IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.

Interferon-alpha (IFN-alpha) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomas in vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-alpha1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferation in vitro by 40% at 10(3) U/mL (p = 0.028). In vivo, IFN-alpha1,8 inhibited SVR tumor volume by 71% (p = 0.047) and MS1-VEGF volume by 79% (p = 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p = 0.005) and in MS1-VEGF tumors by 58% (p = 0.001). Sera from IFN-alpha1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p = 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-alpha1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p < 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p = 0.001). Given the magnitude of the in vivo response, these data suggested that the antitumor effects of IFN-alpha1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation.     

Topography of median eminence somatostatinergic innervation

Somatostatin (SRIF) in the central nervous system is mostly concentrated in the median eminence (ME). Immunocytochemical methods have revealed high densities of SRIF-positive perikarya between the preoptic area and the periventricular nucleus of the hypothalamus (NPE). The aim of the present study was to define more precisely the specific pathways of SRIF neurons from NPE to the ME. SRIF levels were measured by radioimmunoassay, following various hypothalamic transections. Frontal periventricular sections decreased SRIF-ME content by 70% (P less than 0.01), when located at the anterior end of the ME but no diminution was observed when the cuts were located anteriorly or posteriorly. Parasaggital transections decreased SRIF-ME levels by 50% (P less than 0.05) when located at the outer border of the ventromedial and premammillary nucleus, but the decrease was not significant when cuts were located anteriorly. Taken together, our data indicate that most SRIF-containing neurons, originating in the NPE, do not reach the ME directly along the border of the 3rd ventricle; instead they form a loop across the medial forebrain bundle before re-entering the mediobasal hypothalamus at the ME level.     

The effect of estradiol valerate and allylestrenol on endometrial transformation in hypergonadotropic hypogonadic women

The effect of estradiol valerate and allylestrenol on the endometrial transformation of five hypergonadotropic hypogonadic women was evaluated. Estradiol valerate was administered throughout the whole induced cycle (28 days), while allylestrenol was added during the second half of the cycle. Endometrial biopsies were performed during allylestrenol treatment and were evaluated histologically. Samples of endometrium were also subjected to one-dimensional SDS electrophoresis. Of ten biopsies performed, only one was interpreted to be in-phase, while the others were dated proliferative (4 biopsies) or showed abortive or out-of-phase secretory transformation. The highest mean serum progesterone level, detected under allylestrenol treatment, was 1.5 ng/ml. Protein electrophoresis demonstrated relative sequential changes in the protein patterns of the 115 kDa and 150 kDa protein bands. It is concluded that allylestrenol, although having gestagen properties, may not be efficient for the induction of an adequate secretory transformation of human endometrium in the absence of ovaries.     

Feasibility of near real-time image-guided sinus surgery using intraoperative fluoroscopic computed axial tomography.

OBJECTIVE: One of the main limitations of image-guided surgery is that navigation relies on the use of a CT scan obtained before surgery and is unable to be updated during the procedure. A software addition has been developed to allow reconstruction of CT-like images from a series of fluoroscopic scans and integrate these into an image-guided system (GE Healthcare Surgical Navigation, Lawrence, MA). We report our initial experience with a series of patients undergoing intraoperative fluoroscopic navigation in sinus surgery. STUDY DESIGN AND SETTINGS: After institutional review board clearance, we prospectively studied 14 consecutive patients undergoing image-guided sinus surgery with the use of intraoperative fluoroscopy. RESULTS: All patients had preoperative and postoperative fluoroscopic images reconstructed into CT-like images. By the conclusion of the study, images were adequate in quality and accurate navigation was achieved. CONCLUSION: Real-time image-guided sinus surgery using fluoroscopy is feasible. Future studies will need to focus on defining the procedures that could benefit, such as tumor resection, to enhance patient safety during these operations.     

Regional distribution of somatostatin binding sites in the human hypothalamus: a quantitative autoradiographic study.

Using in vitro quantitative autoradiography and [125I]Tyr0-D-Trp8SRIF 14 as radioligand, we characterized the detailed distribution of somatostatin binding sites in human hypothalamus of both infants and adults. Guanosine triphosphate pretreatment, before incubation, allowed us to detect higher [125I]Tyr0-D-Trp8SRIF 14 binding site densities in hypothalamic structures such as preoptic and anterior hypothalamic areas and ventromedial and dorsomedial nuclei. In contrast, guanosine triphosphate was without effect in the other hypothalamic regions. The regional effects of guanosine triphosphate pretreatment were not different in infant and adult hypothalamus. Scatchard analysis showed that in a guanosine triphosphate-sensitive region (preoptic area) and a guanosine triphosphate-insensitive area (infundibular nucleus), [125I]Tyr0-D-Trp8SRIF 14 bound to a single class of binding sites. Affinities were similar in both regions, not modified by guanosine triphosphate pretreatment and not different in the adult (1.5 +/- 1.2 nM vs 3.2 +/- 2.1 nM for preoptic area and infundibular nucleus, respectively) and infant (0.9 +/- 0.5 nM vs 2.4 +/- 1.7 nM for preoptic area and infundibular nucleus). [125I]Tyr0-D-Trp8SRIF 14 binding sites were widely distributed in the anterior, mediobasal and posterior hypothalamus. Somatostatin 28 was twice as potent as somatostatin 14 to displace [125I]Tyr0-D-Trp8SRIF 14 binding in the preoptic area and infundibular nucleus. However, IC50s were 30 times lower in the preoptic area as compared with the infundibular nucleus. In adult as well as in infant, high densities were found mainly in the diagonal band of Broca, preoptic area and infundibular nucleus. Intermediate densities were localized in the anterior hypothalamic area, ventromedial, dorsomedial and lateral mammillary nuclei. The dorsal hypothalamic area, the paraventricular and medial mammillary nuclei displayed low but measurable densities. The only marked difference in the distribution of [125I]Tyr0-D-Trp8SRIF 14 binding sites in adult vs infant was observed in the medial and tuberal nuclei where the concentrations were seven-fold higher in adult hypothalamus.