Human infection with non-typhoidal Salmonella serovars (NTS) infrequently causes invasive systemic disease and bacteremia. To understand better the nature of invasive NTS (iNTS), we studied the gene content and the pathogenicity of bacteremic strains from twelve serovars (Typhimurium, Enteritidis, Choleraesuis, Dublin, Virchow, Newport, Bredeney, Heidelberg, Montevideo, Schwarzengrund, 9,12:l,v:- and Hadar). Comparative genomic hybridization using a Salmonella enterica microarray revealed a core of 3233 genes present in all of the iNTS strains, which include the Salmonella pathogenicity islands 1–5, 9, 13, 14; five fimbrial operons (bcf, csg, stb, sth, sti); three colonization factors (misL, bapA, sinH); and the invasion gene, pagN. In the iNTS variable genome, we identified 16 novel genomic islets; various NTS virulence factors; and six typhoid-associated virulence genes (tcfA, cdtB, hlyE, taiA, STY1413, STY1360), displaying a wider distribution among NTS than was previously known. Characterization of the bacteremic strains in C3H/HeN mice showed clear differences in disease manifestation. Previously unreported characterization of serovars Schwarzengrund, 9,12:l,v:-, Bredeney and Virchow in the mouse model showed low ability to elicit systemic disease, but a profound and elongated shedding of serovars Schwarzengrund and 9,12:l,v:- (as well as Enteritidis and Heidelberg) due to chronic infection of the mouse. Phenotypic comparison in macrophages and epithelial cell lines demonstrated a remarkable intra-serovar variation, but also showed that S. Typhimurium bacteremic strains tend to present lower intracellular growth than gastroenteritis isolates. Collectively, our data demonstrated a common core of virulence genes, which might be required for invasive salmonellosis, but also an impressive degree of genetic and phenotypic heterogeneity, highlighting that bacteremia is a complex phenotype, which cannot be attributed merely to an enhanced invasion or intracellular growth of a particular strain.

ABSIRACT We have found that poly(L-lysine) can be a very effective agent in preventing the growth of Ehrlich ascites tumors in mice. When given optimal doses of poly(L-lysine) (Mr 60 X 103) intraperitoneally for 5 consecutive days, beginning on day 1 after inoculation with Ehrlich ascites cells, White Swiss mice show nearly a 100% remission from subsequent tumor growth. Rechallenge of "cured" animals with tumor cells, however, shows no long-term immunological protection. In tissue culture, poly(L-lysine) shows a related potent cytotoxicity with HeLa cells; interestingly, the D isomer has properties strikingly different from those of the L isomer. In addition, there is a strong molecular weight dependence in that the small polylysine (Mr 3 X 103) possess less than 1/20th the cytotoxicity of large polymers (Mr 70 X 103) on a weight basis in both cell culture and animal studies. At the same time, none of these lysine polymers gives any significant increase in life span to BDF1 mice infected with L1210 murine leukemia cells. We have also further explored the mechanism by which the polylysines express their cytotoxicity. These data indicate that lysine polymers show cell specificity in their action and in some cases they may be beneficial as potent antineoplastic agents, particularly when molecular weight is taken into consideration. For more than 25 years, poly(L-lysine) has been known to have unusual biological properties. Early studies showed that it decreased the infectivity of tobacco mosaic virus (1), disturbed thrombin formation in rats (2), blocked the development of bacteriophage (3, 4), protected chicken embryos from animal viruses (5, 6), and possessed antibacterial activity (7). There was also an early report that indicated that polylysine had some activity against murine tumors (8). More recently, polylysine has been found to exhibit a large number of unique membrane properties. These include the ability to enhance the cellular uptake of macromolecules (9), to inhibit iodide uptake by thyroid slices (10), to produce pathogenesis of the glomerular epithelium (11), to act as an anticholinesterase (12), to specifically agglutinate the lymphocytes from cancer patients (13), and to either increase or decrease the transport of specific radioisotopes into cells (14). These effects are probably associated with the polycationic character of polylysine and are probably due to specific interactions on the cell membrane.Recently, we have been examining the ability of polylysine to serve as an efficient drug carrier (15). In doing the controls for these studies, we found that poly(L-lysitie)s of a certain Mr, (60 X 103) could induce 100% remissions in mice inoculated with Ehrlich ascites when the polymer was administered at increased doses. This paper presents results on the antineoplastic activity and toxicity as functions of polymer molecular weight and concentration. Also, we will provide further information into the mechanism accounting for the antineoplastic and cytotoxic activities of polylysine. MATERIALS AND ...

(EP) in rodents are challenging, and available data are sparse. Herein, we utilized a novel type of bipolar electrode to evaluate the atrial EP of rodents through small lateral thoracotomy. In anesthetized rats and mice, we attached two bipolar electrodes to the right atrium and a third to the right ventricle. This standard setup enabled high-resolution EP studies. Moreover, a permanent implantation procedure enabled EP studies in conscious freely moving rats. Atrial EP was evaluated in anesthetized rats, anesthetized mice (ICR and C57BL6 strains), and conscious rats. Signal resolution enabled atrial effective refractory period (AERP) measurements and first time evaluation of the failed 1:1 atrial capture, which was unexpectedly longer than the AERP recorded at near normal cycle length by 27.2 Ϯ 2.3% in rats (P Ͻ 0.0001; n ϭ 35), 31.7 Ϯ 8.3% in ICR mice (P ϭ 0.0001; n ϭ 13), and 57.7 Ϯ 13.7% in C57BL6 mice (P ϭ 0.015; n ϭ 4). While AERP rate adaptation was noted when 10 S1s at near normal basic cycle lengths were followed by S2 at varying basic cycle length and S3 for AERP evaluation, such rate adaptation was absent using conventional S1S2 protocols. Atrial tachypacing in rats shortened the AERP values on a timescale of hours, but a reverse remodeling phase was noted thereafter. Comparison of left vs. right atrial pacing in rats was also feasible with the current technique, resulting in similar AERP values recorded in the low right atrium. In conclusion, our findings indicate that in vivo rate adaptation of the rodent atria is different than expected based on previous ex vivo recordings. In addition, atrial electrical remodeling of rats shows unique remodelingreverse remodeling characteristics that are described here for the first time. Further understanding of these properties should help to determine the clinical relevance as well as limitations of atrial arrhythmia models in rodents.atrial effective refractory period; rate adaptation; electrical remodeling MICE AND RATS ARE USED EXTENSIVELY in cardiac research, and reliable models of cardiac pathologies have been developed and applied in these species (4,19,31). Moreover, genetically altered mice have become invaluable tools for studying the molecular basis of cardiac pathologies including ventricular arrhythmias (7, 28). Use of rodents for studying atrial arrhythmias has been largely limited, but in recent years atrial tachyarrhythmias have been repeatedly produced in rats and mice, and rodents are increasingly used for studying various molecular, cellular, and pharmacological aspects of atrial function (1,5,8,24,36,37). In addition, mice with genetic alterations are providing important insights in this field as well (17,23,27,32).Due to the small size of the rodent heart and, more so, the rodent atria, electrode implantation for studies of functional electrophysiology is challenging. Several techniques were developed to increase the applicability of such studies (2, 23). The transesophageal approach, which is least invasive, necessitates the use of high e...

Iatrogenic superior mesenteric vein injury is a rare, severe, and underreported complication of both open and laparoscopic right colectomy for colonic adenocarcinoma. We identified several mechanisms of injury such as anatomic misperception, excessive traction and pulling on the venous system, extensive tumor involvement of the mesentery, and uncontrolled suturing attempts at hemostasis. We believe that increased awareness of this complication with profound understanding of vascular anatomy and the different mechanisms of injury will allow surgeons to avoid this often devastating complication.

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The measurement of intestinal permeability is widely used to assess different aspects of mucosal barrier disorders and related disease states, and has been proposed for evaluation of disease activity. To provide a simple method for assessment of intestinal permeability, we examined the permeation of inulin-fluorescein (InFl) in rat models of small intestinal injury and colitis. Small intestinal or colonic inflammation was induced by either i.p. administration of indomethacin or rectal administration of trinitrobenzene sulfonic acid (TNBS), respectively. For monitoring of intestinal permeability, InFl was administered orally or rectally to rats with small intestinal or colonic inflammation, respectively, and its level in blood was determined by the fluorescence intensity in the plasma. In small intestinal injury, InFl reached its peak in plasma 3 h after oral administration, while in colitis the InFl peak was reached 1 h after rectal administration. The highest permeability was observed at 72 h or 12 h after induction of small intestinal or colonic inflammation, respectively. In small intestinal injury the InFl permeation, as measured by its plasma level prior to sacrifice, was in agreement with intestinal damage evaluated after sacrifice. In colitis, the permeability at 12 h after induction of the disease correlated well with mortality. These findings demonstrate that InFl can be used as a novel, safe and easy-to-use probe for the evaluation of gut permeation and follow-up of gastrointestinal injury.

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