CANCRO e TERAPIA RIORDINANTE del pH, con Bicarbonati
Visionare questa intervista:
http://www.curenaturalicancro.org/base_schermo_grande_testimonianza_dottore.htm
vedi: Terapia G. Puccio: dimostrazioni effetti del Bicarbonato di Sodio
L’acidosi e’ la base fisiologica del Cancro – Il Conflitto Spirituale Irrisolto, ne e’ la Causa primaria
Cancro = Combattere l’acidita’ per sconfiggerlo – Le ultime ricerche
Nutriterapia Biologica Metabolica x Cancro
Visionate il libro di Giorgio Bogoni: “La verita’ che il tuo oncologo non puo’ dirti”
Circolazione sanguigna: prevenzione degli infarti e del cancro. I citrati eliminano calcificazioni arteriose. Gli ascorbati fanno il resto !
Paolo-Lissoni: i-segreti-della-pineale-anticancro-io-oncologo-vi-spiego-perche-la-medicina-esclude-di-bella/
Oltre 75 anni fa (1931) furono assegnati al medico Otto Warburg due premi Nobel per le sue teorie che indicavano che il cancro fosse causato da un indebolimento del “respiro” delle cellule (il flusso del fluido intercellulare menzionato sopra), che procurava una mancanza di ossigeno nella cellula.
Il medico aveva dimostrato come il cancro prospera in condizioni anaerobiche – in mancanza d’ossigeno – cioè acide. Ricerche successive, fatte dai medici Keith Brewer e H. Satori hanno mostrato che, aumentando il pH – il contenuto dell’ossigeno – nella cellulae/o nel tessuto, a pH 8.0, si crea un ambiente ostile al cancro.
http://www.communicationagents.com/rinaldo_lampis/2006/03/06/come_evitare_la_formazione_del_cancro.htm
Quindi, Otto Heinrich Warburg nel 1931 scoprì la causa del cancro e vinse il nobel.
Infatti Egli afferma: “Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar”.
Traduzione: Il cancro, ancor più che per altre malattie, ha una serie illimitata di cause secondarie. Ma, anche per il cancro, c’è una causa primaria.
Riassumendo: la causa prima del cancro, è la sostituzione della respirazione di ossigeno nelle normali cellule del corpo con la fermentazione dello zucchero.
A questo punto le domande sono:
1 – Perché nei testi di medicina ufficiale le parole di Warburg sono state cambiate ?
2 – Perché, se la causa è stata scoperta, le ricerche in quella direzione si sono ridotte quasi a zero ?
Risposta:
Perche’ gli interessi…. si sono spostati verso la “gestione della malattia e del malato per fare “business“….
Qui l’articolo originale in Inglese: http://healingtools.tripod.com/primecause1.html/
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Studio medico sull’effetto della chemio a base di BDS (Bicarbonato di Sodio) nell’inibizione delle metastasi.
Recentemente è apparso uno studio medico che cerca di capire se il bicarbonato di sodio possa avere qualche funzione nel curare il cancro.
Datato 10 Marzo 2009 questo è uno studio firmato da: Ian F. Robey,1 Brenda K. Baggett,1 Nathaniel D. Kirkpatrick,1 Denise J. Roe,1 Julie Dosescu,2 Bonnie F. Sloane,2 Arig Ibrahim Hashim,3 David L. Morse,3 Natarajan Raghunand,1 Robert A. Gatenby,3 and Robert J. Gillies3
1Arizona Cancer Center, University of Arizona, Tucson, Arizona; 2Department of Pharmacology, Wayne State University, Detroit, Michigan; and 3H. Lee Moffitt Cancer Center and Research Institute, Tampa,
Florida – Studio pubblicato su Publimed
I risultati che si prefiggevano i ricercatori erano probabilmente più ambiziosi ma anche quelli raggiunti non sono per nulla da sottovalutare. Si tratta di una prima ricerca medica che ha coinvolto delle cavie (topi) immunodepressi ai quali sono stati indotti dei tumori, lasciati crescere e poi si è cominciata la sperimentazione a “doppio cieco”.
I risultati ottenuti sono sicuramente importanti soprattutto se paragonati allo stesso effetto anti-metastasi di preparati chimici odierni definiti genericamente chemioterapici.
Gli stessi ricercatori che hanno scritto questo documento chiedono che altri, dopo averne presa visione, conducano successive sperimentazioni variando dosaggi (che per questo primo test erano minimi per paura di complicazioni dovute ad alcalosi metabolica la quale non si è verificata) e soprattutto tipi di tumore per conoscere meglio i limiti di applicabilità di questa terapia.
In due casi la riduzione di metastasi tra i topi trattati è stata “sorprendente” rispetto a quelli che non hanno ricevuto il bicarbonato, ma nel terzo tipo di tumore indotto non vi è stata differenza significativa tra i due gruppi di cavie.
vedi: Acidosi e Cancro + Come fare i clisteri di acqua basica + Nutriterapia per il cancro
“Do fungi play a role in the aetiology of cancer ? “, Reviews in Medical Microbiology
13(1):37-42, January 2002, Wainwright, Milton
Abstract:
The recent recognition that the bacterium Helicobacter pylori potentially plays a role in the aetiology of gastric cancer has highlighted the possibility that other non-virus microorganisms, including yeasts and filamentous fungi, may also cause cancer in humans. For more than a century fungi have been implicated in the aetiology of cancer. Initially, attention was directed to yeasts in the so-called blastomycete-theory of cancer; more recently filamentous fungi have also been implicated in carcinogenesis, based largely on their ability to produce potentially carcinogenic mycotoxins. Here, the widely spread literature on the role of fungi in carcinogenesis is reviewed in the hope that it will stimulate a re-evaluation of the potential carcinogenic role of fungi.
(C) 2002 Lippincott Williams & Wilkins, Inc.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=99379706
http://www.nexusmagazine.com/articles/CancerIsAFungus.html
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Il Cancro nasce in sintesi e secondo la Medicina naturale, perche’ organismo del canceroso e’ intossicato, infiammato,immunodepresso, con enzimi e flora batterica alterata, pH digestivo non regolare (e quindi l’organismo e’ mancante di minerali evitamine), e molto facilmente parassitato da certi, parassiti, batteri e funghi (candida) i quali producono anche tossine ed ulteriori infiammazioni, ma e’ “gestito” come Causa primordiale dai Conflitti Spirituali (consci ed inconsci) e dall’intenso stress – Esso e’ quindi una malattia MULTIFATTORIALE.
Quindi il medico, il terapeuta od il soggetto stesso DEVE operare seguendo la stessa strada percorsa per l’ammalamento.
Cioe’ deve lavorare per disintossicare il malato + disinfiammare l’organismo ed i tessuti interessati, ripristinare il pH digestivo, e normalizzare le digestioni + il malassorbimento sempre presente nel malato ed eliminare quei parassiti, batteri e funghi, che hanno proliferato in modo abnorme, per mancanza dei loro antagonisti + rinforzare il sistema immunitario SEMPRE compromesso in TUTTI i malati, cancerosi compresi ed eliminare i Conflitti spirituali (quali Cause) e lo stress esistenti.
E tuttavia, laddove ci sia anche una piccola volontà e speranza di vivere, un’adeguata terapia fito-nutrizionale (NdR: anche via endovena con soluzioni mineral – vitaminiche – vedi QUI il medico che utilizza con successo questo sistema – l’ideale e utilizzare quelli non di sintesi chimica, ma di estrazione naturale – assieme all’assunzione via orale di fermenti lattici appropriati a seconda del paziente ed enzimi) può rendere normale il guarire naturalmente dal tumore, cosa che oggi vogliono farci ritenere impossibile o puramente miracoloso (vedi quei medici che alle volte preferiscono spedire il malato a Lourdes piuttosto che permettergli di curarsi naturalmente).
L’acidosi e’ la base fisiologica del Cancro – Il Conflitto Spirituale Irrisolto, ne e’ la Causa primaria
Cancro = Combattere l’acidita’ per sconfiggerlo – Le ultime ricerche
Nutriterapia Biologica Metabolica x il Cancro e non solo + Terapia Biologica Metabolica CRAP + Cura metabolica per il Cancro + Stress Ossidativo + PREVENZIONE, TERAPIA per il Cancro, perche’ NON si vuole applicare ? + Terreno Oncologico + Bioelettronica + Semeiotica e Biofisica
Documenti provanti l’indispensabilita’ delle Vitamine della Frutta e verdura, oltre ai sali minerali:
Doc.1 + Doc.2 + Doc.3 + Doc.4 + Doc.5 + Doc.6 + Doc.7 + Doc.8 + Doc.9 + Doc.10 + Doc.11 + Doc.12 + Doc.13 + Doc.14 + Doc.15 + Doc.16 + Doc.17 + Doc.18 + Doc.19 + Doc.20 + Doc.21 + Doc.22 + Doc.23 + Doc.24 + Doc.61
vedi anche : CURE Naturali del Cancro + Documentazione + Protocollo G. Puccio + Diritti negati + Ricercatore ostacolato dalla Oncologia Ufficiale + Giornale di Sicilia + Come fare i clisteri di acqua basica + Cancro e Medicina Naturale + 1.000 Piante per il Cancro + Libro del dott. Nacci (Italiano) + Libro del dott. Nacci in Inglese + Condiloma eliminato con acqua basica al Bicarbonato di Sodio + Protocollo della Salute + Cancro + Diagnosi precoce
Seria RICERCA sul CANCRO (ostacolata dall’Oncologia ufficiale)
La guerra contro il Cancro e’ stata definitivamente vinta cinquant’anni fa, ma nessun medico oncologo-ospedaliero ve lo confessera’ mai.
vedi: 1.000 Piante per il Cancro + Libro del dott. Nacci (Italiano) + Libro del dott. Nacci in Inglese + Condiloma eliminato con acqua basica al Bicarbonato di Sodio
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pH and Chemotherapy – A., Raghunand N. B., Gillies RJ.
University of Arizona Health Sciences Center, Cancer Center Division, Tucson 85724-5024, USA.
In vivo pH measurements by magnetic resonance spectroscopy reveal the presence of large regions of acidic extracellular pH in tumours, with the intracellular pH being maintained in the neutral-to-alkaline range.
This acid-outside plasmalemmal pH gradient acts to exclude weak base drugs such as the anthracyclines and vinca alkaloids, a behaviour that is predicted by the decrease in octanol-water partition coefficients of mitoxantrone and doxorubicin with decreasing solution pH.
This pH gradient can be reduced or eliminated in mouse models of breast cancer by systemic treatment with sodium bicarbonate. We have demonstrated tumour alkalinization following chronic ad libitum administration of NaHCO3 and acute intraperitoneal administration of NaHCO3 to tumour-bearing mice.
Chronic treatment of tumour-bearing SCID mice with NaHCO3 results in an enhancement in MCF-7 tumour xenograft response to doxorubicin. Intraperitoneal administration of NaHCO3 to tumour-bearing C3H/Hen mice prior to treatment with mitoxantrone results in a greater-than 4.5-fold increase in cell-kill in the syngeneic C3H mammary tumour model. Most combination chemotherapy regimens include at least one weak base drug. Our results suggest that agents such as sodium bicarbonate, Carbicarb and the diuretic furosemide–which are known to induce metabolic alkalosis in humans–may be useful in enhancing the efficacy of these treatment regimens in humans. – PMID: 11727930
1: Cancer Res 1989 Aug 15;49(16):4373-84 Related Articles, Books, LinkOut
Acid pH in tumors and its potential for therapeutic exploitation.
Tannock IF, Rotin D. – Department of Medicine, Ontario Cancer Institute, Toronto, Canada.
Measurement of pH in tissue has shown that the microenvironment in tumors is generally more acidic than in normal tissues. Major mechanisms which lead to tumor acidity probably include the production of lactic acid and hydrolysis of ATP in hypoxic regions of tumors. Further reduction in pH may be achieved in some tumors by administration of glucose (+/- insulin) and by drugs such as hydralazine which modify the relative blood flow to tumors and normal tissues. Cells have evolved mechanisms for regulating their intracellular pH. The amiloride-sensitive Na+/H+ antiport and the DIDS-sensitive Na+-dependent HCO3-/Cl- exchanger appear to be the major mechanisms for regulating pHi under conditions of acid loading, although additional mechanisms may contribute to acid extrusion. Mitogen-induced initiation of proliferation in some cells is preceded by cytoplasmic alkalinization, usually triggered by stimulation of Na+/H+ exchange; proliferation of other cells can be induced without prior alkalinization. Mutant cells which lack Na+/H+ exchange activity have reduced or absent ability to generate solid tumors; a plausible explanation is the failure of such mutant cells to withstand acidic conditions that are generated during tumor growth. Studies in tissue culture have demonstrated that the combination of hypoxia and acid pHe is toxic to mammalian cells, whereas short exposures to either factor alone are not very toxic. This interaction may contribute to cell death and necrosis in solid tumors. Acidic pH may influence the outcome of tumor therapy.
There are rather small effects of pHe on the response of cells to ionizing radiation but acute exposure to acid pHe causes a marked increase in response to hyperthermia; this effect is decreased in cells that are adapted to low pHe. Acidity may have varying effects on the response of cells to conventional anticancer drugs. Ionophores such as nigericin or CCCP cause acid loading of cells in culture and are toxic only at low pHc; this toxicity is enhanced by agents such as amiloride or DIDS which impair mechanisms involved in regulation of pHi.
It is suggested that acid conditions in tumors might allow the development of new and relatively specific types of therapy which are directed against mechanisms which regulate pHi under acid conditions.
1: Biull Eksp Biol Med 1992 Apr;113(4):352-5 Related Articles, Books, LinkOut
Dynamics of bioelectric activity of the brain and erythrocyte ultrastructure after intravenous infusion of sodium bicarbonate to oncologic patients].
[Article in Russian]
Davydova IG, Kassil’ VL, Raikhlin NT, Filippova NA.
23 patients with malignant tumors of different location and histogenesis were investigated. There were no metastases in 9 cases. 10 patients had metastases in regional areas and 4–distant. The results were compared with those obtained in 4 patients with nonmalignant diseases. EEG, blood gases, plasma acid–base balance and ultrastructure of erythrocytes were explored before and after intravenous infusion of 4.2% sodium bicarbonate solution. The metabolic alkalosis induced amelioration of EEG, which was changed basically, the condense of pre-membrane layer disappeared or decreased in erythrocytes, and disaggregation of erythrocytes took place in cancer patients vs those with nonmalignant tumors.
The results confirm the suggestion of generalized intracellular acidosis in malignant tumor patients.
This acidosis can be temporarily avoided or diminished artificially by blood alkalosis.
1: Br J Cancer 1996 Oct;74(8):1206-15 Related Articles, Books, LinkOut
Fluorescence ratio imaging of interstitial pH in solid tumours: effect of glucose on spatial and temporal gradients.
Dellian M, Helmlinger G, Yuan F, Jain RK.
Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Tumour pH plays a significant role in cancer treatment. However, because of the limitations of the current measurement techniques, spatially and temporally resolved pH data, obtained non-invasively in solid tumours, are not available. Fluorescence ratio imaging microscopy (FRIM) has been used previously for noninvasive, dynamic evaluation of pH in neoplastic tissue in vivo (Martin GR, Jain RK 1994, Cancer Res., 54, 5670-5674). However, owing to problems associated with quantitative fluorescence in thick biological tissues, these studies were limited to thin (50 microns) tumours. We, therefore, adapted the FRIM technique for pH determination in thick (approximately 2 mm) solid tumours in vivo using a pinhole illumination-optical sectioning (PIOS) method. Results show that (1) steep interstitial pH gradients (5 microns resolution), with different spatial patterns, exist between tumour blood vessels; (2) pH decreased by an average of 0.10 pH units over a distance of 40 microns away from the blood vessel wall, and by 0.33 pH units over a 70 microns distance; (3) the maximum pH drop, defined as the pH difference between the intervessel midpoint and the vessel wall, was positively correlated with the intervessel distance; (4) 45 min following a systemic glucose injection (6 g kg-1 i.v), interstitial pH gradients were shifted to lower pH values by an average of 0.15 pH units, while the spatial gradient (slope) was maintained, when compared with preglucose values. This pH decrease was not accompanied by significant changes in local blood flow. pH gradients returned to near-baseline values 90 min after glucose injection; (5) interstitial tumour pH before hyperglycaemia and the glucose-induced pH drop strongly depended on the local vessel density; and (6) sodium bicarbonate treatment, either acute (1 M, 0.119 ml h-1 for 3 h i.v.) or chronic (1% in drinking water for 8 days), did not significantly change interstitial tumour pH. Modified FRIM may be combined with other optical methods (e.g. phosphorescence quenching) to evaluate non-invasively the spatial and temporal characteristics of extracellular pH, intracellular pH and pO2 in solid tumours.
This will offer unique information about tumour metabolism and its modification by treatment modalities used in different cancer therapies.
1: Biochim Biophys Acta 1996 Jun 13;1282(1):131-9 Related Articles, Books, LinkOut
Effects of extracellular pH on intracellular pH-regulation and growth in a human colon carcinoma cell-line.
Bischof G, Cosentini E, Hamilton G, Riegler M, Zacherl J, Teleky B, Feil W, Schiessel R, Machen TE, Wenzl E.
University Clinic of Surgery, Vienna, Austria. georg.bischof@vm.akh-wien.ac.at
Mechanisms of intracellular pH (pHi) regulation seem to be involved in cellular growth and cell division.
Little is known about how extracellular acidosis, known to occur in central regions of solid tumors, or alkaline conditions affect pHi regulation in colonic tumors. pHi changes in the colonic adenocarcinoma cell-line SW-620 were recorded by spectrofluorimetric monitoring of the pH-sensitive, fluorescent dye BCECF, and proliferative activity was assessed by [3H]thymidine uptake. Resting pHi in Hepes-buffered solution was 7.53 +/- 0.01 (n = 36). Both 1 mM amiloride and Na(+)-free solution inhibited pHi recovery from acidification and decreased pHi in resting cells. In HCO3-/CO2-buffered media resting pH1 was 7.42 +/- 0.01 (n = 36). Recovery from acidification was Na(+)-dependent, CI(-)-independent, and only partially blocked by 1 mM amiloride. In the presence of amiloride and 200 microM H2DIDS pHi recovery was completely inhibited. In Na(+)-free solution pHi decreased from 7.44 +/- 0.04 to 7.29 +/- 0.03 (n = 6) and no alkalinization was observed in CI(-)-free medium. Addition of 5 microM tributyltin bromide (an anion/OH-exchange ionophore) caused pHi to decrease from 7.43 +/- 0.05 to 7.17 +/- 0.08 (n = 5).
The effects of pH0 on steady-state pHi, pHi recovery from acidification and proliferative activity after 48 h were investigated by changing buffer [CO2] and [HCO3-]. In general, increases in pH0 between 6.7 and 7.4 increased pHi recovery, steady-state pHi and growth rates. In summary, SW-620 cells have a resting pHi > 7.4 at 25 degrees C, which is higher than other intestinal cells. Acid extrusion in physiological bicarbonate media is accomplished by a pHi-sensitive Na+/H+ exchanger and a pHi-insensitive Na(+)-HCO3-cotransporter, both of which are operational in control cells at the resting pHi.
No evidence for activity of a CI-/HCO3- exchanger was found in these cells, which could account for the high pHi observed and may explain why the cells continue to grow in acidic tumor environments.
1: Hepatology 1995 Aug;22(2):588-97 Related Articles, Books, LinkOut
Intracellular pH regulation in Hep G2 cells: effects of epidermal growth factor, transforming growth factor-alpha, and insulinlike growth factor-II on Na+/H+ exchange activity.
Strazzabosco M, Poci C, Spirli C, Zsembery A, Granato A, Massimino ML, Crepaldi G.
Istituto di Medicina Interna, Universita di Padova, Italy.
Intracellular pH (pHi) plays an important role in the metabolic activation of quiescent cells after a proliferative stimulus, and Na+/H+ exchange activity is required for growth in some extrahepatic tumors.
To investigate intracellular acid/base homeostasis in hepatoma cells and the effects of putative liver growth factors on Na+/h+ exchange activity, we have studied intracellular pH (pHi) regulation in Hep G2 cells, a well-differentiated hepatoma cell line, both in resting conditions and after administration of epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and insulinlike growth factor-II (IGF-II).
The effects of fetal calf serum, TGF alpha, and amiloride on 3H-Thymidine incorporation were also studied. Amiloride (1 mmol/L) and external Na+ removal decreased baseline pHi in both HEPES and KRB.
In HEPES, cells recovered from an acid load (20 mmol/L NH4Cl) by an amiloride inhibitable Na+/H+ exchange. In KRB, an additional, DIDS-inhibitable, Na(+)- and HCO3- dependent, but Cl(-)-independent acid extruder (Na:HCO3 cotransport) was activated. No evidence was found for a Cl/HCO3 exchange acting as acid loader. Administration of EGF and TGF alpha, but not of IGF-II, induced a dose-dependent, amiloride-inhibitable increase in baseline pHi, together with an increase in Na+/H+ exchange activity, shifting to the right the JH/pHi curve. Finally, 3H-thymidine incorporation in Hep G2 cells, in the presence of FCS or TGF alpha, was strongly inhibited by amiloride. In conclusion, in Hep G2 cells, pHi is mainly regulated by Na+/H+ exchange, which activity can be stimulated by EGF and TGF alpha, but not by IGF-II. Administration of TGF alpha stimulates DNA synthesis, an effect that is blocked by amiloride, an inhibitor of Na+/H+ exchanger. These data suggest that Na+/H+ exchange activation may play a critical role in the growth of some hepatic tumors.
1: Dtsch Tierarztl Wochenschr 1995 Apr;102(4):161-2 Related Articles, Books
Regulation of intracellular pH in the colonic epithelial cell line HT29 clone 19A.
Busche R, Bartels J, von Engelhardt W.
Department of Physiology, School of Veterinary Medicine Hannover.
Intracellular pH (pHi) of the colonic tumor cell line HT29 cl. 19A was studied by microspectrofluorometry using the pH-sensitive dye BCECF. Single cells within a confluent monolayer grown in a polarized manner on permeable supports were examined. An amiloride-sensitive Na(+)-H+ exchange and a stilbene-insensitive Cl(-)-HCO3- exchange mechanism have been identified in the basolateral membrane. This Na(+)-H+ exchange mechanism in the basolateral membrane is an acid extruder, whereas the Cl(-)-HCO3- exchanger is an acid loader. Both of these in the basolateral membrane located mechanisms are important for the maintenance of intracellular pH in HT29 cl. 19A cells.
1: Vestn Ross Akad Med Nauk 1995;(4):24-5 Related Articles, Books, LinkOut
[Characteristics of the effects of artificial alkalosis on electrical activity of the brain and ultrastructure of blood cells in oncologic patients].
[Article in Russian]
Davydova IG, Kassil’ VL, Filippova NA, Barinov MV.
The authors examined 40 patients with malignant tumors of various histogenesis, sites and extent, as well as 5 patients with benign tumors and other non-tumorous diseases. They also studied their electroencephalography and peripheral blood lymphocytic and erythrocytic ultrastructure in metabolic alkalosis temporarily induced by intravenous sodium hydrogen carbonate. In cancer patients without late metastases, alkalosis caused a transient normalization of previously altered electroencephalography, erythrocyte disaggregation and substantially reduced the count of killer cells in small and middle lymphocytes. These findings suggest that patients with malignant neoplasms have a generalized intracellular acidosis which can be temporarily abolished by plasma alkalinization.
1: Pflugers Arch 1994 Sep;428(2):179-85 Related Articles, Books, LinkOut
pH regulation in HT29 colon carcinoma cells.
Kottgen M, Leipziger J, Fischer KG, Nitschke R, Greger R.
Physiologisches Institut, Albert-Ludwigs-Universitat, Freiburg, Germany.
The pH regulation in HT29 colon carcinoma cells has been investigated using the pH-sensitive fluorescent indicator 2′,7′-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF). Under control conditions, intracellular pH (pHi) was 7.21 +/- 0.07 (n = 22) in HCO3(-)-containing and 7.21 +/- 0.09 (n = 12) in HCO3(-)-free solution. HOE-694 (10 mumol/l), a potent inhibitor of the Na+/H+ exchanger, did not affect control pH.
As a means to acidify cells we used the NH4+/NH3 (20 mmol/l) prepulse technique. The mean peak acidification was 0.37 +/- 0.07 pH units (n = 6). In HCO3(-)-free solutions recovery from acid load was completely blocked by HOE-694 (1 mumol/l), whereas in HCO3(-)-containing solutions a combination of HOE-694 and 4,4′-diisothiocyanatostilbene-2,2′-disulphonate (DIDS, 0.5 mmol/l) was necessary to show the same effect. Recovery from acid load was Na(+)-dependent in HCO3(-)-containing and HCO3(-)-free solutions. Removal of external Cl- caused a rapid, DIDS-blockable alkalinization of 0.33 +/- 0.03 pH units (n = 15) and of 0.20 +/- 0.006 pH units (n = 5), when external Na+ was removed together with Cl-. This alkalinization was faster in HCO3(-)-containing than in HCO3(-)-free solutions. The present observations demonstrate three distinct mechanisms of pHi regulation in HT29 cells: (a) a Na+/H+ exchanger, (b) a HCO3-/Cl- exchanger and (c) a Na(+)-dependent HCO3- transporter, probably the Na(+)-HCO3-/Cl- antiporter.(ABSTRACT TRUNCATED AT 250 WORDS)
1: J Biol Chem 1992 Sep 5;267(25):17665-9 Related Articles, Books, LinkOut
Regulatory volume decrease in the presence of HCO3- by single osteosarcoma cells UMR-106-01.
Star RA, Zhang BX, Loessberg PA, Muallem S.
Department of Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9040.
The technique for the simultaneous recording of cell volume changes and pHi in single cells was used to study the role of HCO3- in regulatory volume decrease (RVD) by the osteosarcoma cells UMR-106-01. In the presence of HCO3-, steady state pHi is regulated by Na+/H+ exchange, Na+ (HCO3-)3 cotransport and Na(+)-independent Cl-/HCO3- exchange. Following swelling in hypotonic medium, pHi was reduced from 7.16 +/- 0.02 to 6.48 +/- 0.02 within 3.4 +/- 0.28 min. During this period of time, the cells performed RVD until cell volume was decreased by 31 +/- 5% beyond that of control cells (RVD overshoot). Subsequently, while the cells were still in hypotonic medium, pHi slowly increased from 6.48 +/- 0.02 to 6.75 +/- 0.02.
This increase in pHi coincided with an increase in cell volume back to normal (recovery from RVD overshoot or hypotonic regulatory volume increase (RVI)). The same profound changes in cell volume and pHi after cell swelling were observed in the complete absence of Cl- or Na+, providing HCO3- was present.
On the other hand, depolarizing the cells by increasing external K+ or by inhibition of K+ channels with quinidine, Ba2+ or tetraethylammonium prevented the changes in pHi and RVD. These findings suggest that in the presence of HCO3-, RVD in UMR-106-01 cells is largely mediated by the conductive efflux of K+ and HCO3-. Removal of external Na+ but not Cl- prevented the hypotonic RVI that occurred after the overshoot in RVD. Amiloride had no effect, whereas pretreatment with 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) strongly inhibited hypotonic RVI. Thus, hypotonic RVI is mediated by a Na+(out)-dependent, Cl(-)-independent and DIDS-inhibitable mechanism, which is indicative of a Na+(HCO3-)3 cotransporter. This is the first evidence for the involvement of this transporter in cell volume regulation. The present results also stress the power of the new technique used in delineating complicated cell volume regulatory mechanisms in attached single cells.
Requirement of the Na+/H+ exchanger for tumor growth.
Rotin D, Steele-Norwood D, Grinstein S, Tannock I.
Department of Medicine and Medical Biophysics, Ontario Cancer Institute, Toronto, Canada.
The Na+/H+ exchanger is involved in a variety of cellular processes, including regulation of intracellular pH and possibly the control of cell growth and proliferation. To study the role of the Na+/H+ exchanger in tumor growth, human sodium proton exchanger-deficient (HSPD) mutants were derived from the human bladder carcinoma cell line MGH-U1 (EJ) by the proton suicide selection technique (J. Pouyssegur et al., Proc. Natl. Acad. Sci. USA, 81: 4833-4837, 1984). The HSPD cells were approximately 40% larger and contained approximately 70% more DNA than the parental cells. They were unable to grow in vitro in the absence of bicarbonate at pH less than 7.0, whereas the parental cells grew well at pH greater than or equal to 6.6. This difference in acid sensitivity was abolished in the presence of bicarbonate. In contrast to the parental MGH-U1 cells, the Na+/H+-deficient HSPD cells either failed to grow tumors, or showed severely retarded tumor growth when implanted into immune-deprived mice. This difference in tumor growth was not attributed to differences in cell size and DNA content, because Na+/H+ exchange-competent large cells (HLC), derived during the same proton suicide selection process as the HSPD cells, grew tumors at a rate close to that of the parental cells. Cells derived from the few tumors which grew after implantation of HSPD mutant cells were revertants which had regained Na+/H+ activity. HSPD cells also failed to form spheroids in culture, and the only spheroid formed consisted of revertant cells which had regained both Na+/H+ exchange activity and tumorigenic capacity. These results suggest that the Na+/H+ exchanger is important for tumor growth.
1: Eur J Biochem 1987 Dec 30;170(1-2):43-9 Related Articles, Books
Properties of the Na+-dependent Cl-/HCO3- exchange system in U937 human leukemic cells.
Ladoux A, Krawice I, Cragoe EJ Jr, Abita JP, Frelin C.
Institut National de la Sante et de la Recherche Medicale Unite 204, Hopital Saint-Louis, Paris, France.
U937 cell possess two mechanisms that allow them to recover from an intracellular acidification.
The first mechanism is the amiloride-sensitive Na+/H+ exchange system. The second system involves bicarbonate ions. Its properties have been defined from intracellular pH (pHi) recovery experiments, 22Na+ uptake experiments, 36Cl- influx and efflux experiments. Bicarbonate induced pHi recovery of the cells after a cellular acidification to pHi = 6.3 provided that Na+ ions were present in the assay medium. Li+ or K+ could not substitute for Na+. The system seemed to be electroneutral. 22Na+ uptake experiments showed the presence of a bicarbonate-stimulated uptake pathway for Na+ which was inhibited by 4,4′-diisothiocyanostilbene-2,2′-disulfonate. The bicarbonate-dependent 22Na+ uptake component was reduced by depleting cells of their internal Cl- and increased by removal of external Cl-. 36Cl- efflux experiments showed that the presence of both external Na+ and bicarbonate stimulated the efflux of 36Cl- at a cell pHi of 6.3. Finally a 36Cl- uptake pathway was documented. It was inhibited by 4,4′-diisothiocyanostilbene-2,2′-disulfonate (K0.5 = 10 microM) and bicarbonate (K0.5 = 2 mM).
These results are consistent with the presence in U937 cells of a coupled exchange of Na+ and bicarbonate against chloride. It operates to raise the intracellular pH. Its pHi and external Na+ dependences were defined. No evidence for a Na+-independent Cl-/HCO3- exchange system could be found.
The Na+-dependent Cl-/HCO3- exchange system was relatively insensitive to (aryloxy)alkanoic acids which are potent inhibitors of bicarbonate-induced swelling of astroglia and of the Li(Na)CO3-/Cl- exchange system of human erythrocytes. It is concluded that different anionic exchangers exist in different cell types that can be distinguished both by their biochemical properties and by their pharmacological properties.
1: Cancer Res 1992 Jan 1;52(1):144-8 Related Articles, Books
Intracellular acidification is associated with enhanced morphological transformation in Syrian hamster embryo cells.
LeBoeuf RA, Lin PY, Kerckaert G, Gruenstein E.
Procter and Gamble Co., Miami Valley Laboratories, Cincinnati, Ohio 45239-8707.
A series of studies has indicated that the frequency of morphological transformation induced by chemical carcinogens in early passage Syrian hamster embryo (SHE) cells is significantly higher when these cells are cultured in medium of reduced bicarbonate concentration and pH (6.70) compared with cells cultured in medium of higher pH. It has also been shown that intercellular gap junctional communication is decreased in these cells when they are cultured at pH 6.70 compared with medium of higher pH.
The purpose of the studies reported here was to characterize the effect of changing extracellular pH on intracellular pH in SHE cells. The frequency of morphological transformation induced by benzo(a)pyrene was established at various extracellular pHs and compared with intracellular pH values.
Cells cultured in medium of pH ranging from 6.70 to 7.35 were loaded with the pH-sensitive fluorescent dye 2′,7′-bis(carboxyethyl)-5,6-carboxyfluorescein, and either the steady-state intracellular pH values or the kinetics of change in intracellular pH following refeeding of the cultures with medium of pH ranging from pH 6.70 to pH 7.35 was monitored via image analysis techniques. Results from these studies indicate that, at culture medium pH above 6.95, SHE cells were relatively insensitive to changes in extracellular pH, maintaining an intracellular pH of 7.30 to 7.35 in medium containing 0% serum or pH 7.05 to 7.10 in medium containing 20% fetal bovine serum. At extracellular pHs below 6.95, intracellular pH decreased and, in the presence of serum, equilibrated with extracellular pH. The decrease in intracellular pH was closely associated with an increase in benzo(a)pyrene-induced morphological transformation frequency observed in parallel studies. These results indicate that SHE cells have active intracellular pH regulatory activities and suggest that intracellular acidification plays a role in the increased frequency of transformation observed in SHE cells cultured under acidic conditions.
1: Br J Cancer 1999 Jun;80(7):1005-11 Related Articles, Books, LinkOut
Enhancement of chemotherapy by manipulation of tumour pH.
Raghunand N, He X, van Sluis R, Mahoney B, Baggett B, Taylor CW, Paine-Murrieta G, Roe D, Bhujwalla ZM, Gillies RJ.
Arizona Cancer Center, Tucson 85724-5024, USA.
The extracellular (interstitial) pH (pHe) of solid tumours is significantly more acidic compared to normal tissues. In-vitro, low pH reduces the uptake of weakly basic chemotherapeutic drugs and, hence, reduces their cytotoxicity. This phenomenon has been postulated to contribute to a ‘physiological’ resistance to weakly basic drugs in vivo. Doxorubicin is a weak base chemotherapeutic agent that is commonly used in combination chemotherapy to clinically treat breast cancers. This report demonstrates that MCF-7 human breast cancer cells in vitro are more susceptible to doxorubicin toxicity at pH 7.4, compared to pH 6.8. Furthermore 31P-magnetic resonance spectroscopy (MRS) has shown that the pHe of MCF-7 human breast cancer xenografts can be effectively and significantly raised with sodium bicarbonate in drinking water. The bicarbonate-induced extracellular alkalinization leads to significant improvements in the therapeutic effectiveness of doxorubicin against MCF-7 xenografts in vivo.
Although physiological resistance to weakly basic chemotherapeutics is well-documented in vitro and in theory, these data represent the first in vivo demonstration of this important phenomenon.
1: Cancer Res 1998 May 1;58(9):1901-8 Related Articles, Books, LinkOut
Heterogeneity of intracellular pH and of mechanisms that regulate intracellular pH in populations of cultured cells.
Lee AH, Tannock IF.
Department of Medical Biophysics, Ontario Cancer Institute, Toronto, Canada.
Cells within solid tumors are known to exist in a microenvironment that may be acidic and depend on membrane-based mechanisms (Na+/H+ antiport and Na+-dependent Cl-/HCO3- exchanger) that regulate intracellular pH (pHi). We have used the fluorescent pH indicator 2′,7′-bis-(2-carboxyethyl) 5 (and 6)-carboxyfluorescein and flow cytometry to study the distribution of pHi and the activity of these pHi-regulating mechanisms among populations of murine mammary sarcoma (EMT6), human breast cancer (MCF-7), and Chinese hamster ovary cells exposed to different levels of extracellular pH (pHe).
Cells were exposed to Na+ buffer in the presence or absence of HCO3- and of 5-(N-ethyl-N-isopropyl)-amiloride (a potent inhibitor of the Na+/H+ antiport) to determine the relative importance of each exchanger in the regulation of pHi. Our results indicate that: (a) the distribution of pHi at any value of pHe is broader than can be accounted for by machine noise; (b) cells maintain levels of pHi that are higher than pHe under acidic conditions; (c) the distribution of pHi is narrower when the Na+-dependent Cl-/HCO3- exchanger is active; and (d) populations that are derived from selected cells with values of pHi at lower and higher ends of the pHi distribution generate pHi distributions that are similar to those of controls, suggesting a stochastic variation in the activity of membrane-based mechanisms that regulate pHi. Our data suggest that the Na+-dependent Cl-/HCO3- exchanger is the dominant mechanism for regulation of pHi under moderately acidic conditions such as may occur in the microenvironment of solid tumors.
Commento NdR:
In uno dei vari scambi di opinione che ho avuto con il dott. Tullio Simoncini ho fatto presente che:
La Candida Albicans e’ un fungo saprofita, cioe’ essa produce sostanze utili e si nutre di parti morti od ammalate dei tessuti, di fatto essa e’ uno degli spazzini dell’organismo; essa fino a quando, per la presenza di microbi antagonisti che la controllano, rimane nei valori quantitativi necessari vitali, essa e’ utile all’organismo, ma quando per la mancanza di antagonisti per l’alterazione della flora autoctona residente, prolifera a dismisura, essa diviene patogena, cioe’ produce anche sostanze tossiche ed inizia a veicolarsi in certe parti del corpo ove essa si puo’ recare attirata dal terreno-tessuto-cellule intossicato ed in acidosi, in loco tende a proliferare a dismisura (sempre la mancanza degli antagosnisti accorpando i tessuti e quindi formando la massa tumorale che tenta alle volte anche di fagocitare.
Il bicarbonato agisce si sulla proliferazione della candida, basicizzando la zona ove essa prolifera.
Il rendere basici i tessuti od i liquidi serve a normalizzare il pH in loco ed a far rientrare l’abnorme proliferazione della candida in modo che essa riprenda le sue normali funzioni di aiuto all’organismo.
In questo modo anche le cellule si rimettono a funzionare bene immediatamente ove la normalizzazione del pH e’ avvenuta.
Per cui in certe ricerche effettuate e’ possibile, come in questo nel modello animale indicato qui, che la parte studiata-analizzata ove e’ presente la Candida, non abbia tutte le condizioni reali che si presentano nei vari tipi di tessuto UMANO canceroso (intossicazione + acidosi + infiammazione + alterazione di flora autoctona + Conflitto spirituale irrisolto) ed ecco che essa svolge il suo normale lavoro di aiuto e non quello contro la vita dell’ospitante.
Ecco perche’ NON condivido tutto cio’ che afferma il dott. Tullio Simoncini sulla Candida, essa NON e’ l’unica Causa fisiologica, ma una con-causa efficace della formazione del tumore (freddo o caldo), cosi come descritto nella mia tesina: CANCRO e MEDICINA NATURALE (Principi, Cause, con-Cause, Diagnosi, Terapia); il cancro come tutte le malattie, e’ quindi una malattia Multifattoriale.
Inoltre occorre dire che ogni malato che segue le terapie della Medicina Naturale, subisce a sua insaputa o meno la “crisi di eliminazione“, cioe’ il corpo tende ad eliminare le sostanze tossiche depositate nei tessuti; in quel “frangente” se l’organismo non e’ piu’ che supportato dalle adatte terapie naturali, per poter sopportare quella crisi di eliminazione, egli puo’ soccombere e morire.
Altra considerazione, occorre tenere presente che NON tutti coloro che seguono le terapie naturali e che sono malati di cancro, guariscono.
Alcuni bloccano solo l’avanzata del tumore o del cancro, altri guariscono totalmente, ma sono pochi, altri infine muoiono, in quanto non riescono a superare la “crisi di eliminazione” e/o sono arrivati tardi ad applicarle, quando le loro riserve vitali erano ormai state esaurite da Chemio, Radio terapia, od altro, per cui non ce la fanno, come non ce la fanno le centinaia di migliaia di cancerosi che affidandosi esclusivamente alla Chemio ed alla Radioterapia, muoiono (salvo quelli che si operano chirurgicamente i quali hanno maggiori possibilita’ di sopravvivenza.
Le statistiche a livello mondiale parlano del 2-5 % di possibilita’ di sopravvivenza nel primi 10 anni, dalla diagnosi di cancro, dei malati curati con la Chemio-Radio terapia… e’ veramente deprimente come questa medicina ufficiale sia totalmente impotente davanti al male del secolo.
IMPORTANTE:
Come Portale segnaliamo vari personaggi che hanno avuto contrasti con le autorita’ mediche, e per essere precisi, affermiamo che NON condividiamo in toto le loro terapie (quelle monoterapeutiche), in quanto per noi, seguaci della Medicina Naturale lamalattia (cancro compreso) e’ MULTIFATTORIALE, quindi NESSUN prodotto puo’, da solo, guarire dalla malattia della quale si e’ malati !
vedi: Protocollo della Salute + Legge di Guarigione (Crisi di eliminazione) + Cancro e Medicina Naturale + Condiloma eliminato con acqua basica al Bicarbonato di Sodio
E tuttavia, laddove ci sia anche una piccola volontà e speranza di vivere, un’adeguata terapia fito-nutrizionale (NdR: anche via endovena con soluzioni mineral – vitaminiche – vedi QUI il medico che utilizza con successo questo sistema – l’ideale e utilizzare quelli non di sintesi chimica, ma di estrazione naturale – assieme all’assunzione via orale di fermenti lattici appropriati a seconda del paziente ed enzimi) può rendere normale il guarire naturalmente dal tumore, cosa che oggi vogliono farci ritenere impossibile o puramente miracoloso (vedi quei medici che alle volte preferiscono spedire il malato a Lourdes piuttosto che permettergli di curarsi naturalmente).
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ACQUA IONIZZATA
La cura dell’acqua ionizzata (basica od acida) ormai e’ utilizzata anche in certi ospedali nel mondo con risultati eclatanti, sconosciuti aimedici allopati che non conoscono la Medicina Naturale.
Essa puo’ essere utilizzata a seconda dei casi, sia per via orale, da bere, sia per l’esterno del corpo per le malattie della pelle(anche per ferite da trauma o da operazioni chirurgiche).
Nel sito qui riportato si possono vedere dei video che illustrano le varie applicazioni dell’acqua ionizzata.
vedi: http://glowing-health.com/alkaline-water/videos-aw.html
Vedere qualche applicazione di quest’acqua: ACIDA e/o BASICA + CISTE (eliminata con l’acqua basica)