An early but intense cytokine production within the islets may be predictive for type 1 diabetes occurrence in the Bio Breeding (BB) rat

The Bio Breeding (BB) rat is a useful animal model of type 1 autoimmune diabetes. The aim of this study was to observe and follow the cytokine and antigenic expressions within the islets of Langerhans in young non-diabetic, in pre-diabetic hyperglycemic, and in overtly diabetic animals. BB rats were therefore checked at day 21 up to day 90 of life for blood glucose, insulin levels, degree of islet infiltration, expression of proinflammatory and protective cytokines and antibodies including CD4, CD8, CD25, LFA-1, and ICAM-1. Animals were treated with insulin as they became diabetic. We found that islets of non-diabetic BB rats became positive to both IL-1beta and IL-4 very early on, confirming a local but intense production of both cytokines within the islets during the initial non-diabetic period. In addition, we observed that the production of these interleukins together with the expression levels of CD4 and CD25 are events predictive for type 1 diabetes onset in non-diabetic BB rats, as for non-obese diabetic (NOD) mice. In particular, the production of IL-1beta and IL-4 during the non-diabetic period together with the lack of enhancement of CD4 and CD25, indicating selective recruitment of activated T cells, may explain the failure of anti-diabetic treatments in this animal model of type 1 diabetes.     

MitoNuc: a database of nuclear genes coding for mitochondrial proteins. Update 2002

Mitochondria, besides their central role in energy metabolism, have recently been found to be involved in a number of basic processes of cell life and to contribute to the pathogenesis of many degenerative diseases. All functions of mitochondria depend on the interaction of nuclear and organelle genomes. Mitochondrial genomes have been extensively sequenced and analysed and data have been collected in several specialised databases. In order to collect information on nuclear coded mitochondrial proteins we developed MitoNuc, a database containing detailed information on sequenced nuclear genes coding for mitochondrial proteins in Metazoa. The MitoNuc database can be retrieved through SRS and is available via the web site http://bighost.area.ba.cnr.it/mitochondriome where other mitochondrial databases developed by our group, the complete list of the sequenced mitochondrial genomes, links to other mitochondrial sites and related information, are available. The MitoAln database, related to MitoNuc in the previous release, reporting the multiple alignments of the relevant homologous protein coding regions, is no longer supported in the present release. In order to keep the links among entries in MitoNuc from homologous proteins, a new field in the database has been defined: the cluster identifier, an alpha numeric code used to identify each cluster of homologous proteins. A comment field derived from the corresponding SWISS-PROT entry has been introduced; this reports clinical data related to dysfunction of the protein. The logic scheme of MitoNuc database has been implemented in the ORACLE DBMS. This will allow the end-users to retrieve data through a friendly interface that will be soon implemented.     

New arylsparteine derivatives as positive inotropic drugs

Positive inotropic agents are fundamental in the treatment of heart failure; however, their arrhythmogenic liability and the increased myocardial oxygen demand strongly limit their therapeutic utility. Pursuing our study on cardiovascular activities of lupin alkaloid derivatives, several 2-(4-substituted-phenyl)-2-dehydrosparteines and 2-(4-substituted-phenyl)sparteines were prepared and tested for inotropic and chronotropic activities on isolated guinea pig atria. Four compounds (6b, 6e, 7b, and 7f) exhibited significant inotropism that, at the higher concentrations, was followed by negative inotropism or toxicity. Compound 7e (2-(4-tolyl)sparteine) exhibited a steep dose-depending inotropic activity up to the highest concentration tested (300?µM) with an E_max of 116.5?±?3.4% of basal force, proving less potent but much more active in comparison to the highest concentrations tested of digoxin and milrinone having E_max of 87.5?±?3.1% and 52.2?±?1.1%, respectively. Finally, docking studies suggested that the relevant sparteine derivatives could target the sigma-1 receptor, whose involvement in cardiac activity is well documented.     

Structural investigations on the inner core region of lipopolysaccharides from Salmonella minnesota rough mutants

The structure of the inner core region (L-glycero-D-mannoheptose/2-keto-3-deoxy-D-mannooctulosonic acid region) of lipopolysaccharides from Salmonella minnesota rough mutants was investigated. Using conventional methods (neutral sugar analysis, Smith degradation and methylation analysis) combined with gas chromatography/mass spectrometry (GC/MS) of higher oligosaccharides (up to tetrasaccharide), the linkages of the core sugars of lipopolysaccharides from S. minnesota rough mutants, strains R4 (Rd2P-), R7 (Rd1P-) and R5 (RcP-) were determined as: (formula see text) with R representing H in R4, L-glycero-D-mannoheptopyranosyl in R7, and D-glucopyranosyl-(1----3)-L-glycero-D-mannoheptopyranosyl in R5, respectively. In addition, it is shown that heterogeneity within the neutral sugar part of these lipopolysaccharides is low.     

Cultivation of the warble-fly Oestromyia leporina pall. (Diptera, Hypodermatidae) and its biological prerequisites (author's transl)]

The warble-fly Oestromyia leporina was cultivated for four generations in the laboratory. In the present paper the technic of laboratory mating and the modus of experimental infection of the host are described. The fertility of females is tested by experiments and by dissections. It is shown how the diapause of the puparia can be shortened and how it can be omitted. The successful infection of several species of small mammals demonstrates that O. leporina can be colonized not only on the natural host but also on some common laboratory animals like mice and rats.     

Pigmentation Genes Show Evidence of Repeated Divergence and Multiple Bouts of Introgression in Setophaga Warblers

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