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Angiotensin II-mediated vasoconstriction in chronic congestive heart failure, and response to converting enzyme inhibition.

To judge the efficacy of converting enzyme inhibitors in the management of congestive heart failure, it is necessary to interpret this in the context of the factors that stimulate renin release and the subsequent formation of angiotensin and aldosterone. The pharmacologic properties of individual converting enzyme inhibitors must be considered, and the alterations in both renin angiotensin activity and long-term converting enzyme inhibition that interact in complementary or offsetting ways to influence the long-term therapeutic result must be understood.

Angiotensin-Converting Enzyme Inhibitors↗

The pharmacokinetics of oxytocin as they apply to labor induction.

OBJECTIVE: Our purpose was to determine the relationship among plasma oxytocin levels, metabolic clearance rate of oxytocin, and uterine activity in gravid women undergoing labor induction. STUDY DESIGN: Ten women receiving oxytocin for labor induction and agreeing to participate had blood sampled before initiation of oxytocin and at different levels of uterine pressure. Samples were analyzed with 200 microliter extracts from 1 ml of plasma with an oxytocin radioimmunoassay. The intraassay coefficient of variation was < 3%. Sensitivity of the assay was 1.5 pg/ml. Pharmacokinetic parameters including plasma levels and metabolic clearance rates were calculated. Data were analyzed with the paired t test and linear and logistic regression. RESULTS: Mean oxytocin levels and metabolic clearance rates were 26.6 pg/ml and 7.97 ml/min. There was no correlation between changes in oxytocin level and metabolic clearance rate. Increases in infusion rates were correlated with increases in oxytocin levels (r = 0.71, p < 0.001). Cervical dilatation and uterine contraction pressures did not correlate with oxytocin levels. CONCLUSION: Peripheral plasma levels of oxytocin may not accurately reflect uterine activity or progress in labor. Plasma levels of oxytocin may merely reflect the rate of oxytocin infusion.

Adult↗

A technique for converting a needle-catheter jejunostomy into a standard jejunostomy.

The benefits of enteral nutrition for surgical patients have been well documented in the literature, and needle catheter jejunostomy is frequently used at initial surgical exploration. Occasionally, the need arises for prolonged use of the catheter, and problems occur with occlusion of the catheter. A simple technique is described for converting the needle-catheter jejunostomy into a standard-feeding jejunostomy.

Catheters, Indwelling↗

Purification and characterization of the aromatic desulfinase, 2-(2'-hydroxyphenyl)benzenesulfinate desulfinase.

2-(2(')-Hydroxyphenyl)benzenesulfinate desulfinase (HPBS desulfinase) catalyzes the cleavage of the carbon-sulfur bond of 2-(2(')-hydroxyphenyl)benzenesulfinate (HPBS) to form hydroxybiphenyl and sulfite. This is the final step in the desulfurization of dibenzothiophene, the organosulfur compound used to study biodesulfurization of petroleum middle distillate. HPBS desulfinase was purified 1600-fold from Rhodococcus IGTS8. The purification was monitored using a spectrofluorimetric assay and SDS-PAGE. The pI of HPBS desulfinase is 5.6, the temperature optimum is 35 degrees C, and the pH optimum is 7.0. HPBS desulfinase has a K(m) of 0.90+/-0.15 microM and a k(cat) of 1.3+/-0.07 min(-1). Several analogs were tested for their ability to act as substrates or inhibitors of HPBS desulfinase. No alternative substrates and very few inhibitors were identified. HPBS desulfinase activity decreases in the presence of Cu(2+) and Zn(2+), while no metals significantly enhance enzyme activity. HPBS desulfinase is susceptible to tyrosine, tryptophan, and cysteine specific modification agents.

Cells, Cultured↗

Metabolism of benzo(a)pyrene by a dioxygenase enzyme system of the freshwater green alga Selenastrum capricornutum.

The green alga Selenastrum capricornutum was incubated with benzo(a)-pyrene under an atmosphere of 20% (18)O2: 80% N2. The cis-11,12-dihydro-11,12-dihydroxybenzo(a)pyrene, cis-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene and cis-4,5-dihydro-4,5-dihydroxybenzo(a)pyrene, were isolated by HPLC and analyzed by mass spectrometry. The metabolites produced molecular ions at m/z 290 and 286. Elemental analysis of the ion at m/z 290 gave an elemental composition of C20H14(18)O2 with 13% (18)O2 incorporation. The results indicate that S. capricornutum produces cis vicinal dihydrodiols from molecular oxygen via a dioxygenase enzyme pathway. The dioxygenase enzymes are characteristic of the bacterial metabolic pathway and unlike those of eukaryotic organisms which involve monooxygenase enzymes.

Benzo(a)pyrene↗

Drug and ECT treatment of depression in the elderly, 1996-2001: a literature review.

A computer-based literature search of all antidepressant and electroconvulsive therapy (ECT) treatment studies published between 1995 and September 2001 was conducted. In addition, a review of published chapters, review articles, and metaanalyses was also conducted. Articles were categorized into those reporting comparative studies, those in which the therapeutic agent was not compared with another, articles about ECT, and review articles. These recent publications support the conclusions from prior reviews that antidepressants and ECT are effective and safe treatments for depressed elderly patients. Differences in efficacy and side effects appear to be slight among the various types of antidepressants. Research studies of depressed elderly increased markedly since 1995 compared with all previous years although more studies are still necessary.

Aged↗

Assessment of the aquatic and terrestrial toxicity of five biodegradable polymers.

Radiofrequency countermeasures (i.e., chaff) may be released by fighter jets during tactical countermeasures training. Chaff cartridges, pistons, and endcaps (i.e., chaff dispenser materials), all currently made of styrene, are also released into the environment. Accumulation of chaff dispenser materials in the environment is a concern of the Department of Defense. The US Navy is exploring the possibility of constructing degradable chaff dispenser components made of biodegradable polymers. Five polymers are being considered. Degradability and toxicity tests are two of several criteria being used to evaluate various available biodegradable options. Dissolution products from four of five polymers being considered were toxic to aquatic organisms with LC50s/LOELs ranging between 1.24 and 731.30 mg total organic concentration/L. Supernatant from dissolving a 90:10 polyester amide/polyvinyl alcohol copolymer in water for 24h inhibited shoot growth of Brassica rappa and Lepidium sativum. Since our results were obtained using fractions of saturated degradable polymer solutions (1 or 10 g/L), we conclude that the tested degradable polymers were of low toxicity to the seven aquatic organisms and two terrestrial plant species used in our assays. However, our characterization of the toxicity of these degradable polymers may not be applicable to all species or environmental situations. Information gained from these studies will be used for making decisions on which polymers should be used in the engineering of environmentally friendly chaff dispenser cartridges, pistons, and endcaps.

Aircraft↗

The effect of ozone associated with summertime photochemical smog on the frequency of asthma visits to hospital emergency departments.

A retrospective study using ambient ozone, temperature, and other environmental variables and their effect on the frequency of hospital visits for asthma was conducted in New Jersey, an area that often exceeds the allowable national standard for ozone. Data on emergency department visits for asthma, bronchitis, and finger wounds (a nonrespiratory control) were analyzed for the period May through August for 1988 and 1989. Asthma visits were correlated with temperature while the correlation between asthma visits and ozone concentration was nonsignificant. However, when temperature was controlled for in a multiple regression analysis, a highly significant relationship between asthma visits and ozone concentration was identified. Between 13 and 15% of the variability of the asthma visits was explained in the regression model by temperature and ambient ozone levels. This association, when compared to similar studies in Canada, shows the contribution of ozone to asthma admissions to be stronger in areas with higher ozone concentrations. Thus, among regions with periodic accumulations of ozone in the ambient atmosphere, an exposure-response relationship may be discernible. This supports the need to attain air quality standards for ozone to protect individuals in the general population from the adverse health effects caused by ambient ozone exposure.

Asthma↗

Decrease in canine proximal femoral ultimate strength and stiffness due to fatigue damage.

Fractures of the proximal femur represent a significant health concern especially in the elderly. Fatigue damage and microfractures have been implicated in the etiology of hip fractures; however, the extent to which these factors are sufficient to bring about significant reductions in proximal femur strength and stiffness is unknown. This study examined the hypothesis that fatigue loading of the proximal femur results in highly correlated decreases in bone stiffness and strength through the accumulation of bone microdamage. One canine femur from each of 10 pairs was monotonically loaded to failure to determine the ultimate strength. The contralateral femur was then cyclically loaded at 50% of the ultimate load value for either 3600 cycles or until a 40% reduction in stiffness was achieved. This femur was then monotonically loaded to failure. For two additional femur pairs, the fatigued femur was histologically processed to reveal bone microdamage. In support of the hypothesis, the data demonstrated a linear relationship between strength loss and stiffness loss (Adj. R2 = 0.79, p < 0.0004) with significant decreases in residual whole bone strength (p < 0.004) following cyclic loading. In addition, damage (microcracks) in the cortical bone and broken trabeculae were observed in the neck and head region of the femur fatigued until its stiffness was reduced by 40% but not fractured subsequent to cyclic loading.

Animals↗

Femoral strength is better predicted by finite element models than QCT and DXA.

Clinicians and patients would benefit if accurate methods of predicting and monitoring bone strength in-vivo were available. A group of 51 human femurs (age range 21-93; 23 females, 28 males) were evaluated for bone density and geometry using quantitative computed tomography (QCT) and dual energy X-ray absorptiometry (DXA). Regional bone density and dimensions obtained from QCT and DXA were used to develop statistical models to predict femoral strength ex vivo. The QCT data also formed the basis of a three-dimensional finite element (FE) models to predict structural stiffness. The femurs were separated into two groups; a model training set (n = 25) was used to develop statistical models to predict ultimate load, and a test set (n = 26) was used to validate these models. The main goal of this study was to test the ability of DXA, QCT and FE techniques to predict fracture load non-invasively, in a simple load configuration which produces predominantly femoral neck fractures. The load configuration simulated the single stance phase portion of normal gait; in 87% of the specimens, clinical appearing sub-capital fractures were produced. The training/test study design provided a tool to validate that the predictive models were reliable when used on specimens with "unknown" strength characteristics. The FE method explained at least 20% more of the variance in strength than the DXA models. Planned refinements of the FE technique are expected to further improve these results. Three-dimensional FE models are a promising method for predicting fracture load, and may be useful in monitoring strength changes in vivo.

Absorptiometry, Photon↗

Reversed-phase high-performance liquid chromatography studies of alpha-MSH fragments.

alpha-Melanotropin (alpha-MSH) is a linear tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2), that is primarily known for its ability to stimulate melanosome dispersion within integumental melanocytes (F. J. H. Tilders, D. F. Swaab and T. B. van Wimersma Greidanus (Editors), Frontiers of Hormone Research, Vol. 4, Karger, Basel, 1977; J. Ramachandran, S. W. Farmer, S. Liles and C. H. Li, Biochim. Biophys. Acta, 428 (1976) 347). In our efforts to understand the relationships of structure and conformation to the biological activities of alpha-MSH, we have prepared a series of diastereoisomeric analogues based on the highly potent analogue Ac-[Nle4, D-Phe7]-alpha-MSH4-11-NH2 (T. K. Sawyer, V. J. Hruby, B. C. Wilkes, M. T. Draelos, M. E. Hadley and J. Bergsneider, J. Med. Chem., 25 (1982) 1022). These analogues differed only in the amino acid substituted in the seven position, which was thought to be a critical residue for the biological activity of alpha-MSH. The chromatographic behavior of these analogues was examined on a C18 Vydac (16-micron) reversed-phase column with five different mobile phases. The selectivity (alpha) for the analogues was compared in 0.10% trifluoroacetic acid (TFA), 0.10% heptafluorobutyric acid (HFBA) and 0.25 M triethylammonium phosphate (TEAP) using either acetonitrile or methanol as the organic modifier. With only one exception all analogues substituted with a D-amino acid in the seven position were eluted prior to their L-amino acid counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗

In vitro stability and intestinal absorption characteristics of hexapeptide endothelin receptor antagonists.

Endothelins are potent vasoconstrictor peptides which have a wide range of tissue distribution and three receptor subtypes (ET(A), ET(B) and ET(C)). Among the linear hexapeptide ET(A)/ET(B) receptor antagonists, PD 145065 (Ac-D-Bhg-L-Leu-L-Asp-L-Ile-L-Ile-L-Trp, Bhg = (10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)-Gly) and PD 156252 (Ac-D-Bhg-L-Leu-L-Asp-L-Ile-(N-methyl)-L-Ile-L-Trp) were selected to evaluate the metabolic stability and intestinal absorption in the absence and/or in the presence of protease inhibitors. In vitro stability of both compounds was investigated in fresh plasma, lumenal perfusate, intestinal and liver homogenates. PD 156252 was more stable than PD 145065 in intestinal tissue homogenate (63.4% vs. 20.5% remaining) and liver homogenate (74.4% vs. 35.5% remaining), while both compounds showed relatively good stability in the fresh plasma (94.5% vs. 86.7% remaining) and lumenal perfusate (85.8% vs. 72.3% remaining). The effect of protease inhibitors on the degradation of PD 145065 and PD 156252 was also investigated. Amastatin, thiorphan, chymostatin and the mixture of these three inhibitors were effective in reducing the degradation of both compounds. The pharmacokinetic parameters of PD 156252, calculated by using a non-compartmental model, were 6.95 min (terminal half-life), 191 mL (Vss), and 25.5 mL/min (Cl(tot)) after intravenous administration in rats. The intestinal absorption of PD 156252 in rats was evaluated in the absence and/or in the presence of protease inhibitors. The results indicate that the major elimination pathway of PD 156252 appears to be the biliary excretion and protease inhibitors increase the intestinal absorption of PD 156252 through increasing metabolic stability.

Animals↗

Toxic contaminants and their biological effects in coastal waters of Xiamen, China. I. Organic pollutants in mussel and fish tissues.

Organochlorines and organophosphates were measured in four fish species (Lateolabrax japonicus, Pagrasomus major, Miichthys miiuy and Epinephalus awoara) and the mussel Perna viridis collected from aquaculture cages in coastal waters of Xiamen, China. Polycyclic aromatic hydrocarbon (PAH) metabolites were also measured in fish bile. Sites in Xiamen coastal waters (the harbour, Maluan and Tongan) are compared with a "cleaner" reference site at Dongshan Island. DDT was found in livers of all fish sampled (May 1998, 1999 and December 1999) ranging from 0.15 to 2.2 microg/g WW, but levels in muscle tissue (<0.5 ng/g to 0.22 microg/g WW) were at least an order of magnitude lower in the harbour, and were not detectable (<0.5 ng/g) in Tongan samples. All other pesticides examined were not detected in fish or mussels, except for dieldrin in one liver sample (0.07 microg/g WW). Food of the caged fish, small fish and dried pellets, had very low (0.015-0.027 microg/g WW) or non-detectable levels of DDT, indicating significant bioaccumulation of contaminants in caged fish and/or other possible sources of uptake (water and sediments). DDT levels in fish varied with species. DDT contamination in fish livers and whole mussels varied significantly with location. Highest concentrations in fish occurred in the harbour, and less consistently so in Tongan. Dongshan and Maluan had comparatively low levels of DDT. Relatively low residues of DDT in both fish and mussels at Dongshan likely reflect lower levels of pesticide input at this reference site. However, the low levels of DDT contamination in fish tissues from Maluan were unexpected in view of the close proximity of the harbour and possibly reflect the removal of particulate-bound contaminants by the intensive bivalve culture there. Consistently high proportions of DDT in the form of the parent compound (p,p'-DDT: fish 30-45%; mussels 40-65%) from all sites suggest recent releases of this chemical to the environment. Levels of two main groups of PAH metabolites (naphthalene and phenanthrene) in fish bile suggest a different environmental distribution pattern than that of pesticides, in that Dongshan fish appear to be no less exposed to hydrocarbons than those from Xiamen coastal waters.

Animals↗

Executive functioning in adults and children with developmental dyslexia.

The performance of developmentally dyslexic children and adults was studied upon a range of tasks that involved executive functioning. Both adult and child samples of dyslexics were found to under-perform on the group-embedded figures test. This test required the identification of constituent parts from within complex visual arrays, with good performance necessitating the inhibition of the processing of the surrounding context. A general deficit on visual-spatial tasks was eliminated as an explanation as dyslexics performed normally upon a range of other non-verbal assessments. The dyslexics consistently demonstrated a deficit in digit span tasks, a decrement that was increased with distractors, again suggesting difficulties in inhibiting the processing of the surrounding context. A deficit was also identified upon a verbal fluency task without a deficit in vocabulary level. Additionally, a specific deficit in the recollection of the temporal order of the presentation of items was in evidence, without a deficit in the recognition of the items themselves. The findings taken as a whole suggest that dyslexic individuals show deficiencies in executive functions relating to inhibition of distractors and to sequencing of events, a set of tasks associated with left prefrontal cortex functioning in the acquired neuropsychology literature.

Adolescent↗

Coxsackievirus-mediated hyperglycemia is enhanced by reinfection and this occurs independent of T cells.

The induction of autoimmunity by viruses has been hypothesized to occur by a number of mechanisms. Coxsackievirus B4 (CB4) induces hyperglycemia in SJL mice resembling diabetes in humans. While virus is effectively cleared within 2 weeks, hyperglycemia does not appear until about 8-12 weeks postinfection at a time when replicative virus is no longer detectable. In SJL mice, reinfection with CB4 enhanced the development of hyperglycemia. As predicted, the immune system responded more rapidly to the second infection and virus was cleared more swiftly. However, while infiltrating T cells were found within the pancreas, depletion of the CD4 T cell population prior to secondary infection or use of CD8 knock-out mice had no effect on the development of virus-mediated hyperglycemia. In conclusion, enhanced hyperglycemia induced by CB4 occurs independent of the T cell response.

Animals↗