Immunogold staining for Bcl-xL and morphological analysis of rat and human vascular smooth muscle cells undergoing apoptosis induced by c-myc or staurosporine.
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Animals↗
Biomedical subjects
D K Agrawal
Publications and source records attributed to D K Agrawal.
Functional and morphological evaluation of canine veins following preservation in different storage media.
Injuries of endothelial and smooth muscle cells of autologous vein due to preservation in standard storage media may be responsible for graft failure. The effects of vein preservation with University of Wisconsin solution (UWs) on endothelial and smooth muscle cell function and morphology were compared to the effects of preservation with autologous whole blood (AWB) and normal saline (NS), which are frequently used in cardiovascular surgery. Canine external jugular and common femoral vein segments were preserved in the different solutions at 4 degrees C for 45 min and 24 hr. Rings (4-5 mm in length) from control and preserved veins were evaluated by isometric tension studies at 37 degrees C and by scanning and transmission electron microscopy. Differences between groups were evaluated by Student's t test or Mann-Whitney U test and by analysis of the variance, and considered to be significant at P < 0.05. Sensitivities to norepinephrine (NE) showed that a 45-min vein storage in AWB (5.7 +/- 0.2 mumol/L) but not in NS (5.8 +/- 0.2 mumol/L) or UWs (6.5 +/- 0.2 mumol/L) had a deleterious effect on function of smooth muscle (P < 0.05) when compared to control veins (6.6 +/- 0.2 mumol/L). Maximum contractile responses and sensitivities to NE were significantly altered (P < 0.05) after 24-hr vein storage in AWB (0.09 +/- 0.02 g/mm2 and 5.4 +/- 0.07 mumol/L) and NS (0.12 +/- 0.03 g/mm2 and 5.6 +/- 0.08 mumol/L) but not in UWs (0.36 +/- 0.06 g/mm2 and 6.4 +/- 0.07 mumol/L). With both storage times, acetylcholine-induced endothelium-dependent maximum relaxations and sensitivities were significantly reduced (P < 0.05) in veins stored in AWB and NS, but not in UWs, compared with controls. Similarly, transmission electron microscopy revealed marked neutrophil migration beneath the intimal surface of vessels and extensive separation and desquamation of endothelial cells with exposure of subendothelial structures in veins stored in AWB and NS. The results suggest that UWs is a suitable storage medium when compared to AWB and NS.
Animals↗
Hydropericardium syndrome (HPS) in India: a preliminary study on the causative agent and control of the disease by inactivated autogenous vaccine.
Hydropericardium syndrome (HPS) in broiler birds of 3 to 6 weeks of age was recorded for the first time in the Haldwani area of Nainital district (UP) in India in November, 1994. The overall mortality in 6 poultry farms was 61.62 per cent. The disease was experimentally transmitted by bacteria free infected liver homogenate extract passed through membrane filters of 0.22 and 0.1 mu APD. The aetiological agent was inactivated by heat treatment at 56 degrees C for one hour and 80 degrees C for 10 min. A precipitin band was demonstrated in agar gel immunodiffusion and counter immunoelectrophoresis using infected liver homogenate extract as antigen and homologous antisera raised in the laboratory. The disease was effectively controlled by formalinised and heat inactivated autogenous vaccine prepared from the infected livers of birds which died of natural infection.
Animals↗
Short-term preservation of autogenous vein grafts: effectiveness of University of Wisconsin solution.
BACKGROUND: Suboptimal preservation of autologous veins in storage solutions causes endothelial cell damage that can contribute to graft failure. The purpose of this study was to compare the effects of short-term storage of veins in autologous whole blood (AWB), 0.9% normal saline solution (NS), and University of Wisconsin solution (UWs) on vein structure and function after grafting. METHODS: Autogenous jugular and femoral veins were atraumatically harvested from mongrel dogs. One vein segment was immediately implanted to serve as a control, and the other segments were stored for 45 minutes in AWB, NS, or UWs. The veins were implanted as reversed interposition graft in the carotid or femoral arteries. After 6 weeks light and scanning electron microscopy and isometric tension studies were performed on explanted vein grafts. RESULTS: Morphologic studies revealed an intact endothelium that stained positively for factor VIII. Intimal thickness was similar between controls (48 +/- 12 microns) and veins stored in UWs (53 +/- 8 microns) (p = not significant), but it was significantly increased in veins stored in AWB (151 +/- 29 microns) and NS (149 +/- 18 microns) (p < 0.05). Sensitivity and maximum contraction to norepinephrine were not altered in veins preserved in UWs (6.0 +/- 0.1 mumol/L and 0.19 +/- 0.02 gm/mm2) but were significantly reduced (p < 0.05) in those stored in AWB (7.2 +/- 0.1 mumol/L and 0.08 +/- 0.02 gm/mm2) and NS (7.0 +/- 0.3 mumol/L and 0.09 +/- 0.02 gm/mm2) compared with controls (5.9 +/- 0.2 mumol/L and 0.20 +/- 0.02 gm/mm2). The sensitivity and maximum relaxation to acetylcholine and sodium nitroprusside of veins preserved in AWB, NS, and UWs were similar to controls (p = not significant). CONCLUSIONS: Vein storage in UWs preserves smooth muscle cell function compared with veins stored in NS or AWB. Therefore UWs is a more suitable medium for short-term preservation of veins in cardiovascular operation.
Adenosine↗
Cell adhesion molecules and insulin-like growth factor-1 in vascular disease.
PURPOSE: Recent advances in the understanding of the biologic mechanisms of vascular diseases suggest that multifactorial stimulation of the endothelial cell and its subsequent adhesion to leukocytes is a prerequisite to the formation of atherosclerotic and restenotic lesions. As leukocyte-endothelial cell interaction is coordinated by a variety of cell adhesion molecules (CAMs), we hypothesized that the expression of certain CAMs is up-regulated in the vasculature of patients who have peripheral vascular disease. In addition, we proposed that insulin-like growth factor-1 (IGF-1) increases monocyte-endothelial adhesion by means of upregulation of these CAMs. METHODS: Using immunohistochemical techniques, the expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin was examined in human vascular disease specimens. Normal aortas obtained from the organ retrieval system were studied as control specimens. Adhesion studies between human umbilical vein endothelial cells (HUVECs) incubated with IGF-1 and purified human blood monocytes labeled with 51chromium were completed. Western blotting and flow cytometry were performed to show CAM expression on IGF-1-treated HUVECs. RESULTS: Of the CAMs, ICAM-1, P-selectin, and E-selectin were distinctly increased in diseased specimens when compared with control specimens (p < 0.05). Adhesion studies showed an increase in monocyte-endothelial cell adhesion of as much as 40% to 45% (p < 0.01) over baseline, with peak adherence occurring 4 hours after treatment with IGF-1. IGF-1 increased adherence in a dose- and time-dependent manner. The threshold concentration of IGF-1 that induced increased adhesion was 20 ng/ml, with a maximum effect occurring at 150 ng/ml. This increased adhesion was attenuated by pretreatment with IGF-I receptor antibody, as well as with genistein and herbimycin-A, which are potent and selective tyrosine kinase inhibitors. Increased adhesion correlated with an increase in the expression of CAMs on the surface of the HUVECs. An additive effect on adhesion was observed between IGF-1 and tumor necrosis factor-alpha (TNF-alpha) and endothelin-1 (ET-1). Finally, immunohistochemical analysis of human vascular disease specimens revealed an increased expression of IGF-1 receptors as compared with control specimens (p < 0.05). CONCLUSIONS: These results suggest that IGF-1 may be important in the pathogenesis of peripheral vascular disease by increasing endothelial cell-monocyte adhesion by means of an increase in the expression of ICAM-1 and VCAM-1.
Aorta↗
Morphological and biochemical characterization and analysis of apoptosis.
Apoptosis is a form of programmed cell death serving physiologic and homeostatic functions. However, recent evidence implicating apoptosis in the etiology and pathophysiology of known human diseases, such as heart diseases, cancer, AIDS, and neurodegenerative and autoimmune diseases are continually surfacing. This has spawned the need for identifying which methods are the most effective and well accepted to decipher its presence in a variety of research settings. We have therefore detailed the morphology and biochemical features of apoptotic cell death, with an emphasis on discriminating it from necrosis. In addition, we describe specific and selective techniques which are optimal to target hallmark apoptotic features, such as microscopy, Annexin V labeling, in situ nick-end labeling (TUNEL), and DNA fragmentation analysis by gel electrophoresis and ELISA for oligonucleosome-sized DNA. The advantages and disadvantages of each technique are discussed, as well as their experimental importance relative to one another. The methods have been described in a stepwise fashion, and can readily be applied in the majority of cell systems. Whether working on the tissue or single cell level, these methods are highly effective in qualifying and quantifying apoptosis. The application of these methods in conjunction with molecular techniques can further delineate the underlying mechanisms of apoptosis.
Acquired Immunodeficiency Syndrome↗
A novel thromboxane synthetase inhibitor, DP-1904, inhibits human blood eosinophil degranulation.
Eosinophils have been recognized to be associated with various immune responses and disease processes including bronchial asthma. Eosinophils release a number of cytotoxic and neurotoxic mediators. However, the factors regulating such release and the underlying mechanisms are unclear. In this study, we investigated the effect of a selective and potent thromboxane synthase inhibitor, DP-1904, on the release of eosinophil cationic protein (ECP) in platelet activating factor (PAF) and IgG-stimulated human blood eosinophils. PAF (1 microM) and IgG both released ECP which constituted about 25-30% of the total ECP content. The control protein, ovalbumin, did not release any ECP over the basal values. DP-1904 in two different concentrations, 10 microM and 100 microM, significantly attenuated the release of ECP in response to PAF or IgG. The mean percent inhibition by 10 microM DP-1904 was 49 +/- 10 and 31 +/- 2 against PAF and IgG-induced ECP release, respectively. However, at 100 microM DP-1904 the percent inhibition was 76 +/- 14 and 67 +/- 2, respectively. These data suggest that TXA2 is an important mediator in the regulation of eosinophil degranulation, and DP-1904 thus might prove beneficial in the treatment of bronchial asthma.
Asthma↗
Endothelin-1 induces tyrosine phosphorylation in human blood monocytes.
Mediators including the neuropeptide endothelin-1 (ET-1), which are released in response to injury, modulate the expression of cell adhesion molecules on leukocytes and endothelial cells. The mechanisms underlying this process are not clear. In this study we investigated the effect of endothelin-1 on the expression of tyrosine phosphorylated proteins in human blood monocytes. Endothelin-1 caused an increase in tyrosine phosphorylated proteins in monocytes in a time-dependent and dose-dependent manner, the Mr 60, 80 and 110 kDa proteins being the most prominent. This effect was blocked by pre-incubating the monocytes with the selective tyrosine kinase inhibitors genistein or herbimycin A. Endothelin-1 induced upregulation of tyrosine phosphorylated proteins appears to be mediated by the ETA receptor. Unlike our previously reported studies in endothelial cells, immunoprecipitation with anti-src or anti-JAK antibodies followed by immunoblotting with PY20 in human blood monocytes revealed that these proteins of Mr 60, 80 and 110 kDa were not related to src or JAK kinases. These findings suggest that ET- exerts its effect on monocytes by a pathway involving tyrosine kinases other than src or JAK kinases.
Adult↗
Identification of guanine nucleotide binding regulatory proteins in bovine tracheal smooth muscle.
The identity of G-proteins in airway smooth muscle is not well elucidated. In the present study, by immunoblotting using AS/7 antibody specific for Gi alpha-1/2, EC/2 antibody specific for Gi alpha-3 and RM/1 antibody specific for Gs alpha, we identified, respectively, Mr 39, 41, 46 and 52 KDa, Mr 41 and 43 KDa, and Mr 43 and 46 KDa polypeptides of conventional (heterotrimeric) G-proteins in purified membranes of bovine tracheal smooth muscle. The identity of the Mr 41, 43 and 52 KDa Gi alpha, and the Mr 43 and 46 Gs alpha was also confirmed by ADP-ribosylation with pertussis and cholera toxins, respectively. In addition, the common antibody (AG/1) for both Gi alpha and Gs alpha revealed the presence of all the above polypeptides, except the Mr 52 KDa band. By nitrocellulose blot overlay with [35S]s alpha GTP gamma S, we also detected seven low molecular weight GTP-binding proteins of Mr 18-30 KDa in the bovine tracheal smooth muscle. Photoaffinity crosslinking of [alpha-32P]GTP demonstrated the presence of high molecular GTP-binding proteins of Mr 55, 75 and 110 KDa. It is concluded that plasma membranes of bovine tracheal smooth muscle contain various types of conventional, low molecular weight and high molecular weight G-proteins. This warrantes further attention to elucidate the functional roles of G-proteins in airway smooth muscle.
Adenosine Diphosphate Ribose↗
Ischemia-induced peripheral arterial vasospasm role of alpha 1- and alpha 2-adrenoceptors.
Ischemia produces functional and structural alterations in peripheral blood vessels. Our study was designed to investigate alpha-adrenoceptor modifications induced by prolonged ischemia and their role in enhancing the contractile response during reperfusion in canine femoral arteries. Unilateral vessel ischemia was created by double crossclamping a femoral artery and was maintained for 3 hr. Reperfusion was allowed for 1 hr. The contralateral femoral artery was utilized as a control. The vessels were harvested for contractile and binding studies. Isometric tension studies revealed that the magnitude of the maximum contractile response to norepinephrine (NE), potassium chloride (KCl), and methoxamine was 671 +/- 82 mg/mm2 versus 245 +/- 43 mg/mm2 (P < 0.01), 485 +/- 46 mg/mm2 versus 229 +/- 62 mg/mm2 (P < 0.05), and 486 +/- 88 mg/mm2 versus 126 +/- 38 mg/mm2 (P < 0.01), respectively for ischemic and nonischemic femoral arteries. EC50 values showed that ischemic vessels were more sensitive to NE, KCl, and methoxamine (P < 0.05). Sodium nitroprusside induced concentration-dependent and complete relaxation in all arterial rings (100% relaxation) but the ischemic femoral artery showed less sensitivity (P < 0.05). Binding studies showed that the number of binding sites (Bmax) for [3H]Prazosin and [3H]Rauwolscine were significantly increased in ischemic versus nonischemic vessels (1261 +/- 95 fmole/mg versus 704 +/- 113 fmole/mg, P < 0.03, and 490 +/- 86 fmole/mg versus 175 +/- 15 fmole/mg, P < 0.04, respectively). Furthermore, a significant decrease in affinity (Kd) for [3H]Prazosin and [3H]Rauwolscine was observed in ischemic versus nonischemic tissues (9.4 +/- 1.7 nM versus 4 +/- 0.2 nM, P < 0.02, and 6.4 +/- 1.5 nM versus 1.8 +/- 0.6 nM, P < 0.01, respectively). The increase in canine femoral artery vasoreactivity, following prolonged ischemia, seems to be also due to an increased density and functional activity of alpha-adrenoceptors expressed by the ischemic arterial smooth muscle cells.
Animals↗
G-proteins in guinea pig airway smooth muscle: identification and functional involvement.
In airway smooth muscle, G-proteins have not been identified directly as yet. This study was an attempt to detect various types of conventional Gi- and Gs-proteins in purified membranes of guinea pig airway smooth muscle and to assess the involvement of the G-proteins in agonist-induced contractile response of the smooth muscle. Immunoblotting using AS/7 antibody which recognizes Gi-1/2 demonstrated the presence of polypeptides of M(r) 34, 41 and 75 kDa. Polypeptides of M(r) 43, 46 and 48 kDa were identified with RM/1 antibody that detects Gs-type G-proteins. The AG/1 antibody that recognizes alpha-subunits common to all Gi- and Gs-proteins detected two polypeptides of M(r) 41 and 75 kDa. Heterotrimeric structure of the G-proteins was confirmed by the identification of a single dense beta-subunit band at M(r) 39 kDa with SW/1 antibody. Pertussis toxin (PT) ADP-ribosylated three Gi alpha polypeptides of M(r) 41, 43, and 62 kDa. On the other hand, cholera toxin (CT) catalysed the ADP-ribosylation of two Gs alpha polypeptides of M(r) 46 and 62 kDa. Both PT and CT attenuated the maximum contractile responses of the airway smooth muscle to the muscarinic agonist, methacholine. Pretreatment of the tissues with the sulphydryl alkylating G-protein inhibitor, N-ethylmaleimide, also inhibited the maximum contractions to methacholine. These data suggest that plasma membranes of guinea pig airway smooth muscle contain a variety of conventional, including Gs and Gi, and other types of G-proteins, and at least a portion of the proteins present may be involved in mediating the contractile responses of the smooth muscle to an agonist such as methacholine.
Animals↗
Platelet-activating factor-induced inositol 1,4,5-trisphosphate generation in undifferentiated and differentiated U937 cells: role of tyrosine kinase.
We compared the effect of platelet-activating factor (PAF) on inositol 1,4,5-trisphosphate (IP3) content in undifferentiated and differentiated U937 cells. In both cell types, PAF induced a rapid transient and concentration-dependent elevation of IP3 content. The production of IP3 in response to PAF was greater in differentiated than in undifferentiated cells. The increases in IP3 produced by PAF in both types of cell were inhibited by the PAF receptor antagonist, WEB 2086, as well as by the tyrosine kinase inhibitor, genistein. PAF also caused increased tyrosine phosphorylation of a 32 kDa protein substrate in both undifferentiated and differentiated cells. The magnitude of the phosphorylation was, however, greater in the differentiated cells. Genistein reduced the PAF-induced tyrosine phosphorylation of the substrate in both cell preparations. The specific binding of [3H]PAF was also markedly enhanced in differentiated cells. This effect was attenuated by genistein. The results indicate that PAF induces the production of IP3 in U937 cells via tyrosine kinase-mediated mechanisms and this process is augmented in differentiated cells.
Azepines↗
Effects of ischaemia and reperfusion on vasoactive neuropeptide levels in the canine infrarenal aortic revascularization model.
Infrarenal aortic cross-clamping is associated with remote vascular events, including myocardial infarction and renal insufficiency. The purpose of this study was to determine whether hindlimb ischaemia and reperfusion associated with infrarenal aortic cross-clamping results in the production of vasoactive regulatory neuropeptides. A canine model of infrarenal aortic cross-clamping was used for the study. Serial blood samples were drawn, prior to, at the time of, and serially following placement of the clamp and subsequent release of the clamp and reperfusion. Ischaemia resulted in increased mean(s.e.m.) plasma levels of neuropeptide Y (NPY) (initial 10.0(1.8) pmol/l versus ischaemia 24.7(2.3) pmol/l, P < 0.001) and vasoactive intestinal polypeptide (VIP) (initial 2.53(0.5) pmol/l versus ischaemia, 7.3(1.3) pmol/l, P < 0.05). Reperfusion produced three-fold elevation of VIP (initial 2.5(0.5) pmol/l versus reperfusion 9.6(1.5) pmol/l, P < 0.001), two-fold elevation in the plasma levels of endothelin-1 (initial 1.3(0.1) pmol/l versus reperfusion maximum 2.5(0.3) pmol/l, P < 0.01) and NPY (initial 10.0(0.8) pmol/l versus reperfusion maximum 23.9(2.3) pmol/l, P < 0.001). Ischaemia and reperfusion did not alter calcitonin gene-related peptide (CGRP) (a potent vasodilator) levels. Endothelin-1 (ET-1) plasma levels were also increased following haemorrhagic shock (initial 1.3(0.1) pmol/l versus exsanguination 3.4(0.4) pmol/l, P < 0.001), but not during ischaemia (initial 1.3(0.1) pmol/l versus ischaemia maximum 1.7(0.2) pmol/l, P = 0.7). It was concluded that vasoactive regulatory peptides are released following ischaemia, reperfusion and shock in the canine infrarenal aortic revascularization model and, therefore could contribute to remote vascular events observed with infrarenal aortic cross-clamping.
Animals↗
Modulation of monocyte adherence to endothelial cells by endothelin-1 involvement of Src (p60src) and JAK1-like kinases.
PURPOSE: The purpose of this study was to determine the transmembrane signaling pathway by which endothelin-1 (ET-1) enhances monocyte adherence to human umbilical vein endothelial cells (HUVECs) and to investigate the role of tyrosine kinases in this mechanism. METHODS: Adherence of purified human blood monocytes to HUVEC monolayers was assessed with radiolabeled monocytes. Tyrosine kinase activation was examined by immunoprecipitation and Western blotting. RESULTS: ET-1 potentiated monocyte adherence to HUVECs in a biphasic manner with peaks at 10(-10) mol/L and 10(-7) mol/L. A potent antagonist to ET B receptors, when used alone, had no effect. However, the antagonist, when combined with ET-1, significantly enhanced monocyte adherence to HUVECs. Incubation of ET-1 (10(-12) mol/L to 10(-7) mol/L) with HUVECs activated tyrosine kinases in a biphasic manner as identified by immunoblotting with PY20 antibody to tyrosine phosphorylated proteins. Phosphorylated proteins with Mr 60, 110, and 130 kDa were observed after ET-1 stimulation of HUVECs. Of interest, ET A or ET B receptor antagonists failed to antagonize the effect of ET-1. Rather, these receptor antagonists significantly augmented ET-1 induced tyrosine phosphorylation in HUVECs. Immunoprecipitation with antibodies to p60SRC and JAK1 kinases followed by immunoblotting with PY20 antibody suggested that ET-1 receptor response coupling in HUVECs involves the activation of p60SRC and JAK1-like kinases. CONCLUSIONS: These data suggest an association between activation of p60SRC and JAK1-like kinases and monocyte adherence in response to ET-1. ET-1-induced monocyte adherence is upregulated by ET B receptor antagonist, suggesting a negative feedback on cell adhesion through this receptor.
Blotting, Western↗
Performance of broiler chicks fed on alkali-treated neem (Azadirachta indica) kernel cake as a protein supplement.
1. An experiment was conducted to evaluate growth and nutrient efficiency of broiler chicks from 3 to 42 d fed on diets containing alkali-treated neem (Azadirachta indica A. juss) kernel cake (NKC) as a protein supplement in place of peanut meal (PNM). 2. NKC was treated with sodium hydroxide at 10 (ANKC 1) or 20 g (ANKC 2)/kg and incorporated into the test diets at 135 or 300 g/kg to replace 50 (low-L) or 100 (High-H)% of the PNM protein of the reference diet. 3. Despite comparable retentions of dry matter and total carbohydrate on L-ANKC 1 and 2, fibre on L-and H-ANKC 2 and nitrogen, calcium and acid detergent fibre on all experimental diets compared to the retentions of chicks on the reference diet, only the chicks fed L-ANKC 2 were found to grow and utilise food as well as those on the reference diet. 4. The activities of serum alkaline phosphatase on H-ANKC 1 and alanine amino transferase on all test diets were depressed (P < 0.05), but the activity of serum aspartate amino transferase, total erythrocyte count and concentration of blood haemoglobin and urea were similar in all chicks. 5. No significant differences were noticed in the qualitative and quantitative characteristics of the meat of chicks fed on the reference diet and on diets incorporating ANKC at the lower concentrations. Feeding ANKC protein did not impart any untoward taste as evaluated in pressure cooked meat by a semitrained panel on a 7 point Hedonic scale. 6. Except for duodenal and jejunal inflammation in chicks on both reference and test diets, all the vital organs were normal, ruling out any adverse affects caused by residual neem bitters. 7. Comparable performance and cost of chicks fed on the reference and L-ANKC 2 diets, warrants the utilisation of hitherto wasted protein-rich NKC after alkali treatment in broiler chick diets to spare peanut meal for human consumption in developing countries.
Alanine Transaminase↗
A noninjury, diet-induced swine model of atherosclerosis for cardiovascular-interventional research.
To investigate whether atherosclerotic vascular disease in the microswine model can be induced by atherogenic diet alone and does not require balloon injury or endothelial denudation as widely stated in the literature, 28 female Yucatan microswine were fed a high-fat, high-cholesterol diet, including 2% sodium cholate, for an average of 310 +/- 13 days. Four control swine were placed on a regular diet for an average of 287.2 +/- 7.8 days. Selective coronary arteriography and morphologic and histologic studies were performed at the end of this period. Coronary arteries were fixed in vivo by pressure perfusion of formalin. Angiograms and sequential histologic sections were reviewed by a double-blind team. The angiography did not show apparent disease in all vessels but generally revealed mild irregularity. Quantitatively, there was a 30.5 +/- 3.5% stenosis (mean +/- standard error, P < 0.05 vs. control) in left anterior descending (LAD), 40.7 +/- 4.5% of stenosis in right coronary artery (RCA) (P < 0.01 vs. control), and 24.8 +/- 3.7% of stenosis in left circumflex artery (LCX). The lesions were eccentric in 95% of LCA, 95.8% of RCA, and 75% of LCX, and the remainder were concentric lesions. Typical lesions were characterized by significant intimal proliferation, cholesterol clefts, necrotic cores, heavy extracellular fat deposition, and calcification. Control animals had only occasional, minimal intimal lipid deposition in coronary arteries. These findings suggest that the Yucatan microswine is an ideal coronary atherosclerosis animal model for vascular research. Lesions can be induced by atherogenic diet alone. Cholesterol uptake is increased by adding sodium cholate to the feed. Moreover, balloon injury of the intima or media is not required to induce significant atherosclerotic lesions in coronary arteries.
Animals↗
Increased hypodense eosinophils after activation with PAF-acether and calcium ionophore in asthmatic subjects.
Eosinophils play a major role in the pathogenesis of bronchial asthma. In this study, we examined the density characteristics of blood eosinophils from 9 normal healthy individuals and 9 allergic asthmatic patients. Furthermore, the effect of platelet-activating factor, a potent mediator of inflammation, and calcium ionophore, A23187, on the density of normodense eosinophils (density > 1.085 g/ml) has also been examined. Initially, asthmatic patients had 27.0 +/- 1.1% eosinophils of lighter density (density < or = 1.081 g/ml), significantly greater than that in the normal individuals (7.5 +/- 0.5%). After exposure to platelet-activating factor (1 microM) or calcium ionophore (A23187, 1 microgram/ml), the normodense eosinophils switched to hypodense in both groups: 16.7 +/- 2.1% and 54.2 +/- 3.7%, respectively, in normal individuals, and 30.6 +/- 5.7% and 77.4 +/- 2.3%, respectively, in asthmatic patients. These data demonstrated that a certain percentage of normodense eosinophils from asthmatics and normal subjects switched to hypodense after activation with platelet-activating factor or calcium ionophore. Furthermore, eosinophils from asthmatics switched to a greater degree than in normal subjects, suggesting that the normodense eosinophils in asthmatics become primed probably by endogenously released mediators.
Adult↗
Pharmacokinetic, angiographic, and histologic comparison of catheter-directed chemoembolization versus systemic chemotherapy in a canine model.
Chemotherapy with selective intraarterial embolization may promote sustained contact of the drug with the tumor and thus could be more effective in the treatment. In this phenomenon, pharmacokinetics of a drug such as mitomycin C (MMC) play a significant role in guiding the therapy. Therefore, we have compared the pharmacokinetics of MMC and assessed angiographic, morphologic, and histologic changes in the kidney following intravenous MMC versus renal artery infusion with and without embolization with embolic agents, Rhizoma Bletillae (RB) and Gelfoam (GF). Dogs randomly divided into four groups underwent selective infusion protocols. Blood samples from renal and common iliac veins were analyzed for MMC levels. Angiography and pathology were performed at 4 days. Intravenous MMC (IV-MMC) caused significantly lower renal vein MMC levels than intraarterial MMC (IA-MMC) and GF + MMC. RB + MMC produced the lowest MMC levels in both veins (p < 0.05). Common iliac MMC levels were not significantly different after IV-MMC, IA-MMC, or GF + MMC. Angiographic and histologic studies showed extensive bleeding, necrosis, and vasculitis with thrombosis of the target kidneys after RB + MMC, GF + MMC, or IA-MMC, but not IV-MMC. Selective Rhizoma Bletillae chemoembolization can decrease systemic levels of MMC. Gelfoam does not provide sustained local release of MMC or decrease systemic levels of MMC compared with intravenous infusion. Selective renal MMC infusion without an effective embolic agent does not reduce systemic levels compared with intravenous delivery.
Adjuvants, Pharmaceutic↗