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Biomedical subjects

D B Chandler

Publications and source records attributed to D B Chandler.

At least 55 records · Page 3Linked to original sources
PubMed1985

The effect of bleomycin on lung metabolism of prostaglandin E2 in hamster.

Lung is a major site of prostaglandin synthesis and degradation. One site of metabolism has been shown to be the endothelial cell. Metabolism of prostaglandins has been shown to be influenced by both physiological and pathological mechanism. Furthermore, it has been suggested that a relationship might exist between pulmonary disease and the lung's ability to synthesize and/or degrade prostaglandins. Therefore, we evaluated if bleomycin-induced fibrosis, a model of human pulmonary fibrosis, affects the ability of lung to metabolize prostaglandins. Single pass metabolism of prostaglandin E2 was evaluated in an isolated, perfused and ventilated lung of hamsters at 5 and 500 nM concentrations 4,7,14,21 and 28 days after intratracheal bleomycin. The metabolism of prostaglandin E2 was not changed at the 5 nM level, but was significantly decreased at 500 nM level on day 14 and day 28 after intratracheal bleomycin. The results suggest that intratracheal bleomycin causes alterations in prostaglandin metabolism; the mechanism(s) is unknown but may be related to endothelial cell damage and possible changes in alveolar-capillary surface area.

Animals↗
PubMed1985

The effect of endotoxin on bleomycin-induced lung fibrosis in the rat.

Bleomycin is a commonly used antineoplastic agent which produces dose- and time-dependent pneumonitis and fibrosis in humans. The mechanism of bleomycin-induced lung injury is uncertain. However, current data shows that bleomycin can generate reactive oxygen species such as superoxide and hydroxyl radicals. We therefore investigated whether intraperitoneal (i.p.) injection of endotoxin, a protectant for hyperoxia, could modulate the biochemical and morphological estimates of bleomycin-induced lung fibrosis in rats. However, pretreatment with multiple i.p. injections of endotoxin, combined with intratracheal bleomycin instillation, resulted in increased lung collagen content compared to bleomycin treatment alone and controls. Furthermore, morphological estimates of the severity of lung lesions present in the endotoxin-bleomycin treatment group were increased when compared with saline and endotoxin control lung lesions. These data indicate, in the current study design, that endotoxin did not reduce, but instead increased the severity of bleomycin-induced pulmonary fibrosis in rats. The mechanism for this increase in fibrosis may be the result of pre-existing endotoxin-induced cell injury.

Animals↗
PubMed1985

The effect of deferoxamine on bleomycin-induced lung fibrosis in the hamster.

Bleomycin is a commonly used antineoplastic compound that can produce a dose- and time-dependent pneumonitis and fibrosis in humans. The mechanism of bleomycin-induced fibrosis is not known. However, current data suggest that the production of oxygen radicals by way of a ferrous ion-molecular oxygen mechanism might be related to the pulmonary fibrosis. Therefore, we evaluated the possibility that parenterally administered deferoxamine, an iron chelating compound, could modulate the morphologic and biochemical estimates of bleomycin-induced lung fibrosis in hamsters. Deferoxamine pretreatment and daily injection for 21 days after intratracheally administered bleomycin resulted in a 33% reduction in lung collagen accumulation compared with that after bleomycin treatment alone. However, fibrosis was still present in the bleomycin-deferoxamine group; the animals showed a 142 and 150% increase in lung collagen compared with that in saline- and deferoxamine-treated control animals, respectively. Morphologic estimates of the severity of fibrosis in the bleomycin-deferoxamine treatment group were reduced when compared with the bleomycin treatment group alone, but was increased compared with saline- and saline-deferoxamine-treated control animals. These data indicate that deferoxamine treatment reduces the severity of bleomycin-induced pulmonary fibrosis in hamsters. The mechanism might be by the prevention of iron-catalyzed, free-radical formation.

Animals↗
PubMed1984

Scanning electron microscopy of vascular casts in experimental ocular vasoproliferation.

Scanning electron microscopy of vascular casts was used to investigate three experimental models of neovascularization. In each experimental situation, the casts provided a valuable three dimensional representation of the newly formed blood vessels and permitted subclassification of the vessels within normal and proliferating vascular networks. They defined also the predominant origin of new vessels from venules and capillaries, and enabled the evolution of proliferating vessels into arterioles and venules to be documented. Although vascular casts must be interpreted with caution in light of the possibility of incomplete filling and other artifacts, they are a valuable tool in the study of ocular vasoproliferation.

Animals↗
PubMed1983

Macular pucker. I. Prognostic criteria.

Thirty-three eyes with symptomatic epimacular membranes were treated by vitreous surgery and membrane removal. Vision improved in 79%. Eyes with clinically transparent membranes, but without preoperative cystoid macular edema, were most likely to achieve good vision, while opaque membranes had worse vision. Because cystoid macular edema was the most common obstacle to improved vision, membranes should be removed before this process begins, or as soon as possible thereafter. Angiography should precede consideration of surgery. Even though large parts of the internal limiting lamina of the retina were often peeled with the membranes, excellent vision was possible.

Humans↗
PubMed1983

Macular pucker. II. Ultrastructure.

Twenty symptom-producing epimacular membranes removed during vitreous surgery were examined by light microscopy, scanning and transmission electron microscopy. These membranes contain cells of glial and pigment epithelial origin, but one also finds myofibroblasts and fibroblasts which cannot be identified morphologically as to their origin. The membranes can be classified into two types. Membranes in one group are composed of numerous alternating layers of collagen and cells and some internal limiting lamina. The second type of membrane is generally composed of a single layer of cells with large sheets of internal limiting lamina from the retinal surface and little if any collagen. Both types of membranes have cells on the retinal side of the removed internal limiting lamina, presumably derived from neurosensory retina.

Humans↗
PubMed1983

Effects of paraquat on plasma glucose, cortisol, catecholamines, and insulin in the beagle.

Paraquat is known to produce hyperglycemia in rodents, although the mechanisms responsible for the hyperglycemic effect of paraquat are not clearly understood. In this study we report the effects of paraquat (25 mg/kg iv) on plasma glucose, cortisol, catecholamines, and insulin in dogs. Paraquat caused a significant increase in plasma glucose level at all times of measurement except at 0.5 hr following paraquat administration. The cortisol levels after paraquat treatment were increased to 133, 305, 279, 418, 517, 672, and 567% above zero time control at 0.5, 1.5, 3, 6, 12, and 24 hr, and at death time respectively. The catecholamines at these times were increased to 42, 17, 72, 118, 138, 226, and 435% above the control. In contrast to cortisol and catecholamines, the plasma insulin levels after paraquat treatment were significantly decreased at 3, 6, 12, and 24 hr. These hormonal observations can explain, at least in part, the observed hyperglycemia, since all promote hyperglycemic states. For example, cortisol is gluconeogenic, catecholamines are glycogenolytic, and lower insulin levels result in depressed peripheral glucose utilization.

Animals↗
PubMed1983

Increases in lung prolyl hydroxylase and superoxide dismutase activities during bleomycin-induced lung fibrosis in hamsters.

Intratracheal administration of bleomycin causes pulmonary fibrosis in hamsters. Using this model the activities of lung prolyl hydroxylase and superoxide dismutase and the accumulation of neutral salt soluble and insoluble collagens have been determined. One unit of bleomycin was injected intratracheally to hamsters, whereas control animals received an equivalent volume of sterile saline by the same route. Total lung prolyl hydroxylase activity was significantly elevated at all times following bleomycin treatment. The activity was increased as early as 2 days, peaked to a maximum value of 400% of the control at 14 days, followed by a sharp decline to 235% and 180% of the control activity at 21 and 28 days after bleomycin treatment, respectively. Except for the earliest time (2 days), lung prolyl hydroxylase specific activity was also significantly elevated at all times after bleomycin treatment. A significant increase in both total and specific activities of lung superoxide dismutase was also observed at all times after bleomycin treatment. Total activity peaked to a maximum value of 315% of the control activity at 14 days and the specific activity to a maximum value of 190% of the control at 21 days after bleomycin treatment. Thereafter, both activities declined, but were still significantly elevated over the control at 28 days after the treatment. Lung proline pool size was significantly increased at all times and attained a maximum value of 372% of the control at 14 days after bleomycin treatment. Increases in the lung prolyl hydroxylase and superoxide dismutase activities and in the proline pool size preceded the significant increases in neutral salt soluble and insoluble collagens which occurred at 7 days after bleomycin treatment and continued to be significantly elevated for the remaining period of the study.

Animals↗
PubMed1983

The in vitro synthesis and degradation of prostaglandins during the development of bleomycin-induced pulmonary fibrosis in hamsters.

Subsequent to optimization of conditions for enzyme assay, we examined the in vitro synthesis and degradation of prostaglandins by the lung during the development of bleomycin-induced pulmonary fibrosis in hamsters. It was found that the microsomal protein content on a per lung basis was significantly increased to 144, 129, 134, and 121% of control (2.3 mg protein/lung) at 4, 7, 14 and 21 days post-treatment, respectively. The synthesis of PGD2 was significantly elevated to 10.2, 10.8, and 12.5 nmoles/lung at 7, 21 and 28 days, respectively, as compared to the control value of 5.6 nmoles/lung. Significant increases in PGF2 alpha synthesis from the control value of 3.3 nmoles/lung to 5.2, 8.2 and 5.5 nmoles/lung were found at 4, 7 and 21 days post-treatment, respectively. The synthesis of PGE2 also showed significant increases above the control value of 6.1 nmoles/lung to 10.5, 12.2 and 11.0 nmoles/lung at 7, 21 and 28 days post-treatment, respectively. Similarly, the synthesis of 6-keto-PGF1 alpha was significantly increased to 7.4, 7.5 and 8.6 nmoles/lung at 7, 21 and 28 days post-treatment, respectively, as compared to the control value of 4.4 nmoles/lung. The synthesis of TxB2 was also significantly increased from the control value of 3.9 nmoles/lung to 7.5 and 6.4 nmoles/lung at 7 and 21 days post-treatment, respectively. Accompanying the increased synthesis of prostaglandins in general, the in vitro degradation of PGF2 alpha was significantly increased from the control value of 71.1 nmoles/lung to 173.5, 131.7 and 143.3 nmoles/lung at 2, 4 and 7 days after bleomycin treatment, respectively. We conclude that bleomycin-induced pulmonary fibrosis leads to changes in prostaglandin synthesis and degradation possibly as a result of an accompanying inflammatory response and resident cellular proliferation.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Corneal neovascularization as studied by scanning electron microscopy of vascular casts.

Rat corneas were cauterized chemically, and the induced neovascularization was studied by scanning electron microscopy of vascular casts. Casts were prepared by filling the pericorneal and intracorneal vessels with an acrylic monomer by an intracardiac injection. The initial response to injury was a vasodilation of pericorneal vessels and the appearance of impressions in the walls of veins and venules consistent with those of marginating leukocytes. The first new vascular buds emerged from the pericorneal venules and capillaries at 27 hours after injury. These sprouts lengthened and multiplied by 72 hours to produce a rich anastomosing plexus. New vessels were not seen arising from arteries and arterioles. By 7 days, numerous channels reached the cautery site and, by 13 days, many of the redundant intracorneal vessels had regressed leaving large looping channels connecting either with a pericorneal artery or a vein. The casts of those continuous with the artery had surface features suggesting arterial or arteriolar differentiation, whereas the smooth surfaces of the remaining channels were consistent with those of veins or capillaries. Transmission electron microscopy confirmed this differentiation by documenting intracorneal vessels with the smooth muscle and prominent endothelial cell nuclei which characterize arteries and arterioles. Vascular casts have several advantages in the study of neovascularization. They depict the three-dimensional characteristics of new vessel formation and reflect the vascular and cellular events in the accompanying acute inflammatory response; define more readily than histologic sections the time that the first new buds appear; emphasize capillaries and venules as the predominant source of new vessels; and suggest that certain new intracorneal vessels assume morphologic features of arteries or arterioles, whereas others retain capillary or venous characteristics.

Animals↗
PubMed1983

Morphometric estimates of infiltrative cellular changes during the development of bleomycin-induced pulmonary fibrosis in hamsters.

The sequence of cellular infiltration into interstitial lung tissue subsequent to intratracheal administration of bleomycin was examined in hamsters. Quantitation of lesions following bleomycin treatment showed a transient increase in the percentage of lung involved, which peaked at 21 days and decreased thereafter. Associated with these lesions was a significant increase in interstitial cell profile density at 21 and 28 days. The total number of cell profiles decreased after 28 days. The cellular composition of the lesion was dominated by monocytes, neutrophils, and macrophages in the initial phase of the fibrosis. Subsequently, monocytes were significantly decreased at 21, 28, and 42 days, as compared with the 7-day value. Similarly, neutrophils were significantly decreased at 21 and 28 days, as compared with the 7-day value. In contrast, macrophages were significantly decreased in the initial phase (7 days) of the cellular infiltration and the later phase at 35 and 42 days, as compared with the value at 4 days after treatment. Lesion composition in the later phase exhibited significant increases in fibroblasts and eosinophils, accompanied by a general increase in lymphocytes. It is concluded that bleomycin-induced inflammatory sequela exhibits temporally based changes in cellular composition of the infiltrate and that the temporal changes in cellularity might be one of the determinants in the pathophysiology of pulmonary fibrosis induced by bleomycin.

Animals↗
PubMed1981

Glucocorticosteroid inhibition of intraocular proliferation after injury.

Perforating injuries were produced in the posterior segment of rabbit eyes. We studied the inhibitory effect of a slowly water-soluble corticosteroid, dexamethasone alcohol, on fibroblast growth. The treated group received a single intravitreal injection of 1 mg of the corticosteroid. The eyes were observed for four weeks. Transvitreal proliferation was significantly decreased and wound healing was delayed as compared to a control group. Inhibition of intraocular proliferation by high doses of intravitreally injected corticosteroid may be useful in the treatment of eyes with penetrating and perforating injuries.

Animals↗
PubMed1981

Effects of acute paraquat toxicity on circulating levels of arachidonic acid, PGF2 alpha and PGE2 in the beagle.

We studied the effects of paraquat (25 mg/kg, free base, I.V.) on the circulating plasma levels of arachidonic acid, PGF2 alpha and PGE2 in the beagle. The arachidonic acid level was quantified by GLC and prostaglandins by radioimmunoassay. The plasma levels of arachidonic acid after paraquat treatment were decreased to 50.8% of control at 0.5 hrs. Thereafter the levels increased with time reaching a maximum level of 127.8% at 12 hrs, from which it decreased to 82.8% of control at 24 hrs. Concurrent with these changes in arachidonic acid, the plasma PGE2 levels at 0.5, 1.5, 6.0, 12.0 and 24.0 hrs were significantly decreased to 65.4%, 42.5%, 52.4%, 41.0% and 50.3% of control levels, respectively. In contrast to these findings the plasma levels of PGF2 alpha after paraquat treatment were insignificantly elevated at 0.5, 3.0, 6.0, 12.0, and 24.0 hrs, to 174.3%, 170.4%, 119.3%, 183.3% and 180.3% of control respectively. The ratio of PGE2/PGF2 alpha exhibited a significant decrease at 12.0 and 24.0 hrs. Histopathological studies revealed insignificant changes of the lungs, but marked changes of the kidney. We concluded from these studies that changes in plasma levels of prostaglandins may be related to the acute nephrotoxicity caused by paraquat in dogs.

Animals↗
PubMed1981

Retinal neovascularization after intravitreal fibroblast injection.

We have developed a new model of retinal neovascularization in the rabbit. After intravitreal autotransplantation of 250,000 tissue-cultured skin fibroblasts, we observed strand formation in the midvitreous cavity. These strands grew toward the vascularized part of the retina and attached to it. Once the attachment was established, retinal neovascularization began with growth of vessels along the fibrous strand. After three months, this retinal neovascularization regressed. The presence of immature capillaries was confirmed by electron microscopic examination. Of 43 eyes, 31 (72%) developed neovascularization.

Animals↗
PubMed1981

Vascular casts of experimental retinal neovascularization.

Autotransplantation of skin fibroblasts into the vitreous cavity of the rabbit eye resulted in the formation of fibrous strands that rapidly vascularized. To study this neovascularization, we injected methylmethacrylate monomer via the common carotid artery and made plastic casts between three days and three months after transplantation. Budding of new vessels into the fibrous tissue from retinal veins was observed as soon as three days after transplantation. The new vessels grew rapidly into the fibrous tissue matrix and an increasing number of anastomoses developed during the observation period. Neovascular fans developed at the proximal end of the proliferating fibrous tissue two to four weeks after injection. As the strands contracted, changes in blood flow resulted in aneurysmal dilatations and glomerular formations.

Animals↗