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Introduction: In photon brachytherapy (BT), experimental dosimetry is needed to verify treatment plans if planning algorithms neglect varying attenuation, absorption or scattering conditions. The detector's response is energy dependent, including the detector material to water dose ratio and the intrinsic mechanisms. The local mean photon energy E(r) must be known or another equivalent energy quality parameter used. We propose the brachytherapy photon radiation quality index Q(BT) ((E) over bar), to characterize the photon radiation quality in view of measurements of distributions of the absorbed dose to water, D-w, around BT sources. Materials and methods: While the external photon beam radiotherapy (EBRT) radiation quality index Q(EBRT) ((E) over bar) = TPR1020((E) over bar) is not applicable to BT, the authors have applied a novel energy dependent parameter, called brachytherapy photon radiation quality index, defined as Q(BT) ((E) over bar) = D-prim(r = 2 cm; theta(0) = 90 degrees)/D-prim(r(0) = 1 cm; theta(0) = 90 degrees), utilizing precise primary absorbed dose data, D-prim, from source reference databases, without additional MC-calculations. Results and discussion: For BT photon sources used clinically, Q(BT) ((E) over bar) enables to determine the effective mean linear attenuation coefficient (mu) over bar (E) and thus the effective energy of the primary photons E-prim(eff)(r(0), theta(0)) at the TG-43 reference position P-ref (r(0) = 1 cm; theta(0) = 90 degrees) being close to the mean total photon energy (E) over bar (tot)(r(0), theta(0)). If one has calibrated detectors, published (E) over bar (tot)(r) and the BT radiation quality correction factor k(Q, Q0)(BT) ((E) over bar, r, theta) for different BT radiation qualities Q and Q(0), the detector's response can be determined and D-w(r, theta) measured in the vicinity of BT photon sources. Conclusions: This novel brachytherapy photon radiation quality index Q(BT) characterizes sufficiently accurate and precise the primary photon` s penetration probability and scattering potential. (C) 2016 Published by Elsevier Ltd on behalf of Associazione Italiana di Fisica Medica.

KATP channels are heteromeric complexes of inwardly rectifying K+ channel subunits and sulfonylurea receptors (SURs). SUR2A and SUR2B, which differ within the carboxyl terminal exon 38, are characteristic for the cardiac and smooth muscle type channels, respectively. Here we compare binding of the tritiated KATP channel opener, [3H]P1075, to membranes from human embryonic kidney (HEK) cells transfected with murine SUR2A and 2B at 37 degrees C. Binding to both SURs required addition of Mg2+ and ATP in the low micromolar range. In the presence of MgATP, micromolar concentrations of MgADP, formed by the ATPase activity of the membrane preparation, increased binding to SUR2A but inhibited binding to SUR2B. Decreasing temperatures strongly reduced [3H]P1075 binding to SUR2A, whereas binding to SUR2B was increased in a bell-shaped manner. Kinetic experiments revealed a faster dissociation of the [3H]P1075-SUR2A complex, whereas the association rate constants for [3H]P1075 binding to SUR2A and 2B were similar. Openers inhibited [3H]P1075 binding to SUR2A with potencies approximately 4 times lower than to SUR2B; in contrast, glibenclamide inhibited [3H]P1075 binding to SUR2A approximately 8 times more potently than to SUR2B. The data suggest that SUR2A and 2B represent the opener receptors of cardiac and vascular smooth muscle KATP channels, respectively, and show that MgADP is an important modulator of opener binding to SUR. The different carboxyl termini of SUR2A and 2B lead to differences in the MgADP dependence and the thermodynamics of [3H]P1075 binding, as well as in the affinities for openers and glibenclamide, underlining the importance of this part of the molecule for KATP channel modulator binding.

In low stages of Hodgkin's disease radiotherapy alone is still considered to be the treatment of choice, as so called mantle fields and so called inverted Y-fields. According to the early onset of chemotherapy in stages I-IIIA radiation technique and radiation dose have to be adapted. With regard to stage, histologic type and adjuvant chemotherapy in Hodgkin's disease risks of radiation therapy are evaluated. Recommendations for modified radiation techniques are given.

In this study, ligands from various chemical classes were investigated with respect to their relative affinities to calmodulin (CaM) and troponin C (TnC), using the fluorescent dye 3,3'-dipropylthiocarbocyanine iodide (diS-C3-5'). In parallel, functional tests were carried out determining the effects of the ligands on the CaM activated cyclic nucleotide phosphodiesterase (PDE) activity and the TnC mediated Ca-sensitivity of skinned myocardial fibres and cardiac myofibrils. The following results were obtained: 1) As a rule, most of the ligands tested had higher affinities to CaM than to TnC. 2) Even within one and the same pharmacological class (e.g. phenothiazines) the relative affinities for CaM and TnC varied considerably, trifluoperazine (TFP) or levomepromazine (LMP) showing low or no CaM specificity, methophenazine (MP) on the other hand being highly selective for CaM by a factor of more than 200. 3) In all cases tested, the functional tests were in good quantitative agreement with the binding data, showing inhibition of CaM stimulated PDE activity and Ca-sensitizing effects in concentrations corresponding well with the respective drug affinities to CaM and TnC, respectively. 4) It is concluded that a) interaction of ligands with TnC can lead to Ca-sensitization of the cardiac contractile system and a positive inotropic effect without a concomitant elevation of the intracellular level of activator Ca. This may result in a novel cardiotonic principle avoiding the common side effects of 'classical' positive inotropic agents due to Ca-overload. b) drug selectivity for TnC or CaM appears chemically achievable.

The interaction of several phenothiazines, benzodiazepines, butyrophenones, polycyclic neuroleptics and tricyclic antidepressants with calmodulin and troponin C was investigated using the fluorescent dye 3,3'-dipropylthiocarbocyanine iodide. In the presence of Ca2+, trifluoperazine (2-trifluoromethyl-10-[3-(1-methylpiperazinyl-4)propyl]-phenothiaz ine dihydrochloride, TFP), which is commonly used as a selective calmodulin inhibitor, half maximally increased the fluorescence of the complex formed of the fluorescent dye with calmodulin at a concentration of 4 mumol/l, and with troponin C at 24 mumol/l. TFP completely inhibited the calmodulin dependent stimulation of cyclic nucleotide phosphodiesterase with a Ki of 4 mumol/l and decreased the maximum Ca2+ dependent troponin C mediated activation of actomyosin ATPase by 35% at a concentration of 100 mumol/l. Metofenazate (3,4,5-trimethoxybenzoate-2-chlor-10-(3-[(beta-oxyethyl) piperazinyl-4]-propyl)phenothiazine diethanesulfonate, methophenazine, MP) produced half maximal fluorescence enhancement of the calmodulin dye complex at a concentration of 6 mumol/l and did not influence the fluorescence of the troponin C dye complex at concentrations of up to 1000 mumol/l. MP also completely inhibited the calmodulin dependent stimulation of phosphodiesterase with a Ki of 7 mumol/l but it had not effect on maximum Ca2+ stimulation of actomyosin ATPase. MP increased the Ca2+ sensitivity of skinned cardiac muscle with an about 10fold lower potency than TFP. In view of these results, we propose MP as a useful tool for distinction between processes mediated by either calmodulin or troponin C.