Chronological response of prostacyclin changes to moderately low doses of radiation in rat cervical spinal cord

Background: Study of vascular and its secretory profile changes is an important issue in pathogenesis of radiation myelopathy. This paper reports the prostacyclin concentration changes after low-moderate doses of X-irradiation within a short period of time. Materials and Methods: Cervical cords of Wistar rats were irradiated to doses of 0.5, 1, 2, 4 and 6 Gy X-rays. After 24 hours, 2 and 13 weeks post-irradiation, prostacyclin contents were quantified and cords specimens were also stained routinely for histological studies. Results: Twenty four hours post-irradiation, showed a decrease in the content of prostacyclin after doses of 0.5 and 1 Gy 91.67±1.47 96.80±2.17 of respectively age-matched control group. After 2 weeks the concentration of prostacyclin showed significant decreases after 6 Gy. After 13 weeks irradiation shows marked differences even after a small dose of 2 Gy (p<0.001), and after doses of the low dose group. The differences between concentration values at doses of 4 Gy and 6 Gy were significant in comparison with the control (p<0.001 and p<0.002, respectively). Conclusion: Results suggested that the response of the vascular tissues to low and moderate doses of radiation occurs prior to that of the nervous tissue of the spinal cord. It means that the asymptomatic interval after radiation is characterized by sequential physiological changes which are imperfectly reflected in routine histological study and that even in the histologically unaffected spinal cord; severe impairment is present in substructures and biochemistry of irradiated spinal

Common iliac aneurysms with short or absent proximal necks: Endoluminal repair with a covered endoprosthesis

AbstractEur J Vasc Endovasc Surg 26, 334-336 (2003

Fiducial markers in prostate cancer image-guided radiotherapy

Background: Image-guided radiotherapy (IGRT) is recommended to reduce the risk of geometrical miss when modern radiotherapy technologies with high grades of conformity are used. The purpose of this study was to evaluate the efficacy of fiducial markers (FMs) for electronic portal imaging in prostate cancer radiotherapy in term of evaluating the complications associated with FMs implantation, quantifying inter-fraction prostate motion, and determination of optimal planning target volume (PTV) margins. Methods: In this single institution, prospective, consecutive study, 27 patients underwent implantation of three-gold seed FMs into the prostate gland before prostate radiotherapy. Prior to computed tomography planning, all patients were asked to report any complication associated with FMs implantation that have experienced to date. Daily pre-treatment electronic portal images were captured, and prostate position errors were corrected if they were greater than 2 mm along three translational directions. Optimal PTV expansions were computed using van Herk formula PTV-margin= 2.5Z + 0.7a. Results: FMs implantation was successful with an acceptable toxicity profile in all patients. Without IGRT, margins of 5.4 mm, 5.8 mm and 5.5 mm, in vertical, longitudinal and lateral directions, respectively, are needed for a 95% confidence level of complete clinical target volume (CTV) coverage in each treatment session. The PTV margins of 3.0 mm, 3.3 mm and 4.0 mm in corresponding directions were calculated when FMs based electronic portal imaging was applied. Conclusion: FMs based electronic portal imaging is an effective tool for prostate cancer IGRT. © Iran University of Medical Sciences

Prospective Acid Reflux Study of Iran (PARSI): Methodology and study design

<p>Abstract</p> <p>Background</p> <p>Gastroesophageal reflux disease is a common and chronic disorder but long term, prospective studies of the fate of patients seeking medical advice are scarce. This is especially prominent when looking at non-erosive reflux disease (NERD) patients.</p> <p>Methods</p> <p>We designed a prospective cohort to assess the long term outcome of GERD patients referring to gastroenterologists. Consecutive consenting patients, 15 years of age and older, presenting with symptoms suggestive of GERD referring to our outpatient clinics undergo a 30 minute interview. Upper gastrointestinal endoscopy is performed for them with protocol biopsies and blood samples are drawn. Patients are then treated according to a set protocol and followed regularly either in person or by telephone for at least 10 years.</p> <p>Discussion</p> <p>Our data show that such a study is feasible and follow-ups, which are the main concern, can be done in a fairly reliable way to collect data. The results of this study will help to clarify the course of various subgroups of GERD patients after coming to medical attention and their response to treatment considering different variables. In addition, the basic symptoms and biological database will fuel further molecular epidemiologic studies.</p

Effect of thrombin peptide 508 (TP508) on bone healing during distraction osteogenesis in rabbit tibia

Thrombin-related peptide 508 (TP508) accelerates bone regeneration during distraction osteogenesis (DO). We have examined the effect of TP508 on bone regeneration during DO by immunolocalization of Runx2 protein, a marker of osteoblast differentiation, and of osteopontin (OPN) and bone sialoprotein (BSP), two late markers of the osteoblast lineage. Distraction was performed in tibiae of rabbits over a period of 6 days. TP508 (30 or 300 μg) or vehicle was injected into the distraction gap at the beginning and end of the distraction period. Two weeks after active distraction, tissue samples were harvested and processed for immunohistochemical analysis. We also tested the in vitro effect of TP508 on Runx2 mRNA expression in osteoblast-like (MC3T3-E1) cells by polymerase chain reaction analysis. Runx2 and OPN protein were observed in preosteoblasts, osteoblasts, osteocytes of newly formed bone, blood vessel cells and many fibroblast-like cells of the soft connective tissue. Immunostaining for BSP was more restricted to osteoblasts and osteocytes. Significantly more Runx2- and OPN-expressing cells were seen in the group treated with 300 μg TP508 than in the control group injected with saline or with 30 μg TP508. However, TP508 failed to increase Runx2 mRNA levels significantly in MC3T3-E1 cells after 2–3 days of exposure. Our data suggest that TP508 enhances bone regeneration during DO by increasing the proportion of cells of the osteoblastic lineage. Clinically, TP508 may shorten the healing time during DO; this might be of benefit when bone regeneration is slow

Insulin-like growth factor binding protein 3 chemosensitizes pancreatic ductal adenocarcinoma through its death receptor

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. Gemcitabine and doxorubicin are commonly used as the chemotherapy agents, but most of PDAC tumors eventually acquired resistance to chemotherapy. Accumulating evidence indicates that Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role against tumor growth but its expression has commonly suppressed. The present study was designed to evaluate IGFBP-3 effects in chemotherapy sensitization of PDAC cells. Here, we report that the re-sensitization of chemoresistant PDAC cells was occurred by IGFBP-3 through recruitment of its death receptor (IGFBP-3R). Using gemcitabine, doxorubicin-resistant PDAC cell lines, we found that IGFBP-3 sensitized chemoresistant cells by activating apoptosis (as evaluated by Bax up-regulation, Bcl-2 down-regulation as well as Caspase-3 and Caspase 8 activation). IGFBP-3R was also found to have higher expression level in resistant AsPc-1 and MIA PaCa-2 cells in comparison to parental cells. IGFBP-3R was also highly expressed in PDAC tumor which exposed to chemotherapy in comparison to un-treated PDAC tumors. In addition, we confirmed our finding by using specific siRNA to knocking down of IGFBP-3R which prevents IGFBP-3 Chemosensitization. Taken together, the present study for the first time indicates the clinical relevance for combining IGFBP-3 with chemotherapy to reduce chemoresistance in PDAC

Crystal structure of the surfactin synthetase-activating enzyme sfp: a prototype of the 4'-phosphopantetheinyl transferase superfamily.

The Bacillus subtilis Sfp protein activates the peptidyl carrier protein (PCP) domains of surfactin synthetase by transferring the 4'-phosphopantetheinyl moiety of coenzyme A (CoA) to a serine residue conserved in all PCPs. Its wide PCP substrate spectrum renders Sfp a biotechnologically valuable enzyme for use in combinatorial non-ribosomal peptide synthesis. The structure of the Sfp-CoA complex determined at 1.8 A resolution reveals a novel alpha/beta-fold exhibiting an unexpected intramolecular 2-fold pseudosymmetry. This suggests a similar fold and dimerization mode for the homodimeric phosphopantetheinyl transferases such as acyl carrier protein synthase. The active site of Sfp accommodates a magnesium ion, which is complexed by the CoA pyrophosphate, the side chains of three acidic amino acids and one water molecule. CoA is bound in a fashion that differs in many aspects from all known CoA-protein complex structures. The structure reveals regions likely to be involved in the interaction with the PCP substrate