Experimental electrocoagulation of dog esophageal and duodenal mucosa

The per review system for the assessment of research proposals is widely respected by working scientists. Nevertheless two problems associated with the operation of this system by the US National Institutes of Health are identified. First the scientist has no control over which committee will review an application and it may be considered by a quite inappropriate group. Second analysis of the committee composition suggests that in some of the groups several members are not active scientists and therefore not the "peers" of the applicant.     

Experimental Investigations on Microstructure,Properties and Workability Behavior of Zinc Oxide Reinforced Al–Si–Mg Matrix Composites

Silicon - Al-Si based alloy matrix composites are now broadly utilized by the industrial sectors like automobile, structural, aerospace and more practical industrial applications due to its...     

Concrete made from ceramic industry waste: Durability properties

Concrete which contains waste products as aggregate is called ‘Green’ concrete. Use of hazardous waste in concrete-making will lead to green environment and sustainable concrete technology and so such concrete can also be called as ‘Green’ concrete. Concrete made with ceramic electrical insulator waste as coarse aggregate shows good workability, compressive, tensile and flexural strengths and modulus of elasticity. Further, study of its durability will ensure greater reliability in its usage. Permeation characters are used widely to quantify durability properties of concrete. This paper presents an experimental investigation on the permeation characteristics [volume of voids and water absorption (ASTM C642-06), chloride penetration (ASTM C1202-10), and sorption] of concrete with ceramic electrical insulator waste coarse aggregate (hereafter it is called recycled aggregate concrete) of six different water–cement ratios in comparison with those of corresponding conventional concrete mixes. From the results it has been observed that there is no significant change in the basic trend of permeation characteristics of this recycled aggregate concrete when compared to the conventional concrete. This recycled aggregate concrete possesses higher permeation characteristic values than those of conventional concrete. These values decrease with decrease in water–cement ratio for both the recycled aggregate concrete and the conventional concrete.     

GLUT4 and transferrin receptor are differentially sorted along the endocytic pathway in CHO cells

The trafficking of GLUT4, a facilitative glucose transporter, is examined in transfected CHO cells. In previous work, we expressed GLUT4 in neuroendocrine cells and fibroblasts and found that it was targeted to a population of small vesicles slightly larger than synaptic vesicles (Herman, G.A, F. Bonzelius, A.M. Cieutat, and R.B. Kelly. 1994. Proc. Natl. Acad. Sci. USA. 91: 12750-12754.). In this study, we demonstrate that at 37 degrees C, GLUT4-containing small vesicles (GSVs) are detected after cell surface radiolabeling of GLUT4 whereas uptake of radioiodinated human transferrin does not show appreciable accumulation within these small vesicles. Immunofluorescence microscopy experiments show that at 37 degrees C, cell surface-labeled GLUT4 as well as transferrin is internalized into peripheral and perinuclear structures. At 15 degrees C, endocytosis of GLUT4 continues to occur at a slowed rate, but whereas fluorescently labeled GLUT4 is seen to accumulate within large peripheral endosomes, no perinuclear structures are labeled, and no radiolabeled GSVs are detectable. Shifting cells to 37 degrees C after accumulating labeled GLUT4 at 15 degrees C results in the reappearance of GLUT4 in perinuclear structures and GSV reformation. Cytosol acidification or treatment with hypertonic media containing sucrose prevents the exit of GLUT4 from peripheral endosomes as well as GSV formation, suggesting that coat proteins may be involved in the endocytic trafficking of GLUT4. In contrast, at 15 degrees C, transferrin continues to traffic to perinuclear structures and overall labels structures similar in distribution to those observed at 37 degrees C. Furthermore, treatment with hypertonic media has no apparent effect on transferrin trafficking from peripheral endosomes. Double-labeling experiments after the internalization of both transferrin and surface-labeled GLUT4 show that GLUT4 accumulates within peripheral compartments that exclude the transferrin receptor (TfR) at both 15 degrees and 37 degrees C. Thus, GLUT4 is sorted differently from the transferrin receptor as evidenced by the targeting of each protein to distinct early endosomal compartments and by the formation of GSVs. These results suggest that the sorting of GLUT4 from TfR may occur primarily at the level of the plasma membrane into distinct endosomes and that the organization of the endocytic system in CHO cells more closely resembles that of neuroendocrine cells than previously appreciated.     

NaF potentiates a K(+)-selective ion channel in G292 osteoblastic cells

In a previous study, isoelectrofocusing of serum from liver-diseased and healthy dogs revealed three different types of the acute phase protein, alpha-1-antitrypsin: Pi (protease inhibitor) F, Pi I and Pi S. Moreover, accumulated alpha-1-antitrypsin was found immunohistochemically in liver sections from dogs with chronic liver disease, predominantly in association with Pi I in serum. The present study was made to further the relationship between alpha-1-antitrypsin and the pathogenesis of chronic liver disease in dogs. Aliquots of samples of purified canine Pi F, Pi I and Pi S were examined for elastase inhibitory capacity, the main function of alpha-l-antitrypsin, and for polymerization tendency, a possible cause of accumulation of alpha-1-antitrypsin in the liver. These parameters were studied after incubation of the proteins at different temperatures (4, 37 and 42 degrees C) and pH values (6.8, 7.8 and 8.5) and for different periods (< or = 24 h and 5 days). In contrast to findings with Pi Z, the human alpha-1-antitrypsin variant associated with liver disease, polymers of canine Pi F, Pi I or Pi S could not be detected under any of the conditions tested. However, Pi I was sensitive to pH, as was demonstrated by reduced elastase inhibitory capacity after incubation at pH 6.8 for < or = 24 h or 5 days, or at pH 8.5 for 5 days. However, after incubation at pH 7.8 for < or = 24 h or 5 days at 4, 37 or 42 degrees C, Pi I was completely stable. Pi F retained its elastase inhibitory capacity, even after prolonged incubation, at all pH values and temperatures tested. Due to low yield, Pi S was tested only after incubation for < or = 24 h at pH 6.8 and at 4 degrees C; under these conditions its elastase inhibitory capacity was equal to that of Pi F. Taken together, these findings indicate molecular and functional differences between Pi I and Pi F and further support a role for alpha-1-antitrypsin in the pathogenesis of canine liver disease.     

Solution structure of acidic fibroblast growth factor bound to 1,3, 6-naphthalenetrisulfonate: a minimal model for the anti-tumoral action of suramins and suradistas

Recent data show that anti-angiogenesis may provide a promising route to treat cancer. Fibroblast growth factors (FGFs) are powerful angiogenic polypeptides, whose mitogenic activity requires the presence of heparin-like compounds. It has been shown that angiogenesis promoted by FGFs on inhibition by monoclonal antibodies and antisense targeting can also inhibit tumour growth. Derivatives of suramin, a polysulfonated binaphthyl urea and binaphthylsulfonated derivatives of distamycin, suradistas, constitute an important group of potential anti-cancer agents. These compounds compete with heparin in forming tight complexes with FGFs. This inhibits the recognition of these growth factors by their tyrosine kinase membrane receptors thereby suppressing their angiogenic activity. Here we show that 1,3,6-naphthalenetrisulfonate, a common chemical function of the suramins and suradistas with the highest anti-angiogenic activity inhibits the mitogenic activity of acidic fibroblast growth factor, and that this inhibition is relieved by increasing concentrations of heparin in the assay. We have also solved the three-dimensional structure in solution of the protein complexed to this compound. The structural data provide clues that may help in understanding the inhibitory effect of suramins and suradistas, and could contribute to the development of new anti-tumoral drugs.     

Preparation and in vitro characterization of gentamycin-impregnated biodegradable beads suitable for treatment of osteomyelitis

A new method for preparing poly(L-lactide) (PLA) biodegradable beads impregnated with an ionic aminoglycoside, gentamycin, is described. The process employs hydrophobic ion pairing to solubilize gentamycin in a solvent compatible with PLA, followed by precipitation with a compressed antisolvent (supercritical carbon dioxide). The resulting precipitate is a homogeneous dispersion of the ion-paired drug in PLA microspheres. The microspheres are approximately 1 microm in diameter and can be compressed into beads (3-6 mm in diameter) strung on surgical sutures for implantation. The bead strings exhibit no significant change in release kinetics upon sterilization with a hydrogen peroxide plasma (Ster-Rad). The kinetics of gentamycin release from the PLA beads are consistent with a matrix-controlled diffusion mechanism. While nonbiodegradable poly(methyl methacrylate) (PMMA) beads initially release gentamycin in a similar manner, the drug release from PMMA ceases after 8 or 9 weeks, while the PLA beads continue to release drug for over 4 months. Moreover, only 10% of the gentamycin is released from the PMMA beads, while PLA beads release more than 60% of their load, if serum is present in the release medium. The PLA system displays improved release kinetics relative to PMMA, is biodegradable, is unaltered by gas sterilization, can be used for a range of antibiotics, and can be manipulated without disintegration. These are all desirable properties for an implantable drug delivery system for the prevention or treatment of osteomyelitis.     

Biliary dyskinesia: natural history and surgical results

Patients with biliary dyskinesia have symptoms consistent with biliary colic and an abnormal gallbladder ejection fraction (GEF) in the absence of cholelithiasis. Cholecystokinin hepatobiliary scan quantifies gallbladder function and may assist in selecting patients with acalculous biliary pain who would benefit from cholecystectomy. Seventy-eight patients with an abnormal GEF (< 35%) on cholecystokinin hepatobiliary scan without cholelithiasis were studied retrospectively. Patients were divided into groups based on diagnosis and treatment. In Group I, the patients who underwent cholecystectomy, 80 per cent (35 of 44) had complete symptomatic resolution whereas the remaining 20 per cent (9 of 44) had symptomatic improvement. Pathology reports demonstrated chronic cholecystitis in 95 per cent of specimens. Group II were patients with symptoms attributable to biliary dyskinesia, but did not undergo cholecystectomy. Persistence of symptoms was noted in 75 per cent (18 of 24) of patients whereas 25 per cent (6 of 24) had symptomatic resolution without any treatment. Group III consisted of patients with an abnormal ejection fraction who had improvement of symptoms after treatment for an alternative diagnosis (n = 10). These findings suggest that an abnormal ejection fraction does not always indicate gallbladder disease. Alternative diagnoses must be investigated and treated. Patients with persistent biliary type symptoms in combination with an abnormal GEF in the absence of other attributable causes can expect a favorable response to cholecystectomy.