Preliminary in vitro evaluation of a tooth-lightening prophylaxis paste.
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Biomedical subjects
Publications and source records attributed to J Browning.
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OBJECTIVE: This study explored the effect of comorbid anxiety disorders in patients admitted to an inpatient specialist Mood Disorders Unit for the treatment of a primary major depressive episode. METHOD: Subjects were assessed on admission and discharge. DSM-III-R diagnoses for major depression and anxiety disorders were established using CIDI-Auto; comorbid anxiety disorders were coexistent in time with the major depression, with both conditions meeting diagnostic criteria at the time of assessment. Severity of illness was assessed using the Hamilton Depression/Melancholia Scale, the revised Hamilton Anxiety Scale and the revised Beck Depression Inventory. RESULTS: For the analysis, the study cohort was divided into three groups: depression alone (n = 33), one comorbid anxiety disorder (n = 15), and two or more comorbid anxiety disorders (n = 24). No particular anxiety disorder predominated. Interestingly, the presence or absence of comorbid anxiety with severe major depression made no significant difference to treatment choice or outcome results. Specifically, there was no significant difference between the three groups in the utilisation of electroconvulsive therapy and pharmacotherapy (including antidepressants, benzodiazepines and neuroleptics); all subjects improved significantly on both depression and anxiety ratings, and length of inpatient stay did not vary significantly between the three groups. CONCLUSIONS: The existence of comorbid anxiety disorders in those patients who presented for treatment of a primary major depressive episode did not significantly effect choice of treatment or treatment outcome, suggesting that there is a close interrelationship between the two conditions.
PURPOSE: To describe a quantifiable model of vascular proliferation in oxygen-induced retinopathy (OIR) in the mouse. METHODS: Neonate Quackenbush mice were subjected to high-ambient oxygen (approximately 95%) for the first 5 days after birth, effecting a total inhibition of retinal vascular growth. Animals then were returned to room air, and the rates of subsequent vascular development in the plane of the retina and estimates of retinal capillary density were measured from flatmounts of ink-perfused eyes. Observations were confirmed with fluorescein isothiocyanate-lectin labeling of the peripheral vasculature. Abnormal growth of vascular sprouts into the vitreous was recorded from cross-sections. Observations in OIR were compared against those of age-matched control animals. RESULTS: The slower rate of retinal revascularization in OIR mice was quantified and compared against the normal rate. Lectin-binding studies confirmed the reliability of ink preparations. The number of vitreous sprouts in OIR peaked 8 to 10 days after animals were returned to room air (13 to 15 postnatal days). Sprouts then regressed, to disappear by postnatal day 20. In all respects, bar a slightly lower peripheral capillary density, the normal retinal vascular pattern was achieved in OIR within 15 days of exposure to room air (as opposed to the 10 days required in control mice). CONCLUSIONS: The protocol described for quantifying retinal proliferation in mouse OIR is reproduced readily, and the data recorded here will allow the effectiveness of subsequent treatments that may affect retinal vascular growth to be evaluated better.
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The rate and equilibrium parameters for the interfacial catalysis by recombinant human nonpancreatic secreted phospholipase A2 were determined. Results show that the enzyme binds to anionic interfaces with considerably higher affinity than to zwitterionic interfaces. The extent of hydrolysis per enzyme on anionic vesicles in the processive scooting mode shows that the enzyme is fully catalytically active as a monomer. Among several secreted phospholipases A2 tested, the human nonpancreatic secreted enzyme is unique in its ability to undergo slow intervesicle exchange either by dissociation from the interface followed by binding to a different vesicle or by promoting the fusion of vesicles. The equilibrium dissociation constants for calcium, substrate analogs, reaction products, and several competitive inhibitors bound to the enzyme at the interface were determined by monitoring the ligand-conferred protection of the active site histidine residue from alkylation by phenacyl bromide. The interfacial Michaelis-Menten parameters were determined from the analysis of the entire reaction progress curve and also by monitoring the effect of competitive inhibitors on the initial rate of hydrolysis in the scooting mode. The interfacial Michaelis constant (KM*) for the substrate 1,2-dimyristoylglycero-sn-3-phosphomethanol was determined to be considerably above the maximal attainable mole fraction of unity for the substrate in the bilayer. Substrate specificity studies show that the enzyme does not significantly discriminate between phospholipids that differ in the type of polar head group or in the degree of unsaturation of the fatty acyl chains. Competitive inhibitors are described that display a high degree of selectivity for binding to the nonpancreatic versus pancreatic phospholipase A2. The kinetic properties of the human nonpancreatic secreted phospholipase A2 suggest that the enzyme has evolved to hydrolyze substrates at anionic interfaces and at high calcium concentrations.
The body's response to infection/inflammation is initiated by the elaboration of cytokines, such as tumor necrosis factor, interleukin 1-beta (IL-1-beta), IL-6, and IL-8. Cytokines, in turn, stimulate the pituitary-adrenal axis, and it has been suggested that the corticosteroids elaborated serve as negative feedback signals to diminish inflammatory events. To test this hypothesis, we administered hydrocortisone shortly before endotoxin administration to normal volunteers. Steroids greatly reduced the clinical response to endotoxin and attenuated the appearance of tumor necrosis factor, IL-6, and IL-8 in the circulation. In contrast, IL-1-receptor antagonist, a competitive antagonist of the IL-1 receptor, was unaffected by steroid administration. These data suggest that IL-1-receptor antagonist may act in synergism with corticosteroids to reduce inflammation. Elevation of concentrations of these two factors, corticosteroids and IL-1-receptor antagonist, in plasma appears to be the mechanism used by the body to overcome the effects of inflammatory cytokines.
Human non-pancreatic PLA2 has been the object of intense scrutiny for a relatively short period of time. Its role in physiology remains enigmatic. While PLA2 may serve to remodel or remove peroxidised or senescent phospholipids, the enormous magnitude of its upregulation during infectious or inflammatory episodes is consistent with a role in host defense. However, the nature of this role remains elusive. Attempts to relegate this enzyme to the genre of acute phase reactants have not been helpful in unravelling its role. Difficulty in obtaining adequate amounts of native snp-PLA2 prior to the availability of recombinant snp-PLA2 led to the widespread use of snake venom homologs, particularly in studies of the biology of PLA2. This review has underscored the pitfalls inherent in that approach given the major differences between some venom PLA2s as compared to snp-PLA2. In addition, it bears reiterating that the complex composition of venom allows for potentiation of PLA2 activity by other constituents present in venom. Whether human host defense networks employ this interactive strategy is largely unknown. Nonetheless, in spite of these reservations, some very compelling data have emerged in recent years implicating snp-PLA2 in the initiation or potentiation of local and systemic inflammatory processes. These include sepsis and associated acute lung injury as well as inflammatory arthritides, with rheumatoid arthritis as the prototype. The mechanisms of snp-PLA2 homeostasis are considerably better understood, and it has become apparent that snp-PLA2 is an integral part of a larger network of proinflammatory cytokines, growth factors and lipid mediators. The interrelationship between the functions of secretory and cytosolic PLA2s remains to be defined. A number of selective PLA2 inhibitors have been identified which will allow for discrimination between the actions of these classes of PLA2. The availability of synthetic inhibitors in conjunction with endogenous modulators of PLA2s will shift the biology of PLA2 from the realm of the inferential to that of the mechanistic.
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Newborn mice exposed to high (greater than 98%) ambient oxygen during the newborn period and subsequently removed to room air will develop a proliferative retinopathy which mimics the neovascular component of acute retinopathy of prematurity. In this paper, we report preliminary ultrastructural findings on the vitreous new vessels in the mouse model of oxygen-induced retinopathy, and argue that the model is appropriate for research on non surgical treatments for ROP in particular and angiogenesis in general.
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Thirty-seven patients with carcinoma of the cervix were prospectively staged by examination under anaesthesia (EUA), transvaginal and transrectal ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Pathological correlation was available for 20 patients. In the pathologically staged patients, EUA agreed with the staging in 17, understaging three patients. Endosonography agreed with the staging in 19, CT in 16 and MRI in 18 patients. For the remaining 17 patients, endosonography agreed with the EUA findings in 13, CT in 12 and MRI in 12. This study has shown that endosonography and MRI are more accurate than CT in the local staging of carcinoma of the cervix. Computed tomography was least accurate in staging early tumours and differentiating between Stage Ib and IIb disease. Lymph node involvement was detected with equal frequency by both CT and MRI. Magnetic resonance imaging was useful in identifying vaginal and bladder wall involvement and in one patient showed features due to an unsuspected early pregnancy.
Oxygen-induced retinopathy was produced by exposing 3-day-old kittens to 80% oxygen between 60 and 105 hours. They were then allowed to survive in room air until day 15, 21 or 28 when they were sacrificed after perfusion with colloidal carbon. Specimens were prepared for transmission electron microscopy. Ninety separate vitreous capillaries from oxygen-treated animals were examined. A total of 235 intercellular junctions were examined, 116 of them from the 15-day old animals. In the 15-day old animals, five junctions of 116 were open and the remainder were tight. No open junctions were seen in 21- or 28-day-old animals. In one capillary from a 15-day animal, fenestrated endothelium was seen in an aberrant, intraluminal loop of endothelium which formed no part of the blood/tissue barrier. The wall thickness of the vitreous new vessels seemed to decrease and the number of vesicles and vacuoles appeared to increase with increasing age. The basement membrane of the vitreous new vessels was scanty. In some sections, cells, presumably macrophages, were seen outside the new vessels. It is concluded that the increased permeability of the vitreous new vessels in 15-day-old animals can be explained by, and is possibly totally due to, the presence of open endothelial junctions.