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Biomedical subjects

D K Das

Publications and source records attributed to D K Das.

At least 163 records · Page 9Linked to original sources
PubMed1994

Protective role of intracoronary vasoactive intestinal peptide in ischemic and reperfused myocardium.

Vasoactive intestinal peptide (VIP) has been shown to exert vasodilatory action and positive ionotropic effect on the heart and to possess free radical-scavenging ability. Because these properties are likely to make this peptide a suitable agent for myocardial preservation, we examined the role of VIP in myocardial ischemia and reperfusion. Isolated rat heart perfused by the Langendorff technique was subjected to 30 min of normothermic ischemia followed by 60 min of reperfusion. A significant amount of VIP was found to be released from the ischemic reperfused heart. The amount of VIP released from the heart increased progressively with the duration of reperfusion and paralleled the release of creative kinase from the heart. In another set of experiments, hearts were divided into two groups. The experimental group received three different doses of VIP (0.1 microM, 0.3 microM and 1 microM) before ischemia. After perfusing the isolated heart with VIP for 15 min, ischemia was induced for 30 min by terminating the coronary flow, which was followed by 60 min of reperfusion. The results of our study indicated a significant improvement of myocardial functions by VIP (0.3 and 1 microM), as evidenced by enhanced left ventricular functions and coronary flow, and reduction of tissue injury, as judged by the decrease in creatine kinase release (0.3 microM only). Intracellular Ca++ ([Ca++]i) transients increased during ischemia and further increased during reperfusion. The increase in [Ca++]i transients was significantly reduced in the VIP-treated hearts. A significant amount of hydroxyl radical was detected in the ischemic reperfused heart, but the quantity of the hydroxyl radical was much lower in the VIP-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Human papillomavirus DNA sequences in adenocarcinoma of the uterine cervix in Indian women.

BACKGROUND: Infection with human papillomavirus (HPV) is considered to be the principal causal agent in the development of squamous cell carcinoma of the uterine cervix. Although adenocarcinoma of the cervix originates adjacent to the squamous epithelial neoplastic lesions, the etiopathogenesis of adenocarcinoma is not yet clearly understood. Recent studies have raised more controversy, rather than answering the question of whether specific HPV infection also plays a role in the development of adenocarcinoma of the cervix. Molecular DNA hybridization techniques were used to detect HPV types prevalent in both adenocarcinoma and squamous cell carcinoma of the uterine cervix, which is the most common cancer in Indian women. METHODS: Histologically confirmed, formaldehyde-fixed, paraffin-embedded tissue sections from 12 cases of adenocarcinoma and 30 cases of squamous cell carcinoma of the uterine cervix were analyzed retrospectively for the presence of HPV DNA types 6b, 11, 16, and 18 by both Southern blot hybridization and in situ hybridization. RESULTS: Of 12 adenocarcinomas, 5 (41.67%) tumors were positive for HPV DNA: All five cases were positive for HPV 16, and two (16.6%) of these were hybridized again to the HPV 18-specific DNA probe. All tumors were negative for HPV 6b and 11. In addition, no biopsy specimens were positive after hybridization with a mixed probe of HPV 31, 33, 35, 39, and 45. These results were compared to those obtained for 30 squamous cell carcinomas of the cervix. Although 20 (66%) were exclusively positive for HPV 16 and 6 (20%), more tumors were of HPV 16 related types as detected under nonstringent conditions of hybridization, only one (3%) was positive for HPV 18. The results of in situ hybridization were found to be in good agreement with those of Southern blotting. CONCLUSIONS: HPV 16 is the type present almost exclusively in squamous cell carcinoma of Indian women. A higher frequency of HPV 16 in adenocarcinoma of Indian women, in contrast to HPV 18, as reported from other regions, may be attributed to geographic variation rather than to histologic differences only, and both HPV 16 and 18 may be present in adenocarcinoma of the uterine cervix.

Adenocarcinoma↗
PubMed1993

Induction of differential heat shock gene expression in heart, lung, liver, brain and kidney by a sympathomimetic drug, amphetamine.

Amphetamine, a sympathomimetic drug, can elevate the body temperature by causing enhancement of endogenous lipolysis. This study was designed to examine whether this drug could induce the expression of the genes of heat shock proteins (HSP) in different tissues. Subcutaneous administration of amphetamine (10 mg/kg wt) to the rats increased the rectal temperature of the rats to 42 degrees C within 60 min. After 3 hr rats were sacrificed; and heart, lung, liver, kidney and brain tissue were removed to examine the induction of mRNAs for HSPs by Northern blot analysis using cDNA probes of 27 kDa, 70 kDa and 89 kDa HSPs. The results of this study indicate striking regional and cell type differences in the pattern of induction of the HSP mRNAs by amphetamine suggesting that different organs and cell types respond differently to amphetamine.

Amphetamine↗
PubMed1993

Attenuation of myocardial reperfusion injury by reducing intracellular calcium overloading with dihydropyridines.

The effects of three different dihydropyridine (DHP) calcium channel antagonists, nisoldipine, nimodipine, and nifedipine, on myocardial ischemic and reperfusion injury were studied using isolated rat hearts subjected to ischemia and reperfusion. Hearts were perfused with Krebs-Henseleit bicarbonate buffer containing 0, 4, 16, 64 and 100 nM concentrations of the above dihydropyridines for 15 min. Global ischemia was then induced by terminating the aortic flow for 30 min at 37 degrees, followed by 30 min of reperfusion. Left ventricular (LV) functional (LV developed pressure, its first derivative and coronary flow) and biochemical parameters (creatine kinase release) were monitored prior to ischemia and during reperfusion. In separate group of hearts, intracellular free Ca2+ ([Ca2+]i) was monitored with an intracellular calcium analyzer using a fluorescent Ca2+ indicator (Fura-2 AM). Tissue Ca2+ was also measured by atomic absorption spectroscopy after perfusing the hearts with ion-free cold buffer to wash out extracellular Ca2+. Significant recovery of the coronary flow was observed in all hearts treated with a high concentration (100 nM) of DHPs compared with the control group (P < 0.05), while a lower dose of nisoldipine (16 nM) and nifedipine (64 nM) also improved the coronary flow effectively. Reduction of myocardial creatine kinase release and improvement of the recovery of LV developed pressure, dp/dtmax, were achieved by DHPs in a concentration-dependent manner. A higher concentration of DHPs also decreased the formation of myocardial thiobarbituric acid reactive substances, although these compounds did not possess direct free radical scavenging effects in vitro. Tissue Ca2+ content was reduced significantly in treated groups. The rise of [Ca2+]i during ischemia and reperfusion appeared to be attenuated by these DHPs. The concentration-response study of the three DHPs showed the effective concentrations for reducing [Ca2+]i to be 16, 64 and 100 nM nisoldipine, nifedipine and nimodipine, respectively, in this experimental setting. The above results indicate that pretreatment with DHPs can attenuate the myocardial reperfusion injury by modulating Ca2+ overloading and decreasing the susceptibility of the membrane to free radical attack.

Animals↗
PubMed1993

Comparisons of ESR and HPLC methods for the detection of OH. radicals in ischemic/reperfused hearts. A relationship between the genesis of free radicals and reperfusion arrhythmias.

In this study we compared two methods, electron spin resonance (ESR) spectroscopy and high performance liquid chromatography (HPLC), which are currently used to detect directly hydroxyl radical (OH.) formation in the ischemic and reperfused heart. Isolated buffer-perfused rat hearts were subjected to 30 min of normothermic global ischemia followed by 30 min of reperfusion. 5,5-Dimethyl-pyrroline-N-oxide (DMPO) was used as a spin-trap agent to detect OH. radicals by ESR and HPLC. In additional HPLC studies, salicylic acid was infused into the heart for the detection of OH. radicals. In all studies, the effects of superoxide dismutase (SOD) and catalase (CAT) on the OH. generation were examined. The results of our studies indicate that, irrespective of the method, OH. was always detected when an ischemic heart was reperfused and showed ventricular fibrillation. The OH. concentration increased dramatically between 60 and 90 sec of reperfusion, peaked between 180 and 210 sec, and then progressively decreased. In all cases, both SOD and CAT were able to reduce the formation of OH. radicals, with SOD being relatively more effective. Our results indicate that OH. was produced only in the fibrillating hearts that peaked between 180 and 210 sec (1.64 +/- 0.09 nmol/mL measured by ESR), but not in the non-fibrillating hearts. Although SOD or CAT reduced the OH. formation, they had no effects on the incidence of reperfusion-induced ventricular fibrillation (VF) and ventricular tachycardia (VT). However, when SOD (5 x 10(4) IU/L) was coadministered with CAT (5 x 10(4) IU +/- L), the incidence of reperfusion-induced VF (total) and VT was reduced from their control value of 92 and 100 to 33 (P < 0.05) and 50% (P < 0.05), respectively. The results of this study indicate that the HPLC method, as well as ESR, can be used to detect OH. formation in ischemic/reperfused hearts. Because of the convenience, reproducibility and greater sensitivity, the HPLC technique may be more suitable for OH. detection. Our results further suggest the potential therapeutic value of the combination therapy of SOD and CAT for the reduction of reperfusion-induced VF and VT.

Animals↗
PubMed1993

Estimation of the extent of lipid peroxidation in the ischemic and reperfused heart by monitoring lipid metabolic products with the aid of high-performance liquid chromatography.

Estimation of lipid peroxidation (LPO) through malonaldehyde (MDA) formation measured by assaying thiobarbituric acid reactive products remains the method of choice to study the development of oxidative stress to assess myocardial ischemic reperfusion injury. However, MDA estimation by this assay is non-specific and often gives erroneous results. In this report, we describe a method to estimate MDA, formaldehyde (FDA), acetaldehyde (ADA), and acetone, the degradation products of oxygen free radicals (OFR) and polyunsaturated fatty acids (PUFA), as presumptive markers for LPO. Isolated rat hearts were made ischemic for 30 min, followed by 60 min of reperfusion. The perfusates were collected, derivatized with 2,4-dinitrophenylhydrazine, and extracted with pentane. Aliquots of 25 microliters in acetonitrile were injected on a Beckman Ultrasphere C18 (3 microns) column. The products were eluted isocratically with a mobile phase containing acetonitrile-water-acetic acid (40:60:0.1, v/v/v). The peaks were identified by co-chromatography with the hydrazine derivatives of authentic standards. The retention times of MDA, FDA, ADA and acetone were 5.0, 6.3, 9.8 and 15.7 min, respectively. The results of our study indicated progressive increase in all four lipid metabolites with reperfusion time. Thus, our results demonstrate that the release of lipid metabolites from the isolated heart increased in response to oxidative stress. Since MDA, FDA, ADA, and acetone are the products of OFR-PUFA interactions, this method allows proper estimation of LPO to monitor the oxidative stress developed during the reperfusion of ischemic myocardium.

Animals↗
PubMed1993

Fine-needle aspiration diagnosis of intra-thoracic and intra-abdominal lesions: review of experience in the pediatric age group.

Review of fine-needle aspiration (FNA) smears from 121 pediatric patients with intra-thoracic and intra-abdominal lesions revealed 42 (34.7%) cases of neoplasms, 35 (28.9%) cases of tuberculosis, 12 (9.9%) cases of non-tuberculous inflammations, 4 (3.3%) cases of benign cystic lesions, and 28 (23.1%) inadequate/inconclusive cases. The age of the patients ranged from 20 days to 18 yr. Ultrasound and/or CT study done in 105 cases localized the lesions in following common sites: lungs (19 cases), mediastinum (22 cases), liver (14 cases), intestines (11 cases), and lymph nodes (17 cases). The neoplastic lesions consisted of 39 malignant, one suspicious, and two benign neoplasms. Among the neoplasms, the small round cell tumors were the most frequent (27 cases), followed by germ cell tumors (eight cases) and miscellaneous neoplasms (seven cases). The common small round cell tumors were non-Hodgkins lymphoma (eight cases), hepatoblastoma (seven cases), neuroblastoma (five cases), and nephroblastoma (three cases). A combined clinical, imaging, and FNA cytology approach was found to be useful in arriving at a tissue diagnosis.

Abdomen↗
PubMed1993

Fine-needle aspiration cytology diagnosis of non-Hodgkin lymphoma of thyroid: a report of four cases.

Four cases of non-Hodgkin lymphoma of thyroid, diagnosed by fine-needle aspiration (FNA) cytology during a period of 3 1/2 yr constituted 0.2% of 1,716 thyroid FNAs and 3.4% of 118 thyroid neoplasms. The age of the patients ranged from 42 to 78 yr with an average of 63 yr and all were females. Three cases had thyroid swellings, and one case had cervical lymphadenopathy and fullness in the thyroid region. The lymphomas were categorized as mixed small and large cell lymphomas, large cell lymphoma, small noncleaved lymphoma (non-Burkitt-type), and plasmacytoid lymphoma. Histopathology as well as immunohistochemistry confirmed the cytodiagnosis of lymphoma in the first and fourth cases. In the second case where possibility of anaplastic carcinoma could not be ruled out altogether at initial cytologic examination, the histopathology report was undifferentiated carcinoma but immunohistochemically it was proved to be a B-cell neoplasm.

Adult↗
PubMed1993

Pacing-induced ventricular fibrillation leading to oxygen free radical formation in aerobically perfused rat hearts.

The objective of this study was to determine whether electrically-induced ventricular fibrillation can elicit oxygen free radical formation, even in the absence of ischemia and reperfusion. Rat hearts (n = 8 in each group) were perfused aerobically at 37 degrees C and ventricular fibrillation was induced by pacing (20 Hz, 1200 beats/min) for 10 min, during which time no changes in coronary flow rates were observed. In this study, electron spin resonance (ESR) studies using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) demonstrated the formation of oxygen free radicals consisting of 1:2:2:1 quartet with peak concentration at the 3rd min of fibrillation in non-ischemic electrically fibrillating hearts. Since there were no significant changes in coronary flow rates during ventricular fibrillating (22.3 +/- 1.3 ml/min in control vs 22.3 +/- 0.9 ml/min in pacing-induced fibrillating group), the formation of oxygen free radicals could not be attributed to a pacing-induced ischemic event. In additional studies, hearts were paced by 10 Hz (600 beats/min), to demonstrate whether ventricular tachycardia could elicit free radical formation. In these experiments the genesis of oxygen free radicals was not observable after 1 min, 5 min, and 10 min of tachycardia, but a small amount of OH. radicals was detected at the 3rd min of ventricular tachycardia. When DMPO was infused into the heart giving a final perfusate concentration of 2.5 mmoles/litre during the pacing-induced fibrillation period, myocardial function (aortic flow, cardiac output, left ventricular developed pressure, first derivative of left ventricular developed pressure, and end-diastolic pressure) was significantly improved after the postfibrillating period. In conclusion, our studies clearly show that electrically-induced ventricular fibrillation is capable of eliciting free radical formation even in the absence of ischemia and reperfusion, and the cardioprotective effect of the spin trap is directly originated from its free radical trapping property and not from the other pharmacological activities of DMPO.

Aerobiosis↗
PubMed1993

Postischemic deterioration of sarcoplasmic reticulum: warm versus cold blood cardioplegia.

Impaired cardiac sarcoplasmic reticulum (SR) function, as evidenced by reduced SR Ca2+ uptake rate and decreased SR Ca(2+)-adenosine triphosphatase activity, has been found in postischemic "stunned" myocardium and in hearts subjected to hypothermic arrest. In this study, we compared the effects of retrograde continuous coronary sinus warm blood cardioplegia (WBC) and retrograde intermittent cold blood cardioplegia (CBC) on cardiac SR function and postischemic ventricular functional recovery in pig hearts. Twelve in situ isolated pig hearts supported by cardiopulmonary bypass were subjected to 120 minutes of cardioplegic arrest with either WBC (37 degrees C) or CBC (6 degrees to 10 degrees C), followed by 60 minutes of 37 degrees C reperfusion. Left ventricular global contractile function and coronary blood flow were measured before arrest and during reperfusion. Cardiac SR was isolated from left ventricular biopsy specimens, and 45Ca2+ uptake by SR and SR Ca(2+)-adenosine triphosphatase activity were determined. The recovery of left ventricular global contractile function as indicated by the maximum of the first derivative of left ventricular pressure was significantly improved in the WBC group compared with that of the CBC group (70% versus 46%; p < 0.05). The SR Ca(2+)-adenosine triphosphatase activity was better preserved after 60 minutes reperfusion in WBC compared with CBC (0.31 +/- 0.02 versus 0.20 +/- 0.03 microM Pi/min/mg protein, p < 0.05), and the recovery of SR Ca2+ uptake was significantly improved by WBC compared with CBC (1.15 +/- 0.12 versus 0.83 +/- 0.04 microM Ca2+/min/mg protein; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of SOD, catalase, and a novel antiarrhythmic drug, EGB 761, on reperfusion-induced arrhythmias in isolated rat hearts.

Effects of superoxide dismutase (SOD), catalase, EGB 761 (Tanakan), and their combination on reperfusion-induced ventricular fibrillation (VF), tachycardia (VT), and the formation of oxygen free radicals were studied after 30 min of global ischemia followed by reperfusion in isolated rat hearts. In the first series of studies, rats received a daily dose of 10(4), 2 x 10(4), or 5 x 10(4) U/kg of SOD (i.v.); 2.5 x 10(4), 5 x 10(4), or 10(5) U/kg of catalase (i.v.); and 25, 50, 100, or 200 mg/kg of EGB 761 (per os), respectively, for 10 d (chronic administration). Neither SOD nor catalase alone reduced the incidence of reperfusion arrhythmias, but EGB 761 dose-dependently reduced the incidence of such arrhythmias. The coadministration of SOD (5 x 10(4) U/kg) with catalase (5 x 10(4) U/kg) significantly reduced the incidence of VF and VT. The same reduction in the incidence of VF and VT was observed when SOD (5 x 10(4) U/kg) was given in combination with EGB 761 (50 mg/kg). In the second series of studies, hearts were isolated and perfused with 5 x 10(4) U/l of SOD plus 5 x 10(4) U/l of catalase (acute treatment), and the incidence of reperfusion-induced VF and VT was significantly reduced. The combination of SOD (5 x 10(4) U/l) with EGB 761 (50 mg/l) also reduced the incidence of VF and VT. In these experiments, we studied the time course of oxygen radical formation using 5,5-dimethyl-pyrroline-N-oxide (DMPO), a spin trap, and it was found that EGB 761 (200 mg/l) or the coadministration of EGB 761 (50 mg/l) with SOD (5 x 10(4) U/l) almost completely abolished the formation of oxygen radicals during reperfusion measured by electron spin resonance (ESR) spectroscopy. Although SOD or catalase alone significantly reduced the formation of oxygen radicals, these drugs failed to prevent the development of reperfusion arrhythmias, while their combination significantly attenuated both the formation of free radicals and the incidence of reperfusion-induced arrhythmias. Our results indicate that the combination therapy may synergistically reduce the formation of free radicals and the incidence of reperfusion-induced VF and VT.

Animals↗
PubMed1993

Molecular adaptation of cellular defences following preconditioning of the heart by repeated ischaemia.

OBJECTIVE: The molecular mechanism of preconditioning the heart by repeated ischaemia was investigated by examining the expression of stress related and antioxidative genes and proteins. METHODS: Isolated buffer-perfused rat hearts were made ischaemic for 5 min followed by 10 min of reperfusion (1 x PC). Another group of experiments was performed by repeating the ischaemia/reperfusion episode four times (4 x PC). Both 1 x PC and 4 x PC groups were reperfused for 60 min. Control experiments were performed by perfusing the hearts with buffer using the same time frame, but without ischaemia/reperfusion. The induction of the expression of two oncogenes (c-fos and c-myc), three heat shock protein (HSP) genes (HSP 27, HSP 70, and HSP 89 mRNAs) and two antioxidative enzyme genes (Mn-superoxide dismutase (SOD) and catalase mRNAs) by northern hybridisation, as well as the activities of four major antioxidative enzymes (SOD, catalase, glutathione peroxidase, and glutathione reductase) were examined in control and 1 x PC and 4 x PC hearts. In addition, 2-D gel electrophoresis of the proteins in all groups was performed to examine the induction of any new protein. Myocardial preservation was studied by examining left ventricular functions. RESULTS: Northern hybridisation detected enhanced level of c-fos 2.2 kb mRNA and c-myc 2.4 kb mRNA in 4 x PC hearts after 60 min of reperfusion, induction being stronger for c-fos. 1 x PC hearts showed minimal expression of c-fos mRNA, but not c-myc mRNA. 4 x PC hearts also showed the induction of HSP 27, HSP 70, and HSP 89 mRNAs as well as catalase and Mn-SOD mRNAs, whereas 1 x PC hearts showed some induction of HSP 70 mRNA and catalase mRNA only. 2-D gel electrophoresis revealed the expression of 15-20 new proteins in 4 x PC hearts only. The activities of three major antioxidative enzymes, Mn-SOD, peroxisomal catalase, and glutathione peroxidase, but not Cu/Zn-SOD, cytosolic catalase, and glutathione reductase, were enhanced after 60 min of reperfusion in 4 x PC hearts only compared to both 1 x PC and baseline values. 4 x PC hearts, but not 1 x PC hearts, showed reduction of subsequent myocardial ischaemic and reperfusion injury. CONCLUSIONS: Repeated ischaemia and reperfusion (4 x PC), and not 1 x PC, caused the induction of several stress related and antioxidant genes including HSP 27, 70, and 89 genes, Mn-SOD and catalase genes, and proto-oncogenes (c-fos and c-myc), as well as the expression of several stress inducible proteins and stimulation of three antioxidative enzymes. Mn-SOD, peroxisomal catalase, and glutathione peroxidase, simultaneously protecting the heart from subsequent ischaemia-reperfusion injury. The expression of stress inducible and antioxidant genes and stimulation of antioxidant enzyme activities may reflect the heart's response enabling it to survive against ischaemic stress by eliminating the oxidative assault.

Animals↗
PubMed1993

Reduction of myocardial ischemic reperfusion injury by sialylated glycosphingolipids, gangliosides.

Gangliosides, sialic acid-containing glycosphigolipids, are localized mostly to the outer leaflet of the lipid bilayer in the plasma membrane, particularly in brain. Gangliosides reduce edema formation, restore glucose metabolism, and increase cerebral blood flow after focal ischemia in the rat brain. We wished to determine whether gangliosides could also reduce myocardial ischemic and reperfusion injury. Isolated rat heart perfused by Langendorff technique was pretreated with gangliosides (1 microM) purified from the rat brain. After 15-min perfusion with gangliosides, hearts were made ischemic for 30 min by termination of coronary flow, followed by 60-min reperfusion. Ganglioside-treated heart exhibited better myocardial preservation, as evidenced by reduction in creatine kinase release and lipid peroxidation product formation enhanced coronary flow and contractile functions [left ventricular developed pressure (LVDP) and maximum first derivative of LVDP, LVdp/dtmax]. In addition, gangliosides reduced the hydroxyl radical formed during reperfusion of ischemic myocardium, as shown by high-performance liquid chromatography (HPLC)-electrochemical detection technique. In vitro studies demonstrated that these gangliosides were direct scavengers of superoxide anions (IC50 0.8 microM), and hydroxyl radicals (IC50 10 microM), as well hypohalite radicals (IC50 0.7 microM). Furthermore, ganglioside pretreatment was accompanied by reduced intracellular calcium overloading during ischemia and reperfusion as compared with untreated controls. The results of this study thus suggest that gangliosides can reduce ischemic reperfusion injury in isolated heart, probably by inhibiting intracellular calcium overloading and/or by directly scavenging the free radicals generated during reperfusion of ischemic myocardium.

Animals↗
PubMed1993

Molecular adaptation of vascular endothelial cells to oxidative stress.

Cellular organisms respond at the cellular and molecular level when confronted with sudden changes in environment, and molecular adaptation represents the ability of the cells to acclimate themselves to their new environment. In this study we examined the response of bovine vascular endothelial cells (VEC) to the oxidative stress by exposing the cultured cells to two different concentrations of H2O2, 0.04 or 0.08 mM, for 18-24 h. H2O2-exposed VEC displayed good viability (85-90% for 0.04 mM H2O2; 75-80% for 0.08 mM H2O2) and exhibited normal morphology. H2O2 treatment of the VEC was associated with the expression of a number of new proteins, as demonstrated by two-dimensional gel electrophoresis of total cell lysate. Cells exposed to 0.04 mM H2O2 expressed 25 new proteins, whereas 19 newly expressed proteins were detected when the cells were exposed to 0.08 mM H2O2. Western blot analysis of H2O2-treated VEC using specific antibodies to heat-shock proteins (HSP) identified one of these proteins as a member of the HSP 70 family. In addition, H2O2 induced an increase in antioxidative enzyme activities in the VEC, including superoxide dismutase, catalase, and glutathione peroxidase. Moreover, these changes were a truly adaptive phenomenon because challenging the VEC with brief exposure to toxic levels of H2O2 (1 mM for 30 min) showed increased viability (by Trypan blue exclusion test) and decreased injury (by lactate dehydrogenase supernatant-to-cellular ratio determination) in adapted cells (preexposed to 0.04 or 0.08 mM H2O2) compared with control cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1993

Interleukin-1 alpha preconditioning reduces myocardial ischemia reperfusion injury.

BACKGROUND: Interleukin-1 (IL-1) has been shown to induce superoxide dismutase (SOD) activity and to express heat shock protein (HSP). Since the reperfusion of ischemic heart is associated with the reduction of antioxidative enzymes including SOD and expression of HSP, it was hypothesized that IL-1 could be beneficial against ischemic reperfusion injury. METHODS AND RESULTS: Rats were injected with recombinant IL-1 alpha (30 micrograms/kg IP); after 48 hours, they were anesthetized and hearts were removed, isolated, and perfused by the Langendorff technique. Myocardial functions were studied by measuring left ventricular developed pressure (LVDP) and its maximum first derivative (LV dP/dt), and cellular injury was studied by estimating creatine kinase (CK) release. Induction of the expression of HSP27 mRNA and HSP27 protein was examined by Western blot analysis and Northern blot analysis, respectively. Antioxidant enzymes were assayed by enzymatic analysis. Our results indicated reduction of ischemic reperfusion injury by IL-1 alpha, as evidenced by better recovery in postischemic ventricular functions (LVDP [mm Hg]: control, 63 +/- 14; IL-1, 102 +/- 11; P < .05), increased coronary flow (mL/min) (control, 2.93 +/- 0.58; IL-1, 5.17 +/- 0.43; P < .03), and reduced creatine kinase release (IU/L) (control, 110 +/- 5.78; IL-1, 81.76 +/- 7.71; P < .01). IL-1 alpha induced the expression of HSP27 mRNA within 2 hours as examined by Northern blot analysis and the expression of HSP27 after 48 hours. In addition, hearts pretreated with IL-1 alpha for 48 hours and then subjected to 30-minute ischemia and 60-minute reperfusion enhanced the activities (nmol/min/mg protein) of Cu/Zn SOD (control, 1.55 +/- 0.22; IL-1 alpha, 2.92 +/- 0.04; P < .004), Mn-SOD (control, 4.54 +/- 0.19; IL-1 alpha, 6.33 +/- 0.09, P < .001), catalase (control, 15.53 +/- 0.37; IL-1 alpha, 21.67 +/- 0.72; P < .002), glutathione peroxidase (control, 17.49 +/- 0.35; IL-1 alpha, 25.87 +/- 0.58; P < .001), and glucose-6-phosphate dehydrogenase (control, 22.71 +/- 0.44; IL-1 alpha, 29.53 +/- 0.48; P < .001). CONCLUSIONS: The results of this study indicate that low doses of IL-1 alpha can be used as a therapeutic agent to precondition a heart from ischemia reperfusion injury.

Animals↗
PubMed1993

Induction of interleukin-8 expression during cardiopulmonary bypass.

BACKGROUND: Patients undergoing cardiopulmonary bypass (CPB) are known to suffer from a postsurgical systemic inflammatory response, the nature of which remains to be fully elucidated. Interleukin-8 (IL-8) is a newly described, powerful leukocyte chemotactic factor known to be generated after stimulation of interleukin-1 (IL-1). As we have previously documented the generation of IL-1 beta after CPB, it followed that IL-8 generation should be measured in a comparable group of patients. METHODS AND RESULTS: Twenty-two adult patients aged 41 to 81 years undergoing coronary revascularization were studied for measurements of C3a, C5a, IL-1, IL-8, and OH(.). Blood was collected before surgery, after CPB, and at 24, 48, and 72 hours. A significant increase in IL-1 beta and IL-8 was detected in circulating leukocytes with peak levels at 24 hours after bypass. No IL-1 beta or IL-8 antigen was detected at any time in patient plasma. Comparable to interleukin generation, human complement-derived C5a also peaked after 24 hours, whereas C3a was increased dramatically immediately after CPB, followed by a decline at 24 hours and a progressive increase over the next 48 hours. CONCLUSIONS: The results demonstrated for the first time the presence of cell-associated IL-8 in CPB patients. This suggests that this powerful polymorphonuclear and T-lymphocyte chemotactic factor may be an important element in leukocyte activation and recruitment after CPB.

Adult↗