Role of mitochondria in metabolism-secretion coupling of insulin release in the pancreatic beta-cell

The control of insulin secretion from the pancreatic beta-cell involves a complex cascade of events in which the mitochondria play a central role. In the consensus model this role is essentially restricted to the production of ATP promoting membrane depolarisation and a rise in cytosolic [Ca2+]. Evidence for the generation of an additional mitochondrial factor implicated in metabolism-secretion coupling is provided in this review. Although not yet identified, the formation of this putative factor requires an increase of [Ca2+] in the mitochondrial matrix together with a supply of carbons to the tricarboxylic acid (TCA) cycle. In this model, calcium activates matrix dehydrogenases, in particular those of the TCA cycle. This enables the synthesis of the mitochondrial factor from the TCA cycle intermediates. Experimental evidence gathered in permeabilised cells largely supports this model.     

The psychosomatic network: foundations of mind-body medicine

Research in the 1980s uncovered ubiquitous neuropeptide-receptor distribution in brain structures associated with emotional processing, and throughout many organ systems. This finding supported neuropeptides as biochemical substrates of emotion, and the neuropeptide-receptor network as a parasynaptic system crossing traditional brain-body boundaries. The medical relevance of these findings was affirmed by psychoneuroimmunology research: neuropeptides help to regulate immunocyte trafficking, there is bidirectional communication between nervous and immune system components, immunocytes produce neuropeptides, and nerve cells produce immune-associated cytokines. In the past decade, the concept of a unified psychosomatic network has been strengthened by animal and human research demonstrating relationships between behavior and neuropeptide-mediated regulation of immune functions. Research on emotional expression or disclosure in healthy human subjects as well as in cancer and HIV-positive patients has shown significant positive correlations with clinically relevant immune functions and/or positive health outcomes. Psychosocial interventions emphasizing emotional expression or active coping have evidenced survival benefits in breast cancer and melanoma. These findings suggest that emotional expression generates balance in the neuropeptide-receptor network and a functional healing system. Emotional expression is also a marker for psychospiritual vitalization, and further research should evaluate links between energy-based models of health and neuropeptide-receptor-based models under the rubric of an informational paradigm.     

Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial

OBJECTIVE: We examined the effects of aprotinin on graft patency, prevalence of myocardial infarction, and blood loss in patients undergoing primary coronary surgery with cardiopulmonary bypass. METHODS: Patients from 13 international sites were randomized to receive intraoperative aprotinin (n = 436) or placebo (n = 434). Graft angiography was obtained a mean of 10.8 days after the operation. Electrocardiograms, cardiac enzymes, and blood loss and replacement were evaluated. RESULTS: In 796 assessable patients, aprotinin reduced thoracic drainage volume by 43% (P < .0001) and requirement for red blood cell administration by 49% (P < .0001). Among 703 patients with assessable saphenous vein grafts, occlusions occurred in 15.4% of aprotinin-treated patients and 10.9% of patients receiving placebo (P = .03). After we had adjusted for risk factors associated with vein graft occlusion, the aprotinin versus placebo risk ratio decreased from 1.7 to 1.05 (90% confidence interval, 0.6 to 1.8). These factors included female gender, lack of prior aspirin therapy, small and poor distal vessel quality, and possibly use of aprotinin-treated blood as excised vein perfusate. At United States sites, patients had characteristics more favorable for graft patency, and occlusions occurred in 9.4% of the aprotinin group and 9.5% of the placebo group (P = .72). At Danish and Israeli sites, where patients had more adverse characteristics, occlusions occurred in 23.0% of aprotinin- and 12.4% of placebo-treated patients (P = .01). Aprotinin did not affect the occurrence of myocardial infarction (aprotinin: 2.9%; placebo: 3.8%) or mortality (aprotinin: 1.4%; placebo: 1.6%). CONCLUSIONS: In this study, the probability of early vein graft occlusion was increased by aprotinin, but this outcome was promoted by multiple risk factors for graft occlusion.     

Crypt-equivalent algebraic specifications

Summary Equivalence is a fundamental notion for the semantic analysis of algebraic specifications. In this paper the notion of crypt-equivalence is introduced and studied w.r.t. two loose approaches to the semantics of an algebraic specification T: the class of all first-order models of T and the class of all term-generated models of T. Two specifications are called crypt-equivalent if for one specification there exists a predicate logic formula which implicitly defines an expansion (by new functions) of every model of that specification in such a way that the expansion (after forgetting unnecessary functions) is homologous to a model of the other specification, and if vice versa there exists another predicate logic formula with the same properties for the other specification. We speak of first-order crypt-equivalence if this holds for all first-order models, and of inductive crypt-equivalence if this holds for all term-generated models. Characterizations and structural properties of these notions are studied. In particular, it is shown that first order crypt-equivalence is equivalent to the existence of explicit definitions and that in case of positive definability two first-order crypt-equivalent specifications admit the same categories of models and homomorphisms. Similarly, two specifications which are inductively crypt-equivalent via sufficiently complete implicit definitions determine the same associated categories. Moreover, crypt-equivalence is compared with other notions of equivalence for algebraic specifications: in particular, it is shown that first-order cryptequivalence is strictly coarser than abstract semantic equivalence and that inductive crypt-equivalence is strictly finer than inductive simulation equivalence and implementation equivalence.     

Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.     

Etude electrochimique de differentes ilmenites

The electrochemical behaviour of several natural ilmenites has been studied by cyclic voltammetry. From the analysis of the current-voltage curves it was concluded that the valences of the metal ions in FeTiO₃ are Fe^II and Ti^IV. It was also found that little amounts of Fe^III and excess of Ti^IV (probably TiO₂) can enter into the composition of the ilmenites.     

Characterization of Precursor-Derived Silicon-Carbon-Nitrogen Ceramics after Creep Testing

Precursor-derived Si-C-N ceramics after creep testing in air were characterized using X-ray diffractometry (XRD) and transmission electron microscopy (TEM). XRD analysis showed that the crept Si-C-N ceramics were covered by an α-cristobalite layer. TEM observations revealed that the precipitated nanocrystallites in the crept Si-C-N ceramics were β-SiC. Between α-cristobalite and crept Si-C-N ceramic, there was an intermediate zone in which Si₂N₂O nanocrystallites were distributed homogeneously. Moreover, Si₂N₂O nanocrystallites were often found covering the surface of nanosized gas channels in the crept Si-C-N ceramics, where no α-cristobalite phase was detected. Based on these observations, a two-step oxidation mechanism of Si-C-N ceramics during creep testing in air was proposed.     

An axisymmetric model for thread forming in polycarbonate and polypropylene screw and boss fasteners

Plastic boss and screw fasteners are an economical means of securing automotive components, such as instrument or body panels. However, new materials and/or suboptimal design present challenges to the boss/screw effectiveness. Failure of a boss/screw can result is loss of functional performance or increased squeak and rattle. Failure is often controlled by what occurs during the initial thread‐forming process. Thus, the goal of this paper is to develop an FEA model to elucidate the thread‐forming process so that we can facilitate subsequent design and/or process optimization, and understand potential failure modes. The FEA must accommodate nonlinear couplings, such as large strain and heat transfer. Heat generation is present in the forms of interfacial shear heating and plastic work associated with the large deformation of the interface between the boss and screw. Strain rate‐dependent materials are included using the Eyring theory for plastic flow of polymeric materials. Results of the model are presented and compared to experimentally determined torque curves and temperatures. Polym. Eng. Sci. 44:1498–1508, 2004. © 2004 Society of Plastics Engineers.