Effect of mucosal immunomodulation with fed cholera toxin on healing of experimental colonic anastomosis

PURPOSE: The aim of this study was to investigate in rats whether preoperative orogastric administration of low doses of cholera toxin would influence the mechanical strength of experimental colonic anastomosis on the basis of the gut mucosal immunomodulation effect of this antigen. METHODS: The cholera toxin group (n = 14) was fed 10 g of cholera toxin in phosphate-buffered saline three times before surgery at 10-day intervals, whereas the controls (n = 14) received phosphate-buffered saline only. Twenty-four hours after the last dose of cholera toxin (or placebo in control group), the animals underwent left colonic transection and anastomosis. Seven days after colonic transection-anastomosis, the bursting pressure of the anastomotic segment was recorded in situ. Perianastomotic and extra-anastomotic tissue samples were obtained for measurements of tissue transforming growth factor-beta, interleukin-6, and interferon-gamma levels with enzyme-linked immunosorbent assay. RESULTS: Cholera toxin administration resulted in a significantly higher bursting pressure than in the control group (165.78 ± 12.37 vs. 138.4 ± 7.87 mmHg; P < 0.001). Compared with the control group, the heightened mechanical strength of colonic anastomosis provided by cholera toxin was associated with significant increases in the perianastomotic tissue levels of transforming growth factor-beta (199.34 ± 24.85 vs. 70.66 ± 10.63 pg/ml; P < 0.001) and interleukin-6 (439.31 ± 95.14 vs. 289.57 ± 96.59 pg/ml; P = 0.001), whereas interferon-gamma was significantly lower (174.04 ± 44.82 vs. 219.00 ± 31.35 pg/ml; P < 0.05). This cytokine pattern induced by cholera toxin in the wound milieu was also found to be similar in the extra-anastomotic colon. CONCLUSION: The mechanical strength of uncomplicated experimental colonic anastomosis increased significantly with gut mucosal immunomodulation with repeated low preoperative doses of cholera toxin. This enhanced healing had significant positive correlation with the colonic tissue level of transforming growth factor-beta and inverse correlation with interferon-gamma. If the relevant dose regimen is identified and its safety is assured in humans, gut mucosal immunomodulation might provide an efficient, safe, and inexpensive tool to improve surgical outcome in colorectal surgery, particularly in high-risk situations.     

Maternal administration of granulocyte colony-stimulating factor improves neonatal rat survival after a lethal group B streptococcal infection

Maternally administered recombinant human granulocyte colony- stimulating factor (rhG-CSF) has been shown to cross the placenta and induce a peripheral neutrophilia and increases in the marrow and spleen neutrophil storage pools in fetal and newborn rats. In the present study, we have used this model system to investigate the efficacy of prenatally administered rhG-CSF on neonatal defense to a lethal challenge with Group B-beta hemolytic Streptococcus (GBS). Pregnant rats were injected with rhG-CSF twice daily beginning 6 days before parturition. At birth, all pups were infected with a dose of GBS that is lethal for 90% of infected pups (LD90). Survival was monitored daily for 5 days. Survival of infected pups from saline-treated mothers beyond 60 hours after infection was 10%. No difference in survival was observed among pups from mothers treated 2 and 4 days before parturition. In contrast, we determined that survival was 82.5% among infected pups from mothers treated for 6 days before parturition with rhG-CSF. Our results demonstrate that maternal administration of rhG- CSF augments neonatal defenses against a lethal bacterial challenge.     

The psychosocial determinants of hypertension

AIM: To present currently available evidence on the role that adverse psychosocial factors play in the pathogenesis of hypertension. The specific objectives of the review were to (1) provide a picture of what is known about the relationship between psychosocial factors and hypertension, (2) summarize the major methodological and conceptual pitfalls, and (3) identify gaps in the literature and suggest areas for future research. DATA SYNTHESIS: The scope of the literature review was adults and the literature published since 1990 (acknowledging that some articles published earlier would need to be taken into account). A number of journal searches were carried out. They included Medline, PsychInfo, and SocioFile, with keywords, such as hypertension, blood pressure, psychosocial, psychological, social, acculturation, occupation, socio-economic status, social class, education, depression, anger, and anxiety. The search included articles related to hypertension in developed countries and was limited to studies in the English language. CONCLUSION: A growing body of evidence supports the thesis that psychosocial factors play a role in the pathogenesis for hypertension.     

De novo design of catalytic proteins

The de novo design of catalytic proteins provides a stringent test of our understanding of enzyme function, while simultaneously laying the groundwork for the design of novel catalysts. Here we describe the design of an O(2)-dependent phenol oxidase whose structure, sequence, and activity are designed from first principles. The protein catalyzes the two-electron oxidation of 4-aminophenol (k(cat)/K(M) = 1,500 M(-1).min(-1)) to the corresponding quinone monoimine by using a diiron cofactor. The catalytic efficiency is sensitive to changes of the size of a methyl group in the protein, illustrating the specificity of the design.     

Subclasses of cyclic AMP-specific phosphodiesterase in left ventricular muscle and their involvement in regulating myocardial contractility

Ventricular muscle contains a low Km, cyclic AMP-specific form of phosphodiesterase (PDE III), which is believed to represent the site of action for several of new cardiotonic agents including imazodan (CI-914), amrinone, cilostamide, and enoximone. However, species differences in the inotropic response to these agents have raised questions about the relationship between PDE III inhibition and cardiotonic activity. The present study demonstrates that these differences can be accounted for by the presence of two subclasses of PDE III in ventricular muscle and variations in the intracellular localization of these two enzymes. For these experiments, PDE III was initially isolated from canine, guinea pig, and rat left ventricular muscle. The results demonstrate that canine left ventricular muscle contains two functional subclasses of PDE III: an imazodan-sensitive form, which is membrane bound, and an imazodan-insensitive form, which is soluble. Although only weakly inhibited by imazodan, this latter enzyme is potently inhibited by the selective PDE III inhibitors, Ro 20-1724 and rolipram. Guinea pig ventricular muscle also contains the imazodan-sensitive subclass of PDE III. Unlike canine left ventricle, however, thi enzyme is soluble in the guinea pig. No membrane-bound subclass of PDE III was observed in the guinea pig. Rat left ventricle possesses only the soluble form of PDE III, which apparently represents a mixture of the imazodan-sensitive and imazodan-insensitive subclasses of PDE III. Measurement of in vivo contractility in these three species showed that imazodan exerts a potent positive inotropic effect only in the dog, in which the imazodan-sensitive subclass of PDE III is membrane bound.(ABSTRACT TRUNCATED AT 250 WORDS)     

Disseminated unicellular green algal infection in two sheep in India

Unicellular green algae infected and disseminated in two adult Nellore brown rams in India. At necropsy multiple green lesions were observed in the lungs, liver and kidneys of both sheep. Histological examination revealed necrotizing granulomas that contained numerous spheroidal to elliptical organisms ranging from 5-20 micrometers in diameter. These organisms occurred in several reproductive stages: small (5-9 micrometers) single, undifferentiated cells; intermediate (9-15 micrometers) cells undergoing nuclear and cytoplasmic cleavage; and large, mature, endosporulating cells containing two to six or more endospores. In addition, occasional large (20-35 micrometers), round thick-walled forms were among the typical cells. The cytoplasm of the algal cells contained numerous, large, irregularly-shaped and densely packed granules of varying sizes, which were strongly stained by the Gridley fungus, periodic acid-Schiff, and Gomori methenamine silver procedures. Electron microscopic studies revealed chloroplasts in the cytoplasm of these organisms. The chloroplasts consisted of smoothly contoured electron-lucent or electron-dense granules, 0.5 to 3.0 micrometers in diameter, that were either surrounded by or contiguous to two or more tightly appressed membranes or multidisc bands. Some of the alternating membranes appeared to be spirally twisted or associated with several cytoplasmic granules in one plane of section. This is the first record of algal infections in India.