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D K Das

Publications and source records attributed to D K Das.

At least 181 records · Page 10Linked to original sources

Effects of extracellular magnesium manipulation on reperfusion-induced arrhythmias and myocardial ion shifts in isolated ischemic reperfused rat hearts.

Isolated rat hearts were subjected to global ischemia followed by reperfusion, and a reduction in the incidence of reperfusion-induced ventricular fibrillation and ventricular tachycardia was brought about by increasing the extracellular Mg concentration in the perfusion buffer. Thus the incidence of ventricular fibrillation was reduced from its control value of 100% in 1.2 mM Mg to 83% by 2.4 mM Mg (P = N.S.), to 42% by 3.6 mM Mg (P < .05), to 17% by 4.8 mM Mg (P < .001) and to 17% by 9.6 mM Mg (P < .001). The corresponding values for ventricular tachycardia were 100% (control, 1.2 mM Mg) vs. 92% (P = N.S.), 50% (P < .05), 25% (P < .01) and 25% (P < .01), respectively. In further studies, extracellular Ca was reduced by 50% (1.2 mM) in the perfusion buffer just before ischemia and during reperfusion. The incidence of ventricular fibrillation was reduced from its control value of 83% in 1.2 mM Mg to 75% by 1.8 mM Mg (P = N.S.), to 33% by 2.4 mM Mg (P < .05), to 17% by 3.6 mM Mg (P < .01) and to 8% by 4.8 mM Mg (P < .01). The incidence of ventricular tachycardia followed the same pattern. Myocardial Na, K, Ca and Mg were measured by atomic absorption spectrophotometer after the removal of ions from the extracellular space. In controls, 30 min of ischemia resulted in 3- and 4-fold accumulation of myocardial Na and Ca, respectively, and during reperfusion these values were similar to the values for 30-min ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Potassium channel openers and blockers: do they possess proarrhythmic or antiarrhythmic activity in ischemic and reperfused rat hearts?

Cromakalim is a member of the new antihypertensive drug family possessing an action that involves an increased K efflux in vascular and cardiac muscle. We studied the contribution of opening of ATP-sensitive K channel to the development of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that of Na, K, Ca and Mg in isolated rat hearts. After 30 min of global ischemia, cromakalim (1 to 30 microM) failed to reduce reperfusion arrhythmias. On the postischemic-reperfused myocardium in a subset of hearts unresponsive to reperfusion-induced arrhythmias (duration of ischemia was reduced to 25 min), cromakalim treatment was associated with a higher incidence of reperfusion ventricular fibrillation (VF) and ventricular tachycardia (VT) as compared to the controls (100% VF and 100% VT in treated vs. 41% VF and 50% VT in controls, P < .05). Proarrhythmic effects of cromakalim were also reflected in a maldistribution of myocardial ions. At concentrations of 3, 10 and 30 microM of glibenclamide, a K channel blocker, a significant reduction in the incidence of reperfusion-induced VF and VT was observed, and an attenuation in the maldistribution of myocardial ion contents induced by ischemia/reperfusion was found. The reduction in myocardial contractility was detected at relatively high concentrations (10 and 30 microM) in both cromakalim- and glibenclamide-treated groups. The proarrhythmic effect of cromakalim (30 microM) was abolished by 3 microM of glibenclamide, suggesting that the increased tendency to develop reperfusion arrhythmias is associated with the cromakalim-induced K efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Estimation of reduction of life-time risk of cervical cancer through one life-time screening.

The purpose of screening for cervical cancer is to prevent the appearance of invasive disease by the detection and treatment of precancerous lesions. Based on data from the developed countries, recommendations have been made regarding the age at which cytology screening should begin and the interval with which rescreening should be performed. However, these recommendations may not be applicable for a developing country like India due to human and financial resource constraints. WHO has recommended that for countries where resources are limited the aim should be to screen every woman at least once in her life-time at an appropriate age. Hence, it is essential to determine the age at which screening may be offered to derive maximum gains. With this in background, based on the data of national cancer registries, an attempt has been made for Indian population to estimate the reduction in the cumulative incidence rate of cervical carcinoma which can be achieved in a cohort of women aged 20-64 years by screening once in her life-time at an appropriate age. Our findings revealed that the first screening offered at 45 years of age could produce gains to the extent of 20-27%, while the screening offered at 50 or 55 years produced the maximum gains to the extent of 25-29%. However, keeping in view the produce years of lives lost in younger women, it may be reasonable to offer once in life-time screening to women aged 45 years.

Adult↗

Reduction of postischaemic ventricular dysfunction and arrhythmias by trapping hydroxyl radicals with salicylic acid.

Recent studies have suggested the ability of salicylic acid (SA) to trap the hydroxyl radicals (.OH) generated in reperfused ischaemic myocardium. This study was designed to examine the effect of SA on reperfusion-induced arrhythmias and postischaemic ventricular dysfunction. Isolated rat hearts perfused by the Langendorff technique were preperfused with SA for 10 min. Hearts were then made ischaemic for 30 min, followed by 30 min of reperfusion. The left-ventricular contractile functions, including left-ventricular developed pressure (LVDP) and its first derivative (LV dp/dt), and creatine kinase (CK) release, were determined before and after ischaemia. Epicardial electrocardiograms (ECG) were also employed to analyse the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF). SA improved LVDP and LV dp/dt, and reduced CK release, as compared to the control group (p < 0.05). The incidence of VT and VF during reperfusion was also significantly reduced by SA (p < 0.05). Analysis of tissue thiobarbituric acid-reactive products indicates that SA decreased oxidative stress during reperfusion. In conclusion, these results suggest that SA reduces ventricular dysfunction and attenuates ventricular arrhythmias by trapping OH radicals upon reperfusion in isolated rat hearts.

Animals↗

Selective cervical cytology screening: discriminant analysis approach.

Cervical cancer is one of the leading malignancies seen in Indian women. It has been well established that organized cervical cytology screening program is the mainstay for control of cervical cancer. It is not possible to carry out cervical cytology screening for masses in India due to paucity of human and financial resources. Hence there is a need for development of an alternate strategy to concentrate on women with high risk. In the present communication attempt was made to define a high risk group based on sociodemographic factors, viz. age, parity, education and clinical features. A total of 67,000 women were screened of which in 250 malignancy was detected. The rate of malignancy was observed to be high in women above 40 years (10.5/1000) with more than two children (6.1/1000) and in illiterate group (4.9/1000) as compared to women below 40 years, more than 3 children and illiterate group. Similarly, the rates were higher in women with clinical diagnosis of cervical erosion which bled on touch, unhealthy cervix and suspicious looking cervix, malignancy rates were 17.1, 24.7, 263.2 (per 1000), respectively. An attempt was made to study the combined effect of all the six factors (sociodemographic and clinical) by employing the technique of linear discriminant analysis to find out the discrimination power between the normal and malignant women. Discriminant score thus obtained would help to classify the case for subjecting to cervical cytology. It was observed that the model containing sociodemographic and clinical variables was able to classify 69% of malignant cases correctly. When the clinical variables were dropped from the model, the sensitivity dropped to 65%. The above exercise indicated that based on the discriminant score even in the absence of facilities for clinical examination of women, it may be possible to identify women of high risk group for subjecting them to cervical cytology screening.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗