Rectal planning risk volume correlation with acute and late toxicity in 3-dimensional conformal radiation therapy for prostate cancer.

The purpose of this study was to evaluate rectum motion during 3-Dimensional conformal radiation therapy (3D-CRT) in prostate cancer patients, to derive a planning volume at risk (PRV) and to correlate the PRV dose-volume histograms (DVH) with treatment complications.This study was conducted in two phases. Initially, the PRV was defined prospectively in 50 consecutive prostate cancer patients (Group 1) who received a radical course of 3-D CRT. Then, the obtained PRV was used in the radiotherapy planning of these same 50 patients plus another 59 prostate cancer patients (Group 2) previously treated between 2004 and 2008. All these patients' data, including the rectum and PRV DVHs, were correlated to acute and late complications, according to the Common Toxicity Criteria (CTC) v4.0.The largest displacement occurred in the anterior axis. Long-term gastrointestinal (GI) complications grade ≥ 2 were seen in 9.2% of the cases. Factors that influenced acute GI reactions were: doses at 25% (p 5 0.011) and 40% (p 5 0.005) of the rectum volume and at 40% of the PRV (p 5 0.012). The dose at 25% of the rectum volume (p 5 0.033) and acute complications ≥ grade 2 (p 5 0.018) were prognostic factors for long-term complications. The PRV DVH did not correlate with late toxicity. The rectum showed a significant inter-fraction motion during 3D-CRT for prostate cancer. PRV dose correlated with acute gastrointestinal complications and may be a useful tool to predict and reduce their occurrence.

The role played by endogenous and exogenous electric fields in DNA signaling and repair.

Comments are made and new insights are provided on the key role played by endogenous and exogenous electric fields, where the former starts and conducts the repairing chain, while the latter is able to scramble the completion of the repair process and, as a consequence, may have important potential as a radiation sensitizer for clinical application.

The role played by endogenous and exogenous electric fields in DNA signaling and repair

Comments are made and new insights are provided on the key role played by endogenous and exogenouselectric fields, where the former starts and conducts the repairing chain, while the latter is able to scramblethe completion of the repair process and, as a consequence, may have important potential as a radiationsensitizer for clinical application.

Early nuclear alterations and immunohistochemical expression of Ki-67, Erb-B2, vascular endothelial growth factor (VEGF), transforming growth factor (TGF-beta1) and integrine-linked kinase (ILK) two days after tamoxifen in breast carcinoma.

The purpose of the present study was to evaluate breast carcinoma samples before and two days after treatment with tamoxifen in order to analyse early histopathological alterations--particularlynuclear alterations-- as well as immunohistochemical expression of Ki-67, Erb-B2, VEGF, TGF-beta1 and ILK proteins. Twenty one cases of invasive ductal and lobular breast carcinoma were studied. Patients were submitted to biopsy of the lesion and, after confirmation of the diagnosis, they received 20 mg of tamoxifen a day, beginning two days before surgery. The samples obtained during biopsy and after surgery were stained with HE for histopathological diagnosis. Estrogen receptor was positive in 18 cases and negative in 3. The immunohistochemical method was applied for the detection of Ki-67, Erb-B2, protein, vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta1) and integrin linked kinase (ILK). Two days after tamoxifen treatment, the following results were observed: 1) decrease in the cell volume, chomatine condensation, nucleoli less evident and clearly defined nuclear limits; 2) significant reduction in the expression of Erb-B2 protein and significant increase in the expression of TGF-beta1 protein; 3) expression of others proteins (Ki-67, VEGF and ILK) was not altered during the indicated time frame. Our results suggest that analyzing nuclear alterations and expression of Erb-B2 and TGF-beta1 proteins would be useful to assess the initial response to tamoxifen.

Structural, cytochemical, immunocytochemical and ultrastructural characterization of blood granulocytes of the roadside hawk Buteo magnirostris (Gmelin, 1788) (Avian, Falconiform).

In the peripheral blood of the roadside hawk, Buteo magnirostris, the following types of granulocytic leucocytes were identified: heterophil, eosinophil and basophil. The heterophils presented acidophilic and spindle shaped granules, the eosinophils possess spherical eosinophilic granules and the basophils showed spherical and basophilic granules. The heterophils and eosinophils presented positive cytochemical reaction to glycogen and basic polyaminoacid, while the eosinophils presented sudanophilic granules, which were also positive for myeloperoxidase. The heterophils, alone, presented positivity for acid phosphatase in some granules and immunoreactivity to TGF-beta1 was observed only in the cytoplasm of the eosinophils. Electron microscopy demonstrated the heterophil granules as predominantly spindle shaped, being strongly electron-dense, while the eosinophils had numerous uniformly electron-dense spherical granules and the basophils presented three different types of granules identified according to their electron-density and the aspect of their matrix.

Effects of ionizing radiation on progressive experimental renal disease: a hemodynamic approach.

In order to evaluate the progression of renal disease, Munich-Wistar rats were submitted to 5/6 nephrectomy and given whole-body x- or gamma-irradiation with or without remnant kidney protection or were submitted only to remnant kidney irradiation. All groups received a single 6-Gy dose immediately after surgery. Whole-kidney function, glomerular hemodynamics, 24-hour proteinuria and histopathology were assessed 60 days after surgery and irradiation. The irradiated nephrectomized animals presented whole-kidney function parameters comparable to those of normal rats. In addition, they were less hypertensive and had higher hematocrit. They showed glomerular hyperfiltration and hypertension even greater than their respective nephrectomized controls. However, the interrelations among the glomerular filtration determinants were somewhat different in irradiated animals. Their 24-hour proteinuria was significantly lower and the sclerosis index and tubulointerstitial injury score were markedly smaller. Among irradiated animals, the worst sclerosis index was observed in those with a shielded remnant kidney and the best in those without protection of the remnant kidney. This led us to speculate about a possible influence of resident mesangial cells on the early events following renal mass ablation and on the maintenance of subsequent physiopathologic changes. Therefore, radiation undoubtedly provoked a beneficial change in the course of renal disease when the renal mass ablation model was employed. Many factors could have contributed to this favorable feature including lower levels of systemic arterial pressure, less increment in DeltaP, diminished proteinuria, and maintenance of tubulointerstitial space integrity. Our data also suggest that development of glomerulosclerosis seems to be determined by events occurring immediately after injury.

Acute effects on bone marrow after association between Radiosensitizer and X rays-NN/N method

A histopathological and morphometric study was performed in the bone marrow of mice after association of cisdiamminedi-choroplatinum II (3.0 mg/kg) plus X-rays (103.20 mC/Kg 400R). Rstimation of bone marrow effects was assessed by counting the number of non nucleated-erythrocytes (NN) and nucleated (N) cells, and establishing (NN/N) ratio. The morphomeric method used correlates and makes possible quantification of histopathologic changes of bone marrow through relation of vascular stroma and cellular parenchyma. It can be used as a biological dosimetry parameter and to estimate injury and recovery of hematologic evolution of different myelotoxic agents

Acute, subacute, and chronic x-ray effects on glomerular hemodynamics in rats.

In order to evaluate the effects of x-rays on glomerular hemodynamics, surgically exposed left kidneys of Munich-Wistar rats were irradiated with 15 Gy in a single dose. The animals were studied 45 min (acute group, n = 8), 14 days (subacute group, n = 7), and 60 days (chronic group, n = 7) after irradiation and compared with their respective controls. A decrease in total glomerular filtration (55%) and renal plasma flow (40%) rates with marked elevation of total renal vascular resistance (180%), p < 0.05, occurred within 45 min. Significant changes also occurred in the microcirculation; i.e., single-nephron glomerular filtration (SNGFR), glomerular plasma flow (QA), and glomerular capillary hydraulic pressure (PGC) declined by 35%, 40%, and 12%, respectively, due to an increase in total arteriolar resistance (90%), p < 0.05. Within 14 days, SNGFR was similar to control in spite of a moderate elevation of afferent arteriolar resistance (26%) and reduction in PGC (11%), p < 0.05, and QA (20%). Kf was significantly elevated (46%), p < 0.05. The chronic group presented a response pattern similar to that of the acute group, although less severe. Histopathological changes were not relevant and were restricted to tubules. The present results suggest that: (a) Acutely, there was a marked reduction in filtration, flow, and PGC with significant elevation of resistances. (b) Within 14 days, the maintenance of SNGFR was probably the result of an offsetting effect between QA and PGC decreases and Kf elevation. (c) After 60 days, the homeostatic mechanism was not sufficient to maintain normal renal function. (d) A functional effect is probably the most important pathogenetic mechanism, at least during the initial phase, for the development of radiation nephropathy since no morphological alterations were observed.

Ultrastructure of convoluted proximal tubule of kidney mice before and after X-ray exposure.

Ultrastructural initial changes study of convoluted proximal tubule after single dose of 154.8 mC/kg (600R), X-ray whole body radiation was performed in 12 C57BL mice. Twenty-four hours later, mitochondria evidenced proeminent changes such as cristolyses, dilatation and vacuolization. Within 72 hours, heterochromatin nuclei increased and vanished 144 hours after X-ray exposure. Such findings suggest that recovery probably happened because convoluted proximal tubules take place, regeneration occurs in a slow rate.

Evaluation of the effect of ionizing radiation of mouse hemocytopoietic tissue by reticulocyte count

The effects of exposure to a single, whole body X-ray dose of 154.8 mC/Kg (600 R) on mouse (Mus musculus) hemocytopoietic tissue were analyzed by means of reticulocyte counts in peripheral blood, evaluating indirectly variations of the erythrocyte sector of bone marrow. The efficiency of the method for the evaluation of this tissue was demonstrated, constituting one more radiobiologic parameter to corroborate those existing already

[Ultrastructural and morphometric study of the myeloid parenchyma cells of mice prior and after X-ray exposure]. / Estudo ultra-estrutural e morfométrico de células do parênquima mielóide de camundongos antes e depois da exposição aos raios X.

An electron microscopic study of initial X-ray changes in ultrastructures of bone marrow cells was performed. Such changes reached nucleous and cytoplasm organellas early (1 hour) after radiation, but were more proeminent later on. Subsequent readings (2, 6 hours) showed them more proeminent in cytoplasm structures, and the morphologic appearance was close to normal within 12, 14 days. Quantitative analyses were performed using the marrow recovery coefficient (MRC).

[Evaluation of the effects of ionizing radiation and cyclophosphamide on the bone marrow of mice, by counting non-nucleated and nucleated cells]. / Avaliação dos efeitos da radiação ionizante e da ciclofosfamida na medula óssea de camundongos, pela contagem das células não nucleadas e nucleadas.

Bone marrow injury after exposure to ionizing radiation and cyclophosphamide was evaluated by morphologic analysis and by the ratio erythrocytes/nucleated cells (NN/N). The authors show the efficiency of the method proposed, which can be determined in bone marrow samples of variable and unpredictable size.