Lähettäjä: Soijuv Lähetetty: 13.1.2005 12:07
Amerikassa glutationia käytetään joillakin klinikoilla borrelioosiin, fatiikkiin, neurologisiin sairauksiin. Sitä käytetään IV:nä osana kelaatiohoitoja. Markkinoilla on myös sumutteena käytettävää glutationia ja siitä on saatu tutkimuksen (2000) mukaan hyötyä astman, keuhkoputkentulehdusten ym. hengitysteiden ongelmissa:
.... Dr. Patricia Kane and Dr. Neil Speight believe they have developed an effective approach to chronic fatigue, lyme disease and neurological illnesses by detoxifying the body with intravenous glutathione and intravenous lipids. As they write in the Townsend newsletter, â??GSH infusion by fast intravenous push has been a remarkable tool to unload the body burden of heavy metals and neurotoxins in both pediatric and adult patients.â?
GLUTATIONISTA
Valvojat: Jatta1001, Borrelioosiyhdistys, Bb
Lähettäjä: Soijuv Lähetetty: 13.1.2005 12:11
Tässä em. tutkimus:
The Use of Nebulized Glutathione in the Treatment of Emphysema: a Case Report
Alternative Medicine Review, Oct, 2000 by Davis W. Lamson, Matthew S. BrignallAbstract
We present the case of a 95-year-old man with an acute respiratory crisis secondary to emphysema and apparent bronchial infection. Treatment with nebulized glutathione led to a rapid resolution of the crisis, as well as a marked improvement in the chronic course of the disease. This treatment has been used since for a number of patients with emphysema. The safety and bioavailability of this method of delivery have been established in human studies. Preliminary results suggest efficacy for nebulized administration of glutathione in this patient population. We suggest this treatment can be considered an option for acute respiratory crises due to COPD.
(Altern Med Rev 2000;5(5):429-431)
Introduction
Chronic obstructive pulmonary disease (COPD), a designation which includes emphysema, is a leading cause of death in America. This case study reports on the successful treatment of both acute and chronic emphysema with a novel agent.
Much of the tissue damage in emphysema is thought to be mediated by an oxidative down-regulation of the activity of [Alpha]-1-proteinase inhibitor.[1] This down-regulation has been shown in vitro to be slowed by glutathione, a sulfhydryl-containing tripeptide known to be a major antioxidant in the lung.[2]
Glutathione concentrations in bronchoalveolar fluid have been found to be inversely correlated with the degree of inflammatory activity in the lungs of smokers.[3] Thiol compounds (i.e., compounds containing an -- SH group) like glutathione have a history of use as mucolytics as well.[4] Previous clinical trials of nebulized reduced glutathione have demonstrated the bioavailability and safety of up to 600 mg twice daily.[5,6] The absorption of oral glutathione remains controversial, with animal studies suggesting significant absorption and some human studies showing little to none.[7,8] Based on these findings, it appears inhalation might be the preferred route of administration for respiratory and perhaps systemic effect. We report the case of a man with an acute respiratory crisis due to emphysema and apparent bronchial infection that responded favorably to treatment with nebulized glutathione.
Case Report
In 1997, a 95-year-old male with emphysema presented in a wheelchair and using an oxygen tank and mask necessitated by his acute illness. He was alert, responsive, and reported a productive cough with colorless sputum. His breathing was obviously labored. He refused hospitalization and antibiotic treatment. We chose to try a single trial dose of 2 ml of a 60 mg/ml glutathione solution (prepared by Apothecure Pharmacy, Dallas, TX) nebulized and inhaled over a 5-10 minute period. Due to the obvious immediate benefit, it was decided to continue this treatment with twice-daily administration and close monitoring by his family of his overall condition. He returned to the office in three days without wheelchair or oxygen tank. He showed no signs of respiratory distress, and no adventitious lung sounds were noted on auscultation. The patient reported his breathing was better than it had been in years. He continued daily treatment with glutathione until his death from congestive heart failure over two years later.
Conclusion
While resolution of the acute episode due to a mucolytic effect was the desired outcome of the glutathione treatment, the lasting improvement in breathing was unexpected. Since we have no serial spirometry data available on this patient, placebo effect cannot be ruled out as an explanation for his marked response. However, given the progressive nature of his disease, the dramatic and rapid change in physical findings, and the emphatic insistence of the patient for continued treatment, we believe placebo response to be an unlikely explanation.
We have subsequently prescribed this preparation for six patients with emphysema, five of whom reported improved breathing after a single in-office application and who later requested to continue treatment. We also have found nebulized glutathione is best administered daily from 4 ml vials. We have also seen improved respiratory function associated with nebulized glutathione treatment in cases of chronic bronchitis and asthma.[9] In the case of asthma patients we feel it is advisable to check urinary sulfite excretion to verify proper metabolism of sulfur compounds, as certain individuals appear to experience exacerbation of respiratory symptoms from exogenous sulfur compounds.[10] In three cases of non-small cell lung cancer with effusion, the effusion resolved completely. Given the safety and promise of this treatment, combined with the paucity of other effective treatments for emphysema, we suggest this treatment be considered for widespread use.
References
[1.] Wiedemann HP, Stoller JK. Lung disease due to alpha 1-antitrypsin deficiency. Curr Opin Pulm Med 1996;2:155-160.
[2.] Gressier B, Lebegue S, Gosset P, et al. Protective role of glutathione on alpha-1-proteinase inhibitor inactivation by the myeloperoxidase system. Hypothetic study for therapeutic strategy in the management of smokers' emphysema. Fundam Clin Pharmacol 1994;8:518-524.
[3.] Linden M, Hakansson L, Ohlsson K, et al. Glutathione in bronchoalveolar lavage fluid from smokers is related to humoral markers of inflammatory cell activity. Inflammation 1989; 13:651-658.
[4.] Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev 1998;3:114-127.
[5.] Holroyd KJ, Buhl R, Borok Z, et al. Correction of glutathione deficiency in the lower respiratory tract of HIV seropositive individuals by glutathione aerosol treatment. Thorax 1993;48:985-989.
[6.] Borok Z, Buhl R, Grimes GJ, et al. Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis. Lancet 1991; 338:215-216.
[7.] Hagen TM, Wierzbicka GT, Sillau AH, et al. Bioavailability of dietary glutathione: effect on plasma concentration. Am J Physiol 1990;259:G524-G529.
[8.] Witschi A, Reddy S, Stofer B, et al. The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992;43:667-669.
[9.] Bagnato GE Gulli S, De Pasquale R, et al. Effect of inhaled glutathione on airway response to `Fog' challenge in asthmatic patients. Respiration 1999;66:518-521.
[10.] Marrades RM, Roca J, Barbera JA, et al. Nebulized glutathione induces bronchoconstriction in patients with mild asthma. Am J Respir Crit Care Med 1997;156:425-430.
Is your Alternative Medicine Therapy Helping Cancer Patients?
The National Cancer Institute, the U.S. Federal government's agency responsible for cancer research, invites you to submit data from your best cases for review by conventional research and alternative medicine experts. Successful approaches can receive financial support and recommendations for further research, visibility among the clinical research community, and feedback on the strengths and limitations of your approach. For details or a submission package, contact NCI's office of Cancer Complementary and Alternative Medicine, National Cancer Institute, EPN/Suite 102, Bethesda, MD 20892; (301) 435-7980 (phone); (301) 480-7980 (fax); ncioccam-r@mail.nih.qov (email); or http:// occam.nci.nih.gov and click on Best Case Series Program.
Please contact me with any questions or comments you may have about this announcement. Thank you for your consideration.
Jana Johnston National Cancer Institute Bldg 31, Rm 10A03 Bethesda, MD 20892 (301) 436-7790 johnstoj0occ.nci.nih.gov
Davis W. Lamson, MS, ND - Coordinator of Oncology, Bastyr University, Kenmore, WA. Private practice, Tahoma Clinic, Kent, WA. Correspondence address: 9803 17th Ave NE, Seattle, WA 98115. E-mail: davisl@seanet.com
Matthew S. Brignall, ND -Private practice: Cascade Cancer Center, Kirkland, WA. E-mail: mattandmolly@home.com
COPYRIGHT 2000 Thorne Research Inc.
COPYRIGHT 2000 Gale Group
Tässä em. tutkimus:
The Use of Nebulized Glutathione in the Treatment of Emphysema: a Case Report
Alternative Medicine Review, Oct, 2000 by Davis W. Lamson, Matthew S. BrignallAbstract
We present the case of a 95-year-old man with an acute respiratory crisis secondary to emphysema and apparent bronchial infection. Treatment with nebulized glutathione led to a rapid resolution of the crisis, as well as a marked improvement in the chronic course of the disease. This treatment has been used since for a number of patients with emphysema. The safety and bioavailability of this method of delivery have been established in human studies. Preliminary results suggest efficacy for nebulized administration of glutathione in this patient population. We suggest this treatment can be considered an option for acute respiratory crises due to COPD.
(Altern Med Rev 2000;5(5):429-431)
Introduction
Chronic obstructive pulmonary disease (COPD), a designation which includes emphysema, is a leading cause of death in America. This case study reports on the successful treatment of both acute and chronic emphysema with a novel agent.
Much of the tissue damage in emphysema is thought to be mediated by an oxidative down-regulation of the activity of [Alpha]-1-proteinase inhibitor.[1] This down-regulation has been shown in vitro to be slowed by glutathione, a sulfhydryl-containing tripeptide known to be a major antioxidant in the lung.[2]
Glutathione concentrations in bronchoalveolar fluid have been found to be inversely correlated with the degree of inflammatory activity in the lungs of smokers.[3] Thiol compounds (i.e., compounds containing an -- SH group) like glutathione have a history of use as mucolytics as well.[4] Previous clinical trials of nebulized reduced glutathione have demonstrated the bioavailability and safety of up to 600 mg twice daily.[5,6] The absorption of oral glutathione remains controversial, with animal studies suggesting significant absorption and some human studies showing little to none.[7,8] Based on these findings, it appears inhalation might be the preferred route of administration for respiratory and perhaps systemic effect. We report the case of a man with an acute respiratory crisis due to emphysema and apparent bronchial infection that responded favorably to treatment with nebulized glutathione.
Case Report
In 1997, a 95-year-old male with emphysema presented in a wheelchair and using an oxygen tank and mask necessitated by his acute illness. He was alert, responsive, and reported a productive cough with colorless sputum. His breathing was obviously labored. He refused hospitalization and antibiotic treatment. We chose to try a single trial dose of 2 ml of a 60 mg/ml glutathione solution (prepared by Apothecure Pharmacy, Dallas, TX) nebulized and inhaled over a 5-10 minute period. Due to the obvious immediate benefit, it was decided to continue this treatment with twice-daily administration and close monitoring by his family of his overall condition. He returned to the office in three days without wheelchair or oxygen tank. He showed no signs of respiratory distress, and no adventitious lung sounds were noted on auscultation. The patient reported his breathing was better than it had been in years. He continued daily treatment with glutathione until his death from congestive heart failure over two years later.
Conclusion
While resolution of the acute episode due to a mucolytic effect was the desired outcome of the glutathione treatment, the lasting improvement in breathing was unexpected. Since we have no serial spirometry data available on this patient, placebo effect cannot be ruled out as an explanation for his marked response. However, given the progressive nature of his disease, the dramatic and rapid change in physical findings, and the emphatic insistence of the patient for continued treatment, we believe placebo response to be an unlikely explanation.
We have subsequently prescribed this preparation for six patients with emphysema, five of whom reported improved breathing after a single in-office application and who later requested to continue treatment. We also have found nebulized glutathione is best administered daily from 4 ml vials. We have also seen improved respiratory function associated with nebulized glutathione treatment in cases of chronic bronchitis and asthma.[9] In the case of asthma patients we feel it is advisable to check urinary sulfite excretion to verify proper metabolism of sulfur compounds, as certain individuals appear to experience exacerbation of respiratory symptoms from exogenous sulfur compounds.[10] In three cases of non-small cell lung cancer with effusion, the effusion resolved completely. Given the safety and promise of this treatment, combined with the paucity of other effective treatments for emphysema, we suggest this treatment be considered for widespread use.
References
[1.] Wiedemann HP, Stoller JK. Lung disease due to alpha 1-antitrypsin deficiency. Curr Opin Pulm Med 1996;2:155-160.
[2.] Gressier B, Lebegue S, Gosset P, et al. Protective role of glutathione on alpha-1-proteinase inhibitor inactivation by the myeloperoxidase system. Hypothetic study for therapeutic strategy in the management of smokers' emphysema. Fundam Clin Pharmacol 1994;8:518-524.
[3.] Linden M, Hakansson L, Ohlsson K, et al. Glutathione in bronchoalveolar lavage fluid from smokers is related to humoral markers of inflammatory cell activity. Inflammation 1989; 13:651-658.
[4.] Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev 1998;3:114-127.
[5.] Holroyd KJ, Buhl R, Borok Z, et al. Correction of glutathione deficiency in the lower respiratory tract of HIV seropositive individuals by glutathione aerosol treatment. Thorax 1993;48:985-989.
[6.] Borok Z, Buhl R, Grimes GJ, et al. Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis. Lancet 1991; 338:215-216.
[7.] Hagen TM, Wierzbicka GT, Sillau AH, et al. Bioavailability of dietary glutathione: effect on plasma concentration. Am J Physiol 1990;259:G524-G529.
[8.] Witschi A, Reddy S, Stofer B, et al. The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992;43:667-669.
[9.] Bagnato GE Gulli S, De Pasquale R, et al. Effect of inhaled glutathione on airway response to `Fog' challenge in asthmatic patients. Respiration 1999;66:518-521.
[10.] Marrades RM, Roca J, Barbera JA, et al. Nebulized glutathione induces bronchoconstriction in patients with mild asthma. Am J Respir Crit Care Med 1997;156:425-430.
Is your Alternative Medicine Therapy Helping Cancer Patients?
The National Cancer Institute, the U.S. Federal government's agency responsible for cancer research, invites you to submit data from your best cases for review by conventional research and alternative medicine experts. Successful approaches can receive financial support and recommendations for further research, visibility among the clinical research community, and feedback on the strengths and limitations of your approach. For details or a submission package, contact NCI's office of Cancer Complementary and Alternative Medicine, National Cancer Institute, EPN/Suite 102, Bethesda, MD 20892; (301) 435-7980 (phone); (301) 480-7980 (fax); ncioccam-r@mail.nih.qov (email); or http:// occam.nci.nih.gov and click on Best Case Series Program.
Please contact me with any questions or comments you may have about this announcement. Thank you for your consideration.
Jana Johnston National Cancer Institute Bldg 31, Rm 10A03 Bethesda, MD 20892 (301) 436-7790 johnstoj0occ.nci.nih.gov
Davis W. Lamson, MS, ND - Coordinator of Oncology, Bastyr University, Kenmore, WA. Private practice, Tahoma Clinic, Kent, WA. Correspondence address: 9803 17th Ave NE, Seattle, WA 98115. E-mail: davisl@seanet.com
Matthew S. Brignall, ND -Private practice: Cascade Cancer Center, Kirkland, WA. E-mail: mattandmolly@home.com
COPYRIGHT 2000 Thorne Research Inc.
COPYRIGHT 2000 Gale Group
Viimeksi muokannut Bb, Su Huhti 18, 2010 18:32. Yhteensä muokattu 2 kertaa.
Lähettäjä: Soijuv Lähetetty: 13.1.2005 12:33
Erilaisia tutkimustuloksia glutationin hyödystä keuhkosairauksissa:
Authors Roum JH. Borok Z. McElvaney NG. Grimes GJ. Bokser AD. Buhl R. Crystal RG.
Title Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis
Source Journal of Applied Physiology. 87(1):438-443, 1999 Jul.
Abstract Cystic fibrosis (CF)
is characterized by accumulation of activated neutrophils and macrophages on
the respiratory epithelial surface (RES); these cells release toxic
oxidants, which contribute to the marked epithelial derangements seen in CF.
These deleterious consequences are magnified, since reduced glutathione
(GSH), an antioxidant present in high concentrations in normal respiratory
epithelial lining fluid (ELF), is deficient in CF ELF. To evaluate the
feasibility of increasing ELF GSH levels and enhancing RES antioxidant
protection, GSH aerosol was delivered (600 mg twice daily for 3 days) to
seven patients with CF. ELF total, reduced, and oxidized GSH increased (P <
0.05, all compared with before GSH therapy), suggesting adequate RES
delivery and utilization of GSH. Phorbol 12-myristate 13-acetate-stimulated
superoxide anion (O-2(-).) release by ELF inflammatory cells decreased after
GSH therapy (P < 0.002). This paralleled observations that GSH added in
vitro to CF ELF inflammatory cells suppressed O-2(-). release (P < 0.001).
No adverse effects were noted during treatment. Together, these observations
demonstrate the feasibility of using GSH aerosol to restore RES
oxidant-antioxidant balance in CF and support the rationale for further
clinical evaluation. [References: 45] Publication Type Article
--------------------------------
Authors Bernorio S. Pecis M. Zucchi A. Guerra G. Migliorini V. Negri L.
Corsano A.
Title GLUTATHIONE IN BRONCHIAL HYPERRESPONSIVENESS
Source Journal
of Aerosol Medicine-Deposition Clearance & Effects in the Lung.
9(2):207-213, 1996 Sum.
Abstract Alterations of oxidants and antioxidants
now appear to be pivotal in the development of bronchial hyperresponsiveness
and bronchial asthma, To evaluate the potential protective role of the
antioxidant reduced glutathione (GSH) administered by ultrasonic nebulizer
on metacholine-induced bronchoconstriction, we designed a double-blind,
randomized study enrolling 18 subjects,vith mild asthma and previous
bronchoconstriction after a methacholine challenge; we did not find a
statistically significant decrease in bronchoconstriction after
premedication with inhaled GSH, Further investigation under different
experimental conditions is warranted because our information about the mode
of action and pharmacokinetics of GSH is still incomplete and sometimes the
data are conflicting. [References: 19] Publication Type Article
http://www.thorne.com/n_acetylcysteine.html :
Significance of glutathione in lung disease and implications for therapy.
Glutathione is a tripeptide that contains an important thiol (sulfhydryl)
group within the central cysteine amino acid. Glutathione is involved in
numerous vital processes where the reducing potential of the thiol is used.
Several lung disorders are believed to be characterized by an increase in
alveolar oxidant burden, potentially depleting alveolar and lung
glutathione. Low glutathione has been linked to abnormalities in the lung
surfactant system and the interaction between glutathione and antiproteases
in the epithelial lining fluid of patients. Normal levels of intracellular
glutathione may exert a critical negative control on the elaboration of
proinflammatory cytokines. The increase of intracellular reactive oxygen
species is believed to correlate with the activation of NF-kappa B, a
strongly implicate free radical injury in the genesis and maintenance of
several lung disorders in humans. This information is substantial and will
help the development of clinical studies examining a variety of inflammatory
lung disorders.Morris PE;Bernard GR. Significance of glutathione in lung
disease and implications for therapy. Am J Med Sci 307:119-127;1994
Authors Marrades RM. Roca J. Barbera JA. Dejover L. Macnee W. Rodriguezroisin R.
Title NEBULIZED GLUTATHIONE INDUCES BRONCHOCONSTRICTION IN PATIENTS WITH MILD ASTHMA
Source American Journal of Respiratory & Critical Care Medicine. 156(2):425-430, 1997 Aug.
Abstract To assess the effects on bronchial responsiveness of nebulized glutathione (GSH), one of
the most efficient scavengers of oxidant substances in the airways, we
studied eight patients with mild asthma (FEV1, 88 +/- 11% predicted [SD]) in
a randomized, double-blind, cross-over, placebo-controlled fashion.
Bronchial challenge was measured using both FEV1 and total pulmonary
resistance (Rrs) by the forced oscillation technique. Patients received
nebulized GSH (600 mg with 4 ml of 0.9% sodium chloride) or placebo
(identical saline solution) over a period of 25 min, 1 wk apart. Placebo
provoked subclinical mild bronchoconstriction (changes from baseline: FEV1,
-1%; Rrs, +17%); by contrast, GSH caused major airway narrowing (changes
from baseline: FEV1, -19%; Rrs, +61%) and induced cough (four patients) or
breathlessness (three patients). Differences between placebo and GSH after
challenge were also noticeable in both FEV1 (p = 0.03) and Rrs (p = 0.02).
Neither osmolarity (660 mosm . kg(-1)) nor pH (3.0) of the GSH solution
accounted for these effects. Nebulized salbutamol (5.0 mg) given before the
GSH challenge blocked GSH-induced bronchoconstriction. Furthermore,
GSH-induced FEV1 falls were inversely correlated with metabisulfite
bronchoprovocation (provocative dose [PD20], 1.49 +/- 1.83 mu mol) but not
with methacholine challenge. The detrimental effects of nebulized GSH on the
airway bronchial tone in patients with mild asthma strongly suggests
bronchoconstriction provoked by sulfite formation. [References: 29]
Publication Type Article
-----------------------------
Authors Grimble RF.
Title MODIFICATION OF INFLAMMATORY ASPECTS OF IMMUNE FUNCTION BY NUTRIENTS
Source Nutrition Research. 18(7):1297-1317, 1998 Jul.
Abstract
The pro-inflammatory cytokines interleukin 1 (IL1) interleukin 6 (IL6) and
tumour necrosis factor-alpha (TNF), and reactive oxygen species (ROS), play
a-major role in inflammatory aspects of immune function. They are closely
linked with pathology in a wide range of diseases and condition which have
an inflammatory basis. Alterations in the intake of fats, antioxidant
nutrients, protein and specific amino acids change many aspects of
inflammation by interacting with cytokine and ROS biology, thereby providing
a means of modulating inflammation. Mortality and morbidity, in a diverse
range of diseases, have been linked with excessive or untimely oxidant and
pro-inflammatory cytokine production. Evidence of oxidative damage has been
observed in sepsis, HIV and hepatitis infection, cancer, diabetes mellitus,
alcoholic liver disease and cystic fibrosis. ROS produced during the
inflammatory response enhances pro-inflammatory cytokine production by
activation of nuclear factor kappa B (NF kappa B). The interaction is an
important part of the up-regulation of inflammatory aspects of immune
function. The interaction between ROS and cytokines has the potential to
damage the host but is held in check by the antioxidant defences. Nutrient
intake directly and indirectly influences antioxidant defence. Glutathione
is a major endogenous antioxidant and is important for lymphocyte
replication. Vitamin B, and riboflavin participate in the maintenance of
glutathione status. Vitamin B, acts as a cofactor in the synthesis of
cysteine (the rate limiting precursor for glutathione biosynthesis) and
riboflavin is a cofactor for glutathione reductase. Deficiencies in vitamins
E, B, and riboflavin reduce cell numbers in lymphoid tissues of experimental
animals and produce functional abnormalities in the cell mediated immune
response. Sulphur amino acid deficient rats exhibit an impaired ability to
synthesise glutathione during inflammation and have increased numbers of
neutrophils in lung. Ascorbic acid and tocopherols exert anti-inflammatory
effects in studies in man and animals. In humans, dietary supplementation
with ascorbic-acid, tocopherols and vitamin B, enhances a number of aspects
of lymphocyte function-In smokers indices of inflammation inversely relate
to the intakes of vitamins C and E. Studies in healthy subjects, patients
and experimental animals clearly demonstrate that unsaturated fats modulate
pro-inflammatory cytokine biology. In general n-6 polyunsaturated fatty
acids enhance, and n-3 PUFAs and monounsaturated fatty acids suppress,
cytokine mediated aspects of inflammation. In addition, n-6 PUFAs and
cholesterol enhance and n-3 PUFAs suppress cytokine production. Fats rich in
n-3 PUFAs are efficacious in a number of inflammatory diseases, however in
smokers indices of inflammation are enhanced in subjects consuming greater
than 5% of dietary energy in the form of n-6 PUFAs. Fats may modulate
cytokine biology by a number of mechanisms closely linked to membrane
phospholipid composition. As a consequence of diet induced change,
alterations in prostaglandin, leukotriene and diacyl glycerol production,
protein kinase C activation and fluidity may occur. Recent studies suggest
that changes in bulk membrane fluidity are unlikely to underlie the
substantial modulatory effects of fats on cytokine biology.
In conclusion nutrients have a major potential for modulating inflammatory
aspects of immune function due to interaction with three main areas whereby
inflammation is prosecuted and controlled. Firstly by changing provision of
substrate for the synthesis of molecules for components for the executive
and control systems (protein, sulphur amino acids, glutamine).
Secondly by modulating the composition of the membranes of cells involved
in the inflammatory process (unsaturated fatty acids and cholesterol) and
thirdly by influencing the interaction between ROS and NF kappa B activation
(sulphur amino acids, vitamins C and E, and riboflavin). (C) 1998 Elsevier
Science Inc. [References: 130]
Erilaisia tutkimustuloksia glutationin hyödystä keuhkosairauksissa:
Authors Roum JH. Borok Z. McElvaney NG. Grimes GJ. Bokser AD. Buhl R. Crystal RG.
Title Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis
Source Journal of Applied Physiology. 87(1):438-443, 1999 Jul.
Abstract Cystic fibrosis (CF)
is characterized by accumulation of activated neutrophils and macrophages on
the respiratory epithelial surface (RES); these cells release toxic
oxidants, which contribute to the marked epithelial derangements seen in CF.
These deleterious consequences are magnified, since reduced glutathione
(GSH), an antioxidant present in high concentrations in normal respiratory
epithelial lining fluid (ELF), is deficient in CF ELF. To evaluate the
feasibility of increasing ELF GSH levels and enhancing RES antioxidant
protection, GSH aerosol was delivered (600 mg twice daily for 3 days) to
seven patients with CF. ELF total, reduced, and oxidized GSH increased (P <
0.05, all compared with before GSH therapy), suggesting adequate RES
delivery and utilization of GSH. Phorbol 12-myristate 13-acetate-stimulated
superoxide anion (O-2(-).) release by ELF inflammatory cells decreased after
GSH therapy (P < 0.002). This paralleled observations that GSH added in
vitro to CF ELF inflammatory cells suppressed O-2(-). release (P < 0.001).
No adverse effects were noted during treatment. Together, these observations
demonstrate the feasibility of using GSH aerosol to restore RES
oxidant-antioxidant balance in CF and support the rationale for further
clinical evaluation. [References: 45] Publication Type Article
--------------------------------
Authors Bernorio S. Pecis M. Zucchi A. Guerra G. Migliorini V. Negri L.
Corsano A.
Title GLUTATHIONE IN BRONCHIAL HYPERRESPONSIVENESS
Source Journal
of Aerosol Medicine-Deposition Clearance & Effects in the Lung.
9(2):207-213, 1996 Sum.
Abstract Alterations of oxidants and antioxidants
now appear to be pivotal in the development of bronchial hyperresponsiveness
and bronchial asthma, To evaluate the potential protective role of the
antioxidant reduced glutathione (GSH) administered by ultrasonic nebulizer
on metacholine-induced bronchoconstriction, we designed a double-blind,
randomized study enrolling 18 subjects,vith mild asthma and previous
bronchoconstriction after a methacholine challenge; we did not find a
statistically significant decrease in bronchoconstriction after
premedication with inhaled GSH, Further investigation under different
experimental conditions is warranted because our information about the mode
of action and pharmacokinetics of GSH is still incomplete and sometimes the
data are conflicting. [References: 19] Publication Type Article
http://www.thorne.com/n_acetylcysteine.html :
Significance of glutathione in lung disease and implications for therapy.
Glutathione is a tripeptide that contains an important thiol (sulfhydryl)
group within the central cysteine amino acid. Glutathione is involved in
numerous vital processes where the reducing potential of the thiol is used.
Several lung disorders are believed to be characterized by an increase in
alveolar oxidant burden, potentially depleting alveolar and lung
glutathione. Low glutathione has been linked to abnormalities in the lung
surfactant system and the interaction between glutathione and antiproteases
in the epithelial lining fluid of patients. Normal levels of intracellular
glutathione may exert a critical negative control on the elaboration of
proinflammatory cytokines. The increase of intracellular reactive oxygen
species is believed to correlate with the activation of NF-kappa B, a
strongly implicate free radical injury in the genesis and maintenance of
several lung disorders in humans. This information is substantial and will
help the development of clinical studies examining a variety of inflammatory
lung disorders.Morris PE;Bernard GR. Significance of glutathione in lung
disease and implications for therapy. Am J Med Sci 307:119-127;1994
Authors Marrades RM. Roca J. Barbera JA. Dejover L. Macnee W. Rodriguezroisin R.
Title NEBULIZED GLUTATHIONE INDUCES BRONCHOCONSTRICTION IN PATIENTS WITH MILD ASTHMA
Source American Journal of Respiratory & Critical Care Medicine. 156(2):425-430, 1997 Aug.
Abstract To assess the effects on bronchial responsiveness of nebulized glutathione (GSH), one of
the most efficient scavengers of oxidant substances in the airways, we
studied eight patients with mild asthma (FEV1, 88 +/- 11% predicted [SD]) in
a randomized, double-blind, cross-over, placebo-controlled fashion.
Bronchial challenge was measured using both FEV1 and total pulmonary
resistance (Rrs) by the forced oscillation technique. Patients received
nebulized GSH (600 mg with 4 ml of 0.9% sodium chloride) or placebo
(identical saline solution) over a period of 25 min, 1 wk apart. Placebo
provoked subclinical mild bronchoconstriction (changes from baseline: FEV1,
-1%; Rrs, +17%); by contrast, GSH caused major airway narrowing (changes
from baseline: FEV1, -19%; Rrs, +61%) and induced cough (four patients) or
breathlessness (three patients). Differences between placebo and GSH after
challenge were also noticeable in both FEV1 (p = 0.03) and Rrs (p = 0.02).
Neither osmolarity (660 mosm . kg(-1)) nor pH (3.0) of the GSH solution
accounted for these effects. Nebulized salbutamol (5.0 mg) given before the
GSH challenge blocked GSH-induced bronchoconstriction. Furthermore,
GSH-induced FEV1 falls were inversely correlated with metabisulfite
bronchoprovocation (provocative dose [PD20], 1.49 +/- 1.83 mu mol) but not
with methacholine challenge. The detrimental effects of nebulized GSH on the
airway bronchial tone in patients with mild asthma strongly suggests
bronchoconstriction provoked by sulfite formation. [References: 29]
Publication Type Article
-----------------------------
Authors Grimble RF.
Title MODIFICATION OF INFLAMMATORY ASPECTS OF IMMUNE FUNCTION BY NUTRIENTS
Source Nutrition Research. 18(7):1297-1317, 1998 Jul.
Abstract
The pro-inflammatory cytokines interleukin 1 (IL1) interleukin 6 (IL6) and
tumour necrosis factor-alpha (TNF), and reactive oxygen species (ROS), play
a-major role in inflammatory aspects of immune function. They are closely
linked with pathology in a wide range of diseases and condition which have
an inflammatory basis. Alterations in the intake of fats, antioxidant
nutrients, protein and specific amino acids change many aspects of
inflammation by interacting with cytokine and ROS biology, thereby providing
a means of modulating inflammation. Mortality and morbidity, in a diverse
range of diseases, have been linked with excessive or untimely oxidant and
pro-inflammatory cytokine production. Evidence of oxidative damage has been
observed in sepsis, HIV and hepatitis infection, cancer, diabetes mellitus,
alcoholic liver disease and cystic fibrosis. ROS produced during the
inflammatory response enhances pro-inflammatory cytokine production by
activation of nuclear factor kappa B (NF kappa B). The interaction is an
important part of the up-regulation of inflammatory aspects of immune
function. The interaction between ROS and cytokines has the potential to
damage the host but is held in check by the antioxidant defences. Nutrient
intake directly and indirectly influences antioxidant defence. Glutathione
is a major endogenous antioxidant and is important for lymphocyte
replication. Vitamin B, and riboflavin participate in the maintenance of
glutathione status. Vitamin B, acts as a cofactor in the synthesis of
cysteine (the rate limiting precursor for glutathione biosynthesis) and
riboflavin is a cofactor for glutathione reductase. Deficiencies in vitamins
E, B, and riboflavin reduce cell numbers in lymphoid tissues of experimental
animals and produce functional abnormalities in the cell mediated immune
response. Sulphur amino acid deficient rats exhibit an impaired ability to
synthesise glutathione during inflammation and have increased numbers of
neutrophils in lung. Ascorbic acid and tocopherols exert anti-inflammatory
effects in studies in man and animals. In humans, dietary supplementation
with ascorbic-acid, tocopherols and vitamin B, enhances a number of aspects
of lymphocyte function-In smokers indices of inflammation inversely relate
to the intakes of vitamins C and E. Studies in healthy subjects, patients
and experimental animals clearly demonstrate that unsaturated fats modulate
pro-inflammatory cytokine biology. In general n-6 polyunsaturated fatty
acids enhance, and n-3 PUFAs and monounsaturated fatty acids suppress,
cytokine mediated aspects of inflammation. In addition, n-6 PUFAs and
cholesterol enhance and n-3 PUFAs suppress cytokine production. Fats rich in
n-3 PUFAs are efficacious in a number of inflammatory diseases, however in
smokers indices of inflammation are enhanced in subjects consuming greater
than 5% of dietary energy in the form of n-6 PUFAs. Fats may modulate
cytokine biology by a number of mechanisms closely linked to membrane
phospholipid composition. As a consequence of diet induced change,
alterations in prostaglandin, leukotriene and diacyl glycerol production,
protein kinase C activation and fluidity may occur. Recent studies suggest
that changes in bulk membrane fluidity are unlikely to underlie the
substantial modulatory effects of fats on cytokine biology.
In conclusion nutrients have a major potential for modulating inflammatory
aspects of immune function due to interaction with three main areas whereby
inflammation is prosecuted and controlled. Firstly by changing provision of
substrate for the synthesis of molecules for components for the executive
and control systems (protein, sulphur amino acids, glutamine).
Secondly by modulating the composition of the membranes of cells involved
in the inflammatory process (unsaturated fatty acids and cholesterol) and
thirdly by influencing the interaction between ROS and NF kappa B activation
(sulphur amino acids, vitamins C and E, and riboflavin). (C) 1998 Elsevier
Science Inc. [References: 130]