Mitigation of radiation nephropathy after internal alpha-particle irradiation of kidneys

PURPOSE: Internal irradiation of kidneys as a consequence of radioimmunotherapy, radiation accidents, or nuclear terrorism can result in radiation nephropathy. We attempted to modify pharmacologically, the functional and morphologic changes in mouse kidneys after injection with the actinium ((225)Ac) nanogenerator, an in vivo generator of alpha- and beta-particle emitting elements. METHODS AND MATERIALS: The animals were injected with 0.35 muCi of the (225)Ac nanogenerator, which delivers a dose of 27.6 Gy to the kidneys. Then, they were randomized to receive captopril (angiotensin-converting enzyme inhibitor), L-158,809 (angiotensin II receptor-1 blocker), spironolactone (aldosterone receptor antagonist), or a placebo. RESULTS: Forty weeks after the (225)Ac injection, the placebo-control mice showed a significant increase in blood urea nitrogen (BUN) (87.6 +/- 6.9 mg/dL), dilated Bowman spaces, and tubulolysis with basement membrane thickening. Captopril treatment accentuated the functional (BUN 119.0 +/- 4.0 mg/dL; p <0.01 vs. placebo controls) and histopathologic damage. In contrast, L-158,809 offered moderate protection (BUN 66.6 +/- 3.9 mg/dL; p = 0.02 vs. placebo controls). Spironolactone treatment, however, significantly prevented the development of histopathologic and functional changes (BUN 31.2 +/- 2.5 mg/dL; p <0.001 vs. placebo controls). CONCLUSIONS: Low-dose spironolactone and, to a lesser extent, angiotensin receptor-1 blockade can offer renal protection in a mouse model of internal alpha-particle irradiation.     

Fabrication of the Zirconium Diboride-Reinforced Composites by a Combination of Planetary Ball Milling,Turbula Mixing and Spark Plasma Sintering

The aim of this study was to carry out the consolidation of zirconium diboride-reinforced composites using the SPS technique. The effect of the adopted method of powder mixture preparation (mixing in Turbula or milling in a planetary mill) and of the reinforcing phase content and sintering temperature on the microstructure, physical properties, strength and tribological properties of sintered composites was investigated. Experimental data showed that the maximum relative density of 94–98% was obtained for the composites sintered at 1100 °C. Milling in a planetary mill was found to contribute to the homogeneous dispersion and reduced clustering of ZrB₂ particles in the steel matrix, improving in this way the properties of sintered steel + ZrB₂ composites. Morphological and microstructural changes caused by the milling process in a planetary mill increase the value of Young’s modulus and improve the hardness, strength and wear resistance of steel + ZrB₂ composites. Higher content of ZrB₂ in the steel matrix is also responsible for the improvement in Young’s modulus, hardness and abrasive wear resistance.     

PAX-5 expression in pulmonary neuroendocrine neoplasms: its usefulness in surgical and fine-needle aspiration biopsy specimens

The World Health Organization classification of lung tumors recognizes 4 histologic subtypes of pulmonary neuroendocrine carcinomas (NECs), which include typical carcinoids (TCs), atypical carcinoids (ACs), small cell carcinomas (SCCs), and large cell NECs (LCNECs). These tumors can be misclassified owing to morphologic parallels, indicating the necessity for adjunctive tests for correct classification. We evaluated immunohistochemical expression of PAX-5 in histologic and fine-needle aspiration (FNA) specimens of pulmonary NECs. Staining was stratified by intensity (0 to 3+) and percentage of cells stained as focal (<10%) or diffuse (=10%). PAX-5 expression was present in 29/37 (78%) of high-grade NECs (22/26 SCCs, 1/2 LCNECs, and 6/9 combined tumors) and none of 51 TCs and ACs; FNA specimens showed concordant staining. This study confirmed that PAX-5 is a useful marker in FNA and surgical specimens for the discrimination of low- to intermediate-grade NECs from high-grade NECs with 100% specificity and 79% sensitivity in surgical specimens.     

Primary B cell lymphoma of the thyroid and its relationship to Hashimoto's thyroiditis

Twenty-one cases were selected from 236 thyroidectomies with a diagnosis of Hashimoto's disease for detailed clinicopathologic study on the basis of "early" changes in three cases and an unusually heavy lymphoplasmacytic infiltrate in 18 cases. These cases were studied in conjunction with ten cases of high-grade non-Hodgkin's lymphoma of the thyroid. Immunoglobulin light chain restriction was demonstrated in five cases of Hashimoto's thyroiditis and the diagnosis was accordingly changed to low-grade lymphoma. All ten high-grade lymphoma cases were of B phenotype and light chain restriction could be demonstrated in eight of them. The study revealed close homology between the lymphoplasmacytic infiltrate in Hashimoto's thyroiditis and normal mucosa-associated lymphoid tissue (MALT). Like lymphomas of mucosal sites, thyroid lymphoma appears to be derived from the parafollicular ("centrocyte-like") B cells. The high-grade thyroid lymphomas appear to be derived from low-grade tumors. There were close histologic, immunohistologic, and clinical similarities between low- and high-grade non-Hodgkin's lymphomas of the thyroid and those appearing in mucosal sites. This study confirms the close association between Hashimoto's thyroiditis and B cell lymphoma of the thyroid gland and suggests that this tumor belongs to the group of non-Hodgkin's lymphomas derived from MALT.