Effect of obstructive sleep apnoea on retinal microvascular function: a randomised controlled trial

Graefe's Archive for Clinical and Experimental Ophthalmology - Retinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases....     

Pathogenic capacity of proteases from Serratia marcescens and Pseudomonas aeruginosa and their suppression by chicken egg white ovomacroglobulin.

The pathogenicities of three proteases from Serratia marcescens, two proteases from Pseudomonas aeruginosa, and one thermolysin from Bacillus stearothermophilus were examined. All proteases tested caused acute liquefactive necrosis of the cornea and descemetocele formation in guinea pig eyes after intrastromal injection, with the exception of the 60-kilodalton protease from S. marcescens, which produced only an opaque lesion. When injected into guinea pig skin, the protease also enhanced vascular permeability, which was followed by edema formation. The permeability-enhancing activity of the proteases increased in parallel with the concentration of the enzymes. When tested in vitro for its effect on these bacterial proteases, chicken egg white ovomacroglobulin (ovoM) inhibited the enzymatic activity of all the proteases after a short incubation period at an enzyme/inhibitor ratio (molar) of 1:1 to 1:4 or at a lower concentration after a longer incubation period. Such treatment of the proteases with chicken egg white ovoM before injection intrastromally into the eyes or intradermally into the clipped flanks of guinea pigs protected the cornea from destruction or completely prevented the permeability reaction and edema formation. No inhibitory effects of plasma protease inhibitors against these bacterial proteases were noted. Since the proteases are critical in the pathogenic processes caused by the bacteria, these results suggest a beneficial effect of ovoM against bacterial infections.     

Degradation of protease inhibitors, immunoglobulins, and other serum proteins by Serratia protease and its toxicity to fibroblast in culture

We investigated the effect of the extracellular protease of Serratia marcescens on human serum constituents such as immunoglobulins, fibronectin, alpha 1-protease inhibitor, alpha 2-macroglobulin, lysozyme, and transferrin. At a very low concentration of Serratia 56-kilodalton protease (56K protease), purified human plasma fibronectin was degraded rapidly into three structural domains or small fragments. Immunoglobulin G3 (IgG3) and IgA1 were also degraded within 30 min with 1 microgram of this protease per ml, more rapidly than their other subclass of IgG or IgA. alpha 1-Protease inhibitor, which did not inhibit the 56K protease, was degraded similarly by the protease. These events were demonstrated by fluorescence polarization and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protease was considerably inhibited by human alpha 2-macroglobulin and chicken ovomacroglobulin. However, when there was a 2 M excess of ovomacroglobulin or a 4 M excess of alpha 2-macroglobulin over the 56K protease, about 25 or 40% proteolytic activity remained, respectively. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the protease degraded the alpha 2-macroglobulin extensively during prolonged incubation, which paralleled with regeneration of the protease activity. The protease also cleaved human lysozyme, although moderately. Human serum transferrin was degraded slightly, and human serum albumin was almost resistant to the 56K protease. The enzyme seemed to have no effect on reconstituted collagen, but it degraded rat tropocollagen and yielded fragments of beta and gamma chains by cleaving the intramolecular cross-links. Most of the above proteolysis by the 56K protease appears to result in a limited type of substrate specificity. Thus, the present study demonstrates that the protease is capable of degrading defense-oriented humoral proteins and tissue constituents. Furthermore, it is toxic to fibroblasts. These findings also clarified the possible role of Serratia protease as a virulence factor in the pathogenesis of serratial infections. We recently demonstrated this notion in vivo with rabbit cornea (R. Kamata et al., Ophthalmology 92:1452-1459, 1985).     

Plasmid analysis of Shigella dysenteriae type 1 isolates obtained from widely scattered geographical locations.

Plasmid profiles and antimicrobial susceptibility patterns of 343 strains of Shigella dysenteriae type 1, obtained from 18 different geographical locations, were analyzed. Three plasmids, with molecular sizes of 140, 6, and 2 megadaltons (MDa), were present in 94, 98, and 96%, respectively, of the 343 strains isolated during either epidemic or nonepidemic periods from 1965 to 1987. In addition to these plasmids, 83% of the strains harbored a 4-MDa plasmid and 25% harbored a 20-MDa plasmid. Various plasmid profiles were observed in which the 140-, 6-, and 2-MDa plasmids occurred commonly, irrespective of the place of isolation and drug resistance pattern of the strains. Certain profiles showed significant association with drug resistance patterns. These findings suggest that three plasmids, of molecular sizes 140, 6, and 2 MDa, are unique to S. dysenteriae type 1 strains and may indicate the global spread of a pathogenic bacterial clone. Additionally, these core plasmids, plus plasmids of various other sizes, could be used to identify emerging subclones which are causing both epidemic and sporadic disease. Thus, plasmid profiles of S. dysenteriae type 1 strains can be used to monitor possible pandemic strains as well as individual epidemic strains.     

Inactivation of chemotactic activity of C5a by the serratial 56-kilodalton protease.

The effects of the 56-kilodalton protease (56K protease) from Serratia marcescens on complement-derived chemotactic activity were examined. Fresh human serum was incubated with zymosan to produce C5a. This activated serum was then incubated with various concentrations of 56K protease, and the chemotactic activity of mouse peritoneal exudate polymorphonuclear leukocytes (PMN) and macrophages was evaluated. A significant dose-dependent decrease of chemotactic activity was observed after protease treatment. Furthermore, treatment of human recombinant C5a with 56K protease at a dose of 1.0 microgram/ml resulted in a complete loss of chemotactic activity. When the living bacteria of the virulent strain, which produced about 10 times more protease than did the less virulent strain, were injected intraperitoneally into mice, the magnitude of infiltration of polymorphonuclear leukocytes into the peritoneal cavity was much lower than that caused by the less virulent strain. Because complement-dependent chemotactic activity is an initial response to bacterial infection, these results suggest indirect pathogenic functions of serratial proteases that suppress chemotactic activity.     

Isolation of Campylobacter fetus subsp. jejuni from Bangladeshi children.

To determine the prevalence of infection with Campylobacter fetus subsp. jejuni in Bangladesh, culture surveys were conducted among three populations. In Dacca, Campylobacter was isolated from 5.2% of 97 individuals with clinical dysentery and from 12.3% of 204 patients with only diarrhea. This difference may have resulted from a greater representation of young children in the second group. Campylobacter was isolated from 17.7% of the 141 healthy village children aged 1 to 5.5 years and from 38.8% of the 1-year-old children. More infected children (48%) had a history of recent diarrheal illness than did a group of matched controls (20%; P = 0.016). These findings suggest that campylobacter infection is common for Bangladeshi children. However, this organism may not cause diarrheal illness in all instances in which it is isolated.     

Protocols for the dosimetry of high-energy photon and electron beams: a comparison of the IAEA TRS-398 and previous international codes of practice. International Atomic Energy Agency

A new international Code of Practice for radiotherapy dosimetry co-sponsored by several international organizations has been published by the IAEA, TRS-398. It is based on standards of absorbed dose to water, whereas previous protocols (TRS-381 and TRS-277) were based on air kerma standards. To estimate the changes in beam calibration caused by the introduction of TRS-398, a detailed experimental comparison of the dose determination in reference conditions in high-energy photon and electron beams has been made using the different IAEA protocols. A summary of the formulation and reference conditions in the various Codes of Practice, as well as of their basic data, is presented first. Accurate measurements have been made in 25 photon and electron beams from 10 clinical accelerators using 12 different cylindrical and plane-parallel chambers, and dose ratios under different conditions of TRS-398 to the other protocols determined. A strict step-by-step checklist was followed by the two participating clinical institutions to ascertain that the resulting calculations agreed within tenths of a per cent. The maximum differences found between TRS-398 and the previous Codes of Practice TRS-277 (2nd edn) and TRS-381 are of the order of 1.5-2.0%. TRS-398 yields absorbed doses larger than the previous protocols, around 1.0% for photons (TRS-277) and for electrons (TRS-381 and TRS-277) when plane-parallel chambers are cross-calibrated. For the Markus chamber, results show a very large variation, although a fortuitous cancellation of the old stopping powers with the ND,w/NK ratios makes the overall discrepancy between TRS-398 and TRS-277 in this case smaller than for well-guarded plane-parallel chambers. Chambers of the Roos-type with a 60Co ND,w calibration yield the maximum discrepancy in absorbed dose, which varies between 1.0% and 1.5% for TRS-381 and between 1.5% and 2.0% for TRS-277. Photon beam calibrations using directly measured or calculated TPR20,10 from a percentage dose data at SSD = 100 cm were found to be indistinguishable. Considering that approximately 0.8% of the differences between TRS-398 and the NK-based protocols are caused by the change to the new type of standards, the remaining difference in absolute dose is due either to a close similarity in basic data or to a fortuitous cancellation of the discrepancies in data and type of chamber calibration. It is emphasized that the NK-ND,air and ND,w formalisms have very similar uncertainty when the same criteria are used for both procedures. Arguments are provided in support of the recommendation for a change in reference dosimetry based on standards of absorbed dose to water.     

Comparison of the costs of compliance with nutrition education messages to improve the diets of Bangladeshi breastfeeding mothers and weaning-age children

Local market prices in rural Bangladesh were used to compute the costs of filling the nutrient gaps between actual intakes and safe nutrient requirements, and the costs of compliance with nutrition messages, for 78 lactating mothers and 61 weaning-age breastfed children. (The gap is the difference between the requirement and the amount of nutrient consumed.) To fill the mother's energy gap of approximately 1050 kcal (4393 kJ) would cost an additional 21% of the daily wage, or almost double the value of food she was presently eating. Given social reality, these costs would probably be much greater, as the mother would also need to increase the allocation of food to other household members. The weaning-age children's energy gap could theoretically be closed for less than one-third of the cost of improving the mothers' diets, or about 8% of the daily wage. The increase in food intake equivalent to 2% of the daily wage actually achieved through nutrition education resulted in a significant improvement in child weight gain, though not ideal. These findings suggest that, in the absence of programs which reduce economic barriers, it is economically feasible for families to close the nutrient gaps for weaning-age breastfed children in Bangladesh, but not for lactating women. Thus, education to improve women's diets should be incorporated into programs that make these improvements affordable, whereas education to improve weaning-age children's diets can be implemented with or without other program supports.