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Biomedical subjects

R C Dunn

Publications and source records attributed to R C Dunn.

14 recordsLinked to original sources

Synergistic effect of intraperitoneally administered calcium channel blockade and recombinant tissue plasminogen activator to prevent adhesion formation in an animal model.

Previous reports have shown the benefits of calcium channel blockers and recombinant tissue plasminogen activator to prevent postoperative adhesion formation in animal models. To assess the potential benefit of synergistic therapy for the prevention of postoperative adhesion formation, these agents were studied in a rabbit uterine horn model. Four groups of New Zealand White rabbits (n = 8 per group) had a bilateral devascularization injury to the uterine horns. Before closure saline solution, verapamil hydrochloride (2.5 mu/kg/hour), recombinant tissue plasminogen activator (4 mg total dose), or a combination of verapamil and recombinant tissue plasminogen activator at the stated doses were instilled by means of an Alzet osmotic pump x 200 hours. Adhesion scores were evaluated after this time period by estimating the total uterine horn surface involved in adhesions at a terminal laparotomy and by clinically grading the response to determine whether minimal adhesions formed. Results of the total uterine horn surface scores were (mean score +/- SE): saline solution, 44% +/- 3.7%; verapamil, 19% +/- 4.8%; recombinant tissue plasminogen activator, 11% +/- 3.6%; combined, 3% +/- 1% (p less than 0.01 to control and p less than 0.05 to single-drug therapy). Results of the number of animals per group with minimal adhesions were as follows: saline solution, 0; verapamil, 1; recombinant tissue plasminogen activator, 3; combined, 8 (P less than 0.01). These results show a synergistic benefit of verapamil and recombinant tissue plasminogen activator to prevent postsurgical adhesion formation when delivered via the intraperitoneal route.

Analysis of Variance

Picosecond study of the near infrared absorption band of hemoglobin after photolysis of carbonmonoxyhemoglobin.

Picosecond absorption spectroscopy is used to examine the position and band shape of the near infrared absorption band of hemoglobin as a function of time after the photodissociation of CO from carbonmonoxyhemoglobin. For the earliest delay time probed, 35 ps, the peak of the transient spectrum is at 765 nm, red shifted by 6 nm from that characteristic of equilibrium deoxyhemoglobin. No evolution in either the peak position or band shape is observed for time delays up to 60 ns. In addition, the position and shape of the spectrum are independent of photolysis energies ranging from 15 microJ/pulse to 150 microJ/pulse, spanning conditions under which the photon/heme ratio is varied from 0.01 to 2.0. This indicates that the geometry in the heme group is unrelaxed and that equilibration of the surrounding protein structure occurs on a time scale longer than 60 ns.

Carboxyhemoglobin

Subconjunctival high dose plasminogen activator in rabbit filtration surgery.

The primary cause of failure in glaucoma filtration surgery is fibroblastic proliferation and subconjunctival fibrosis at the bleb site resulting in decreased aqueous flow. We evaluated New Zealand white rabbits in a masked, placebo controlled pilot study to determine the potential reduction of episcleral fibrosis at the surgical bleb site utilizing 0.3 mls of: balanced salt solution (n = 11); an inert gel delivery vehicle (n = 13); the gel delivery vehicle with incorporated recombinant tissue plasminogen activator (tpa; n = 14), 1 mg/ml. Statistical analysis of computer assisted area measurements from multiple histologic sections demonstrated a significant decrease in episcleral fibrosis in the t-PA group as compared to the two other groups (p less than 0.05). Results from the t-PA group did not demonstrate an effect on intraocular pressure. There was no clinical evidence of toxicity or healing complications in the t-PA group.

Animals

Tubal pregnancy with normal hysterosalpingogram and negative serum pregnancy test.

A patient undergoing evaluation for primary infertility with regular menses had a normal hysterosalpingogram in the follicular phase and underwent diagnostic laparoscopy the next day, with the finding of a tubal pregnancy. The patient had a negative serum pregnancy test. Although a normal hysterosalpingogram and negative serum pregnancy test are each rare with a tubal pregnancy, the combination of the two occurring in a tubal pregnancy is previously unreported and did not exclude the diagnosis in this case.

Adult

Molecular forms of acetylcholinesterase from the skeletal muscle of the ammocoete of the lamprey Petromyzon marinus.

1. We have studied the cholinesterase activity from the skeletal muscle of the ammocoete of the lamprey Petromyzon marinus. 2. On the basis of pharmacologic and kinetic criteria, we conclude that the enzyme is true acetylcholinesterase, not pseudocholinesterase. 3. The acetylcholinesterase was found to be present in both globular and asymmetric forms. 4. In contrast to muscle of adult spawning lamprey, where globular esterase is almost exclusively G4, we found that muscle from ammocoete also contains significant amounts of G1 and G2. 5. This difference may be related to the physiological states of the lamprey during the various stages of its life cycle.

Acetylcholinesterase

Recombinant tissue plasminogen activator reduces adhesion formation in a rabbit uterine horn model.

To evaluate the potential benefit of recombinant tissue plasminogen activator (rt-PA) as an agent for reducing postoperative adhesions, a rabbit uterine horn model was studied. Fifty-five rabbits underwent laparotomy, at which time the uterus was abraded with scalpel and a thermal injury was induced with electrocautery. Before abdominal closure, rt-PA was applied topically in various dosages. Adhesions were evaluated at a second laparotomy performed 2 weeks later. Treatment significantly reduced both adhesion quantity (P less than 0.001) and adhesion density (P less than 0.001). In the second phase of the study, the efficacy of rt-PA as an adjunct to surgical adhesiolysis was investigated. Again, a dose-related treatment effect was observed (P less than 0.001). No wound healing or bleeding complications were seen.

Animals

Low-density lipoproteins increase intracellular calcium in aequorin-loaded platelets.

Low-density lipoproteins activate isolated human platelets. The mechanism of this activation is unknown, but may involve increased phosphoinositide turnover. We have examined the effect of low-density lipoproteins on intracellular calcium concentrations in platelets loaded with the photoprotein aequorin. The lipoproteins induced concentration-dependent increases in intracellular calcium, associated with shape change and aggregation. These responses could be partially inhibited by the removal of extracellular calcium and by pre-incubation with acetylsalicylic acid. They were also antagonised by agents which increase cellular concentrations of cyclic adenosine and guanosine monophosphates. It is not clear whether the platelet-lipoprotein interaction involves a 'classical' lipoprotein receptor.

Aequorin

Changes in the secondary structure of apolipoprotein B-100 after Cu2+-catalysed oxidation of human low-density lipoproteins monitored by Fourier transform infrared spectroscopy.

Fourier transform infrared (FTIR) spectra have been obtained of human low-density lipoproteins (LDL) in H2O and 2H2O buffers. The absorption bands are assigned to vibrations of the lipid and apolipoprotein B-100 components. The analysis of second-derivative spectra allowed an assignment of individual protein bands to alpha-helical, random, coil or beta-structure and beta-turn conformations. Changes in the FTIR spectra after Cu2+-catalysed oxidation of the LDL particles indicate that the structure of apolipoprotein B-100 becomes less ordered, with some alterations of alpha-helical and beta-turn conformation. The main beta-structure absorption at 1620 cm-1 is unaffected by oxidation. Taking into account the resistance to oxidation and the slow H-2H exchange it is suggested that the beta-structure is hidden from external factors whereas other structures are mostly present on the surface of the LDL particle. Oxidation affects mainly the surface region of apolipoprotein B-100 and leads to a structural rearrangement which consequently changes the receptor specificity of the LDL.

Apolipoprotein B-100

Synapse development within the spinal trigeminal nucleus.

Pars interpolaris of the spinal trigeminal nucleus of kittens has been studied with the electron microscope at birth and at several subsequent ages during the first month of life. Attention has been given to ultrastructural maturational changes that occur in this neuropil, especially events in synaptogenesis. The results of this investigation include the following observations: (1) the neuropil, even at the earliest ages studied (three-hour-old kittens), is strikingly mature, necessitating a quantitative assessment in order to determine subtle developmental changes in synaptic patterns; (2) the number of axoaxonic contacts at birth are few, and their emergence is essentially a postnatal phenomenon; (3) it appears that the immature Gray type II or symmetrical synapse possesses distinct cleft material and dense, parallel membrane specializations. Synaptic vesicle accumulation at this contact appears to occur after the membrane specializations have formed. A previous study by Kerr26 has shown a reduced potential for primary afferent reorganization with the spinal trigeminal nucleus when kittens are subjected to trigeminal rhizotomy after three days of age. Our observations on the development of axoaxonic synaptic arrangements in the neonatal period may provide an explanation for these earlier results.

Age Factors

Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta.

The vascular endothelium, in response to pulsatile flow and vasoactive agents including acetylcholine, secretes the endothelium-derived relaxing factor (EDRF), a substance which regulates vascular tone. Recent interest in EDRF has focused on its possible dysfunction in atherosclerosis. In animal models of the disease, endothelium-dependent relaxation is markedly reduced. The continuous exposure of the endothelium in hyperlipidaemia to high concentrations of low-density lipoprotein (LDL), a known atherogenic risk factor, may explain this dysfunction. Here, we demonstrate that pathophysiological concentrations of LDL directly inhibit endothelium-dependent relaxation. Chemically modified LDL, in contrast, is inactive, implying that the inhibition is through a receptor-dependent mechanism.

Acetylcholine