Significant Increase In Infections Research Articles

Peroxiredoxins from Trypanosoma cruzi: Virulence factors and drug targets for treatment of Chagas disease?

Cytosolic and mitochondrial Trypanosoma cruzi tryparedoxin peroxidases belong to the family of 2-Cys peroxiredoxins. These enzymes play an essential role as antioxidants by their peroxidase and peroxynitrite reductase activities. TXNPx are key components of the trypanosomatid peroxide detoxification pathways. The aim of this work was to determine the role of TXNPx as virulence factors in the parasite, and whether these enzymes are good candidates for drug design. We observed that peroxiredoxins are not highly abundant proteins expressed at similar levels throughout the T. cruzi life cycle. In order to study the role of c-TXNPx and m-TXNPx in invasion and infectivity, parasites overexpressing TXNPx were produced, and infection experiments were carried out using phagocytic and non-phagocytic cells. Parasites overexpressing peroxiredoxins showed a significant increase in infectivity with respect to the control ones. The results presented in this work point out that the T. cruzi peroxiredoxins are important in survival, replication and differentiation of T. cruzi and could constitute virulence factors. Moreover, their expression in the infective forms of the life cycle and their low intracellular concentration make them good candidates to become targets for drug design.

Cochlear Implant Complications

To explore the suitability of the Manufacturer User Facility and Distributor Experience (MAUDE) database (which is maintained by the Food and Drug Administration and has a mandatory reporting requirement) for systemic analysis of cochlear implant complications and treatments and, in so doing, analyze trends in cochlear implant complications for 2 periods, 2002 and pre-1998. All events from 2002 and from before 1998 were considered. Events and action taken were categorized and tabulated. Because there was no null hypothesis, statistical analysis (chi2) was only used in comparing the 2 time frames. Structural limitations of the database, in addition to disparate reporting quality, made systematic analysis difficult. It was noted that spontaneous device failure accounted for the greatest single number of adverse events for both 2002 and the pre-1998 period (267/654 [41%] and 74/129 [57%], respectively), confirming earlier studies. A statistically significant decrease in spontaneous device failure and a significant increase in infections from the pre-1998 period to 2002 was observed. Flap problems ranging from extrusion to infection that required explantation were less frequently reimplanted than other problems requiring explantation, such as device failure or trauma. We considered new directions, including close collaboration with the new MedSun reporting system and conclude that while a valuable resource for narrative data, the current structure of the MAUDE database is only modestly useful for analyzing trends in complications and cannot answer several crucial questions, including device type comparisons. We suggest changing the current report format to include patient age, duration of implant, presence of anatomical abnormalities, and details on spontaneous device failures.

Signal transduction and functional changes in neutrophils with aging.

It is well known that the immune response decreases during aging, leading to a higher susceptibility to infections, cancers and autoimmune disorders. Most widely studied have been alterations in the adaptive immune response. Recently, the role of the innate immune response as a first-line defence against bacterial invasion and as a modulator of the adaptive immune response has become more widely recognized. One of the most important cell components of the innate response is neutrophils and it is therefore important to elucidate their function during aging. With aging there is an alteration of the receptor-driven functions of human neutrophils, such as superoxide anion production, chemotaxis and apoptosis. One of the alterations underlying these functional changes is a decrease in signalling elicited by specific receptors. Alterations were also found in the neutrophil membrane lipid rafts. These alterations in neutrophil functions and signal transduction that occur during aging might contribute to the significant increase in infections in old age.

Outcomes in Open Tibia Fractures: Relationship between Delay in Treatment and Infection

Emergent irrigation and debridement has been accepted as a mainstay of open fracture treatment. The purpose of this study was to evaluate the infectious outcome of open tibia fractures relative to the time from injury to operative irrigation and debridement. One hundred seventy-eight patients with 191 consecutive fractures were retrospectively reviewed. Of these, 103 patients with 106 fractures were available for this study, with an average follow-up of 10.23 months. Results revealed 21.7% type I fractures, 43.4% type II fractures, 16.0% type IIIa fractures, 11.3% type IIIb fractures, and 7.5% type IIIc fractures. Of all fracture types, 22.6% became infected and 5.7% went on to have osteomyelitis. The average time to treatment was not significantly different in infected versus noninfected fractures across fracture types. No infection occurred when the time to surgery was within 2 hours; however, no significant increase in infection was discovered with respect to patients treated after 6 hours compared with those treated within 6 hours. The results support the Gustilo grading system of open fractures as a significant prognostic indicator for infectious complication. We continue to support the emergent treatment of open tibia fractures.

A specific cis-hairpin ribozyme facilitates infection of a TMV-based DNA vector in tobacco protoplasts

The effect of a specific cis-hairpin ribozyme on TMV-based vectors in the infection of tobacco protoplasts was studied. Vectors contained full-length TMV genome cDNA linked to a T7 promoter or a CaMV 35S promoter at the 5′-end and an NOS gene polyadenylation signal at the 3′-end. The coat protein (CP) gene was replaced with the green fluorescent protein (GFPuv) gene allowing quantification of protoplast infection. In plasmids pTMVGFPRIB (T7-driven) and pSTMVGFPRIB (CaMV 35S-driven), the cDNA fragment of the cis-hairpin ribozyme (designed to specifically cleave the transcripts immediately downstream of the 3′-terminus of TMV RNA) was inserted between the 3′-terminus of TMV genome and NOS sequence. The in vitro transcript TMVGFPRIB was three- to fivefold more infectious than the control TMVGFPNOS. Northern blot analysis indicated that the 3′-terminal non-viral sequence had been cleaved from the in vitro transcripts by the cis-hairpin ribozyme soon after in vitro transcription. pSTMVGFPRIB and pSTMVGFPNOS plasmid DNAs were, as expected, less infectious than their in vitro transcript counterparts. However, pSTMVGFPRIB was somewhat more infectious than pSTMVGFPNOS. Northern blot analysis indicated that pSTMVGFPRIB synthesized more genomic and sub-genomic RNAs in the protoplasts. The significant increase in infectivity and viral RNA synthesis is due to the specific activity of the cis-hairpin ribozyme in vivo. Therefore, the cis-hairpin ribozyme described here may improve TMV-based vectors in the expression of foreign protein in plants.

Evolving trends in multiple-antibiotic-resistant bacteria in liver transplant recipients: a longitudinal study of antimicrobial susceptibility patterns.

The incidence, sources, impact on outcome, and temporal trends in multiple-antibiotic-resistant bacteria in liver transplant recipients over the last decade (from 1990 through 1999) were assessed. Of 165 consecutive patients who underwent transplantation, 31% (51 of 165 patients) had at least 1 infection caused by multiple-antibiotic-resistant bacteria. Overall, 69% (66 of 96 infections) of all bacterial infections were multiple-antibiotic resistant. Ninety-one percent (45 of 49 isolates) of the Staphylococcus aureus isolates, 50% (6 of 12 isolates) of the enterococci, and 54% of the gram-negative bacteria (47%; 7 of 15 Pseudomonas aeruginosa, and 60%; 12 of 20 Enterobacteriaceae) were multiple-antibiotic resistant. A significant trend toward an increase in infections caused by multiple-antibiotic-resistant bacteria (P =.003), largely caused by an increase in gram-positive infections, was documented through the decade. There was a significant increase in infections caused by methicillin-resistant S aureus (P =.0001) and vancomycin-resistant enterococci (P =.04) over time. The proportion of gram-negative isolates that were multiple-antibiotic resistant (P =.447) did not increase significantly over time. However, a strikingly high frequency of resistance to piperacillin or ceftazidime suggests that extended-spectrum beta-lactamase production in our Enterobacteriaceae may have been more prevalent than realized. Mortality at 1 year was significantly greater in patients with multiple-antibiotic resistant bacteria compared with all other patients (P =.001). These longitudinal trends have implications not only for guiding therapeutic practices, but ultimately for devising strategies to curtail multiple-antibiotic resistance in liver transplant recipients.

Vaginal candidosis: epidemiological and etiological factors

A review is presented of the emerging problem of candidal colonization regarding epidemiological and etiological factors. In recent years a change in epidemiological trends has been observed. Vaginal candidosis seems to show a higher frequency to recur and a significant increase in infections caused by non albicans species of candidas has been stated. The three stage mechanisms of adhesion, blastopore germination and epithelium invasion are emphasized. There is a balance between candidal organisms and vaginal defense factors (lactobacilli, cellular and humoral immunity) controlling and limiting fungal growth. Vaginitis appears because of an increased number or an enhanced virulence of candidas. In some other patients, a decreased vaginal defense mechanism is a determinant factor. There are still a number of factors involved in clinical candidal vulvovaginitis that need to be clarified.

Involvement of spindles of an entomopoxvirus (EPV) in infectivity of the EPVs to their host insect.

The biological function of entomopoxvirus (EPV) spindles (inclusion bodies that lack virions), has not been elucidated. We characterized the function of EPV spindles in the cupreous chafer, Anomala cuprea (Coleoptera: Scarabaeidae). Spheroids or spheroids mixed with spindles of Anomala cuprea EPV were administered per os to the A. cuprea larvae. A significant increase in infectivity was induced by the addition of spindles to the spheroids, strongly suggesting that the spindles play an important role in the infection of the host insect.

Mycophenolate mofetil in cardiac transplantation.

Mycophenolate mofetil (MMF) is a new immunosuppressive agent with proven efficacy in the prevention of rejection in renal transplant recipients. Clinical studies in heart transplantation have suggested efficacy in patients with refractory and persistent rejection. A large multicenter randomized primary prevention trial in heart transplant patients has just been completed and suggests benefits of MMF in survival and treated rejection episodes. This drug appears to be well tolerated without significant increase in infection or other complications. MMF appears to be an important immunosuppressive agent in cardiac transplant recipients.

Virulence factors of influenza A viruses: WSN virus neuraminidase required for plaque production in MDBK cells.

The genetic basis for the distinctive capacity of influenza A/WSN/33 (H0N1) virus (WSN virus) to produce plaques on bovine kidney (MDBK) cells was found to be related to virus neuraminidase. Recombinant viruses that derived only the neuraminidase of WSN virus were capable of producing plaques, whereas recombinant viruses identical to WSN except for neuraminidase did not produce plaques. With viruses that do not contain WSN neuraminidase, infectivity of virus yields from MDBK cells was increased approximately 1,000-fold after in vitro treatment with trypsin. In contrast, no significant increase in infectivity was observed after trypsin treatment of viruses containing WSN neuraminidase. In addition, polyacrylamide gel analysis of proteins of WSN virus obtained after infection of MDBK cells demonstrated that hemagglutinin was present in the cleaved form (HA1 + HA2), whereas only uncleaved hemagglutinin was obtained with a recombinant virus that derived all of its genes from WSN virus except its neuraminidase. These data are in accord with the hypothesis that neuraminidase may facilitate production of infectious particles by removing sialic acid residues and exposing appropriate cleavage sites on hemagglutinin.

Translation of turnip yellow mosaic virus RNA in vitro: a closed and an open coat protein cistron.

Sucrose gradient centrifugation of heat-denatured RNA of turnip yellow mosaic virus permitted the isolation of five RNA classes with molecular weights ranging from 2.0 to 0.25 X 10(6). The infectivity was shown to be confined to an RNA molecule of molecular weight 2.0 X 10(6). No significant increase in infectivity was obtained by combination of the latter RNA with the RNA classes of smaller size. Translation in vitro of the RNAs of different size classes in a wheat germ cell-free system revealed that the infectious RNA (molecular weight 2.0 X 10(6) does not promote the synthesis of the coat protein of turnip yellow mosaic virus. Efficient production of this coat protein was found exclusively when the smallest RNA class (molecular weight 250,000) was used as a messenger. It is concluded that RNA molecules of turnip yellow mosaic virus of molecular weight 2.0 X 10(6) contain a closed coat protein cistron and that RNA molecules of molecular weight about 2 to 3 X 10(5) with an open coat protein cistron can be isolated from the virions.

The Effects of Benomyl on Sensitive and Tolerant Isolate of Botrytis cinerea infecting Strawberries

SUMMARYStrawberry plants cv. Cambridge Vigour growing in a walk‐through polyethylene tunnel were experimentally inoculated with one benomyl‐sensitive and two benomyl‐tolerant isolates of Botrytis cinerea alone and in combination.Three applications of benpmyl significantly increased the number of infected fruits in four out of the six treatments. There was no significant increase in infection on plants inoculated only with the benomyl‐sensitive isolate. Plants inoculated only with a slow growing, benomyl‐tolerant isolate showed an increase in infection which was not quite enough to be significant at the 5 per cent level.The fast growing benomyl‐tolerant isolate spread more rapidly from plot to plot than the slow growing isolate.

Sugar-induced enhancement of tobacco mosaic virus ribonucleic acid infectivity

The addition of sugars to tobacco mosaic virus ribonucleic acid (TMV-RNA) inocula increased their infectivity over that of control inocula. Sucrose increased infectivity on Phaseolus vulgaris var. Pinto, while the same inoculum on Nicotiana glutinosa L., N. tabacum L. var. Xanthi-nc and Chenopodium amaranticolor Coste & Reyn produced no significant increase. Enhancement by sucrose was greatest when the TMV-RNA was in acetate buffer at pH 7.0 (133% increase) and distilled H 2O (116% increase). No significant increase in infectivity occurred when citrate, Tris, and phosphate buffers were used at this pH. Maximum enhancement was obtained when sucrose and TMV-RNA were applied to the leaf simultaneously. Treatments which increased the infectivity of TMV-RNA or the susceptibility of leaves decreased enhancement by sucrose. Conversely, enhancement occurred only under conditions where relatively few lesions were induced by the control inoculum. Preinoculation heat-dark and dark treatment reduced enhancement by sucrose 80 and 77%, respectively. Other sugars, disaccharides and monosaccharides, and polyalcohols increased infectivity in a comparable fashion to sucrose. The molar concentrations for optimum enhancement by sucrose and glucose were similar, hence, the effect seemed dependent on the colligative properties of the sugars. No interaction of sugar with the RNA was detectable by ultraviolet spectrophotometry. Sucrose did not stabilize the TMV-RNA, but increased its rate of inactivation, especially if the sucrose had been autoclaved. The argument is advanced that enhancement is brought about by the action of sucrose on the cell penetration phase of the infection process. Sucrose does not enhance the infectivity of the virion, and for this reason the mechanism of penetration by the viral RNA is thought to be different.

Induction of amebiasis in tissues of white mice and rats by subcutaneous inoculation of small free-living, inquilinic, and parasitic amebas with associated coliform bacteria

Amebas from the genera Acanthamoeba, Vahlkampfia, Hartmannella, Entamoeba, and Endolimax were isolated from water samples or from fecal contents of various snakes and lizards and cultured with their associated bacteria on Neff's agar slants. Saline suspensions of trophic and encysted amebas and bacteria were injected intraperitoneally into white laboratory mice, or intramuscularly into white laboratory rats. The animals were sacrificed after 6 weeks, and trophic and encysted amebas were identified from the coelom, lung, liver, lymph nodes, and kidney of the mice, and from the coelom, lung, spleen, liver, peritoneum, kidney, lymph nodes, blood, and brain of the rats. Cortisone-acetate-treated rats gave no significant increase in infectivity over nontreated rats. The significance of infection of mammalian hosts by free-living, inquilinic or poikilothermic parasites is discussed.

Exploratory tests to prevent leaf roll infection transmitted by aphids

Experiments were conducted at Presque Isle, Maine, to determine whether single applications of foliar sprays of several substances would affect spread of leaf roll virus by the green peach aphidMyzus persicae (Sulzer) to potato plants of the Chippewa variety growing in cages in the field. In 1958, little, if any, protection from leaf roll was afforded from 1 or 1/2% water extract of rice polish. In 1960, the 21% protection from the American Cyanamid antifeeding compound CL-24055 (1,1-dimethyl-3-(p-acetamidophenyl) triazene) at 3 lb/100 gal was significant, and that from reconstituted skim milk nearly so ; a significant increase in infection of 20% occurred when the plants were sprayed with whey from non-pasteurized skim milk, and a similar tendency with whey from pasteurized skim milk ; no appreciable effect was obtained with raw or pasteurized whole milk, a 1:1 dilution of juice from the leaf roll-resistant seedling B3559-53 and water, or a 1 1/2% water suspension of rice polish. Protection or lack of protection from the virus was probably by inhibiting or stimulating aphid feeding.