Popliteal artery trauma in a forward deployed Mobile Army Surgical Hospital: lessons learned from the war in Kosovo.
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Adult↗
Biomedical subjects
J M Bruce
Publications and source records attributed to J M Bruce.
Modulation of testosterone-metabolizing hepatic cytochrome P-450 enzymes in developing Sprague-Dawley rats following in utero exposure to p,p'-DDE.
1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) causes sexual developmental aberrations in male rats through a likely mechanism of androgen receptor antagonism. DDE is also known to induce liver cytochrome P-450 (CYP). The expression of CYP enzymes is regulated by steroid hormones, which, in turn, are inactivated in the liver by CYP-catalyzed hydroxylations and subsequent conjugations. This study was undertaken to examine the potential of in utero DDE exposure to affect the developmental expression of the hepatic CYP enzymes that are responsible for testosterone hydroxylations. Pregnant Sprague-Dawley rats were dosed daily by gavage with DDE at 0, 10, or 100 mg/kg body weight or with flutamide at 40 mg/kg body weight from gestation day 14 to 18. Additional adult male rats were given seven daily doses of DDE at 100 mg/kg. Liver samples were collected from the offspring of the dosed dams on postnatal days (PND) 10 and 21 and from the adult rats a day after the last dosing. Assays for regioselective and sterospecific testosterone hydroxylase activities were performed using hepatic microsomal preparations. Specific liver CYP proteins were detected by immunoblotting. While the CYP2B1 and 3A1 and their hydroxylated testosterone products were highly elevated by the DDE treatments in both adult and developing rats, the responses of 2C11 and 2A1 were development-dependent. The flutamide treatment had little effect on CYP enzyme expression. This study demonstrated that developing offspring rats are susceptible to the hepatic CYP enzyme-modulating action of DDE following its administration to the pregnant dams.
Age Factors↗
Diffusion of nonoxynol-9 into human semen in vitro.
The diffusion of [125I]-nonoxynol-9 into human semen was investigated in vitro before and after liquefaction. No significant difference was found in the distribution of [125I]-nonoxynol-9 within columns of preliquefied semen, liquefied semen, seminal plasma, or water after < or = 120 minutes of diffusion; however, significantly more nonoxynol-9 entered preliquefied semen. The concentration of nonoxynol-9 that entered semen in vitro was greater than its ED100 and the bioavailability was confirmed by demonstration of the retention of spermicidal action. These results indicate that the gel state of preliquefied semen does not inhibit the entry or action of nonoxynol-9 and, consequently, sperm would be exposed to it immediately when it is used in vivo as a vaginal spermicide.
Adult↗
A desmoid tumor of the pancreas. Sporadic intra-abdominal desmoids revisited.
CONCLUSIONS: Desmoid tumors may rarely develop at the site of an unrelated surgical procedure. This is an index description of a desmoid tumor occurring at the line of a pancreatic resection. Because sporadic intra-abdominal desmoids are markedly less prone to recurrence than genetically determined desmoids, it is reasonable to suggest re-resection for the infrequent recurrence in sporadic cases. BACKGROUND: Intra-abdominal desmoid tumors are infrequently encountered in surgical practice and, when seen, are most often those genetically determined tumors associated with Gardner's Syndrome or familial polyposis. In contrast, fewer than 100 cases of sporadic intra-abdominal desmoid tumors have been reported; only 16 of these sporadic tumors have occurred at the site of a previous surgical procedure. The current report describes a case of sporadic desmoid tumor that developed at the pancreatic suture line 18 mo following distal pancreatectomy for a nonsecreting islet cell tumor. METHODS: An extensive literature search was focused on desmoid tumors in general, and sporadic intra-abdominal desmoids in particular. RESULTS: During the course of this collective review, it was noted that the high rate of postoperative recurrence for intra-abdominal desmoids in genetically determined cases differed markedly from the low rate of recurrence after section of sporadic tumors.
Adenoma, Islet Cell↗
Influence of hydrocarbon tail structure on quinone binding and electron-transfer performance at the QA and QB sites of the photosynthetic reaction center protein.
Binding free energies of 37 functional replacement quinone cofactors with systematically altered hydrocarbon tail structures have been determined for the QA and QB redox catalytic sites of the reaction center protein isolated from Rhodobacter sphaeroides and solubilized in aqueous and in hexane solutions. The first two and part of the third isoprene units of the 10-unit tail of the native ubiquinone-10 cofactor interact with the protein interior at each site. Contributions of the same tail structures to the binding free energies of quinones at the QA and QB sites are comparable, suggesting that the binding domains share common features. Comparison of the affinities of a homologous series of 10 n-alkyl-substituted ubiquinones resolves the binding forces along the length of the tail binding domain and shows that strong steric constraints oppose accommodation of the tail in its extended conformation. Differences in the contributions of identical tail substituents to ubiquinone- and menaquinone-QA site affinities, and tail-induced changes of up to 5-fold in the rates of QA site-mediated electron-transfer reactions, suggest that the tail adjusts the position of the quinone ring. Substitution of ubiquinone with the native 10-unit isoprene tail does not alter the affinity for the sites as determined in hexane solution. However, one- and two-isoprene-substituted quinones bind more tightly than analogs substituted with saturated-alkyl tail substituents. The sites therefore exhibit binding specificity for the native isoprene tail structure. Calculations indicate that the binding specificity arises primarily from a lower integrated torsion potential energy in the bound isoprene tails. The results suggest that the in vivo tail-protein interaction is designed to deter competitive interference of quinone function by amphiphilic species present in the native membrane.
Crystallography, X-Ray↗
Evidence for the formation of a quinone methide during the oxidation of the insect cuticular sclerotizing precursor 1,2-dehydro-N-acetyldopamine.
1,2-Dehydro-N-acetyldopamine (dehydro-NADA) is an important catecholamine derivative involved in the cross-linking of insect cuticular components during sclerotization. Since sclerotization is a vital process for the survival of insects, and is closely related to melanogenesis, it is of interest to unravel the chemical mechanisms participating in this process. The present paper reports on the mechanism by which dehydro-NADA is oxidatively activated to form reactive intermediate(s) as revealed by pulse radiolysis, electron spin resonance spectroscopy, high performance liquid chromatography, and ultraviolet-visible spectroscopic analysis. Pulse radiolytic one-electron oxidation of dehydro-NADA by N3. (k = 5.3 x 10(9) M-1 s-1) or Br2.- (k = 7.5 x 10(8) M-1 s-1) at pH6 resulted in the rapid generation of the corresponding semiquinone radical, lambda max 400 nm, epsilon = 20,700 M-1 cm-1. This semiquinone decayed to form a second transient intermediate, lambda max 485 nm, epsilon = 8000 M-1 cm-1, via a second order disproportionation process, k = 6.2 x 10(8) M-1 s-1. At pH 6 in the presence of azide, the first order decay of this second intermediate occurred over milliseconds; the rate decreases at higher pH. At pH 6 in the presence of bromide, the intermediate decayed much more slowly over seconds, k = 0.15 s-1. Under such conditions, the dependence of the first order decay constant upon parent dehydro-NADA concentration led to a second order rate constant of 8.5 x 10(2) M-1 s-1 for reaction of the intermediate with the parent, probably to form benzodioxan "dimers." (The term dimer is used for convenience; the products are strictly bisdehydrodimers of dehydro-NADA (see "Discussion" and Fig. 11)) Rate constants of 5.9 x 10(5), 4.5 x 10(5), 2.8 x 10(4) and 3.5 x 10(4) M-1 s-1 were also obtained for decay of the second intermediate in the presence of cysteine, cysteamine, o-phenylenediamine, and p-aminophenol, respectively. By comparison with the UV-visible spectroscopic properties of the two-electron oxidized species derived from dehydro-NADA and from 1,2-dehydro-N-acetyldopa methyl ester, it is concluded that the transient intermediate exhibiting absorbance at 485 nm is the quinone methide tautomer of the o-quinone of dehydro-NADA. Sclerotization of insect cuticle is discussed in the light of these findings.
Animals↗
Compatibility between the spermicide nonoxynol 9 and mid-cycle human cervical mucus.
The rate of diffusion of [125I]-nonoxynol 9 into mid-cycle human cervical mucus was measured and found to be negligible compared with D-glucose (used as an uncharged small molecule for comparison with nonoxynol 9). These data were confirmed by observation of the lack of inhibition of the movement of spermatozoa in mucus that had been in surface contact, for 3 hours, with a concentration 30 times greater than the ED100 of nonoxynol 9. These results show that the entry of nonoxynol 9 into mucus could be minimal under conditions that would exist in vivo and highlights a limitation of this compound as a vaginal contraceptive.
Cervix Mucus↗
Reduction of anthralin-induced inflammation by application of amines.
Twenty-two primary, secondary, and tertiary amines were studied to determine whether they could reduce anthralin-induced inflammation. Amine solutions of 0.18 mol/L were applied after anthralin application to normal forearm skin. Inflammation was measured with the use of Harpenden calipers by the increase in skin thickness at 48 hours. Inflammation was reduced by 66% to 95% with the use of nine different amines. There was no overall correlation between the inhibiting effect and either amine basicity or octanol/water partition coefficient. However, within each of the series of primary, secondary, and tertiary alkylamines there appeared to be some correlation between inhibitory effect and alkyl chain size, which may reflect differences in transdermal flux. Some of these amines are used in cosmetics and skin cleansers and could help reduce the inflammation that accompanies anthralin therapy for psoriasis.
Administration, Cutaneous↗
The effect of triethanolamine application on anthralin-induced inflammation and therapeutic effect in psoriasis.
Twenty patients with chronic plaque psoriasis were treated with short-contact anthralin followed by 10% triethanolamine application to one side of the body and aqueous cream to the other. Anthralin-induced inflammation was inhibited on the triethanolamine-treated side whereas anthralin therapy had to be temporarily stopped in 18 patients on the aqueous cream side because of anthralin-induced inflammation. Therapeutic response was not different in the two sides. This study shows that anthralin-induced inflammation and its therapeutic effect can be dissociated.
Adolescent↗
Anthralin-derived transients--II. Formation of the radical by spontaneous fragmentation of both singlet and triplet states of the 10,10'-dehydrodimer: radical pair multiplicity effects.
The singlet and triplet states of the anthralin (1,8-dihydroxy-9-anthrone) dehydrodimer have been produced selectively in benzene via pulsed laser excitation and pulse radiolysis respectively. The lifetime of S1 is less than or equal to 30 ps, that of T1 short but unspecified. Both states fragment spontaneously to yield a pair of anthralin radicals. The singlet radical pair predominantly undergoes geminate recombination within the solvent cage. In contrast, the corresponding triplet radical pair undergoes essentially exclusive cage escape to give the anthralin free radical (lambda max 370, 490 and 720 nm) which recombines under normal diffusive conditions. Both recombination processes lead, at least in part, to one or more species which have been assigned as tautomeric forms of the original dimer. The anthralin free radical in benzene is insensitive to the vitamin E model 6-hydroxy-2,2,5,7,8-pentamethylchroman and reacts only slowly with oxygen.
Anthralin↗
A new method of solvation analysis: applications to quinones.
A new method of analysis of the factor contributing to solvation of small molecules is described. Approximations of the energetic contributions to the entry of a molecule into water have been derived from partition coefficient data of solutes and selected derivatives from a multiplicity of solvents. These include taking separate account energy of the cost of introduction of a molecular cavity in water, the strength of solute-water dipolar interactions, and the strengths of hydrogen bond formation with water of the lone pairs and hydroxylic hydrogens associated with the molecule. In this report the solvation-free energies of benzoquinone and hydroquinone in water are described. We also consider the solvation of the semiquinone anion and show it to be fundamentally different from that of either the quinone or hydroquinone; this is discussed as a potentiality for selective binding ("solvation") of quinone, semiquinone and hydroquinone in sites of redox catalysis such as those found in the photosynthetic reaction center.
Kinetics↗
One-electron reduction of adriamycin and daunomycin: short-term stability of the semiquinones.
Pulse radiolysis studies of the one-electron reduction of adriamycin have now been extended to daunomycin. The daunomycin semiquinone has a pKa for phenolic dissociation of 2.8 +/- 0.1. Measurement of the one-electron reduction potential using several redox references at pH values within the range pH 6 to 12 indicated no significant difference between the semiquinones of adriamycin and those of daunomycin. A value of E1(7) = -341 +/- 15 mV (vs NHE) fitted the complete set of data for both compounds, with a pKa of the NH+3 group of the sugar moiety of 9.2 +/- 0.1. Measurement of equilibria between the semiquinones and the parent quinones and their fully reduced products showed a maximum semiquinone stability around pH 9. At pH 7 the stability constant is 0.04 for both adriamycin and daunomycin. From the equilibrium and E1 data, the second one-electron and the two-electron reduction potentials have been calculated over the pH range 7 to 12. E2(7) is -260 +/- 15 mV and Em7 is -300 +/- 15 mV for both compounds. The pKa values for the reduced anthracyclines have been calculated from the equilibrium data in the approximate pH range 7-12 to be 8.1 +/- 0.1 and 9.0 +/- 0.2 for the first two hydroxy groups and the two possible combinations for the ionization of the sugar NH+3 groups, with the remaining two hydroxy groups ionizing above pH 14.
Daunorubicin↗
Anthralin-derived transients--I. The triplet state and the products of its reaction with oxygen in benzene.
Direct laser excitation in benzene of 1,8-dihydroxy-9-anthrone (anthralin) does not lead to transient species with lifetimes in the nanosecond time regime or longer. The triplet state has been produced in benzene by pulse radiolysis and characterised in terms of its absorption spectrum (lambda max 560 nm), natural lifetime (11 microseconds), self-quenching properties (kmicrosecond = 2.6 x 10(7) l mol-1 s-1) and triplet energy (234 kJ mol-1). There is no tendency in the non-polar medium for production of either the triplet or ground state in a tautomeric form. The observed triplet state reacts with oxygen with a typical rate constant, 2.2 x 10(9) l mol-1 s-1. The products of this reaction are singlet oxygen (approximately 64%) and the anthralin radical (approximately 14%).
Anthralin↗
Penetration of the blood-brain barrier by the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine in a rat model of herpes encephalitis.
The blood-brain barrier penetration of a radiohalogenated (125I) derivative of the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) was investigated in a rat model of herpes encephalitis. CNS delivery was assessed by external gamma camera scintigraphic imaging in vivo, a technique which may have general application in evaluating brain specific delivery of drugs, and by autoradiography of cryostat sections of rat brain. Radiohalogenated IVDU was found to be almost totally excluded from the CNS. These findings may be explained in terms of the poor lipid solubility of IVDU (in vitro oil/aqueous salt solution partition coefficient 0.012). Since IVDU appears in CSF after carotid artery administration, our results stress the necessity, in the design of compounds for the treatment of CNS infections, of distinguishing blood-brain, blood-CSF, and CSF-brain drug barriers. The significance of our data both in relation to the development of neuro-radiological diagnosis and antiviral chemotherapy of CNS infection is discussed.
Animals↗
Reduction of anthralin inflammation by potassium hydroxide and Teepol.
Application of 1% potassium hydroxide (KOH) reduced subsequent development of anthralin inflammation without loss of its therapeutic effect on psoriasis. Teepol had a similar but smaller effect on subsequent development of inflammation. The action of KOH appears to have resulted from enhanced oxidation of anthralin to inactive products and the action of Teepol to have increased anthralin solubility and removal. The effect of KOH and Teepol decreased with time after anthralin application and both were ineffective by 24 h, indicating that anthralin persists on the skin in an active form for up to 24 h after a single application. The reduction of anthralin inflammation without loss of therapeutic effect is potentially useful in short contact anthralin therapy.
Adolescent↗
Voltammetric measurements of quinones.
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Electrodes↗
Determination of partition coefficients of quinones by high-performance liquid chromatography.
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Chromatography, High Pressure Liquid↗
Possible intermediates in the action of adriamycin--a pulse radiolysis study.
Over a wide range of pH, the semiquinone free radicals formed by reduction of adriamycin exist as a form which is strongly stabilised by internal hydrogen bonding and resonance. They protonate with pKa = 2.9. Below this pH they exhibit absorption maxima at 430 nm (Emax = 13,200 dm3 mol-1 cm-1) and approximately 720 nm (Emax = 4,200 dm3 mol-1 cm-1). Above pH 2.9 they have maxima at 480 nm (Emax = 14,600 dm3 mol-1 cm-1) and approximately 700 nm (Emax = 3,400 dm3 mol-1 cm-1). In acid and alkaline solution the radicals rapidly disappear by disproportionation, but within the approximate pH range 6 to 11 they appear to be relatively stable for at least 10-20 ms, existing in transient equilibrium with parent adriamycin and the full reduced form. Some rate constants for the formation and reactions of the semiquinone are given, including the reaction with oxygen to give O2.-. Fully reduced adriamycin has absorption maxima at 410 nm (Emax = 11,000 dm3 mol-1 cm-1) at pH 5 and 430 nm (Emax = 19,000 dm3 mol-1 cm-1) at pH 11. It undergoes decomposition within a few hundred ms. The intermediates from daunomycin would be expected to have properties similar to those from adriamycin.
Benzoquinones↗