RESUMO
Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.
Assuntos
Acidose , Hiperpotassemia , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Masculino , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/induzido quimicamente , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/complicações , Hiperpotassemia/tratamento farmacológico , Acidose/induzido quimicamente , Acidose/complicações , Acidose/tratamento farmacológico , Rim , Estudos RetrospectivosRESUMO
Severe metabolic acidosis is defined by a pH < 7.2 with HCO3− < 8 mE- q/L in plasma. Its best treatment is to correct the underlying cause. However, acidemia produces multiple complications such as resistance to the action of catecholamines, pulmonary vasoconstriction, impaired cardiovascular function, hyperkalemia, immunological dysregulation, respiratory muscle fatigue, neurological impairment, cellular dysfunction, and finally, it contributes to multisystemic failure. Intravenous NaHCO3 buffers severe acidemia, preventing the associated damage and gains time while the causal disease is corrected. Its indication requires a risk-benefit assessment, considering its complications. These are hypernatremia, hypokalemia, ionic hypocalcemia, rebound alkalosis, and intracellular acidosis. For this reason, therapy must be "adapted" and administered judiciously. The patient will require monitoring with serial evaluation of the internal environment, especially arterial blood gases, plasma electrolytes, and ionized calcium. Isotonic solutions should be preferred instead of hypertonic bicarbonate. The development of hypernatremia must be prevented, calcium must be provided for hypocalcemia to improve cardiovascular function. Furthermore, in mechanically ventilated patients, a respiratory response similar to the one that would develop physiologically, must be established to be able to extract excess CO2 and thus avoid intracellular acidosis. It is possible to estimate the bicarbonate deficit, speed, and volume of its infusion. However, the calculations are only for reference. More important is to start intravenous NaHCO3 when needed, administer it judiciously, manage its side effects, and continue it to a safe goal. In this review we address all the necessary elements to consider in the administration of intravenous NaHCO3, highlighting why it is the best buffer for the management of severe metabolic acidosis.
Assuntos
Humanos , Acidose/tratamento farmacológico , Bicarbonato de Sódio/administração & dosagem , Bicarbonato de Sódio/efeitos adversos , Índice de Gravidade de Doença , Medição de Risco , Administração IntravenosaRESUMO
Severe metabolic acidosis is defined by a pH < 7.2 with HCO3- < 8 mE- q/L in plasma. Its best treatment is to correct the underlying cause. However, acidemia produces multiple complications such as resistance to the action of catecholamines, pulmonary vasoconstriction, impaired cardiovascular function, hyperkalemia, immunological dysregulation, respiratory muscle fatigue, neurological impairment, cellular dysfunction, and finally, it contributes to multisystemic failure. Intravenous NaHCO3 buffers severe acidemia, preventing the associated damage and gains time while the causal disease is corrected. Its indication requires a risk-benefit assessment, considering its complications. These are hypernatremia, hypokalemia, ionic hypocalcemia, rebound alkalosis, and intracellular acidosis. For this reason, therapy must be "adapted" and administered judiciously. The patient will require monitoring with serial evaluation of the internal environment, especially arterial blood gases, plasma electrolytes, and ionized calcium. Isotonic solutions should be preferred instead of hypertonic bicarbonate. The development of hypernatremia must be prevented, calcium must be provided for hypocalcemia to improve cardiovascular function. Furthermore, in mechanically ventilated patients, a respiratory response similar to the one that would develop physiologically, must be established to be able to extract excess CO2 and thus avoid intracellular acidosis. It is possible to estimate the bicarbonate deficit, speed, and volume of its infusion. However, the calculations are only for reference. More important is to start intravenous NaHCO3 when needed, administer it judiciously, manage its side effects, and continue it to a safe goal. In this review we address all the necessary elements to consider in the administration of intravenous NaHCO3, highlighting why it is the best buffer for the management of severe metabolic acidosis.
Assuntos
Acidose , Bicarbonato de Sódio , Humanos , Acidose/tratamento farmacológico , Bicarbonato de Sódio/administração & dosagem , Bicarbonato de Sódio/efeitos adversos , Administração Intravenosa , Medição de Risco , Índice de Gravidade de DoençaRESUMO
Feedlot cattle is submitted to a diet rich in energy and reduced in fibres that induces the sub-acute ruminal acidosis (SARA) with its lesions and clinical signs. Recent studies have demonstrated some amelioration of this condition by the use of isoquinolone alkaloids found in Macleaya cordata (Papaveraceae) such as Sanguinarine and Chelerythrine. These compounds have demonstrated antimicrobial, antiinflammatory and immune-modulatory effects in both humans and animals The aim on this study, using histopathology and a score system, was to evaluate the differences between a non-treated and a treated group feed with these alkaloids, present in trade preparation Sangrovit-RS® as a source of sanguinarine (SG), chelerythrine (CH) and protropine (PA) standardized to 0.15% w/w SG, using feedlot cattle under a high-grain diet as an inflammatory model for gastrointestinal system. The samples of forestomachs were evaluated and graded using scores ranging from zero (0) to three (3) obtained at light-microscopic fields of 400X. Parameters such as inflammation, hydropic degeneration, hyperkeratosis, and vesicle formation were accessed in the different layers of the tissues, considering the severity and dispersion of the microscopic lesions. The soft tissues such as the abomasum, small intestine, cecum and colon had their total amount of inflammatory cells counted at light-microscopic fields of 200X. The rumen of the SG-CH-PRO-treated group showed a significant reduction in the epithelial hydropic degeneration scores (p ≤ 0.001) and lamina propria inflammation (p ≤ 0.001).The reticulum had a similar reduction in scores of epithelial (p ≤ 0.002) and stratum corneum hydropic degeneration (p ≤ 0.001), hyperkeratosis (p ≤ 0.002) and inflammation in lamina propria (p ≤ 0.001) and epithelium (p ≤ 0.002). The omasum had no significant differences. All non-keratinized tissues, except for ileum, had a significant decrease (p ≤ 0.001) in the total counting of inflammatory cells. In this trial, the feedlot cattle feed with high grain diet and treated with isoquinolone alkaloids expressed lesions that indicate ameliorations and worsening's. Ameliorating effects of the alkaloids were better demonstrated in tissues with reduced or no corneal layer in the mucosa and in the absence of a lipopolysaccharides rich acidic environment reinforcing the notion of the topic action, the dependence of the media pH and the time of exposure modulating the pharmacological mechanisms of these alkaloids. The observed cytolytic (oncolysis) effect in epithelial forestomachs cells under low pH values, worsening the osmotic status, should be considered before clinical applications.(AU)
As dietas para bovinos confinados possuem alta quantidade de alimentos energéticos com menor quantidade de alimentos volumosos (fibras), favorecendo a indução de acidose ruminal subaguda com formação de lesões gastrointestinais e sintomas clínicos deletérios. Recentes trabalhos têm demonstrado alguma amenização desta condição pelo uso de alcaloides isoquinolínicos encontrados na Macleaya cordata (Papaveraceae) tais como a sanguinarina e a cheleretrina, os quais tem demonstrado efeitos anti-inflamatórios, antimicrobianos e imuno modulatórios em humanos e animais. O objetivo deste estudo foi, através da histopatologia e de um sistema de escores, avaliar as diferenças entre um grupo não tratado e um grupo tratado com alcaloides isoquinolínicos, presentes na formulação Sangrovit RS® como fonte de sanguinarina (SG), chelerethrina (CH) and protropina (PA) padronizadas em 0,15 % w/w SG, usando bovinos em confinamento recebendo uma dieta rica em grãos como modelo inflamatório para o sistema gastrointestinal. Amostras dos pré-estômagos foram avaliadas por escores variando de zero a três, obtidos por microscopia de luz em diferentes campos em aumentos de 400X. Inflamação, degeneração hidrópica, hiperqueratose e formação de vesículas foram avaliadas nas diferentes camadas dos pré-estômagos tendo em vista a intensidade e a extensão das lesões. Tecidos não queratinizados como abomaso e intestino delgado, ceco e cólon tiveram seu total de células inflamatórias contadas por microscopia de luz em diferentes campos com aumentos de 200X. No rumem do grupo tratado houve uma redução significante no número de campos contendo degeneração hidrópica epitelial (p ≤ 0,001) e inflamação de lâmina própria (p ≤ 0,001). O retículo teve uma redução similar nos escores scores de degeneração hidrópica epitelial (p ≤ 0.002), degeneração hidrópica no estrato córneo (p ≤ 0.001), hiperqueratose (p ≤ 0.002) e inflamação na lamina própria (p ≤ 0.001) e inflamação epitelial (p ≤ 0.002). Não foram encontradas diferenças significantes no omaso. Todos os tecidos não queratinizados, exceto pelo íleo, tiveram uma redução significativa (p ≤ 0.001) no total de células inflamatórias. Neste experimento, bovinos em confinamento recebendo dieta rica em grãos e tratados com alcaloides isoquinolínicos tiveram lesões que tiveram melhoras e pioras. Os efeitos de melhora foram melhor demonstrados em tecidos sem camada córnea e na ausência de um meio ácido rico em lipopolisacarídeos, reforçando a noção da ação tópica, da dependência do pH do meio e do tempo de exposição modulando os mecanismos farmacológicos destes alcalóides. O efeito citolítico (oncólise) sobre células epiteliais de pré-estômagos em baixos valores de pH, piorando o estado osmótico das células, deveria ser considerado antes das aplicações clínicas.(AU)
Assuntos
Animais , Acidose/tratamento farmacológico , Bovinos , Alcaloides/efeitos adversos , Gastroenterite/tratamento farmacológico , Trato Gastrointestinal/lesõesRESUMO
INTRODUCCIÓN: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad de betaína. en pacientes con homocistinuria aislada (HCT) o en combinación a acidosis metilmalónica (AMM). Así, la médica endocrinóloga pediatra y genetista. La homocistinuria (HST) es un desorden del metabolismo caracterizado por niveles elevados del aminoácido homocisteína. Existen diferentes tipos de HST que se caracterizan por la acumulación anormal de homocisteína y sus metabolitos en sangre y orina : 1) HST provocada por defectos en el metabolismo intracelular de la cobalamina con la presencia de diferentes grupos de complementación (cblA-J); 2) HST clásica: defecto de la enzima cistationina B-sintetasa (CBS), y 3) defecto en la enzima metiltetrahidrofolato que convierte el 5-10-metil-tetrahidrofolato en 5-metil-tetrahidrofolato en el proceso de remetilación de la homocisteína. Las HST puede presentarse de forma aislada o en combinación con otras manifestaciones clínicas, como la acidemia metilmalónica (AMM). La betaína es un pequeño aminoácido con absorción rápida a nivel del íleo. Este aminoácido puede ser producido de manera endógena a partir de la oxidación de la colina en el organismo, principalmente en el hígado y riñones. La betaína cumple una función muy importante en la HST ya que es un donador de grupos metilo en la reacción enzimática de la enzima betaína-homocisteína-metiltransferasa que convierte (a través de la re-metilación) homocisteína a metionina. METODOLOGIA: Se realizó una búsqueda de literatura científica en relación a la eficacia y seguridad del uso de betaína anhidra en pacientes con homocistinuria aislada (HCT) o en combinación de acidosis metilmalónica (AMM). Se dio preferencia a guías de práctica clínica, revisiones sistemáticas con o sin meta-análisis y ensayos clínicos aleatorizados. Asimismo, se consideró extraer información con una estrategia de "bola de nieve" mediante la revisión de las referencias bibliográficas de las guías de práctica clínica, revisiones sistemáticas, estudios primarios, estudios descriptivos y revisiones narrativas seleccionadas, relevantes a la pregunta PICO a evaluar. La búsqueda de la literatura se realizó en las bases de datos The National Library of Medicine (Pubmed), y Cochrane Library. Asimismo, se buscó información en los metabuscadores Epistemonikos, y Translating Research into Practice (TRIPDATABASE). Específicamente, la búsqueda de guías de prácticas clínicas se realizó en las páginas de internet de la National Institute for Health and Care Excellence (NICE); y The National Guideline of Clearinghouse (NGC), el repositorio creado por la Agencia para la Investigación en Salud y Calidad (AHRQ). Finalmente, se hizo una búsqueda en la página de registro de ensayos clínicos www.clinicaltrials.gov, para identificar estudios primarios en elaboración o que no hayan sido publicados aún. RESULTADOS: Se realizó la búsqueda bibliográfica y de evidencia científica que sustente el uso de betaína en pacientes pediátricos con homocistinuria (HCT) aislada o en combinación con academia metilmalónica (AMM). Luego de revisar un total de 265 referencias, un total de 12 artículos fueron revisados a texto completo de los cuales sólo dos referencias fueron finalmente seleccionadas para ser analizadas, al ser las únicas que respondían a nuestra pregunta PICO en evaluación. CONCLUSIONES: En la presente evaluación de tecnología sanitaria se presenta la evidencia recabada sobre el uso de betaína anhidra en pacientes pediátricos con homocistinuria (HST) aislada o en combinación con acidosis metilmalónica (AMM). La evidencia encontrada que evalúa el uso de la betaína en pacientes pediátricos con HST es escasa. Se ha identificado evidencia proveniente de un estudio observacional y una revisión sistemática de reportes y series de casos. El reporte de casos muestra que una dosis de 3g/día de betaína anhidra se reduce los niveles AMM y HST luego de cinco meses de suplementación, además, mejoran los indicadores de percentiles de peso, longitud y perímetro cefálico. La agrupación de resultados de varios reportes y series de casos en la revisión sistemática mostró que la suplementación de betaína anhidra tiene un efecto beneficioso en el desarrollo psicomotor y el aumento de la sobrevida. La calidad de evidencia de los estudios incluidos es baja. Si bien la betaína anhidra ha mostrado tener efectos beneficiosos en el tratamiento de la HST, es importante tener en cuenta que el tratamiento de las HST está conformado por la combinación de varios suplementos incluyendo a la cobalamina, ácido fólico, carnitina, entre otros. Por esta razón, no es posible atribuir los resultados de los estudios a los efectos de la betaína anhidra de manera individual, por lo que estos deben ser tomados con precaución para la toma de decisiones sobre la mejor estrategia terapéutica a utilizar. Adicionalmente, los estudios incluidos presentan ciertas limitaciones metodológicas debido a que se incluyen dentro del análisis descriptivo a estudios observacionales de tipo reporte de caso o serie de caso. No obstante, en las enfermedades innatas del metabolismo, como es el caso de la HST, los pacientes presentan características clínicas muy similares entre sí, el tratamiento indicado es parecido para todos los pacientes, y el cegamiento de los evaluadores no influye en los desenlaces clínicos, por lo que se podría subvaluar la severidad de estas limitaciones. En base a aspectos teóricos, en ninguna de las causas de la HST el mecanismo de acción de la betaína anhidra ayuda de manera directa a solucionar el defecto existente. Sin embargo, la suplementación de betaína tiene como objetivo saturar a la célula y potenciar la reacción enzimática de la enzima metionina sintetasa para convertir la homocisteína en metionina, y así reducir la HST. Además, no existen otras alternativas terapéuticas específicas para la disminución de la HST, por lo que el tratamiento con betaína podría ser una terapia efectiva para esta enfermedad. Los expertos en pediatría reportan que el uso de betaína, en conjunto con otras terapias como la dieta hipoproteica y la suplementación de cobalamina, carnitina y ácido fólico, es el mejor método terapéutico a emplear en pacientes en pacientes con HST aislada o en combinación con AMM, con el objetivo de prevenir complicaciones tromboembólicas y, secundarias a estas, la aparición de diversas complicaciones neurológicas, cardiacas, retraso en el crecimiento y desarrollo cognitivo, síndrome urémico hemolítico, postración, microangiopatía trombótica con capacidad de generar necrosis a nivel de los tejidos, entre otras. Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación IETSI, aprueba el uso de betaína anhidra en pacientes con HST aislada o en combinación con AMM, según las condiciones establecidas en el Anexo 01. El presente Dictamen Preliminar tiene una vigencia de dos años a partir de la fecha de publicación.
Assuntos
Humanos , Acidose/tratamento farmacológico , Homocistinúria/tratamento farmacológico , Betaína/uso terapêutico , Eficácia , Análise Custo-BenefícioRESUMO
REASONS FOR PERFORMING STUDY: Treatment of metabolic acidosis using sodium bicarbonate solutions is safe when blood gas analysis is available. The evidence that solutions containing metabolisable buffers can be used as an alternative for treatment of metabolic acidosis in horses is of practical interest. OBJECTIVES: To investigate the safety and efficacy of a polyionic solution containing 84 mEq/l of lactate (L84) for the correction of induced hyperchloraemic metabolic acidosis. STUDY DESIGN: Non-randomised crossover design. METHODS: Five healthy, adult, crossbred horses were used. A solution containing 100 mmol/l of HCl was infused intravenously (100 ml/kg bwt) for 5 h to induce metabolic acidosis. Metabolic acidosis was induced in each horse twice, with a minimum 15-day interval after recovery from the first induction: the first time no treatment was administered (control group) and the second time horses were treated with an intravenous infusion of L84 solution, 100 ml/kg bwt for 5 h, beginning 3 h after the end of HCl infusion. Venous blood samples were taken at 0, 2.5, 5, 8, 10.5, 13, 24 and 48 h; and urine at 0, 5, 8 and 13 h. Laboratory data included pH (blood and urine), PCO2 , HCO3- , base excess, total plasma protein concentration, l-lactate, Na+ , K+ , Cl- , strong ion difference (SID4 ), anion gap, change in plasma volume and fractional excretions of Na+ , K+ and Cl- . Effects of time and treatment were tested by 2-way repeated measures ANOVA. RESULTS: Severe hyperchloraemic metabolic acidosis was induced. In the untreated horses, correction of the imbalance occurred gradually, and mild acidosis was still present at 48 h. In horses treated with the L84 solution, acidosis was corrected by the end of the infusion. There were no adverse effects with the administration of the L84 solution. CONCLUSIONS: A polyionic solution containing 84 mEq/l of lactate effectively corrected induced metabolic acidosis in horses within 5 h.
Assuntos
Acidose/veterinária , Eletrólitos/farmacologia , Doenças dos Cavalos/induzido quimicamente , Ácido Clorídrico/toxicidade , Ácido Láctico/uso terapêutico , Desequilíbrio Ácido-Base , Acidose/induzido quimicamente , Acidose/tratamento farmacológico , Animais , Estudos Cross-Over , Eletrólitos/administração & dosagem , Feminino , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Injeções Intravenosas , Ácido Láctico/administração & dosagem , MasculinoRESUMO
BACKGROUND: Being born preterm implies comorbidities, among them the risk of intraventricular hemorrhage (IVH). The use of sodium bicarbonate has been linked to the presence of IVH. The main purpose of this study was to determine if the infusion of sodium bicarbonate during the first 24 hours increases the risk of IVH in preterm infants. METHODS: Our study is a cohort; we analyzed the files of 160 patients and divided them into two groups: one in which sodium bicarbonate was not used and another in which it was; this latter group was subdivided into two considering if the use was therapeutic of prophylactic. RESULTS: In our total group of patients 10 % presented IVH; had a mean weight of 1500 g and 31 weeks of gestational age. The incidence of IVH was identical between both groups, although patients in which bicarbonate was used were more premature, unstable, and in worse clinical conditions. CONCLUSIONS: Our data indicate the need of large scale studies to determine if the clinical benefits of the use of sodium bicarbonate outweigh the risk of IVH.
Introducción: nacer prematuro conlleva riesgos, como la posibilidad de sufrir hemorragia intraventricular. El 90 % de los casos se presenta dentro de los primeros 4 a 7 días; Se ha relacionado el uso de bicarbonato de sodio con su aparición. El propósito de este estudio fue determinar si el uso de bicarbonato en infusión continua, en las primeras 24 horas, aumenta el riesgo de hemorragia intraventricular. Métodos: cohorte retrospectiva, se revisaron 160 expedientes formándose 2 grupos: uno sin y otro con uso de bicarbonato. Posteriormente, el grupo con uso se dividió en dos: uso terapéutico y profiláctico. Resultados: Del total de los prematuros, 10 % presentaron hemorragia intraventricular, tenían un peso promedio de 1,500 g y una edad gestacional promedio de 31 semanas. La incidencia fue idéntica entre los grupos, aunque en el grupo con bicarbonato había pacientes más prematuros, y clínicamente más inestables. Se realizó una regresión logística donde se observó asociación entre la incidencia de hemorragia intraventricular y el peso al nacimiento (OR de 0.99); así como en el caso del uso de bicarbonato de sodio con una OR 1.22. Conclusiones: Nuestros datos indican la necesidad de evaluación sistemática del uso de bicarbonato, con el fin de determinar si los beneficios sobrepasan el riesgo de hemorragia intraventricular.
Assuntos
Acidose/tratamento farmacológico , Hemorragia Cerebral/induzido quimicamente , Doenças do Prematuro/induzido quimicamente , Bicarbonato de Sódio/efeitos adversos , Acidose/prevenção & controle , Hemorragia Cerebral/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Doenças do Prematuro/epidemiologia , Infusões Intravenosas , Masculino , Estudos Retrospectivos , Bicarbonato de Sódio/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: This study was designed to investigate the activation of the unfolded protein response (UPR) in tumor associated endothelial cells (TECs) and its association with chemoresistance during acidic pH stress. MATERIALS AND METHODS: Endothelial cells from human oral squamous cell carcinomas (OSCC) were excised by laser capture microdissection (LCM) followed by analysis of UPR markers (Grp78, ATF4 and CHOP) using quantitative PCR. Grp78 expression was also determined by immunostaining. Acidic stress was induced in primary human dermal microvascular endothelial cells (HDMECs) by treatment with conditioned medium (CM) from tumor cells grown under hypoxic conditions or by adjusting medium pH to 6.4 or 7.0 using lactic acid or hydrochloric acid (HCl). HDMEC resistance to the anti-angiogenic drug Sunitinib was assessed with SRB assay. RESULTS: UPR markers, Grp78, ATF4 and CHOP were significantly upregulated in TECs from OSCC compared to HDMECs. HDMECs cultured in acidic CM (pH 6.0-6.4) showed increased expression of the UPR markers. However, severe acidosis led to marked cell death in HDMECs. Alternatively, HDMECs were able to adapt when exposed to chronic acidosis at pH 7.0 for 7 days, with concomittant increase in Grp78 expression. Chronic acidosis also confers drug resistance to HDMECs against Sunitinib. Knockdown of Grp78 using shRNA resensitizes HDMECs to drug treatment. CONCLUSIONS: UPR induction in ECs under acidic pH conditions is related to chemoresistance and may contribute to therapeutic failures in response to chemotherapy. Targeting Grp78, the key component of the UPR pathway, may provide a promising approach to overcome ECs resistance in cancer therapy.
Assuntos
Acidose/patologia , Derme/patologia , Resistencia a Medicamentos Antineoplásicos , Endotélio Vascular/patologia , Proteínas de Choque Térmico/metabolismo , Neoplasias Bucais/patologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Acidose/tratamento farmacológico , Acidose/metabolismo , Inibidores da Angiogênese/farmacologia , Apoptose , Western Blotting , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Ciclo Celular , Proliferação de Células , Células Cultivadas , Derme/efeitos dos fármacos , Derme/metabolismo , Chaperona BiP do Retículo Endoplasmático , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Imunofluorescência , Proteínas de Choque Térmico/genética , Humanos , Concentração de Íons de Hidrogênio , Técnicas Imunoenzimáticas , Microdissecção e Captura a Laser , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We examined the isolated and combined effects of beta-alanine (BA) and sodium bicarbonate (SB) on high-intensity intermittent upper-body performance in judo and jiu-jitsu competitors. 37 athletes were assigned to one of four groups: (1) placebo (PL)+PL; (2) BA+PL; (3) PL+SB or (4) BA+SB. BA or dextrose (placebo) (6.4 g day⻹) was ingested for 4 weeks and 500 mg kg⻹ BM of SB or calcium carbonate (placebo) was ingested for 7 days during the 4th week. Before and after 4 weeks of supplementation, the athletes completed four 30-s upper-body Wingate tests, separated by 3 min. Blood lactate was determined at rest, immediately after and 5 min after the 4th exercise bout, with perceived exertion reported immediately after the 4th bout. BA and SB alone increased the total work done in +7 and 8 %, respectively. The co-ingestion resulted in an additive effect (+14 %, p < 0.05 vs. BA and SB alone). BA alone significantly improved mean power in the 2nd and 3rd bouts and tended to improve the 4th bout. SB alone significantly improved mean power in the 4th bout and tended to improve in the 2nd and 3rd bouts. BA+SB enhanced mean power in all four bouts. PL+PL did not elicit any alteration on mean and peak power. Post-exercise blood lactate increased with all treatments except with PL+PL. Only BA+SB resulted in lower ratings of perceived exertion (p = 0.05). Chronic BA and SB supplementation alone equally enhanced high-intensity intermittent upper-body performance in well-trained athletes. Combined BA and SB promoted a clear additive ergogenic effect.