RESUMEN
BACKGROUND: Prostate cancer in younger men is rare but not exceptional. Radiotherapy is a cornerstone of prostate cancer treatment and yet, its impact on fertility is scarcely reported in literature. Given the radiosensitivity of testicular tissue, this study aimed to determine the testicular dose using modern radiotherapy techniques for definitive prostate irradiation. METHODS: One hundred radiotherapy plans were reviewed. Testicles were contoured retrospectively without dosimetric optimization on testicles. RESULTS: The median testicular dose was 0.58 Gy: 0.18 Gy in stereotactic plans, 0.62 Gy in Volumetric Modulated Arc Therapy plans and 1.50 Gy in Tomotherapy plans (p < 0.001). Pelvic nodal irradiation increased the median testicular dose to 1.18 Gy versus 0.26 Gy without nodal irradiation (p < 0.001). Weight and BMI were inversely associated with testicular dose (p < 0.005). 65% of patients reached the theoretical dose threshold for transient azoospermia, and 10% received more than 2 Gy, likely causing definitive azoospermia. CONCLUSION: Despite being probably lower than doses from older techniques, the testicular dose delivered with modern prostate radiotherapy is not negligible and is often underestimated because the contribution of daily repositioning imaging is not taken into account and most Treatment Planning Systems underestimate the out of field dose. Radiation oncologists should consider the impact on fertility and gonadal endocrine function, counseling men on sperm preservation if they wish to maintain fertility. TRIAL REGISTRATION: retrospectively registered.
Asunto(s)
Neoplasias de la Próstata , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Testículo , Humanos , Masculino , Neoplasias de la Próstata/radioterapia , Estudios Retrospectivos , Testículo/efectos de la radiación , Persona de Mediana Edad , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Órganos en Riesgo/efectos de la radiación , Anciano , Adulto , Traumatismos por Radiación/etiología , Fertilidad/efectos de la radiaciónRESUMEN
PURPOSE: Stereotactic body radiotherapy (SBRT) of prostate cancer is associated with rectal toxicities, which can be reduced by using a hydrogel spacer. The object of this retrospective study was to show the feasibility of spacer placement under local anesthesia and utility of hydrogel spacer to reduce the dose to the rectal wall. MATERIAL AND METHODS: We collected data from all patients with localised prostate cancer treated with SBRT (40Gy in 5 fractions) between 2018 and 2020. A hydrogel spacer (SpaceOAR®) was placed depending on the availability of the product. We collected dosimetric data for target volumes and organs at risk. We calculated mean values, which were compared using non-parametric tests. RESULTS: Among 35 patients, mean age was 75 years. Seventeen had a spacer placed, with a mean space created of 10mm. No complication was reported during the intervention. High doses to the rectal wall were significantly lower in spacer group (V38: 0.39 cm3 vs. 0.72 cm3; P=0.02). PTV were better covered in spacer group (P=0.07). Doses to the bladder wall were similar in both groups. CONCLUSION: Spacer procedure under local anesthesia was well tolerated. Hydrogel spacer allowed to reduce doses to the rectum while improving PTV coverage.
Asunto(s)
Hidrogeles/administración & dosificación , Neoplasias de la Próstata/radioterapia , Traumatismos por Radiación/prevención & control , Radiocirugia/métodos , Recto/efectos de la radiación , Anciano , Anciano de 80 o más Años , Anestesia Local , Estudios de Factibilidad , Humanos , Masculino , Persona de Mediana Edad , Órganos en Riesgo/efectos de la radiación , Neoplasias de la Próstata/patología , Radiocirugia/efectos adversos , Dosificación Radioterapéutica , Estudios Retrospectivos , Estadísticas no Paramétricas , Vejiga Urinaria/efectos de la radiaciónRESUMEN
Water soluble 8-methylureido-10-amino-10-methyl-imidazo[1,2-a]indeno[1,2-e]pyraz ine-4-one 4 represents a novel class of highly potent and selective AMPA receptors antagonists with in vivo activity. The dextrorotatory isomer (+)-4 was found to display the highest affinity with an IC50 of 10 nM. It also exhibited very good anticonvulsant effects after i.p., s.c. and i.v. administration in mice subjected to electrical convulsions (MES) and i.p. in audiogenic seizure-e in DBA/2 mice (ED50's < or = 10 mg/kg).
Asunto(s)
Anticonvulsivantes/síntesis química , Imidazoles/química , Imidazoles/síntesis química , Pirazinas/química , Pirazinas/farmacología , Receptores AMPA/antagonistas & inhibidores , Animales , Anticonvulsivantes/química , Anticonvulsivantes/metabolismo , Anticonvulsivantes/farmacología , Química Encefálica , Corteza Cerebral/metabolismo , Imidazoles/metabolismo , Ácido Kaínico/farmacología , Masculino , Ratones , Microinyecciones , Estructura Molecular , Oocitos/fisiología , Técnicas de Placa-Clamp , Pirazinas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ensayo de Unión Radioligante , Ratas , Estereoisomerismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/metabolismoRESUMEN
Indeno¿1,2-bpyrazin-2,3-diones have been identified as a novel series of potent ligands on the glycine site of the NMDA receptor. To improve their in vivo activities, an acetic acid-type side chain was introduced to the 5-position, giving water-soluble compounds when formulated as the sodium salt (>10 mg/mL). Introduction of a chlorine atom in the 8-position led to a dramatic improvement of anticonvulsant activity and this was surprising since this change did not improve binding affinity. A plausible explanation is a reduced recognition by a Na(+),K(+)-ATPase active transport system responsible for the excretion of these compounds from the brain and kidney. This promising new chemical series led to the optically active isomer (-)-10i (RPR 118723), a glycine/NMDA antagonist with nanomolar binding affinity and in vivo activity in animal model of convulsions and electrophysiology at doses in the range of 2-3 mg/kg following iv administration.
Asunto(s)
Antagonistas de Aminoácidos Excitadores/síntesis química , Pirazinas/síntesis química , Receptores de Glicina/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Animales , Anticonvulsivantes/síntesis química , Anticonvulsivantes/química , Anticonvulsivantes/metabolismo , Anticonvulsivantes/farmacología , Células Cultivadas , Cerebelo/citología , Corteza Cerebral/metabolismo , Antagonistas de Aminoácidos Excitadores/química , Antagonistas de Aminoácidos Excitadores/metabolismo , Antagonistas de Aminoácidos Excitadores/farmacología , Técnicas In Vitro , Potenciación a Largo Plazo/efectos de los fármacos , Ratones , Neuronas/efectos de los fármacos , Neuronas/fisiología , Técnicas de Placa-Clamp , Pirazinas/química , Pirazinas/metabolismo , Pirazinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Glicina/metabolismo , Receptores de Glicina/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/fisiología , EstereoisomerismoRESUMEN
A novel series of readily water soluble 8-methylureido-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]++ +pyrazines were synthesized. The -10-yl acetic acid ((+)-3) and -10-carboxylidene (4) derivatives exhibit potent affinities (IC50=4 and 19 nM, respectively) and antagonist properties (IC50 = 2 and 3 nM, respectively) at the ionotropic AMPA receptor. These compounds also display anticonvulsant properties against both electrically and sound-induced convulsions in mice after ip, sc and iv administration with ED50 values between 0.9 and 11 mg/kg, thus suggesting adequate brain penetration.
Asunto(s)
Antagonistas de Aminoácidos Excitadores/síntesis química , Pirazinas/síntesis química , Receptores AMPA/antagonistas & inhibidores , Animales , Anticonvulsivantes/síntesis química , Anticonvulsivantes/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Isoquinolinas/farmacología , Ratones , Oocitos/metabolismo , Pirazinas/farmacología , Quinoxalinas/farmacología , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Convulsiones/tratamiento farmacológico , Convulsiones/genética , Tetrazoles/farmacología , Xenopus laevisRESUMEN
Original spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives were synthesised and led to the identification of 3e which showed good affinities for both the AMPA and the NMDA glycine-site receptors, and displayed good anticonvulsant effects after i.p. and i.v. administrations in the electroshock-induced convulsion assay in mice. The corresponding dextrorotatory isomer (+)-3e was notably more potent than the levorotatory isomer (-)-3e in in vitro and in vivo assays.
Asunto(s)
Antagonistas de Aminoácidos Excitadores/farmacología , Glicina/metabolismo , Pirazinas/farmacología , Receptores AMPA/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Compuestos de Espiro/farmacología , Animales , Sitios de Unión , Antagonistas de Aminoácidos Excitadores/química , Antagonistas de Aminoácidos Excitadores/metabolismo , Ratones , Pirazinas/química , Pirazinas/metabolismo , Receptores AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Compuestos de Espiro/química , Compuestos de Espiro/metabolismo , Relación Estructura-ActividadRESUMEN
A serial neurophysiological study has been performed of 2 children during the clinical course of Creutzfeldt-Jakob disease after human growth hormone (hGH) treatment. Evolution of the EEG pattern was typical: slow waves, periodic sharp wave complexes, then extinction. VEP components were moderately altered. BAERs performed in only 1 child were normal. The blink reflex (BR) showed an early alteration of the R1 component. The ERG exhibited early and profound anomalies. Pathological changes were obvious at the first recording, at the beginning of the second month after clinical onset: increase in peak latencies, morphological changes and important reduction of b wave amplitude (a/b amplitude ratio > or = 0.70; normal range 0.27-0.41). The ERG was completely absent a few months later. These results are compared with the similar retinopathy described in CJD- or scrapie-infected rodents. In the 2 children, pathological changes in ERG and in BR were obvious several months before the development of the typical EEG pattern. Therefore, early ERG and BR recording can be helpful in the diagnosis of CJD, especially in this ataxic form following hGH treatment.