Mucositis and salivary antioxidants in patients undergoing bone marrow transplantation (BMT).

OBJECTIVES: High doses of chemotherapy generate DNA damage in patients undergoing bone marrow transplantation (BMT), due to the production of reactive oxygen species (ROS). In order to evaluate the local defensive effectiveness of the patient undergoing BMT, the concentrations of the antioxidants superoxide dismutase (SOD) and uric acid (UA) were measured in saliva. STUDY DESIGN: Basal saliva samples were collected from 20 patients undergoing BMT at the Oncology Department, Sanatorio Allende (Córdoba), in the stages: initial, prior to conditioning therapy (I); middle: 7 to 10 days after BMT (M) and final stage, 30 days after discharge from isolation (F). SOD levels were determined using a RANDOX kit (RANSOD superoxide dismutase manual), and for uric acid enzymatic UOD / PAP spectrophotometric method, ( Trinder Color Kit , Wiener Lab) was used. RESULTS: 85% of the patients developed oral mucositis. SOD concentration in the M stage was significantly higher (p<0.01) compared with stage I, and it reversed in stage F. UA concentration was significantly lower (p<0.001) in stage M compared with stage I, and in stage F it recovered the initial values. CONCLUSIONS: SOD increase in stage M coincided with the appearance of mucositis, which could be interpreted as a defensive mechanism of saliva against oxidative stress produced by chemotherapy. UA decrease in stage M would favour the development of higher degrees of mucositis.

Analysis of saliva samples from oncological patients treated with 5-fluorouracil and leucovorin calcium by scanning electron microscopy with energy dispersive system.

This work presents a chemical and morphological analysis of samples of saliva taken from patients who were under treatment with intravenous chemotherapy with 5-fluorouracil and leucovorin calcium. Samples of saliva were extracted from fifteen patients during the three stages of the treatment: The initial stage (previous to the chemotherapy), the intermediate stage (during the chemotherapy), and the final stage (twenty-one days after finishing the treatment). An amount of 50 µl was collected in each visit. Chemical contrast images were taken by means of scanning electron microscopy, and X-ray characteristic spectra were obtained from all the studied samples by using an energy dispersive system from all the studied samples. Images that correspond to the intermediate stage showed important differences with respect to the initial and final stages. In addition, X-ray spectra provided information about the present elements in saliva and their relative abundance allowed us to determine variations in the chemical composition. The backscattered electron images and X-ray spectra from the intermediate stage showed clusters of crystals with fluorine content higher than those obtained in initial and final stages. This fact probably indicates the passage of metabolites of 5-fluorouracil and leucovorin calcium from the plasma to the oral cavity. This finding enhances the hypothesis proposed by other authors about the secondary effects of the drugs on the stomatognathic system such as oral mucositis, dysgeusia, and xerostomia with or without hyposalivation.

Functional impairment in submandibular gland of rats induced by 5-fluorouracil and calcium leucovorin.

One of the main clinical problems during chemotherapy is the occurrence of severe systemic toxicities, including those related to the stomatognathic system, which contribute to reducing the patient's quality of life. The most frequent oral complications are mucositis, dysgeusia, inflammation, gingival bleeding and decreased salivary flow or hyposalivation, a factor that predisposes to xerostomia, and other local complications that alter the homeostasis of the system. The purpose of this study was to evaluate the functional activity of salivary glands in Wistar rats subject to chemotherapy by measuring salivary flow, glycogen levels and glandular tissue response to autonomic nervous system agonists. Five experimental groups were used: 1) Control group fed "ad libitum"; 2) 5-fluorouracil (20 mg/kg body weight); 3) Calcium leucovorin (10 mg/kg body weight); 4) 5-fluorouracil + calcium leucovorin (20 and 10 mg/kg, respectively) by intraperitoneal injection for five consecutive days and 5) control with paired diet. Groups 1 and 5 did not receive drugs. Treatment with fluorouracil + leucovorin produced an increase in stimulated salivary flow and a higher response to increasing doses of beta agonists compared to other experimental groups. In both groups treated with cytostatic drugs, blocking of glycogen consumption at the end of the experimental period was observed. Our work suggests that salivary secretion may be affected by a dual mechanism: the first would be toxicity induced by 5-FU, which would cause depression of the process of glucose utilization. The second mechanism would affect the sympathetic autonomic reflex arc. In this instance, the synergistic action of 5-FU + LV would have a negative effect on the nerve activity with a reduction of salivary secretion. This would explain the hyposalivation, cited by several authors in patients undergoing the 5-FU + LV scheme in the treatment of colon carcinoma.

Assessing the determination of salivary electrolytes and anti-Ro and anti-La antibodies for the diagnosis of Sjögren's syndrome (SS).

UNLABELLED: The aim of this study was to assess changes in salivary electrolyte flow and composition and the presence of anti-Ro/SSA and anti-La/SSB serum and saliva antibodies and their implications for the non-invasive diagnosis of SS. STUDY DESIGN: 73 patients were studied, divided into the following experimental groups: primary Sjögren syndrome (SSp) (n=15), secondary SS (SSs) (n=17), dry mouth, dry eye without Sjögren's syndrome (BO) (n=20) and healthy controls (C) (n=21). We conducted a baseline assessment of salivary flow and saliva sampling for the measurement of sodium, chlorine, potassium, calcium and phosphate electrolytes, and the determination of anti-Ro/SSA and La/SSB antibodies; a serum sampling was made to assess antibody positivity. RESULTS: Salivary flow in SSp, SSs and BO was significantly lower (p<0.001) relative to C. The salivary composition of SS showed an increase of inorganic components. Anti-Ro/SSA and anti-La/SSB antibodies occurred more frequently in serum and saliva in SS patients compared with BO and C, with higher frequency of positivity in serum compared with saliva. CONCLUSION: Our results suggest new tools that could aid the non-traumatic diagnosis of the origin of hyposalivation.

Oral signs of intravenous chemotherapy with 5-Fluorouracil and Leucovorin calcium in colon cancer treatment.

UNLABELLED: Several studies have shown how cytostatics may cause hypofunction of salivary glands but failed to elucidate any potentially related side effects. Keeping in mind the sialochemical assistance and the role of saliva on the homeostasis of the stomatognathic system, the aim of this study was to establish potential gland disorders in patients submitted to 5- Fluorouracil (5-Fu) and Leucovorin calcium (LV) as well as their correlation with certain oral health disorders that diminish the quality of life. MATERIALS AND METHODS: the focus of this research was observational and longitudinal. Twenty-five patients diagnosed with colon cancer at an initial, intermediate and late phase submitted to specifically devised therapy were assessed. Clinical history, oral health indexes and basal or stimulated saliva samples were recorded. RESULTS: Basal and stimulated flow dropped in the intermediate stage. Stimulated saliva pH decreased during treatment. On basal saliva, urea, sodium and potassium rose during the intermediate phase. Löe and Silness rates as well as simplified bleeding increased during therapy but reverted by the end of the treatment. Depth index of the vestibular gingival sulcus rose during the intermediate phase but did not return. CONCLUSION: This treatment caused functional salivary gland disorders as evidenced by basal and stimulated hyposialia, and acidification of stimulated saliva pH during the intermediate phase. Increase in basal urea may be due to proteic catabolism arising from plasma or glands. Variation in Na+ and K+ of basal saliva concentrates might be assumed as a possible duct disorder. Recovery of bleeding and Löe and Silness rates may point to a transient inflammatory effect associated to a decrease in salivary flow. Increase in the depth rates of the periodontal vestibular sulcus could be correlated with a higher risk of periodontal disease.

Mucositis and salivary antioxidants in patients undergoing bone marrow transplantation (BMT)

OBJECTIVES: High doses of chemotherapy generate DNA damage in patients undergoing bone marrow transplantation (BMT), due to the production of reactive oxygen species (ROS). In order to evaluate the local defensive effectiveness of the patient undergoing BMT, the concentrations of the antioxidants superoxide dismutase (SOD) and uric acid (UA) were measured in saliva. STUDY DESIGN: Basal saliva samples were collected from 20 patients undergoing BMT at the Oncology Department, Sanatorio Allende (Córdoba), in the stages: initial, prior to conditioning therapy (I); middle: 7 to 10 days after BMT (M) and final stage, 30 days after discharge from isolation (F). SOD levels were determined using a RANDOX kit (RANSOD superoxide dismutase manual), and for uric acid enzymatic UOD / PAP spectrophotometric method, ( Trinder Color Kit , Wiener Lab) was used.RESULTS:85% of the patients developed oral mucositis. SOD concentration in the M stage was significantly higher (p<0.01) compared with stage I, and it reversed in stage F. UA concentration was significantly lower (p<0.001) in stage M compared with stage I, and in stage F it recovered the initial values. CONCLUSIONS: SOD increase in stage M coincided with the appearance of mucositis, which could be interpreted as a defensive mechanism of saliva against oxidative stress produced by chemotherapy. UA decrease in stage M would favour the development of higher degrees of mucositis

Functional impairment in submandibular gland of rats induced by 5-fluorouracil and calcium leucovorin

One of the main clinical problems during chemotherapy is the occurrence of severe systemic toxicities, including those related to the stomatognathic system, which contribute to reducing the patient's quality of life. The most frequent oral complications are mucositis, dysgeusia, inflammation, gingival bleeding and decreased salivary flow or hyposalivation, a factor that predisposes to xerostomia, and other local complications that alter the homeostasis of the system. The purpose of this study was to evaluate the functional activity of salivary glands in Wistar rats subject to chemotherapy by measuring salivary flow, glycogen levels and glandular tissue response to autonomic nervous system agonists. Five experimental groups were used: 1) Control group fed "ad libitum"; 2) 5-fluorouracil (20mg/ kg body weight); 3) Calcium leucovorin (10 mg/kg body weight); 4) 5-fluorouracil + calcium leucovorin (20 and 10 mg / kg, respectively) by intraperitoneal injection for five consecutive days and 5) control with paired diet. Groups 1 and 5 did not receive drugs. Treatment with fluorouracil + leucovorin produced an increase in stimulated salivary flow and a higher response to increasing doses of beta agonists compared to other experimental groups. In both groups treated with cytostatic drugs, blocking of glycogen consumption at the end of the experimental period was observed. Our work suggests that salivary secretion may be affected by a dual mechanism: the first would be toxicity induced by 5-FU, which would cause depression of the process of glucose utilization. The second mechanism would affect the sympathetic autonomic reflex arc. In this instance, the synergistic action of 5-FU + LV would have a negative effect on the nerve activity with a reduction of salivary secretion. This would explain the hyposalivation, cited by several authors in patients undergoing the 5-FU+LV scheme in the treatment of colon carcinoma.

Uno de los principales problemas clinicos durante la quimioterapia es la aparicion de graves efectos toxicos sistemicos, incluidos los relacionados con el sistema estomatognatico, que contribuyen a la reduccion de la calidad de vida del paciente. Las complicaciones orales mas frecuentes son la mucositis, disgeusia, inflamacion, sangrado gingival y la disminucion del flujo salival o hiposalivacion, un factor que predispone a la xerostomia, y otras complicaciones locales que alteran la homeostasis del sistema. El objetivo de este estudio fue evaluar la actividad funcional de las glandulas salivales de ratas Wistar sometidas a quimioterapia, a traves de la medicion del flujo salival, los niveles de glucogeno y la respuesta del tejido glandular a agonistas del sistema nervioso autonomo. Se utilizaron cinco grupos experimentales: 1) Control con alimentacion "ad libitum"; 2) 5 - fluorouracilo (20 mg / kg de peso corporal); 3) Leucovorina calcica (10 mg/ kg de peso corporal); 4) 5 - fluorouracilo + leucovorina calcica (20 y 10 mg / kg, respectivamente) por via intraperitoneal durante cinco dias consecutivos, y 5) control con dieta apareada. Grupos 1 y 5 no recibieron drogas. El tratamiento con 5 - fluorouracilo + leucovorina produjo un aumento de flujo salival estimulado y una mayor respuesta a dosis crecientes de agonistas beta en comparacion con otros grupos experimentales. En ambos grupos tratados con citostaticos, se observo bloqueo del consumo de glucogeno al final del periodo. Nuestro trabajo sugiere que la secrecion salival puede estar afectada por un doble mecanismo: el primero seria la toxicidad inducida por 5-FU que causaria depresion del proceso de utilizacion de la glucosa. El segundo mecanismo afectaria el arco reflejo autonomo simpatico. En este caso, la accion sinergica de ambos farmacos de 5-FU + LV repercutiria negativamente sobre la actividad nerviosa con una reduccion de la secrecion salival. Esto explicaria la hiposalivacion citada por varios autores en pacientes sometidos al esquema 5-FU + LV en el tratamiento del carcinoma colorrectal.

Glucose metabolism in isolated uteri of immature rats. Influence of prostaglandins and nitric oxide.

We studied the contractile activity and glucose metabolism, in terms of production of 14CO2 from [14C] glucose, in isolated uteri of immature rats. Immaturity was due to age or exposure to a restricted diet. The contractile activity in both prepubertal groups persisted for a period of 60 minutes and fell when indomethacin was added to the KRB medium. The production of 14CO2 was greater than for adult rats and fell as a result of the addition of indomethacin. The metabolism of [14C] arachidonic acid showed that the percentage of eicosanoids released in age related immature uteri was greater than that in restricted diet related immature uteri. In animals that are immature as a result of exposure to a restricted diet, 14CO2 fell due to the effect of NAME. Sodium nitroprusside and L-arginine increased the production of 14CO2. This effect was reverted by NAME and indomethacin. Conversely, the uteri of age related prepubertal rats were not affected. The level of activity of nitric oxide synthase was higher in restricted diet related immature animals and fell following the addition of NS-398. We may conclude that in rats exposed to a restricted diet, NO and COX-2 participate in glucose metabolism whereas they would not be involved in age related prepubertal animals.

Assessing the determination of salivary electrolytes and anti-Roand anti-La antibodies for the diagnosis of Sjögren’s Syndrome (SS)

The aim of this study was to assess changes in salivary electrolyte flow and composition and the presence ofanti-Ro/SSA and anti-La/SSB serum and saliva antibodies and their implications for the non-invasive diagnosisof SS.Study design: 73 patients were studied, divided into the following experimental groups: primary Sjögren syndrome(SSp) (n=15), secondary SS (SSs) (n=17), dry mouth, dry eye without Sjögren’s syndrome (BO) (n=20)and healthy controls (C) (n=21). We conducted a baseline assessment of salivary flow and saliva sampling for themeasurement of sodium, chlorine, potassium, calcium and phosphate electrolytes, and the determination of anti-Ro/SSA and La/SSB antibodies; a serum sampling was made to assess antibody positivity.Results: Salivary flow in SSp, SSs and BO was significantly lower (p<0.001) relative to C. The salivary compositionof SS showed an increase of inorganic components. Anti-Ro/SSA and anti-La/SSB antibodies occurred morefrequently in serum and saliva in SS patients compared with BO and C, with higher frequency of positivity inserum compared with saliva.Conclusion: Our results suggest new tools that could aid the non-traumatic diagnosis of the origin of hyposalivation (AU)

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Oral signs of intravenous chemotherapy with 5- Fluorouracil and Leucovorin calcium in colon cancer treatment

Several studies have shown how cytostatics may cause hypofunction of salivary glands but failed to elucidate any potentially related side effects. Keeping in mind the sialochemical assistance and the role of saliva on the homeostasis of the stomatognathic system, the aim of this study was to establish potential gland disorders in patients submitted to 5- Fluorouracil (5-Fu) and Leucovorin calcium(LV) as well as their correlation with certain oral health disorders that diminish the quality of life. Materials and methods: the focus of this research was observational and longitudinal. Twenty-five patients diagnosed with colon cancer at an initial, intermediate and late phase submitted to specifically devised therapy were assessed. Clinical history, oral health indexes and basal or stimulated saliva samples were recorded. Results: Basal and stimulated flow dropped in the intermediate stage. Stimulated saliva pH decreased during treatment. On basal saliva, urea, sodium and potassium rose during the intermediate phase. Löe and Silness rates as well as simplified bleeding increased during therapy but reverted by the end of the treatment. Depth index of the vestibular gingival sulcus rose during the intermediate phase but did not return. Conclusion: This treatment caused functional salivary gland disorders as evidenced by basal and stimulated hyposialia, and acidification of stimulated saliva pH during the intermediate phase. Increase in basal urea may be due to proteic catabolism arising from plasma or glands. Variation in Na+ and K+ of basal saliva concentrates might be assumed as a possible duct disorder. Recovery of bleeding and Löe and Silness rates may point to a transient inflammatory effect associated to a decrease in salivary flow. Increase in the depth rates of the periodontal vestibular sulcus could be correlated with a higher risk of periodontal disease (AU)