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Biomedical subjects

D K Das

Publications and source records attributed to D K Das.

At least 19 recordsLinked to original sources
PubMed1992

Phospholipase D signaling in ischemic heart.

Phospholipase D (PLD) activity was found to be present in the membrane fraction of rat myocardial cells by in vitro assays (36.7 +/- 4.1 nmol/mg protein per h against 1-palmitoyl-2-arachidonoyl- phosphatidylcholine) and demonstrated in intact cells by the specific transphosphatidylation reaction (in the presence of 0.02% ethanol) quantitated using n-[1-14C]butanol (201.16 +/- 7.1 pmol/min per g dry weight in the whole heart). Both methods showed a significant increase in PLD activity (by 62 and 44%, respectively) in hearts subjected to reversible (30 min) global normothermic ischemia followed by reperfusion (30 min). In hearts prelabeled with [1-14C]arachidonic acid, ischemia/reperfusion induced a significant increase in the amount of radiolabel incorporated into phosphatidic acid (PtdOH) (by 49.6%) and diacylglycerol (DG) (by 259%). DG kinase inhibition by 100 microM dioctanoylethylene glycol did not affect the ischemia/reperfusion DG and PtdOH levels while PtdOH phosphohydrolase inhibition with 40 microM propranolol produced a further increase in PtdOH (to 2.36-fold the baseline level) and a reduction in DG (to only 145% over the baseline levels). Put together, all these results suggest an activation of PLD during myocardial ischemia/reperfusion generating intracellular PtdOH, part of which is converted by PtdOH phosphohydrolase to DG. We further investigated the possible pathophysiological significance of the observed PLD activation. Stimulation of PLD with sodium oleate (20 microM) induced a significant improvement of functional recovery of ischemic hearts during reperfusion (as monitored by coronary flow and left intraventricular pressure measurements) and an attenuation of cellular injury as expressed by lactate dehydrogenase and creatine kinase release in the coronary effluent during reperfusion. These results suggest a PLD-mediated signaling in the ischemic heart which may benefit functional recovery during reperfusion.

Animals↗
PubMed1992

Superficial and deep-seated tuberculous lesions: fine-needle aspiration cytology diagnosis of 574 cases.

Over a period of 2 yr (1987-1988), FNA smears in 574 cases were found to have cytologic features suggestive of or consistent with tuberculous lesions. The age of the patients ranged from 6 mo to 75 ye, with a median of 24 yr. The male to female ratio was 273:301. Sites of FNA were superficial lymph nodes (SLN) in 440 (76.7 percent) cases, superficial extranodal sites (SENS) in 50 (8.7 percent), both SLN and SENS in 7 (1.2%), the thoracic cavity in 16 (2.8%), and the abdominal cavity in 61 (10.6%). Cytologic features were described under 3 major cytologic patterns, i.e., type I: epithelioid granuloma without necrosis, type II: epithelioid granuloma with necrosis, type III: necrosis without epithelioid granuloma. Type I, II, and III reactions were observed in 181 (31.5%), 183 (31.9%), and 210 (36.6%) cases, respectively. The overall AFB positivity was 30.8%. The AFB positivities for type I, II, and III cytologic reactions were 5.4%, 32.0%, and 48.5%, respectively. The AFB positivity was low (less than 30.0%) in swellings of the body surface (23.8%) and abdominal organs (18.9%). High positivity (greater than 60.0%) was observed in lesions of the thorax (63.6%) and thyroid (62.5%).

Adolescent↗
PubMed1992

Supportive role of image analysis and DNA ploidy pattern in the diagnosis of thyroid tumors.

To evaluate the supportive role of image cytometry and DNA ploidy pattern in the diagnosis of thyroid tumors, a preliminary study was performed on fine needle aspirates of 30 cases. Of these, 10 cases each were of colloid goiter, follicular neoplasm, and papillary carcinoma. The nuclear area and DNA value of 50 cells in each case were measured. The mean nuclear area in colloid goiter (69.50 + 12.62 sq.microns) was significantly lower than the mean nuclear area in a follicular neoplasm (88.71 + 15.51 sq.microns) (P less than 0.05). Similar differences between the mean nuclear area in colloid goiter and papillary carcinoma (124.0 + 12.27 sq microns) was also highly significant (P less than 0.001). The results obtained by image cytometry were compared with estimated DNA ploidy pattern of follicular cells from the same cases. All colloid goiter had mean nuclear area below 100 sq.microns with diploid DNA value. However, papillary carcinoma showed aneuploid DNA pattern in eight cases (80.0%), but mean nuclear area was above 100 sq.microns. A diagnostically useful finding obtained in two of the 10 cases of follicular neoplasm was the association of aneuploid DNA pattern with mean nuclear area of the follicular cells above 100 sq.microns indicating a high probability of carcinoma and thus demanding an urgent open biopsy. These cases were readily distinguished from other cases of the same category showing diploid DNA pattern and mean nuclear area of follicular cells below 100 sq.microns.

Cell Nucleus↗
PubMed1992

Leiomyosarcoma of the orbit: diagnosis of its recurrence by fine-needle aspiration cytology.

An 8 1/2-yr-old boy with proptosis was diagnosed to have low-grade leiomyosarcoma of the orbit following lateral orbitotomy and histology of an incompletely excised intraconal mass. He received chemotherapy but had recurrence of proptosis at the age of 12 yr. Ultrasonography revealed a solid mass and its fine-needle aspiration cytology features were consistent with recurrence of leiomyosarcoma. A year later, the cytodiagnosis was confirmed by histology of the excised tumor from a second lateral orbitotomy. Masson's trichrome stain confirmed the smooth muscle nature of the neoplasm and ultrastructural features were in favor of leiomyosarcoma. The patient received intermittent chemotherapy, and is clinically free from disease at the age of 17 yr.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

A high frequency of human papillomavirus DNA sequences in cervical carcinomas of Indian women as revealed by Southern blot hybridization and polymerase chain reaction.

Ninety-six colposcopically directed biopsies from squamous epithelial carcinoma of the uterine cervix and 22 age-matched normal control biopsy specimens were examined by both Southern blot hybridization and polymerase chain reaction (PCR) for the presence of different human papillomavirus (HPV) DNA types. Cancer of the uterine cervix, which is the most common malignant disease in Indian women, showed a high frequency (98%) of HPV as compared to those reported from other parts of the world. HPV type 16 was found to be the dominant (64%) type while the frequency of HPV type 18 was very low (3%). On individual typing of HPV, no biopsy was found to contain any other known HPV types under stringent conditions of hybridization except a single case of HPV type 11. Only one case of double infection with HPV types 16 and 18 was recorded. Under low stringency conditions of hybridization with a mixed probe of HPV types 16 and 18, 29 additional biopsies were found to be positive. Southern blot hybridization alone detected HPV DNA in 92% of the cases but none in the controls. By PCR, six (6.25%) more cases and four (18.18%) healthy women were found to be positive for HPVs. Analysis of the physical state of HPV 16 indicated integration in about 70% of carcinoma cases while 30% of them were in episomal form. The findings suggest that infection with HPV is an important etiologic factor for the development of cervical cancer, that a number of such tumours may arise without HPV infection, and that integration of the viral DNA into host genome is not always essential for malignant progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Attenuation of myocardial reperfusion injury by sulfhydryl-containing angiotensin converting enzyme inhibitors.

Recent studies have suggested the beneficial effects of angiotensin converting enzyme (ACE) inhibitors against myocardial ischemic-reperfusion injury. This study was designed to compare the cardioprotective effects of two sulfhydryl ACE inhibitors, captopril and zofenopril, with those of a nonsulfhydryl ACE inhibitor, fosinopril. The efficacy of these ACE inhibitors to scavenge oxygen radicals in vitro were also examined. Isolated rat hearts perfused by the Langendorff technique were preperfused in the presence or absence of ACE inhibitors (50 microns for 15 minutes, and the hearts were then subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Zofenopril and captopril, but not fosinopril, improved postischemic left ventricular functions and reduced myocardial cellular injury, as evidenced by improved recovery of the first derivative of left ventricular pressure development and reduced creatine kinase release compared with control (p less than .05). Coronary flow was significantly increased by captopril and zofenopril only. The same two drugs also inhibited the enhanced lipid peroxidation during reperfusion. Although significant differences were not noticed in the postischemic myocardial membrane phospholipid composition, captopril and zofenopril reduced nonesterified fatty acid contents, including palmitic, linoleic, oleic, and arachidonic acids. In vitro studies demonstrated that captopril and zofenopril were able to scavenge hydroxyl radicals. These results indicate that among three ACE inhibitors, two sulfhydryl-containing drugs, captopril and zofenopril, possess cardioprotective as well as free-radical scavenging abilities. Attenuation of phospholipid degradation and lipid peroxidation may be contributory to the protective effects observed in this study.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Oxygen-derived free radicals and hemolysis during open heart surgery.

Reperfusion injury occurs during open-heart surgery after prolonged cardioplegic arrest. Cardiopulmonary bypass also is known to cause hemolysis. Since reperfusion of ischemic myocardium is associated with the generation of oxygen free radicals, and since free radicals can attack a protein molecule, it seems reasonable to assume that hemolysis might be the consequence of free radical attack on hemoglobin protein. The results of this study demonstrated that reperfusion following ischemic arrest caused an increase in free hemoglobin and free heme concentrations, simultaneously releasing free iron and generating hydroxyl radicals. In vitro studies using pure hemoglobin indicated that superoxide anion generated by the action of xanthine oxidase on xanthine could release iron from the heme ring and cause deoxygenation of oxyhemoglobin into ferrihemoglobin. This study further demonstrated that before the release of iron from the heme nucleus, oxyhemoglobin underwent deoxygenation to ferrihemoglobin. The released iron can catalyze the Fenton reaction, leading to the formation of cytotoxic hydroxyl radical (OH.). In fact, the formation of OH. in conjunction with hemolysis occurs during cardiac surgery, and when viewed in the light of the in vitro results, it seems likely that oxygen-derived free radicals may cause hemolysis during cardiopulmonary bypass and simultaneously release iron from the heme ring, which can catalyze the formation of OH..

Cardiac Surgical Procedures↗
PubMed1992

Reduced free radical generation during reperfusion of hypothermically arrested hearts.

Several studies indicate the presence of hydroxyl radical (OH.) as well as its involvement in the myocardial reperfusion injury. A transition metal-like iron is necessary for the conversion of superoxide anion (O2-) to a highly reactive and cytotoxic hydroxyl radical (OH.). In the present study, we have examined the generation of OH. and free iron in reperfused hearts following either normothermic (37 degrees C) or hypothermic ischemia (5 degrees C). Employing the Langendorff technique, isolated rat hearts were subjected to global ischemia for 30 min at 37 degrees C or 5 degrees C and were then reperfused for 15 min at 37 degrees C. The results of the study suggest that both the OH. generation in myocardium and free iron release into perfusate were significantly lower in hearts made ischemic at 5 degrees C as compared to 37 degrees C. Release of myoglobin and lactic acid dehydrogenase into perfusate also followed a similar pattern. Furthermore, in in vitro studies, chemically generated O2- at 5 degrees C caused a significantly lower rate of oxidation of oxymyoglobin as well as generation of OH. and free iron as compared to 37 degrees C. These results suggest that (1) reperfusion of hypothermic ischemic heart is associated with a reduction in the generation of OH. and cellular damage compared to that of normothermic ischemic heart, and (2) myoglobin, an intracellular protein, is a source of free iron and plays a role in the reperfusion injury mediated by free radicals.

Animals↗
PubMed1992

Moderation of myocardial ischemia reperfusion injury by calcium channel and calmodulin receptor inhibition.

Intracellular Ca2+ accumulation is implicated in the pathogenesis of myocardial reperfusion injury. To study approaches designed to modify Ca2+ uptake during coronary revascularization after acute infarction, a pig heart surgical infarct model (left anterior descending artery occlusion for 60 min) was subjected to 60 min hypothermic potassium cardioplegic arrest, followed by 60 min of global reperfusion. Four groups of six hearts each were studied in a randomized manner, i.e., cardioplegia alone (control), cardioplegia + 10 microM diltiazem (Ca2+ slow channel blocker), cardioplegia + 10 microM trifluoperazine (TFP), (a Ca(2+)-calmodulin antagonist), and cardioplegia+diltiazem (10 microM) + TFP (10 microM). Left ventricular contractility (global and segmental), metabolism (coronary blood flow and O2 consumption), and creatine kinase generation were measured during reperfusion. Both the Ca2+ channel blocker, diltiazem, and the calmodulin antagonist, TFP, improved myocardial global and regional function as well as myocardial metabolism. While diltiazem better restored global and regional contractility, trifluoperazine had a greater effect on coronary blood flow and myocardial oxygen consumption. Enzyme release and lipid peroxidation were equally moderated by both drugs. From this study it can be concluded that Ca2+ influx does play a role in ischemic and reperfusion injury. The mechanisms of its effect are complex, but can be successfully antagonized by Ca2+ blockers as well as by calmodulin antagonists, with improved myocardial preservation.

Animals↗
PubMed1992

Salicylate reduces ventricular dysfunction and arrhythmias during reperfusion in isolated rat hearts.

Recent studies have shown the ability of salicylic acid (SA) to trap hydroxyl radicals (OH.) generated during reperfusion in ischemic myocardium. Since OH. is implicated in the pathogenesis of reperfusion injury, we examined the effect of SA on reperfusion-induced arrhythmias and postischemic ventricular dysfunction. Isolated rat hearts perfused by the Langendorff technique were preperfused with Krebs-Henseleit buffer containing SA for 10 min. Hearts were then made ischemic for 30 min, followed by 30 min of reperfusion. In a separate group, SA was administered only at the onset of reperfusion. The left ventricular contractile functions, left ventricular developed pressure (LVDP) and its first derivative (LV dP/dt), coronary flow (CF), and creatine kinase (CK) release were determined before and after ischemia. Epicardial electrocardiogram (ECG) was also recorded to analyze the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF). SA improved LVDP, LV dp/dt, and CF recovery and reduced CK release compared to the control group. The incidence of VT and VF during reperfusion was also significantly reduced by SA. Analysis of tissue thiobarbituric acid-reactive products indicates that SA decreased oxidative stress during reperfusion. In conclusion, these results suggest that SA reduces myocardial reperfusion injury and attenuates ventricular arrhythmias by trapping OH. radicals upon reperfusion in isolated rat hearts.

Animals↗
PubMed1992

Inflammatory lesions of the breast: diagnosis by fine needle aspiration.

Amongst 1061 breast lesions diagnosed by fine needle aspiration (FNA) over a period of 6 years (1985-1990), 128 were reported to be showing changes consistent with an inflammatory lesion. On review, the cytodiagnosis was found to be inaccurate in 31 cases. The cytological features of the 97 cases that were correctly reported are described in this report. The cytological diagnoses issued in these 97 cases were acute mastitis or breast abscess (57 cases) and tuberculous mastitis (30 cases). Non-specific chronic mastitis and miscellaneous conditions accounted for four and six cases respectively. Acid fast bacilli (AFB) were demonstrated in 28.0% of tuberculous mastitis cases and 10.0% of those diagnosed as acute mastitis or breast abscess. FNA cytology was found to be useful for the diagnosis of inflammatory lesions of breast and their classification, as only five out of 57 cases of acute mastitis/breast abscess and one out of 30 tuberculous mastitis cases were suspected on clinical grounds.

Abscess↗
PubMed1992

Protection from cold injury by deferoxamine, an iron chelator.

The presence of hydroxyl radical (OH) has been implicated in the pathogenesis of cold injury. Since iron is known to catalyze the OH formation responsible for cellular injury, this study was designed to examine whether an iron chelator such as deferoxamine can salvage a tissue from cold injury. Cold injury was induced in the hind limbs of rabbits. The experimental group received 0.6 mM of deferoxamine through the femoral vein prior to cooling of the limbs. Deferoxamine reduced the tissue injury, as evidenced by the decreased release of lactate dehydrogenase, a nonspecific marker for cellular injury. In addition, this drug inhibited OH formation and lipid peroxidation when examined by monitoring the formation of conjugated dienes and malonaldehyde, presumptive markers for lipid peroxidation. Rewarming of the cooled limbs was also associated with the loss of membrane phospholipids, with the corresponding accumulation of lysophosphoglycerides and free fatty acids, especially linoleic and arachidonic acids. Deferoxamine prevented the loss of phospholipids and inhibited the accumulation of amphipathic lipid products. These results indicates that deferoxamine salvaged the tissue from cold injury, possibly by preventing the formation of OH presumably by chelating iron, thus protecting the phospholipids from free radical attack.

Animals↗
PubMed1992

Generation of singlet oxygen and hydroxyl radical from sodium chlorite and lactic acid.

Reperfusion of ischemic tissue is associated with the formation of hydroxyl radical (OH.). In this report, a novel mechanism for (OH.) generation from (1O2) is proposed based on the experimental evidence from the present study. A number of experiments were performed which conclusively demonstrated the formation of 1O2 from the reaction of lactic acid and hypohalite radical. Singlet oxygen attacks the unsaturated olefinic derivatives, which are also formed during reperfusion of ischemic tissue. The reaction between 1O2 and olefinic compounds produces hydroperoxides, which ultimately form OH. radical. The validity of the above mechanism of OH. radical formation is warranted from our experimental results.

Alkenes↗
PubMed1992

Preconditioning of heart by repeated stunning: adaptive modification of myocardial lipid membrane.

Recent studies indicate that preconditioning of a heart by repeated stunning protects it from subsequent ischemic injury. Such myocardial preservation is likely to be due to adaptive modification of lipid composition and dynamic structure of cellular membrane. To test this hypothesis, swine heart was subjected to four episodes of 5 min stunning by LAD occlusion, followed by 10 min of reperfusion after each stunning. Heart was then made regionally ischemic for 60 min by LAD occlusion, followed by 6 h reperfusion. Control heart was perfused for 60 min, followed by 60 min ischemia and 6 h reperfusion. Free fatty acids (FFA) accumulated in control heart during ischemia as expected, which was further enhanced by reperfusion. The FFA level was also enhanced during ischemia in stunned myocardium. However, this FFA level was almost restored during reperfusion. The levels of polyunsaturated fatty acids (PUFA) such as oleate, linoleate, and arachidonate followed a similar pattern. Membrane fluidity, monitored by fluorescence polarization, was decreased during ischemia and reperfusion in the unstunned heart, with the corresponding increase in microviscosity. The increased microviscosity was significantly reduced by stunning. Since FFA are presumably generated from membrane phospholipids, these results suggest that stunning may cause the incorporation of a greater proportion of PUFA in membrane phospholipids, leading to preservation of membrane phospholipids and maintaining the membrane fluidity, which may be at least partially responsible for the attenuation of ischemic reperfusion injury.

Adaptation, Physiological↗
PubMed1992

[Ganglioside protection of the erythrocyte membranes in myocardial ischemia].

Myocardial ischemia was shown to lead to modification of structural and functional organization of rat erythrocyte membranes. Thus, it was found that the activity of Na+, K+-ATP-ase markedly decreased, while accumulation of LPO products and of lysophosphatidylcholine (lyso--PC) took place in erythrocyte membranes of rats subjected to myocardial ischemia. Using nonpenetrating modifier trinitrobenzosulfonic acid, an increase in the content of modified phosphatidylethanolamine in erythrocyte membranes of ischemic rats was revealed as compared to the membranes of control animals. The intravenous administration of gangliosides (30 mg/kg) resulted in partial normalization of Na+, K+(-)ATPase activity, of LPO product and lysoPC content and of transbilayer distribution of lipids.

Animals↗
PubMed1992

Heat shock. A new approach for myocardial preservation in cardiac surgery.

BACKGROUND: Recent studies have indicated that heat shock (HS) induces protective genes and HS protein (HSP) expression, which enhances cellular tolerance to ischemic injury. The present study sought to determine if 42 degrees C blood cardioplegia could be used to induce HSP expression and improved myocardial salvage after 2 hours of cardioplegic arrest. METHODS AND RESULTS: To study this, pig hearts (n = 6) on cardiopulmonary bypass were subjected to HS by continuous infusion to the globally arrested heart of warm blood cardioplegia (K+ = 30 meq/l) at 42 degrees C for 15 minutes followed by 2 hours of intermittent hypothermic (4-6 degrees C) hyperkalemic (30 meq/l) crystalloid cardioplegic arrest and 1 hour of reperfusion (heat shock group). The control group (n = 6) was subjected to only 2 hours of hypothermic crystalloid cardioplegic arrest followed by 1 hour of reperfusion without HS. Left ventricular performance, coronary blood flow, and creatine kinase release were determined before arrest and during reperfusion. Prearrest control biopsies were taken in a separate group of pigs (n = 6) for both HSP and superoxide dismutase activity. Additional biopsies were taken for the same measurements in both control and HS groups at the completion of reperfusion. In a single additional pig in both the control and HS groups, biopsies were taken during the study to estimate changes in HSP expression. The cytosolic protein of ventricular tissue was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the HSP70 family protein was examined by Western blot analysis using monoclonal antibodies. HSP was found to be increasingly expressed from control levels after 15 minutes of HS pretreatment, increasing progressively to a level significantly above the non-HS group. Associated with this increased expression of HSP was a significant increase in superoxide dismutase activity in the HS animals and significant improvement in both global and regional functions and reduced creatine kinase release. CONCLUSIONS: The results show that preconditioning the heart with HS improves postischemic ventricular performance and attenuates cellular injury. HS induces a change in cellular metabolism, prompting the expression of HSP and improving antioxidant activity, leading to improved function and reduced tissue injury during ischemia and reperfusion.

Animals↗
PubMed1992

Preconditioning of heart by repeated stunning. Adaptive modification of antioxidative defense system.

Previous studies demonstrated that preconditioning of a heart by repeated stunning can reduce the cellular injury to the heart from subsequent acute ischemic insult. To examine the possible biochemical mechanism for such myocardial preservation afforded by preconditioning, swine heart was subjected to four episodes of 5 min. stunning by occluding the left anterior descending coronary artery (LAD), followed by 10 min. of reperfusion after each stunning. Heart was then made regionally ischemic for 60 min. by LAD occlusion, followed by 6 hrs. reperfusion. Control heart was perfused for 60 min., followed by 60 min. ischemia and 6 hrs. reperfusion. The results of our studies indicated the stimulation of a number of antioxidative enzymes, including Mn-superoxide dismutase (Mn-SOD), catalase, glutathione peroxidase, and glutathione reductase, after repeated stunning and reperfusion. In addition, a number of new proteins were expressed after preconditioning the heart, including some oxidative-stress related proteins and 72 kDa heat-shock protein. These results suggest that preconditioning of a heart by repeated stunning may lead to strengthening of the oxidative defense system of the heart, which is likely to play a role in myocardial preservation during subsequent ischemic and reperfusion injury.

Adaptation, Physiological↗