Lactobacillus spp. impair the ability of Listeria monocytogenes FBUNT to adhere to and invade Caco-2 cells.

OBJECTIVES: The objective of this study was to evaluate the ability of Lactobacillus curvatus CRL705, CRL1532, and CRL1533 and Lactobacillus sakei CRL1613 to survive under simulated gastrointestinal conditions. Moreover, a microencapsulation approach was proposed to improve gastrointestinal survival. Finally, experiments were performed to demonstrate that Lactobacillus spp. can modulate the ability of Listeria monocytogenes FBUNT to adhere to and invade Caco-2 cells. RESULTS: Lactobacillus strains were encapsulated in alginate beads to enhance the survival of bacteria under in vitro gastrointestinal conditions. All strains hydrolyzed bile salts using chenodeoxycholic acid as a substrate and adhered to Caco-2 cells. Cell-free supernatants (CFSs) showed antimicrobial activity against L. monocytogenes as demonstrated by agar diffusion assays. The average percentages of L. monocytogenes adhesion decreased from 67.74 to 41.75 and 38.7% in the presence of 50 and 90% (v/v), respectively, for all CFSs tested. The highest concentrations of CFSs completely inhibited the L. monocytogenes invasion of Caco-2 cells. CONCLUSIONS: The studied Lactobacillus strains have protective effects against the adhesion and invasion of L. monocytogenes FBUNT. Alginate encapsulation of these bacteria improved gastrointestinal tolerance such that they could be further studied as potential probiotics against intestinal pathogenic bacteria.

Ion channel remodeling in gastrointestinal inflammation.

BACKGROUND: Gastrointestinal inflammation significantly affects the electrical excitability of smooth muscle cells. Considerable progress over the last few years have been made to establish the mechanisms by which ion channel function is altered in the setting of gastrointestinal inflammation. Details have begun to emerge on the molecular basis by which ion channel function may be regulated in smooth muscle following inflammation. These include changes in protein and gene expression of the smooth muscle isoform of L-type Ca(2+) channels and ATP-sensitive K(+) channels. Recent attention has also focused on post-translational modifications as a primary means of altering ion channel function in the absence of changes in protein/gene expression. Protein phosphorylation of serine/theronine or tyrosine residues, cysteine thiol modifications, and tyrosine nitration are potential mechanisms affected by oxidative/nitrosative stress that alter the gating kinetics of ion channels. Collectively, these findings suggest that inflammation results in electrical remodeling of smooth muscle cells in addition to structural remodeling. PURPOSE: The purpose of this review is to synthesize our current understanding regarding molecular mechanisms that result in altered ion channel function during gastrointestinal inflammation and to address potential areas that can lead to targeted new therapies.

The effect of tyrosine nitration of L-type Ca2+ channels on excitation-transcription coupling in colonic inflammation.

BACKGROUND AND PURPOSE: Excitation-transcriptional coupling involves communication between plasma membrane ion channels and gene expression in the nucleus. Calcium influx through L-type Ca(2+) channels induces phosphorylation of the transcription factor, cyclic-AMP response element binding protein (CREB) and downstream activation of the cyclic-AMP response element (CRE) promoter regions. Tyrosine nitration of Ca(2+) channels attenuates interactions with c-Src kinase, decreasing Ca(2+) channel currents and smooth muscle contraction during colonic inflammation. In this study we examined the effect of tyrosine nitration and colonic inflammation on Ca(2+) channel mediated phosphorylation of CREB and CRE activation. EXPERIMENTAL APPROACH: CREB and phospho-CREB were detected by Western blots and CRE activation measured by dual luciferase assay. Chinese hamster ovary (CHO) cells were transfected with hCa(v)1.2b and hCa(v)1.2b c-terminal mutants. Colonic inflammation was induced by intracolonic instillation of 2,4,6 trinitrobenzene sulphonic acid in mouse colon. KEY RESULTS: In hCa(v)1.2b transfected CHO cells and in native colonic smooth muscle, depolarization with 80 mM KCl induced CREB phosphorylation (pCREB). Treatment with peroxynitrite inhibited KCl-induced pCREB. Following experimental colitis, KCl-induced CREB phosphorylation was abolished in smooth muscle, concomitant with tyrosine nitration of Ca(2+) channels. Depolarization increased CRE activation in hCa(v)1.2b CHO cells by 2.35 fold which was blocked by nifedipine and by protein nitration of Ca(2+) channels with peroxynitrite. The Src-kinase inhibitor, PP2, blocked depolarization-induced CRE activation. Mutation of the C-terminus tyrosine residue, Y2134F, but not Y1861F, blocked CRE activation. CONCLUSIONS AND IMPLICATIONS: Post-translational modification of Ca(2+) channels due to tyrosine nitration modified excitation-transcriptional coupling in colonic inflammation.

Ascorbic acid metabolism and polyol pathway in diabetes.

It has been reported previously that the plasma concentration of ascorbic acid (AA) is reduced in streptozocin-induced diabetic rats and can be normalized by treatment with the aldose reductase inhibitor tolrestat. This study was designed to investigate further the relationship between the polyol pathway and AA metabolism in diabetic rats. Disturbance of AA metabolism was demonstrable after 1 wk of diabetes. Dietary myo-inositol supplementation was effective in normalizing plasma AA levels, as was treatment with tolrestat. In untreated diabetes, despite low plasma AA concentration, there was increased urinary excretion of AA that was reversed by treatment with either tolrestat or myo-inositol. In contrast, AA supplementation normalized plasma AA concentrations while further increasing urinary AA excretion. The abnormality of AA metabolism was less severe in galactose-fed rats, which had normal plasma AA levels and only minor increases in urinary AA excretion. These studies demonstrated a disturbance in the regulation of plasma and urinary AA concentration in experimental diabetes and confirmed the relationship of AA with the polyol pathway. Because AA has many important biological functions, abnormalities of AA metabolism could be important in the pathogenesis of some diabetic complications. The interaction of the polyol and AA pathways suggests that this could be another site of action for aldose reductase inhibitors.

Teachers' perceptions concerning the relative values of personal and clinical characteristics and their influence on the assignment of students' clinical grades.

Twenty senior teachers were asked to rank, in order of influence, the seven clinical and five personal characteristics used to grade third-year medicine clerks. Seventeen perceived themselves to be more influenced by clinical characteristics when assigning grades. Independently, the actual ratings completed over a 3-year period by these same teachers were analysed to measure the congruency between their perceived and actual grading behaviour. When actually rating students only nine raters were more influenced by clinical characteristics and just one half of the teachers displayed a congruency between their perceived and actual rating behaviour. The implications of these findings are discussed.

Deficiency of ascorbic acid in experimental diabetes. Relationship with collagen and polyol pathway abnormalities.

The plasma and tissue concentration of ascorbic acid (AA) is reduced in diabetes. This study was designed to investigate the mechanism and significance of this phenomenon. The low plasma AA concentration of diabetic rats can be normalized by dietary AA supplement (20-40 mg/day), a dosage approximately equal to the maximal synthetic rate of this substance in the rats. Treatment of diabetic rats with this regime prevented the decrease in activity of granulation tissue prolyl hydroxylase (PRLase), an AA-dependent enzyme required for maintaining the normal properties of collagen. The decreased plasma AA concentration and granulation tissue PRLase activity in diabetes can also be normalized by the aldose reductase inhibitor tolrestat. We conclude that in diabetic animals there is a true deficiency of AA that may be responsible for some of the changes of collagen observed in diabetes. Treatment with AA or an aldose reductase inhibitor may prevent some of the diabetic complications with underlying collagen abnormalities.

Hepatoma, arterioportal shunting, and hyperkinetic portal hypertension: therapeutic embolization.

Four patients with hepatocellular carcinoma, shunting of blood from the hepatic artery to the portal vein, and hyperkinetic portal hypertension were treated by transcatheter embolization of the hepatic artery. In three acutely bleeding patients variceal hemorrhage was controlled by the embolization. Following embolization hepatofugal portal venous flow became hepatopetal in all four patients. No serious complications were encountered. When hepatoma is complicated by arterioportal shunting and hyperkinetic portal hypertension, occlusion of the fistula by transcatheter embolotherapy can reduce the portal pressure.

Hemobilia following transhepatic biliary drainage: occlusion of an hepatoportal fistula by balloon tamponade.

Acute clinically significant hemobilia occurred after percutaneous transhepatic biliary drainage. Investigations revealed a fistula between a peripheral bile duct and a branch of the portal vein. Hemostasis was obtained by balloon tamponade at the site of the fistula.

Pseudoaneurysm: a complication of faulty technique in femoral arterial puncture.

Pseudoaneurysm is a well-documented but rare complication of retrograde femoral arterial puncture. We present six patients in whom pseudoaneurysm complicated this procedure. The pseudoaneurysm arose from the superficial femoral artery in five patients and from the profunda femoris artery in one. An arteriovenous fistula also arose from the superficial femoral artery in one patient. In no patient did the pseudoaneurysm arise from the common femoral artery. Two mechanisms are postulated as to why pseudoaneurysms rarely complicate puncture of the common femoral artery.

A survey on the 'premedical syndrome'.

The "premedical syndrome" has been widely discussed but only anecdotally described. To learn whether the syndrome exists in the South Carolina schools and which traits compose it, the authors surveyed faculty members and students of 13 undergraduate colleges in the state. Premedical students were perceived as differing from nonpremedical students in being excessively competitive, academically, overspecialized , overachieving , more highly motivated, more highly self-disciplined, goal-oriented, and proud of their career choice. The perception by students and faculty members of the premedical syndrome may have important effects on the undergraduate curriculum and students' choices of major areas of study. Only 3 percent of the premedical students who responded to the survey were majoring in the liberal arts, and only 9 percent of the nonpremedical students were majoring in the natural sciences. These data suggest that the natural science departments in U.S. colleges may have become training grounds for premedical students to the exclusion of others. Modification of medical school admissions policies may be able to reverse some features of the premedical syndrome and some of its effects.

Continuing education needs assessment in dentistry: the SNAP system.

Needs assessment has become an integral step in planning for continuing education. This article describes a computer-based needs assessment system that has been used successfully in planning continuing dental education in South Carolina. The Statewide Needs Assessment Program (SNAP) provides a general purpose system for collecting and analyzing continuing education needs data for large populations. Needs assessment data from 489 practicing dentists in South Carolina are presented and analyzed.

Eczema herpeticum: atopic dermatitis complicated by primary herpetic gingivostomatitis.

Various aspects of eczema herpeticum are discussed, and a case of eczema herpeticum secondary to atopic dermatitis complicated by primary herpetic gingivostomatitis in a young adult is presented. The lesions cleared, and the patient was discharged after treatment via a multiphasic approach directed at the management of pyrexia, prevention of secondary bacterial infections, symptomatic and supportive care for the effects of the viral infection, and close monitoring for evidence of visceral viremia.

Antineoplastic agents and their oral manifestations.

The use of antineoplastic agents is rapidly increasing. A general classification of these drugs and their mechanisms of action is presented. Many of the drugs have an adverse effect on oral tissue, and the practicing dentist today must be well acquainted with these effects. A discussion of the features of these reactions and their management is presented.

Using the computer to prepare multiple-choice examinations: a simplified system.

Program TEST offers a quick, easy, and efficient way to produce objectively-scored exams from an established item bank. It is especially useful in situations where frequent testing is utilized and secretarial help is scarce. The capability of constructing a customized exam the day before its administration should make the exam more reflective of the instruction. The provision for keyed copies has been found to be a useful tool for feedback to the student after the exam. Lastly, use of the program requires little computer assistance.

Appraisal, validation, and evaluation utilized in the assessment of instructional materials.

To maintain the highest standards of instructional quality, it is essential that self-instructional materials used in the teaching effort be systematically assessed. This paper has presented three types of assessment that have proven effective for the Office of Education, College of Dental Medicine, Medical University of South Carolina. The commitment to a regular assessment program has resulted in a more informed selection of materials and a more appropriate use of self-instructional materials by the faculty. Obviously, all of the approaches described may not be appropriate for all institutions. However, all institutions utilizing self-instructional materials have an obligation to assess the effectiveness of the materials to the best of their ability and resources.