ABSTRACT
BACKGROUND: Prone positioning has been found feasible and appropriate for the reduction of radiation exposure of the lungs, but its effects on the heart dose remain controversial. Individual anatomical features were sought for the selection of optimal treatment positioning. MATERIAL AND METHODS: In 138 left-sided breast cancer cases awaiting postoperative whole-breast radiotherapy, conformal radiotherapy plans were generated in both prone and supine positions. RESULTS: The radiation doses to the left anterior descending coronary artery (LAD) and heart in the two positions differed individually, and were strongly related to the body mass index (BMI). Image fusion of the CT scans revealed that prone positioning was detrimental if the heart was situated distant from the chest wall in the supine position, but moved to the chest wall in the prone position. For characterization of the geography of the heart and the breast, the median distance between the LAD and the chest wall (dmedian), and the heart area included in the radiation field on a single CT scan at the middle of the heart in the supine position (Aheart) proved most appropriate. CONCLUSION: A validated statistical model, utilizing the BMI, dmedian and Aheart, permits individualized positioning for maximum heart protection.
Subject(s)
Breast Neoplasms/radiotherapy , Heart/radiation effects , Patient Positioning , Radiation Injuries/prevention & control , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Conformal , Adult , Aged , Algorithms , Body Mass Index , Female , Follow-Up Studies , Humans , Middle Aged , Prognosis , Prone Position , Prospective Studies , Radiotherapy Dosage , Supine Position , Tomography, X-Ray ComputedABSTRACT
The description of the heterogeneous phenomenological, pathophysiological, and etiological nature of schizophrenia is under way; however, the relationships between heterogeneity levels are still unclear. We performed a robust cross-sectional study, including a systematic neuropsychological battery, assessment of clinical symptoms, neurological soft signs, morphogenetic anomalies and smell identification, and measurement of event-related potentials on 50 outpatients with schizophrenia in their compensated states. An explorative fuzzy cluster analysis revealed two subgroups in this sample that could be distinguished from each other on symptomatological, cognitive and neurological levels. The patterns of cognitive dysfunctions and neurological developmental anomalies equally indicate that there may be hemispherical differences between the patients belonging to the different clusters.
Subject(s)
Cognition Disorders/diagnosis , Cognition/physiology , Neuropsychological Tests , Schizophrenia , Schizophrenic Psychology , Acoustic Stimulation/methods , Adult , Algorithms , Cluster Analysis , Cognition Disorders/etiology , Contingent Negative Variation/physiology , Electroencephalography/methods , Evoked Potentials, Auditory/physiology , Female , Humans , Male , Middle Aged , Neurologic Examination , Probability , Psychiatric Status Rating Scales , Schizophrenia/classification , Schizophrenia/complications , Schizophrenia/diagnosis , Smell/physiology , Statistics, Nonparametric , Young AdultABSTRACT
4-Carboxamidobenzimidazoles were previously described as PARP inhibitor compounds. Here we report upon 4-carboxamido-1H-benzimidazoles substituted in the 2-position with nitroxides or their amine or hydroxylamine precursors. Among the new molecules, a highly active PARP inhibitor 4h (IC(50) = 14 nM) was identified with antioxidant/radical scavenger activity. We concluded that in most cases sterically hindered amines are better PARP inhibitors than their oxidized form and structural changes in the 2-substituted 4-carboxamido-1H-benzimidazoles (such as N-substitution or changing the position of the carboxamide group) were detrimental to PARP inhibition activity but not to antioxidant activity. These results indicate the advantages of combining an antioxidant nitroxide or nitroxide precursor with a PARP inhibitor molecule to decrease or eliminate the deleterious processes initiated by reactive oxygen and reactive nitrogen species (ROS and RNS). The radical scavenging capability of 4h was demonstrated by EPR study of urine collected after drug administration.
Subject(s)
Antioxidants/pharmacology , Enzyme Inhibitors/pharmacology , Nitrogen Oxides/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors , Animals , Antioxidants/chemistry , Cell Line , Electron Spin Resonance Spectroscopy , Enzyme Inhibitors/chemistry , Humans , Hydrogen Bonding , Mice , Mice, Inbred C57BL , Nitrogen Oxides/chemistry , Poly (ADP-Ribose) Polymerase-1 , RatsABSTRACT
Los lignanos ingeridos con los alimentos de origen vegetal pueden ser biotransformados por las bacterias del tracto intestinal de los mamíferos y posteriormente absorbidos, dando compuestos detectables en suero, saliva, orina, bilis y fluidos seminales. Estos compuestos son conocidos como enterolignanos o lignanos de mamíferos y, al igual que otros fitoestrógenos, imitan algunos de los efectos de los estrógenos. En la actualidad se cree que pueden ejercer un efecto quimioprotector contra cánceres hormonodependientes como son el cáncer de mama y de próstata
Lignans ingested with food of plant origin are biotransformated by intestinal bacteria of the mammals and then absorbed, giving compounds detectable in serum, saliva, urine, bile and seminal fluids. These compounds are known as enterolignans or mammalian lignans and, like other phytoestrogens, can have some estrogen-like effects. Nowadays it is believed that they could exert a chemoprotective effect against hormone-dependent cancer, such as breast and prostate cancer
Subject(s)
Humans , Lignans/administration & dosage , Lignans/metabolism , Diet , Prostatic Neoplasms/prevention & control , Breast Neoplasms/prevention & control , Biological AvailabilityABSTRACT
En lo que a actividad farmacológica se refiere, los lignanos son principalmente conocidos por su actividad citotóxica, que es particularmente importante en el grupo de los ciclolignanos. No obstante, estos productos naturales también son inhibidores de la fosfodiesterasa del AMPc, confieren protección frente a hepatotoxinas, actúan sobre el tracto gastrointestinal, sistema cardiovascular y sistema nervioso central. También han demostrado tener actividad antiinflamatoria, antivírica y sobre el factor activador de plaquetas (PAF). Finalmente, tienen propiedades fitoestrogénicas, que serán tratadas en la tercera parte de esta serie de artículos sobre lignanos
Regarding the pharmacological activities, lignans are mainly known by their cytotoxic activity that is very important in cyclolignans. Nevertheless, these natural products are also inhibitors of AMPc phosphodiesterase, protectors against hepatotoxins and they act on the gastrointestinal tract, cardiovascular system and central nervous system. They have al so shown antiinflammatory and antiviral activities, as well as on the platelet activating factor (PAF). Finally, they also have phytoestrogenic properties, that will be described in the third part of these series of papers on lignans
