Dose distribution in the thyroid gland following radiation therapy of breast cancer-a retrospective study

<p>Abstract</p> <p>Purpose</p> <p>To relate the development of post-treatment hypothyroidism with the dose distribution within the thyroid gland in breast cancer (BC) patients treated with loco-regional radiotherapy (RT).</p> <p>Methods and materials</p> <p>In two groups of BC patients postoperatively irradiated by computer tomography (CT)-based RT, the individual dose distributions in the thyroid gland were compared with each other; Cases developed post-treatment hypothyroidism after multimodal treatment including 4-field RT technique. Matched patients in Controls remained free for hypothyroidism. Based on each patient's dose volume histogram (DVH) the volume percentages of the thyroid absorbing respectively 20, 30, 40 and 50 Gy were then estimated (V20, V30, V40 and V50) together with the individual mean thyroid dose over the whole gland (MeanTotGy). The mean and median thyroid dose for the included patients was about 30 Gy, subsequently the total volume of the thyroid gland (VolTotGy) and the absolute volumes (cm³) receiving respectively < 30 Gy and ≥ 30 Gy were calculated (Vol < 30 and Vol ≥ 30) and analyzed.</p> <p>Results</p> <p>No statistically significant inter-group differences were found between V20, V30, V40 and V50Gy or the median of MeanTotGy. The median VolTotGy in Controls was 2.3 times above VolTotGy in Cases (ρ = 0.003), with large inter-individual variations in both groups. The volume of the thyroid gland receiving < 30 Gy in Controls was almost 2.5 times greater than the comparable figure in Cases.</p> <p>Conclusions</p> <p>We concluded that in patients with small thyroid glands after loco-radiotherapy of BC, the risk of post-treatment hypothyroidism depends on the volume of the thyroid gland.</p

Sarcoptic mange in three alpacas treated successfully with amitraz

Sarcoptic mange is a serious skin disease in alpacas that can result in high morbidity and even mortality. Three alpacas were presented with sarcoptic mange that had previously failed to respond to repeated topical applications of eprinomectin, and an injection of doramectin. They were moderately to severely pruritic, had extensive lesions of alopecia, erythema, scaling and crusting, and had lost weight. As no drug is currently licensed for the treatment of sarcoptic mange in alpacas in the UK, they were treated with a topical solution of amitraz (50 mL in 10 L) after initial bathing with antibacterial or keratolytic shampoos. The clinical signs completely resolved with no relapse over a 10-month follow-up period. In this small group of alpacas, amitraz was an effective and well-tolerated treatment for sarcoptic mange.Peri Lau, Peter B. Hill, Jan Rybníček and Lynne Stee

Intrinsic Thermodynamics and Structure Correlation of Benzenesulfonamides with a Pyrimidine Moiety Binding to Carbonic Anhydrases I, II, VII, XII, and XIII

<div><p>The early stage of drug discovery is often based on selecting the highest affinity lead compound. To this end the structural and energetic characterization of the binding reaction is important. The binding energetics can be resolved into enthalpic and entropic contributions to the binding Gibbs free energy. Most compound binding reactions are coupled to the absorption or release of protons by the protein or the compound. A distinction between the observed and intrinsic parameters of the binding energetics requires the dissection of the protonation/deprotonation processes. Since only the intrinsic parameters can be correlated with molecular structural perturbations associated with complex formation, it is these parameters that are required for rational drug design. Carbonic anhydrase (CA) isoforms are important therapeutic targets to treat a range of disorders including glaucoma, obesity, epilepsy, and cancer. For effective treatment isoform-specific inhibitors are needed. In this work we investigated the binding and protonation energetics of sixteen [(2-pyrimidinylthio)acetyl]benzenesulfonamide CA inhibitors using isothermal titration calorimetry and fluorescent thermal shift assay. The compounds were built by combining four sulfonamide headgroups with four tailgroups yielding 16 compounds. Their intrinsic binding thermodynamics showed the limitations of the functional group energetic additivity approach used in fragment-based drug design, especially at the level of enthalpies and entropies of binding. Combined with high resolution crystal structural data correlations were drawn between the chemical functional groups on selected inhibitors and intrinsic thermodynamic parameters of CA-inhibitor complex formation.</p></div