Plasma cortisol concentrations in normal dogs given hydrocortisone sodium succinate

OBJECTIVE: To evaluate the effects on plasma cortisol concentration of a continuous infusion of a readily available steroid with equipotent glucocorticoid and mineralocorticoid effects. PROCEDURE: Plasma cortisol concentrations were measured before and regularly after hydrocortisone sodium succinate was administered as a continuous intravenous infusion over 6 h at 0.32 and 0.65 mg kg-1 h-1 to 12 healthy dogs weighing 12 to 22 kg. RESULTS: The infusion at both does rates produced significant and stable increases in plasma cortisol concentrations. The plateau concentrations produced by the large and small doeses were respectively above and below plasma cortisol concentrations likely to provide adequate glucocorticoid and mineralocorticoid activity in stressed dogs with significantly decreased adrenal function. CONCLUSION: This paper presents information regarding the changes in plasma cortisol concentrations in 12 normal dogs given an hydrocortisone sodium succinate infusion at two dose rates. The marked and continuous increase in plasma cortisol concentrations suggests a continuous HSS infusion may be a possible alternative to desoxycorticosterone acetate and dexamethasone in the treatment of acute adrenal dysfunction.     

Evidence for extreme climatic warmth from late cretaceous arctic vertebrates

A Late Cretaceous (92 to 86 million years ago) vertebrate assemblage from the high Canadian Arctic (Axel Heiberg Island) implies that polar climates were warm (mean annual temperature exceeding 14 degreesC) rather than near freezing. The assemblage includes large (2.4 meters long) champsosaurs, which are extinct crocodilelike reptiles. Magmatism at six large igneous provinces at this time suggests that volcanic carbon dioxide emissions helped cause the global warmth.     

Age-related changes of calbindin D-28k-immunoreactive neurons in the myenteric plexus of gerbil duodenum

We examined the age-related changes of calbindin D-28k (CB)-immunoreactive neurons and overall populations of neurons in the myenteric plexus of gerbil duodenum using whole mount preparations and immunohistochemistry. The circumference of duodenum increased age-dependently. CB-immunoreactive neurons were observed in all groups, and most of them had the Dogiel type II morphology. The fully developed cobweb-like structures were observed in the myenteric plexus of duodenum at postnatal month (PM) 3 to 24. Although the highest numbers of CB-immunoreactive neurons and overall population were observed in PM 1.5, it is related with significant increase of the size of circumference between PM 1.5 to PM 3. CB-immunoreactive neurons were slightly decreased with age between PM 3 to PM 24. We have also found that whole numbers of myenteric neurons were also significantly decreased in PM 24 group. These results suggest that loss of overall numbers of myenteric neurons and CB-immunoreactive neurons may be related with age-related neurodegeneration and functional loss of duodenum in the gerbil.     

Variation in susceptibility of six pine species and hybrids to pitch canker caused by Fusarium circinatum

Six pine species or hybrids were tested for susceptibility to pitch canker caused by Fusarium  circinatum. Pinus  densiflora, Pinus  thunbergii, Pinus  x rigitaeda (Pinus  rigida × Pinus  taeda), P. rigida × P. x rigitaeda, Pinus  echinata and Pinus  virginiana were inoculated with three spore loads (50, 500 and 5000 per tree) of F. circinatum. External symptoms, lesion length, and the frequency of reisolation of the fungus were investigated. External symptoms were greatest in P. echinata, followed by P. virginiana, however, P. densiflora was not susceptible to F. circinatum. Based on mean lesion lengths, the six pine species or hybrids differed significantly (p < 0.01) in susceptibility to pitch canker. Pinus  echinata sustained the longest lesions, whereas P. densiflora sustained the shortest lesions. The effect of inoculum density was not significant among three spore treatments within species (p = 0.17), although lesion length was slightly greater at higher spore loads over all pine species. The fungus was reisolated from inoculated stems of all pine species tested, even on trees showing little or no damage from the disease. Additional studies are needed to further explore the basis for resistance to pitch canker.     

Surface modification of poly(lactic acid) by UV/Ozone irradiation

Hydrophobic poly(lactic acid), PLA, was modified to give hydrophilicity and dyeability to cationic dyes via UV/O₃ irradiation. The UV irradiation treatment caused ester linkage of PLA surface to break down resulting in reduced molecular weight and generation of new photooxidized products as indicated in subtracted ATR spectra and ESCA analysis. It was found that water contact angle decreased from 61 ° to 39 ° and surface energy slightly increased with increasing UV energy, which was attributed to significant contribution of polar component rather than nonpolar component resulting from the surface photooxidation of PLA. Also the surface treatment increased dyeability of PLA to C.I. Basic Blue 41 in terms of both K/S and %E. The increased dyeability may be due to photochemically introduced anionic and dipolar dyeing sites which electrostatically interact with the cationic dye as ascertained by the decreased zeta potential and its pH dependence of the modified PLA.     

Antiproliferative effects of carotenoids extracted from Chlorella ellipsoidea and Chlorella vulgaris on human colon cancer cells

The antiproliferative activity of carotenoids separated from marine Chlorella ellipsoidea and freshwater Chlorella vulgaris has been evaluated. HPLC analysis revealed that the main carotenoid from C. ellipsoidea was composed of violaxanthin with two minor xanthophylls, antheraxanthin and zeaxanthin, whereas the carotenoid from C. vulgaris was almost completely composed of lutein. In an MTT assay, both semipurified extracts of C. ellipsoidea and C. vulgaris inhibited HCT116 cell growth in a dose-dependent manner, yielding IC(50) values of 40.73 +/- 3.71 and 40.31 +/- 4.43 microg/mL, respectively. In addition, treatment with both chlorella extracts enhanced the fluorescence intensity of the early apoptotic cell population in HCT116 cells. C. ellipsoidea extract produced an apoptosis-inducing effect almost 2.5 times stronger than that of the C. vulgaris extract. These results indicate that bioactive xanthophylls of C. ellipsoidea might be useful functional ingredients in the prevention of human cancers.     

Alleviating cancer drug toxicity by inhibiting a bacterial enzyme

The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial β-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial β-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.     

Macromolecular depletion modulates the binding of red blood cells to activated endothelial cells

Adhesion of red blood cells (RBCs) to endothelial cells (ECs) is usually insignificant but an enhanced adhesion has been observed in various diseases associated with vascular complications. This abnormal adhesion under pathological conditions such as sickle cell disease has been correlated with increased levels of various plasma proteins but the detailed underlying mechanism(s) remains unclear. Usually it is assumed that the proadhesive effects of plasma proteins originate from ligand interactions cross-linking receptors on adjacent cells, but explicit results detailing binding sites or receptors for some proteins (e.g., fibrinogen) on either RBC or EC surfaces that would support this model are missing. In this study, the authors tested whether there is an alternative mechanism. Their results demonstrate that dextran 2 MDa promotes the adhesion of normal RBCs to thrombin-activated ECs and that this effect becomes more pronounced with increasing thrombin concentration or with prolonged thrombin incubation time. It is concluded that depletion interaction originating from nonadsorbing macromolecules (i.e., dextran) can modulate the adhesion of red blood cells to thrombin-activated EC. This study thereby suggests macromolecular depletion as an alternative mechanism for the adhesion-promoting effects of nonadsorbing plasma proteins. These findings should not only aid in getting a better understanding of diseases associated with vascular complications but should also have many potential applications in biomedical or biotechnological areas that require the control of cell-cell or cell surface interactions.