Role of magnetic Field in the Healing of Cutaneous Leishmaniasis Lesions in Mice.

Leishmaniasisis an important tropical cutaneous disease that is endemic in the Middle East, including Iran. There is no consensus on the appropriate therapeutic method, dose, and duration for this disease. The pentavalent antimonial compounds are the first-line treatments of leishmaniasis. With regard to the resistance of this disease against drugs and its treatment failure in some patients, the present study was conducted to investigate the role of alternating magnetic field (AMF) in the treatment of cutaneous leishmaniasis lesionsin mice. To this end, 45 male Balb/c mice with the age of 3-4 weeks and weight of 18-20 g were purchased from the Pasteur Institute, Tehran, Iran, to be investigated. The mice were infected with Leishmania promastigote (2×106) injected in the upper end of the tail.After 3 weeks, the animals were screened for developing lesions. Finally, 15 mice were selected and randomly divided into three equal groups of positive control (treated with the standard drug), negative control (without treatment), and experimental (subjected to AMF at a frequency of 50 kHz for 30 min on a daily basis for 4 weeks). The subjects were followed up for 4 weeks, and the size of their lesions was measured weekly. The data were analyzed by repeated measures test in SPSS software (version 20) at a p-value of < 0.05. There was no significant difference between the experimental and positive control groups (P>0.05). However, the negative control group showed a significant difference with the positive control and experimental groups (P=0.0001). As the findings indicated, AMF was seemingly able to decrease the size of lesions to the same extent as the standard drug. Consequently, AMF could be suggested as a noninvasive and complementary tool against cutaneous leishmaniasis. However, it is required to perform more studies to address different aspects of this domain.

Observed fingerprint of a weakening Atlantic Ocean overturning circulation.

The Atlantic meridional overturning circulation (AMOC)-a system of ocean currents in the North Atlantic-has a major impact on climate, yet its evolution during the industrial era is poorly known owing to a lack of direct current measurements. Here we provide evidence for a weakening of the AMOC by about 3 ± 1 sverdrups (around 15 per cent) since the mid-twentieth century. This weakening is revealed by a characteristic spatial and seasonal sea-surface temperature 'fingerprint'-consisting of a pattern of cooling in the subpolar Atlantic Ocean and warming in the Gulf Stream region-and is calibrated through an ensemble of model simulations from the CMIP5 project. We find this fingerprint both in a high-resolution climate model in response to increasing atmospheric carbon dioxide concentrations, and in the temperature trends observed since the late nineteenth century. The pattern can be explained by a slowdown in the AMOC and reduced northward heat transport, as well as an associated northward shift of the Gulf Stream. Comparisons with recent direct measurements from the RAPID project and several other studies provide a consistent depiction of record-low AMOC values in recent years.

Suppression of NDA-type alternative mitochondrial NAD(P)H dehydrogenases in arabidopsis thaliana modifies growth and metabolism, but not high light stimulation of mitochondrial electron transport.

The plant respiratory chain contains several pathways which bypass the energy-conserving electron transport complexes I, III and IV. These energy bypasses, including type II NAD(P)H dehydrogenases and the alternative oxidase (AOX), may have a role in redox stabilization and regulation, but current evidence is inconclusive. Using RNA interference, we generated Arabidopsis thaliana plants simultaneously suppressing the type II NAD(P)H dehydrogenase genes NDA1 and NDA2. Leaf mitochondria contained substantially reduced levels of both proteins. In sterile culture in the light, the transgenic lines displayed a slow growth phenotype, which was more severe when the complex I inhibitor rotenone was present. Slower growth was also observed in soil. In rosette leaves, a higher NAD(P)H/NAD(P)⁺ ratio and elevated levels of lactate relative to sugars and citric acid cycle metabolites were observed. However, photosynthetic performance was unaffected and microarray analyses indicated few transcriptional changes. A high light treatment increased AOX1a mRNA levels, in vivo AOX and cytochrome oxidase activities, and levels of citric acid cycle intermediates and hexoses in all genotypes. However, NDA-suppressing plants deviated from the wild type merely by having higher levels of several amino acids. These results suggest that NDA suppression restricts citric acid cycle reactions, inducing a shift towards increased levels of fermentation products, but do not support a direct association between photosynthesis and NDA proteins.

Suppression of the external mitochondrial NADPH dehydrogenase, NDB1, in Arabidopsis thaliana affects central metabolism and vegetative growth.

Ca(2+)-dependent oxidation of cytosolic NADPH is mediated by NDB1, which is an external type II NADPH dehydrogenase in the plant mitochondrial electron transport chain. Using RNA interference, the NDB1 transcript was suppressed by 80% in Arabidopsis thaliana plants, and external Ca(2+)-dependent NADPH dehydrogenase activity became undetectable in isolated mitochondria. This was linked to a decreased level of NADP(+) in rosettes of the transgenic lines. Sterile-grown transgenic seedlings displayed decreased growth specifically on glucose, and respiratory metabolism of (14)C-glucose was increased. On soil, NDB1-suppressing plants had a decreased vegetative biomass, but leaf maximum quantum efficiency of photosystem II and CO2 assimilation rates, as well as total respiration, were similar to the wild-type. The in vivo alternative oxidase activity and capacity were also similar in all genotypes. Metabolic profiling revealed decreased levels of sugars, citric acid cycle intermediates, and amino acids in the transgenic lines. The NDB1-suppression induced transcriptomic changes associated with protein synthesis and glucosinolate and jasmonate metabolism. The transcriptomic changes also overlapped with changes observed in a mutant lacking ABAINSENSITIVE4 and in A. thaliana overexpressing stress tolerance genes from rice. The results thus indicate that A. thaliana NDB1 modulates NADP(H) reduction levels, which in turn affect central metabolism and growth, and interact with defense signaling.

Light-responsive metabolite and transcript levels are maintained following a dark-adaptation period in leaves of Arabidopsis thaliana.

• The effect of previous light conditions on metabolite and transcript levels was investigated in leaves of Arabidopsis thaliana during illumination and after light-enhanced dark respiration (LEDR), when dark respiration was measured. • Primary carbon metabolites and the expression of light-responsive respiratory genes were determined in A. thaliana leaves before and after 30 min of darkness following different light conditions. In addition, metabolite levels were determined in the middle of the night and the in vivo activities of cytochrome and alternative respiratory pathways were determined by oxygen isotope fractionation. • A large number of metabolites were increased in leaves of plants growing in or transiently exposed to higher light intensities. Transcript levels of respiratory genes were also increased after high light treatment. For the majority of the light-induced metabolites and transcripts, the levels were maintained after 30 min of darkness, where higher and persistent respiratory activities were also observed. The levels of many metabolites were lower at night than after 30 min of darkness imposed in the day, but respiratory activities remained similar. • The results obtained suggest that 'dark' respiration measurements, as usually performed, are probably made under conditions in which the overall status of metabolites is strongly influenced by the previous light conditions.

An alternatively spliced domain of the NDC1 NAD(P)H dehydrogenase gene strongly influences the expression of the ACTIN2 reference gene in Arabidopsis thaliana.

In plant respiratory chains, alternative pathways for NAD(P)H oxidation are mediated by type II NAD(P)H dehydrogenases belonging to the NDA, NDB, and NDC families. For the latter type, Arabidopsis thaliana contains a single gene, NDC1, whose functional role has not previously been analyzed in the plant. We found that A. thaliana NDC1 is alternatively spliced. Four base pairs at the 3' end of intron 5 are spliced out in NDC1-1, but retained in the NDC1-2 mRNA, which therefore contains a truncated reading frame. Both variants are conserved in dicotyledonous and monocotyledonous plants and their relative abundance varies between organs and in response to light. Three analyzed NDC1 T-DNA insertion lines all displayed an early bolting phenotype. A dramatic upregulation of ACTIN2 was characteristic of two lines containing T-DNA inserts upstream of intron 5, whereas a line with an insertion downstream of the NDC1-2 reading frame had an ACTIN2 expression level identical to the wildtype. Thus, the alternatively spliced 5' domain of NDC1 strongly influences the expression of the functionally unrelated ACTIN2, which is a common reference gene for quantitative RT-PCR. Also for other reference genes, strong expressional effects were observed when comparing various mutants and wildtypes in microarray databases.

Involvement of mitochondria in the control of plant cell NAD(P)H reduction levels.

NADPH and NADH mediate reductant flow between cellular processes, linking central carbon and energy metabolism with intermediary metabolism, stress defence and development. Recent investigations have revealed paths of functional interactions, and have suggested that mitochondrial NADPH oxidation, especially together with the oxidative pentose phosphate pathway, is an important regulator of the cytosolic NADPH reduction level. Furthermore, stress-dependent metabolic pathways substantially affect the NADPH reduction level in particular physiological situations. The mitochondrial impact on the NADPH reduction level provides a model example of the physiological significance of the mitochondrial NAD(P)H dehydrogenase set-up, which is more complex in plants than in other organisms.

A redox-mediated modulation of stem bolting in transgenic Nicotiana sylvestris differentially expressing the external mitochondrial NADPH dehydrogenase.

Cytosolic NADPH can be directly oxidized by a calcium-dependent NADPH dehydrogenase, NDB1, present in the plant mitochondrial electron transport chain. However, little is known regarding the impact of modified cytosolic NADPH reduction levels on growth and metabolism. Nicotiana sylvestris plants overexpressing potato (Solanum tuberosum) NDB1 displayed early bolting, whereas sense suppression of the same gene led to delayed bolting, with consequential changes in flowering time. The phenotype was dependent on light irradiance but not linked to any change in biomass accumulation. Whereas the leaf NADPH/NADP(+) ratio was unaffected, the stem NADPH/NADP(+) ratio was altered following the genetic modification and strongly correlated with the bolting phenotype. Metabolic profiling of the stem showed that the NADP(H) change affected relatively few, albeit central, metabolites, including 2-oxoglutarate, glutamate, ascorbate, sugars, and hexose-phosphates. Consistent with the phenotype, the modified NDB1 level also affected the expression of putative floral meristem identity genes of the SQUAMOSA and LEAFY types. Further evidence for involvement of the NADPH redox in stem development was seen in the distinct decrease in the stem apex NADPH/NADP(+) ratio during bolting. Additionally, the potato NDB1 protein was specifically detected in mitochondria, and a survey of its abundance in major organs revealed that the highest levels are found in green stems. These results thus strongly suggest that NDB1 in the mitochondrial electron transport chain can, by modifying cell redox levels, specifically affect developmental processes.

Activity and expression of nitric oxide synthase in rat bladder after sacral neuromodulation.

The aim of our study is to investigate the effects of chronic sacral neuromodulation on Nitric Oxide (NO) metabolism in the rat bladder. 26 female Sprangue-Dawley rats were considered: group I, normal control rats; group II, a sham treatment, in whom catheters for electrical stimulation were placed in the S1 foramen bilaterally and left in place for 21 days, without performing neuromodulation; group III in whom electrical sacral neuromodulation was performed for 21 days. Finally a cystectomy was performed and the bladder biopsy specimens were sent for immunostaining with n-NOS and i-NOS. Morphological and immunohistochemical analysis was carried out, and evaluated in urothelial cells, endothelial cells and muscle fibers of the muscularis propria. Differences between the 3 groups were analyzed by Student Newman-Keuls test. We could observe that urothelial and endothelial i-NOS (37.00+/-4.69 and 59.00+/-7.42 respectively) and urothelial n-NOS (36.80+/-7.85) expression are significantly increased in neuromodulated rats, compared to groups 1 and 2 (p<0.005). In conclusion, the increase of i-NOS expression on endothelial cells after sacral neuromodulation could be in some way related to angiogenetic responses in the microvascular structures; the increase of n-NOS and i-NOS expression on urothelial cells can suggest that NO is able to influence the plasticity of bladder response, inducing the release of messengers within the urothelium. This study can therefore improve our understanding of the mechanisms of sacral neuromodulation on chronic bladder dysfunction; further studies will need to better demonstrate the role of angiogenesis in the bladder after sacral neuromodulation and to investigate the effects of neuromodulation in rats with chronically induced bladder dysfunction.

RNAIII-inhibiting peptide and/or nisin inhibit experimental vascular graft infection with methicillin-susceptible and methicillin-resistant Staphylococcus epidermidis.

OBJECTIVE: To investigate the efficacy of RNAIII-inhibiting peptide (RIP) and nisin as prophylactic agents in a rat model of vascular graft infection. DESIGN: Prospective, randomized, controlled animal study. MATERIALS: Two hundred and twenty adult male Wistar rats. Staphylococcus epidermidis ATCC 12228 and one clinical isolate of methicillin-resistant S. epidermidis. Drugs: RIP, nisin and rifampin. METHODS: Graft infections were established in the dorsal subcutaneous tissue by implantation of 1 cm(2) sterile Dacron grafts, followed by topical bacterial inoculation: grafts were retrieved at 7 days. The study included a control group (without inoculation) and two series composed of five groups for each staphylococcal strain: one contaminated group that did not receive any antibiotic prophylaxis, three contaminated groups that received grafts soaked with 10 mg/l RIP, 10 mg/l nisin, 10 mg/l rifampin, or RIP+nisin. The main outcome measure was the extent of bacterial at graft harvest. RESULTS: The bacterial counts for methicillin-resistant S. epidermidis on explanted grafts were 6.1+/-2.8x10(2), 7.8+/-3.0x10(3) and 5.5+/-2.9x10(4) for RIP, nisin and rifampin, respectively. RIP and nisin used in combination reduced the bacterial count to <10. The results for S. epidermidis were similar. CONCLUSIONS: RIP and nisin could be used in combination to coat medical devices to prevent drug resistant S. epidermidis infections.

Survival and behavior of freshwater turtles after rehabilitation from an oil spill.

An oil spill in February 2000 at the John Heinz National Wildlife Refuge in southeastern Pennsylvania affected four species of freshwater turtles including painted turtles (Chrysemys picta), snapping turtles (Chelydra serpentina), red-eared slider turtles (Trachemys scripta), and red-bellied turtles (Pseudemys rubriventris). In the summer and fall of 2000, there were no differences in survival, home range, and temperature preference of 16 oil exposed/rehabilitated (OER) turtles, 18 possibly exposed (PE) turtles, and 32 non-exposed (NE) turtles as measured with temperature sensitive radio transmitters. Post-release mortality or transmitter loss was not correlated to oil exposure (OER = 25%, PE = 22%, NE = 31%). There were no statistically significant differences in home range minimum convex polygon area, (0.28

Antiendotoxin activity of antimicrobial peptides and glycopeptides.

An animal study was performed to investigate the efficacy of two glycopeptides and two cationic peptides in the prevention of lethality in a septic shock rat model. Adult Wistar rats were given an intraperitoneal injection of 2x10(10) CFU of Escherichia coli ATCC 25922, with the exception of an uninfected control group (C0). Animals were randomized to receive, immediately after bacterial challenge, intraperitoneally isotonic sodium chloride solution (control group C1), 3 mg/Kg teicoplanin (group 1), 7 mg/Kg vancomycin (group 2), 1 mg/Kg colistin (group 3), 1 mg/Kg buforin II (group 4), or 60 mg/Kg piperacillin (group C(PIP)). In addition, four groups (1a, 2a, 3a, and 4a) received the above mentioned drugs in combination with piperacillin. All compounds and combinations significantly reduced the lethality and the number of E. coli in abdominal fluid compared with C1 group, with the exception of the glycopeptides. Colistin and buforin II combined with piperacillin significantly decreased the lethality compared with piperacillin alone. Finally, colistin, buforin II, and teicoplanin significantly reduced plasma endotoxin concentration in comparison with piperacillin and saline treatment. Antimicrobial peptides and teicoplanin act as antiendotoxin agents and enhance the efficacy of piperacillin.

Administration of protegrin peptide IB-367 to prevent endotoxin induced mortality in bile duct ligated rats.

BACKGROUND: Postoperative morbidity in patients with obstructive jaundice remains high because of increased susceptibility to endotoxin and the inflammatory cascade. AIMS: An experimental study was designed to investigate the efficacy of protegrin peptide IB-367, an antimicrobial positively charged peptide, in neutralising Escherichia coli 0111:B4 lipopolysaccharide (LPS) in bile duct ligated rats. METHODS: Adult male Wistar rats were injected intraperitoneally with 2 mg/kg E coli 0111:B4 LPS one week after sham operation or bile duct ligation (BDL). Six groups were studied: sham with placebo, sham with 120 mg/kg tazobactam-piperacillin (TZP), sham with 1 mg/kg IB-367, BDL with placebo, BDL with 120 mg/kg TZP, and BDL with 1 mg/kg IB-367. RESULTS: Main outcome measures were: endotoxin and tumour necrosis factor alpha (TNF-alpha) concentrations in plasma, evidence of bacterial translocation in blood and peritoneum, and lethality. After LPS, TNF-alpha plasma levels were significantly higher in BDL rats compared with sham operated animals. IB-367 caused a significant reduction in plasma endotoxin and TNF-alpha concentrations compared with placebo and TZP treated groups. In contrast, both TZP and IB-367 significantly reduced bacterial growth compared with saline treatment. Finally, LPS induced 60% and 55% lethality in BDL placebo and TZP treated rats and no lethality in sham operated rats, while only IB-367 significantly reduced lethality to 10%. CONCLUSIONS: By virtue of its dual antimicrobial and antiendotoxin properties, IB-367 could be an interesting compound to inhibit bacterial translocation and endotoxin release in obstructive jaundice.

Quinupristin/dalfopristin bonding in combination with intraperitoneal antibiotics prevent infection of knitted polyester graft material in a subcutaneous rat pouch model infected with resistant Staphylococcus epidermidis.

OBJECTIVE: to investigate the efficacy of quinupristin/dalfopristin in the prevention of prosthetic graft infection in a rat subcutaneous pouch model. METHODS: graft infections were established in the subcutaneous tissue of 140 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with Staphylococcus epidermidis with intermediate resistance to glycopeptides. The study included one group without contamination, one contaminated group without prophylaxis, one contaminated group that received 50mg/l quinupristin/dalfopristin-soaked graft, one contaminated group that received 10mg/kg intraperitoneal levofloxacin, one contaminated group that received 3mg/kg intraperitoneal doxycycline, and two contaminated groups that received 50mg/l quinupristin/dalfopristin-soaked plus 10mg/kg intraperitoneal levofloxacin or 3mg/kg intraperitoneal doxycycline. Each group included 20 animals. The grafts were removed after 7 days and evaluated by quantitative culture. RESULTS: quinupristin/dalfopristin showed a significantly higher efficacy than levofloxacin and doxycycline, even though quantitative graft cultures for rats that received only quinupristin/dalfopristin-soaked graft showed bacterial growth. Otherwise, the efficacy of levofloxacin was similar to that of doxycycline. Only the group treated with quinupristin/dalfopristin combined with levofloxacin or doxycycline showed no evidence of staphylococcal infection. CONCLUSIONS: quinupristin/dalfopristin as adjunctive topical antibiotic prophylaxis can be useful for the prevention of vascular graft infections caused by staphylococcal strains with high levels of resistance.

Antiseptic compounds still active against bacterial strains isolated from surgical wound infections despite increasing antibiotic resistance.

The in vitro activities of povidone iodine, potassium peroxymonosulfate, and dimethyldidecylammonium chloride were investigated against 379 nosocomial isolates of Staphylococcus aureus and Pseudomonas aeruginosa responsible for surgical wound infections in patients operated on between July 1995 and June 2001. Overall, the isolates were inhibited by the antiseptics at concentrations below those used routinely. In spite of increasing resistance to the various antibiotics used to treat surgical wound infections, no significant variation in the susceptibility to antiseptics was demonstrated during this 6-year study.

Therapeutic efficacy of the polymyxin-like peptide ranalexin in an experimental model of endotoxemia.

BACKGROUND: A rat model was used to investigate the efficacy of a polycationic peptide, the polymyxin-like ranalexin, in the prevention of lethality in a rat model of septic shock. The effect of ranalexin was compared with those of polymyxin B and imipenem. METHODS: Adult male Wistar rats (weight range: 250-300 g) were used for all the experiments. The study included five groups: an uninfected control group C(0), an untreated control group C(1), and three drug-treated groups that received 1 mg/kg ranalexin (group 2), 20 mg/kg imipenem (group 3), and 3 mg/kg polymyxin B (group 4). Rats, with the exception of the uninfected control group (C(0)), were given an intraperitoneal injection of 2 x 10(10) colony-forming units of Escherichia coli. Each group included 15 animals. Bacterial growth in abdominal exudate and plasma; endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma, and mortality were evaluated. RESULTS: Results were evaluated 48 h after inoculation. Ranalexin, imipenem, and polymyxin B significantly reduced the lethality (survival was 93.3, 80.0, and 93.3%, respectively) and the growth of E. coli both in abdominal fluid and plasma compared with saline treatment. Ranalexin showed higher antimicrobial activity than polymyxin B and imipenem and, at the same time, exhibited an antiendotoxin activity similar to that of polymyxin B (< or =0.015 EU/mL). Finally, ranalexin and polymyxin B significantly reduced plasma TNF-alpha levels (< or =4 pg/mL). CONCLUSION: Monodose ranalexin treatment prevents bacterial growth, endotoxemia, and mortality in rats with septic shock.

Effect of mono-dose intraperitoneal cecropins in experimental septic shock.

OBJECTIVE: To investigate the efficacy of three cecropins, cecropin A, cecropin B, and cecropin P1, in preventing lethality in a rat model of septic shock. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Rats were given an intraperitoneal injection of 2 x 10(10) colony forming units of Escherichia coli, with the exception of the uninfected control group (C0). Animals were randomized to receive, immediately after bacterial challenge, intraperitoneally isotonic sodium chloride solution (untreated control group C1), 1 mg/kg cecropin A (group 2), 1 mg/kg cecropin B (group 3), 1 mg/kg cecropin P1 (group 4), 20 mg/kg imipenem (group 5), or 60 mg/kg piperacillin (group 6). Each group included 15 animals. MEASUREMENTS AND MAIN RESULTS: We measured bacterial growth (quantitative agar culture) in abdominal exudate and plasma, endotoxin and tumor necrosis factor-alpha concentration in plasma, and mortality. Results were evaluated at 48 hrs after inoculation. Cecropins, piperacillin, and imipenem significantly reduced the lethality and the number of E. coli in abdominal fluid compared with saline treatment. In addition, cecropin B significantly decreased the lethality compared with piperacillin treatment. Finally, only cecropins significantly reduced plasma endotoxin concentration. CONCLUSIONS: Mono-dose cecropin treatment prevents bacterial growth, endotoxemia, and mortality in rats with septic shock. Cecropin B was the most effective compound in reducing all variables measured.

Nursing informatics: yesterday, today and tomorrow.

Today, at the beginning of the 21st century, nursing informatics has become a part of our professional activities. Informatics has advanced the field of nursing by bridging the gap from nursing as an art to nursing as a science. This article discusses the major milestones that have influenced the growth of computer technology and the specific efforts that have influenced yesterday's creation of the nursing informatics movement. It also provides an overview of nursing informatics in today's health care industry, while highlighting the administrative, management, research and educational applications and initiatives. In addition, it provides an overview of Saba's Home Health Care Classification, a nursing language system that has influenced the field. Finally, it provides a prediction of how computer technology will impact the nursing profession in the 21st century.

Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability.

BACKGROUND: Studies have implicated a role for prostaglandin (PG) E(2)-dependent matrix metalloproteinase (MMP) biosynthesis in the rupture of atherosclerotic plaque. Cyclooxygenase-2 (COX-2) and PGE synthase (PGES) are coregulated in nucleated cells by inflammatory stimuli. The aim of this study was to characterize the expression of COX-2 and PGES in carotid plaques and to correlate it with the extent of inflammatory infiltration and MMP activity and with clinical features of patients' presentation. METHODS AND RESULTS: Plaques were obtained from 50 patients undergoing carotid endarterectomy and divided into 2 groups (symptomatic and asymptomatic) according to clinical evidence of recent transient ischemic attack or stroke. Plaques were analyzed for COX-2, PGES, MMP-2, and MMP-9 by immunocytochemistry and Western blot, whereas zymography was used to detect MMP activity. Immunocytochemistry was used to identify CD68+ macrophages, CD3+ T lymphocytes, and HLA-DR+ cells. The percentage of macrophage-rich areas was larger (P<0.0001) in symptomatic plaques. COX-2, PGES, and MMPs were detected in all specimens; enzyme concentration, however, was significantly higher in symptomatic plaques. COX-2, PGES, and MMPs were especially noted in shoulders of symptomatic plaques, colocalizing with HLA-DR+ macrophages. All symptomatic plaques contained activated forms of MMPs. Finally, inhibition of COX-2 by NS-398 was accompanied by decreased production of MMPs that was reversed by PGE(2). CONCLUSIONS: This study demonstrates the colocalization of COX-2 and PGES in symptomatic lesions and provides evidence that synthesis of COX-2 and PGES by activated macrophages is associated with acute ischemic syndromes, possibly through metalloproteinase-induced plaque rupture.

Prophylaxis against Staphylococcus aureus vascular graft infection with mupirocin-soaked, collagen-sealed dacron.

A rat model was used to investigate the efficacy of mupirocin in the prevention of vascular prosthetic graft infections. The effect of mupirocin-soaked Dacron was compared with the effect of rifampin-soaked, collagen-sealed Dacron in the rat model of graft infection caused by methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus. Graft infections were established in the back subcutaneous tissue of 195 adult male Wistar rats by implantation of 1-cm(2) Dacron prostheses followed by topical inoculation with 5 x 10(7) colony-forming units of S. aureus. The study included a control group (no graft contamination), two contaminated groups that did not receive any antibiotic prophylaxis, two contaminated groups in which perioperative intraperitoneal amoxicillin clavulanate prophylaxis (50 mg/kg) was administered, four contaminated groups that received mupirocin- or rifampin-soaked graft, and four contaminated groups that received mupirocin- or rifampin-soaked graft and perioperative intraperitoneal amoxicillin clavulanate prophylaxis (50 mg/kg). The grafts were sterilely removed 7 days after implantation and the infection was evaluated by using sonication and quantitative agar culture. Data analysis showed that the efficacy of mupirocin against both strains was significantly different from that of the untreated control. In addition, mupirocin was more effective than rifampin against the methicillin-resistant strain. Finally, only the combination of mupirocin and amoxicillin clavulanate produced complete suppression of growth of all strains.