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Retrograde flush perfusion with low-potassium solutions for improvement of experimental pulmonary preservation.

BACKGROUND: Optimal preservation of post-ischemic organ function is a continuing challenge in clinical lung transplantation. Retrograde instillation of preservation solutions has the theoretic advantage of achieving homogeneous distribution in the lung because of perfusing both the pulmonary and the bronchial circulation. So far, we have seen no experimental studies that include stereologic analysis of intrapulmonary edema concerning the influence of retrograde preservation on post-ischemic lung function after preservation with Perfadex and Celsior. METHODS: In an extracorporeal rat model, we perfused 8 lungs, each, using either antegrade or retrograde perfusion technique with Celsior (CE(ant)/CE(ret)) and Perfadex (PER(ant)/PER(ret)). Results were compared with low-potassium Euro-Collins. Post-ischemic lungs were reventilated and reperfused mechanically. We continuously monitored relative oxygenation capacity (ROC), pulmonary artery pressure, flush time, and wet/dry ratio. Furthermore, we used stereologic means to evaluate edema formation. Statistics comprised different analysis of variance models. RESULTS: Relative oxygen capacity of CE(ant)-protected lungs was superior to that of PER(ant) preservation (p = 0.05). Use of PER(ret) resulted in significantly higher ROC as compared with PER(ant) (p < 0.001) and was comparable to results obtained with CE-preservation, which was not further improved with retrograde application. CONCLUSIONS: Celsior provides better lung preservation than does Perfadex when administered antegradely. Retrograde application of Perfadex results in significant functional improvement as compared with antegrade perfusion, which reaches the standard of Celsior-protected organs. Additional in vivo experiments in combination with ultrastructural analysis are warranted to further evaluate retrograde delivery of preservation solutions, which could be used in clinical lung transplantation to further optimize current results.

Animals↗

Effect of tides on solute flushing from a strait: imaging flow and transport in the East River with SF6.

In June 2003, two injections of approximately 3.9 mol of sulfur hexafluoride (SF6) were made 8 days apart in the East River, a 25 km tidal strait, to observe solute mixing and dissipation. The first injection occurred at slack before flood, and the second at slack before ebb (flood = northward flow). Tidally synchronized surveys of the SF6 tracer patch, supplemented by vertical profiles, were conducted by boat for 6 and 4 days following the flood and ebb injections, respectively. Residence times for the tracer-tagged water mass in the East River were estimated to be 3.3 +/- 0.7 days and 1.7 +/- 0.5 days for the flood and ebb injections, respectively, after correcting SF6 inventories for losses of SF6 from the water column by air-water gas exchange. The data indicate that the majority of East River solutes are transported to New York Harbor and that tidal mixing dominates subtidal circulation with respectto solute transport. Surveys of the adjacent lower Hudson River revealed a northward-moving, intermediate layer of East River water. Our results suggest that tidal phasing of contaminant discharges in the East River could reduce environmental impacts, by increasing flushing rates and directing a greater fraction of material away from Long Island Sound.

Environmental Monitoring↗

Development of apple superficial scald, soft scald, core flush, and greasiness is reduced by MCP.

1-Methylcyclopropene (MCP) was used to evaluate the role of ethylene in development of apple (Malus x domestica Borkh.) physiological disorders during storage. Granny Smith, Red Chief Delicious, and Fuji apple fruit were treated with MCP at a concentration of 1 microL L(-)(1) for 12 h at 20 degrees C. For all varieties stored at 0 degrees C, ethylene production and respiration rates were reduced for several months following MCP treatment, and firmness and titratable acidity of treated fruit were higher compared to controls. Apples treated with MCP did not develop superficial scald or peel greasiness through 6 months storage plus ripening at 20 degrees C for 7 days. Core flush was not observed in MCP-treated fruit until 6 months after treatment when the incidence was still lower compared to control fruit. MCP delayed the rise in production of alpha-farnesene and reduced accumulation of its oxidation products.

Cyclopropanes↗

Novel chromene-derived selective estrogen receptor modulators useful for alleviating hot flushes and vaginal dryness.

A novel SERM (selective estrogen receptor modulators), 1-(R), a chromene-derived bisbenzopyran, was discovered to alleviate hot flushes and effectively increase vaginal fluidity in rats. Moreover, 1-(R) was found to have beneficial effects on plasma cholesterol and bone metabolism while maintaining antiestrogenic activity in the uterus. The biological profile of its enantiomer 1-(S) was also evaluated.

Animals↗

Tolerance to nicotinic acid flushing.

The mechanism of tolerance to nicotinic acid flushing was determined in subjects during a 5-day course of treatment. Objective measures of skin blood flow were used to confirm the development of tolerance. Plasma levels of nicotinic acid showed marked intraindividual variability but were not decreased with the development of tolerance. However plasma levels of 9-alpha 11-beta prostaglandin F2, a stable metabolite of prostaglandin D2, became undetectable in most subjects with the development of tolerance. Thus tolerance is not associated with decreased levels of nicotinic acid or development of tolerance to the prostaglandin mediator, but with decreased levels of the mediator.

Administration, Oral↗

Results on quantitative trait loci for flushing date in oaks can be transferred to different segregating progenies.

Flushing date (bud burst) is one of the most important traits for the adaptation to different environments and climates in the temperate zone. Because of their wide geographic distribution, Quercus robur L. and Q. petraea (Matt.) Liebl. are suitable as model plants to study the genetic basis of bud burst. QTLs (Quantitative Trait Loci) with comparatively large effects have been mapped in a former study in a Q. robur x Q. robur full-sib family (French cross). In the present study, we performed a Bulked Segregant Analysis (BSA) in the F (1) progeny comprising 144 seedlings derived from a cross between a single Q. robur tree as common seed parent and five different pollen donors both from Q. robur and Q. petraea (Q. robur x Q. spp., Diekholzen crosses). In addition, markers linked to two bud burst QTLs with comparably strong effect in the above-mentioned full-sib family (French cross) were tested for their association with bud burst in the Q. robur x Q. spp. (Diekholzen) progeny. Using three microsatellite markers as anchor points, we could map QTLs on linkage group 7 and on linkage group 2, together explaining 16.2 % of the total phenotypic variance (PVE) in 1999 and 38.1 % in 2003. Out of 10 markers that segregated in both mapping progenies, four markers including the two microsatellite markers, showed a significant effect on bud burst in both materials. At microsatellite loci ssrQpZAG1/5 (linkage group 7) and ssrQpZAG119 (linkage group 2) alleles associated with early (allele 166 bp in ssrQpZAG1/5) and late bud burst (allele 57 bp in ssrQpZAG119) in the Q. robur x Q. robur full-sib family (French cross) showed a highly significant association with the same polarity of the effect in the Q. robur x Q. spp. (Diekholzen) progeny. The usefulness of these markers for marker-assisted selection in full-sib and half-sib families is discussed.

Genetic Linkage↗

Excision of Tn10 from the donor site during transposition occurs by flush double-strand cleavages at the transposon termini.

Tn10 transposition is accomplished without extensive replication of the transposon sequences. Replicative cointegrate formation is precluded by efficient separation of transposon sequences from flanking donor DNA at an early stage in the transposition reaction. We report here that excision of Tn10 from its donor site occurs by a pair of flush double-strand breaks. Breaks occur at each end of the element precisely between the terminal base pair of the element and the first base pair of flanking DNA. This observation provides definitive evidence that cleavage of both strands of the element occurs under the direct control of Tn10 transposase protein. It is highly likely that transposase itself is directly responsible for these cleavages. The implications of this possibility are discussed.

Base Sequence↗

Characterizations of the first flush in storm water runoff from an urban roadway.

Storm water runoff from urban roadways contains anthropogenic pollutants, which are mainly generated from traffic-related activities. The purpose of this study was to evaluate the characteristics of pollutants from the roadway runoff as well as first flush effects. Storm water runoff was sampled during five storm events from the experimental site in Otsu, Shiga, Japan. From the hydrographs and pollutographs for the roadway runoff, the concentration of pollutants increased with increasing runoff flow in the low flow rate event, but did not significantly increase in the high flow rate event. Moreover, according to the analysis of cumulative pollutant mass versus runoff volume curves from five storm events, the first 50% of the runoff volume transported 62% of TOC and Mo, 60% of SS, 59% of Fe, Mn and Cu, 58% of Ni, 57% of Cd and Pb, 56% of Al, 55% of Zn, and 54% of Cr, as the mean values. The first 30% and 80% of the runoff volume also transported 34-43% mass of the pollutants and 82-88% mass of the pollutants, respectively. This study for storm water runoff may also provide useful information to correctly design treatment facilities, such as detention tanks and ponds, filtration and adsorption systems.

Adsorption↗

Reduction in Legionella pneumophila through heat flushing followed by continuous supplemental chlorination of hospital hot water.

An increase in endemic rate of nosocomial Legionella pneumophila pneumonia prompted an investigation that revealed 16.2% (12/74) of patient care hot-water sites surveyed were culture-positive for L. pneumophila. No positive cultures were recovered from cooling towers, air intakes, or construction areas. Heat flushing of hospital hot-water outlets to temperatures greater than 60 degrees C for 30 min achieved a 66% reduction in positive Legionella cultures. After 4 1/2 months, different serotypes recurred in previously eradicated areas and there were new positive cultures. Continuous supplemental chlorination of the hot-water system (2 parts per million [ppm]) significantly reduced the number of culture-positive samples from 37.4% (43/115) to 7.0% (8/115) after 6 weeks (P less than .005). Of 30 sites surveyed 6 months after hot-water chlorination, 67% (20) were still culture-negative. Of those positive, 70% had less than or equal to 150 L. pneumophila/ml and 90% were from bathtubs. Adverse effects of chlorination on users and plumbing have not been seen. There have been no definite cases of nosocomial L. pneumophila in areas served by supplemental chlorine during the first 17 months of the chlorination project. Technology allowing tighter regulation of chlorine and use of silicates to control corrosion have made continuous hot-water chlorination a safe and effective option in Legionella control.

Chlorine↗

Purification of heparin-binding epidermal growth factor-like growth factor from pig uterine luminal flushings, and its production by endometrial tissues.

Pig uterine luminal flushings contain at least four heparin-binding growth factors (HBGF) that stimulate fibroblast [3H]thymidine incorporation. One of these factors, which appeared to be a relatively minor HBGF, was eluted from heparin affinity columns by 1.0 M NaCl and was found to compete with 125I-epidermal growth factor (EGF) for binding to an endometrial carcinoma cell line. This EGF receptor (EGF-R)-binding property was abolished by an antiserum to heparin-binding EGF-like growth factor (HB-EGF) that specifically blocks binding of HB-EGF to the EGF-R. Reverse-phase HPLC resulted in the purification of two EGF-R-binding activities correlated with 13,500 and 17,000 M(r) proteins that reacted with an antiserum raised against residues 9-26 of human HB-EGF. Uterine extracts also contained an EGF-R-binding factor that was eluted from heparin by 1.0 M NaCl and was antagonized by HB-EGF antiserum. Endometrial mRNA subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR through the use of HB-EGF-specific primers yielded fragments of the predicted size. Cloning of the nested PCR product revealed a 380-bp porcine HB-EGF cDNA sequence that was 78-85% homologous to primate or rodent HB-EGF. HB-EGF was immunohistochemically localized primarily to the luminal epithelium in both pregnant and nonpregnant animals.

Animals↗

Characterization of 16- to 20-kilodalton (kDa) connective tissue growth factors (CTGFs) and demonstration of proteolytic activity for 38-kDa CTGF in pig uterine luminal flushings.

Connective tissue growth factor (CTGF) is a growth and chemotactic factor for fibroblasts encoded by an immediate early gene that is transcriptionally activated by transforming growth factor ss. Although the primary translational product of the pig CTGF gene is predicted to be of approximate Mr 38 000, pig uterine luminal flushings (ULF) contained 10- to 20-kDa CTGF proteins that were heparin-binding and mitogenic, whereas 38-kDa CTGF was not apparent. The N-termini of two microheterogeneous forms of 16-kDa CTGF, as well as 18-kDa and 20-kDa forms of CTGF, commenced at, respectively, Cys199, Ala197, Asp186, and Asp186 and did not correspond to intron-exon boundaries in the CTGF gene. Northern blotting revealed a single porcine (p) CTGF transcript of 2.4 kilobases in endometrium from Day 10 to 16 cycling or pregnant pigs. Ten- to twenty-kilodalton pCTGF proteins in ULF were stable for 48 h at 37 degreesC whereas native 38-kDa pCTGF was degraded within 10 min under the same conditions. CTGF-degrading activity in pig ULF was heat-sensitive and concentration- and time-dependent. Ten- to twenty-kilodalton CTGF levels in ULF peaked on Day 16 of the cycle and on Day 12 of pregnancy and were highly correlated with the levels of proteolytic activity for 38-kDa CTGF. Collectively these data suggest that bioactive 10- to 20-kDa CTGF proteins are generated in utero through limited proteolysis of the 38-kDa CTGF primary translational product.

Amino Acid Sequence↗

Sir John Harington, Thomas Crapper, and the flush toilet.

With the population explosion of the last century, major changes in sewage removal and sanitation were necessary. Two men offered important designs for the modern flush toilet. Sir John Harington was a poet in 16th Century England, while Thomas Crapper was a plumber and businessman in the same country 300 years later. Harington will be remembered for eloquent words about the toilet and Crapper may be assured even greater remembrance for selling toilets and being named Crapper.

England↗

Evaluation of hypertonic citrate flushing solution for kidney preservation using the isolated perfused rat kidney.

The isolated perfused rat kidney has been used to study the effects of cold ischaemia during ice storage. Tissue adenine nucleotide levels in freeze-clamped kidneys were closely correlated with their function after circulation had been reestablished in the perfusion circuit. The ATP content was depleted to a greater extent than total adenine nucleotide after 8 hr of cold ischaemia but both were considerably diminished after 24 hr. The model was also used to compare four solutions which are available clinically for preliminary flushing of organs in the ice storage preservation technique. The results indicated that for periods of 8 and 24 hr of cold ischaemia, renal function and adenine nucleotide content were significantly better maintained with a solution based on hyperosmolar citrate than with Collins, Sacks, or Perfudex solutions. This study confirmed recent observations of the clinical efficacy of citrate solution, while demonstrating how the isolated perfused rat kidney could be used for rapid screening of modifications in preservation techniques.

Adenine Nucleotides↗

Flush solution 2, a new concept for one-to-three-day hypothermic renal storage preservation. Functional recovery after preservation in Euro-Collins, Collins' C2, hypertonic citrate, and F.2 solution.

Experiments were performed on the quality of renal functional recovery after 24, 48, or 72-hr hypothermic storage preservation of canine kidneys in Euro-Collins solution (EC), Collins' solution C2, hypertonic citrate solutions (HC, HC-D2O), or our new flush solution 2 (F.2). Clearance tests (inulin, paraaminohippuric acid, and creatinine) and resorption rates for sodium, potassium, and glucose indicated a high superiority in the early functional recovery of F.2-preserved kidneys after all preservation periods tested. The excellent function after preservation in F.2 contrasted especially with the poor or even absent function after 72-hr preservation in HC and HC-D2O or EC. Thus F.2--a hyperosmolar solution containing sucrose with a balanced Na-K relation on the basis of "heavy water" (D2O)--is especially suitable for preservation up to 72 hr if cyclosporine is used for immunosuppression in the recipient. The recipient can be supplied with an organ with immediate good functional recovery because cyclosporine banishes the higher risk for rejection of these well-functioning organs; simultaneously, the possibility for continuous functional supervision allows avoidance of nephrotoxic side effects from the immunosuppressant.

Animals↗

Beneficial effect of additional cardioplegia flush during hypothermic static cardiac preservation.

BACKGROUND: The effects of various preservative solutions and methods have been studied to prolong the safety period of cardiac preservation. In this study, we used cardioplegic solution (CS) during cardiac preservation and investigated how flush CS yields good preservation of isolated hearts compared with only cold immersion. METHODS: Male Wistar rat hearts were arrested with 4 degrees C St. Thomas crystalloid CS. All hearts were immersed for 6 hr in a 4 degrees C Euro-Collins solution. Hearts were classified into seven groups by period and number of infusions of CS (20 ml/kg) during simple immersion of hearts. Infusion of CS during preservation was not used for group I. Infusion was performed at two hours after starting immersion for group II, at 3 hr for group III, at 4 hr for group IV, at 5 hr for group V, every hour for group VI, and every 2 hr for group VII. After preservation, the hearts were reperfused with blood using a support rat. Myocardial adenosine triphosphate was measured immediately after immersion of hearts. Biochemical examination of coronary effluents was performed at 15 min after reperfusion, and cardiac function was evaluated at 40 min after reperfusion. Myocardial specimens were subsequently taken for measurement of water content. RESULTS: Percentage recovery of left ventricular developed pressure and dp/dt in groups III, VI, and VII were higher than those in group I at each balloon volume, and left ventricular end-diastolic pressure in these groups was also significantly lower than that in group I. Levels of creatine kinase-MB and lactate in groups VI and VII after reperfusion were significantly lower than those in group I. Myocardial adenosine triphosphate was significantly better preserved in groups III, IV, VI, and VII than in group I. However, no significant difference in cardiac function or myocardial adenosine triphosphate was found among groups III, IV, VI, and VII. CONCLUSIONS: The use of CS during cardiac preservation is effective in preserving cardiac function and myocardial enzymes, and infusion may be sufficient if performed once-only at 3 or 4 hr from starting immersion in 6 hr storage of isolated rat hearts.

Adenosine Triphosphate↗

Relief of hot flushes with new plant-derived 10-component synthetic conjugated estrogens.

OBJECTIVE: A study was conducted to evaluate the safety and efficacy of 3 different doses of synthetic conjugated estrogens B, a new plant-derived 10-component conjugated estrogens product, for the treatment of menopausal vasomotor symptoms. METHODS: This was a randomized, double-blind, placebo-controlled trial. Highly symptomatic menopausal women (N = 281) received 12 weeks of a once-daily oral treatment with 0.3 mg, 0.625 mg, or 1.25 mg of 10-component synthetic conjugated estrogen or placebo. Patients recorded the daily frequency and severity of hot flushes. Statistical analyses compared results at weeks 4, 8, and 12 with baseline values. RESULTS: Statistically significant reductions (P <.05) in the frequency and severity of vasomotor symptoms were observed for all 3 dosage strengths of 10-component synthetic conjugated estrogen compared with placebo. The most commonly reported adverse events in all treatment groups were headaches. No difference in the incidence of treatment-related adverse events was seen between placebo and 10-component synthetic conjugated estrogen groups. CONCLUSION: The 0.3-mg, 0.625-mg and 1.25-mg dose strengths of 10-component synthetic conjugated estrogen significantly reduced the frequency and severity of vasomotor symptoms compared with placebo, and were well tolerated during this 12-week study. LEVEL OF EVIDENCE: I

Administration, Oral↗

Hypothermic retrograde jugular vein flush in heatstroke rats provides brain protection by maintaining cerebral blood flow but not by hemodilution.

OBJECTIVE: To determine the fundamental mechanism of brain protection by hypothermic retrograde jugular vein flush (HRJVF) in heatstroke rats. DESIGN: Randomized, controlled, and prospective study. SETTING: University physiology research laboratory. SUBJECTS: Sprague-Dawley rats (270-320 g, males). INTERVENTIONS: Rats were randomized into four groups as follows: a) normothermic control (NC, n = 8); b) heatstroke rats without cold saline delivery (HS, n = 8); c) heatstroke rats treated with cold saline via femoral vein (HS+F, n = 8); and d) heatstroke rats treated with HRJVF (HS+J, n = 8). Right external jugular vein and right femoral vein were cannulated in each rat. The cannulation in the jugular vein was with cranial direction. To produce heatstroke, rats were placed in a chamber with an ambient temperature of 43 degrees C. The cold saline (4 degrees C, 1.7 mL/100 g) was delivered via the cannula in either the femoral vein or jugular vein immediately after the onset of heatstroke. Glutamate release in the brain, cerebral blood flow (CBF), and hematocrit of arterial blood were determined. MEASUREMENTS AND MAIN RESULTS: After onset of heatstroke, HRJVF significantly decreased the glutamate release. In contrast, cold saline delivery via femoral vein could only delay the elevation of glutamate release in the brain. The CBF of HS and HS+F rats decreased rapidly after the onset of heatstroke, but the CBF of HS+J rats was initially elevated by HRJVF and was maintained at baseline 30 mins after onset of heatstroke. Hematocrit in all the rats did not change after testing. CONCLUSIONS: HRJVF protects the brain by maintaining cerebral blood flow in rats after heatstroke. To preserve brain function and prolong survival after severe heatstroke, maintenance of cerebral blood flow is important in the management of heatstroke.

Animals↗

Hot flushes, common symptoms, and social relations among middle-aged nonmenopausal French women in the GAZEL cohort.

OBJECTIVE: Many symptoms, including hot flushes (HFs) may appear during the years preceding menopause. Hypotheses to explain these symptoms include biomedical, demographic, and cultural risk factors. Social relations are also associated with various aspects of health. The aim of this study was to analyze the association between social relations and the reporting of HFs and other common symptoms among middle-aged nonmenopausal French women taking into account other factors, including biomedical characteristics. DESIGN: Data came from self-administered questionnaires mailed to 1,180 pre- or perimenopausal women aged 45 to 54 years participating in the French GAZEL cohort. Bivariate and multivariate analyses examined the association between symptoms (HFs, general, psychological, osteoarticular, and breast symptoms) and three scores of social relations (social network, social relations, and satisfaction with social relations). RESULTS: After adjustment, low social support was associated with psychological symptoms (odds ratio [OR] = 2.65; 95% CI: 1.33-5.29) and unsatisfactory social relations were associated with psychological (OR = 2.04; 95% CI: 1.49-2.79) and breast symptoms (OR = 1.38; 95% CI: 1.03-1.84). HFs were not associated with social relations but were related to common symptoms (OR = 2.80; 95% CI: 1.94-4.03). Perimenopausal women were more likely to report HF than premenopausal women (OR = 2.63; 95% CI: 1.88-3.71). CONCLUSION: Social relations were associated with psychological and breast symptoms, but not with HFs. The strong association between common symptoms and HFs suggests that biomedical factors have a greater influence than social relations on the occurrence of HFs.

Cohort Studies↗