Objective: To determine the correlation between pH and bicarbonate of soda in blood and saliva in child and adolescent  patients during the administration of 3g/m2   of methotrexate. Method: A controlled clinical test was performed  on 23 patients diagnosed with Acute Lymphoblastic Leukemia. Ages ranged from 4 to 18. The Spearman Correlation  Coefficient was used to interpret the data. Results: No significant correlation was found between pH levels and seric  and salivary sodium bicarbonate. However, there was a significant correlation between the levels of sodium bicarbonate  in the body fluids evaluated (rs 0.2576, p=0.0354). Conclusions: Changes modifying the microenvironment of  the oral cavity probably do not allow saliva to be used to determine blood pH and seric bicarbonate

Chaparro, Neira

Navas, Rita

Rojas de Morales, Thais

Viera, Ninoska

Álvarez, Carmen

Repositori d'Objectes Digitals per a l'Ensenyament la Recerca i la Cultura

E456Med Oral Patol Oral Cir Bucal. 2008 Jul 1;13(7):E456-9.                                                                                                                                        Seric-salivary correlation of pH and sodium bicarbonate                                                                           Med Oral Patol Oral Cir Bucal.  2008 Jul 1;13(7):E456-9.                                                                                                                                     Seric-salivary correlation of pH and sodium bicarbonatepH and salivary sodium bicarbonate in cancer patients: Correlation with seric concentrationThais Rojas-Morales 1, Rita Navas 1,  Ninoska Viera 2, Carmen Julia Álvarez 3, Neira Chaparro 2(1) Full Professor(2) Associate Professor(3) Adjunct Professor. Research Institute, Faculty of Dentistry, Universidad  del ZuliaCorrespondence:Dr. Rojas-Morales, Thais.Calle 65 esquina con Av.19. Edificio Ciencia y Salud. 3er piso. Maracaibo. Zulia.  Venezuela. Postal Code 400. E-mail: moralesrojas@cantv.netReceived: 07/10/2007Accepted: 13/02/2008Rojas-Morales T, Navas R, Viera N, Álvarez C J, Chaparro N. pH and sa-livary sodium bicarbonate in cancer patients: Correlation with seric con-centration. Med Oral Patol Oral Cir Bucal. 2008 Jul 1;13(7):E456-9.© Medicina Oral S. L. C.I.F. B 96689336 - ISSN 1698-6946http://www.medicinaoral.com/medoralfree01/v13i7/medoralv13i7p456.pdfAbstractObjective: To determine the correlation between pH and bicarbonate of soda in blood and saliva in child and adoles-cent patients during the administration of 3g/m2 of methotrexate. Method: A controlled clinical test was performed on 23 patients diagnosed with Acute Lymphoblastic Leukemia. Ages ranged from 4 to 18. The Spearman Correlation Coefficient was used to interpret the data. Results: No significant correlation was found between pH levels and seric and salivary sodium bicarbonate. However, there was a significant correlation between the levels of sodium bicarbo-nate in the body fluids evaluated (rs 0.2576, p=0.0354). Conclusions: Changes modifying the microenvironment of the oral cavity probably do not allow saliva to be used to determine blood pH and seric bicarbonate.Key words: Salivary pH, sodium bicarbonate, blood, saliva, methotrexate, leukemia.Indexed in: -Index Medicus / MEDLINE  /  PubMed            -EMBASE, Excerpta Medica-SCOPUS-Indice Médico Español                                                        -IBECS              Article Number: 1111111493              © Medicina Oral S. L. C.I.F. B 96689336 - ISSN 1698-6946               eMail:  medicina@medicinaoral.com IntroductionSaliva is a secretion of the salivary glands and oral mucosa –of vital importance for maintaining oral health. For the last ten years, researchers have shown increasing interest in using saliva as a body fluid (1,2) since technological advances have provided them with useful measures for diagnosing and predicting the progression of malignant and infectious diseases, endocrine disorders, for supervi-sing the levels of therapeutic and illicit drugs, hormonal levels and for determining antibodies that protect the body from infectious processes (3-8). It has also been reported that patients suffering from certain systemic illnesses and taking medicaments that could produce a collateral effect on the central or peripheral nervous system may present the same alterations in their saliva as those observed in their blood (7).   Easy non-invasive collection and the relationship between oral fluid concentrations and plasma confer  clinical value on saliva (5,6). Whole saliva is the most frequently used for diagnosing systemic diseases, with the oral cavity re-ceiving the seric components via the local vasculature of the salivary glands and gingival fluid (9).A comparison of blood and saliva sampling reveals that the greatest advantage of the latter is that it can be used in clinically difficult situations, such as dealing with children, the physically impaired and anxious patients, where blood sampling would be a complex task. That is why substitu-ting oral fluid for blood provides a clinical alternative, because it represents a diagnostic advantage (9).In the case of pediatric cancer patients, one of the cytosta-tic agents contemplated in the protocols for the treatment of divers pathologies, especially of Acute Lymphoblastic Leukemia (ALL), is Methotrexate (Mtx), an acid subs-tance which, when administered in doses over 2 g/m², requires the prior use of sodium bicarbonate and for 72 Med Oral Patol Oral Cir Bucal. 2008 Jul 1;13(7):E456-9.                                                                                                                                        Seric-salivary correlation of pH and sodium bicarbonate                                                                           Med Oral Patol Oral Cir Bucal.  2008 Jul 1;13(7):E456-9.                                                                                                                                     Seric-salivary correlation of pH and sodium bicarbonateE457hours thereafter, with determination of pH being neces-sary for administering the optimum dose of the alkaline substance and thus obtain alkaline diuresis (10). There is evidence that the buffering action of sodium bicarbonate (NaHCO3) used prior to and during the administration of high doses of Mtx probably allows the buffering capacity of saliva to be maintained at medium-high levels (11).Clinical tests on saliva are promising. However, they may not replace blood tests on all applications, so research in this area must be continued before the clinical value of saliva as a diagnostic fluid can be determined (12). As a continuation of the study performed by Rojas de Morales T, Navas R, Viera N, Álvarez CJ, Chaparro N, Griman D (13), in which it was concluded that the dose of sodium bicarbonate considered in the administration protocol of 3 g/m² mtx kept pH neutral and sodium carbonate levels in saliva within normal ranges. The authors recommended that further studies should include the relationship of pH values and sodium bicarbonate in blood and saliva. The present study therefore set out to determine the correla-tion existing between pH and sodium bicarbonate in the blood and saliva of child and adolescent patients during the administration of 3 g/m2  mtx.Methods- PatientsThe population was made up of the children and adoles-cents that attended the Oncohematological Unit of the Hospital of Pediatric Specialties. (Hep), state of Zulia, Venezuela, between April 2004 and May 2005. The sample comprised 23 patients ranging from 4 to 18 years of  age.  As the inclusion criterion, the patient had to present a diagnosis of acute lympho-blastic leukemia (all) in accordance with the (fab) (14) that received the total XV protocol of st jude children’s research hospital, which includes the administration of 3 g/m² mtx and hyperhydration with sodium bicarbonate. The presence of active carious cavities was considered as the exclusion criterion. This study was approved by the HEP’s Ethics Committee. Each parent or guardian signed an agreement report once the purpose of the study was explained to him or her.To determine the relationship of  pH and bicarbonate levels of the body fluids under evaluation, three samples of  blood and saliva per patient were processed: a) on admission, coinciding with the preparatory phase; b) twelve hours after intravenous administration of sodium bicarbonate and c) before the administration of Mtx; the last sample was taken three hours after the application of the antineoplastic. The pH and sodium bicarbonate in saliva and blood were determined with the Chiron-Diagnostic 378.- Collecting the saliva sample    The saliva sample was taken with the patient sitting upright and relaxed. Saliva production was stimulated by their chewing a paraffin capsule. 3 Cc of mixed saliva were collected, having made sure that the patient had not eaten any food during the previous two hours. To facilitate sam-ple processing, the saliva was collected in a 15-cc syringe, extracting the air and sealing it with a rubber stopper.   - Collecting the blood sample Two ccs of peripheral blood samples were extracted from the middle basilic vein, with asepsis of the area, using the Vacutainer® system, with no anticoagulant. - Statistical analysis  The Spearman Correlation Coefficient at 5% significance level was used to quantify the relationship between pH levels and sodium bicarbonate in blood and saliva.Results  The blood and saliva samples of 23 patients with ages ranging between 4 and 18 years were analyzed, with the greatest frequency being observed in ages less than or equal to (≤) 5 years, followed by 5 patients of 10 to 15 years and 4 patients of 5 to 10 years and older than 15, respectively. Relating pH values in blood and saliva produced rs= -0.01739, considered a non-significant correlation. The result of the correlation of bicarbonate in blood and saliva was rs= 0.2576, with a 5% significance level of  p<0.0354 (Figure 1).   Evaluation of  the correlation between the parameters under consideration in each of the body fluids produced values of pH and sodium bicarbonate in blood that were not significant (rs = -0.04439), whereas the correlation between pH and bicarbonate of soda in saliva was rs= 0.7371, evidencing an extremely significant statistical correlation: p< 0.0001 (Figure 2).DiscussionIn this study, there was no positive correlation of seric pH with salivary pH, probably because whole saliva is modified by factors such as oral hygiene, the quantity and quality of microorganisms, diet and medicaments (12). In this sense, it has been reported that consumption of milk with other sugar aggregates (15) and/or the use of syrups in long-term medication (16), tend to cause a reduction of the pH of the bacterial plaque. Moreover, the use of stimulated saliva in the experimental procedure of this stu-dy could be an intervening condition because the salivary flow produced by chewing gum (stimulated saliva) induces changes in the electrolytes and proteins secreted by the parotid and submandibular glands (17). Lynge et al. (10) evaluated a group of patients with Sjögren's Syndrome and found that the reduction of salivary flow favors aciduric oral microflora and, consequently, modifications of the pH. In the patients evaluated, the chemotherapy they receive as the basis of the antineoplastic treatment may in-duce changes in salivation, which produces modifications in the composition of whole saliva, as well as a reduction E458Med Oral Patol Oral Cir Bucal. 2008 Jul 1;13(7):E456-9.                                                                                                                                        Seric-salivary correlation of pH and sodium bicarbonate                                                                           Med Oral Patol Oral Cir Bucal.  2008 Jul 1;13(7):E456-9.                                                                                                                                     Seric-salivary correlation of pH and sodium bicarbonateof the salivary flow rate (18). Under normal physiological conditions, NaHCO3 concentration in saliva is similar to or below that of the plasmatic level (19). The present study evidenced a positive correlation of seric and salivary sodium bicarbonate after the administration of high doses of Mtx (an acid substance). A possible explanation may be due to the high doses of sodium bicarbonate used before and during the administration of Mtx to maintain alkaline diuresis, which coincided with sample taking. The results of this study did not show any correlation between pH and seric sodium bicarbonate, which could probably be explained because of the use of two opposing chemical substances: Mtx, an acid substance and pH, an alkaline substance, and the time at which the sample was taken. The correlation found between pH and salivary sodium bicarbonate supports the already existing theory: that sodium bicarbonate is the main buffer of salivary pH (20). It is concluded that the changes that modify the microen-vironment of the oral cavity probably do not allow the use of saliva to determine blood pH. Likewise, in spite of the correlation found between seric and salivary bicarbonate, saliva is perhaps not the appropriate medium to measure seric bicarbonate. For a definitive corroboration and veri-fication of these findings, more studies should be carried out, controlling salivary flow as the modifying variable of the event under study.  References 1. Lo Muzio L, Falaschini S, Rappelli G, Bambini F, Baldoni A, Pro-caccini M, et al.  Saliva as a diagnostic matrix for drug abuse. Int J Immunopathol Pharmacol. 2005 Jul-Sep;18(3):567-73. 2. Todorović T, Dozić I, Pavlica D, Marković D, Brajović G, Ivanović M, et al. Use of saliva as a diagnostic fluid in dentistry. Srp Arh Celok Lek. 2005 Jul-Aug;133(7-8):372-8. 3. Nieuw Amerongen AV, Ligtenberg AJ, Veerman EC. Implications for diagnostics in the biochemistry and physiology of saliva. Ann N Y Acad Sci. 2007 Mar;1098:1-6. 4. Wong DT. Salivary diagnostics powered by nanotechnologies, proteo-mics and genomics. J Am Dent Assoc. 2006 Mar;137(3):313-21. 5. Llena-Puy C. The rôle of saliva in maintaining oral health and as an aid to diagnosis. Med Oral Patol Oral Cir Bucal. 2006 Aug;11(5):E449-55. Spearman Correlation  rs: 0,2576  p value: 0,0354 Blood200 5 10 15 20 25 30 35 40010SalivaSpearman Correlation rs: 0,7371 p<0.0001 5.5 6.0 6.5 7.0 7.5 8.001020pHBicarbonateFig. 1. Correlation of seric and salivary bicarbonate. Fig. 2. Correlation of pH and salivary sodium bicarbonate.Med Oral Patol Oral Cir Bucal. 2008 Jul 1;13(7):E456-9.                                                                                                                                        Seric-salivary correlation of pH and sodium bicarbonate                                                                           Med Oral Patol Oral Cir Bucal.  2008 Jul 1;13(7):E456-9.                                                                                                                                     Seric-salivary correlation of pH and sodium bicarbonateE4596. Choo RE, Huestis MA. Oral fluid as a diagnostic tool. Clin Chem Lab Med. 2004;42(11):1273-87. 7. Aps JK, Martens LC. Review: The physiology of saliva and transfer of drugs into saliva. Forensic Sci Int. 2005 Jun 10;150(2-3):119-31.  8. Abdollahi M, Radfar M. A review of drug-induced oral reactions. J Contemp Dent Pract. 2003 Feb 15;4(1):10-31.  9. Kaufman E, Lamster IB. The diagnostic applications of saliva--a review. Crit Rev Oral Biol Med. 2002;13(2):197-212. 10. Pedersen AM, Bardow A, Nauntofte B. Salivary changes and dental caries as potential oral markers of autoimmune salivary gland dysfunction in primary Sjogren’s syndrome. BMC Clin Pathol. 2005 Mar 1;5(1):4. 11. Rojas-Morales T, Lugo Z, Santana Y, Navas R, Zambrano O, Viera N, et al. Capacity buffer of the saliva in children and adolescents with cancer: Variations induced by the administration of metotrexate or cyclophosphamide. Med Oral Patol Oral Cir Bucal. 2005 Jul 1;10 Suppl 2:E103-8. 12. Tayanin GL, Petersson GH, Bratthall D. Caries risk profiles of 12-13-year-old children in Laos and Sweden. Oral Health Prev Dent. 2005;3(1):15-23. 13. Rojas de Morales T, Navas R, Viera N, Alvarez CJ, Chaparro N, Gri-man D. pH and salivary sodium bicarbonate during the administration protocol for methotrexate in children with leukemia. Med Oral Patol Oral Cir Bucal. 2007 Oct 1;12(6):E435-9. 14. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gral-nick HR, et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976 Aug;33(4):451-8. 15. Danchaivijitr A, Nakornchai S, Thaweeboon B, Leelataweewud P, Phonghanyudh A, Kiatprajak C, et al. The effect of different milk formu-las on dental plaque pH. Int J Paediatr Dent. 2006 May;16(3):192-8. 16. Marathaki E, Pollard MA, Curzon ME. The effect of sucrose in medicines on plaque pH. Int J Paediatr Dent. 1995 Dec;5(4):231-5. 17. Dawes C, Kubieniec K. The effects of  prolonged gum chewing on salivary flow rate and composition. Arch Oral Biol. 2004 Aug;49(8):665-9. 18. Jensen SB, Mouridsen HT, Reibel J, Brünner N, Nauntofte B. Adju-vant chemotherapy in breast cancer patients induces temporary salivary gland hypofunction. Oral Oncol. 2008 Feb;44(2):162-73. 19. Bardow A, Madsen J, Nauntofte B. The bicarbonate concentration in human saliva does not exceed the plasma level under normal physio-logical conditions. Clin Oral Investig. 2000 Dec;4(4):245-53. 20. Fenoll-Palomares C, Muñoz Montagud JV, Sanchiz V, Herreros B, Hernández V, Mínguez M, et al. Unstimulated salivary flow rate, pH and buffer capacity of saliva in healthy volunteers. Rev Esp Enferm Dig. 2004 Nov;96(11):773-83. AcknowledgementOur thanks to Council for Scientific and Humanistic Development. CONDES. University of Zulia, for financial support and to the On-cohematology Unit and the Clinical Laboratory of Hospital of Pediatric Specialties (HEP) , State of Zulia-Venezuela, for their invaluable contri-bution to the execution of this research project.

pH and salivary sodium bicarbonate in cancer patients : correlation with seric concentration

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