16. Ameliorative effects of ferulic Acid against lead acetate-induced oxidative stress, mitochondrial dysfunctions and toxicity in prepubertal rat brain.

    PubMed

    Lalith Kumar, Venkareddy; Muralidhara

    2014-12-01

    Epidemiological evidence has shown higher susceptibility of Children to the adverse effects of lead (Pb) exposure. However, experimental studies on Pb-induced neurotoxicity in prepubertal (PP) rats are limited. The present study aimed to examine the propensity of ferulic acid (FA), a commonly occurring phenolic acid in staple foods (fruits, vegetables, cereals, coffee etc.) to abrogate Pb-induced toxicity. Initially, we characterized Pb-induced adverse effects among PP rats exposed to Pb acetate (1,000-3,000 ppm in drinking water) for 5 weeks in terms of locomotor phenotype, activity of 5-aminolevulinic acid dehydratase (ALAD) in the blood, blood Pb levels and oxidative stress in brain regions. Further, the ameliorative effects of oral supplements of FA (25 mg/kg bw/day) were investigated in PP rats exposed to Pb (3,000 ppm). Pb intoxication increased the locomotor activity and FA supplements partially reversed the phenotype, while the reduced ALAD activity was also restored. FA significantly abrogated the enhanced oxidative stress in cerebellum (Cb) and hippocampus (Hc) as evidenced in terms of ROS generation, lipid peroxidation and protein carbonyls. Further, Pb-mediated perturbations in the glutathione levels and activity of enzymic antioxidants were also markedly restored. Furthermore, the protective effect of FA was discernible in striatum in terms of reduced oxidative stress, restored cholinergic activity and dopamine levels. Interestingly, reduced activity levels of mitochondrial complex I in Cb and enhanced levels in Hc among Pb-intoxicated rats were ameliorated by FA supplements. FA also decreased the number of damaged cells in cornu ammonis area CA1 and dentate gyrus as reflected by the histoarchitecture of Hc among Pb intoxicated rats. Collectively, our findings in the PP model allow us to hypothesize that ingestion of common phenolics such as FA may significantly alleviate the neurotoxic effects of Pb which may be largely attributed to its ability

  17. Application of Titanium Dioxide (TiO2) Nanoparticles in Photodynamic Therapy (PDT) of an Experimental Tumor

    NASA Astrophysics Data System (ADS)

    Miyoshi, Norio; Kume, Kyo; Tsutumi, Kotaro; Fukunaga, Yukihiro; Ito, Shinnji; Imamura, Yoshiaki; Bibin, Andriana B.

    2011-12-01

    Nano-sized particles has been used for the photodynamic and sonodynamic treatments of pre-clinical cancer study in previous studies [1-7]. In this study, the 5-aminolevulinic acid (5-ALA) solution mixed with TiO2 nanoparticles was oral-administrated into the nude mouse transplanted under the skin with a human prostate cancer cell line. The experimental tumor model tissue (7×7×7 mm3) was measured of the size at different times after the photodynamic therapy (PDT) by laser to take a growth curve of the tumor. The treatment efficacy was jugged from the growth curves comparing different conditions. In the presence of the nanoparticle, the PDT treatment effect was enhanced those in the absence of the particles. Furthermore, the sonodynamic therapy (SDT) effect also enhanced with the nanoparticle to produce more OH radicals by ultrasound irradiation. These combination therapy of PDT and SDT with nanoparticles was very effectively resulted to be useful as a clinical use in future.

  18. Photodynamic and Antibiotic Therapy in Combination to Fight Biofilms and Resistant Surface Bacterial Infections

    PubMed Central

    Barra, Federica; Roscetto, Emanuela; Soriano, Amata A.; Vollaro, Adriana; Postiglione, Ilaria; Pierantoni, Giovanna Maria; Palumbo, Giuseppe; Catania, Maria Rosaria

    2015-01-01

    Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, light and O2, has been principally considered for the treatment of specific types of cancers, other applications exist, including the treatment of infections. Unfortunately, PDT does not always guarantee full success since it exerts lethal effects only in cells that have taken up a sufficient amount of photosensitizer and have been exposed to adequate light doses, conditions that are not always achieved. Based on our previous experience on the combination PDT/chemotherapy, we have explored the possibility of fighting bacteria that commonly crowd infected surfaces by combining PDT with an antibiotic, which normally does not harm the strain at low concentrations. To this purpose, we employed 5-aminolevulinic acid (5-ALA), a pro-drug that, once absorbed by proliferating bacteria, is converted into the natural photosensitizer Protoporphyrin IX (PpIX), followed by Gentamicin. Photoactivation generates reactive oxygen species (ROS) which damage or kill the cell, while Gentamicin, even at low doses, ends the work. Our experiments, in combination, have been highly successful against biofilms produced by several Gram positive bacteria (i.e., Staphylococcus aureus, Staphylococcus epidermidis, etc.). This original approach points to potentially new and wide applications in the therapy of infections of superficial wounds and sores. PMID:26343645

  19. Fluorescence guidance during stereotactic biopsy

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert; Beyer, Wolfgang; Brucker, David; Ehrhardt, Andre; Fischer, Stefan; Goebel, Werner; Goetz, Marcus; Guenther, Bettina; Hennig, Georg; Herms, Jochen; Irion, Klaus-Martin; Johansson, Ann; Kienast, Yvonne; Kniebuehler, Gesa; Li, Pan; Ruehm, Adrian; Sandner, Sabine

    2012-02-01

    Objective: When a stereotactic biopsy is taken to enable histopathological diagnosis of a suspected brain tumor, it is essential to i) do this safely, that is not injure a major blood vessel and ii) to obtain relevant vital material from the tumor. We are investigating the suitability of Indocyanine Green (ICG) fluorescence for blood vessel recognition and 5- Aminolevulinic acid (5-ALA) induced Protoporphyrin IX (PpIX) fluorescence for identification of proliferative brain tumor tissue. Methods: A fiber-optic endoscopic approach was studied to generate and detect both fluorescence signals. PpIX concentrations in brain tumors have been measured by chemical extraction. Preliminary equipment was studied in a mouse model. Results: PpIX-concentrations in glioblastoma tissue showed high inner- and inter-patient variability, but each patient out of 15 with interpretable data showed at least one sample with a PpIX-concentration exceeding 2.4 μmol/l, which is easily detectable by state-of-the-art fiberoptic fluorescence spectroscopy and imaging. The imaging fluoroscope with 30,000 pixels resolution could be introduced through a position controlled stereotactic needle. ICG-fluorescence from vessels with diameters >= 0.1 mm can be detected with a contrast of 2-2.5 against surrounding tissue. Conclusion: Fluorescence detection during stereotactic biopsy might increase safety and precision of the procedure significantly.

  20. Development and clinical applications of digitized fluorescence endoscopic imaging system for the detection of early neoplasms in the oral cavity and uterine-cervix

    NASA Astrophysics Data System (ADS)

    Zheng, Wei; Tay, Sun K.; Soo, K. C.; Olivo, Malini

    2002-05-01

    A digitized fluorescence endoscopic imaging (DFEI) system combined with 5-Aminolevulinic Acid (5-ALA) induced protoporphyrin IX (PPIX) was developed for the detection of neoplasms in the oral cavity and uterine-cervix. The system has the capability of producing both the digital and video fluorescence images in real time, and also quantifying the fluorescence images. The results show that using the DFEI system associated with the fluorescence image quantification method, both high sensitivity and specificity can be achieved during the head and neck, and obstetric and gynaecology clinical trials. The red fluorescence intensity distribution in the lesion area can also be obtained after digital image processing to better understand the situation of PPIX accumulation in the tissues. Furthermore, applying the intensity ratio IR/IB at red and blue wavelength regions of the tissue targeted, where IR includes the intensity of PPIX fluorescence and red tissue autofluorescence, and IB is the intensity of diffusely back-scattered excitation blue light, different histopathological grades of lesions can be classified by the DEFI system, suggesting a significant potential of the noninvasive optical biopsy for the early cancer detection.

  1. Early [18F]FET-PET in Gliomas after Surgical Resection: Comparison with MRI and Histopathology

    PubMed Central

    Gempt, Jens; Ringel, Florian; Lapa, Constantin; Krause, Bernd Joachim

    2015-01-01

    Background The precise definition of the post-operative resection status in high-grade gliomas (HGG) is crucial for further management. We aimed to assess the feasibility of assessment of the resection status with early post-operative positron emission tomography (PET) using [18F]O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET). Methods 25 patients with the suspicion of primary HGG were enrolled. All patients underwent pre-operative [18F]FET-PET and magnetic resonance imaging (MRI). Intra-operatively, resection status was assessed using 5-aminolevulinic acid (5-ALA). Imaging was repeated within 72h after neurosurgery. Post-operative [18F]FET-PET was compared with MRI, intra-operative assessment and clinical follow-up. Results [18F]FET-PET, MRI and intra-operative assessment consistently revealed complete resection in 12/25 (48%) patients and incomplete resection in 6/25 cases (24%). In 7 patients, PET revealed discordant findings. One patient was re-resected. 3/7 experienced tumor recurrence, 3/7 died shortly after brain surgery. Conclusion Early assessment of the resection status in HGG with [18F]FET-PET seems to be feasible. PMID:26502297

  2. Phytochrome B Mediates the Regulation of Chlorophyll Biosynthesis through Transcriptional Regulation of ChlH and GUN4 in Rice Seedlings

    PubMed Central

    Kagawa, Takatoshi; Tanaka, Ayumi; Ueno, Osamu; Shimada, Hiroaki; Takano, Makoto

    2015-01-01

    Accurate regulation of chlorophyll synthesis is crucial for chloroplast formation during the greening process in angiosperms. In this study, we examined the role of phytochrome B (phyB) in the regulation of chlorophyll synthesis in rice seedlings (Oryza sativa L.) through the characterization of a pale-green phenotype observed in the phyB mutant grown under continuous red light (Rc) irradiation. Our results show that the Rc-induced chlorophyll accumulation can be divided into two components—a phyB-dependent and a phyB-independent component, and that the pale-green phenotype is caused by the absence of the phyB-dependent component. To elucidate the role of the missing component we established an Rc-induced greening experiment, the results of which revealed that several genes encoding proteins on the chlorophyll branch were repressed in the phyB mutant. Notable among them were ChlH and GUN4 genes, which encode subunit H and an activating factor of magnesium chelatase (Mg-chelatase), respectively, that were largely repressed in the mutant. Moreover, the kinetic profiles of chlorophyll precursors suggested that Mg-chelatase activity simultaneously decreased with the reduction in the transcript levels of ChlH and GUN4. These results suggest that phyB mediates the regulation of chlorophyll synthesis through transcriptional regulation of these two genes, whose products exert their action at the branching point of the chlorophyll biosynthesis pathway. Reduction of 5-aminolevulinic acid (5-ALA) synthesis could be detected in the mutant, but the kinetic profiles of chlorophyll precursors indicated that it was an event posterior to the reduction of the Mg-chelatase activity. It means that the repression of 5-ALA synthesis should not be a triggering event for the appearance of the pale-green phenotype. Instead, the repression of 5-ALA synthesis might be important for the subsequent stabilization of the pale-green phenotype for preventing excessive accumulation of hazardous

  3. Phytochrome B Mediates the Regulation of Chlorophyll Biosynthesis through Transcriptional Regulation of ChlH and GUN4 in Rice Seedlings.

    PubMed

    Inagaki, Noritoshi; Kinoshita, Keisuke; Kagawa, Takatoshi; Tanaka, Ayumi; Ueno, Osamu; Shimada, Hiroaki; Takano, Makoto

    2015-01-01

    Accurate regulation of chlorophyll synthesis is crucial for chloroplast formation during the greening process in angiosperms. In this study, we examined the role of phytochrome B (phyB) in the regulation of chlorophyll synthesis in rice seedlings (Oryza sativa L.) through the characterization of a pale-green phenotype observed in the phyB mutant grown under continuous red light (Rc) irradiation. Our results show that the Rc-induced chlorophyll accumulation can be divided into two components--a phyB-dependent and a phyB-independent component, and that the pale-green phenotype is caused by the absence of the phyB-dependent component. To elucidate the role of the missing component we established an Rc-induced greening experiment, the results of which revealed that several genes encoding proteins on the chlorophyll branch were repressed in the phyB mutant. Notable among them were ChlH and GUN4 genes, which encode subunit H and an activating factor of magnesium chelatase (Mg-chelatase), respectively, that were largely repressed in the mutant. Moreover, the kinetic profiles of chlorophyll precursors suggested that Mg-chelatase activity simultaneously decreased with the reduction in the transcript levels of ChlH and GUN4. These results suggest that phyB mediates the regulation of chlorophyll synthesis through transcriptional regulation of these two genes, whose products exert their action at the branching point of the chlorophyll biosynthesis pathway. Reduction of 5-aminolevulinic acid (5-ALA) synthesis could be detected in the mutant, but the kinetic profiles of chlorophyll precursors indicated that it was an event posterior to the reduction of the Mg-chelatase activity. It means that the repression of 5-ALA synthesis should not be a triggering event for the appearance of the pale-green phenotype. Instead, the repression of 5-ALA synthesis might be important for the subsequent stabilization of the pale-green phenotype for preventing excessive accumulation of hazardous

  4. Phytochrome B Mediates the Regulation of Chlorophyll Biosynthesis through Transcriptional Regulation of ChlH and GUN4 in Rice Seedlings.

    PubMed

    Inagaki, Noritoshi; Kinoshita, Keisuke; Kagawa, Takatoshi; Tanaka, Ayumi; Ueno, Osamu; Shimada, Hiroaki; Takano, Makoto

    2015-01-01

    Accurate regulation of chlorophyll synthesis is crucial for chloroplast formation during the greening process in angiosperms. In this study, we examined the role of phytochrome B (phyB) in the regulation of chlorophyll synthesis in rice seedlings (Oryza sativa L.) through the characterization of a pale-green phenotype observed in the phyB mutant grown under continuous red light (Rc) irradiation. Our results show that the Rc-induced chlorophyll accumulation can be divided into two components--a phyB-dependent and a phyB-independent component, and that the pale-green phenotype is caused by the absence of the phyB-dependent component. To elucidate the role of the missing component we established an Rc-induced greening experiment, the results of which revealed that several genes encoding proteins on the chlorophyll branch were repressed in the phyB mutant. Notable among them were ChlH and GUN4 genes, which encode subunit H and an activating factor of magnesium chelatase (Mg-chelatase), respectively, that were largely repressed in the mutant. Moreover, the kinetic profiles of chlorophyll precursors suggested that Mg-chelatase activity simultaneously decreased with the reduction in the transcript levels of ChlH and GUN4. These results suggest that phyB mediates the regulation of chlorophyll synthesis through transcriptional regulation of these two genes, whose products exert their action at the branching point of the chlorophyll biosynthesis pathway. Reduction of 5-aminolevulinic acid (5-ALA) synthesis could be detected in the mutant, but the kinetic profiles of chlorophyll precursors indicated that it was an event posterior to the reduction of the Mg-chelatase activity. It means that the repression of 5-ALA synthesis should not be a triggering event for the appearance of the pale-green phenotype. Instead, the repression of 5-ALA synthesis might be important for the subsequent stabilization of the pale-green phenotype for preventing excessive accumulation of hazardous

  5. Multifunctional gold nanoparticles for photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Khaing Oo, Maung Kyaw

    As an important and growing branch of photomedicine, photodynamic therapy (PDT) is being increasingly employed in clinical applications particularly for the treatment of skin cancer. This dissertation focuses on the synthesis, characterization and deployment of gold nanoparticles for enhanced PDT of fibrosarcoma cancer cells. We have developed robust strategies and methods in fabrication of gold nanoparticles with positively- and negatively-tethered surface charges by photo-reduction of gold chloride salt using branched polyethyleneimine and sodium citrate respectively. An optimal concentration window of gold salt has been established to yield the most stable and monodispersed gold nanoparticles. 5-aminolevulinic acid (5-ALA), a photosensitizing precursor, has been successfully conjugated on to positively charged gold nanoparticles through electrostatic interactions. The 5-ALA/gold nanoparticle conjugates are biocompatible and have shown to be preferably taken up by cancer cells. Subsequent light irradiation results in the generation of reactive oxygen species (ROS) in cancer cells, leading to their destruction without adverse effects on normal fibroblasts. We have demonstrated for the first time that gold nanoparticles can enhance PDT efficacy by 50% compared to the treatment with 5-ALA alone. Collected evidence has strongly suggested that this enhancement stems from the elevated formation of ROS via the strongly localized electric field of gold nanoparticles. Through single cell imaging using surface-enhanced Raman scattering enabled by the very same gold nanoparticles, we have shown that multifunctionality of gold nanoparticles can be harvested concurrently for biomedical applications in general and for PDT in specific. In other words, gold nanoparticles can be used not only for targeted drug delivery and field-enhanced ROS formation, but also for monitoring cell destructions during PDT. Finally, our COMSOL Multiphysics simulation of the size-dependent electric

  6. Long-term follow-up of topical 5-aminolaevulinic acid photodynamic therapy diode laser single session for non-melanoma skin cancer.

    PubMed

    Souza, C S; Felicio, L B A; Ferreira, J; Kurachi, C; Bentley, M V B; Tedesco, A C; Bagnato, V S

    2009-01-01

    Photodynamic therapy (PDT) is based on the association of a light source and light sensitive agents in order to cause the selective death of tumor cells. To evaluate topical 5-aminolaevulinic acid (5-ALA) and diode laser photodynamic single session therapy single session for non-melanoma skin cancer (NMSC), a long-term follow-up was performed. Nineteen Bowen's disease (BD) and 15 basal cell carcinoma (BCC) lesions were submitted to 6-h topical and occlusive 20% 5-ALA plus DMSO and EDTA, and later were exposed to 630 nm diode laser, 100 or 300 J cm(-2) dose. At 3 months tumor-free rate was 91.2% (31/34) whereas at 60 months, 57.7% (15/26), slightly higher in BCC (63.6%; 7/11). The relation between the reduction of the clinical response and the increase of tumor dimension observed at 18 months was lost at 60 months. The sBCC recurrence was earlier compared to the nBCC one. ALA-PDT offered important advantages: it is minimally invasive, an option for patients under risk of surgical complications; clinical feasibility; treatment of multiple lesions in only one session or lesions in poor healing sites and superior esthetical results. However, the recurrence rate increase after ALA-PDT diode laser single session can be observed at long-term follow-up, and the repetitive sessions, an additional advantage of the method, is strongly recommended. The clinical response and recurrence time seem to be related to the laser light dose and NMSC types/sub-types, thickness and dimension, which must be considered for the choice of the ALA-PDT.

  7. Critical role of ABCG2 in ALA-photodynamic diagnosis and therapy of human brain tumor.

    PubMed

    Ishikawa, Toshihisa; Kajimoto, Yoshinaga; Inoue, Yutaka; Ikegami, Yoji; Kuroiwa, Toshihiko

    2015-01-01

    Primary brain tumors occur in around 250,000 people per year globally. Survival rates in primary brain tumors depend on the type of tumor, patient's age, the extent of surgical tumor removal, and other factors. Photodynamic diagnosis (PDD) is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma and meningiomas, whereas clinical application of photodynamic therapy (PDT) to brain tumor therapy has just recently started. Both PDD and PDT are achieved by a photon-induced physicochemical reaction, which is induced by the excitation of porphyrins exposed to light. In fluorescence-guided gross-total resection, PDD can be achieved by the administration of 5-aminolevulinic acid (5-ALA) as the precursor of protoporphyrin IX (PpIX). Exogenously administered ALA induces biosynthesis and accumulation of PpIX, a natural photosensitizer, in cancer cells. However, ATP-binding cassette transporter ABCG2 plays a critical role in regulating the cellular accumulation of porphyrins in cancer cells and thereby its expression and function can affect the efficacy of PDD and PDT. In response to the photoreaction of porphyrins leading to oxidative stress, the nuclear factor erythroid-derived 2-related transcription factor can transcriptionally upregulate ABCG2, which may reduce the efficacy of PDD and PDT. On the other hand, certain protein kinase inhibitors potentially enhance the efficacy of PDD and PDT by blocking ABCG2-mediated porphyrin efflux from cancer cells. In this context, it is of great interest to develop ABCG2 inhibitors that can be applied to PDD or PDT for the therapy of brain tumor and other tumors.

  8. Co-expression of autophagic markers following photodynamic therapy in SW620 human colon adenocarcinoma cells

    PubMed Central

    Ziółkowska, Barbara; Woźniak, Marta; Ziółkowski, Piotr

    2016-01-01

    Photodynamic therapy (PDT) is a minimally invasive cancer treatment. It involves the combination of a photosensitizer and light of a specific wavelength to generate singlet oxygen and other reactive oxygen species that lead to tumor cell death. Autophagy is one of the pathways that tumor cells undergo during photodamage and it is common in photodynamic therapy. The aim of this study was to examine the effect of in vitro PDT on the expression of autophagy-related proteins, autophagy related 7 (Atg7), light chain 3 (LC3) and Beclin-1. Human SW620 colon carcinoma cells were treated with 5-aminolevulinic acid (ALA)-based PDT at a dose of 3 mM. The irradiation was performed using 4.5 J/cm2 total light and a fluence rate of 60 mW/cm2. Autophagy was evaluated by immunocytochemistry using specific antibodies to Atg7, Beclin-1 and LC3. The evaluation was repeated at several time points (0, 4, 8 and 24 h) following irradiation. The induction of autophagy was observed directly following the 5-ALA-mediated PDT procedure with the strongest expression of autophagy-related proteins at 4 and 8 h after irradiation as demonstrated using immunocytochemistry. It was characterized by significantly increased expression of Beclin-1, Atg7 and LC3. To the best of our knowledge this is the first study to analyze Beclin-1, Atg7 and LC3 expression in a PDT-related experiment. This study enhances the understanding of the role of autophagy in PDT, which may contribute to better and more effective tumor responses to this therapy. PMID:27485939

  9. Detection limits of 405 nm and 633 nm excited PpIX fluorescence for brain tumor detection during stereotactic biopsy

    NASA Astrophysics Data System (ADS)

    Markwardt, Niklas; Götz, Marcus; Haj-Hosseini, Neda; Hollnburger, Bastian; Sroka, Ronald; Stepp, Herbert; Zelenkov, Petr; Rühm, Adrian

    2016-04-01

    5-aminolevulinic-acid-(5-ALA)-induced protoporphyrin IX (PpIX) fluorescence may be used to improve stereotactic brain tumor biopsies. In this study, the sensitivity of PpIX-based tumor detection has been investigated for two potential excitation wavelengths (405 nm, 633 nm). Using a 200 μm fiber in contact with semi-infinite optical phantoms containing ink and Lipovenös, PpIX detection limits of 4.0 nM and 200 nM (relating to 1 mW excitation power) were determined for 405 nm and 633 nm excitation, respectively. Hence, typical PpIX concentrations in glioblastomas of a few μM should be well detectable with both wavelengths. Additionally, blood layers of selected thicknesses were placed between fiber and phantom. Red excitation was shown to be considerably less affected by blood interference: A 50 μm blood layer, for instance, blocked the 405- nm-excited fluorescence completely, but reduced the 633-nm-excited signal by less than 50%. Ray tracing simulations demonstrated that - without blood layer - the sensitivity advantage of 405 nm rises for decreasing fluorescent volume from 50-fold to a maximum of 100-fold. However, at a tumor volume of 1 mm3, which is a typical biopsy sample size, the 633-nm-excited fluorescence signal is only reduced by about 10%. Further simulations revealed that with increasing fiber-tumor distance, the signal drops faster for 405 nm. This reduces the risk of detecting tumor tissue outside the needle's coverage, but diminishes the overlap between optically and mechanically sampled volumes. While 405 nm generally offers a higher sensitivity, 633 nm is more sensitive to distant tumors and considerably superior in case of blood-covered tumor tissue.

  10. Intensified oxidative and nitrosative stress following combined ALA-based photodynamic therapy and local hyperthermia in rat tumors.

    PubMed

    Frank, Juergen; Lambert, Christine; Biesalski, Hans Konrad; Thews, Oliver; Vaupel, Peter; Kelleher, Debra K

    2003-12-20

    Oxidative stress-related changes in tumors upon localized hyperthermia (HT), 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) and their combination (ALA+HT) were examined after the observation that the antitumor effects of ALA-PDT could be significantly enhanced upon simultaneous application of HT. Rats bearing s.c. DS-sarcomas (0.6-1.0 ml) on the hind foot dorsum were anesthetized and underwent one of the following treatments: (i) ALA-PDT (375 mg/kg 5-ALA i.v.); (ii) localized HT, 43 degrees C for 60 min; (iii) combined ALA-PDT and HT [=ALA+HT]. Appropriate control experiments were also performed. After treatment, tumors were excised and rapidly frozen for later analysis of nitrosative stress (protein nitration), apoptotic events (TUNEL, caspase activation, DNA and RNA fragmentation), expression of heat shock proteins (hsp70 and HO-1), glutathione (GSH) levels and glutathione peroxidase (GPx) activity. Protein nitration was found to increase upon treatment, being especially pronounced in the ALA+HT group, and could partially be related to areas surrounding microvessels. The extent of nitrosative stress also correlated well with the appearance of the markers of apoptosis and the inhibition of in vivo tumor growth as seen in a previous study. GSH levels decreased upon treatment, the reduction being most prominent in the ALA-PDT and ALA+HT groups. GPx activity, however, showed a significant decrease only in the ALA-PDT group. Whereas hsp70 expression increased upon HT, ALA-PDT caused a decrease, and these opposing effects were nullified with ALA+HT. The results obtained point to a number of cellular mechanisms-including effects on cellular defense mechanisms and an abrogation of the heat shock defense mechanism-that may interact to achieve the potentiated tumor response rate seen in vivo upon combined treatment. PMID:14601053

  11. Enhancement and optimization of PpIX-based photodynamic therapy of skin cancer: translational studies from bench to clinic

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Anand, Sanjay; Baran, Christine; Honari, Golara; Lohser, Sara; Kyei, Angela; Bailin, Philip; Pogue, Brian W.

    2009-02-01

    Nonmelanoma skin carcinomas are the most common of all human cancers. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) has been used to treat these tumors, but has shown variable results. We are pursuing a multifaceted approach toward optimizing tumor responsiveness. First, a new paradigm is being developed in which tumors are pretreated with differentiation-inducing agents, e.g. methotrexate or Vitamin D, to enhance synthesis of protoporphyrin IX (PpIX) and improve tumor cell killing upon exposure to 635 nm light. This principle was first elucidated in cell culture studies, and has now been shown to hold true for murine skin tumors, and for a human subcutaneous tumor model (A431 cells injected in nude mice). Clinical trials to test methotrexate and Vitamin D as augmenting agents for ALA-PDT of nonmelanoma skin cancer are being designed. Second, better methods to measure PpIX in patients' skin tumors in real time are being developed. In a clinical study to measure PpIX in patients with dysplastic skin lesions, in vivo fluorescence dosimetry was used to measure the accumulation of PpIX over time, and revealed that intralesional PpIX may reach clinically-useful levels earlier than previously thought for the treatment of actinic keratoses. In a second clinical study to examine depth of PpIX production in nonmelanoma skin cancer, the depth of PpIX within BCC tumors was found at relatively deep levels (>1 mm) in some tumor nests, but not in others. Production of PpIX in deep squamous cell carcinoma was very low. In summary, molecular approaches such as differentiation therapy to enhance ALA-PDT for individual patients may ultimately be needed to help to improve skin cancer responses to this modality.

  12. The use of photodynamic therapy for treatment of acne vulgaris.

    PubMed

    Nestor, Mark S

    2007-01-01

    Current topical and most oral therapies for acne vulgaris have limited efficacy, especially in moderate to severe cases. Photodynamic therapy with 5-aminolevulinic acid and recently methyl aminolevulinate has been shown to be a safe and effective modality for the treatment of acne vulgaris. Consensus guidelines suggest that 30 to 60 minutes is sufficient 5-aminolevulinic acid contact time before photoactivation with blue light, red light, yellow light, broadband light, halogen, or pulsed dye laser devices. An average of three treatment can yield significant long-term improvement. PMID:17126741

  13. Folic Acid

    MedlinePlus

    Folic acid is a B vitamin. It helps the body make healthy new cells. Everyone needs folic acid. For women who may get pregnant, it is really important. Getting enough folic acid before and during pregnancy can prevent major birth ...

  14. Folic Acid

    MedlinePlus

    Folic acid is used to treat or prevent folic acid deficiency. It is a B-complex vitamin needed by ... Folic acid comes in tablets. It usually is taken once a day. Follow the directions on your prescription label ...

  15. Amino acids

    MedlinePlus

    ... amino acids are: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan , and valine. Nonessential amino acids "Nonessential" means that our bodies produce an amino ...

  16. Acid Rain.

    ERIC Educational Resources Information Center

    Openshaw, Peter

    1987-01-01

    Provides some background information on acid deposition. Includes a historical perspective, describes some effects of acid precipitation, and discusses acid rain in the United Kingdom. Contains several experiments that deal with the effects of acid rain on water quality and soil. (TW)

  17. Acid rain

    SciTech Connect

    Not Available

    1985-01-01

    This report has four parts: they discuss acid rain in relation to acid soils, agriculture, forests, and aquatic ecosystems. Among findings: modern sources of acid deposition from the atmosphere for all the acid soils in the world, nor even chiefly responsible for those of northern U.S. Agriculture has its problems, but acid precipitation is probably not one of them. More research is needed to determine to what extent acid precipitation is responsible for forest declines and for smaller detrimental effects on forest growth where no damage to the foliage is evident. Many lakes and streams are extremely sensitive to added acids.

  18. Aminocaproic Acid

    MedlinePlus

    Aminocaproic acid is used to control bleeding that occurs when blood clots are broken down too quickly. This type ... the baby is ready to be born). Aminocaproic acid is also used to control bleeding in the ...

  19. Ethacrynic Acid

    MedlinePlus

    Ethacrynic acid, a 'water pill,' is used to treat swelling and fluid retention caused by various medical problems. It ... Ethacrynic acid comes as a tablet to take by mouth. It is usually taken once or twice a day ...

  20. Aristolochic Acids

    MedlinePlus

    ... Sciences NIH-HHS www.niehs.nih.gov Aristolochic Acids Key Points Report on Carcinogens Status Known to be human carcinogens Aristolochia Clematitis Aristolochic Acids n Known human carcinogens n Found in certain ...

  1. Obeticholic Acid

    MedlinePlus

    Obeticholic acid is used alone or in combination with ursodiol (Actigall, Urso) to treat primary biliary cholangitis (PBC; a ... were not treated successfully with ursodiol alone. Obeticholic acid is in a class of medications called farnesoid ...

  2. Acid mucopolysaccharides

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003368.htm Acid mucopolysaccharides To use the sharing features on this page, please enable JavaScript. Acid mucopolysaccharides is a test that measures the amount ...

  3. Fatty acids - trans fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The data supporting a negative effect of dietary trans fatty acids on cardiovascular disease risk is consistent. The primary dietary sources of trans fatty acids include partially hydrogenated fat and rudiment fat. The adverse effect of trans fatty acids on plasma lipoprotein profiles is consisten...

  4. Heme precursor injection is effective for Arthromyces ramosus peroxidase fusion protein production by a silkworm expression system.

    PubMed

    Hayashi, Kounosuke; Lee, Jae Man; Tomozoe, Yusuke; Kusakabe, Takahiro; Kamiya, Noriho

    2015-10-01

    Recombinant peroxidase from Arthromyces ramosus, fused with domains of antibody-binding proteins, was successfully obtained by a silkworm larvae expression system. The catalytic activity of the fusion peroxidase was increased 6-fold with the injection of 5-aminolevulinic acid into silkworm larvae as a heme precursor.

  5. Modulation of chlorophyll biosynthesis by water stress in rice seedlings during chloroplast biogenesis.

    PubMed

    Dalal, Vijay K; Tripathy, Baishnab C

    2012-09-01

    To understand the impact of water stress on the greening process, water stress was applied to 6-day-old etiolated seedlings of a drought-sensitive cultivar of rice (Oryza sativa), Pusa Basmati-1 by immersing their roots in 40 mm polyethylene glycol (PEG) 6000 (-0.69 MPa) or 50 mm PEG 6000 (-1.03 MPa) dissolved in half-strength Murashige and Skoog (MS)-nutrient-solution, 16 h prior to transfer to cool-white-fluorescent + incandescent light. Chlorophyll (Chl) accumulation substantially declined in developing water-stressed seedlings. Reduced Chl synthesis was due to decreased accumulation of chlorophyll biosynthetic intermediates, that is, glutamate-1-semialdehyde (GSA), 5-aminolevulinic acid, Mg-protoporphyrin IX monomethylester and protochlorophyllide. Although 5-aminolevulinic acid synthesis decreased, the gene expression and protein abundance of the enzyme responsible for its synthesis, GSA aminotransferase, increased, suggesting its crucial role in the greening process in stressful environment. The biochemical activities of Chl biosynthetic enzymes, that is, 5-aminolevulinic acid dehydratase, porphobilinogen deaminase, coproporphyrinogen III oxidase, porphyrinogen IX oxidase, Mg-chelatase and protochlorophyllide oxidoreductase, were down-regulated due to their reduced protein abundance/gene expression in water-stressed seedlings. Down-regulation of protochlorophyllide oxidoreductase resulted in impaired Shibata shift. Our results demonstrate that reduced synthesis of early intermediates, that is, GSA and 5-aminolevulinic acid, could modulate the gene expression of later enzymes of Chl biosynthesis pathway.

  6. Aspartic acid

    MedlinePlus

    ... Hormone production and release Normal nervous system function Plant sources of aspartic acid include: Legumes such as soybeans, garbanzo beans, and lentils Peanuts, almonds, walnuts, and flaxseeds Animal ...

  7. In vitro photodynamic therapy based on magnetic-luminescent Gd2O3:Yb,Er nanoparticles with bright three-photon up-conversion fluorescence under near-infrared light.

    PubMed

    Li, Hao; Song, Shaoxin; Wang, Wei; Chen, Kezheng

    2015-09-28

    Yb(3+) and Er(3+) co-doped Gd2O3 nanoparticles were synthesized via a simple homogeneous precipitation method followed by subsequent heat treatment. Morphology characterization results showed that these nanoparticles were almost spherical in shape with diameters of 200-400 nm. The particles were further modified by polyethylene glycol (PEG) to improve their suspensibility in water. The sintering temperature was found to greatly influence the fluorescent properties of the products. After calcination at 700-1200 °C, the Gd2O3:Yb,Er nanoparticles could emit bright up-conversion fluorescence under 980 nm near-infrared (NIR) laser light excitation. The mechanism of up-conversion fluorescence was studied in detail and a three-photon process was observed for both green and red up-conversion fluorescence of the Gd2O3:Yb,Er nanoparticles. Different from many other Yb(3+),Er(3+) co-doped up-conversion materials, the prepared Gd2O3:Yb,Er nanoparticles emitted much stronger red light than green light. The reason was investigated and ascribed to the presence of abundant hydroxyl groups on the surface of the nanoparticles as a result of PEGylation. The nanoparticles could be taken up by the human cervical cancer (HeLa) cells and presented low toxicity. Well-selected photodynamic therapy (PDT) drugs, methylene blue (MB) with a UV/Vis absorption maximum (λmax) of 665 nm and 5-aminolevulinic acid (5ALA) which is a precursor of the natural photosensitizer photoporphyrin IX (PpIX) with a λmax of 635 nm, were loaded onto the nanoparticles respectively to obtain Gd2O3:Yb,Er-MB and Gd2O3:Yb,Er-5ALA nanoparticles. Being up-conversion nanoparticles (UCNPs), the taken up Gd2O3:Yb,Er nanoparticles exposed to 980 nm laser light emitted red fluorescence which activated the loaded MB and PpIX, and then killed the HeLa cells via a PDT mechanism. In vitro therapeutic investigation evidenced the prominent PDT effects of Gd2O3:Yb,Er-MB and Gd2O3:Yb,Er-5ALA upon NIR light irradiation. In

  8. Usnic acid.

    PubMed

    Ingólfsdóttir, K

    2002-12-01

    Since its first isolation in 1844, usnic acid [2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyl-1,3(2H,9bH)-dibenzo-furandione] has become the most extensively studied lichen metabolite and one of the few that is commercially available. Usnic acid is uniquely found in lichens, and is especially abundant in genera such as Alectoria, Cladonia, Usnea, Lecanora, Ramalina and Evernia. Many lichens and extracts containing usnic acid have been utilized for medicinal, perfumery, cosmetic as well as ecological applications. Usnic acid as a pure substance has been formulated in creams, toothpaste, mouthwash, deodorants and sunscreen products, in some cases as an active principle, in others as a preservative. In addition to antimicrobial activity against human and plant pathogens, usnic acid has been shown to exhibit antiviral, antiprotozoal, antiproliferative, anti-inflammatory and analgesic activity. Ecological effects, such as antigrowth, antiherbivore and anti-insect properties, have also been demonstrated. A difference in biological activity has in some cases been observed between the two enantiomeric forms of usnic acid. Recently health food supplements containing usnic acid have been promoted for use in weight reduction, with little scientific support. The emphasis of the current review is on the chemistry and biological activity of usnic acid and its derivatives in addition to rational and ecologically acceptable methods for provision of this natural compound on a large scale.

  9. Acid rain

    SciTech Connect

    Elsworth, S.

    1985-01-01

    This book was written in a concise and readable style for the lay public. It's purpose was to make the public aware of the damage caused by acid rain and to mobilize public opinion to favor the elimination of the causes of acid rain.

  10. Acid rain

    SciTech Connect

    White, J.C. )

    1988-01-01

    This book presents the proceedings of the third annual conference sponsored by the Acid Rain Information Clearinghouse (ARIC). Topics covered include: Legal aspects of the source-receptor relationship: an energy perspective; Scientific uncertainty, agency inaction, and the courts; and Acid rain: the emerging legal framework.

  11. How Acidic Is Carbonic Acid?

    PubMed

    Pines, Dina; Ditkovich, Julia; Mukra, Tzach; Miller, Yifat; Kiefer, Philip M; Daschakraborty, Snehasis; Hynes, James T; Pines, Ehud

    2016-03-10

    Carbonic, lactic, and pyruvic acids have been generated in aqueous solution by the transient protonation of their corresponding conjugate bases by a tailor-made photoacid, the 6-hydroxy-1-sulfonate pyrene sodium salt molecule. A particular goal is to establish the pK(a) of carbonic acid H2CO3. The on-contact proton transfer (PT) reaction rate from the optically excited photoacid to the carboxylic bases was derived, with unprecedented precision, from time-correlated single-photon-counting measurements of the fluorescence lifetime of the photoacid in the presence of the proton acceptors. The time-dependent diffusion-assisted PT rate was analyzed using the Szabo-Collins-Kimball equation with a radiation boundary condition. The on-contact PT rates were found to follow the acidity order of the carboxylic acids: the stronger was the acid, the slower was the PT reaction to its conjugate base. The pK(a) of carbonic acid was found to be 3.49 ± 0.05 using both the Marcus and Kiefer-Hynes free energy correlations. This establishes H2CO3 as being 0.37 pK(a) units stronger and about 1 pK(a) unit weaker, respectively, than the physiologically important lactic and pyruvic acids. The considerable acid strength of intact carbonic acid indicates that it is an important protonation agent under physiological conditions. PMID:26862781

  12. Acid rain

    SciTech Connect

    Sweet, W.

    1980-06-20

    Acid precipitation includes not only rain but also acidified snow, hail and frost, as well as sulfur and nitrogen dust. The principal source of acid precipitation is pollution emitted by power plants and smelters. Sulfur and nitrogen compounds contained in the emissions combine with moisture to form droplets with a high acid content - sometimes as acidic as vinegar. When sufficiently concentrated, these acids can kill fish and damage material structures. Under certain circumstances they may reduce crop and forest yields and cause or aggravate respiratory diseases in humans. During the summer, especially, pollutants tend to collect over the Great Lakes in high pressure systems. Since winds typically are westerly and rotate clockwise around high pressure systems, the pollutants gradually are dispersed throughout the eastern part of the continent.

  13. Asparagusic acid.

    PubMed

    Mitchell, Stephen C; Waring, Rosemary H

    2014-01-01

    Asparagusic acid (1,2-dithiolane-4-carboxylic acid) is a simple sulphur-containing 5-membered heterocyclic compound that appears unique to asparagus, though other dithiolane derivatives have been identified in non-food species. This molecule, apparently innocuous toxicologically to man, is the most probable culprit responsible for the curious excretion of odorous urine following asparagus ingestion. The presence of the two adjacent sulphur atoms leads to an enhanced chemical reactivity, endowing it with biological properties including the ability to substitute potentially for α-lipoic acid in α-keto-acid oxidation systems. This brief review collects the scattered data available in the literature concerning asparagusic acid and highlights its properties, intermediary metabolism and exploratory applications.

  14. Acid rain

    SciTech Connect

    Bess, F.D.

    1980-01-01

    The acid rain problem in the northeastern U.S. has been growing in severity and geographical areas affected. Acid rain has damaged, or will result in damage to visibility, physical structures and materials, aquatic life, timber, crops, and soils. The principal causes of acid rain in the northeastern U.S. are sulfur oxide and nitrogen oxide emissions from large power plants and smelters in the Ohio River Valley. Immediate corrective action and appropriate research are needed to reduce acid precipitation. Short-term programs that will define the rate of environmental deterioration, remaining environmental capacity to resist sudden deterioration, mechanisms of acid rain formation, and costs of various control options must be developed. (3 maps, 13 references, 1 table)

  15. Asparagusic acid.

    PubMed

    Mitchell, Stephen C; Waring, Rosemary H

    2014-01-01

    Asparagusic acid (1,2-dithiolane-4-carboxylic acid) is a simple sulphur-containing 5-membered heterocyclic compound that appears unique to asparagus, though other dithiolane derivatives have been identified in non-food species. This molecule, apparently innocuous toxicologically to man, is the most probable culprit responsible for the curious excretion of odorous urine following asparagus ingestion. The presence of the two adjacent sulphur atoms leads to an enhanced chemical reactivity, endowing it with biological properties including the ability to substitute potentially for α-lipoic acid in α-keto-acid oxidation systems. This brief review collects the scattered data available in the literature concerning asparagusic acid and highlights its properties, intermediary metabolism and exploratory applications. PMID:24099657

  16. Acid fog

    SciTech Connect

    Hileman, B.

    1983-03-01

    Fog in areas of southern California previously thought to be pollution-free has been shown to have a pH as low as 1.69. It has been found to be most acidic after smoggy days, suggesting that it forms on the aerosol associated with the previously exiting smog. Studies on Whiteface Mountain in the Adirondacks show that fog water is often 10 times as acidic as rainwater. As a result of their studies, California plans to spend $4 million on acid deposition research in the coming year. (JMT)

  17. Tranexamic Acid

    MedlinePlus

    ... is used to treat heavy bleeding during the menstrual cycle (monthly periods) in women. Tranexamic acid is in ... tablets for more than 5 days in a menstrual cycle or take more than 6 tablets in a ...

  18. Mefenamic Acid

    MedlinePlus

    ... as mefenamic acid may cause ulcers, bleeding, or holes in the stomach or intestine. These problems may ... like coffee grounds, blood in the stool, or black and tarry stools.Keep all appointments with your ...

  19. Acid Precipitation

    ERIC Educational Resources Information Center

    Likens, Gene E.

    1976-01-01

    Discusses the fact that the acidity of rain and snow falling on parts of the U.S. and Europe has been rising. The reasons are still not entirely clear and the consequences have yet to be well evaluated. (MLH)

  20. Acidic precipitation

    SciTech Connect

    Martin, H.C.

    1987-01-01

    At the International Symposium on Acidic Precipitation, over 400 papers were presented, and nearly 200 of them are included here. They provide an overview of the present state of the art of acid rain research. The Conference focused on atmospheric science (monitoring, source-receptor relationships), aquatic effects (marine eutrophication, lake acidification, impacts on plant and fish populations), and terrestrial effects (forest decline, soil acidification, etc.).

  1. Salicylic acids

    PubMed Central

    Hayat, Shamsul; Irfan, Mohd; Wani, Arif; Nasser, Alyemeni; Ahmad, Aqil

    2012-01-01

    Salicylic acid is well known phytohormone, emerging recently as a new paradigm of an array of manifestations of growth regulators. The area unleashed yet encompassed the applied agriculture sector to find the roles to strengthen the crops against plethora of abiotic and biotic stresses. The skipped part of integrated picture, however, was the evolutionary insight of salicylic acid to either allow or discard the microbial invasion depending upon various internal factors of two interactants under the prevailing external conditions. The metabolic status that allows the host invasion either as pathogenesis or symbiosis with possible intermediary stages in close systems has been tried to underpin here. PMID:22301975

  2. Stearic Acid

    ERIC Educational Resources Information Center

    Young, Jay A.

    2004-01-01

    A chemical laboratory information profile (CLIP) is presented for the chemical, stearic acid. The profile lists the chemical's physical and harmful characteristics, exposure limits, and symptoms of major exposure, for the benefit of teachers and students, who use the chemical in the laboratory.

  3. Trichloroacetic acid

    Integrated Risk Information System (IRIS)

    Trichloroacetic acid ( TCA ) ; CASRN 76 - 03 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Nonca

  4. Acrylic acid

    Integrated Risk Information System (IRIS)

    Acrylic acid ( CASRN 79 - 10 - 7 ) Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  5. Selenious acid

    Integrated Risk Information System (IRIS)

    Selenious acid ; CASRN 7783 - 00 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  6. Dichloroacetic acid

    Integrated Risk Information System (IRIS)

    Dichloroacetic acid ; CASRN 79 - 43 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogeni

  7. Cacodylic acid

    Integrated Risk Information System (IRIS)

    Cacodylic acid ; CASRN 75 - 60 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  8. Phosphoric acid

    Integrated Risk Information System (IRIS)

    Phosphoric acid ; CASRN 7664 - 38 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  9. Benzoic acid

    Integrated Risk Information System (IRIS)

    Benzoic acid ; CASRN 65 - 85 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effec

  10. Formic acid

    Integrated Risk Information System (IRIS)

    Formic acid ; CASRN 64 - 18 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effect

  11. [Hyaluronic acid].

    PubMed

    Pomarede, N

    2008-01-01

    Hyaluronic Acid (HA) is now a leader product in esthetic procedures for the treatment of wrinkles and volumes. The structure of HA, its metabolism, its physiological function are foremost breaking down then its use in aesthetic dermatology: steps of injection, possible side effects, benefits and downsides of the use of HA in aesthetic dermatology.

  12. Hydroxycarboxylic acids and salts

    DOEpatents

    Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N

    2015-02-24

    Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.

  13. ALA-mediated fluorescence-guided resection (FGR) and PDT of glioma

    NASA Astrophysics Data System (ADS)

    Johansson, Ann; Stepp, Herbert; Beck, Tobias; Beyer, Wolfgang; Pongratz, Thomas; Sroka, Ronald; Meinel, Thomas; Stummer, Walter; Kreth, Friedrich-Wilhelm; Tonn, Jörg-Christian; Baumgartner, Reinhold

    2009-06-01

    A summary of clinical trials employing photodynamic diagnosis (PDD) and photodynamic therapy (PDT) for the diagnosis and treatment of brain malignancies is presented. Intra-cavity PDT has been performed within the surgical cavity following FGR, employing oral administration of 5-aminolevulinic acid (5-ALA), either targeting fluorescing tissue regions that were not removed during FGR due to safety reasons (referred to as focal PDT, n=20) or illuminating the entire resection cavity (referred to as integral PDT, n=9). Both approaches proved technically feasible and safe. Spectroscopic measurements performed pre-, during and post-PDT revealed Protoporphyrin IX (PpIX)-photobleaching of more than 95% after the delivery of 200 J/cm2. This light dose did not induce any side effects. Furthermore, interstitial PDT (iPDT) has been employed within one feasibility trial (n=10) and one Phase I/II trial (n=15). Here, three to six cylindrical light diffusors (20-30 mm length, 200 mW/cm, 720 J/cm) were positioned within the target tissue under stereotactic guidance. Pre-treatment planning was performed with the intent to target the entire tumour volume with a sufficient light dose while also minimising the risk of any light-induced temperature increase. For the feasibility trial patients with small, recurrent gliomas were included, resulting in a median survival of 15 months as well as some unexpected longterm survivals (up to 5 years). The Phase I/II trial employed the same clinical procedures. Here, the 12-month survival was 35% and the median progression-free survival was 6 months. In summary, stereotactic iPDT in combination with treatment-planning could be shown to be a safe and feasible treatment modality. These trials are presently being extended to also include on-line monitoring of PpIX fluorescence and photobleaching kinetics. Preliminary data has revealed dramatically different PpIX levels and photobleaching kinetics. Such data could possibly be employed for realtime

  14. Methylmalonic acid blood test

    MedlinePlus

    ... acid is a substance produced when proteins, called amino acids, in the body break down. The health care ... Cederbaum S, Berry GT. Inborn errors of carbohydrate, ammonia, amino acid, and organic acid metabolism. In: Gleason CA, Devaskar ...

  15. Folic Acid and Pregnancy

    MedlinePlus

    ... 5 Things to Know About Zika & Pregnancy Folic Acid and Pregnancy KidsHealth > For Parents > Folic Acid and ... before conception and during early pregnancy . About Folic Acid Folic acid, sometimes called folate, is a B ...

  16. Understanding Acid Rain

    ERIC Educational Resources Information Center

    Damonte, Kathleen

    2004-01-01

    The term acid rain describes rain, snow, or fog that is more acidic than normal precipitation. To understand what acid rain is, it is first necessary to know what an acid is. Acids can be defined as substances that produce hydrogen ions (H+), when dissolved in water. Scientists indicate how acidic a substance is by a set of numbers called the pH…

  17. [Lead toxicity in its joint administration with the aluminium oxide nanoparticles to rats].

    PubMed

    Shumakova, A A; Trushina, E N; Mustafina, O K; Soto, S Kh; Gmoshinsky, I V; Khotimchenko, S A

    2015-01-01

    In this paper we studied the effect of aluminum oxide (Al2O3) nanoparticles (NPs) on the accumulation and biomarkers of toxic action of lead (Pb) when co-administered to rats in subacute experiment. 36 Wistar rats with initial body weight 120-140 g were divided into 4 groups. Animal of group 1 (control group) were given distilled water by gavage. Rats in group 2 received Pb acetate solution in a dose of 20 mg/kg body weight (based on Pb), animal in the 3rd and 4th groups additionally to this received suspension of Al2O3 NPs in doses of 1 and 100 mg/kg body weight, respectively. The experiment lasted 22 days. Body and organ weight, standard haematologic parameters, protein, creatinine, uric acid level, aminotransferase activity (ALT and AST) in serum, urinary 5-aminolevulinic acid (5-ALA) concentration were measured. Apoptosis of hepatocytes was studied by flow cytometry. Pb content was determined by atomic absorption spectrometry. It has been shown that the administration of Al2O3 NPs together with Pb resulted in a significant dose-dependent increase in the relative weight of the kidneys (0.88 ± 0.03% and 0.94 ± 0.06% vs. 0.74 ± 0.02% and 0.85 ± 0.01% in control and group 1). The excretion of 5-ALA in the urine of animals treated with lead acetate significantly (p < 0.001) increased compared to the animals of group 1 (0.80 ± 0.08/µmol/l); while any dependence of this parameter on the dose of Al2O3 NPs was absent (p > 0.05) (group 2: 4.54 ± 0.56 µmol/l; group 3: 7.34 ± 1.35 µmol/l; group 4: 5.71 ± 1.74 µmol/l). The hemoglobin content was significantly reduced in animals of groups 2-4 (134.0 ± 2.9; 133.6 ± 1.8 and 129.9 ± 2.9 g/l) compared to the animals of the control group (144.6 ± 1.5 g/l), the dependence of this parameter on the dose of Al2O3 NPs was also absent. A marked and significant increase of the level of glucose has been noticed on the background of the Al2O3 and NPs (7.46 ± 0.49 u 8.24 ± 0.80 vs. 6.28 ± 0.34 mmol/l in group 2), and its

  18. [Lead toxicity in its joint administration with the aluminium oxide nanoparticles to rats].

    PubMed

    Shumakova, A A; Trushina, E N; Mustafina, O K; Soto, S Kh; Gmoshinsky, I V; Khotimchenko, S A

    2015-01-01

    In this paper we studied the effect of aluminum oxide (Al2O3) nanoparticles (NPs) on the accumulation and biomarkers of toxic action of lead (Pb) when co-administered to rats in subacute experiment. 36 Wistar rats with initial body weight 120-140 g were divided into 4 groups. Animal of group 1 (control group) were given distilled water by gavage. Rats in group 2 received Pb acetate solution in a dose of 20 mg/kg body weight (based on Pb), animal in the 3rd and 4th groups additionally to this received suspension of Al2O3 NPs in doses of 1 and 100 mg/kg body weight, respectively. The experiment lasted 22 days. Body and organ weight, standard haematologic parameters, protein, creatinine, uric acid level, aminotransferase activity (ALT and AST) in serum, urinary 5-aminolevulinic acid (5-ALA) concentration were measured. Apoptosis of hepatocytes was studied by flow cytometry. Pb content was determined by atomic absorption spectrometry. It has been shown that the administration of Al2O3 NPs together with Pb resulted in a significant dose-dependent increase in the relative weight of the kidneys (0.88 ± 0.03% and 0.94 ± 0.06% vs. 0.74 ± 0.02% and 0.85 ± 0.01% in control and group 1). The excretion of 5-ALA in the urine of animals treated with lead acetate significantly (p < 0.001) increased compared to the animals of group 1 (0.80 ± 0.08/µmol/l); while any dependence of this parameter on the dose of Al2O3 NPs was absent (p > 0.05) (group 2: 4.54 ± 0.56 µmol/l; group 3: 7.34 ± 1.35 µmol/l; group 4: 5.71 ± 1.74 µmol/l). The hemoglobin content was significantly reduced in animals of groups 2-4 (134.0 ± 2.9; 133.6 ± 1.8 and 129.9 ± 2.9 g/l) compared to the animals of the control group (144.6 ± 1.5 g/l), the dependence of this parameter on the dose of Al2O3 NPs was also absent. A marked and significant increase of the level of glucose has been noticed on the background of the Al2O3 and NPs (7.46 ± 0.49 u 8.24 ± 0.80 vs. 6.28 ± 0.34 mmol/l in group 2), and its

  19. Precipitation: its acidic nature.

    PubMed

    Frohliger, J O; Kane, R

    1975-08-01

    A comparison of the free hydrogen ion concentration and the total hydrogen ion concentration of rain samples shows that rain is a weak acid. The weak acid nature of rain casts doubt on the concepts that the acidity of rain is increasing and that these increases are due to strong acids such as sulfuric acid.

  20. Amino Acid Metabolism Disorders

    MedlinePlus

    ... defects & other health conditions > Amino acid metabolism disorders Amino acid metabolism disorders E-mail to a friend Please ... baby’s newborn screening may include testing for certain amino acid metabolism disorders. These are rare health conditions that ...

  1. Carbolic acid poisoning

    MedlinePlus

    Phenol poisoning; Phenylic acid poisoning; Hydroxybenzene poisoning; Phenic acid poisoning; Benzenol poisoning ... Below are symptoms of carbolic acid poisoning in different parts of the ... urine Decreased urine output No urine output EYES, EARS, ...

  2. Azelaic Acid Topical

    MedlinePlus

    Azelaic acid gel is used to clear the bumps, lesions, and swelling caused by rosacea (a skin disease that ... redness, flushing, and pimples on the face). Azelaic acid cream is used to treat acne. Azelaic acid ...

  3. Uric acid test (image)

    MedlinePlus

    Uric acid urine test is performed to check for the amount of uric acid in urine. Urine is collected over a 24 ... testing. The most common reason for measuring uric acid levels is in the diagnosis or treatment of ...

  4. Facts about Folic Acid

    MedlinePlus

    ... Information For... Media Policy Makers Facts About Folic Acid Language: English Español (Spanish) Recommend on Facebook Tweet ... of the baby's brain and spine. About folic acid Folic acid is a B vitamin. Our bodies ...

  5. Acid Lipase Disease

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Acid Lipase Disease Information Page Synonym(s): Cholesterol Ester Storage ... Trials Related NINDS Publications and Information What is Acid Lipase Disease ? Acid lipase disease or deficiency occurs ...

  6. Acid distribution in phosphoric acid fuel cells

    SciTech Connect

    Okae, I.; Seya, A.; Umemoto, M.

    1996-12-31

    Electrolyte acid distribution among each component of a cell is determined by capillary force when the cell is not in operation, but the distribution under the current load conditions had not been clear so far. Since the loss of electrolyte acid during operation is inevitable, it is necessary to store enough amount of acid in every cell. But it must be under the level of which the acid disturbs the diffusion of reactive gases. Accordingly to know the actual acid distribution during operation in a cell is very important. In this report, we carried out experiments to clarify the distribution using small single cells.

  7. In vivo skin absorption dynamics of topically applied pharmaceuticals monitored by fiber-optic diffuse reflectance spectroscopy

    NASA Astrophysics Data System (ADS)

    Kim, Ki-Hong; Jheon, Sanghoon; Kim, Jong-Ki

    2007-03-01

    A simple non-invasive ultra-violet/visible (UV/vis) diffusive reflectance spectroscopy combined with fiber-optics was investigated to elicit the dynamics of skin penetration in vivo of a pharmaceutical, aminolevulinic acid polyethylene glycol cream (5-ALA-PEG cream). Temporal data of the reflectance, R( λ), were measured from a bare skin region and from a skin region treated with 5-ALA cream. The difference in apparent optical density [(ΔAOD) = Δ log[1/ R( λ)

  8. Acid tolerance in amphibians

    SciTech Connect

    Pierce, B.A.

    1985-04-01

    Studies of amphibian acid tolerance provide information about the potential effects of acid deposition on amphibian communities. Amphibians as a group appear to be relatively acid tolerant, with many species suffering increased mortality only below pH 4. However, amphibians exhibit much intraspecific variation in acid tolerance, and some species are sensitive to even low levels of acidity. Furthermore, nonlethal effects, including depression of growth rates and increases in developmental abnormalities, can occur at higher pH.

  9. Bioconversions of ferulic acid, an hydroxycinnamic acid.

    PubMed

    Mathew, Sindhu; Abraham, T Emilia

    2006-01-01

    Ferulic acid is the most abundant hydroxycinnamic acid in the plant world and is ester linked to arabinose, in various plant polysaccharides such as arabinoxylans and pectins. It is a precursor to vanillin, one of the most important aromatic flavor compound used in foods, beverages, pharmaceuticals, and perfumes. This article presents an overview of the various biocatalytic routes, focusing on the relevant biotransformations of ferulic acid using plant sources, microorganisms, and enzymes.

  10. Photodynamic therapy using light-emitting diodes for the treatment of viral warts.

    PubMed

    Ohtsuki, Akiko; Hasegawa, Toshio; Hirasawa, Yusuke; Tsuchihashi, Hitoshi; Ikeda, Shigaku

    2009-10-01

    Photodynamic therapy with topical 5-aminolevulinic acid is an effective and safe treatment for actinic keratosis and superficial non-melanoma skin cancer. Further, some studies have reported good efficacy when using photodynamic therapy to treat viral warts. The light-emitting diode is an incoherent, narrow-spectrum light source. The purpose of this study is to evaluate the efficacy of photodynamic therapy using a light-emitting diode for viral warts. Six patients with a total of 41 foot and hand warts were recruited in this study. They were treated with 20% 5-aminolevulinic acid cream under occlusion for 5 h. Thereafter, the treated area was irradiated with the light from a red light-emitting diode (633 +/- 6 nm) with a dose of 126 J/cm(2). This treatment was repeated at 2- or 3-week intervals. The rate of improvement observed in patients was 68.3%. The adverse effects included mild to moderate pain and erythema, which was well-tolerated by all six patients. No patients withdrew from the study due to the adverse effects. Photodynamic therapy with topical 5-aminolevulinic acid using the light from a red light-emitting diode has the advantage of non-invasiveness, minimal associated adverse reactions, and production of good results in a significant proportion of cases: therefore, it is an alternative treatment for recalcitrant viral warts.

  11. Acid Thunder: Acid Rain and Ancient Mesoamerica

    ERIC Educational Resources Information Center

    Kahl, Jonathan D. W.; Berg, Craig A.

    2006-01-01

    Much of Mesoamerica's rich cultural heritage is slowly eroding because of acid rain. Just as water dissolves an Alka-Seltzer tablet, acid rain erodes the limestone surfaces of Mexican archaeological sites at a rate of about one-half millimeter per century (Bravo et al. 2003). A half-millimeter may not seem like much, but at this pace, a few…

  12. Quantity of acid in acid fog

    SciTech Connect

    Deal, W.J.

    1983-07-01

    This communication notes the actual magnitude of the acidity in acidic fog particles and suggests a possible line of inquiry into the health effects of such fog so that it can be determined whether a typical fog is detrimental or beneficial relative to dry air.

  13. Lactic acid test

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003507.htm Lactic acid test To use the sharing features on this page, please enable JavaScript. Lactic acid is mainly produced in muscle cells and red ...

  14. Omega-6 Fatty Acids

    MedlinePlus

    ... types of fats. Some types are found in vegetable oils, including corn, evening primrose seed, safflower, and soybean ... from studying specific omega-6 fatty acids or plant oils containing omega-6 fatty acids. See the separate ...

  15. Fatty acid analogs

    DOEpatents

    Elmaleh, David R.; Livni, Eli

    1985-01-01

    In one aspect, a radioactively labeled analog of a fatty acid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fatty acid.

  16. Deoxycholic Acid Injection

    MedlinePlus

    Deoxycholic acid injection is used to improve the appearance and profile of moderate to severe submental fat ('double chin'; fatty tissue located under the chin). Deoxycholic acid injection is in a class of medications called ...

  17. Aminocaproic Acid Injection

    MedlinePlus

    Aminocaproic acid injection is used to control bleeding that occurs when blood clots are broken down too quickly. This ... the baby is ready to be born). Aminocaproic acid injection is also used to control bleeding in ...

  18. Zoledronic Acid Injection

    MedlinePlus

    ... acid (Reclast) is used to prevent or treat osteoporosis (condition in which the bones become thin and ... Zoledronic acid (Reclast) is also used to treat osteoporosis in men, and to prevent or treat osteoporosis ...

  19. Uric Acid Test

    MedlinePlus

    ... limited. Home Visit Global Sites Search Help? Uric Acid Share this page: Was this page helpful? Also known as: Serum Urate; UA Formal name: Uric Acid Related tests: Synovial Fluid Analysis , Kidney Stone Analysis , ...

  20. Methylmalonic Acid Test

    MedlinePlus

    ... limited. Home Visit Global Sites Search Help? Methylmalonic Acid Share this page: Was this page helpful? Also known as: MMA Formal name: Methylmalonic Acid Related tests: Vitamin B12 and Folate , Homocysteine , Intrinsic ...

  1. Hydrochloric acid poisoning

    MedlinePlus

    Hydrochloric acid is a clear, poisonous liquid. It is highly corrosive, which means it immediately causes severe ... discusses poisoning due to swallowing or breathing in hydrochloric acid. This article is for information only. Do ...

  2. Mixed Acid Oxidation

    SciTech Connect

    Pierce, R.A.

    1999-10-26

    Several non-thermal processes have been developed to destroy organic waste compounds using chemicals with high oxidation potentials. These efforts have focused on developing technologies that work at low temperatures, relative to incineration, to overcome many of the regulatory issues associated with obtaining permits for waste incinerators. One such technique with great flexibility is mixed acid oxidation. Mixed acid oxidation, developed at the Savannah River Site, uses a mixture of an oxidant (nitric acid) and a carrier acid (phosphoric acid). The carrier acid acts as a non-volatile holding medium for the somewhat volatile oxidant. The combination of acids allows appreciable amounts of the concentrated oxidant to remain in the carrier acid well above the oxidant''s normal boiling point.

  3. Plant fatty acid hydroxylases

    DOEpatents

    Somerville, Chris; Broun, Pierre; van de Loo, Frank

    2001-01-01

    This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fatty acids in transgenic plants. In addition, the use of genes encoding fatty acid hydroxylases or desaturases to alter the level of lipid fatty acid unsaturation in transgenic plants is described.

  4. PRODUCTION OF TRIFLUOROACETIC ACID

    DOEpatents

    Haworth, W.N.; Stacey, M.

    1949-07-19

    A method is given for the production of improved yields of trifluoroacetic acid. The compound is prepared by oxidizing m-aminobenzotrifluoride with an alkali metal or alkaline earth metal permanganate at a temperature in the range of 80 deg C to 100 deg C while dissolved ln a mixture of water with glacial acetic acid and/or trifluoroacetic acid. Preferably a mixture of water and trifluoroacetic acid ls used as the solvent.

  5. Quantity of acid in acid fog

    SciTech Connect

    Deal, W.J.

    1983-07-01

    The chemical composition of fog particles has become of considerable interest, because of both the possibility of interpreting atmospheric- chemistry processes in fog particles in terms of the principles of aqueous chemistry and the potential health effects of species present in fog particles. The acidity of fog particles has received wide attention. This communication noted the actual magnitude of the excess acidity in acidic fog particles and suggested a possible line of inquiry into the health effects of such fog so that it can be determined whether a typical fog is detrimental or beneficial relative to dry air. (DP)

  6. Acid Rain Study Guide.

    ERIC Educational Resources Information Center

    Hunger, Carolyn; And Others

    Acid rain is a complex, worldwide environmental problem. This study guide is intended to aid teachers of grades 4-12 to help their students understand what acid rain is, why it is a problem, and what possible solutions exist. The document contains specific sections on: (1) the various terms used in conjunction with acid rain (such as acid…

  7. The Acid Rain Reader.

    ERIC Educational Resources Information Center

    Stubbs, Harriett S.; And Others

    A topic which is often not sufficiently dealt with in elementary school textbooks is acid rain. This student text is designed to supplement classroom materials on the topic. Discussed are: (1) "Rain"; (2) "Water Cycle"; (3) "Fossil Fuels"; (4) "Air Pollution"; (5) "Superstacks"; (6) "Acid/Neutral/Bases"; (7) "pH Scale"; (8) "Acid Rain"; (9)…

  8. What Is Acid Rain?

    ERIC Educational Resources Information Center

    Likens, Gene E.

    2004-01-01

    Acid rain is the collective term for any type of acidified precipitation: rain, snow, sleet, and hail, as well as the presence of acidifying gases, particles, cloud water, and fog in the atmosphere. The increased acidity, primarily from sulfuric and nitric acids, is generated as a by-product of the combustion of fossil fuels such as coal and oil.…

  9. [alpha]-Oxocarboxylic Acids

    ERIC Educational Resources Information Center

    Kerber, Robert C.; Fernando, Marian S.

    2010-01-01

    Several [alpha]-oxocarboxylic acids play key roles in metabolism in plants and animals. However, there are inconsistencies between the structures as commonly portrayed and the reported acid ionization constants, which result because the acids are predominantly hydrated in aqueous solution; that is, the predominant form is RC(OH)[subscript 2]COOH…

  10. Nucleic acid detection compositions

    DOEpatents

    Prudent, James R.; Hall, Jeff G.; Lyamichev, Victor I.; Brow, Mary Ann; Dahlberg, James L.

    2008-08-05

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

  11. Cleavage of nucleic acids

    DOEpatents

    Prudent, James R.; Hall, Jeff G.; Lyamichev, Victor I.; Brow, Mary Ann D.; Dahlberg, James E.

    2000-01-01

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

  12. Nucleic acid detection assays

    DOEpatents

    Prudent, James R.; Hall, Jeff G.; Lyamichev, Victor I.; Brow, Mary Ann; Dahlberg, James E.

    2005-04-05

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

  13. Cleavage of nucleic acids

    DOEpatents

    Prudent, James R.; Hall, Jeff G.; Lyamichev, Victor L.; Brow, Mary Ann D.; Dahlberg, James E.

    2007-12-11

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

  14. Cleavage of nucleic acids

    SciTech Connect

    Prudent, James R.; Hall, Jeff G.; Lyamichev, Victor I.; Brow; Mary Ann D.; Dahlberg, James E.

    2010-11-09

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

  15. Editorial: Acid precipitation

    SciTech Connect

    1995-09-01

    This editorial focuses on acid rain and the history of public and governmental response to acid rain. Comments on a book by Gwineth Howell `Acid Rain and Acid Waters` are included. The editor feels that Howells has provide a service to the environmental scientific community, with a textbook useful to a range of people, as well as a call for decision makers to learn from the acid rain issue and use it as a model for more sweeping global environmental issues. A balance is needed among several parameters such as level of evidence, probability that the evidence will lead to a specific direction and the cost to the global community. 1 tab.

  16. [Safety of folic acid].

    PubMed

    Ströhle, Alexander; Wolters, Maike; Hahn, Andreas

    2015-08-01

    Improving dietary folate intake is a central public health goal. However, critical voices have become louder warning of too high intake of folic acid. Safety concerns of a high folic acid exposure are usually limited to synthetic folic acid contained in drugs and food supplements. Against this background, the present article focuses on two matters: (a) How do the absorption and metabolism of synthetic folic acid differ from that of other folates? (b) How has the longterm safety of folic acid to be judged, especially regarding the risk of colorectal cancer, autism, asthma, impaired immune defence, masking vitamin B12 deficiency and interactions with the methotrexate metabolism?

  17. Amino acid analysis

    NASA Technical Reports Server (NTRS)

    Winitz, M.; Graff, J. (Inventor)

    1974-01-01

    The process and apparatus for qualitative and quantitative analysis of the amino acid content of a biological sample are presented. The sample is deposited on a cation exchange resin and then is washed with suitable solvents. The amino acids and various cations and organic material with a basic function remain on the resin. The resin is eluted with an acid eluant, and the eluate containing the amino acids is transferred to a reaction vessel where the eluant is removed. Final analysis of the purified acylated amino acid esters is accomplished by gas-liquid chromatographic techniques.

  18. Acidic Ionic Liquids.

    PubMed

    Amarasekara, Ananda S

    2016-05-25

    Ionic liquid with acidic properties is an important branch in the wide ionic liquid field and the aim of this article is to cover all aspects of these acidic ionic liquids, especially focusing on the developments in the last four years. The structural diversity and synthesis of acidic ionic liquids are discussed in the introduction sections of this review. In addition, an unambiguous classification system for various types of acidic ionic liquids is presented in the introduction. The physical properties including acidity, thermo-physical properties, ionic conductivity, spectroscopy, and computational studies on acidic ionic liquids are covered in the next sections. The final section provides a comprehensive review on applications of acidic ionic liquids in a wide array of fields including catalysis, CO2 fixation, ionogel, electrolyte, fuel-cell, membrane, biomass processing, biodiesel synthesis, desulfurization of gasoline/diesel, metal processing, and metal electrodeposition.

  19. Nucleic acid detection kits

    DOEpatents

    Hall, Jeff G.; Lyamichev, Victor I.; Mast, Andrea L.; Brow, Mary Ann; Kwiatkowski, Robert W.; Vavra, Stephanie H.

    2005-03-29

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof. The present invention further relates to methods and devices for the separation of nucleic acid molecules based on charge. The present invention also provides methods for the detection of non-target cleavage products via the formation of a complete and activated protein binding region. The invention further provides sensitive and specific methods for the detection of nucleic acid from various viruses in a sample.

  20. Acidic Ionic Liquids.

    PubMed

    Amarasekara, Ananda S

    2016-05-25

    Ionic liquid with acidic properties is an important branch in the wide ionic liquid field and the aim of this article is to cover all aspects of these acidic ionic liquids, especially focusing on the developments in the last four years. The structural diversity and synthesis of acidic ionic liquids are discussed in the introduction sections of this review. In addition, an unambiguous classification system for various types of acidic ionic liquids is presented in the introduction. The physical properties including acidity, thermo-physical properties, ionic conductivity, spectroscopy, and computational studies on acidic ionic liquids are covered in the next sections. The final section provides a comprehensive review on applications of acidic ionic liquids in a wide array of fields including catalysis, CO2 fixation, ionogel, electrolyte, fuel-cell, membrane, biomass processing, biodiesel synthesis, desulfurization of gasoline/diesel, metal processing, and metal electrodeposition. PMID:27175515

  1. Boric acid and boronic acids inhibition of pigeonpea urease.

    PubMed

    Reddy, K Ravi Charan; Kayastha, Arvind M

    2006-08-01

    Urease from the seeds of pigeonpea was competitively inhibited by boric acid, butylboronic acid, phenylboronic acid, and 4-bromophenylboronic acid; 4-bromophenylboronic acid being the strongest inhibitor, followed by boric acid > butylboronic acid > phenylboronic acid, respectively. Urease inhibition by boric acid is maximal at acidic pH (5.0) and minimal at alkaline pH (10.0), i.e., the trigonal planar B(OH)3 form is a more effective inhibitor than the tetrahedral B(OH)4 -anionic form. Similarly, the anionic form of phenylboronic acid was least inhibiting in nature.

  2. Biotransformation of cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid by plant cell cultures of Eucalyptus perriniana.

    PubMed

    Katsuragi, Hisashi; Shimoda, Kei; Kubota, Naoji; Nakajima, Nobuyoshi; Hamada, Hatsuyuki; Hamada, Hiroki

    2010-01-01

    Biotransformations of phenylpropanoids such as cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid were investigated with plant-cultured cells of Eucalyptus perriniana. The plant-cultured cells of E. perriniana converted cinnamic acid into cinnamic acid β-D-glucopyranosyl ester, p-coumaric acid, and 4-O-β-D-glucopyranosylcoumaric acid. p-Coumaric acid was converted into 4-O-β-D-glucopyranosylcoumaric acid, p-coumaric acid β-D-glucopyranosyl ester, 4-O-β-D-glucopyranosylcoumaric acid β-D-glucopyranosyl ester, a new compound, caffeic acid, and 3-O-β-D-glucopyranosylcaffeic acid. On the other hand, incubation of caffeic acid with cultured E. perriniana cells gave 3-O-β-D-glucopyranosylcaffeic acid, 3-O-(6-O-β-D-glucopyranosyl)-β-D-glucopyranosylcaffeic acid, a new compound, 3-O-β-D-glucopyranosylcaffeic acid β-D-glucopyranosyl ester, 4-O-β-D-glucopyranosylcaffeic acid, 4-O-β-D-glucopyranosylcaffeic acid β-D-glucopyranosyl ester, ferulic acid, and 4-O-β-D-glucopyranosylferulic acid. 4-O-β-D-Glucopyranosylferulic acid, ferulic acid β-D-glucopyranosyl ester, and 4-O-β-D-glucopyranosylferulic acid β-D-glucopyranosyl ester were isolated from E. perriniana cells treated with ferulic acid.

  3. Process for the preparation of lactic acid and glyceric acid

    DOEpatents

    Jackson, James E [Haslett, MI; Miller, Dennis J [Okemos, MI; Marincean, Simona [Dewitt, MI

    2008-12-02

    Hexose and pentose monosaccharides are degraded to lactic acid and glyceric acid in an aqueous solution in the presence of an excess of a strongly anionic exchange resin, such as AMBERLITE IRN78 and AMBERLITE IRA400. The glyceric acid and lactic acid can be separated from the aqueous solution. Lactic acid and glyceric acid are staple articles of commerce.

  4. Well acidizing compositions and methods

    SciTech Connect

    Swanson, B. L.

    1980-12-23

    Gelled acidic compositions suitable for matrix acidizing or fracture acidizing of subterranean formations are provided comprising water, a water-dispersible polymeric viscosifier such as a polymer of acrylamide, an acid, and a polyphenolic material such as lignite.

  5. Bile acids but not acidic acids induce Barrett's esophagus.

    PubMed

    Sun, Dongfeng; Wang, Xiao; Gai, Zhibo; Song, Xiaoming; Jia, Xinyong; Tian, Hui

    2015-01-01

    Barrett's esophagus (BE) is associated with the development of esophageal adenocarcinoma (EAC). Bile acids (BAs) refluxing into the esophagus contribute to esophageal injury, which results in BE and subsequent EAC. We developed two animal models to test the role of BAs in the pathogenesis of BE. We surgically generated BA reflux, with or without gastric acid, in rats. In a second experiment, we fed animals separately with BAs and gastric acid. Pathologic changes were examined and the expression of Muc2 and Cdx2 in BE tissue was tested by immunostaining. Inflammatory factors in the plasma, as well as differentiation genes in BE were examined through highly sensitive ELISA and semi-quantitative RT-PCR techniques. We found that BAs are sufficient for the induction of esophagitis and Barrett's-like metaplasia in the esophagus. Overexpression of inflammatory cells, IL-6, and TNF-α was observed both in animals fed with BAs and surgically generated BA reflux. Furthermore, elevated levels of Cdx2, Muc2, Bmp4, Kit19, and Tff2 (differentiation genes in BE) were found in BA-treated rats. In conclusion, BAs, but not gastric acid, are a major causative factor for BE. We confirmed that BAs contribute to the development of BE by inducing the inflammatory response in the esophagus. Inhibiting BAs may be a promising therapy for BE.

  6. Microorganisms for producing organic acids

    DOEpatents

    Pfleger, Brian Frederick; Begemann, Matthew Brett

    2014-09-30

    Organic acid-producing microorganisms and methods of using same. The organic acid-producing microorganisms comprise modifications that reduce or ablate AcsA activity or AcsA homolog activity. The modifications increase tolerance of the microorganisms to such organic acids as 3-hydroxypropionic acid, acrylic acid, propionic acid, lactic acid, and others. Further modifications to the microorganisms increase production of such organic acids as 3-hydroxypropionic acid, lactate, and others. Methods of producing such organic acids as 3-hydroxypropionic acid, lactate, and others with the modified microorganisms are provided. Methods of using acsA or homologs thereof as counter-selectable markers are also provided.

  7. 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

  8. Acid-Base Homeostasis.

    PubMed

    Hamm, L Lee; Nakhoul, Nazih; Hering-Smith, Kathleen S

    2015-12-01

    Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3(-) and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3(-) is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.

  9. Citric Acid Alternative to Nitric Acid Passivation

    NASA Technical Reports Server (NTRS)

    Lewis, Pattie L. (Compiler)

    2013-01-01

    The Ground Systems Development and Operations GSDO) Program at NASA John F. Kennedy Space Center (KSC) has the primary objective of modernizing and transforming the launch and range complex at KSC to benefit current and future NASA programs along with other emerging users. Described as the launch support and infrastructure modernization program in the NASA Authorization Act of 2010, the GSDO Program will develop and implement shared infrastructure and process improvements to provide more flexible, affordable, and responsive capabilities to a multi-user community. In support of the GSDO Program, the purpose of this project is to demonstratevalidate citric acid as a passivation agent for stainless steel. Successful completion of this project will result in citric acid being qualified for use as an environmentally preferable alternative to nitric acid for passivation of stainless steel alloys in NASA and DoD applications.

  10. Enzymatic gallic acid esterification.

    PubMed

    Weetal, H H

    1985-02-01

    Gallic acid esters of n-propyl and amyl alcohols have been produced by enzymatic synthesis in organic solvents using immobilized tannase. Studies indicate that maximum esterification of gallic acid occurs with amyl alcohol. The enzyme shows broad alcohol specificity. However, the enzyme exhibits absolute specificity for the acid portion of the ester. Studies were carried out on K(m), V(max), pH, and temperature optima.

  11. Amino acids and proteins.

    PubMed

    van Goudoever, Johannes B; Vlaardingerbroek, Hester; van den Akker, Chris H; de Groof, Femke; van der Schoor, Sophie R D

    2014-01-01

    Amino acids and protein are key factors for growth. The neonatal period requires the highest intake in life to meet the demands. Those demands include amino acids for growth, but proteins and amino acids also function as signalling molecules and function as neurotransmitters. Often the nutritional requirements are not met, resulting in a postnatal growth restriction. However, current knowledge on adequate levels of both amino acid as well as protein intake can avoid under nutrition in the direct postnatal phase, avoid the need for subsequent catch-up growth and improve later outcome.

  12. USGS Tracks Acid Rain

    USGS Publications Warehouse

    Gordon, John D.; Nilles, Mark A.; Schroder, LeRoy J.

    1995-01-01

    The U.S. Geological Survey (USGS) has been actively studying acid rain for the past 15 years. When scientists learned that acid rain could harm fish, fear of damage to our natural environment from acid rain concerned the American public. Research by USGS scientists and other groups began to show that the processes resulting in acid rain are very complex. Scientists were puzzled by the fact that in some cases it was difficult to demonstrate that the pollution from automobiles and factories was causing streams or lakes to become more acidic. Further experiments showed how the natural ability of many soils to neutralize acids would reduce the effects of acid rain in some locations--at least as long as the neutralizing ability lasted (Young, 1991). The USGS has played a key role in establishing and maintaining the only nationwide network of acid rain monitoring stations. This program is called the National Atmospheric Deposition Program/National Trends Network (NADP/NTN). Each week, at approximately 220 NADP/NTN sites across the country, rain and snow samples are collected for analysis. NADP/NTN site in Montana. The USGS supports about 72 of these sites. The information gained from monitoring the chemistry of our nation's rain and snow is important for testing the results of pollution control laws on acid rain.

  13. Recovery of organic acids

    DOEpatents

    Verser, Dan W.; Eggeman, Timothy J.

    2011-11-01

    A method is disclosed for the recovery of an organic acid from a dilute salt solution in which the cation of the salt forms an insoluble carbonate salt. A tertiary amine and CO.sub.2 are introduced to the solution to form the insoluble carbonate salt and a complex between the acid and an amine. A water immiscible solvent, such as an alcohol, is added to extract the acid/amine complex from the dilute salt solution to a reaction phase. The reaction phase is continuously dried and a product between the acid and the solvent, such as an ester, is formed.

  14. Recovery of organic acids

    DOEpatents

    Verser, Dan W.; Eggeman, Timothy J.

    2009-10-13

    A method is disclosed for the recovery of an organic acid from a dilute salt solution in which the cation of the salt forms an insoluble carbonate salt. A tertiary amine and CO.sub.2 are introduced to the solution to form the insoluble carbonate salt and a complex between the acid and an amine. A water immiscible solvent, such as an alcohol, is added to extract the acid/amine complex from the dilute salt solution to a reaction phase. The reaction phase is continuously dried and a product between the acid and the solvent, such as an ester, is formed.

  15. Mutant fatty acid desaturase

    DOEpatents

    Shanklin, John; Cahoon, Edgar B.

    2004-02-03

    The present invention relates to a method for producing mutants of a fatty acid desaturase having a substantially increased activity towards fatty acid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fatty acid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fatty acids, thereby selecting for recipient cells which have received and which express a mutant fatty acid desaturase with an elevated specificity for fatty acid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fatty acid products.

  16. Amino Acid Crossword Puzzle

    ERIC Educational Resources Information Center

    Sims, Paul A.

    2011-01-01

    Learning the 20 standard amino acids is an essential component of an introductory course in biochemistry. Later in the course, the students study metabolism and learn about various catabolic and anabolic pathways involving amino acids. Learning new material or concepts often is easier if one can connect the new material to what one already knows;…

  17. Toxicology of Perfluoroalkyl acids

    EPA Science Inventory

    The Perfluoroalkyl acids(PFAAs) area a family of organic chemicals consisting of a perflurinated carbon backbone (4-12in length) and a acidic functional moiety (Carboxylate or sulfonate). These compounds have excellent surface-tension reducing properties and have numerous industr...

  18. Uric acid - blood

    MedlinePlus

    ... High levels of uric acid can sometimes cause gout or kidney disease. You may have this test if you have had or are about to have certain types of chemotherapy. Rapid weight loss, which may occur with such treatments, can increase the amount of uric acid in ...

  19. Bile acid transporters

    PubMed Central

    Dawson, Paul A.; Lan, Tian; Rao, Anuradha

    2009-01-01

    In liver and intestine, transporters play a critical role in maintaining the enterohepatic circulation and bile acid homeostasis. Over the past two decades, there has been significant progress toward identifying the individual membrane transporters and unraveling their complex regulation. In the liver, bile acids are efficiently transported across the sinusoidal membrane by the Na+ taurocholate cotransporting polypeptide with assistance by members of the organic anion transporting polypeptide family. The bile acids are then secreted in an ATP-dependent fashion across the canalicular membrane by the bile salt export pump. Following their movement with bile into the lumen of the small intestine, bile acids are almost quantitatively reclaimed in the ileum by the apical sodium-dependent bile acid transporter. The bile acids are shuttled across the enterocyte to the basolateral membrane and effluxed into the portal circulation by the recently indentified heteromeric organic solute transporter, OSTα-OSTβ. In addition to the hepatocyte and enterocyte, subgroups of these bile acid transporters are expressed by the biliary, renal, and colonic epithelium where they contribute to maintaining bile acid homeostasis and play important cytoprotective roles. This article will review our current understanding of the physiological role and regulation of these important carriers. PMID:19498215

  20. Analysis of Organic Acids.

    ERIC Educational Resources Information Center

    Griswold, John R.; Rauner, Richard A.

    1990-01-01

    Presented are the procedures and a discussion of the results for an experiment in which students select unknown carboxylic acids, determine their melting points, and investigate their solubility behavior in water and ethanol. A table of selected carboxylic acids is included. (CW)

  1. Omega-3 Fatty Acids

    MedlinePlus

    Omega-3 fatty acids are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount of triglycerides (a fat-like ... people with very high triglycerides. Omega-3 fatty acids are in a class of medications called antilipemic ...

  2. Toxicology of Perfluoroalkyl Acids*

    EPA Science Inventory

    The perfluoroalkyl acids (PFAAs) are a family of organic chemicals consisting of a perfluorinated carbon backbone (4-12 in length) and an acidic functional moiety (carboxylate or sulfonate). These compounds are chemically stable, have excellent surface-tension reducing properties...

  3. Salicylic Acid Topical

    MedlinePlus

    ... skin blemishes in people who have acne. Topical salicylic acid is also used to treat skin conditions that involve scaling or overgrowth of skin ... water for 15 minutes.Do not apply topical salicylic acid to skin that is broken, red, swollen, irritated, or infected. ...

  4. Uric acid and hypertension.

    PubMed

    Feig, Daniel I

    2011-09-01

    A link between serum uric acid and the development of hypertension was first hypothesized in the 1870s. Although numerous epidemiologic studies in the 1980s and 1990s suggested an association, relatively little attention was paid to it until recently. Animal models have suggested a two-step pathogenesis by which uric acid initially activates the renin angiotensin system and suppresses nitric oxide, leading to uric acid-dependent increase in systemic vascular resistance, followed by a uric acid-mediated vasculopathy, involving renal afferent arterioles, resulting in a late sodium-sensitive hypertension. Initial clinical trials in young patients have supported these mechanisms in young patients but do not yet support pharmacologic reduction of serum uric acid as first-line therapy for hypertension.

  5. Biosynthesis of pulcherriminic acid

    PubMed Central

    MacDonald, J. C.

    1965-01-01

    1. Candida pulcherrima was grown on a complex medium to which various compounds had been added to determine their effect on the biosynthesis of pulcherriminic acid. Most of the pulcherriminic acid synthesized by C. pulcherrima PRL2019 was derived from the l-[1-14C]leucine added to the medium. 2. The cyclic dipeptide of l-leucine (cyclo-l-leucyl-l-leucyl) was shown, by trapping experiments involving cycloleucyl-leucyl isomers, to be synthesized by strain PRL2019. Cyclo-l-leucyl-l-leucyl was derived from l-leucine and was converted into pulcherriminic acid. Cyclo-l-leucyl-l-leucyl was a precursor of pulcherriminic acid in strain PRL2007 also. 3. The results supported the hypothesis that pulcherriminic acid is derived from l-leucine and that cyclo-l-leucyl-l-leucyl is an intermediate in the biosynthesis. PMID:5837792

  6. Total syntheses of cis-cyclopropane fatty acids: dihydromalvalic acid, dihydrosterculic acid, lactobacillic acid, and 9,10-methylenehexadecanoic acid.

    PubMed

    Shah, Sayali; White, Jonathan M; Williams, Spencer J

    2014-12-14

    cis-Cyclopropane fatty acids (cis-CFAs) are widespread constituents of the seed oils of subtropical plants, membrane components of bacteria and protozoa, and the fats and phospholipids of animals. We describe a systematic approach to the synthesis of enantiomeric pairs of four cis-CFAs: cis-9,10-methylenehexadecanoic acid, lactobacillic acid, dihydromalvalic acid, and dihydrosterculic acid. The approach commences with Rh2(OAc)4-catalyzed cyclopropenation of 1-octyne and 1-decyne, and hinges on the preparative scale chromatographic resolution of racemic 2-alkylcycloprop-2-ene-1-carboxylic acids using a homochiral Evan's auxiliary. Saturation of the individual diastereomeric N-cycloprop-2-ene-1-carbonylacyloxazolidines, followed by elaboration to alkylcyclopropylmethylsulfones, allowed Julia-Kocienski olefination with various ω-aldehyde-esters. Finally, saponification and diimide reduction afforded the individual cis-CFA enantiomers. PMID:25321346

  7. Gluconic acid production.

    PubMed

    Anastassiadis, Savas; Morgunov, Igor G

    2007-01-01

    Gluconic acid, the oxidation product of glucose, is a mild neither caustic nor corrosive, non toxic and readily biodegradable organic acid of great interest for many applications. As a multifunctional carbonic acid belonging to the bulk chemicals and due to its physiological and chemical characteristics, gluconic acid itself, its salts (e.g. alkali metal salts, in especially sodium gluconate) and the gluconolactone form have found extensively versatile uses in the chemical, pharmaceutical, food, construction and other industries. Present review article presents the comprehensive information of patent bibliography for the production of gluconic acid and compares the advantages and disadvantages of known processes. Numerous manufacturing processes are described in the international bibliography and patent literature of the last 100 years for the production of gluconic acid from glucose, including chemical and electrochemical catalysis, enzymatic biocatalysis by free or immobilized enzymes in specialized enzyme bioreactors as well as discontinuous and continuous fermentation processes using free growing or immobilized cells of various microorganisms, including bacteria, yeast-like fungi and fungi. Alternatively, new superior fermentation processes have been developed and extensively described for the continuous and discontinuous production of gluconic acid by isolated strains of yeast-like mold Aureobasidium pullulans, offering numerous advantages over the traditional discontinuous fungi processes.

  8. Trans Fatty Acids

    NASA Astrophysics Data System (ADS)

    Doyle, Ellin

    1997-09-01

    Fats and their various fatty acid components seem to be a perennial concern of nutritionists and persons concerned with healthful diets. Advice on the consumption of saturated, polyunsaturated, monounsaturated, and total fat bombards us from magazines and newspapers. One of the newer players in this field is the group of trans fatty acids found predominantly in partially hydrogenated fats such as margarines and cooking fats. The controversy concerning dietary trans fatty acids was recently addressed in an American Heart Association (AHA) science advisory (1) and in a position paper from the American Society of Clinical Nutrition/American Institute of Nutrition (ASCN/AIN) (2). Both reports emphasize that the best preventive strategy for reducing risk for cardiovascular disease and some types of cancer is a reduction in total and saturated fats in the diet, but a reduction in the intake of trans fatty acids was also recommended. Although the actual health effects of trans fatty acids remain uncertain, experimental evidence indicates that consumption of trans fatty acids adversely affects serum lipid levels. Since elevated levels of serum cholesterol and triacylglycerols are associated with increased risk of cardiovascular disease, it follows that intake of trans fatty acids should be minimized.

  9. Sulfuric Acid on Europa

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Frozen sulfuric acid on Jupiter's moon Europa is depicted in this image produced from data gathered by NASA's Galileo spacecraft. The brightest areas, where the yellow is most intense, represent regions of high frozen sulfuric acid concentration. Sulfuric acid is found in battery acid and in Earth's acid rain.

    This image is based on data gathered by Galileo's near infrared mapping spectrometer.

    Europa's leading hemisphere is toward the bottom right, and there are enhanced concentrations of sulfuric acid in the trailing side of Europa (the upper left side of the image). This is the face of Europa that is struck by sulfur ions coming from Jupiter's innermost moon, Io. The long, narrow features that crisscross Europa also show sulfuric acid that may be from sulfurous material extruded in cracks.

    Galileo, launched in 1989, has been orbiting Jupiter and its moons since December 1995. JPL manages the Galileo mission for NASA's Office of Space Science, Washington DC. JPL is a division of the California Institute of Technology, Pasadena, CA.

  10. Strongly Acidic Auxin Indole-3-Methanesulfonic Acid

    PubMed Central

    Cohen, Jerry D.; Baldi, Bruce G.; Bialek, Krystyna

    1985-01-01

    A radiochemical synthesis is described for [14C]indole-3-methanesulfonic acid (IMS), a strongly acidic auxin analog. Techniques were developed for fractionation and purification of IMS using normal and reverse phase chromatography. In addition, the utility of both Fourier transform infrared spectrometry and fast atom bombardment mass spectrometry for analysis of IMS has been demonstrated. IMS was shown to be an active auxin, stimulating soybean hypocotyl elongation, bean first internode curvature, and ethylene production. IMS uptake by thin sections of soybean hypocotyl was essentially independent of solution pH and, when applied at a 100 micromolar concentration, IMS exhibited a basipetal polarity in its transport in both corn coleoptile and soybean hypocotyl sections. [14C]IMS should, therefore, be a useful compound to study fundamental processes related to the movement of auxins in plant tissues and organelles. PMID:16664007

  11. Understanding acid rain

    SciTech Connect

    Budiansky, S.

    1981-06-01

    The complexities of the phenomenon of acid rain are described. Many factors, including meteorology, geology, chemistry, and biology, all play parts. Varying weather, varying soils, the presence of other pollutants and species differences all act to blur the connections between industrial emissions, acid rain, and environmental damage. Some experts believe that the greatest pH shock to lakes occurs during snow melt and runoff in the spring; others believe that much of the plant damage ascribed to acid rain is actually due to the effects of ozone. Much work needs to be done in the area of sampling. Historical data are lacking and sampling methods are not sufficiently accurate. (JMT)

  12. Understanding Acid Base Disorders.

    PubMed

    Gomez, Hernando; Kellum, John A

    2015-10-01

    The concentration of hydrogen ions is regulated in biologic solutions. There are currently 3 recognized approaches to assess changes in acid base status. First is the traditional Henderson-Hasselbalch approach, also called the physiologic approach, which uses the relationship between HCO3(-) and Pco2; the second is the standard base excess approach based on the Van Slyke equation. The third approach is the quantitative or Stewart approach, which uses the strong ion difference and the total weak acids. This article explores the origins of the current concepts framing the existing methods to analyze acid base balance.

  13. Acid rain and soil.

    PubMed

    vanLoon, G W

    1984-08-01

    A summary of important chemical properties of soil is given and the way in which acid rain may affect these properties is discussed. Acid rain may suppress microbiological decomposition and nitrification processes, thus influencing the nutrient status of soils. It has also been found that soil organic matter is less soluble in more acid solutions. Changed nutrient availability patterns are predicted in a low pH environment and enhanced leaching of essential elements from the soil exchange complex has been observed. Increased solubility of potentially toxic elements such as aluminium may also occur from soils which have been exposed to acidified rainfall.

  14. Disorders of Amino Acid Metabolism

    MedlinePlus

    ... Aspiration Syndrome Additional Content Medical News Disorders of Amino Acid Metabolism By Lee M. Sanders, MD, MPH NOTE: ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism Amino acids are ...

  15. Pantothenic acid and biotin

    MedlinePlus

    ... well as other nutrients, are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board ... level that is thought to ensure enough nutrition. Dietary Reference Intakes for pantothenic acid: Age 0 to 6 months: ...

  16. Amino Acid Metabolism Disorders

    MedlinePlus

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup ...

  17. [Hydrofluoric acid burns].

    PubMed

    Holla, Robin; Gorter, Ramon R; Tenhagen, Mark; Vloemans, A F P M Jos; Breederveld, Roelf S

    2016-01-01

    Hydrofluoric acid is increasingly used as a rust remover and detergent. Dermal contact with hydrofluoric acid results in a chemical burn characterized by severe pain and deep tissue necrosis. It may cause electrolyte imbalances with lethal consequences. It is important to identify high-risk patients. 'High risk' is defined as a total affected body area > 3% or exposure to hydrofluoric acid in a concentration > 50%. We present the cases of three male patients (26, 31, and 39 years old) with hydrofluoric acid burns of varying severity and describe the subsequent treatments. The application of calcium gluconate 2.5% gel to the skin is the cornerstone of the treatment, reducing pain as well as improving wound healing. Nails should be thoroughly inspected and possibly removed if the nail is involved, to ensure proper healing. In high-risk patients, plasma calcium levels should be evaluated and cardiac monitoring is indicated.

  18. Folic acid - test

    MedlinePlus

    ... folic acid before and during pregnancy helps prevent neural tube defects, such as spina bifida. Women who ... take more if they have a history of neural tube defects in earlier pregnancies. Ask your provider ...

  19. Nitric acid poisoning

    MedlinePlus

    Symptoms from swallowing nitric acid may include: Abdominal pain - severe Burns to skin or mouth Drooling Fever Mouth pain - severe Rapid drop in blood pressure (shock) Throat swelling, which leads to breathing difficulty ...

  20. [Hydrofluoric acid burns].

    PubMed

    Holla, Robin; Gorter, Ramon R; Tenhagen, Mark; Vloemans, A F P M Jos; Breederveld, Roelf S

    2016-01-01

    Hydrofluoric acid is increasingly used as a rust remover and detergent. Dermal contact with hydrofluoric acid results in a chemical burn characterized by severe pain and deep tissue necrosis. It may cause electrolyte imbalances with lethal consequences. It is important to identify high-risk patients. 'High risk' is defined as a total affected body area > 3% or exposure to hydrofluoric acid in a concentration > 50%. We present the cases of three male patients (26, 31, and 39 years old) with hydrofluoric acid burns of varying severity and describe the subsequent treatments. The application of calcium gluconate 2.5% gel to the skin is the cornerstone of the treatment, reducing pain as well as improving wound healing. Nails should be thoroughly inspected and possibly removed if the nail is involved, to ensure proper healing. In high-risk patients, plasma calcium levels should be evaluated and cardiac monitoring is indicated. PMID:27189091

  1. Difficult Decisions: Acid Rain.

    ERIC Educational Resources Information Center

    Miller, John A.; Slesnick, Irwin L.

    1989-01-01

    Discusses some of the contributing factors and chemical reactions involved in the production of acid rain, its effects, and political issues pertaining to who should pay for the clean up. Supplies questions for consideration and discussion. (RT)

  2. Hyaluronic acid fillers.

    PubMed

    Monheit, Gary D; Coleman, Kyle M

    2006-01-01

    Although hyaluronic acids are a relatively new treatment for facial lines and wrinkles, they have provided numerous advances in the area of cosmetic surgery. This article discusses the inherent properties of hyaluronic acid fillers that make them ideal for treatment of facial lines. It encompasses a review of the current literature on U.S. Food and Drug Administration-approved hyaluronic acid fillers and the role that each of these fillers currently has in facial cosmetics. This article also discusses the potential pitfalls and adverse effects that can be associated with using hyaluronic acids for filling facial lines. Finally, it serves as an overview of current techniques for clinical assessment of patients as well as administration and treatment of facial lines and wrinkles.

  3. Boric acid poisoning

    MedlinePlus

    Borax poisoning ... The main symptoms of boric acid poisoning are blue-green vomit, diarrhea, and a bright red rash on the skin. Other symptoms may include: Blisters Collapse Coma Convulsions Drowsiness ...

  4. Stomach acid test

    MedlinePlus

    Gastric acid secretion test ... The test is done after you have not eaten for a while so fluid is all that remains in ... injected into your body. This is done to test the ability of the cells in the stomach ...

  5. Aminolevulinic Acid Topical

    MedlinePlus

    ... under the skin that result from exposure to sunlight and can develop into skin cancer) of the ... acid will make your skin very sensitive to sunlight (likely to get sunburn). Avoid exposure of treated ...

  6. Amino Acids and Chirality

    NASA Technical Reports Server (NTRS)

    Cook, Jamie E.

    2012-01-01

    Amino acids are among the most heavily studied organic compound class in carbonaceous chondrites. The abundance, distributions, enantiomeric compositions, and stable isotopic ratios of amino acids have been determined in carbonaceous chondrites fi'om a range of classes and petrographic types, with interesting correlations observed between these properties and the class and typc of the chondritcs. In particular, isomeric distributions appear to correlate with parent bodies (chondrite class). In addition, certain chiral amino acids are found in enantiomeric excess in some chondrites. The delivery of these enantiomeric excesses to the early Earth may have contributed to the origin of the homochirality that is central to life on Earth today. This talk will explore the amino acids in carbonaceous chondritcs and their relevance to the origin of life.

  7. (Acid rain workshop)

    SciTech Connect

    Turner, R.S.

    1990-12-05

    The traveler presented a paper entitled Susceptibility of Asian Ecosystems to Soil-Mediated Acid Rain Damage'' at the Second Workshop on Acid Rain in Asia. The workshop was organized by the Asian Institute of Technology (Bangkok, Thailand), Argonne National Laboratory (Argonne, Illinois), and Resource Management Associates (Madison, Wisconsin) and was sponsored by the US Department of Energy, the United Nations Environment Program, the United Nations Economic and Social Commission for Asia and the Pacific, and the World Bank. Papers presented on the first day discussed how the experience gained with acid rain in North America and Europe might be applied to the Asian situation. Papers describing energy use projections, sulfur emissions, and effects of acid rain in several Asian countries were presented on the second day. The remaining time was allotted to discussion, planning, and writing plans for a future research program.

  8. Folic acid in diet

    MedlinePlus

    ... a regular supply of the vitamin in the foods you eat. ... vitamins have been added to the food. Many foods are now fortified with folic acid. Some of these are enriched breads, cereals, flours, ...

  9. Valproic Acid and Pregnancy

    MedlinePlus

    ... in the treatment of epilepsy, and to treat bipolar disorder and migraines. I have been taking valproic acid ... that women with seizure disorders and women with bipolar disorder might have menstrual problems and difficulty getting pregnant. ...

  10. Citric acid urine test

    MedlinePlus

    ... The test is used to diagnose renal tubular acidosis and evaluate kidney stone disease. Normal Results The ... level of citric acid may mean renal tubular acidosis and a tendency to form calcium kidney stones. ...

  11. Folic Acid Quiz

    MedlinePlus

    ... more easily than natural food folate. Close × Answer: D CORRECT: Folic acid reduces the risk for spina ... g., orange juice and green vegetables). Close × Answer: D CORRECT: Spina bifida and anencephaly are neural tube ...

  12. Hydrofluoric acid poisoning

    MedlinePlus

    ... your skin or eyes, you may have: Blisters Burns Pain Vision loss Hydrofluoric acid poisoning can have ... urine tests Camera down the throat to see burns in the esophagus and the stomach (endoscopy) Fluids ...

  13. Portable nucleic acid thermocyclers.

    PubMed

    Almassian, David R; Cockrell, Lisa M; Nelson, William M

    2013-11-21

    A nucleic acid thermal cycler is considered to be portable if it is under ten pounds, easily carried by one individual, and battery powered. Nucleic acid amplification includes both polymerase chain reaction (e.g. PCR, RT-PCR) and isothermal amplification (e.g. RPA, HDA, LAMP, NASBA, RCA, ICAN, SMART, SDA). There are valuable applications for portable nucleic acid thermocyclers in fields that include clinical diagnostics, biothreat detection, and veterinary testing. A system that is portable allows for the distributed detection of targets at the point of care and a reduction of the time from sample to answer. The designer of a portable nucleic acid thermocycler must carefully consider both thermal control and the detection of amplification. In addition to thermal control and detection, the designer may consider the integration of a sample preparation subsystem with the nucleic acid thermocycler. There are a variety of technologies that can achieve accurate thermal control and the detection of nucleic acid amplification. Important evaluation criteria for each technology include maturity, power requirements, cost, sensitivity, speed, and manufacturability. Ultimately the needs of a particular market will lead to user requirements that drive the decision between available technologies.

  14. Neutron Nucleic Acid Crystallography.

    PubMed

    Chatake, Toshiyuki

    2016-01-01

    The hydration shells surrounding nucleic acids and hydrogen-bonding networks involving water molecules and nucleic acids are essential interactions for the structural stability and function of nucleic acids. Water molecules in the hydration shells influence various conformations of DNA and RNA by specific hydrogen-bonding networks, which often contribute to the chemical reactivity and molecular recognition of nucleic acids. However, X-ray crystallography could not provide a complete description of structural information with respect to hydrogen bonds. Indeed, X-ray crystallography is a powerful tool for determining the locations of water molecules, i.e., the location of the oxygen atom of H2O; however, it is very difficult to determine the orientation of the water molecules, i.e., the orientation of the two hydrogen atoms of H2O, because X-ray scattering from the hydrogen atom is very small.Neutron crystallography is a specialized tool for determining the positions of hydrogen atoms. Neutrons are not diffracted by electrons, but are diffracted by atomic nuclei; accordingly, neutron scattering lengths of hydrogen and its isotopes are comparable to those of non-hydrogen atoms. Therefore, neutron crystallography can determine both of the locations and orientations of water molecules. This chapter describes the current status of neutron nucleic acid crystallographic research as well as the basic principles of neutron diffraction experiments performed on nucleic acid crystals: materials, crystallization, diffraction experiments, and structure determination. PMID:26227050

  15. Neutron Nucleic Acid Crystallography.

    PubMed

    Chatake, Toshiyuki

    2016-01-01

    The hydration shells surrounding nucleic acids and hydrogen-bonding networks involving water molecules and nucleic acids are essential interactions for the structural stability and function of nucleic acids. Water molecules in the hydration shells influence various conformations of DNA and RNA by specific hydrogen-bonding networks, which often contribute to the chemical reactivity and molecular recognition of nucleic acids. However, X-ray crystallography could not provide a complete description of structural information with respect to hydrogen bonds. Indeed, X-ray crystallography is a powerful tool for determining the locations of water molecules, i.e., the location of the oxygen atom of H2O; however, it is very difficult to determine the orientation of the water molecules, i.e., the orientation of the two hydrogen atoms of H2O, because X-ray scattering from the hydrogen atom is very small.Neutron crystallography is a specialized tool for determining the positions of hydrogen atoms. Neutrons are not diffracted by electrons, but are diffracted by atomic nuclei; accordingly, neutron scattering lengths of hydrogen and its isotopes are comparable to those of non-hydrogen atoms. Therefore, neutron crystallography can determine both of the locations and orientations of water molecules. This chapter describes the current status of neutron nucleic acid crystallographic research as well as the basic principles of neutron diffraction experiments performed on nucleic acid crystals: materials, crystallization, diffraction experiments, and structure determination.

  16. Utilization of acid tars

    SciTech Connect

    Frolov, A.F.; Denisova, T.L.; Aminov, A.N.

    1987-01-01

    Freshly produced acid tar (FPAT), obtained as refinery waste in treating petroleum oils with sulfuric acid and oleum, contains 80% or more sulfuric acid. Of such tars, pond acid tars, which contain up to 80% neutral petroleum products and sulfonated resins, are more stable, and have found applications in the production of binders for paving materials. In this article the authors are presenting results obtained in a study of the composition and reactivity of FPAT and its stability in storage in blends with asphalts obtained in deasphalting operations, and the possibility of using the FPAT in road construction has been examined. In this work, wastes were used which were obtained in treating the oils T-750, KhF-12, I-8A, and MS-14. Data on the change in group chemical composition of FPAT are shown, and the acidity, viscosity, needle penetration, and softening point of acid tars obtained from different grades of oils are plotted as functions of the storage time. It is also shown that the fresh and hardened FPATs differ in their solubilities in various solvents.

  17. Method for isolating nucleic acids

    SciTech Connect

    Hurt, Jr., Richard Ashley; Elias, Dwayne A.

    2015-09-29

    The current disclosure provides methods and kits for isolating nucleic acid from an environmental sample. The current methods and compositions further provide methods for isolating nucleic acids by reducing adsorption of nucleic acids by charged ions and particles within an environmental sample. The methods of the current disclosure provide methods for isolating nucleic acids by releasing adsorbed nucleic acids from charged particles during the nucleic acid isolation process. The current disclosure facilitates the isolation of nucleic acids of sufficient quality and quantity to enable one of ordinary skill in the art to utilize or analyze the isolated nucleic acids for a wide variety of applications including, sequencing or species population analysis.

  18. Acidification and Acid Rain

    NASA Astrophysics Data System (ADS)

    Norton, S. A.; Veselã½, J.

    2003-12-01

    Air pollution by acids has been known as a problem for centuries (Ducros, 1845; Smith, 1872; Camuffo, 1992; Brimblecombe, 1992). Only in the mid-1900s did it become clear that it was a problem for more than just industrially developed areas, and that precipitation quality can affect aquatic resources ( Gorham, 1955). The last three decades of the twentieth century saw tremendous progress in the documentation of the chemistry of the atmosphere, precipitation, and the systems impacted by acid atmospheric deposition. Chronic acidification of ecosystems results in chemical changes to soil and to surface waters and groundwater as a result of reduction of base cation supply or an increase in acid (H+) supply, or both. The most fundamental changes during chronic acidification are an increase in exchangeable H+ or Al3+ (aluminum) in soils, an increase in H+ activity (˜concentration) in water in contact with soil, and a decrease in alkalinity in waters draining watersheds. Water draining from the soil is acidified and has a lower pH (=-log [H+]). As systems acidify, their biotic community changes.Acidic surface waters occur in many parts of the world as a consequence of natural processes and also due to atmospheric deposition of strong acid (e.g., Canada, Jeffries et al. (1986); the United Kingdom, Evans and Monteith (2001); Sweden, Swedish Environmental Protection Board (1986); Finland, Forsius et al. (1990); Norway, Henriksen et al. (1988a); and the United States (USA), Brakke et al. (1988)). Concern over acidification in the temperate regions of the northern hemisphere has been driven by the potential for accelerating natural acidification by pollution of the atmosphere with acidic or acidifying compounds. Atmospheric pollution ( Figure 1) has resulted in an increased flux of acid to and through ecosystems. Depending on the ability of an ecosystem to neutralize the increased flux of acidity, acidification may increase only imperceptibly or be accelerated at a rate that

  19. Discovery of essential fatty acids

    PubMed Central

    Spector, Arthur A.; Kim, Hee-Yong

    2015-01-01

    Dietary fat was recognized as a good source of energy and fat-soluble vitamins by the first part of the 20th century, but fatty acids were not considered to be essential nutrients because they could be synthesized from dietary carbohydrate. This well-established view was challenged in 1929 by George and Mildred Burr who reported that dietary fatty acid was required to prevent a deficiency disease that occurred in rats fed a fat-free diet. They concluded that fatty acids were essential nutrients and showed that linoleic acid prevented the disease and is an essential fatty acid. The Burrs surmised that other unsaturated fatty acids were essential and subsequently demonstrated that linolenic acid, the omega-3 fatty acid analog of linoleic acid, is also an essential fatty acid. The discovery of essential fatty acids was a paradigm-changing finding, and it is now considered to be one of the landmark discoveries in lipid research. PMID:25339684

  20. Boric acid catalyzed chemoselective esterification of alpha-hydroxycarboxylic acids.

    PubMed

    Houston, Todd A; Wilkinson, Brendan L; Blanchfield, Joanne T

    2004-03-01

    Boric acid catalyzes the selective esterification of alpha-hydroxycarboxylic acids without causing significant esterification to occur with other carboxylic acids. The procedure is simple, high-yielding, and applicable to the esterification of alpha-hydroxy carboxylates in the presence of other carboxylic acids including beta-hydroxyacids within the same molecule. [reaction: see text

  1. Acid Rain, pH & Acidity: A Common Misinterpretation.

    ERIC Educational Resources Information Center

    Clark, David B.; Thompson, Ronald E.

    1989-01-01

    Illustrates the basis for misleading statements about the relationship between pH and acid content in acid rain. Explains why pH cannot be used as a measure of acidity for rain or any other solution. Suggests that teachers present acidity and pH as two separate and distinct concepts. (RT)

  2. Amino-acid contamination of aqueous hydrochloric acid.

    NASA Technical Reports Server (NTRS)

    Wolman, Y.; Miller, S. L.

    1971-01-01

    Considerable amino-acid contamination in commercially available analytical grade hydrochloric acid (37% HCl) was found. One bottle contained 8,300 nmol of amino-acids per liter. A bottle from another supplier contained 6,700 nmol per liter. The contaminants were mostly protein amino-acids and several unknowns. Data on the volatility of the amino-acids during HCl distillation were also obtained.

  3. Analysis of Bile Acids

    NASA Astrophysics Data System (ADS)

    Sjövall, Jan; Griffiths, William J.; Setchell, Kenneth D. R.; Mano, Nariyasu; Goto, Junichi

    Bile acids constitute a large family of steroids in vertebrates, normally formed from cholesterol and carrying a carboxyl group in a side-chain of variable length. Bile alcohols, also formed from cholesterol, have similar structures as bile acids, except for the absence of a carboxyl group in the steroid skeleton. The conversion of cholesterol to bile acids and/or bile alcohols is of major importance for maintenance of cholesterol homeostasis, both from quantitative and regulatory points of view (Chiang, 2004; Kalaany and Mangelsdorf, 2006; Moore, Kato, Xie, et al., 2006; Scotti, Gilardi, Godio, et al., 2007). Appropriately conjugated bile acids and bile alcohols (also referred to as bile salts) are secreted in bile and serve vital functions in the absorption of lipids and lipid-soluble compounds (Hofmann, 2007). Reliable analytical methods are required for studies of the functions and pathophysiological importance of the variety of bile acids and bile alcohols present in living organisms. When combined with genetic and proteomic studies, analysis of these small molecules (in today's terminology: metabolomics, steroidomics, sterolomics, cholanoidomics, etc.) will lead to a deeper understanding of the integrated metabolic processes in lipid metabolism.

  4. Optical high acidity sensor

    DOEpatents

    Jorgensen, B.S.; Nekimken, H.L.; Carey, W.P.; O`Rourke, P.E.

    1997-07-22

    An apparatus and method for determining acid concentrations in solutions having acid concentrations of from about 0.1 Molar to about 16 Molar is disclosed. The apparatus includes a chamber for interrogation of the sample solution, a fiber optic light source for passing light transversely through the chamber, a fiber optic collector for receiving the collimated light after transmission through the chamber, a coating of an acid resistant polymeric composition upon at least one fiber end or lens, the polymeric composition in contact with the sample solution within the chamber and having a detectable response to acid concentrations within the range of from about 0.1 Molar to about 16 Molar, a measurer for the response of the polymeric composition in contact with the sample solution, and a comparer of the measured response to predetermined standards whereby the acid molarity of the sample solution within the chamber can be determined. Preferably, a first lens is attached to the end of the fiber optic light source, the first lens adapted to collimate light from the fiber optic light source, and a second lens is attached to the end of the fiber optic collector for focusing the collimated light after transmission through the chamber. 10 figs.

  5. Optical high acidity sensor

    DOEpatents

    Jorgensen, Betty S.; Nekimken, Howard L.; Carey, W. Patrick; O'Rourke, Patrick E.

    1997-01-01

    An apparatus and method for determining acid concentrations in solutions having acid concentrations of from about 0.1 Molar to about 16 Molar is disclosed. The apparatus includes a chamber for interrogation of the sample solution, a fiber optic light source for passing light transversely through the chamber, a fiber optic collector for receiving the collimated light after transmission through the chamber, a coating of an acid resistant polymeric composition upon at least one fiber end or lens, the polymeric composition in contact with the sample solution within the chamber and having a detectable response to acid concentrations within the range of from about 0.1 Molar to about 16 Molar, a measurer for the response of the polymeric composition in contact with the sample solution, and, a comparer of the measured response to predetermined standards whereby the acid molarity of the sample solution within the chamber can be determined. Preferably, a first lens is attached to the end of the fiber optic light source, the first lens adapted to collimate light from the fiber optic light source, and a second lens is attached to the end of the fiber optic collector for focusing the collimated light after transmission through the chamber.

  6. Acid sludge utilization

    SciTech Connect

    Suarez, M.

    1980-09-01

    The Peak Oil Company of Tampa, Florida, in cooperation with the United States Department of Energy, has completed an initial study for the incorporation of acid-sludge derived from the rerefining of used lubricating oil into a useful and salable building material. Both bricks and paving materials have been produced using a formulation developed by Peak. Equipment has been designed and constructed for the specific purpose of preparing emulsions containing the acid-sludge, which is a vital ingredient in the final formulation. Testing of products obtained from these initial efforts shows that the acid in the sludge has been effectively neutralized and that heavy metals are not leached from the bricks or paving material in normal testing. While some properties of the building materials that incorporate the acid-sludge by-product are below standards for clay and shale brick, uses are defined for the product as is, and there is some promise of eventual production of building materials that meet all specifications for competitive materials. Initial cost estimations are encouraging, indicating that a profit can be derived by converting a hazardous and noxious by-product of rerefining to a construction material. Acid-sludge has presented a complex and costly disposal problem to the industry resulting in a serious depletion in the capacity for rerefining used lubricating oil.

  7. Domoic acid epileptic disease.

    PubMed

    Ramsdell, John S; Gulland, Frances M

    2014-03-01

    Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a breadth of insight into clinical presentations, unusual behaviors, brain pathology, and epidemiology. A rat model that replicates key observations of the chronic epileptic syndrome in sea lions has been applied to identify the progression of the epileptic disease state, its relationship to behavioral manifestations, and to define the neural systems involved in these behavioral disorders. Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. We discuss causative mechanisms and neural underpinnings of disease maturation revealed by the rat model to present the concept for olfactory origin of an epileptic disease; triggered in dendodendritic synapases of the olfactory bulb and maturing in the olfactory cortex. We conclude with updated information on populations at risk, medical diagnosis, treatment, and prognosis. PMID:24663110

  8. Domoic Acid Epileptic Disease

    PubMed Central

    Ramsdell, John S.; Gulland, Frances M.

    2014-01-01

    Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a breadth of insight into clinical presentations, unusual behaviors, brain pathology, and epidemiology. A rat model that replicates key observations of the chronic epileptic syndrome in sea lions has been applied to identify the progression of the epileptic disease state, its relationship to behavioral manifestations, and to define the neural systems involved in these behavioral disorders. Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. We discuss causative mechanisms and neural underpinnings of disease maturation revealed by the rat model to present the concept for olfactory origin of an epileptic disease; triggered in dendodendritic synapases of the olfactory bulb and maturing in the olfactory cortex. We conclude with updated information on populations at risk, medical diagnosis, treatment, and prognosis. PMID:24663110

  9. [Lead toxicity at its joint administration with nanostructured silica].

    PubMed

    Shumakova, A A; Trushina, E N; Mustafina, O K; Soto, S Kh; Gmoshinsky, I V; Khotimchenko, S Aa

    2015-01-01

    Nanoparticles (NPs) are present in the composition of the objects in the environment and foods together with contaminants of conventional nature, and may enhance their toxicity in certain conditions. The aim of this work was to study the effect of nanostructured silicon dioxide (SiO2), widely used as a food additive, on the accumulation and manifestation of the toxic effect of lead (Pb) when co-administered to rats in the subacute experiment. Rats were divided into 6 groups. Animals of the 1st group (control) received distilled water intragatrically by gavage. Rats of the 2nd and 3rd groups received dispersion of SiO2 NPs with primary particle size of 5-30 nm in the doses of 1 and 100 mg/kg body weight, respectively, of Group 4--lead acetate in the dose of 20 mg of lead/kg body weight, group 5 and 6--Pb acetate and SiO2 NPs dispersion in doses, respectively 1 and 100 mg/kg body weight, for 22 days by intragastric gavage. The weight of the body and organs, standard haematological parameters, serum protein, creatinine, uric acid, albumin, glucose level, and -alkiline phosphatase, ALT and AST activity, urinary 5-aminolevulinic acid (ALA) were determined. Hepatocyte apoptosis was studied by flow-cytometry. The content of Pb, cadmium (Cd), arsenic (As), selenium (Se), iron (Fe), zinc (Zn), copper (Cu), chromium (Cr), manganese (Mg), aluminum (Al) and cobalt (Co) in organs (liver, kidney, brain) was determined by ICP-MS. The result showed that the introduction of Pb, but not NPs resulted in a significant increase in the mass of the kidneys and testes. Urinary excretion of 5-ALA in animals from groups 4-6 significantly (p < 0.001) increased, compared with animals 1-3 groups, not influenced by SiO2 NPs administration (p > 0.05). Introduction of SiO2 NPs resulted in a dose-dependent increase in blood hemoglobin, the effect of lead on this index had the opposite direction. Marked changes were noticed in the levels of glucose and serum albumin in combined exposure of Pb and

  10. [Lead toxicity at its joint administration with nanostructured silica].

    PubMed

    Shumakova, A A; Trushina, E N; Mustafina, O K; Soto, S Kh; Gmoshinsky, I V; Khotimchenko, S Aa

    2015-01-01

    Nanoparticles (NPs) are present in the composition of the objects in the environment and foods together with contaminants of conventional nature, and may enhance their toxicity in certain conditions. The aim of this work was to study the effect of nanostructured silicon dioxide (SiO2), widely used as a food additive, on the accumulation and manifestation of the toxic effect of lead (Pb) when co-administered to rats in the subacute experiment. Rats were divided into 6 groups. Animals of the 1st group (control) received distilled water intragatrically by gavage. Rats of the 2nd and 3rd groups received dispersion of SiO2 NPs with primary particle size of 5-30 nm in the doses of 1 and 100 mg/kg body weight, respectively, of Group 4--lead acetate in the dose of 20 mg of lead/kg body weight, group 5 and 6--Pb acetate and SiO2 NPs dispersion in doses, respectively 1 and 100 mg/kg body weight, for 22 days by intragastric gavage. The weight of the body and organs, standard haematological parameters, serum protein, creatinine, uric acid, albumin, glucose level, and -alkiline phosphatase, ALT and AST activity, urinary 5-aminolevulinic acid (ALA) were determined. Hepatocyte apoptosis was studied by flow-cytometry. The content of Pb, cadmium (Cd), arsenic (As), selenium (Se), iron (Fe), zinc (Zn), copper (Cu), chromium (Cr), manganese (Mg), aluminum (Al) and cobalt (Co) in organs (liver, kidney, brain) was determined by ICP-MS. The result showed that the introduction of Pb, but not NPs resulted in a significant increase in the mass of the kidneys and testes. Urinary excretion of 5-ALA in animals from groups 4-6 significantly (p < 0.001) increased, compared with animals 1-3 groups, not influenced by SiO2 NPs administration (p > 0.05). Introduction of SiO2 NPs resulted in a dose-dependent increase in blood hemoglobin, the effect of lead on this index had the opposite direction. Marked changes were noticed in the levels of glucose and serum albumin in combined exposure of Pb and

  11. A Demonstration of Acid Rain

    ERIC Educational Resources Information Center

    Fong, Man Wai

    2004-01-01

    A demonstration showing acid rain formation is described. Oxides of sulfur and nitrogen that result from the burning of fossil fuels are the major pollutants of acid rain. In this demonstration, SO[subscript 2] gas is produced by the burning of matches. An acid-base indicator will show that the dissolved gas turns an aqueous solution acidic.

  12. DOCOSAHEXAENOIC ACID AND ARACHIDONIC ACID PREVENT ESSENTIAL FATTY ACID DEFICIENCY AND HEPATIC STEATOSIS

    PubMed Central

    Le, Hau D.; Meisel, Jonathan A.; de Meijer, Vincent E.; Fallon, Erica M.; Gura, Kathleen M.; Nose, Vania; Bistrian, Bruce R.; Puder, Mark

    2012-01-01

    Objectives Essential fatty acids are important for growth, development, and physiologic function. Alpha-linolenic acid and linoleic acid are the precursors of docosahexaenoic and arachidonic acid, respectively, and have traditionally been considered the essential fatty acids. However, we hypothesized that docosahexaenoic acid and arachidonic acid can function as the essential fatty acids. Methods Using a murine model of essential fatty acid deficiency and consequent hepatic steatosis, we provided mice with varying amounts of docosahexaenoic and arachidonic acids to determine whether exclusive supplementation of docosahexaenoic and arachidonic acids could prevent essential fatty acid deficiency and inhibit or attenuate hepatic steatosis. Results Mice supplemented with docosahexaenoic and arachidonic acids at 2.1% or 4.2% of their calories for 19 days had normal liver histology and no biochemical evidence of essential fatty acid deficiency, which persisted when observed after 9 weeks. Conclusion Supplementation of sufficient amounts of docosahexaenoic and arachidonic acids alone without alpha-linolenic and linoleic acids meets essential fatty acid requirements and prevents hepatic steatosis in a murine model. PMID:22038210

  13. Biodegradation of cyanuric acid.

    PubMed

    Saldick, J

    1974-12-01

    Cyanuric acid biodegrades readily under a wide variety of natural conditions, and particularly well in systems of either low or zero dissolved-oxygen level, such as anaerobic activated sludge and sewage, soils, muds, and muddy streams and river waters, as well as ordinary aerated activated sludge systems with typically low (1 to 3 ppm) dissolved-oxygen levels. Degradation also proceeds in 3.5% sodium chloride solution. Consequently, there are degradation pathways widely available for breaking down cyanuric acid discharged in domestic effluents. The overall degradation reaction is merely a hydrolysis; CO(2) and ammonia are the initial hydrolytic breakdown products. Since no net oxidation occurs during this breakdown, biodegradation of cyanuric acid exerts no primary biological oxygen demand. However, eventual nitrification of the ammonia released will exert its usual biological oxygen demand.

  14. Exposures to acidic aerosols.

    PubMed

    Spengler, J D; Keeler, G J; Koutrakis, P; Ryan, P B; Raizenne, M; Franklin, C A

    1989-02-01

    Ambient monitoring of acid aerosols in four U.S. cities and in a rural region of southern Ontario clearly show distinct periods of strong acidity. Measurements made in Kingston, TN, and Steubenville, OH, resulted in 24-hr H+ ion concentrations exceeding 100 nmole/m3 more than 10 times during summer months. Periods of elevated acidic aerosols occur less frequently in winter months. The H+ determined during episodic conditions in southern Ontario indicates that respiratory tract deposition can exceed the effects level reported in clinical studies. Observed 12-hr H+ concentrations exceeded 550 nmole/m3 (approximately 27 micrograms/m3 H2SO4). The maximum estimated 1-hr concentration exceeded 1500 nmole/m3 for H+ ions. At these concentrations, an active child might receive more than 2000 nmole of H+ ion in 12 hr and in excess of 900 nmole during the hour when H2SO4 exceeded 50 micrograms/m3.

  15. Biodegradation of Cyanuric Acid

    PubMed Central

    Saldick, Jerome

    1974-01-01

    Cyanuric acid biodegrades readily under a wide variety of natural conditions, and particularly well in systems of either low or zero dissolved-oxygen level, such as anaerobic activated sludge and sewage, soils, muds, and muddy streams and river waters, as well as ordinary aerated activated sludge systems with typically low (1 to 3 ppm) dissolved-oxygen levels. Degradation also proceeds in 3.5% sodium chloride solution. Consequently, there are degradation pathways widely available for breaking down cyanuric acid discharged in domestic effluents. The overall degradation reaction is merely a hydrolysis; CO2 and ammonia are the initial hydrolytic breakdown products. Since no net oxidation occurs during this breakdown, biodegradation of cyanuric acid exerts no primary biological oxygen demand. However, eventual nitrification of the ammonia released will exert its usual biological oxygen demand. PMID:4451360

  16. Calorimetry of Nucleic Acids.

    PubMed

    Rozners, Eriks; Pilch, Daniel S; Egli, Martin

    2015-12-01

    This unit describes the application of calorimetry to characterize the thermodynamics of nucleic acids, specifically, the two major calorimetric methodologies that are currently employed: differential scanning (DSC) and isothermal titration calorimetry (ITC). DSC is used to study thermally induced order-disorder transitions in nucleic acids. A DSC instrument measures, as a function of temperature (T), the excess heat capacity (C(p)(ex)) of a nucleic acid solution relative to the same amount of buffer solution. From a single curve of C(p)(ex) versus T, one can derive the following information: the transition enthalpy (ΔH), entropy (ΔS), free energy (ΔG), and heat capacity (ΔCp); the state of the transition (two-state versus multistate); and the average size of the molecule that melts as a single thermodynamic entity (e.g., the duplex). ITC is used to study the hybridization of nucleic acid molecules at constant temperature. In an ITC experiment, small aliquots of a titrant nucleic acid solution (strand 1) are added to an analyte nucleic acid solution (strand 2), and the released heat is monitored. ITC yields the stoichiometry of the association reaction (n), the enthalpy of association (ΔH), the equilibrium association constant (K), and thus the free energy of association (ΔG). Once ΔH and ΔG are known, ΔS can also be derived. Repetition of the ITC experiment at a number of different temperatures yields the ΔCp for the association reaction from the temperature dependence of ΔH.

  17. Acid rain in Asia

    NASA Astrophysics Data System (ADS)

    Bhatti, Neeloo; Streets, David G.; Foell, Wesley K.

    1992-07-01

    Acid rain has been an issue of great concern in North America and Europe during the past several decades. However, due to the passage of a number of recent regulations, most notably the Clean Air Act in the United States in 1990, there is an emerging perception that the problem in these Western nations is nearing solution. The situation in the developing world, particularly in Asia, is much bleaker. Given the policies of many Asian nations to achieve levels of development comparable with the industrialized world—which necessitate a significant expansion of energy consumption (most derived from indigenous coal reserves)—the potential for the formation of, and damage from, acid deposition in these developing countries is very high. This article delineates and assesses the emissions patterns, meteorology, physical geology, and biological and cultural resources present in various Asian nations. Based on this analysis and the risk factors to acidification, it is concluded that a number of areas in Asia are currently vulnerable to acid rain. These regions include Japan, North and South Korea, southern China, and the mountainous portions of Southeast Asia and southwestern India. Furthermore, with accelerated development (and its attendant increase in energy use and production of emissions of acid deposition precursors) in many nations of Asia, it is likely that other regions will also be affected by acidification in the near future. Based on the results of this overview, it is clear that acid deposition has significant potential to impact the Asian region. However, empirical evidence is urgently needed to confirm this and to provide early warning of increases in the magnitude and spread of acid deposition and its effects throughout this part of the world.

  18. Acid Precipitation; (USA)

    SciTech Connect

    Rushing, J.W.; Hicks, S.C.

    1991-01-01

    This publication, Acid Precipitation (APC) announces on a monthly basis the current worldwide information on acid precipitation and closely related subjects, including wet and dry deposition, long-range transport, environmental effects, modeling, and socioeconomic factors. Information on the following subjects is included within the scope of this publication, but all subjects may not appear in each issue: Pollution sources and pollution control technology; atmospheric transport and chemistry; terrestrial transport and chemistry; aquatic transport and chemistry; biological effects; corrosive effects; and socioeconomics, policy, and legislation.

  19. Whither acid rain?

    PubMed

    Brimblecombe, P

    2001-04-01

    Acid rain, the environmental cause célèbre of the 1980s seems to have vanished from popular conscience. By contrast, scientific research, despite funding difficulties, has continued to produce hundreds of research papers each year. Studies of acid rain taught much about precipitation chemistry, the behaviour of snow packs, long-range transport of pollutants and new issues in the biology of fish and forested ecosystems. There is now evidence of a shift away from research in precipitation and sulfur chemistry, but an impressive theoretical base remains as a legacy.

  20. NITRIC ACID PICKLING PROCESS

    DOEpatents

    Boller, E.R.; Eubank, L.D.

    1958-08-19

    An improved process is described for the treatment of metallic uranium surfaces preparatory to being given hot dip coatings. The process consists in first pickling the uraniunn surInce with aqueous 50% to 70% nitric acid, at 60 to 70 deg C, for about 5 minutes, rinsing the acid solution from the uranium article, promptly drying and then passing it through a molten alkali-metal halide flux consisting of 42% LiCl, 53% KCla and 5% NaCl into a molten metal bath consisting of 85 parts by weight of zinc and 15 parts by weight of aluminum

  1. Fatty acids of Thiobacillus thiooxidans.

    PubMed

    Levin, R A

    1971-12-01

    Fatty acid spectra were made on Thiobacillus thiooxidans cultures both in the presence and absence of organic compounds. Small additions of glucose or acetate had no significant effect either on growth or fatty acid content. The addition of biotin had no stimulatory effect but did result in slight quantitative changes in the fatty acid spectrum. The predominant fatty acid was a C(19) cyclopropane acid.

  2. Fatty Acids of Thiobacillus thiooxidans

    PubMed Central

    Levin, Richard A.

    1971-01-01

    Fatty acid spectra were made on Thiobacillus thiooxidans cultures both in the presence and absence of organic compounds. Small additions of glucose or acetate had no significant effect either on growth or fatty acid content. The addition of biotin had no stimulatory effect but did result in slight quantitative changes in the fatty acid spectrum. The predominant fatty acid was a C19 cyclopropane acid. PMID:4945206

  3. The Acid-Base Titration of a Very Weak Acid: Boric Acid

    ERIC Educational Resources Information Center

    Celeste, M.; Azevedo, C.; Cavaleiro, Ana M. V.

    2012-01-01

    A laboratory experiment based on the titration of boric acid with strong base in the presence of d-mannitol is described. Boric acid is a very weak acid and direct titration with NaOH is not possible. An auxiliary reagent that contributes to the release of protons in a known stoichiometry facilitates the acid-base titration. Students obtain the…

  4. Lactic acid bacterial cell factories for gamma-aminobutyric acid.

    PubMed

    Li, Haixing; Cao, Yusheng

    2010-11-01

    Gamma-aminobutyric acid is a non-protein amino acid that is widely present in organisms. Several important physiological functions of gamma-aminobutyric acid have been characterized, such as neurotransmission, induction of hypotension, diuretic effects, and tranquilizer effects. Many microorganisms can produce gamma-aminobutyric acid including bacteria, fungi and yeasts. Among them, gamma-aminobutyric acid-producing lactic acid bacteria have been a focus of research in recent years, because lactic acid bacteria possess special physiological activities and are generally regarded as safe. They have been extensively used in food industry. The production of lactic acid bacterial gamma-aminobutyric acid is safe and eco-friendly, and this provides the possibility of production of new naturally fermented health-oriented products enriched in gamma-aminobutyric acid. The gamma-aminobutyric acid-producing species of lactic acid bacteria and their isolation sources, the methods for screening of the strains and increasing their production, the enzymatic properties of glutamate decarboxylases and the relative fundamental research are reviewed in this article. And the potential applications of gamma-aminobutyric acid-producing lactic acid bacteria were also referred to.

  5. Comparison of Buffer Effect of Different Acids During Sandstone Acidizing

    NASA Astrophysics Data System (ADS)

    Umer Shafiq, Mian; Khaled Ben Mahmud, Hisham; Hamid, Mohamed Ali

    2015-04-01

    The most important concern of sandstone matrix acidizing is to increase the formation permeability by removing the silica particles. To accomplish this, the mud acid (HF: HCl) has been utilized successfully for many years to stimulate the sandstone formations, but still it has many complexities. This paper presents the results of laboratory investigations of different acid combinations (HF: HCl, HF: H3PO4 and HF: HCOOH). Hydrofluoric acid and fluoboric acid are used to dissolve clays and feldspar. Phosphoric and formic acids are added as a buffer to maintain the pH of the solution; also it allows the maximum penetration of acid into the core sample. Different tests have been performed on the core samples before and after the acidizing to do the comparative study on the buffer effect of these acids. The analysis consists of permeability, porosity, color change and pH value tests. There is more increase in permeability and porosity while less change in pH when phosphoric and formic acids were used compared to mud acid. From these results it has been found that the buffer effect of phosphoric acid and formic acid is better than hydrochloric acid.

  6. [Studies on interaction of acid-treated nanotube titanic acid and amino acids].

    PubMed

    Zhang, Huqin; Chen, Xuemei; Jin, Zhensheng; Liao, Guangxi; Wu, Xiaoming; Du, Jianqiang; Cao, Xiang

    2010-06-01

    Nanotube titanic acid (NTA) has distinct optical and electrical character, and has photocatalysis character. In accordance with these qualities, NTA was treated with acid so as to enhance its surface activity. Surface structures and surface groups of acid-treated NTA were characterized and analyzed by Transmission Electron Microscope (TEM) and Fourier Transform Infrared Spectrometry (FT-IR). The interaction between acid-treated NTA and amino acids was investigated. Analysis results showed that the lengths of acid-treated NTA became obviously shorter. The diameters of nanotube bundles did not change obviously with acid-treating. Meanwhile, the surface of acid-treated NTA was cross-linked with carboxyl or esterfunction. In addition, acid-treated NTA can catch amino acid residues easily, and then form close combination.

  7. Docosahexaenoic acid and lactation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Docosahexaenoic acid (DHA) is an important component of membrane phospholipids in the retina, and brain, and accumulates rapidly in these tissues during early infancy. DHA is present in human milk, but the amount varies considerably and is largely dependent on maternal diet. This article reviews dat...

  8. Orphenadrinium picrate picric acid

    PubMed Central

    Fun, Hoong-Kun; Hemamalini, Madhukar; Siddaraju, B. P.; Yathirajan, H. S.; Narayana, B.

    2010-01-01

    The asymmetric unit of the title compound N,N-dimethyl-2-[(2-methyl­phen­yl)phenyl­meth­oxy]ethanaminium picrate picric acid, C18H24NO+·C6H2N3O7 −·C6H3N3O7, contains one orphenadrinium cation, one picrate anion and one picric acid mol­ecule. In the orphenadrine cation, the two aromatic rings form a dihedral angle of 70.30 (7)°. There is an intra­molecular O—H⋯O hydrogen bond in the picric acid mol­ecule, which generates an S(6) ring motif. In the crystal structure, the orphenadrine cations, picrate anions and picric acid mol­ecules are connected by strong inter­molecular N—H⋯O hydrogen bonds, π⋯π inter­actions between the benzene rings of cations and anions [centroid–centroid distance = 3.5603 (9) Å] and weak C—H⋯O hydrogen bonds, forming a three-dimensional network. PMID:21580426

  9. Acid Rain Investigations.

    ERIC Educational Resources Information Center

    Hugo, John C.

    1992-01-01

    Presents an activity in which students investigate the formation of solid ammonium chloride aerosol particles to help students better understand the concept of acid rain. Provides activity objectives, procedures, sample data, clean-up instructions, and questions and answers to help interpret the data. (MDH)

  10. The Acid Rain Debate.

    ERIC Educational Resources Information Center

    Oates-Bockenstedt, Catherine

    1997-01-01

    Details an activity designed to motivate students by incorporating science-related issues into a classroom debate. Includes "The Acid Rain Bill" and "Position Guides" for student roles as committee members, consumers, governors, industry owners, tourism professionals, senators, and debate directors. (DKM)

  11. Acid rain bibliography

    SciTech Connect

    Sayers, C.S.

    1983-09-01

    This bibliography identifies 900 citations on various aspects of Acid Rain, covering published bibliographies, books, reports, conference and symposium proceedings, audio visual materials, pamphlets and newsletters. It includes five sections: citations index (complete record of author, title, source, order number); KWIC index; title index; author index; and source index. 900 references.

  12. Acid Rain Classroom Projects.

    ERIC Educational Resources Information Center

    Demchik, Michael J.

    2000-01-01

    Describes a curriculum plan in which students learn about acid rain through instructional media, research and class presentations, lab activities, simulations, design, and design implementation. Describes the simulation activity in detail and includes materials, procedures, instructions, examples, results, and discussion sections. (SAH)

  13. The Acid Rain Debate.

    ERIC Educational Resources Information Center

    Bybee, Rodger; And Others

    1984-01-01

    Describes an activity which provides opportunities for role-playing as industrialists, ecologists, and government officials. The activity involves forming an international commission on acid rain, taking testimony, and, based on the testimony, making recommendations to governments on specific ways to solve the problem. Includes suggestions for…

  14. The Acid Rain Game.

    ERIC Educational Resources Information Center

    Rakow, Steven J.; Glenn, Allen

    1982-01-01

    Provides rationale for and description of an acid rain game (designed for two players), a problem-solving model for elementary students. Although complete instructions are provided, including a copy of the game board, the game is also available for Apple II microcomputers. Information for the computer program is available from the author.…

  15. Targeting tumor acidity

    NASA Astrophysics Data System (ADS)

    Reshetnyak, Yana K.; Engelman, Donald M.; Andreev, Oleg A.

    2012-02-01

    One of the main features of solid tumors is extracellular acidity, which correlates with tumor aggressiveness and metastatic potential. We introduced novel approach in targeting of acidic tumors, and translocation of cell-impermeable cargo molecules across cellular membrane. Our approach is based on main principle of insertion and folding of a polypeptide in lipid bilayer of membrane. We have identified family of pH Low Insertion Peptides (pHLIPs), which are capable spontaneous insertion and folding in membrane at mild acidic conditions. The affinity of peptides of pHLIP family to membrane at low pH is several times higher than at neutral pH. The process of peptides folding occurs within milliseconds. The energy released in a result of folding (about 2 kcal/mol) could be used to move polar cargo across a membrane, which is a novel concept in drug delivery. pHLIP peptides could be considered as a pH-sensitive single peptide molecular transporters and conjugated with imaging probes for fluorescence, MR, PET and SPECT imaging, they represent a novel in vivo marker of acidity. The work is supported by NIH grants CA133890 and GM073857 to OAA, DME, YRK.

  16. Spermatotoxicity of dichloroacetic acid

    EPA Science Inventory

    The testicular toxicity of dichloroacetic acid (DCA), a disinfection byproduct of drinking water, was evaluated in adult male rats given both single and multiple (up to 14 d) oral doses. Delayed spermiation and altered resorption of residual bodies were observed in rats given sin...

  17. Plant fatty acid hydroxylase

    DOEpatents

    Somerville, Chris; van de Loo, Frank

    2000-01-01

    The present invention relates to the identification of nucleic acid sequences and constructs, and methods related thereto, and the use of these sequences and constructs to produce genetically modified plants for the purpose of altering the composition of plant oils, waxes and related compounds.

  18. Alkyl phosphonic acids and sulfonic acids in the Murchison meteorite

    NASA Technical Reports Server (NTRS)

    Cooper, George W.; Onwo, Wilfred M.; Cronin, John R.

    1992-01-01

    Homologous series of alkyl phosphonic acids and alkyl sulfonic acids, along with inorganic orthophosphate and sulfate, are identified in water extracts of the Murchison meteorite after conversion to their t-butyl dimethylsilyl derivatives. The methyl, ethyl, propyl, and butyl compounds are observed in both series. Five of the eight possible alkyl phosphonic acids and seven of the eight possible alkyl sulfonic acids through C4 are identified. Abundances decrease with increasing carbon number as observed of other homologous series indigenous to Murchison. Concentrations range downward from approximately 380 nmol/gram in the alkyl sulfonic acid series, and from 9 nmol/gram in the alkyl phosphonic acid series.

  19. A Direct, Biomass-Based Synthesis of Benzoic Acid: Formic Acid-Mediated Deoxygenation of the Glucose-Derived Materials Quinic Acid and Shikimic Acid

    SciTech Connect

    Arceo, Elena; Ellman, Jonathan; Bergman, Robert

    2010-05-03

    An alternative biomass-based route to benzoic acid from the renewable starting materials quinic acid and shikimic acid is described. Benzoic acid is obtained selectively using a highly efficient, one-step formic acid-mediated deoxygenation method.

  20. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as... sulfuric acid or hydrochloric acid as impurities, when offered for transportation or transported by...

  1. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as... sulfuric acid or hydrochloric acid as impurities, when offered for transportation or transported by...

  2. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as... sulfuric acid or hydrochloric acid as impurities, when offered for transportation or transported by...

  3. Synthesis of acid addition salt of delta-aminolevulinic acid from 5-bromo levulinic acid esters

    DOEpatents

    Moens, Luc

    2003-06-24

    A process of preparing an acid addition salt of delta-aminolevulinc acid comprising: a) dissolving a lower alkyl 5-bromolevulinate and hexamethylenetetramine in a solvent selected from the group consisting of water, ethyl acetate, chloroform, acetone, ethanol, tetrahydrofuran and acetonitrile, to form a quaternary ammonium salt of the lower alkyl 5-bromolevulinate; and b) hydrolyzing the quaternary ammonium salt with an inorganic acid to form an acid addition salt of delta-aminolevulinic acid.

  4. Photostabilization of ascorbic acid with citric acid, tartaric acid and boric acid in cream formulations.

    PubMed

    Ahmad, I; Ali Sheraz, M; Ahmed, S; Shad, Z; Vaid, F H M

    2012-06-01

    This study involves the evaluation of the effect of certain stabilizers, that is, citric acid (CT), tartaric acid (TA) and boric acid (BA) on the degradation of ascorbic acid (AH(2) ) in oil-in-water cream formulations exposed to the UV light and stored in the dark. The apparent first-order rate constants (0.34-0.95 × 10(-3) min(-1) in light, 0.38-1.24 × 10(-2) day(-1) in dark) for the degradation reactions in the presence of the stabilizers have been determined. These rate constants have been used to derive the second-order rate constants (0.26-1.45 × 10(-2) M(-1) min(-1) in light, 3.75-8.50 × 10(-3) M(-1) day(-1) in dark) for the interaction of AH(2) and the individual stabilizers. These stabilizers are effective in causing the inhibition of the rate of degradation of AH(2) both in the light and in the dark. The inhibitory effect of the stabilizers is in the order of CT > TA > BA. The rate of degradation of AH(2) in the presence of these stabilizers in the light is about 120 times higher than that in the dark. This could be explained on the basis of the deactivation of AH(2) -excited triplet state by CT and TA and by the inhibition of AH(2) degradation through complex formation with BA. AH(2) leads to the formation of dehydroascorbic acid (A) by chemical and photooxidation in cream formulations.

  5. Fatty acid-producing hosts

    DOEpatents

    Pfleger, Brian F; Lennen, Rebecca M

    2013-12-31

    Described are hosts for overproducing a fatty acid product such as a fatty acid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at 37.degree. C. Methods of producing a fatty acid product comprising culturing such hosts at 37.degree. C. are also described.

  6. Acid diffusion through polyaniline membranes

    SciTech Connect

    Su, T.M.; Huang, S.C.; Conklin, J.A.

    1995-12-01

    Polyaniline membranes in the undoped (base) and doped (acid) forms are studied for their utility as pervaporation membranes. The separation of water from mixtures of propionic acid, acetic acid and formic acid have been demonstrated from various feed compositions. Doped polyaniline displays an enhanced selectivity of water over these organic acids as compared with undoped polyaniline. For as-cast polyaniline membranes a diffusion coefficient (D) on the order of 10{sup -9} cm{sup 2}/sec has been determined for the flux of protons through the membranes using hydrochloric acid.

  7. Treatment of Bile Acid Amidation Defects with Glycocholic Acid

    PubMed Central

    Heubi, James E.; Setchell, Kenneth D.R.; Jha, Pinky; Buckley, Donna; Zhang, Wujuan; Rosenthal, Philip; Potter, Carol; Horslen, Simon; Suskind, David

    2014-01-01

    Bile acid amidation defects were predicted to present with fat/fat soluble vitamin malabsorption with minimal cholestasis. We identified and treated 5 patients (1 male/4 females) from 4 families with defective bile acid amidation due to a genetically confirmed deficiency in bile acid CoA:amino acid N-acyl transferase (BAAT) with the conjugated bile acid, glycocholic acid (GCA). Fast atom bombardment-mass spectrometry analysis of urine and bile at baseline revealed predominantly unconjugated cholic acid and absence of the usual glycine and taurine conjugated primary bile acids. Treatment with 15 mg/kg GCA resulted in total duodenal bile acid concentrations of 23.3 ± 19.1 mmol/L (mean ± SD) and 63.5 ± 4.0% of the bile acids were secreted in bile in the conjugated form of which GCA represented 59.6 ± 9.3% of the total biliary bile acids. Unconjugated cholic acid continued to be present in high concentrations in bile because of partial intestinal deconjugation of orally administered GCA. Serum total bile acid concentrations did not significantly differ between pretreatment and post-treatment samples and serum contained predominantly unconjugated cholic acid. These findings confirmed efficient intestinal absorption, hepatic extraction and biliary secretion of the administered GCA. Oral tolerance tests for vitamin D2 (1000 IU vitamin D2/kg) and tocopherol (100 IU/kg tocopherol acetate) demonstrated improvement in fat-soluble vitamin absorption after GCA treatment. Growth improved in 3/3 growth-delayed prepubertal patients. Conclusions: Oral glycocholic acid therapy is safe and effective in improving growth and fat-soluble vitamin absorption in children and adolescents with inborn errors of bile acid metabolism due to amidation defects. PMID:25163551

  8. [Lipid synthesis by an acidic acid tolerant Rhodotorula glutinis].

    PubMed

    Lin, Zhangnan; Liu, Hongjuan; Zhang, Jian'an; Wang, Gehua

    2016-03-01

    Acetic acid, as a main by-product generated in the pretreatment process of lignocellulose hydrolysis, significantly affects cell growth and lipid synthesis of oleaginous microorganisms. Therefore, we studied the tolerance of Rhodotorula glutinis to acetic acid and its lipid synthesis from substrate containing acetic acid. In the mixed sugar medium containing 6 g/L glucose and 44 g/L xylose, and supplemented with acetic acid, the cell growth was not:inhibited when the acetic acid concentration was below 10 g/L. Compared with the control, the biomass, lipid concentration and lipid content of R. glutinis increased 21.5%, 171% and 122% respectively when acetic acid concentration was 10 g/L. Furthermore, R. glutinis could accumulate lipid with acetate as the sole carbon source. Lipid concentration and lipid yield reached 3.20 g/L and 13% respectively with the initial acetic acid concentration of 25 g/L. The lipid composition was analyzed by gas chromatograph. The main composition of lipid produced with acetic acid was palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid, including 40.9% saturated fatty acids and 59.1% unsaturated fatty acids. The lipid composition was similar to that of plant oil, indicating that lipid from oleaginous yeast R. glutinis had potential as the feedstock of biodiesel production. These results demonstrated that a certain concentration of acetic acid need not to be removed in the detoxification process when using lignocelluloses hydrolysate to produce microbial lipid by R. glutinis. PMID:27349116

  9. NAPAP (National Acid Precipitation Assessment Program) results on acid rain

    SciTech Connect

    Not Available

    1990-06-01

    The National Acid Precipitation Assessment Program (NAPAP) was mandated by Congress in 1980 to study the effects of acid rain. The results of 10 years of research on the effect of acid deposition and ozone on forests, particularly high elevation spruce and fir, southern pines, eastern hardwoods and western conifers, will be published this year.

  10. Acid Earth--The Global Threat of Acid Pollution.

    ERIC Educational Resources Information Center

    McCormick, John

    Acid pollution is a major international problem, but the debate it has elicited has often clouded the distinction between myth and facts. This publication attempts to concerning the acid pollution situation. This publication attempts to identify available facts. It is the first global review of the problem of acid pollution and the first to…

  11. Usnic acid controls the acidity tolerance of lichens.

    PubMed

    Hauck, Markus; Jürgens, Sascha-René

    2008-11-01

    The hypotheses were tested that, firstly, lichens producing the dibenzofuran usnic acid colonize substrates characterized by specific pH ranges, secondly, this preferred pH is in a range where soluble usnic acid and its corresponding anion occur in similar concentrations, and thirdly, usnic acid makes lichens vulnerable to acidity. Lichens with usnic acid prefer an ambient pH range between 3.5 and 5.5 with an optimum between 4.0 and 4.5. This optimum is close to the pK(a1) value of usnic acid of 4.4. Below this optimum pH, dissolved SO(2) reduces the chlorophyll fluorescence yield more in lichens with than without their natural content of usnic acid. This suggests that usnic acid influences the acidity tolerance of lichens. The putative mechanism of the limited acidity tolerance of usnic acid-containing lichens is the acidification of the cytosol by molecules of protonated usnic acid shuttling protons through the plasma membrane at an apoplastic pH

  12. College Chemistry Students' Mental Models of Acids and Acid Strength

    ERIC Educational Resources Information Center

    McClary, LaKeisha; Talanquer, Vicente

    2011-01-01

    The central goal of this study was to characterize the mental models of acids and acid strength expressed by advanced college chemistry students when engaged in prediction, explanation, and justification tasks that asked them to rank chemical compounds based on their relative acid strength. For that purpose we completed a qualitative research…

  13. Acid hydrolysis of cellulose

    SciTech Connect

    Salazar, H.

    1980-12-01

    One of the alternatives to increase world production of etha nol is by the hydrolysis of cellulose content of agricultural residues. Studies have been made on the types of hydrolysis: enzimatic and acid. Data obtained from the sulphuric acid hydrolysis of cellulose showed that this process proceed in two steps, with a yield of approximately 95% glucose. Because of increases in cost of alternatives resources, the high demand of the product and the more economic production of ethanol from cellulose materials, it is certain that this technology will be implemented in the future. At the same time further studies on the disposal and reuse of the by-products of this production must be undertaken.

  14. [Progress in glucaric acid].

    PubMed

    Qiu, Yuying; Fang, Fang; Du, Guocheng; Chen, Jian

    2015-04-01

    Glucaric acid (GA) is derived from glucose and commonly used in chemical industry. It is also considered as one of the "Top value-added chemicals from biomass" as carbohydrate monomers to produce various synthetic polymers and bioenergy. The demand for GA in food manufacture is increasing. GA has also attracted public attentions due to its therapeutic uses such as regulating hormones, increasing the immune function and reducing the risks of cancers. Currently GA is produced by chemical oxidation. Research on production of GA via microbial synthesis is still at preliminary stage. We reviewed the advances of glucaric acid applications, preparation and quantification methods. The prospects on production of GA by microbial fermentation were also discussed. PMID:26380405

  15. Eucomic acid methanol monosolvate

    PubMed Central

    Li, Guo-Qiang; Li, Yao-Lan; Wang, Guo-Cai; Liang, Zhi-Hong; Jiang, Ren-Wang

    2011-01-01

    In the crystal structure of the title compound [systematic name: 2-hy­droxy-2-(4-hy­droxy­benz­yl)butane­dioic acid methanol monosolvate], C11H12O6·CH3OH, the dihedral angles between the planes of the carboxyl groups and the benzene ring are 51.23 (9) and 87.97 (9)°. Inter­molecular O—H⋯O hydrogen-bonding inter­actions involving the hy­droxy and carb­oxy­lic acid groups and the methanol solvent mol­ecule give a three-dimensional structure. PMID:22091200

  16. Industrial ecotoxicology "acid rain".

    PubMed

    Astolfi, E; Gotelli, C; Higa, J

    1986-01-01

    The acid rain phenomenon was studied in the province of Cordoba, Argentina. This study, based on a previously outlined framework, determined the anthropogenic origin of the low pH due to the presence of industrial hydrochloric acid wastage. This industrial ecotoxicological phenomenon seriously affected the forest wealth, causing a great defoliation of trees and shrubs, with a lower effect on crops. A survey on its effects on human beings has not been carried out, but considering the corrosion caused to different metals and its denouncing biocide effect on plants and animals, we should expect to find some kind of harm to the health of the workers involved or others engaged in farming, and even to those who are far away from the polluting agent. PMID:3758667

  17. Industrial ecotoxicology "acid rain".

    PubMed

    Astolfi, E; Gotelli, C; Higa, J

    1986-01-01

    The acid rain phenomenon was studied in the province of Cordoba, Argentina. This study, based on a previously outlined framework, determined the anthropogenic origin of the low pH due to the presence of industrial hydrochloric acid wastage. This industrial ecotoxicological phenomenon seriously affected the forest wealth, causing a great defoliation of trees and shrubs, with a lower effect on crops. A survey on its effects on human beings has not been carried out, but considering the corrosion caused to different metals and its denouncing biocide effect on plants and animals, we should expect to find some kind of harm to the health of the workers involved or others engaged in farming, and even to those who are far away from the polluting agent.

  18. (Radioiodinated free fatty acids)

    SciTech Connect

    Knapp, Jr., F. F.

    1987-12-11

    The traveler participated in the Second International Workshop on Radioiodinated Free Fatty Acids in Amsterdam, The Netherlands where he presented an invited paper describing the pioneering work at the Oak Ridge National Laboratory (ORNL) involving the design, development and testing of new radioiodinated methyl-branched fatty acids for evaluation of heart disease. He also chaired a technical session on the testing of new agents in various in vitro and in vivo systems. He also visited the Institute for Clinical and Experimental Nuclear Medicine in Bonn, West Germany, to review, discuss, plan and coordinate collaborative investigations with that institution. In addition, he visited the Cyclotron Research Center in Liege, Belgium, to discuss continuing collaborative studies with the Osmium-191/Iridium-191m radionuclide generator system, and to complete manuscripts and plan future studies.

  19. Immunomodulatory spherical nucleic acids.

    PubMed

    Radovic-Moreno, Aleksandar F; Chernyak, Natalia; Mader, Christopher C; Nallagatla, Subbarao; Kang, Richard S; Hao, Liangliang; Walker, David A; Halo, Tiffany L; Merkel, Timothy J; Rische, Clayton H; Anantatmula, Sagar; Burkhart, Merideth; Mirkin, Chad A; Gryaznov, Sergei M

    2015-03-31

    Immunomodulatory nucleic acids have extraordinary promise for treating disease, yet clinical progress has been limited by a lack of tools to safely increase activity in patients. Immunomodulatory nucleic acids act by agonizing or antagonizing endosomal toll-like receptors (TLR3, TLR7/8, and TLR9), proteins involved in innate immune signaling. Immunomodulatory spherical nucleic acids (SNAs) that stimulate (immunostimulatory, IS-SNA) or regulate (immunoregulatory, IR-SNA) immunity by engaging TLRs have been designed, synthesized, and characterized. Compared with free oligonucleotides, IS-SNAs exhibit up to 80-fold increases in potency, 700-fold higher antibody titers, 400-fold higher cellular responses to a model antigen, and improved treatment of mice with lymphomas. IR-SNAs exhibit up to eightfold increases in potency and 30% greater reduction in fibrosis score in mice with nonalcoholic steatohepatitis (NASH). Given the clinical potential of SNAs due to their potency, defined chemical nature, and good tolerability, SNAs are attractive new modalities for developing immunotherapies.

  20. Acid rain in Asia

    SciTech Connect

    Bhatti, N.; Streets, D.G. ); Foell, W.K. )

    1991-01-01

    Acid rain has been an issue of widespread concern in North America and Europe for more than fifteen years. However, there is an emerging feeling that the problem in Europe and North America is nearing solution, largely as a result of existing and newly enacted legislation, decreased energy use due to conservation and efficiency improvements, and/or trends in energy policy away from fossil fuels. The situation in Asia appears much bleaker. Fossil fuels are already used in large quantities, such that local air pollution is becoming a serious problem and high deposition levels are being measured. Emission regulations in most countries (with the notable exception of Japan) are not very stringent. Energy plans in many countries (particularly PRC, India, Thailand, and South Korea) call for very large increases in coal combustion in the future. Finally, there is not presently a strong scientific or public constituency for action to mitigate the potential effects of acid deposition. These factors imply potentially serious problems in the future for long-range transport and deposition of sulfur and nitrogen species and consequent damage to ecosystems and materials. The political ramifications of transboundary environmental pollution in this region are also potentially serious. The purpose of this paper is to provide background information on the acid deposition situation in Asia, with the intention of laying the foundation for the development of a possible research program for this region. 36 refs., 8 figs., 8 tabs.

  1. Immunomodulatory spherical nucleic acids

    PubMed Central

    Radovic-Moreno, Aleksandar F.; Chernyak, Natalia; Mader, Christopher C.; Nallagatla, Subbarao; Kang, Richard S.; Hao, Liangliang; Walker, David A.; Halo, Tiffany L.; Merkel, Timothy J.; Rische, Clayton H.; Anantatmula, Sagar; Burkhart, Merideth; Mirkin, Chad A.; Gryaznov, Sergei M.

    2015-01-01

    Immunomodulatory nucleic acids have extraordinary promise for treating disease, yet clinical progress has been limited by a lack of tools to safely increase activity in patients. Immunomodulatory nucleic acids act by agonizing or antagonizing endosomal toll-like receptors (TLR3, TLR7/8, and TLR9), proteins involved in innate immune signaling. Immunomodulatory spherical nucleic acids (SNAs) that stimulate (immunostimulatory, IS-SNA) or regulate (immunoregulatory, IR-SNA) immunity by engaging TLRs have been designed, synthesized, and characterized. Compared with free oligonucleotides, IS-SNAs exhibit up to 80-fold increases in potency, 700-fold higher antibody titers, 400-fold higher cellular responses to a model antigen, and improved treatment of mice with lymphomas. IR-SNAs exhibit up to eightfold increases in potency and 30% greater reduction in fibrosis score in mice with nonalcoholic steatohepatitis (NASH). Given the clinical potential of SNAs due to their potency, defined chemical nature, and good tolerability, SNAs are attractive new modalities for developing immunotherapies. PMID:25775582

  2. Perfluorooctanoic acid and environmental risks

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acids (PFAA) family of chemicals, which consist of a carbon backbone typically four to fourteen carbons in length and a charged functional moiety.

  3. Folic Acid Questions and Answers

    MedlinePlus

    ... swallow large pills. How can I take a vitamin with folic acid? A : These days, multivitamins with folic acid come in chewable chocolate or fruit flavors, liquids, and large oval or smaller round ...

  4. Omega-3 fatty acids (image)

    MedlinePlus

    Omega-3 fatty acids are a form of polyunsaturated fat that the body derives from food. Omega-3s (and omega-6s) are known as essential fatty acids (EFAs) because they are important for good health. ...

  5. Acid rain: Reign of controversy

    SciTech Connect

    Kahan, A.M.

    1986-01-01

    Acid Rain is a primer on the science and politics of acid rain. Several introductory chapters describe in simple terms the relevant principles of water chemistry, soil chemistry, and plant physiology and discuss the demonstrated or postulated effects of acid rain on fresh waters and forests as well as on statuary and other exposed objects. There follow discussions on the economic and social implications of acid rain (for example, possible health effects) and on the sources, transport, and distribution of air pollutants.

  6. Sedimentation of sulfuric acid in acid tars from current production

    SciTech Connect

    Denisova, T.L.; Frolov, A.F.; Aminov, A.N.; Novosel'tsev, S.P.

    1987-09-01

    Acid tars obtained in treating T-750, KhF-12, and I-8A oils were investigated for purposes of recovering sulfuric acid and asphalt binders from the compositions and of determining the effects of storage time on the recovery. The consumption and sedimentation levels of sulfuric acid during storage for different periods and at different temperatures were assessed. The characteristics of an asphalt binder obtained by neutralizing acid tar with a paste consisting of asphalts from deasphalting operations and slaked lime, followed by oxidation of the mixture with atmospheric air, were determined. The sulfuric acid recovered in the settling process could be burned in order to purify it of organic contaminants.

  7. Sequential injection redox or acid-base titration for determination of ascorbic acid or acetic acid.

    PubMed

    Lenghor, Narong; Jakmunee, Jaroon; Vilen, Michael; Sara, Rolf; Christian, Gary D; Grudpan, Kate

    2002-12-01

    Two sequential injection titration systems with spectrophotometric detection have been developed. The first system for determination of ascorbic acid was based on redox reaction between ascorbic acid and permanganate in an acidic medium and lead to a decrease in color intensity of permanganate, monitored at 525 nm. A linear dependence of peak area obtained with ascorbic acid concentration up to 1200 mg l(-1) was achieved. The relative standard deviation for 11 replicate determinations of 400 mg l(-1) ascorbic acid was 2.9%. The second system, for acetic acid determination, was based on acid-base titration of acetic acid with sodium hydroxide using phenolphthalein as an indicator. The decrease in color intensity of the indicator was proportional to the acid content. A linear calibration graph in the range of 2-8% w v(-1) of acetic acid with a relative standard deviation of 4.8% (5.0% w v(-1) acetic acid, n=11) was obtained. Sample throughputs of 60 h(-1) were achieved for both systems. The systems were successfully applied for the assays of ascorbic acid in vitamin C tablets and acetic acid content in vinegars, respectively.

  8. Nervonic acid and demyelinating disease.

    PubMed

    Sargent, J R; Coupland, K; Wilson, R

    1994-04-01

    Demyelination in adrenoleukodystrophy (ALD) is associated with an accumulation of very long chain saturated fatty acids such as 26:0 stemming from a genetic defect in the peroxisomal beta oxidation system responsible for the chain shortening of these fatty acids. Long chain monoenoic acids such as erucic acid, 22:1(n-9), can normalise elevated serum levels of 26:0 in ALD by depressing their biosynthesis from shorter chain saturated fatty acids. Sphingolipids from post mortem ALD brain have decreased levels of nervonic acid, 24:1(n-9), and increased levels of stearic acid, 18:0. Increased levels of 26:0 are accompanied by decreased nervonic acid biosynthesis in skin fibroblasts from ALD patients. Sphingolipids from post mortem MS brain have the same decreased 24:1(n-9) and increased 18:0 seen in post mortem ALD brain. The 24:1(n-9) content of sphingomyelin is depressed in erythrocytes from multiple sclerosis (MS) patients. Defects in the microsomal biosynthesis of very long chain fatty acids including 24:1(n-9) in 'jumpy' and 'quaking' mice are accompanied by impaired myelination. An impairment in the provision of nervonic acid in demyelinating diseases is indicated, suggesting that dietary therapy with oils rich in very long chain monenoic acid fatty acids may be beneficial in such conditions.

  9. Pantothenic acid biosynthesis in zymomonas

    SciTech Connect

    Tao, Luan; Tomb, Jean-Francois; Viitanen, Paul V.

    2014-07-01

    Zymomonas is unable to synthesize pantothenic acid and requires this essential vitamin in growth medium. Zymomonas strains transformed with an operon for expression of 2-dehydropantoate reductase and aspartate 1-decarboxylase were able to grow in medium lacking pantothenic acid. These strains may be used for ethanol production without pantothenic acid supplementation in seed culture and fermentation media.

  10. An Umbrella for Acid Rain.

    ERIC Educational Resources Information Center

    Randal, Judith

    1979-01-01

    The Environmental Protection Agency has awarded several grants to study effects of and possible solutions to the problem of "acid rain"; pollution from atmospheric nitric and sulfuric acids. The research program is administered through North Carolina State University at Raleigh and will focus on biological effects of acid rain. (JMF)

  11. Carboxylic acid sorption regeneration process

    DOEpatents

    King, C.J.; Poole, L.J.

    1995-05-02

    Carboxylic acids are sorbed from aqueous feedstocks into an organic liquid phase or onto a solid adsorbent. The acids are freed from the sorbent phase by treating it with aqueous alkylamine thus forming an alkylammonium carboxylate which is dewatered and decomposed to the desired carboxylic acid and the alkylamine. 10 figs.

  12. Carboxylic acid sorption regeneration process

    DOEpatents

    King, C. Judson; Poole, Loree J.

    1995-01-01

    Carboxylic acids are sorbed from aqueous feedstocks into an organic liquid phase or onto a solid adsorbent. The acids are freed from the sorbent phase by treating it with aqueous alkylamine thus forming an alkylammonium carboxylate which is dewatered and decomposed to the desired carboxylic acid and the alkylamine.

  13. Heterogeneous uptake of amines by citric acid and humic acid.

    PubMed

    Liu, Yongchun; Ma, Qingxin; He, Hong

    2012-10-16

    Heterogeneous uptake of methylamine (MA), dimethylamine (DMA), and trimethylamine (TMA) onto citric acid and humic acid was investigated using a Knudsen cell reactor coupled to a quadrupole mass spectrometer at 298 K. Acid-base reactions between amines and carboxylic acids were confirmed. The observed uptake coefficients of MA, DMA, and TMA on citric acid at 298 K were measured to be 7.31 ± 1.13 × 10(-3), 6.65 ± 0.49 × 10(-3), and 5.82 ± 0.68 × 10(-3), respectively, and showed independence of sample mass. The observed uptake coefficients of MA, DMA, and TMA on humic acid at 298 K increased linearly with sample mass, and the true uptake coefficients of MA, DMA, and TMA were measured to be 1.26 ± 0.07 × 10(-5), 7.33 ± 0.40 × 10(-6), and 4.75 ± 0.15 × 10(-6), respectively. Citric acid, having stronger acidity, showed a higher reactivity than humic acid for a given amine; while the steric effect of amines was found to govern the reactivity between amines and citric acid or humic acid.

  14. Composition for nucleic acid sequencing

    SciTech Connect

    Korlach, Jonas; Webb, Watt W.; Levene, Michael; Turner, Stephen; Craighead, Harold G.; Foquet, Mathieu

    2008-08-26

    The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. A plurality of labelled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.

  15. Evolution of rosmarinic acid biosynthesis.

    PubMed

    Petersen, Maike; Abdullah, Yana; Benner, Johannes; Eberle, David; Gehlen, Katja; Hücherig, Stephanie; Janiak, Verena; Kim, Kyung Hee; Sander, Marion; Weitzel, Corinna; Wolters, Stefan

    2009-01-01

    Rosmarinic acid and chlorogenic acid are caffeic acid esters widely found in the plant kingdom and presumably accumulated as defense compounds. In a survey, more than 240 plant species have been screened for the presence of rosmarinic and chlorogenic acids. Several rosmarinic acid-containing species have been detected. The rosmarinic acid accumulation in species of the Marantaceae has not been known before. Rosmarinic acid is found in hornworts, in the fern family Blechnaceae and in species of several orders of mono- and dicotyledonous angiosperms. The biosyntheses of caffeoylshikimate, chlorogenic acid and rosmarinic acid use 4-coumaroyl-CoA from the general phenylpropanoid pathway as hydroxycinnamoyl donor. The hydroxycinnamoyl acceptor substrate comes from the shikimate pathway: shikimic acid, quinic acid and hydroxyphenyllactic acid derived from l-tyrosine. Similar steps are involved in the biosyntheses of rosmarinic, chlorogenic and caffeoylshikimic acids: the transfer of the 4-coumaroyl moiety to an acceptor molecule by a hydroxycinnamoyltransferase from the BAHD acyltransferase family and the meta-hydroxylation of the 4-coumaroyl moiety in the ester by a cytochrome P450 monooxygenase from the CYP98A family. The hydroxycinnamoyltransferases as well as the meta-hydroxylases show high sequence similarities and thus seem to be closely related. The hydroxycinnamoyltransferase and CYP98A14 from Coleus blumei (Lamiaceae) are nevertheless specific for substrates involved in RA biosynthesis showing an evolutionary diversification in phenolic ester metabolism. Our current view is that only a few enzymes had to be "invented" for rosmarinic acid biosynthesis probably on the basis of genes needed for the formation of chlorogenic and caffeoylshikimic acid while further biosynthetic steps might have been recruited from phenylpropanoid metabolism, tocopherol/plastoquinone biosynthesis and photorespiration. PMID:19560175

  16. Evolution of rosmarinic acid biosynthesis.

    PubMed

    Petersen, Maike; Abdullah, Yana; Benner, Johannes; Eberle, David; Gehlen, Katja; Hücherig, Stephanie; Janiak, Verena; Kim, Kyung Hee; Sander, Marion; Weitzel, Corinna; Wolters, Stefan

    2009-01-01

    Rosmarinic acid and chlorogenic acid are caffeic acid esters widely found in the plant kingdom and presumably accumulated as defense compounds. In a survey, more than 240 plant species have been screened for the presence of rosmarinic and chlorogenic acids. Several rosmarinic acid-containing species have been detected. The rosmarinic acid accumulation in species of the Marantaceae has not been known before. Rosmarinic acid is found in hornworts, in the fern family Blechnaceae and in species of several orders of mono- and dicotyledonous angiosperms. The biosyntheses of caffeoylshikimate, chlorogenic acid and rosmarinic acid use 4-coumaroyl-CoA from the general phenylpropanoid pathway as hydroxycinnamoyl donor. The hydroxycinnamoyl acceptor substrate comes from the shikimate pathway: shikimic acid, quinic acid and hydroxyphenyllactic acid derived from l-tyrosine. Similar steps are involved in the biosyntheses of rosmarinic, chlorogenic and caffeoylshikimic acids: the transfer of the 4-coumaroyl moiety to an acceptor molecule by a hydroxycinnamoyltransferase from the BAHD acyltransferase family and the meta-hydroxylation of the 4-coumaroyl moiety in the ester by a cytochrome P450 monooxygenase from the CYP98A family. The hydroxycinnamoyltransferases as well as the meta-hydroxylases show high sequence similarities and thus seem to be closely related. The hydroxycinnamoyltransferase and CYP98A14 from Coleus blumei (Lamiaceae) are nevertheless specific for substrates involved in RA biosynthesis showing an evolutionary diversification in phenolic ester metabolism. Our current view is that only a few enzymes had to be "invented" for rosmarinic acid biosynthesis probably on the basis of genes needed for the formation of chlorogenic and caffeoylshikimic acid while further biosynthetic steps might have been recruited from phenylpropanoid metabolism, tocopherol/plastoquinone biosynthesis and photorespiration.

  17. Microbial transformations of isocupressic acid.

    PubMed

    Lin, S J; Rosazza, J P

    1998-07-01

    Microbial transformations of the labdane-diterpene isocupressic acid (1) with different microorganisms yielded several oxygenated metabolites that were isolated and characterized by MS and NMR spectroscopic analyses. Nocardia aurantia (ATCC 12674) catalyzed the cleavage of the 13,14-double bond to yield a new nor-labdane metabolite, 2. Cunninghamella elegans (-) (NRRL 1393) gave 7beta-hydroxyisocupressic acid (3) and labda-7,13(E)-diene-6beta,15, 17-triol-19-oic acid (4), and Mucor mucedo (ATCC 20094) gave 2alpha-hydroxyisocupressic acid (5) and labda-8(17),14-diene-2alpha, 13-diol-19-oic acid (6).

  18. Invasive cleavage of nucleic acids

    DOEpatents

    Prudent, James R.; Hall, Jeff G.; Lyamichev, Victor I.; Brow, Mary Ann D.; Dahlberg, James E.

    2002-01-01

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

  19. Invasive cleavage of nucleic acids

    DOEpatents

    Prudent, James R.; Hall, Jeff G.; Lyamichev, Victor I.; Brow, Mary Ann D.; Dahlberg, James E.

    1999-01-01

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

  20. The politics of acid rain

    SciTech Connect

    Wilcher, M.E. )

    1989-01-01

    This work examines and compares the acid rain policies through the different political systems of Canada, Great Britain and the United States. Because the flow of acid rain can transcend national boundaries, acid rain has become a crucial international problem. According to the author, because of differences in governmental institutions and structure, the extent of governmental intervention in the industrial economy, the degree of reliance on coal for power generation, and the extent of acid rain damage, national responses to the acid rain problem have varied.

  1. [A catalogue of fatty acids].

    PubMed

    Canalejo, E; Martín Peña, G; Gómez Molero, L; Ruiz Galiana, J

    1996-01-01

    Fatty acids structure and function is an area of renewed interest because of its effects on plasma lipids, biosynthesis of prostaglandins, leucotrienes and thromboxanes, and the obligatory demands of some fatty acids, especially for the newborn. Fatty acids are identified in three different ways: by the classical nomenclature, by its trivial name, and by the new methods also known as the omega system. These three different methods have created some confusion. The aim of this article is to revise fatty acids chemical structure and to compile a list of nutritional important fatty acids with the three different terminologies.

  2. Tested Demonstrations: Color Oscillations in the Formic Acid-Nitric Acid-Sulfuric Acid System.

    ERIC Educational Resources Information Center

    Raw, C. J. G.; And Others

    1983-01-01

    Presented are procedures for demonstrating the production of color oscillations when nitric acid is added to a formic acid/concentrated sulfuric acid mixture. Because of safety considerations, "Super-8" home movie of the color changes was found to be satisfactory for demonstration purposes. (JN)

  3. Twinning of dodecanedicarboxylic acid

    NASA Technical Reports Server (NTRS)

    Sen, R.; Wilcox, W. R.

    1986-01-01

    Twinning of 1,10-dodecanedicarboxyl acid (DDA) was observed in 0.1 mm thick films with a polarizing microscope. Twins originated from polycrystalline regions which tended to nucleate on twin faces, and terminated by intersection gone another. Twinning increased dramatically with addition of organic compounds with a similar molecular size and shape. Increasing the freezing rate, increasing the temperature gradient, and addition of silica particles increased twinning. It is proposed that twins nucleate with polycrystals and sometimes anneal out before they become observable. The impurities may enhance twinning either by lowering the twin energy or by adsorbing on growing faces.

  4. Mycophenolic Acid in Silage

    PubMed Central

    Schneweis, Isabell; Meyer, Karsten; Hörmansdorfer, Stefan; Bauer, Johann

    2000-01-01

    We examined 233 silage samples and found that molds were present in 206 samples with counts between 1 × 103 and 8.9 × 107 (mean, 4.7 × 106) CFU/g. Mycophenolic acid, a metabolite of Penicillium roqueforti, was detected by liquid chromatography-mass spectrometry in 74 (32%) of these samples at levels ranging from 20 to 35,000 (mean, 1,400) μg/kg. This compound has well-known immunosuppressive properties, so feeding with contaminated silage may promote the development of infectious diseases in livestock. PMID:10919834

  5. Synthesis of amino acids

    DOEpatents

    Davis, J.W. Jr.

    1979-09-21

    A method is described for synthesizing amino acids preceding through novel intermediates of the formulas: R/sub 1/R/sub 2/C(OSOC1)CN, R/sub 1/R/sub 2/C(C1)CN and (R/sub 1/R/sub 2/C(CN)O)/sub 2/SO wherein R/sub 1/ and R/sub 2/ are each selected from hydrogen and monovalent hydrocarbon radicals of 1 to 10 carbon atoms. The use of these intermediates allows the synthesis steps to be exothermic and results in an overall synthesis method which is faster than the synthesis methods of the prior art.

  6. Beyond acid rain

    SciTech Connect

    Gaffney, J.S.; Streit, G.E.; Spall, W.D.; Hall, J.H.

    1987-06-01

    This paper discussed the effects of the interactions of soluble oxidants and organic toxins with sulfur dioxide and nitrogen dioxide. It suggested that these chemical reactions in the atmosphere produced a more potent acid rain which was harmful not only because it had a low pH but because it contained oxidants and organic toxins which were harmful to surface vegetation and the organisms found in surface waters. It was stressed that air pollution is a global problem and that is is necessary to develop a better fundamental understanding of how air pollution is causing damage to the streams and forests of the world. 50 references.

  7. Interstellar isothiocyanic acid

    NASA Technical Reports Server (NTRS)

    Frerking, M. A.; Linke, R. A.; Thaddeus, P.

    1979-01-01

    Isothiocyanic acid (HNCS) has been identified in Sgr B2 from millimeter-wave spectral line observations. We have definitely detected three rotational lines, and have probably detected two others. The rotational temperature of HNCS in Sgr B2 is 14 plus or minus 5 K, its column density is 2.5 plus or minus 1.0 x 10 to the 13th per sq cm, and its abundance relative to HNCO is consistent with the cosmic S/O ratio, 1/42.

  8. 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids and blood pressure.

    PubMed

    McGiff, J C; Quilley, J

    2001-03-01

    The properties of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids, vasoactivity and modulation of ion transport and mediation/modulation of the effects of vasoactive hormones, such as angiotensin II and endothelin, underscore their importance to renal vascular mechanisms and electrolyte excretion. 20-Hydroxyeicosatetraenoic acid is an integral component of renal autoregulation and tubuloglomerular feedback as well as cerebral autoregulation, eliciting vasoconstriction by the inhibition of potassium channels. Nitric oxide inhibits 20-hydroxyeicosatetraenoic acid formation, the removal of which contributes to the vasodilator effect of nitric oxide. In contrast, epoxyeicosatrienoic acids are generally vasodilatory by activating potassium channels and have been proposed as endothelium-derived hyperpolarizing factors. 20-Hydroxyeicosatetraenoic acid modulates ion transport in key nephron segments by influencing the activities of sodium--potassium-ATPase and the sodium--potassium--chloride co-transporter; however, the primacy of the various arachidonate oxygenases that generate products affecting these activities changes with age. The range and diversity of activity of 20-hydroxyeicosatetraenoic acid is influenced by its metabolism by cyclooxygenase to products affecting vasomotion and salt/water excretion. 20-Hydroxyeicosatetraenoic acid is the principal renal eicosanoid that interacts with several hormonal systems that are central to blood pressure regulation. This article reviews the most recent studies that address 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids in vascular and renal tubular function and hypertension.

  9. New developments in fluorescence detection of ALA-induced protoporphyrin IX for cancer localization

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Baumgartner, Reinhold; Betz, Christian; Bise, Karl; Brand, P.; Gamarra, Fernando; Haeussinger, Karl; Hillemanns, Peter; Huber, Rudolf M.; Knuechel, Ruth; Kriegmair, M.; Leunig, Andreas; Pichler, J.; Rick, Kai; Schulz, H.; Stanzel, F.; Stocker, Susanne; Wagner, Simon; Weigandt, H.

    1997-12-01

    After the very promising clinical results for the detection of bladder cancer in urology, preclinical and clinical studies on aminolevulinic acid (5-ALA) induced protoporphyrin IX (PPIX) are preformed in various disciplines now. This paper provides a brief overview of the progress on 5-ALA assisted fluorescence diagnosis in urology, pulmonology, neurosurgery, gynecology and ENT performed in collaboration with the Laser Research Laboratory at the Department of Urology of the Ludwig-Maximilians-University in Munich. Five-ALA can be applied either topically or systemically to induce an intracellular accumulation of fluorescing PPIX. With appropriate dosage of 5-ALA, malignant tissue can be stained selectively, and irradiation with violet light excites a bright red fluorescence of the tumor. Optical properties of the tissue tend to hamper the precise identification and demarcation of suspect areas in fluorescence images. Multicolor remission and fluorescence imaging, therefore, seems to be indispensable for a reliable tumor localization.

  10. ["... The better to see you with"--phothodynamic diagnostic in superficial bladder cancer].

    PubMed

    Forster, T H; Wyler, S; Ruszat, R; Gasser, T C; Bachmann, A

    2007-10-17

    Fluorescence cystoscopy of the urinary bladder allows to better identify tumors and altered bladder mucosa (e.g. Carcinoma in situ). Instillation of 5-aminolevulinic acid or hexyl aminolevulinate approx. two hours before transurethral resection leads to metabolism of these compounds in the Häm-biosynthesis and to accumulation of protoporphyrin IX (PPIX). PPIX is an excellent fluorochrom, which lights up red when illuminated by blue light. During transurethral resection all tumors and all suspicious mucosal areas can be completely resected. As a consequence recurrence rate drops and patients need less re-operations and hospitalizations.

  11. Quantitative spatial frequency fluorescence imaging in the sub-diffusive domain for image-guided glioma resection

    PubMed Central

    Sibai, Mira; Veilleux, Israel; Elliott, Jonathan T.; Leblond, Frederic; Wilson, Brian C.

    2015-01-01

    Intraoperative 5- aminolevulinic acid induced-Protoporphyrin IX (PpIX) fluorescence guidance enables maximum safe resection of glioblastomas by providing surgeons with real-time tumor optical contrast. However, visual assessment of PpIX fluorescence is subjective and limited by the distorting effects of light attenuation and tissue autofluorescence. We have previously shown that non-invasive point measurements of absolute PpIX concentration identifies residual tumor that is otherwise non-detectable. Here, we extend this approach to wide-field quantitative fluorescence imaging by implementing spatial frequency domain imaging to recover tissue optical properties across the field-of-view in phantoms and ex vivo tissue. PMID:26713206

  12. Liposomally formulated phospholipid-conjugated indocyanine green for intra-operative brain tumor detection and resection.

    PubMed

    Suganami, Akiko; Iwadate, Yasuo; Shibata, Sayaka; Yamashita, Masamichi; Tanaka, Tsutomu; Shinozaki, Natsuki; Aoki, Ichio; Saeki, Naokatsu; Shirasawa, Hiroshi; Okamoto, Yoshiharu; Tamura, Yutaka

    2015-12-30

    Some tumor-specific near-infrared (NIR) fluorescent dyes such as indocyanine green (ICG), IDRye800CW, and 5-aminolevulinic acid have been used clinically for detecting tumor margins or micro-cancer lesions. In this study, we evaluated the physicochemical properties of liposomally formulated phospholipid-conjugated ICG, denoted by LP-iDOPE, as a clinically translatable NIR imaging nanoparticle for brain tumors. We also confirmed its brain-tumor-specific biodistribution and its characteristics as the intra-operative NIR imaging nanoparticles for brain tumor surgery. These properties of LP-iDOPE may enable neurosurgeons to achieve more accurate identification and more complete resection of brain tumor.

  13. Vibrational structure of the polyunsaturated fatty acids eicosapentaenoic acid and arachidonic acid studied by infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Kiefer, Johannes; Noack, Kristina; Bartelmess, Juergen; Walter, Christian; Dörnenburg, Heike; Leipertz, Alfred

    2010-02-01

    The spectroscopic discrimination of the two structurally similar polyunsaturated C 20 fatty acids (PUFAs) 5,8,11,14,17-eicosapentaenoic acid and 5,8,11,14-eicosatetraenoic acid (arachidonic acid) is shown. For this purpose their vibrational structures are studied by means of attenuated total reflection (ATR) Fourier-transform infrared (FT-IR) spectroscopy. The fingerprint regions of the recorded spectra are found to be almost identical, while the C-H stretching mode regions around 3000 cm -1 show such significant differences as results of electronic and molecular structure alterations based on the different degree of saturation that both fatty acids can be clearly distinguished from each other.

  14. Nucleic acid detection methods

    DOEpatents

    Smith, C.L.; Yaar, R.; Szafranski, P.; Cantor, C.R.

    1998-05-19

    The invention relates to methods for rapidly determining the sequence and/or length a target sequence. The target sequence may be a series of known or unknown repeat sequences which are hybridized to an array of probes. The hybridized array is digested with a single-strand nuclease and free 3{prime}-hydroxyl groups extended with a nucleic acid polymerase. Nuclease cleaved heteroduplexes can be easily distinguish from nuclease uncleaved heteroduplexes by differential labeling. Probes and target can be differentially labeled with detectable labels. Matched target can be detected by cleaving resulting loops from the hybridized target and creating free 3-hydroxyl groups. These groups are recognized and extended by polymerases added into the reaction system which also adds or releases one label into solution. Analysis of the resulting products using either solid phase or solution. These methods can be used to detect characteristic nucleic acid sequences, to determine target sequence and to screen for genetic defects and disorders. Assays can be conducted on solid surfaces allowing for multiple reactions to be conducted in parallel and, if desired, automated. 18 figs.

  15. Nucleic Acid Detection Methods

    DOEpatents

    Smith, Cassandra L.; Yaar, Ron; Szafranski, Przemyslaw; Cantor, Charles R.

    1998-05-19

    The invention relates to methods for rapidly determining the sequence and/or length a target sequence. The target sequence may be a series of known or unknown repeat sequences which are hybridized to an array of probes. The hybridized array is digested with a single-strand nuclease and free 3'-hydroxyl groups extended with a nucleic acid polymerase. Nuclease cleaved heteroduplexes can be easily distinguish from nuclease uncleaved heteroduplexes by differential labeling. Probes and target can be differentially labeled with detectable labels. Matched target can be detected by cleaving resulting loops from the hybridized target and creating free 3-hydroxyl groups. These groups are recognized and extended by polymerases added into the reaction system which also adds or releases one label into solution. Analysis of the resulting products using either solid phase or solution. These methods can be used to detect characteristic nucleic acid sequences, to determine target sequence and to screen for genetic defects and disorders. Assays can be conducted on solid surfaces allowing for multiple reactions to be conducted in parallel and, if desired, automated.

  16. Cryoprotection from lipoteichoic acid

    NASA Astrophysics Data System (ADS)

    Rice, Charles V.; Middaugh, Amy; Wickham, Jason R.; Friedline, Anthony; Thomas, Kieth J.; Johnson, Karen; Zachariah, Malcolm; Garimella, Ravindranth

    2012-10-01

    Numerous chemical additives lower the freezing point of water, but life at sub-zero temperatures is sustained by a limited number of biological cryoprotectants. Antifreeze proteins in fish, plants, and insects provide protection to a few degrees below freezing. Microbes have been found to survive at even lower temperatures, and with a few exceptions, antifreeze proteins are missing. Survival has been attributed to external factors, such as the high salt concentration of brine veins and adhesion to particulates or ice crystal defects. We have discovered an endogenous cryoprotectant in the cell wall of bacteria, lipoteichoic acid biopolymers. Adding 1% LTA to bacteria cultures immediately prior to freezing provides 50% survival rate, similar to the results obtained with 1% glycerol. In the absence of an additive, bacterial survival is negligible as measured with the resazurin cell viability assay. The mode of action for LTA cryoprotection is unknown. With a molecular weight of 3-5 kDa, it is unlikely to enter the cell cytoplasm. Our observations suggest that teichoic acids could provide a shell of liquid water around biofilms and planktonic bacteria, removing the need for brine veins to prevent bacterial freezing.

  17. Bicyclic glutamic acid derivatives.

    PubMed

    Meyer, Udo; Bisel, Philippe; Weckert, Edgar; Frahm, August Wilhelm

    2006-05-15

    For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric alpha-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide. PMID:16596563

  18. Ribonucleic acid purification.

    PubMed

    Martins, R; Queiroz, J A; Sousa, F

    2014-08-15

    Research on RNA has led to many important biological discoveries and improvement of therapeutic technologies. From basic to applied research, many procedures employ pure and intact RNA molecules; however their isolation and purification are critical steps because of the easy degradability of RNA, which can impair chemical stability and biological functionality. The current techniques to isolate and purify RNA molecules still have several limitations and the requirement for new methods able to improve RNA quality to meet regulatory demands is growing. In fact, as basic research improves the understanding of biological roles of RNAs, the biopharmaceutical industry starts to focus on them as a biotherapeutic tools. Chromatographic bioseparation is a high selective unit operation and is the major option in the purification of biological compounds, requiring high purity degree. In addition, its application in biopharmaceutical manufacturing is well established. This paper discusses the importance and the progress of RNA isolation and purification, considering RNA applicability both in research and clinical fields. In particular and in view of the high specificity, affinity chromatography has been recently applied to RNA purification processes. Accordingly, recent chromatographic investigations based on biorecognition phenomena occurring between RNA and amino acids are focused. Histidine and arginine have been used as amino acid ligands, and their ability to isolate different RNA species demonstrated a multipurpose applicability in molecular biology analysis and RNA therapeutics preparation, highlighting the potential contribution of these methods to overcome the challenges of RNA purification. PMID:24951289

  19. Titration of phosphonic acid derivatives in mixtures.

    PubMed

    Wittmann, Z

    1980-01-01

    An analytical procedure is described for the determination of the weak acids phosphonomethyliminodiacetic acid and phosphonomethyliminoacetic acid in their mixtures, and the dissociation constants of phosphonomethyliminoacetic acid are reported.

  20. Growth of nitric acid hydrates on thin sulfuric acid films

    NASA Technical Reports Server (NTRS)

    Iraci, Laura T.; Middlebrook, Ann M.; Wilson, Margaret A.; Tolbert, Margaret A.

    1994-01-01

    Type I polar stratospheric clouds (PSCs) are thought to nucleate and grow on stratospheric sulfate aerosols (SSAs). To model this system, thin sulfuric acid films were exposed to water and nitric acid vapors (1-3 x 10(exp -4) Torr H2O and 1-2.5 x 10(exp -6) Torr HNO3) and subjected to cooling and heating cycles. Fourier Transform Infrared (FTIR) spectroscopy was used to probe the phase of the sulfuric acid and to identify the HNO3/H2O films that condensed. Nitric acid trihydrate (NAT) was observed to grow on crystalline sulfuric acid tetrahydrate (SAT) films. NAT also condensed in/on supercooled H2SO4 films without causing crystallization of the sulfuric acid. This growth is consistent with NAT nucleation from ternary solutions as the first step in PSC formation.

  1. Determination of benzoic acid, chlorobenzoic acids and chlorendic acid in water

    SciTech Connect

    Dietz, E.A.; Cortellucci, N.J.; Singley, K.F. )

    1993-01-01

    To characterize and conduct treatment studies of a landfill leachate an analysis procedure was required to determine concentrations of benzoic acid, the three isomers of chlorobenzoic acid and chlorendic acid. The title compounds were isolated from acidified (pH 1) water by extraction with methyl t-butyl ether. Analytes were concentrated by back-extracting the ether with 0.1 N sodium hydroxide which was separated and acidified. This solution was analyzed by C[sub 18] reversed-phase HPLC with water/acetonitrile/acetic acid eluent and UV detection at 222 nm. The method has detection limits of 200 [mu]g/L for chlorendic acid and 100 [mu]g/L for benzoic acid and each isomer of chlorobenzoic acid. Validation studies with water which was fortified with the analytes at concentrations ranging from one to ten times detection limits resulted in average recoveries of >95%.

  2. Acid rain: Rhetoric and reality

    SciTech Connect

    Park, C.C.

    1987-01-01

    Acid rain is now one of the most serious environmental problems in developed countries. Emissions and fallout were previously extremely localized, but since the introduction of tall stacks policies in both Britain and the US - pardoxically to disperse particulate pollutants and hence reduce local damage - emissions are now lifted into the upper air currents and carried long distances downwind. The acid rain debate now embraces many western countries - including Canada, the US, England, Scotland, Wales, Sweden, Norway, Denmark, West Germany, the Netherlands, Austria, Switzerland - and a growing number of eastern countries - including the Soviet Union, Poland, East Germany, and Czechoslovakia. The problem of acid rain arises, strictly speaking, not so much from the rainfall itself as from its effects on the environment. Runoff affects surface water and groundwater, as well as soils and vegetation. Consequently changes in rainfall acidity can trigger off a range of impacts on the chemistry and ecology of lakes and rivers, soil chemistry and processes, the health and productivity of plants, and building materials, and metallic structures. The most suitable solutions to the problems of acid rain require prevention rather than cure, and there is broad agreement in both the political scientific communities on the need to reduce emissions of sulfur and nitrogen oxides to the atmosphere. Book divisions discuss: the problem of acid rain, the science of acid rain, the technology of acid rain, and the politics of acid rain, in an effort to evaluate this growing global problem of acid rain.

  3. Therapeutic targeting of bile acids

    PubMed Central

    Gores, Gregory J.

    2015-01-01

    The first objectives of this article are to review the structure, chemistry, and physiology of bile acids and the types of bile acid malabsorption observed in clinical practice. The second major theme addresses the classical or known properties of bile acids, such as the role of bile acid sequestration in the treatment of hyperlipidemia; the use of ursodeoxycholic acid in therapeutics, from traditional oriental medicine to being, until recently, the drug of choice in cholestatic liver diseases; and the potential for normalizing diverse bowel dysfunctions in irritable bowel syndrome, either by sequestering intraluminal bile acids for diarrhea or by delivering more bile acids to the colon to relieve constipation. The final objective addresses novel concepts and therapeutic opportunities such as the interaction of bile acids and the microbiome to control colonic infections, as in Clostridium difficile-associated colitis, and bile acid targeting of the farnesoid X receptor and G protein-coupled bile acid receptor 1 with consequent effects on energy expenditure, fat metabolism, and glycemic control. PMID:26138466

  4. Bile Acid Metabolism and Signaling

    PubMed Central

    Chiang, John Y. L.

    2015-01-01

    Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans. PMID:23897684

  5. Bile acid interactions with cholangiocytes.

    PubMed

    Xia, Xuefeng; Francis, Heather; Glaser, Shannon; Alpini, Gianfranco; LeSage, Gene

    2006-06-14

    Cholangiocytes are exposed to high concentrations of bile acids at their apical membrane. A selective transporter for bile acids, the Apical Sodium Bile Acid Cotransporter (ASBT) (also referred to as Ibat; gene name Slc10a2) is localized on the cholangiocyte apical membrane. On the basolateral membrane, four transport systems have been identified (t-ASBT, multidrug resistance (MDR)3, an unidentified anion exchanger system and organic solute transporter (Ost) heteromeric transporter, Ostalpha-Ostbeta. Together, these transporters unidirectionally move bile acids from ductal bile to the circulation. Bile acids absorbed by cholangiocytes recycle via the peribiliary plexus back to hepatocytes for re-secretion into bile. This recycling of bile acids between hepatocytes and cholangiocytes is referred to as the cholehepatic shunt pathway. Recent studies suggest that the cholehepatic shunt pathway may contribute in overall hepatobiliary transport of bile acids and to the adaptation to chronic cholestasis due to extrahepatic obstruction. ASBT is acutely regulated by an adenosine 3', 5'-monophosphate (cAMP)-dependent translocation to the apical membrane and by phosphorylation-dependent ubiquitination and proteasome degradation. ASBT is chronically regulated by changes in gene expression in response to biliary bile acid concentration and inflammatory cytokines. Another potential function of cholangiocyte ASBT is to allow cholangiocytes to sample biliary bile acids in order to activate intracellular signaling pathways. Bile acids trigger changes in intracellular calcium, protein kinase C (PKC), phosphoinositide 3-kinase (PI3K), mitogen-activated protein (MAP) kinase and extracellular signal-regulated protein kinase (ERK) intracellular signals. Bile acids significantly alter cholangiocyte secretion, proliferation and survival. Different bile acids have differential effects on cholangiocyte intracellular signals, and in some instances trigger opposing effects on cholangiocyte

  6. Citric acid production patent review.

    PubMed

    Anastassiadis, Savas; Morgunov, Igor G; Kamzolova, Svetlana V; Finogenova, Tatiana V

    2008-01-01

    Current Review article summarizes the developments in citric acid production technologies in East and West last 100 years. Citric acid is commercially produced by large scale fermentation mostly using selected fungal or yeast strains in aerobe bioreactors and still remains one of the runners in industrial production of biotechnological bulk metabolites obtained by microbial fermentation since about 100 years, reflecting the historical development of modern biotechnology and fermentation process technology in East and West. Citric acid fermentation was first found as a fungal product in cultures of Penicillium glaucum on sugar medium by Wehmer in 1893. Citric acid is an important multifunctional organic acid with a broad range of versatile uses in household and industrial applications that has been produced industrially since the beginning of 20(th) century. There is a great worldwide demand for citric acid consumption due to its low toxicity, mainly being used as acidulant in pharmaceutical and food industries. Global citric acid production has reached 1.4 million tones, increasing annually at 3.5-4.0% in demand and consumption. Citric acid production by fungal submerged fermentation is still dominating, however new perspectives like solid-state processes or continuous yeast processes can be attractive for producers to stand in today's strong competition in industry. Further perspectives aiming in the improvement of citric acid production are the improvement of citric acid producing strains by classical and modern mutagenesis and selection as well as downstream processes. Many inexpensive by-products and residues of the agro-industry (e.g. molasses, glycerin etc.) can be economically utilized as substrates in the production of citric acid, especially in solid-state fermentation, enormously reducing production costs and minimizing environmental problems. Alternatively, continuous processes utilizing yeasts which reach 200-250 g/l citric acid can stand in today

  7. Bile acid interactions with cholangiocytes

    PubMed Central

    Xia, Xuefeng; Francis, Heather; Glaser, Shannon; Alpini, Gianfranco; LeSage, Gene

    2006-01-01

    Cholangiocytes are exposed to high concentrations of bile acids at their apical membrane. A selective transporter for bile acids, the Apical Sodium Bile Acid Cotransporter (ASBT) (also referred to as Ibat; gene name Slc10a2) is localized on the cholangiocyte apical membrane. On the basolateral membrane, four transport systems have been identified (t-ASBT, multidrug resistance (MDR)3, an unidentified anion exchanger system and organic solute transporter (Ost) heteromeric transporter, Ostα-Ostβ. Together, these transporters unidirectionally move bile acids from ductal bile to the circulation. Bile acids absorbed by cholangiocytes recycle via the peribiliary plexus back to hepatocytes for re-secretion into bile. This recycling of bile acids between hepatocytes and cholangiocytes is referred to as the cholehepatic shunt pathway. Recent studies suggest that the cholehepatic shunt pathway may contribute in overall hepatobiliary transport of bile acids and to the adaptation to chronic cholestasis due to extrahepatic obstruction. ASBT is acutely regulated by an adenosine 3', 5’-monophosphate (cAMP)-dependent translocation to the apical membrane and by phosphorylation-dependent ubiquitination and proteasome degradation. ASBT is chronically regulated by changes in gene expression in response to biliary bile acid concentration and inflammatory cytokines. Another potential function of cholangiocyte ASBT is to allow cholangiocytes to sample biliary bile acids in order to activate intracellular signaling pathways. Bile acids trigger changes in intracellular calcium, protein kinase C (PKC), phosphoinositide 3-kinase (PI3K), mitogen-activated protein (MAP) kinase and extracellular signal-regulated protein kinase (ERK) intracellular signals. Bile acids significantly alter cholangiocyte secretion, proliferation and survival. Different bile acids have differential effects on cholangiocyte intracellular signals, and in some instances trigger opposing effects on cholangiocyte

  8. Interactions of amino acids, carboxylic acids, and mineral acids with different quinoline derivatives

    NASA Astrophysics Data System (ADS)

    Kalita, Dipjyoti; Deka, Himangshu; Samanta, Shyam Sundar; Guchait, Subrata; Baruah, Jubaraj B.

    2011-03-01

    A series of quinoline containing receptors having amide and ester bonds are synthesized and characterised. The relative binding abilities of these receptors with various amino acids, carboxylic acids and mineral acids are determined by monitoring the changes in fluorescence intensity. Among the receptors bis(2-(quinolin-8-yloxy)ethyl) isophthalate shows fluorescence enhancement on addition of amino acids whereas the other receptors shows fluorescence quenching on addition of amino acids. The receptor N-(quinolin-8-yl)-2-(quinolin-8-yloxy) propanamide has higher binding affinity for amino acids. However, the receptor N-(quinolin-8-yl)-2-(quinolin-8-yloxy)acetamide having similar structure do not bind to amino acids. This is attributed to the concave structure of the former which is favoured due to the presence of methyl substituent. The receptor bis(2-(quinolin-8-yloxy)ethyl) isophthalate do not bind to hydroxy carboxylic acids, but is a good receptor for dicarboxylic acids. The crystal structure of bromide and perchlorate salts of receptor 2-bromo-N-(quinolin-8-yl)-propanamide are determined. In both the cases the amide groups are not in the plane of quinoline ring. The structure of N-(quinolin-8-yl)-2-(quinolin-8-yloxy)acetamide, N-(2-methoxyphenethyl)-2-(quinolin-8-yloxy)acetamide and their salts with maleic acid as well as fumaric acid are determined. It is observed that the solid state structures are governed by the double bond geometry of these two acid. Maleic acid forms salt in both the cases, whereas fumaric acid forms either salt or co-crystals.

  9. Acidity of Strong Acids in Water and Dimethyl Sulfoxide.

    PubMed

    Trummal, Aleksander; Lipping, Lauri; Kaljurand, Ivari; Koppel, Ilmar A; Leito, Ivo

    2016-05-26

    Careful analysis and comparison of the available acidity data of HCl, HBr, HI, HClO4, and CF3SO3H in water, dimethyl sulfoxide (DMSO), and gas-phase has been carried out. The data include experimental and computational pKa and gas-phase acidity data from the literature, as well as high-level computations using different approaches (including the W1 theory) carried out in this work. As a result of the analysis, for every acid in every medium, a recommended acidity value is presented. In some cases, the currently accepted pKa values were revised by more than 10 orders of magnitude. PMID:27115918

  10. Esterification by the Plasma Acidic Water: Novel Application of Plasma Acid

    NASA Astrophysics Data System (ADS)

    Gu, Ling

    2014-03-01

    This work explores the possibility of plasma acid as acid catalyst in organic reactions. Plasma acidic water was prepared by dielectric barrier discharge and used to catalyze esterification of n-heptanioc acid with ethanol. It is found that the plasma acidic water has a stable and better performance than sulfuric acid, meaning that it is an excellent acid catalyst. The plasma acidic water would be a promising alternative for classic mineral acid as a more environment friendly acid.

  11. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid...

  12. Acid rain degradation of nylon

    SciTech Connect

    Kyllo, K.E.

    1984-01-01

    Acid rain, precipitation with a pH less than 5.6, is known to damage lakes, vegetation and buildings. Degradation of outdoor textiles by acid rain is strongly suspected but not well documented. This study reports the effects of sunlight, aqueous acid, heat and humidity (acid rain conditions) on spun delustered nylon 6,6 fabric. Untreated nylon and nylon treated with sulfuric acid of pH 2.0, 3.0, and 4.4 were exposed to light in an Atlas Xenon-arc fadeometer at 63/sup 0/C and 65% R.H. for up to 640 AATCC Fading Units. The untreated and acid treated nylon fabrics were also exposed to similar temperature and humidity condition without light. Nylon degradation was determined by changes in breaking strength, elongation, molecular weight, color, amino end group concentration (NH/sub 2/) and /sup 13/C NMR spectra. Physical damage was assessed using SEM.

  13. A Simpler Nucleic Acid

    NASA Technical Reports Server (NTRS)

    Orgel, Leslie

    2000-01-01

    It has been supposed that for a nucleic acid analog to pair with RNA it must, like RNA, have a backbone with at least a sixatom repeat; a shorter backbone presumably would not stretch far enough to bind RNA properly. The Eschenmoser group has shown, however, that this first impression is incorrect.As they report in their new paper, Eschenmoser and co-workers ( I ) have now synthesized a substantial number of these polymers, which are called (L)-a-threofuranosyl oligonucleotides or TNAs. They are composed of bases linked to a threose sugar-phosphate backbone, with phosphodiester bonds connecting the nucleotides. The investigators discovered that pairs of complementary TNAs do indeed form stable Watson-Crick double helices and, perhaps more importantly, that TNAs form stable double helices with complementary RNAs and DNAs.

  14. [Hydrofluoric acid poisoning: case report].

    PubMed

    Cortina, Tatiana Judith; Ferrero, Hilario Andrés

    2013-01-01

    Hydrofluoric acid is a highly dangerous substance with industrial and domestically appliances. Clinical manifestations of poisoning depend on exposure mechanism, acid concentration and exposed tissue penetrability. Gastrointestinal tract symptoms do not correlate with injury severity. Patients with history of hydrofluoric acid ingestion should undergo an endoscopy of the upper gastrointestinal tract. Intoxication requires immediate intervention because systemic toxicity can take place. We present a 5 year old girl who accidentally swallowed 5 ml of 20% hydrofluoric acid. We performed gastrointestinal tract endoscopy post ingestion, which revealed erythematous esophagus and stomach with erosive lesions. Two months later, same study was performed and revealed esophagus and stomach normal mucous membrane.

  15. Preparation and characterization Al3+-bentonite Turen Malang for esterification fatty acid (palmitic acid, oleic acid and linoleic acid)

    NASA Astrophysics Data System (ADS)

    Abdulloh, Abdulloh; Aminah, Nanik Siti; Triyono, Mudasir, Trisunaryanti, Wega

    2016-03-01

    Catalyst preparation and characterization of Al3+-bentonite for esterification of palmitic acid, oleic acid and linoleic acid has been done. Al3+-bentonite catalyst was prepared from natural bentonite of Turen Malang through cation exchange reaction using AlCl3 solution. The catalysts obtained were characterized by XRD, XRF, pyridine-FTIR and surface area analyser using the BET method. Catalyst activity test of Al3+-bentonite for esterification reaction was done at 65°C using molar ratio of metanol-fatty acid of 30:1 and 0.25 g of Al3+-bentonite catalyst for the period of ½, 1, 2, 3, 4 and 5 hours. Based on the characterization results, the Al3+-bentonite Turen Malang catalyst has a d-spacing of 15.63 Ǻ, acid sites of Brönsted and Lewis respectively of 230.79 µmol/g and 99.39 µmol/g, surface area of 507.3 m2/g and the average of radius pore of 20.09 Å. GC-MS analysis results of the oil phase after esterification reaction showed the formation of biodiesel (FAME: Fatty acid methyl ester), namely methyl palmitate, methyl oleate and methyl linoleate. The number of conversions resulted in esterification reaction using Al3+-bentonite Turen Malang catalyst was 74.61%, 37.75%, and 20, 93% for the esterification of palmitic acid, oleic acid and linoleic acid respectively.

  16. Acidic gas capture by diamines

    SciTech Connect

    Rochelle, Gary; Hilliard, Marcus

    2011-05-10

    Compositions and methods related to the removal of acidic gas. In particular, the present disclosure relates to a composition and method for the removal of acidic gas from a gas mixture using a solvent comprising a diamine (e.g., piperazine) and carbon dioxide. One example of a method may involve a method for removing acidic gas comprising contacting a gas mixture having an acidic gas with a solvent, wherein the solvent comprises piperazine in an amount of from about 4 to about 20 moles/kg of water, and carbon dioxide in an amount of from about 0.3 to about 0.9 moles per mole of piperazine.

  17. Molecular structural studies of lichen substances II: atranorin, gyrophoric acid, fumarprotocetraric acid, rhizocarpic acid, calycin, pulvinic dilactone and usnic acid

    NASA Astrophysics Data System (ADS)

    Edwards, Howell G. M.; Newton, Emma M.; Wynn-Williams, David D.

    2003-06-01

    The FT-Raman and infrared vibrational spectra of some important lichen compounds from two metabolic pathways are characterised. Key biomolecular marker bands have been suggested for the spectroscopic identification of atranorin, gyrophoric acid, fumarprotocetraric acid rhizocarpic acid, calycin, pulvinic dilactone and usnic acid. A spectroscopic protocol has been defined for the detection of these molecules in organisms subjected to environmental stresses such as UV-radiation exposure, desiccation and low temperatures. Use of the protocol will be made for the assessment of survival strategies used by stress-tolerant lichens in Antarctic cold deserts.

  18. Cryoprotection from bacterial teichoic acid

    NASA Astrophysics Data System (ADS)

    Rice, Charles V.; Harrison, William; Kirkpatrick, Karl; Brown, Eric D.

    2009-08-01

    Recent studies from our lab demonstrated that teichoic acid is surrounded by liquid water at -40 °C. The size and shape of the liquid water pockets has been visualized with fluorescence microscopy images of aqueous Rhodamine- B solutions. The long, thin channels surround ice crystals with a size of 5-20 microns. Subsequent studies show that B. subtilis Gram-positive bacteria are sequestered into large pockets without added teichoic acid. Here, the ice crystals are orders of manitude larger. When bacteria are mixed with teichoic acid solutions, the distribution of bacteria changes dramatically. The smaller ice crystals allow the bacteria to align in the thin channels of liquid water seen with teichoic acid only. The role of teichoic acid in the freeze tolerance was examined with live/dead fluorescence assays of bacteria mixed with teichoic acid. These quantitative assays were used to determine if teichoic acid acts in a synergetic fashion to enhance the survivability of E. coli, a gram-negative species which lacks teichoic acid. Additionally, we have obtained B. subtilis mutants lacking wall-associated teichoic acids to evaluate cryoprotection compared to the wild-type strain.

  19. Sulfuric acid as autocatalyst in the formation of sulfuric acid.

    PubMed

    Torrent-Sucarrat, Miquel; Francisco, Joseph S; Anglada, Josep M

    2012-12-26

    Sulfuric acid can act as a catalyst of its own formation. We have carried out a computational investigation on the gas-phase formation of H(2)SO(4) by hydrolysis of SO(3) involving one and two water molecules, and also in the presence of sulfuric acid and its complexes with one and two water molecules. The hydrolysis of SO(3) requires the concurrence of two water molecules, one of them acting as a catalyzer, and our results predict an important catalytic effect, ranging between 3 and 11 kcal·mol(-1) when the catalytic water molecule is substituted by a sulfuric acid molecule or one of its hydrates. In these cases, the reaction products are either bare sulfuric acid dimer or sulfuric acid dimer complexed with a water molecule. There are broad implications from these new findings. The results of the present investigation show that the catalytic effect of sulfuric acid in the SO(3) hydrolysis can be important in the Earth's stratosphere, in the heterogeneous formation of sulfuric acid and in the formation of aerosols, in H(2)SO(4) formation by aircraft engines, and also in understanding the formation of sulfuric acid in the atmosphere of Venus.

  20. Hydrazides of carboxylic acids as inhibitors of steel acidic corrosion

    SciTech Connect

    Aitov, R.G.; Shein, A.B.; Lesnov, A.E.

    1994-09-01

    Hydrazides of carboxylic acids (HCA) inhibit the corrosion of ferrous materials in acids and netral solutions such as stratum and waste waters of oil deposits. In this work, the authors try to explain the above-mentioned difference and to consider HCA as inhibitors of steel hydrogenation.

  1. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances

    PubMed Central

    Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung

    2016-01-01

    Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism. PMID:26742061

  2. A comparison of chromic acid and sulfuric acid anodizing

    NASA Technical Reports Server (NTRS)

    Danford, M. D.

    1992-01-01

    Because of federal and state mandates restricting the use of hexavalent chromium, it was deemed worthwhile to compare the corrosion protection afforded 2219-T87 aluminum alloy by both Type I chromic acid and Type II sulfuric acid anodizing per MIL-A-8625. Corrosion measurements were made on large, flat 2219-T87 aluminum alloy sheet material with an area of 1 cm(exp 2) exposed to a corrosive medium of 3.5-percent sodium chloride at pH 5.5. Both ac electrochemical impedance spectroscopy and the dc polarization resistance techniques were employed. The results clearly indicate that the corrosion protection obtained by Type II sulfuric acid anodizing is superior, and no problems should result by substituting Type II sulfuric acid anodizing for Type I chromic acid anodizing.

  3. Acid rain on Acid soil: a new perspective.

    PubMed

    Krug, E C; Frink, C R

    1983-08-01

    Acid rain is widely believed to be responsible for acidifying soil and water in areas of North America and northern Europe. However, factors commonly considered to make landscapes susceptible to acidification by acid rain are the same factors long known to strongly acidify soils through the natural processes of soil formation. Recovery from extreme and widespread careless land use has also occurred in regions undergoing acidification. There is evidence that acidification by acid rain is superimposed on long-term acidification induced by changes in land use and consequent vegetative succession. Thus, the interactions of acid rain, acid soil, and vegetation need to be carefully examined on a watershed basis in assessing benefits expected from proposed reductions in emissions of oxides of sulfur and nitrogen.

  4. Carbonic Acid Retreatment of Biomass

    SciTech Connect

    Baylor university

    2003-06-01

    This project sought to address six objectives, outlined below. The objectives were met through the completion of ten tasks. (1) Solidify the theoretical understanding of the binary CO{sub 2}/H{sub 2}O system at reaction temperatures and pressures. The thermodynamics of pH prediction have been improved to include a more rigorous treatment of non-ideal gas phases. However it was found that experimental attempts to confirm theoretical pH predictions were still off by a factor of about 1.8 pH units. Arrhenius experiments were carried out and the activation energy for carbonic acid appears to be substantially similar to sulfuric acid. Titration experiments have not yet confirmed or quantified the buffering or acid suppression effects of carbonic acid on biomass. (2) Modify the carbonic acid pretreatment severity function to include the effect of endogenous acid formation and carbonate buffering, if necessary. It was found that the existing severity functions serve adequately to account for endogenous acid production and carbonate effects. (3) Quantify the production of soluble carbohydrates at different reaction conditions and severity. Results show that carbonic acid has little effect on increasing soluble carbohydrate concentrations for pretreated aspen wood, compared to pretreatment with water alone. This appears to be connected to the release of endogenous acids by the substrate. A less acidic substrate such as corn stover would derive benefit from the use of carbonic acid. (4) Quantify the production of microbial inhibitors at selected reaction conditions and severity. It was found that the release of inhibitors was correlated to reaction severity and that carbonic acid did not appear to increase or decrease inhibition compared to pretreatment with water alone. (5) Assess the reactivity to enzymatic hydrolysis of material pretreated at selected reaction conditions and severity. Enzymatic hydrolysis rates increased with severity, but no advantage was detected for

  5. Carbonic Acid Pretreatment of Biomass

    SciTech Connect

    G. Peter van Walsum; Kemantha Jayawardhana; Damon Yourchisin; Robert McWilliams; Vanessa Castleberry

    2003-05-31

    This project sought to address six objectives, outlined below. The objectives were met through the completion of ten tasks. 1) Solidify the theoretical understanding of the binary CO2/H2O system at reaction temperatures and pressures. The thermodynamics of pH prediction have been improved to include a more rigorous treatment of non-ideal gas phases. However it was found that experimental attempts to confirm theoretical pH predictions were still off by a factor of about 1.8 pH units. Arrhenius experiments were carried out and the activation energy for carbonic acid appears to be substantially similar to sulfuric acid. Titration experiments have not yet confirmed or quantified the buffering or acid suppression effects of carbonic acid on biomass. 2) Modify the carbonic acid pretreatment severity function to include the effect of endogenous acid formation and carbonate buffering, if necessary. It was found that the existing severity functions serve adequately to account for endogenous acid production and carbonate effects. 3) Quantify the production of soluble carbohydrates at different reaction conditions and severity. Results show that carbonic acid has little effect on increasing soluble carbohydrate concentrations for pretreated aspen wood, compared to pretreatment with water alone. This appears to be connected to the release of endogenous acids by the substrate. A less acidic substrate such as corn stover would derive benefit from the use of carbonic acid. 4) Quantify the production of microbial inhibitors at selected reaction conditions and severity. It was found that the release of inhibitors was correlated to reaction severity and that carbonic acid did not appear to increase or decrease inhibition compared to pretreatment with water alone. 5) Assess the reactivity to enzymatic hydrolysis of material pretreated at selected reaction conditions and severity. Enzymatic hydrolysis rates increased with severity, but no advantage was detected for the use of carbonic

  6. Anacardic Acid, Salicylic Acid, and Oleic Acid Differentially Alter Cellular Bioenergetic Function in Breast Cancer Cells.

    PubMed

    Radde, Brandie N; Alizadeh-Rad, Negin; Price, Stephanie M; Schultz, David J; Klinge, Carolyn M

    2016-11-01

    Anacardic acid is a dietary and medicinal phytochemical that inhibits breast cancer cell proliferation and uncouples oxidative phosphorylation (OXPHOS) in isolated rat liver mitochondria. Since mitochondrial-targeted anticancer therapy (mitocans) may be useful in breast cancer, we examined the effect of anacardic acid on cellular bioenergetics and OXPHOS pathway proteins in breast cancer cells modeling progression to endocrine-independence: MCF-7 estrogen receptor α (ERα)+ endocrine-sensitive; LCC9 and LY2 ERα+, endocrine-resistant, and MDA-MB-231 triple negative breast cancer (TNBC) cells. At concentrations similar to cell proliferation IC50 s, anacardic acid reduced ATP-linked oxygen consumption rate (OCR), mitochondrial reserve capacity, and coupling efficiency while increasing proton leak, reflecting mitochondrial toxicity which was greater in MCF-7 compared to endocrine-resistant and TNBC cells. These results suggest tolerance in endocrine-resistant and TNBC cells to mitochondrial stress induced by anacardic acid. Since anacardic acid is an alkylated 2-hydroxybenzoic acid, the effects of salicylic acid (SA, 2-hydroxybenzoic acid moiety) and oleic acid (OA, monounsaturated alkyl moiety) were tested. SA inhibited whereas OA stimulated cell viability. In contrast to stimulation of basal OCR by anacardic acid (uncoupling effect), neither SA nor OA altered basal OCR- except OA inhibited basal and ATP-linked OCR, and increased ECAR, in MDA-MB-231 cells. Changes in OXPHOS proteins correlated with changes in OCR. Overall, neither the 2-hydroxybenzoic acid moiety nor the monounsaturated alky moiety of anacardic acid is solely responsible for the observed mitochondria-targeted anticancer activity in breast cancer cells and hence both moieties are required in the same molecule for the observed effects. J. Cell. Biochem. 117: 2521-2532, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990649

  7. Production of Succinic Acid from Citric Acid and Related Acids by Lactobacillus Strains

    PubMed Central

    Kaneuchi, Choji; Seki, Masako; Komagata, Kazuo

    1988-01-01

    A number of Lactobacillus strains produced succinic acid in de Man-Rogosa-Sharpe broth to various extents. Among 86 fresh isolates from fermented cane molasses in Thailand, 30 strains (35%) produced succinic acid; namely, 23 of 39 Lactobacillus reuteri strains, 6 of 18 L. cellobiosus strains, and 1 of 6 unidentified strains. All of 10 L. casei subsp. casei strains, 5 L. casei subsp. rhamnosus strains, 6 L. mali strains, and 2 L. buchneri strains did not produce succinic acid. Among 58 known strains including 48 type strains of different Lactobacillus species, the strains of L. acidophilus, L. crispatus, L. jensenii, and L. parvus produced succinic acid to the same extent as the most active fresh isolates, and those of L. alimentarius, L. collinoides, L. farciminis, L. fructivorans (1 of 2 strains tested), L. malefermentans, and L. reuteri were also positive, to lesser extents. Diammonium citrate in de Man-Rogosa-Sharpe broth was determined as a precursor of the succinic acid produced. Production rates were about 70% on a molar basis with two fresh strains tested. Succinic acid was also produced from fumaric and malic acids but not from dl-isocitric, α-ketoglutaric, and pyruvic acids. The present study is considered to provide the first evidence on the production of succinic acid, an important flavoring substance in dairy products and fermented beverages, from citrate by lactobacilli. PMID:16347795

  8. Acid rain: a background report

    SciTech Connect

    Glustrom, L.; Stolzenberg, J.

    1982-07-08

    This Staff Brief was prepared for the Wisconsin Legislative Council's Special Committee on Acid Rain to provide an introduction to the issue of acid rain. It is divided into four parts. Part I provides an overview on the controversies surrounding the measurement, formation and effects of acid rain. As described in Part I, the term acid rain is used to describe the deposition of acidic components through both wet deposition (e.g., rain or snow) and dry deposition (e.g., direct contact between atmospheric constituents and the land, water or vegetation of the earth). Part II presents background information on state agency activities relating to acid rain in Wisconsin, describes what is known about the occurrence of, susceptibility to and effects of acid rain in Wisconsin, and provides information related to man-made sources of sulfur and nitrogen oxides in Wisconsin. Part III describes major policies and regulations relating to acid rain which have been or are being developed jointly by the United States and Canadian governments, by the United States government and by the State of Wisconsin. Part IV briefly discusses possible areas for Committee action.

  9. Acid Rain: An Educational Opportunity?

    ERIC Educational Resources Information Center

    Marion, James I.

    1984-01-01

    Deals with how educators can handle the subject of acid rain; illustrates suggestions with experiences of grade nine students visiting Frost Valley Environmental Education Center (Oliverea, New York) to learn scientific concepts through observation of outdoor phenomena, including a stream; and discusses acid rain, pH levels, and pollution control…

  10. Acid rain & electric utilities II

    SciTech Connect

    1997-12-31

    This document presents reports which were presented at the Acid Rain and Electric Utilities Conference. Topics include environmental issues and electric utilities; acid rain program overview; global climate change and carbon dioxide; emissions data management; compliance; emissions control; allowance and trading; nitrogen oxides; and assessment. Individual reports have been processed separately for the United States Department of Energy databases.

  11. Acid Rain: The Scientific Challenge.

    ERIC Educational Resources Information Center

    Godfrey, Paul J.

    1991-01-01

    Documents the workings and findings of the Massachusetts Acid Rain Monitoring Project, which has pooled the volunteer efforts of more than 1,000 amateur and professional scientists since 1983. Reports on the origins of air pollution, the prediction of acid rain, and its effects on both water life and land resources. (JJK)

  12. Acid Precipitation: Causes and Consequences.

    ERIC Educational Resources Information Center

    Babich, Harvey; And Others

    1980-01-01

    This article is the first of three articles in a series on the acid rain problem in recent years. Discussed are the causes of acid precipitation and its consequences for the abiotic and biotic components of the terrestrial and aquatic ecosystems, and for man-made materials. (Author/SA)

  13. Acid Rain: What's the Forecast?

    ERIC Educational Resources Information Center

    Bybee, Rodger

    1984-01-01

    Discusses various types of acid rain, considered to be a century-old problem. Topics include: wet and dry deposition, effects on a variety of environments, ecosystems subject to detrimental effects, and possible solutions to the problem. A list of recommended resources on acid rain is provided. (BC)

  14. Synthesis of pyromellitic acid esters

    NASA Technical Reports Server (NTRS)

    Fedorova, V. A.; Donchak, V. A.; Martynyuk-Lototskaya, A. N.

    1985-01-01

    The ester acids necessary for studyng the thermochemical properties of pyromellitic acid (PMK)-based peroxides were investigated. Obtaining a tetramethyl ester of a PMK was described. The mechanism of an esterification reaction is discussed, as is the complete esterification of PMK with primary alcohol.

  15. Getting Back to Basics (& Acidics)

    ERIC Educational Resources Information Center

    Rhodes, Sam

    2006-01-01

    This article describes a few novel acid-base experiments intended to introduce students to the basic concepts of acid-base chemistry and provide practical examples that apply directly to the study of biology and the human body. Important concepts such as the reaction between carbon dioxide and water, buffers and protein denaturation, are covered.…

  16. Acid Tests and Basic Fun.

    ERIC Educational Resources Information Center

    McBride, John W.

    1995-01-01

    Explores acids and bases using different indicators, such as turmeric, purple grape juice, and lichens. Because some of these indicators are not as sensitive as cabbage juice or litmus paper, determining to which acids and bases each indicator is sensitive presents an enjoyable, problem-solving challenge for students. Presents directions for…

  17. Acid rain and environmental policy

    SciTech Connect

    Jacobson, J.S.

    1981-10-01

    Various seemingly paradoxical scientific questions are posed which relate to the problem of acid rain and its effect on the environment and environmental policy. The first paradox discussed concerns the supposed increase in fossil fuel usage over the last several decades, with the resultant increases in emissions of pollutants from the combustion of fuels which cause acid rain. Despite these increases, experts do not agree on whether acidity of rain has increased in eastern North America. The second paradox concerns the effect of acid rain on vegetation. If the rain is supposedly harmful, why have some reports shown increases and others, decreases in the growth of crops and trees with the application of simulated acid rain. The third paradox concerns the effect of acid rains on fish life in lakes. If acid rain falls throughout eastern North America, why have some lakes become acid and lost fish populations while others have not. Since unequivocal answers to these scientific questions are not available, a systematic approach is needed for developing policy which can be useful for solving the problem. It appears that traditional cost-benefit analysis can not be the sole basis for decision-making, but that it will be helpful. Research needs must be identified, and the upper and lower limits for alternative strategies must be determined. 14 references, 1 table.

  18. Impacts of acid rain legislation

    SciTech Connect

    Addison, E.L.

    1983-01-01

    The author warns against hasty acid rain legislation that would involve billions of dollars and affect thousands of jobs. He recommends further study into the causes of high acidity in lakes and streams. He states that there are too many uncertainties of whether the problem would be solved by reducing sulfur dioxide emissions from coal-fired power plants. (DMC)

  19. Acid rain: effects on fish and wildlife

    SciTech Connect

    Mayer, K.S.; Multer, E.P.; Schreiber, R.K.

    1984-01-01

    The following questions concerning acid rain are discussed: what is acid rain; what causes acid rain; where do sulfur and nitrogen oxides originate; what areas in the U.S. are susceptible to acid rain; are there early warning signals of acidification to aquatic resources; how does acid rain affect fishery resources; does acid rain affect wildlife; and how can effects of acid rain be reduced.

  20. Lead-acid battery

    SciTech Connect

    Rowlette, J.J.

    1983-09-20

    A light weight lead-acid battery is disclosed having a positive terminal and a negative terminal and including one or more cells or grid stacks having a plurality of vertically stacked conductive monoplates with positive active material and negative active material deposited on alternating plates in the cell or grid stack. Electrolyte layers positioned between each monoplate are included to provide a battery cell having four sides which is capable of being electrically charged and discharged. Two vertical positive bus bars are provided on opposite sides of the battery cell for connecting the monoplates with positive active material together in parallel current conducting relation. In addition, two negative bus bars on opposite sides of the battery cell each being adjacent the positive bus bars are provided for connecting the monoplates with negative active material together in parallel current conducting relation. The positive and negative bus bars not only provide a low resistance method for connecting the plurality of conductive monoplates of their respective battery terminals but also provides support and structural strength to the battery cell structure. In addition, horizontal orientation of monoplates is provided in a vertical stacking arrangement to reduce electrolyte stratification and short circuiting due to flaking of positive and negative active materials from the monoplates.

  1. Lead-acid battery

    NASA Technical Reports Server (NTRS)

    Rowlette, John J. (Inventor)

    1983-01-01

    A light weight lead-acid battery (30) having a positive terminal (36) and a negative terminal (34) and including one or more cells or grid stacks having a plurality of vertically stacked conductive monoplates (10, 20) with positive active material and negative active material deposited on alternating plates in the cell or grid stack. Electrolyte layers (26, 28) positioned between each monoplate are included to provide a battery cell having four sides which is capable of being electrically charged and discharged. Two vertical positive bus bars (42, 43) are provided on opposite sides of the battery cell for connecting the monoplates (10) with positive active material together in parallel current conducting relation. In addition, two negative bus bars (38, 39) on opposite sides of the battery cell each being adjacent the positive bus bars are provided for connecting the monoplates (20) with negative active material together in parallel current conducting relation. The positive (42, 43) and negative (38, 39) bus bars not only provide a low resistance method for connecting the plurality of conductive monoplates of their respective battery terminals (36, 34) but also provides support and structural strength to the battery cell structure. In addition, horizontal orientation of monoplates (10, 20) is provided in a vertical stacking arrangement to reduce electrolyte stratification and short circuiting due to flaking of positive and negative active materials from the monoplates.

  2. Synthesis of higher monocarboxylic acids

    SciTech Connect

    Taikov, B.F.; Novakovskii, E.M.; Zhelkovskaya, V.P.; Shadrova, V.N.; Shcherbik, P.K.

    1981-01-01

    Brown-coal and peat waxes contain higher monocarboxylic acids, alcohols and esters of them as their main components. In view of this, considerable interest is presented by the preparation of individual compounds among those mentioned above, which is particularly important in the study of the composition and development of the optimum variants of the chemical processing of the waxes. In laboratory practice, to obtain higher monocarboxylic acids use is generally made of electrosynthesis according to Kolbe which permits unbranched higher aliphatic acids with given lengths of the hydrocarbon chain to be obtained. The aim of the present work was to synthesize higher monocarboxylic acids: arachidic, behenic, lignoceric, pentacosanoic, erotic, heptacosanoic, montanic, nonacosanoic, melissic, dotriacontanoic and tetratriacontanoic, which are present in waxes. Characteristics of synthesized acids are tabulated. 20 refs.

  3. Atmospheric dust and acid rain

    SciTech Connect

    Hedin, L.O.; Likens, G.E.

    1996-12-01

    Why is acid rain still an environmental problem in Europe and North America despite antipollution reforms? The answer really is blowing in the wind: atmospheric dust. These airborne particles can help neutralize the acids falling on forests, but dust levels are unusually low these days. In the air dust particles can neutralize acid rain. What can we do about acid rain and atmospheric dust? Suggestions range from the improbable to the feasible. One reasonable suggestion is to reduce emissions of acidic pollutants to levels that can be buffered by natural quantities of basic compounds in the atmosphere; such a goal would mean continued reductions in sulfur dioxide and nitrogen oxides, perhaps even greater than those prescribed in the 1990 Amendments to the Clean Air Act in the U.S. 5 figs.

  4. Amino acid management in cancer

    PubMed Central

    Tsun, Zhi-Yang; Possemato, Richard

    2016-01-01

    Amino acids have a dual role in cellular metabolism, as they are both the building blocks for protein synthesis and intermediate metabolites which fuel other biosynthetic reactions. Recent work has demonstrated that deregulation of both arms of amino acid management are common alterations seen in cancer. Among the most highly consumed nutrients by cancer cells are the amino acids glutamine and serine, and the biosynthetic pathways that metabolize them are required in various cancer subtypes and the object of current efforts to target cancer metabolism. Also altered in cancer are components of the machinery which sense amino acid sufficiency, nucleated by the mechanistic target of rapamycin (mTOR), a key regulator of cell growth via modulation of key processes including protein synthesis and autophagy. The precise ways in which altered amino acid management supports cellular transformation remain mostly elusive, and a fuller mechanistic understanding of these processes will be important for efforts to exploit such alterations for cancer therapy. PMID:26277542

  5. Fumaric acid production by fermentation

    PubMed Central

    Roa Engel, Carol A.; Zijlmans, Tiemen W.; van Gulik, Walter M.; van der Wielen, Luuk A. M.

    2008-01-01

    The potential of fumaric acid as a raw material in the polymer industry and the increment of cost of petroleum-based fumaric acid raises interest in fermentation processes for production of this compound from renewable resources. Although the chemical process yields 112% w/w fumaric acid from maleic anhydride and the fermentation process yields only 85% w/w from glucose, the latter raw material is three times cheaper. Besides, the fermentation fixes CO2. Production of fumaric acid by Rhizopus species and the involved metabolic pathways are reviewed. Submerged fermentation systems coupled with product recovery techniques seem to have achieved economically attractive yields and productivities. Future prospects for improvement of fumaric acid production include metabolic engineering approaches to achieve low pH fermentations. PMID:18214471

  6. Formation of acrylic acid from lactic acid in supercritical water

    SciTech Connect

    Mok, W.S.L.; Antal, M.J. Jr. ); Jones, M. Jr. )

    1989-09-15

    Supercritical (SC) water is an unusual medium in which fast and specific heterolytic reactions can be conducted at temperatures as high as 400{degree}C. In supercritical water, lactic acid decomposes into gaseous and liquid products via three primary reaction pathways. Products of the acid-catalyzed heterolytic decarbonylation pathway are carbon monoxide, water, and acetaldehyde. Products of the homolytic, decarboxylation pathway are carbon dioxide, hydrogen, and acetaldehyde. Products of the heterolytic, dehydration pathway are acrylic acid and water. The intramolecular nucleophilic displacement of the {alpha}-hydroxyl by the carbonyl group of lactic acid, producing {alpha}-propiolactone as an unstable intermediate which subsequently rearranges to become the unsaturated acid, is a likely mechanism for acrylic acid formation, although an intramolecular E2 elimination initiated by attack of the carbonyl oxygen on a methyl hydrogen cannot be ruled out. Support for the former mechanism comes in part from the observed 100% relative yield of acrylic acid from {beta}-propiolactone in SC water.

  7. Synthesis of l-(+)-Tartaric Acid from l-Ascorbic Acid via 5-Keto-d-Gluconic Acid in Grapes

    PubMed Central

    Saito, Kazumi; Kasai, Zenzaburo

    1984-01-01

    5-Keto-l-idionic acid (≡5-keto-d-gluconic acid, d-xylo-5-hexulosonic acid) was found as a metabolic product of l-ascorbic acid in slices of immature grapes, Vitis labrusca L. cv `Delaware'. Specifically labeled compounds, recognized as metabolic products of l-ascorbic acid in grapes, were fed to young grape tissues to investigate the metabolic pathway from l-ascorbic acid to l-(+)-tartaric acid. Label from dehydro-l-[1-14C]ascorbic acid, 2-keto-l-[1-14C]idonic acid (l-xylo-2-hexulosonic acid), l-[1-14C]idonic acid, or 5-keto-l-[1-14C] idonic acid was incorporated into l-(+)-tartaric acid in high yields as it was in the l-[1-14C]ascorbic acid experiment. In a double label experiment involving a mixture of l-[1-14C]idonic acid and l-[2-3H]idonic acid, the 3H/14C ratios of 5-keto-l-idonic acid and l-(+)-tartaric acid synthesized in young grape leaves were almost the same as the value of the l-idonic acid fed. Label from 5-keto-l-[6-14C]idonic acid was incorporated into sugars and insoluble residue in the same way as l-[6-14C]ascorbic acid was metabolized in grapes. These results provide strong evidence that in grapes l-(+)-tartaric acid is synthesized from the C4 fragment that corresponds to the C1 to C4 group of the 5-keto-l-idonic acid derived from l-ascorbic acid via 2-keto-l-idonic acid and l-idonic acid. PMID:16663792

  8. Molten fatty acid based microemulsions.

    PubMed

    Noirjean, Cecile; Testard, Fabienne; Dejugnat, Christophe; Jestin, Jacques; Carriere, David

    2016-06-21

    We show that ternary mixtures of water (polar phase), myristic acid (MA, apolar phase) and cetyltrimethylammonium bromide (CTAB, cationic surfactant) studied above the melting point of myristic acid allow the preparation of microemulsions without adding a salt or a co-surfactant. The combination of SANS, SAXS/WAXS, DSC, and phase diagram determination allows a complete characterization of the structures and interactions between components in the molten fatty acid based microemulsions. For the different structures characterized (microemulsion, lamellar or hexagonal phases), a similar thermal behaviour is observed for all ternary MA/CTAB/water monophasic samples and for binary MA/CTAB mixtures without water: crystalline myristic acid melts at 52 °C, and a thermal transition at 70 °C is assigned to the breaking of hydrogen bounds inside the mixed myristic acid/CTAB complex (being the surfactant film in the ternary system). Water determines the film curvature, hence the structures observed at high temperature, but does not influence the thermal behaviour of the ternary system. Myristic acid is partitioned in two "species" that behave independently: pure myristic acid and myristic acid associated with CTAB to form an equimolar complex that plays the role of the surfactant film. We therefore show that myristic acid plays the role of a solvent (oil) and a co-surfactant allowing the fine tuning of the structure of oil and water mixtures. This solvosurfactant behaviour of long chain fatty acid opens the way for new formulations with a complex structure without the addition of any extra compound. PMID:27241163

  9. Pentadecanoic and Heptadecanoic Acids: Multifaceted Odd-Chain Fatty Acids.

    PubMed

    Pfeuffer, Maria; Jaudszus, Anke

    2016-07-01

    The odd-chain fatty acids (OCFAs) pentadecanoic acid (15:0) and heptadecanoic acid (17:0), which account for only a small proportion of total saturated fatty acids in milk fat and ruminant meat, are accepted biomarkers of dairy fat intake. However, they can also be synthesized endogenously, for example, from gut-derived propionic acid (3:0). A number of studies have shown an inverse association between OCFA concentrations in human plasma phospholipids or RBCs and risk of type 2 diabetes and cardiovascular disease. We propose a possible involvement in metabolic regulation from the assumption that there is a link between 15:0 and 17:0 and the metabolism of other short-chain, medium-chain, and longer-chain OCFAs. The OCFAs 15:0 and 17:0 can be elongated to very-long-chain FAs (VLCFAs) such as tricosanoic acid (23:0) and pentacosanoic acid (25:0) in glycosphingolipids, particularly found in brain tissue, or can be derived from these VLCFAs. Their chains can be shortened, yielding propionyl-coenzyme A (CoA). Propionyl-CoA, by succinyl-CoA, can replenish the citric acid cycle (CAC) with anaplerotic intermediates and, thus, improve mitochondrial energy metabolism. Mitochondrial function is compromised in a number of disorders and may be impaired with increasing age. Optimizing anaplerotic intermediate availability for the CAC may help to cope with demands in times of increased metabolic stress and with aging. OCFAs may serve as substrates for synthesis of both odd-numbered VLCFAs and propionyl-CoA or store away excess propionic acid. PMID:27422507

  10. Pentadecanoic and Heptadecanoic Acids: Multifaceted Odd-Chain Fatty Acids.

    PubMed

    Pfeuffer, Maria; Jaudszus, Anke

    2016-07-01

    The odd-chain fatty acids (OCFAs) pentadecanoic acid (15:0) and heptadecanoic acid (17:0), which account for only a small proportion of total saturated fatty acids in milk fat and ruminant meat, are accepted biomarkers of dairy fat intake. However, they can also be synthesized endogenously, for example, from gut-derived propionic acid (3:0). A number of studies have shown an inverse association between OCFA concentrations in human plasma phospholipids or RBCs and risk of type 2 diabetes and cardiovascular disease. We propose a possible involvement in metabolic regulation from the assumption that there is a link between 15:0 and 17:0 and the metabolism of other short-chain, medium-chain, and longer-chain OCFAs. The OCFAs 15:0 and 17:0 can be elongated to very-long-chain FAs (VLCFAs) such as tricosanoic acid (23:0) and pentacosanoic acid (25:0) in glycosphingolipids, particularly found in brain tissue, or can be derived from these VLCFAs. Their chains can be shortened, yielding propionyl-coenzyme A (CoA). Propionyl-CoA, by succinyl-CoA, can replenish the citric acid cycle (CAC) with anaplerotic intermediates and, thus, improve mitochondrial energy metabolism. Mitochondrial function is compromised in a number of disorders and may be impaired with increasing age. Optimizing anaplerotic intermediate availability for the CAC may help to cope with demands in times of increased metabolic stress and with aging. OCFAs may serve as substrates for synthesis of both odd-numbered VLCFAs and propionyl-CoA or store away excess propionic acid.

  11. Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells.

    PubMed

    Qiao, Li; Xu, Chengshan; Li, Qiang; Mei, Zhusong; Li, Xinji; Cai, Hong; Liu, Wei

    2016-06-01

    5-Aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has been used for part of squamous cell carcinoma (premalignant conditions or in situ cutaneous SCC-Bowen disease). However, mechanism of ALA-PDT is not fully understood yet on the cell apoptosis pathway. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on human squamous carcinoma A431cells. Apoptosis and cell viability after PDT were evaluated using Annexin V-FITC apoptosis detection kit and MTT assay. The mRNA and protein levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Our data showed that 5-ALA-PDT significantly inhibited cell proliferation (p<0.05), but there was no significant difference when the photosensitizer reached to 4.8mM. The inhibition in cell proliferation after 5-ALA-PDT treatment was correlated to more cells being arrested in the G0/G1 phase of the cell cycle (p<0.01). Immunocytochemical observations using anti-active caspase-3 antibodies showed active caspase-3 was translocated from cytoplasm to nuclear during apoptosis. STAT3 and its downstream gene Bax and BCL-2 were changed after 5-ALA-PDT treatment for the mRNA and protein expression. Our studies confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment. PMID:26607555

  12. Acid soil and acid rain, 2nd edition

    SciTech Connect

    Kennedy, I.R.

    1992-01-01

    This book examines the basic chemical processes involved in acidification in order to better assess their long-term effects on the status of soils, the health of plants and other living species that depend on them. It also discusses acidity, pH and protons their significance in bioenergetics and the consequent role of autotrophic organisms in acidifying ecosystems. This edition incorporates and integrates recent findings that render more explanations of the causes of the environmental impacts of acidity, especially in forests and lakes. Also explores current research into acid rain and soil in order to devise appropriate measures for their amelioration.

  13. Functional nucleic acid probes and uses thereof

    DOEpatents

    Nilsen-Hamilton, Marit

    2006-10-03

    The present invention provides functional nucleic acid probes, and methods of using functional nucleic acid probes, for binding a target to carry out a desired function. The probes have at least one functional nucleic acid, at least one regulating nucleic acid, and at least one attenuator. The functional nucleic acid is maintained in an inactive state by the attenuator and activated by the regulating nucleic acid only in the presence of a regulating nucleic acid target. In its activated state the functional nucleic acid can bind to its target to carry out a desired function, such as generating a signal, cleaving a nucleic acid, or catalyzing a reaction.

  14. 21 CFR 184.1021 - Benzoic acid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Benzoic acid. 184.1021 Section 184.1021 Food and... Substances Affirmed as GRAS § 184.1021 Benzoic acid. (a) Benzoic acid is the chemical benzenecarboxylic acid (C7H6O2), occurring in nature in free and combined forms. Among the foods in which benzoic acid...

  15. 21 CFR 184.1021 - Benzoic acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Benzoic acid. 184.1021 Section 184.1021 Food and... Substances Affirmed as GRAS § 184.1021 Benzoic acid. (a) Benzoic acid is the chemical benzenecarboxylic acid (C7H6O2), occurring in nature in free and combined forms. Among the foods in which benzoic acid...

  16. 21 CFR 184.1021 - Benzoic acid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Benzoic acid. 184.1021 Section 184.1021 Food and... Substances Affirmed as GRAS § 184.1021 Benzoic acid. (a) Benzoic acid is the chemical benzenecarboxylic acid (C7H6O2), occurring in nature in free and combined forms. Among the foods in which benzoic acid...

  17. 21 CFR 184.1021 - Benzoic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Benzoic acid. 184.1021 Section 184.1021 Food and....1021 Benzoic acid. (a) Benzoic acid is the chemical benzenecarboxylic acid (C7H6O2), occurring in nature in free and combined forms. Among the foods in which benzoic acid occurs naturally are...

  18. 21 CFR 189.155 - Monochloroacetic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Monochloroacetic acid. 189.155 Section 189.155... Human Food § 189.155 Monochloroacetic acid. (a) Monochloroacetic acid is the chemical chloroacetic acid... in alcoholic and nonalcoholic beverages. Monochloroacetic acid is permitted in food package...

  19. Diabetes and Alpha Lipoic Acid

    PubMed Central

    Golbidi, Saeid; Badran, Mohammad; Laher, Ismail

    2011-01-01

    Diabetes mellitus is a multi-faceted metabolic disorder where there is increased oxidative stress that contributes to the pathogenesis of this debilitating disease. This has prompted several investigations into the use of antioxidants as a complementary therapeutic approach. Alpha lipoic acid, a naturally occurring dithiol compound which plays an essential role in mitochondrial bioenergetic reactions, has gained considerable attention as an antioxidant for use in managing diabetic complications. Lipoic acid quenches reactive oxygen species, chelates metal ions, and reduces the oxidized forms of other antioxidants such as vitamin C, vitamin E, and glutathione. It also boosts antioxidant defense system through Nrf-2-mediated antioxidant gene expression and by modulation of peroxisome proliferator activated receptors-regulated genes. ALA inhibits nuclear factor kappa B and activates AMPK in skeletal muscles, which in turn have a plethora of metabolic consequences. These diverse actions suggest that lipoic acid acts by multiple mechanisms, many of which have only been uncovered recently. In this review we briefly summarize the known biochemical properties of lipoic acid and then discussed the oxidative mechanisms implicated in diabetic complications and the mechanisms by which lipoic acid may ameliorate these reactions. The findings of some of the clinical trials in which lipoic acid administration has been tested in diabetic patients during the last 10 years are summarized. It appears that the clearest benefit of lipoic acid supplementation is in patients with diabetic neuropathy. PMID:22125537

  20. Cycloadditions for Studying Nucleic Acids.

    PubMed

    Kath-Schorr, Stephanie

    2016-02-01

    Cycloaddition reactions for site-specific or global modification of nucleic acids have enabled the preparation of a plethora of previously inaccessible DNA and RNA constructs for structural and functional studies on naturally occurring nucleic acids, the assembly of nucleic acid nanostructures, therapeutic applications, and recently, the development of novel aptamers. In this chapter, recent progress in nucleic acid functionalization via a range of different cycloaddition (click) chemistries is presented. At first, cycloaddition/click chemistries already used for modifying nucleic acids are summarized, ranging from the well-established copper(I)-catalyzed alkyne-azide cycloaddition reaction to copper free methods, such as the strain-promoted azide-alkyne cycloaddition, tetrazole-based photoclick chemistry and the inverse electron demand Diels-Alder cycloaddition reaction between strained alkenes and tetrazine derivatives. The subsequent sections contain selected applications of nucleic acid functionalization via click chemistry; in particular, site-specific enzymatic labeling in vitro, either via DNA and RNA recognizing enzymes or by introducing unnatural base pairs modified for click reactions. Further sections report recent progress in metabolic labeling and fluorescent detection of DNA and RNA synthesis in vivo, click nucleic acid ligation, click chemistry in nanostructure assembly and click-SELEX as a novel method for the selection of aptamers. PMID:27572987