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  • 1
    ISSN: 1573-6776
    Keywords: fatty acids ; Fusarium moniliforme ; gibberellins ; metabolic switching ; sesamol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Sesamol (3,4-methylenedioxyphenol) at 2.5 mM inhibited growth of Fusarium moniliforme by about 40% and lipid accumulation by 35%. Gibberellin (GA3) accumulation was increased by 20-fold, to 63 mg g−1 biomass, in the presence of sesamol indicating that the acetyl-CoA destined for fatty acid biosynthesis was now being switched into secondary metabolite (GA3) accumulation. Synthesis of other metabolites from acetyl-CoA, such as bikaverin and carotenoids, though were not increased in the presence of sesamol. Metabolic switching is therefore feasible by judicious use of selected inhibitors that can thus block primary metabolic routes but which do not affect secondary metabolites.
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  • 2
    ISSN: 1573-904X
    Keywords: HIV protease inhibitor ; cyclic urea ; Caco-2 ; absorption ; transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To optimize the conditions for determining Caco-2 permeation of HIV protease inhibitors and other lipophilic compounds, and to compare cyclic urea HIV protease inhibitors with marketed compounds. Methods. Absorptive and secretory Caco-2 membrane permeation studies were performed with HIV protease inhibitors and various reference compounds, examining the effects of adding the solubilizing agents dimethylacetamide (DMAC) and albumin in donor and reservoir compartments, respectively. Results. DMAC was useful as an additive in the donor vehicles, increasing the dissolved concentrations of poorly water-soluble HIV protease inhibitors, and enabling more reliable determination of Papp values. Donor vehicles containing up to 5% DMAC could be used without altering Caco-2 barrier function, as indicated by the lack of effect on permeabilities of reference compounds with diverse absorption characteristics. The utilization of a reservoir containing albumin resulted in marked increases in absorptive Papp values for some HIV protease inhibitors as well as other lipophilic, highly protein bound compounds, consistent with albumin increasing the release of these compounds from the cell monolayer. Conclusions. Poorly soluble, lipophilic, highly bound compounds may require using solubilizing agents in the donor and reservoir compartments of Caco-2 permeation experiments for estimating in vivo absorption potential. If the reservoir does not provide adequate sink conditions, cellular retention could over-emphasize the contributions of secretory transport. The cyclic ureas, DMP 450, DMP 850, and DMP 851, have Caco-2 permeabilities suggestive of moderate-to-high oral absorption potential in humans.
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  • 3
    ISSN: 1573-0875
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: Abstract The six binary montmorillonite clay-catalyzed reactions of the5′-phosphorimidazolides of adenosine, cytidine, guanosine anduridine were performed and the eight dimers from each reactionwere separated and analyzed by HPLC. A 16–51-fold higher yieldof the 5′-purine-pyrimidine dimers over that of the5′-pyrimidine-purines was observed. The total yield of the5′-purine-pyrimidine dimers was in the 50–70% range while thatof the 5′-pyrimidine-purine dimers was 1.3–7.0%. Less sequenceselectivity was observed in the homodimers formed.Regioselectivity for the formation of 3′, 5′-phosphodiesterbonds over that found in the absence of clay was observed. The5′-purine-pyrimidine, 5′-pyrimidine-pyrimidine and5′-purine-purine dimers had 3′, 5′-links in about half of theirphosphodiester bonds. The percent phosphodiester links in the5′-pyrimidine-pyrimidine dimers was 18%, a value close to thatobserved in the absence of the montmorillonite catalyst. Themontmorillonite-catalyzed reaction of all four activatednucleotides was performed and the 24 products were separated andanalyzed. The trends observed in the binary reactions wereconfirmed and the results also showed that the relativereactivity of the activated monomers was A〉G〉C〉U in theratio 8.2: 4.8: 1.3: 1 respectively. No 5′-pyrimidine-purineswith a 5′-U and pG3′pU, pC3′pAand pC3′pG weredetected. These studies suggest that a limited population ofRNAs would have formed in catalyzed prebiotic reactions.
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  • 4
    ISSN: 1530-0358
    Keywords: Neuropathy ; Femoral nerve ; Colectomy ; Complications ; Retractors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Postoperative femoral neuropathy is an uncommon complication of abdominal surgery. We present four cases occurring after colectomy at our institution and discuss the diagnosis and treatment.
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  • 5
    ISSN: 1572-9516
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Inclusive single jet production in hadron collisions is considered. It is shown that the QCD parton model predicts a nonmonotonic dependence of the inclusive cross section on the fraction of the energy deposited in the jet registered, if it is normalized on the same cross section measured at another collision energy. Specifically, if the cross section is normalized by the one measured at a higher collision energy, it possesses a minimum which depends on jet rapidity. This prediction can be tested at the Fermilab Tevatron, at the CERN LHC, and at the Very Large Hadron Collider under discussion.
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  • 6
    ISSN: 1615-5947
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 2 for a mean duration of 7.4 months preoperatively and 12 patients had exposed bone or tendon. Vascular reconstruction included popliteal (3), tibial (6), and pedal (6) bypass with concomitant myocutaneous free flap, using mostly rectus abdominis or latissimus dorsi muscle. There were no perioperative deaths. One patient suffered a nonfatal myocardial infarction. Two patients had a postoperative wound hematoma and one required vascular graft revision. Patients were followed for 4 to 75 months (mean = 23 months). Four patients have required amputations (3 early, 1 late), three of whom had preoperative renal failure. The limb salvage rate has been 72% at 36 months, with 10 of 11 patients having functional ambulation. Combined revascularization and free tissue transfer is safe and durable, and long-term limb salvage is obtainable. Patients with renal failure had poorer outcomes in this series.
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  • 7
    ISSN: 1468-2869
    Keywords: HIV ; HCV ; HBV ; Injection Drug Use ; Needle-Exchange Program ; Prevention ; Study Bias ; Substance Abuse ; Syringe-Exchange Program
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective Nonrandomized comparisons of the incidence of HIV and hepatitis B and C between injection drug users (IDUs) who do and do not attend voluntary needle-exchange programs may be subject to bias. To explore possible sources of bias, we examined characteristics associated with voluntarily beginning or ceasing to participate in the Seattle needle exchange. Methods In a cohort of 2,879 IDUs, a standardized questionnaire measured characteristics present at enrollment. We examined the relation of these characteristics to the proportion of IDUs who began to use the program during the ensuing 12-month follow-up period and to the proportion of current exchangers who dropped out during that period of time. Results Of the 494 never-exchangers at baseline, 32% attended the exchange program during follow-up; those who reported sharing syringes or who were homeless at enrollment were more likely to become new exchange users (adjusted risk ratio [ARR] for becoming an exchange user = 1.8 for those who shared syringes, and ARR=2.2, for those who were homeless). Of 1,274 current exchangers, 16% stopped using the exchange during follow-up, with daily injectors (ARR=0.6) and those who reported backloading (ARR=0.6) being relatively less likely to drop out of the exchange. Conclusions The analysis suggests that IDUs participating in needle-exchange programs at a given point in time may include a particularly high proportion of those injectors whose pattern of drug use puts them at elevated risk of blood-borne viral infections.
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  • 8
    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract We analytically study the dynamics of evolving populations that exhibit metastability on the level of phenotype or fitness. In constant selective environments, such metastable behavior is caused by two qualitatively different mechanisms. On the one hand, populations may become pinned at a local fitness optimum, being separated from higher-fitness genotypes by a fitness barrier of low-fitness genotypes. On the other hand, the population may only be metastable on the level of phenotype or fitness while, at the same time, diffusing over neutral networks of selectively neutral genotypes. Metastability occurs in this case because the population is separated from higher-fitness genotypes by an entropy barrier: the population must explore large portions of these neutral networks before it discovers a rare connection to fitter phenotypes. We derive analytical expressions for the barrier crossing times in both the fitness barrier and entropy barrier regime. In contrast with ‘landscape’ evolutionary models, we show that the waiting times to reach higher fitness depend strongly on the width of a fitness barrier and much less on its height. The analysis further shows that crossing entropy barriers is faster by orders of magnitude than fitness barrier crossing. Thus, when populations are trapped in a metastable phenotypic state, they are most likely to escape by crossing an entropy barrier, along a neutral path in genotype space. If no such escape route along a neutral path exists, a population is most likely to cross a fitness barrier where the barrier is narrowest, rather than where the barrier is shallowest.
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  • 9
    ISSN: 1530-0358
    Keywords: Thermal imaging ; Bowel ischemia ; Mesenteric ischemia ; Doppler ultrasound ; Fluorescein ; Infrared
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to introduce thermal imaging in the intraoperative detection of bowel ischemia by comparing thermal imaging with conventional techniques in detecting acutely ischemic bowel, using histologic evidence for intestinal necrosis as the standard. METHODS: A prospective study was performed using a porcine model. Laparotomy was performed on four pigs under general anesthesia. A 25-cm segment of mid jejunum was tagged with proximal and distal sutures, and its mesentery was ligated and divided. Thermal imaging, visual inspection, Doppler ultrasound, and fluorescence with Wood's lamp after fluorescein were used to estimate the extent of bowel ischemia five minutes after ligation of the mesentery. Measurements were taken in reference to both the proximal and distal tags to obtain two data points per animal for each method. After two hours of warm ischemia, the jejunum was harvested and sectioned longitudinally. Comparisons were made between the estimated region of necrosis for each method and microscopic evidence of necrosis. RESULTS: Visual inspection was the only method unable to detect a difference between vascularized and devascularized bowel for each of the eight data points. Fluorescein dye missed 3 cm of ischemic bowel. Doppler ultrasound and thermal imaging were 100 percent sensitive for necrotic bowel, with thermal imaging overestimating necrosis to a greater extent than Doppler ultrasound. The positive predictive value of fluorescein dye, Doppler ultrasound, and thermal imaging for determining nonviable bowel was 91.8, 80.8, and 69.5 percent, respectively. CONCLUSIONS: Thermal imaging has the potential to be a useful adjunct in the intraoperative determination of bowel ischemia. Further studies are indicated to study this technique.
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  • 10
    ISSN: 1534-4681
    Keywords: Prophylactic surgery ; BRCA1 ; BRCA2 ; Breast cancer ; Ovarian cancer ; Health insurance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The efficacy of prophylactic mastectomy and oophorectomy in reducing breast and ovarian carcinoma has recently been reported in high-risk women. Because cost has become central to medical decision-making, this study was designed to evaluate currently existing coverage policies for these procedures. Methods: A confidential detailed cross-sectional nationwide survey of 481 edical directors from the American Association of Health Plans, Medicare, and Medicaid was conducted. Results: Of the 150 respondents, 65% (n 5 97) had 100,000 or more enrolled members and 35% (n 5 53) had fewer than 100,000 enrolled members. Only 44% of private plans have specific policies for coverage of prophylactic mastectomy for a strong family history of breast cancer and 38% of plans for a BRCA mutation. Only 20% of total responding plans had a policy for coverage of prophylactic oophorectomy under any clinical circumstance. Governmental carriers were significantly less likely to have any policy for prophylactic surgery (range, 2%–12%) compared with nongovernmental plans (range, 24%–44%; P,.001). No significant regional differences for coverage policies were identified (P.05). Conclusions: Significant variations currently exist for health insurance coverage of prophylactic mastectomy and oophorectomy. As genetic testing becomes widespread, more uniform policies should be established to enable appropriate high-risk candidates equal access and coverage for these procedures.
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