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M E Brezinski

Publications and source records attributed to M E Brezinski.

54 records · Page 3Linked to original sources
PubMed1996

Imaging developing neural morphology using optical coherence tomography.

Imaging technologies offer numerous possibilities to investigate the processes involved in neural development. The optical coherence tomography (OCT) technology is analogous to ultrasound backscatter microscopy except reflections of light are detected rather than sound. The OCT technology combines high-resolution in vivo imaging in a diode-based benchtop instrument capable of micron-scale resolution in transparent and non-transparent biological specimens. In this paper, we examine the potential of using OCT for the investigation of developing neural morphology. To demonstrate the capabilities of this technique in assessing neural development, we have chosen to image early normal and abnormal neural morphology in a common developmental biology model, Xenopus laevis. In vivo images clearly identify gross and subtle differences in neural structure and may offer an alternative to the costly and time-consuming process of repeated histological preparation for neural developmental studies. Because imaging can be performed rapidly and repeatedly, the morphological changes of single specimens can be followed throughout development. To illustrate the future potential of this technique, a state-of-the-art Cr4+:forsterite modelocked laser is used as a broad bandwidth light source to image individual cells in a developing specimen.

Animals↗
PubMed1995

Optical biopsy and imaging using optical coherence tomography.

Optical coherence tomography is a new imaging technique that can perform high-resolution, micrometre-scale, cross-sectional imaging in biological systems. The technology has been developed, and reduced to, preliminary clinical practice in ophthalmology. The challenging problem that OCT may address is the development of 'optical biopsy' techniques. These techniques can provide diagnostic imaging of tissue morphology without the need for excision of specimens. Many investigations remain to identify optimal areas for clinical application, and additional engineering must be done to integrate vertically the technology and to reduce it to clinical practice. Nevertheless, preliminary studies indicate the feasibility of developing this technology for a wide range of clinical and research diagnostic imaging applications. The ability to non-excisionally evaluate tissue morphology using a catheter or an endoscope could have a significant impact on the diagnosis and management of a wide range of diseases.

Arteries↗
PubMed1990

Selective incorporation of (15S)-hydroxyeicosatetraenoic acid in phosphatidylinositol of human neutrophils: agonist-induced deacylation and transformation of stored hydroxyeicosanoids.

The uptake and mobilization of (15S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid (15-HETE), a major product of arachidonic acid metabolism, was examined with human neutrophils (polymorphonuclear leukocytes; PMNs). Upon exposure to labeled 15-HETE, PMNs rapidly (15 sec to 20 min) incorporated approximately 20% of the label into phosphatidylinositol, while less than 4% was associated with other phospholipid classes and neutral lipids. This pattern was distinct from that of either labeled arachidonate or labeled(5S)-hydroxy-8,11,14-cis-6-trans-eicosatetraenoic acid (5-HETE), which within 20 min were predominantly associated with triglycerides and phosphatidylcholine. After reversed-phase HPLC, greater than 98% of the label in phosphatidylinositol, isolated from PMNs, was released with phospholipase A2. Upon exposure to either chemotactic peptide (FMLP), phorbol 12-myristate 13-acetate, or an ionophore (A23187), 15-HETE-labeled PMNs released 15-HETE from phosphatidylinositol and displayed an impaired ability to generate leukotriene B4 (LTB4), 20-OH-LTB4, and 20-COOH-LTB4. Deacylated [3H]15-HETE was converted to (5S,15S)-dihydroxy-6,13-trans-8,11-cis-eicosatetraenoic acid (5,15-DHETE), lipoxin A4, and lipoxin B4, each carrying 3H label. PMNs labeled with 5-HETE also released and transformed this HETE when stimulated. However, the profile of labeled products differed between PMNs with either esterified 15-HETE or 5-HETE. When activated, 5-HETE-labeled PMNs generated both 5,20-DHETE and 5,15-DHETE but not labeled lipoxins. Threshold aggregation induced by FMLP with 15-HETE-labeled PMNs was inhibited (approximately 2 orders of magnitude), while the threshold response was relatively unimpaired with either A23187 or phorbol 12-myristate 13-acetate-induced aggregation. Results indicate that 15-HETE is rapidly esterified into phosphatidylinositol of PMNs, which can be mobilized and transformed upon exposure of the cells to a second signal. Moreover, they suggest that eicosanoid intermediates other than arachidonic acid can be stored by cells, released via signal transduction, and oxygenated to generate alternative profiles of eicosanoids.

Arachidonic Acid↗
PubMed1989

Lipoxins stimulate prostacyclin generation by human endothelial cells.

Cultured human umbilical endothelial cells were incubated with lipoxins and their ability to generate prostacyclin (PGI2) was assessed and compared to that induced by either leukotriene C4 or an ionophore of divalent cations (A-23,187). When exposed to either lipoxin A4, lipoxin B4, or 7-cis,11-trans-lipoxin A4, endothelial cells generated prostacyclin detected as 6-keto-PGF1 alpha. Of the lipoxins examined, 7-cis,11-trans-lipoxin A4 proved to be the most effective with PGI2 production twice that induced by equimolar amounts of A-23,187 (5 microM). On a molar basis, lipoxin A4 and lipoxin B4 were less potent than leukotriene C4 although they were more efficacious. When either lipoxin A4 or lipoxin B4 was added to cells simultaneously with leukotriene C4, the formation of prostacyclin was greater than that induced by leukotriene C4 alone. During the time course of exposure to lipoxins (0-20 min, 37 degrees C), cultured endothelial cells did not further transform these compounds via omega-oxidation as determined by reverse-phase HPLC. These data indicate that lipoxins can stimulate PGI2 generation by human endothelial cells. Moreover, they suggest a role for these lipoxygenase products of arachidonic acid in the regulation of hemostasis, inflammation and vascular reactivity.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Cardioprotective actions of nisoldipine in postreperfusion myocardial ischemia.

Nisoldipine, a dihydropyridine with calcium channel-blocking activity, was studied in myocardial ischemia and reperfusion in cats. At an infusion rate of 3 micrograms/kg/hr, nisoldipine did not significantly alter the product of mean arterial blood pressure and heart rate, the pressure-rate index. When infusion of nisoldipine was started 30 minutes after occlusion and continued for 5 1/2 hours, nisoldipine exerted a marked antiischemic effect. This effect was manifested as a significant reduction in necrotic myocardial tissue expressed either as a percentage of area at risk (p less than 0.01) or as a percentage of total left ventricle (p less than 0.01). The washout of creatine kinase into the circulation was also reduced in nisoldipine-treated cats. When nisoldipine infusion started at 60 minutes after ischemia, the effects were still significant (p less than 0.05) but less striking, and when nisoldipine infusion was delayed until 90 minutes after ischemia, no significant cardioprotection was observed. Nisoldipine also blunted the washout of creatine kinase into the peripheral circulation on reperfusion. Thus nisoldipine exerts a cardioprotective effect in cats during myocardial ischemia independent of reducing myocardial oxygen demand. The effect is optimal when nisoldipine is given during the first 30 minutes of ischemia and declines thereafter, reaching insignificant effects at 90 minutes.

Animals↗
PubMed1988

Lipoxins A4 and B4: comparison of icosanoids having bronchoconstrictor and vasodilator actions but lacking platelet aggregatory activity.

Lipoxins A4 (LxA4) and B4 (LxB4), two lipoxygenase-generated icosanoids of arachidonic acid metabolism, were found to have a distinct biological profile. Both LxA4 and LxB4 slowly contracted pulmonary parenchymal strips isolated from guinea pigs, rabbits, and rats in a concentration-dependent manner over the range 0.1-1 microM. This bronchoconstrictor effect was not associated with release of peptide leukotrienes or thromboxane A2, nor was it blocked by lipoxygenase inhibitors or thromboxane receptor antagonists, suggesting it is a direct effect of lipoxins. However, the leukotriene D4 (LTD4) receptor antagonist LY-171883 reduced the LxA4 response, indicating that LTD4 and LxA4 may share the same receptor. LxA4 and LxB4 also exerted an endothelium-dependent vasorelaxation in guinea pig, rat, and, to a lesser extent, rabbit aortic vascular smooth muscle. In contrast to other vasoactive icosanoids, LxA4 and LxB4 failed to aggregate rat, rabbit, or guinea pig platelets or to inhibit ADP-induced aggregation. LxA4 also enhanced the release of liver lysosomal hydrolases in a liver large granule fraction, indicating a lysosomal labilizing action of LxA4. LxA4 and LxB4 share a similar biological profile. It is not clear yet whether the lipoxins could be mediators of circulatory or pulmonary disease states.

Animals↗
PubMed1988

Cardioprotective actions of human superoxide dismutase in two reperfusion models of myocardial ischaemia in the rat.

1. In rats under ether anaesthesia, the left coronary artery was ligated and reperfused after 10 min of ischaemia. Forty-eight hours later the myocardium was analyzed for creatine kinase (CK) activity. 2. Human superoxide dismutase (h-SOD) given 1 min after occlusion and again 6 h later significantly improved survival and retarded the loss of myocardial CK. 3. In rat isolated hearts perfused at 15% of normal flow for 30 min followed by re-establishment of normal flow for 20 min, perfusion pressure increased by 72% and myocardial CK decreased by 44%. No significant changes occurred in wet-to-dry heart weight ratio. 4. Administration of h-SOD at 2.5 or 5.0 mg, significantly attenuated the elevated post-ischaemic perfusion pressure and the loss of myocardial CK activity in rat perfused hearts. 5. h-SOD appears to be an effective anti-ischaemic agent in the intact animal as well as the isolated perfused heart of the rat subjected to low flow followed by reperfusion at normal flow. The mechanism of this cardioprotective effect is not totally dependent upon the formed elements of the blood, but may be partially due to a direct cytoprotective effect.

Animals↗
PubMed1987

Mechanism of antagonism of thromboxane receptors in vascular smooth muscle.

The mechanism and profile of antagonism of thromboxane receptors were studied in isolated perfused cat coronary arteries and in rat aortic rings. In cat coronary arteries, the thromboxane receptor antagonist (TxRA) BM-13,505 at concentrations from 3 to 300 ng/ml, significantly attenuated the vasoconstrictor effects of both a thromboxane A2 analog (CTA2) and an endoperoxide analog (U-46,619) and did not alter the constrictor responses to leukotriene D4, arginine vasopressin, or angiotensin II. In rat aortic rings precontracted by CTA2 or U-46,619, the effective threshold concentration of BM-13,505 for relaxation was 5 ng/ml. Lower concentrations of BM-13,505 exerted no relaxation, and higher concentrations exhibited faster relaxation to the precontracted baseline levels. This relaxation was not observed in aortic rings precontracted by norepinephrine or angiotensin II. The action of TxRA was not influenced by the absence of the endothelium or by pretreatment with a selective guanylate cyclase inhibitor, methylene blue. Also, thromboxane receptor antagonists do not appear to block thromboxane induced constriction by action as free radical scavengers. It can be concluded that replacing thromboxane A2 on the vascular receptor by a TxRA is the main factor responsible for the antagonism of thromboxane induced vasoconstriction in vascular smooth muscle preparations, not, the presence of the endothelium, activation of guanylate cyclase, or scavenging of superoxide free radicals.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1987

Thromboxane induced red blood cell lysis.

The two thromboxane A2 mimetics, carbocyclic thromboxane A2 (CTA2) and U-46619 (9,11-methanoepoxy PGH2) at concentrations of 400 ng/ml significantly enhanced the release of hemoglobin from both feline and human erythrocyte suspensions. This effect was significantly attenuated by the thromboxane receptor antagonist BM-13,505 indicating that the membrane leakiness is in some way receptor mediated. The effects also appear to be concentration-dependent over the range of 100-400 ng/ml. The membrane labilizing effect of thromboxane analogs is not due to a non-specific eicosanoid effect since iloprost, the stable prostacyclin analog, actually stabilized erythrocyte membranes. Moreover, synthetic thromboxane A2 exerted similar effects to that of the two TxA2-mimetics. This membrane labilizing action of thromboxanes may be important in propagating the other pathophysiologic effects of thromboxane A2 in cardiovascular disease states.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1987

Cardioprotective actions of specific thromboxane receptor antagonist in acute myocardial ischemia.

Thromboxane A2 (TxA2) has been implicated as a potential mediator of myocardial damage during acute ischemia. A potent and specific TxA2 receptor antagonist, SQ-29,548 (2 mg/kg bolus + 2 mg/kg/h) was tested in a cat acute coronary ligation model of myocardial ischemia over a 5-h observation period. Those cats given the TxA2 receptor antagonist had a significant reduction in elevated S-T segment from 0.32 to 0.17 mV (p less than 0.01) in contrast to cats given only vehicle which showed a progressive increase in S-T segment elevation over the 5-h course of the experiment. Furthermore, the rise in plasma creatine kinase (CK) activity during myocardial ischemia was significantly attenuated after SQ-29,548 administration (p less than 0.05). This was confirmed by direct myocardial biopsies which demonstrated a reduction in the loss of myocardial CK and nitrogenous compounds from the ischemic region. Because heart rate (HR), mean arterial blood pressure (MABP), and the pressure rate index (PRI) were unaffected by SQ-29,548 administration, its mechanism of protection probably does not occur through reduction of myocardial oxygen demand. Furthermore, specificity of SQ-29,548 for thromboxane/endoperoxide receptors was demonstrated in the isolated cat coronary arteries. These data suggest that SQ-29,548 reduces the damage associated with myocardial ischemia through direct TxA2 receptor antagonism. The data are also consistent with an important role of TxA2 in the pathophysiology of myocardial ischemia.

Animals↗
PubMed1987

Beneficial actions of the thromboxane receptor antagonist, AH-23,848, in acute myocardial ischemia.

Thromboxane A2 (TxA2) production increases significantly during acute myocardial ischemia. Since TxA2 induces platelet aggregation, coronary vasoconstriction and has a direct cytolytic effect, thromboxane receptor antagonists would be expected to be beneficial in acute myocardial ischemia. A new thromboxane A2 receptor antagonist, AH-23,848, was studied in a cat model of acute myocardial ischemia. Myocardial ischemia was induced by ligation of the left anterior descending (LAD) coronary artery. Thirty minutes later, AH-23,848 or vehicle was given as a bolus (1 mg.kg-1) followed by a continuous infusion (1 mg.kg-1.h-1). AH-23,848 effectively reduced the S-T segment elevation while vehicle treated cats showed an increase. From direct myocardial biopsies, it was also seen that AH-23,848 prevented the loss of creatine kinase (CK) activity from the ischemic myocardium. Furthermore, the loss of amino-nitrogen compounds was also significantly reduced (p less than 0.05) by treatment with the receptor antagonist. This protective effect was not due to an indirect reduction of myocardial oxygen demand since blood pressure, heart rate or their product was unaltered by AH-23,848 administration. Moreover, the specificity of AH-23,848 to thromboxane receptors was confirmed in isolated cat coronary arteries and in cat platelets. These experiments demonstrate that blockade of the thromboxane receptor by AH-23,848 is an effective means of preventing acute myocardial ischemic damage in the cat, and thus thromboxane A2 plays a role in propagating the extension of ischemic damage during acute myocardial ischemia.

Acute Disease↗
PubMed1986

Anti-ischemic actions of a new thromboxane receptor antagonist, SQ-29,548, in acute myocardial ischemia.

Thromboxane A2 (TxA2) has been implicated as a mediator of ischemic damage to the myocardium. A new, selective thromboxane receptor antagonist, SQ-29,548 (2 mg/kg bolus + 2 mg/kg per h infusion) was studied for its effects on the extension of ischemic damage following acute myocardial ischemia (MI) in the rat. Administration of SQ-29,548 to sham MI rats had no significant effect on mean arterial blood pressure or heart rate over the 6 h experimental protocol. Ischemic damage was assessed by measurement of the depletion of creatine kinase (CK) activity and amino-nitrogen concentration from the myocardium. Six hours following ligation of the left main coronary artery, there was a significant loss of both CK (P less than 0.001) and amino-nitrogen (P less than 0.001) from the left ventricular free wall (LVFW). Administration of SQ-29,548 significantly blunted this loss of CK activity (P less than 0.01) and amino-nitrogen concentration (P less than 0.001) from the ischemic myocardium. Furthermore, the survival rate at 6 h following acute coronary artery ligation was 100% (7/7) for rats given SQ-29,548 and 58% (11/19) for rats given only the vehicle (P less than 0.05). These data indicate that SQ-29,548 significantly prevents the extension of ischemic damage in the myocardium and improves survival following acute coronary artery ligation, suggesting an important role for TxA2 in the pathophysiology of acute myocardial ischemia.

Animals↗
PubMed1986

Beneficial effects of tissue-type plasminogen activator in acute myocardial ischemia in cats.

Tissue-type plasminogen activator is a new thrombolytic agent that dissolves intravascular thrombi in coronary and peripheral vessels with less pronounced systemic lysis than that produced by streptokinase. Plasminogen activator was shown to induce reperfusion, and to salvage ischemic myocardium, by lysing experimentally induced coronary artery thrombi. The effect of a melanoma cell-derived tissue-type plasminogen activator was studied in cat myocardium rendered ischemic by coronary artery ligation for 2 hours and reperfused for another 4 hours. Plasminogen activator was infused at a rate of 500 IU X kg-1 X min-1 for the first 30 minutes of reperfusion. The marked increase in plasma creatine kinase activity during reperfusion was significantly lower in plasminogen activator-treated cats at 4, 5 and 6 hours, with 7.7 +/- 1.5 X 10(-3) IU X mg protein-1 (n = 8) in the plasminogen activator group versus 17.8 +/- 3.5 X 10(-3) IU X mg protein-1 (n = 7) in the vehicle group at 6 hours (mean +/- SEM). The area at risk in the two ischemic groups was not different, being 14.6 +/- 1.5 and 16.6 +/- 1.4% of total left ventricular mass for the treated and untreated groups, respectively. However, the mass of necrotic tissue determined histochemically was significantly lower in the plasminogen activator-treated group, accounting for 29.5 +/- 3.9% of the area at risk compared with 46.8 +/- 4.2% of area at risk in cats receiving only the vehicle (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Cardioprotective actions of a new calcium channel blocker in acute myocardial ischemia.

The ability of anipamil, a calcium channel blocker, to protect ischemic myocardial tissue was investigated in pentobarbital anesthetized cats. Two bolus injections of anipamil (1.0 mg/kg i.v.) or their vehicle (i.e., 95% ethanol) were given 30 and 150 min post-ligation of the left anterior descending coronary artery. Anipamil significantly reduced the elevated S-T segment elevation and T wave amplitude suggesting a moderating influence on cellular ischemia. The drug also significantly blunted the loss in myocardial creatine kinase activity and amino-nitrogen concentrations from ischemic myocardial tissue, compared to cats receiving only the vehicle. These changes are suggestive of a cardioprotective effect of this calcium channel blocker. Since no significant change in the pressure rate index was seen with anipamil, a decrease in myocardial oxygen demand does not appear to be the major mechanism of the cardioprotective action of the agent. Therefore, anipamil protected the heart from ischemic damage, possibly by a direct cytoprotective action.

Animals↗
PubMed1985

Anti-ischemic actions of a new thromboxane receptor antagonist during acute myocardial ischemia in cats.

Thromboxane A2 (TxA2) production increases significantly during acute myocardial ischemia. Since TxA2 induces platelet aggregation, coronary vasoconstriction, and has a direct cytolytic effect, thromboxane receptor antagonism would be expected to be beneficial in acute myocardial ischemia. Thirty minutes after ligation of the left anterior descending coronary artery (LAD) in anesthetized cats, the TxA2 receptor antagonist BM-13,177 or its vehicle was given as a bolus injection at 20 mg/kg, followed by continuous infusion of 20 mg/kg/hr for 4.5 hours. ST segment elevation declined significantly (p less than 0.02) after BM-13,177 treatment, suggesting a reduction in cellular ischemia. The loss in myocardial creatine kinase (CK) activity and in free amino-nitrogen concentration in the ischemic area was also significantly reduced (p less than 0.01). No significant changes in blood pressure or heart rate were seen with BM-13,177 during myocardial ischemia or in nonischemic control cats. Blood levels of BM-13,177 were sufficient to inhibit ex vivo platelet aggregation induced by the prostaglandin endoperoxide analog, U-46,619. Data from isolated cat coronary arteries suggest that BM-13, 177 antagonizes the thromboxane/endoperoxide receptor in coronary vascular smooth muscle. These experiments indicate that TxA2 plays a significant role in propagating the extension of ischemic damage, and that thromboxane receptor antagonism is an effective means of reducing the damage provoked by TxA2 in acute myocardial ischemia.

Animals↗
PubMedDate not supplied

Optical coherence tomography: an emerging technology for biomedical imaging and optical biopsy.

Optical coherence tomography (OCT) is an emerging technology for performing high-resolution cross-sectional imaging. OCT is analogous to ultrasound imaging, except that it uses light instead of sound. OCT can provide cross-sectional images of tissue structure on the micron scale in situ and in real time. Using OCT in combination with catheters and endoscopes enables high-resolution intraluminal imaging of organ systems. OCT can function as a type of optical biopsy and is a powerful imaging technology for medical diagnostics because unlike conventional histopathology which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time. OCT can be used where standard excisional biopsy is hazardous or impossible, to reduce sampling errors associated with excisional biopsy, and to guide interventional procedures. In this paper, we review OCT technology and describe its potential biomedical and clinical applications.

Animals↗