Osteopontin expression in human and murine obesity: extensive local up-regulation in adipose tissue but minimal systemic alterations

Obesity is associated with a chronic low-grade inflammation characterized by macrophage infiltration of adipose tissue (AT) that may underlie the development of insulin resistance and type 2 diabetes. Osteopontin (OPN) is a multifunctional protein involved in various inflammatory processes, cell migration, and tissue remodeling. Because these processes occur in the AT of obese patients, we studied in detail the regulation of OPN expression in human and murine obesity. The study included 20 morbidly obese patients and 20 age- and sex-matched control subjects, as well as two models (diet-induced and genetic) of murine obesity. In high-fat diet-induced and genetically obese mice, OPN expression was drastically up-regulated in AT (40 and 80-fold, respectively) but remained largely unaltered in liver (<2-fold). Moreover, OPN plasma concentrations remained unchanged in both murine models of obesity, suggesting a particular local but not systemic importance for OPN. OPN expression was strongly elevated also in the AT of obese patients compared with lean subjects in both omental and sc AT. In addition, we detected three OPN isoforms to be expressed in human AT and, strikingly, an obesity induced alteration of the OPN isoform expression pattern. Analysis of AT cellular fractions revealed that OPN is exceptionally highly expressed in AT macrophages in humans and mice. Moreover, OPN expression in AT macrophages was strongly up-regulated by obesity. In conclusion, our data point toward a specific local role of OPN in obese AT. Therefore, OPN could be a critical regulator in obesity induced AT inflammation and insulin resistance.     

Mixtures of human intermediate and human regular insulin in type 1 diabetic patients. Evaluation of free insulin levels and insulin action on glucose metabolism after combined and separate subcutaneous administration

Recent resorption studies in healthy subjects suggest that intermediate human zinc insulin preparations might diminish the absorption and activity of human short-acting insulin when the two insulins are administered as a single, combined preparation. This study was designed to investigate whether combined and separate administration of human zinc or human NPH insulin with soluble human insulin have different pharmacokinetic characteristics, as evaluated by glucose clamp studies and determination of free insulin levels. Eight type 1 diabetic patients received, in random order, four different, subcutaneously injected preparations of human insulin. Zinc insulin (Monotard HM, Novo-M) and protamine insulin (Protaphan HM, Novo-P) were each given with short-acting insulin (Actrapid HM, Novo-A). These insulins were administered either as a single combined preparation (MA;PA) or as two separate injections (M + A; P + A). Prior to the insulin injection euglycemia was achieved by an overnight intravenous insulin infusion. After the subcutaneous injection of insulin, glucose was monitored at 10-min intervals and euglycemia was maintained by a variable glucose infusion rate for 6 h. The total glucose infusion rate during this period was significantly lower following MA compared with M + A (total glucose infusion: 643 +/- 117 vs. 817 +/- 130 mg/kg, P = 0.009) whereas the glucose infusion rate did not differ between PA and P + A (878 +/- 122 vs. 914 +/- 118 mg/kg, NS(ABSTRACT TRUNCATED AT 250 WORDS)     

Isolation and characterization of polymorphic microsatellite loci for Siphamia tubifer Weber (Perciformes: Apogonidae)

The cardinalfish Siphamia tubifer has been selected as a model for the study of genetic connectivity in reef-associated fishes among marine-protected-areas in Socotra Island in the northwestern Indian Ocean (part of the Socotra Archipelago, a UNESCO World Heritage Site since 2008). Twenty-six novel microsatellite markers are described for S. tubifer and are now available for studies on its genetic population structure. In a population sample from Socotra Island, the newly developed markers possessed between three and 20 alleles. Expected and observed heterozygosity ranged from 0.56–0.96 to 0.55–0.95, respectively. The markers did not show deviations from Hardy–Weinberg equilibrium and were not in linkage disequilibrium.     

Klinik,CRP, Calprotectin,MRT oder Endoskopie?

Close monitoring of the therapeutic efficacy and inflammation in inflammatory bowel diseases (IBD) is important in order to improve outcome and realize individualized treatment. As a symptom-based evaluation only has several limitations more objective tools are necessary. In this aspect C-reactive protein (CRP) especially in Crohn’s disease (CD) and fecal markers, such as calprotectin in both CD and ulcerative colitis (UC) have been shown to be associated with the inflammatory burden and endoscopic activity. Furthermore, they correlate well with treatment response and can be used in order to make a better prediction of disease relapse. Endoscopic evaluation is, however, still often necessary especially for important decisions on either treatment intensification or de-escalation. During therapy CRP and fecal markers can be used to evaluate efficacy and often make endoscopic interventions unnecessary. Ultrasound, magnetic resonance imaging (MRI) and capsule endoscopy are less well evaluated and are reserved for solitary cases. In summary, CRP, fecal calprotectin in addition to endoscopy represent important tools in order to optimize IBD treatment.     

Fine‐tuning of the automated [18F]PSMA‐1007 radiosynthesis

Radiolabeled prostate‐specific membrane antigen (PSMA) targeting PET‐tracers have become desirable radiopharmaceuticals for the imaging of prostate cancer (PC). Recently, the PET radiotracer [¹⁸F]PSMA‐1007 was introduced as an alternative to [⁶⁸Ga]Ga‐PSMA‐11, for staging and diagnosing biochemically recurrent PC. We incorporated a one‐step procedure for [¹⁸F]PSMA‐1007 radiosynthesis, using both Synthra RNplus and GE TRACERlab FxFN automated modules, in accordance with the recently described radiolabeling procedure. Although the adapted [¹⁸F]PSMA‐1007 synthesis resulted in repeatable radiochemical yields (55 ± 5%, NDC), suboptimal radiochemical purities of 87 ± 8% were obtained using both modules. As described here, modifications made to the radiolabeling and the solid‐phase extraction purification steps reduced synthesis time to 32 minutes and improved radiochemical purity to 96.10%, using both modules, without shearing the radiochemical yield.     

Characterization and Epitope Mapping of the Polyclonal Antibody Repertoire Elicited by Ricin Holotoxin-Based Vaccination

Ricin, one of the most potent and lethal toxins known, is classified by the Centers for Disease Control and Prevention (CDC) as a select agent. Currently, there is no available antidote against ricin exposure, and the most promising therapy is based on neutralizing antibodies elicited by active vaccination or that are given passively. The aim of this study was to characterize the repertoire of anti-ricin antibodies generated in rabbits immunized with ricin toxoid. These anti-ricin antibodies exhibit an exceptionally high avidity (thiocyanate-based avidity index, 9 M) toward ricin and an apparent affinity of 1 nM. Utilizing a novel tissue culture-based assay that enables the determination of ricin activity within a short time period, we found that the anti-ricin antibodies also possess a very high neutralizing titer. In line with these findings, these antibodies conferred mice with full protection against pulmonary ricinosis when administered as a passive vaccination. Epitope mapping analysis using phage display random peptide libraries revealed that the polyclonal serum contains four immunodominant epitopes, three of which are located on the A subunit and one on the B subunit of ricin. Only two of the four epitopes were found to have a significant role in ricin neutralization. To the best of our knowledge, this is the first work that characterizes these immunological aspects of the polyclonal response to ricin holotoxin-based vaccination. These findings provide useful information and a possible strategy for the development and design of an improved ricin holotoxin-based vaccine.     

Case report of anorexia nervosa associated with Wilson's disease

Wilson's disease is a recessively inherited disorder of copper metabolism with prominent hepatic, hematopoetic, central nervous system (CNS), and ocular involvement. Psychiatric manifestations are notoriously variable. The following case history of a patient with both anorexia nervosa and Wilson's disease is presented and discussed in the context of organic CNS lesions associated with anorexia nervosa-like syndromes. © 1993 by John Wiley & Sons, Inc.