Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists

The uptake of radiolabeled somatostatin analogs by tumor cells through receptor-mediated internalization is a critical process for the in vivo targeting of tumoral somatostatin receptors. In the present study, the somatostatin receptor internalization induced by a variety of somatostatin analogs was measured with new immunocytochemical methods that allow characterization of trafficking of the somatostatin receptor subtype 2 (sst2), somatostatin receptor subtype 3 (sst3), and somatostatin receptor subtype 5 (sst5) in vitro at the protein level. METHODS: Human embryonic kidney 293 (HEK293) cells expressing the sst2, sst3, or the sst5 were used in a morphologic immunocytochemical internalization assay using specific sst2, sst3 and sst5 antibodies to qualitatively and quantitatively determine the capability of somatostatin agonists or antagonists to induce somatostatin receptor internalization. In addition, the internalization properties of a selection of these agonists have been compared and quantified in sst2-expressing CHO-K1 cells using an ELISA. RESULTS: Agonists with a high sst2-binding affinity were able to induce sst2 internalization in the HEK293 and CHO-K1 cell lines. New sst2 agonists, such as Y-DOTA-TATE, Y-DOTA-NOC, Lu-DOTA-BOC-ATE (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; TATE is [Tyr3, Thr8]-octreotide; NOC is [1-NaI3]-octreotide; and BOC-ATE is [BzThi3, Thr8]-octreotide), iodinated sugar-containing octreotide analogs, or BIM-23244 were considerably more potent in internalizing sst2 than was DTPA-octreotide (where DTPA is diethylenetriaminepentaacetic acid). Similarly, compounds with high sst3 affinity such as KE108 were able to induce sst3 internalization. In sst2- or sst3-expressing cell lines, agonist-induced receptor internalization was efficiently abolished by sst2- or sst3-selective antagonists, respectively. Antagonists alone had no effect on sst2 or sst3 internalization. We also showed that somatostatin-28 and somatostatin-14 can induce sst5 internalization. Unexpectedly, however, potent sst5 agonists such as KE108, BIM-23244, and L-817,818 were not able to induce sst5 internalization under the same conditions. CONCLUSION: Using sensitive and reproducible immunocytochemical methods, the ability of various somatostatin analogs to induce sst2, sst3, and sst5 internalization has been qualitatively and quantitatively determined. Whereas all agonists triggered sst2 and sst3 internalization, sst5 internalization was induced by natural somatostatin peptides but not by synthetic high-affinity sst5 agonists. Such assays will be of considerable help for the future characterization of ligands foreseen for nuclear medicine applications.

Mapping of a new locus for congenital anomalies of the kidney and urinary tract on chromosome 8q24

Congenital anomalies of the kidney and urinary tract (CAKUT) account for the majority of end-stage renal disease in children (50%). Previous studies have mapped autosomal dominant loci for CAKUT. We here report a genome-wide search for linkage in a large pedigree of Somalian descent containing eight affected individuals with a non-syndromic form of CAKUT.

Fourier transform infrared spectroscopy, a new method for rapid determination of total organic and inorganic carbon and biogenic silica concentration in lake sediments

Abstract We demonstrate the use of Fourier transform infrared spectroscopy (FTIRS) to make quantitative measures of total organic carbon (TOC), total inorganic carbon (TIC) and biogenic silica (BSi) concentrations in sediment. FTIRS is a fast and costeffective technique and only small sediment samples are needed (0.01 g). Statistically significant models were developed using sediment samples from northern Sweden and were applied to sediment records from Sweden, northeast Siberia and Macedonia. The correlation between FTIRS-inferred values and amounts of biogeochemical constituents assessed conventionally varied between r = 0.84–0.99 for TOC, r = 0.85– 0.99 for TIC, and r = 0.68–0.94 for BSi. Because FTIR spectra contain information on a large number of both inorganic and organic components, there is great potential for FTIRS to become an important tool in paleolimnology.

New Algorithms for M-Estimation of Multivariate Scatter and Location

We present new algorithms for M-estimators of multivariate scatter and location and for symmetrized M-estimators of multivariate scatter. The new algorithms are considerably faster than currently used fixed-point and related algorithms. The main idea is to utilize a second order Taylor expansion of the target functional and to devise a partial Newton-Raphson procedure. In connection with symmetrized M-estimators we work with incomplete U-statistics to accelerate our procedures initially.

Bouveret's syndrome: presentation of two cases with review of the literature and development of a surgical treatment strategy

BACKGROUND Bouveret's syndrome causes gastric outlet obstruction when a gallstone is impacted in the duodenum or stomach via a bilioenteric fistula. It is a rare condition that causes significant morbidity and mortality and often occurs in the elderly with significant comorbidities. Individual diagnostic and treatment strategies are required for optimal management and outcome. The purpose of this paper is to develop a surgical strategy for optimized individual treatment of Bouveret's syndrome based on the available literature and motivated by our own experience. CASE PRESENTATION Two cases of Bouveret's syndrome are presented with individual management and restrictive surgical approaches tailored to the condition of the patients and intraoperative findings. CONCLUSIONS Improved diagnostics and restrictive individual surgical approaches have shown to lower the mortality rates of Bouveret's syndrome. For optimized outcome of the individual patient: The medical and perioperative management and time of surgery are tailored to the condition of the patient. CT-scan is most often required to secure the diagnosis. The surgical approach includes enterolithotomy alone or in combination with simultaneous or subsequent cholecystectomy and fistula repair. Lower overall morbidity and mortality are in favor of restrictive surgical approaches. The surgical strategy is adapted to the intraoperative findings and to the risk for secondary complications vs. the age and comorbidities of the patient.

Role of Crop Research and Development in food Security of Africa

Food security is the main concern in Africa as the production and productivity of crops are under continuous threat. Indigenous crops also known as orphan- or as underutilized- crops provide key contributions to food security under the present scenario of increasing world population and changing climate. Hence, these crops which belong to the major categories of cereals, legumes, fruits and root crops play a key role in the livelihood of the resource-poor farmers and consumers since they perform better than the major world crops under extreme soil and climate conditions prevalent in the continent. These indigenous crops have the major advantage that they fit well into the general socio-economic and ecological context of the region. However, despite their huge importance, African crops have generally received little attention by the global scientific community. With the current production systems, only a fraction of yield potential was achieved for most of these crops. In order to devise strategies towards boosting crop productivity in Africa, the current production constraints should be investigated and properly addressed. Key traits known to increase productivity and/or improve nutrition and diverse conventional and modern crop improvement techniques need to be implemented. Commitments in the value-chain from the research, production, marketing to distribution of improved seeds are required by relevant national and international institutions as well as African governments to promote food security in a sustainable manner. The review also presents major achievements and suggestions for stakeholders interested in African agriculture.

Preischemic iloprost application for improvement of graft preservation: which route is superior in experimental pig lung transplantation: inhaled or intravenous?

BACKGROUND: Optimal allograft protection is essential in lung transplantation to reduce postoperative organ dysfunction. Although intravenous prostanoids are routinely used to ameliorate reperfusion injury, the latest evidence suggests a similar efficacy of inhaled prostacyclin. Therefore, we compared donor lung-pretreatment using inhaled lioprost (Ventavis) with the commonly used intravenous technique. METHODS: Five pig lungs were each preserved with Perfadex and stored for 27 hours without (group 1) or with (group-2, 100 prior aerosolized of iloprost were (group 3) or iloprost (IV). Following left lung transplantation, hemodynamics, Po(2)/F(i)o(2), compliance, and wet-to-dry ratio were monitored for 6 hours and compared to sham controls using ANOVA analysis with repeated measures. RESULTS: The mortality was 100% in group 3. All other animals survived (P < .001). Dynamic compliance and PVR were superior in the endobronchially pretreated iloprost group as compared with untreated organs (P < .05), whereas oxygenation was comparable overall W/D-ratio revealed significantly lower lung water in group 2 (P = .027) compared with group 3. CONCLUSION: Preischemic alveolar deposition of iloprost is superior to IV pretreatment as reflected by significantly improved allograft function. This strategy offers technique to optimize pulmonary preservation.

Self-made pericardial tube graft: a new surgical concept for treatment of graft infections after thoracic and abdominal aortic procedures

The aim of this study was to evaluate a new surgical concept for the treatment of graft infections after operation or endovascular treatment of thoracic, thoracoabdominal, and abdominal aortic diseases.

Serial analysis of the malapposed and uncovered struts of the new generation of everolimus-eluting bioresorbable scaffold with optical coherence tomography

The aim of this study is to assess the serial changes in strut apposition and coverage of the bioresorbable vascular scaffolds (BVS) and to relate this with the presence of intraluminal masses at 6 months with optical coherence tomography (OCT).