[Determination of some oxidative stress, functional and immunological markers in the saliva of patients undergoing bone marrow transplantation (BMT).] / Determinación de algunos marcadores de estrés oxidativo, funcionales e inmunológicos en saliva de pacientes sometidos a trasplante de médula ósea (TMO).

OBJECTIVE: High doses of chemotherapy used prior to bone marrow transplantation (BMT) promote severe changes in the stomatognathic system. The objective of the present work consisted in evaluating some functional, immunological and oxidative stress markers in saliva of these patients. METHODS: A longitudinal observational study was carried out on 22 patients admitted to the Bone Marrow Transplant Unit of the Oncohematology Service of the Sanatorio Allende between March 2019 and February 2020. Basal saliva collection was carried out in the initial stage (I ) prior to isolation and middle stage (M) 14 days after conditioning therapy and transplantation. The concentration of uric acid (UA), superoxide dismutase (SOD), malondialdehyde (MDA), salivary alpha amylase, secretory immunoglobulin A (Ig As), lactoferrin, ceruloplasmin and urea were analyzed. RESULTS: In (M) the levels of SOD and MAD increased significantly compared to (I) (p <0.01). The concentration of salivary alpha amylase, Ig As, lactoferrin and uric acid was significantly lower in (M) compared to (I ) p <0.0001, p <0.01, p <0.0001, p <0.02 respectively. Ceruloplasmin and Urea did not show variations during treatment. CONSLUSION: In the present study, a decrease in the defensive capacity of saliva was observed as a consequence of a reduction in the concentration of Ig As and lactoferrin. The increase in SOD in (M) could be interpreted as a defense mechanism of saliva against oxidative stress produced by chemotherapy. The decrease in uric acid in stage (M) could allow the worsening of mucositis. The synthesis and release of amylase was affected by treatment with cytostatic drugs.

OBJETIVO: Altas dosis de quimioterapia utilizadas previo al trasplante de médula ósea (TMO) pueden promover severos cambios en el sistema estomatognático. El objetivo consistió en evaluar algunos marcadores funcionales, inmunológicos y de estrés oxidativo en saliva de pacientes sometidos a dicho tratamiento. MÉTODOS: Estudio observacional longitudinal en 22 pacientes de la Unidad de trasplante de Médula Ósea del Servicio de Oncohematología del Sanatorio Allende. Se efectuó recolección de saliva basal en etapa inicial (I) previa al aislamiento y etapa media (M) 14 días posteriores a la terapia de acondicionamiento y trasplante. Se analizó la concentración de ácido úrico (AU), superóxido dismutasa (SOD), malondialdehido (MDA), alfa amilasa salival, inmunoglobulina A secretora (Ig As), lactoferrina, ceruloplasmina y urea. RESULTADOS: En (M) los niveles de SOD y MAD aumentaron significativamente respecto de (I) (p< 0.01). La concentración de  alfa amilasa salival, Ig As, lactoferrina y ácido úrico fue significativamente menor en (M) respecto de ( I ) p < 0.0001, p < 0.01, p < 0.0001, p <0.02 respectivamente. Ceruloplasmina y Urea no mostraron variaciones. CONCLUSIÓN: se observó una disminución de la capacidad defensiva de la saliva como consecuencia de una reducción de la concentración de Ig As y lactoferrina. El incremento de SOD en (M) podría interpretarse como un mecanismo de defensa de la saliva contra el estrés oxidativo producido por la quimioterapia. La disminución de ácido úrico en la etapa (M) podría favorecer el agravamiento de mucositis.  La síntesis y liberación de amilasa fue afectada por el tratamiento con citostáticos.

Efecto de carboplatino sobre malondialdehído como marcador de lipoderoxidación en glándula submandibular de ratas / Effect of carboplatin on malondialdehyde as a marker of lipoderoxidation in the submandibular gland of rats

El objetivo del presente trabajo fue evaluar el efecto de carboplatino (Cp) en homogenato de glándula submandibular de ratas Wistar a través de la determinación de los niveles de malondialdehido (MDA), como principal producto final de la lipoperoxidación, en un modelo experimental. Se utilizaron 16 ratas Wistar macho de tres meses de edad, alojadas en jaulas individuales, con temperatura e iluminación controlada y dieta libre. Se utilizó un diseño completamente aleatorizado y se establecieron dos grupos experimentales: 1) Control (C), administrándose una dosis intraperitoneal de solución salina durante un día, n: 8, 2) Animales tratados con carboplatino (Cp) aplicándose una dosis i.p. de 100 mg/Kg de peso corporal durante un día, n: 8. Los animales fueron ayunados por 24 horas y posteriormente anestesiados. Seguidamente se extirparon ambas glándulas submandibulares. Se analizaron los niveles de malondialdehido en homogenato de glándula submandibular en ambos grupos experimentales. Las variaciones entre los grupos analizados se evaluaron mediante prueba T de Student para muestras apareadas, fijando un p-valor <0,05 para significación estadística. Proyecto aprobado por CICUAL. Facultad de Ciencias Médicas (UNC). El grupo de Ratas C mostró una concentración de 7.32± 0.48µmol/mg de glándula. El grupo Cp tuvo una concentración de 12.57 ± 0,71 µmol/mg de glándula, expresando una disminución significativa respecto del grupo control p<0.0006. Cp en la dosis ensayada provocaría una disminución de la lipoperoxidación en glándula submandibular de ratas. Posiblemente la batería antioxidante glandular neutralizaría el estrés oxidativo de las células acinares. Estos resultados sugieren evaluar a futuro la actividad de superóxido dismutasa (SOD) y niveles de ácido úrico (AU)

5-fluorouracil and cyclophosphamide modify functional activity in submandibular gland of rats / El 5-fluorouracilo y la ciclofosfamida modifican la actividad funcional en la glándula submandibular de las ratas

Objective: Chemotherapy treatment against cancer produce systemic toxicities, among which are those related to important structures of the stomatognathic system and its functional activity. 5 Fluorouracil (5-FU) and cyclophosphamide (Cf) are drugs widely used in solid tumors and in bone marrow transplantation, respectively. The objective of this work was to evaluate the toxicity of these drugs regarding functional activity of the submandibular glands, by measuring the percentage of glycogen consumption in two experimental models. Material and Methods: 84 male Wistar rats aged three months were used, housed in individual cages, with controlled temperature and lighting and ad libitum diet. They were divided into four experimental groups: 1) Control (C); 2) Treated with 5-FU+leucovorin (LV) at 20 and 10mg/Kg of body weight respectively for five consecutive days; 3) treated with Cf i.p. at 50mg/Kg of body weight for two consecutive days; and 4) rats with paired feeding (PF): for five and two days respectively, the amount administered resulted from the average of the ingested food of groups 2 and 3. Both submandibular glands were excised. The submandibular glycogen concentration was analyzed at initial time (t0) and after 60 minutes of mechanical stimulation (t60). Results: the average variation changed significantly between time 0 and 60 in the groups C and PF. (p-value=0.0001), the 5-FU + LV treatment group had an average concentration higher at t0 than groups C and PF, without significant consumption at T60. While group Cf showed a lower average concentration at time 0 with respect to groups C and PF, without significant consumption at T60. Conclusion: 5-FU+LV and Cf affect the metabolism of carbohydrates, decreasing the use of glycogen as a metabolic substrate. In the present experimental model, the toxicity of these drugs affected the functional activity of the submandibular gland.

Objetivo: el tratamiento de quimioterapia contra el cáncer produce toxicidades sistémicas, entre las que se encuentran las relacionadas con estructuras importantes del sistema estomatognático y su actividad funcional. El 5-fluorouracilo (5-FU) y la ciclofosfamida (Cf ) son fármacos ampliamente utilizados en tumores sólidos y en trasplantes de médula ósea, respectivamente. El objetivo de este trabajo fue evaluar la toxicidad de estos fármacos con respecto a la actividad funcional de las glándulas submandibulares, midiendo el porcentaje de consumo de glucógeno en dos modelos experimentales. Material y Métodos: se utilizaron 84 ratas Wistar machos de tres meses de edad, alojadas en jaulas individuales, con temperatura e iluminación controladas y dieta ad libitum. Se dividieron en cuatro grupos experimentales: 1) Control (C); 2) Tratados con 5-FU+leucovorina (LV) a 20 y 10mg/Kg de peso corporal, respectivamente, durante cinco días consecutivos; 3) tratados con Cf i.p. a 50mg/Kg de peso corporal durante dos días consecutivos; y 4) ratas con alimentación por parejas (PF): durante cinco y dos días respectivamente, la cantidad administrada resultó del promedio de los alimentos ingeridos de los grupos 2 y 3. Ambas glándulas submandibulares fueron extirpadas. La concentración de glucógeno submandibular se analizó en el momento inicial (t0) y después de 60 minutos de estimulación mecánica (t60). Resultados: la variación promedio cambió significativamente entre el tiempo 0 y 60 en los grupos C y PF. (p=0,0001), el grupo de tratamiento 5-FU+LV tuvo una concentración promedio más alta en t0 que los grupos C y PF, sin un consumo significativo en T60. Mientras que el grupo Cf mostró una concentración promedio más baja en el tiempo 0 con respecto a los grupos C y PF, sin un consumo significativo en T60. Conclusión: 5-FU + LV y Cf afectan el metabolismo de los carbohidratos, disminuyendo el uso de glucógeno como sustrato metabólico. En el presente modelo experimental, la toxicidad de estos medicamentos afectó la actividad funcional de la glándula submandibular.

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

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.

Effect of platelet-rich plasma on the peri-implant bone response: an experimental study.

Platelet-rich plasma (PRP) is used as a source of growth factors to stimulate and accelerate bone formation and soft tissue healing. The use of PRP in bone regeneration, both around dental implants and in periodontic treatments, has become particularly appealing. The aim of this study was to evaluate the effect of PRP in an experimental model of osteogenesis around laminar implants. Fifteen male Wistar rats, weighing 90 +/- 10 g, were used in this study. One milliliter of blood was obtained from each animal by intracardiac puncture and transferred into Eppendorf tubes containing 10% sodium citrate. The tubes were centrifuged at 1500 rpm for 15 minutes and PRP was prepared. The laminar test was used to evaluate the bone peri-implant response. PRP and a titanium laminar implant were introduced into the right tibia (Ti/PRP group), whereas the left tibia (control) received only a laminar implant (Ti group). Thirty days postimplantation, the tibiae were resected, radiographed, and processed for embedding in acrylic resin. Ground sections (50 microm) were stained with toluidine blue. The peri-implant bone volume was evaluated histomorphometrically. Statistical analysis of the data was performed. The amount of newly formed bone in the Ti/PRP group (30 +/- 7 cm) was significantly greater than in the Ti group (16 +/- 3 cm). A greater volume of peri-implant bone was observed when PRP was used in the laminar implant test model.