Amiloride enhances postischemic ventricular recovery during cardioplegic arrest. A possible role of Na(+)-Ca2+ exchange.
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Amiloride↗
Biomedical subjects
D K Das
Publications and source records attributed to D K Das.
Role of phospholipases A2 and C in myocardial ischemic reperfusion injury.
We investigated the role of phospholipase A2 (PLA2) and phospholipase C (PLC) in myocardial phosholipid degradation and cellular injury during reperfusion of ischemic myocardium. For this purpose, isolated rat hearts were perfused with isotopic arachidonic acid to label its membrane phospholipids. Hearts preperfused with antiphospholipase A2 (anti-PLA2) retained a significantly higher amount of radiolabel in phosphatidylcholine and phosphatidylinositol and a corresponding lower amount of radiolabel in lysophosphatidylcholine and nonesterified fatty acids (P less than 0.05) after 30 min of reperfusion following 30 min of normothermic global ischemia compared with hearts preperfused with nonimmune immunoglobulin G. In similar experiments, antiphospholipase C (anti-PLC)-treated hearts were associated with significantly (P less than 0.05) higher radiolabel in all phospholipids and lower radiolabel in diacyglycerol compared with nonimmune immunoglobulin G-treated hearts. Measurement of phospholipase activity in subcellular organelles of these hearts showed decreased PLA2 activity in cytosol, mitochondria, and microsomes of anti-PLA2-treated hearts and decreased PLC activity of microsomes in anti-PLC-treated hearts. Furthermore, both the antiphospholipases attenuated the release of creatine kinase and lactate dehydrogenase into perfusate and increased contractility as well as coronary flow in the reperfused hearts. Results of this study suggest that both PLA2 and PLC are involved in the degradation of phospholipids and cellular injury that occur during reperfusion of ischemic myocardium.
Animals↗
Reduction of cold injury by superoxide dismutase and catalase.
The pathophysiology of cold injury was examined by cooling a hind leg of an anesthetized New Zealand white rabbit. A flow probe and a thermocouple were placed in the leg to be cooled to monitor the blood flow and tissue temperature. After baseline measurements, the leg was cooled with a freezing mixture up to 0 degrees C, which was followed by rewarming. The other leg served as control. In the experimental group, liposome-bound superoxide dismutase and catalase were infused through the femoral vein 15 minutes prior to putting the freezing mixture on the leg. Salicylic acid was injected through the femoral vein at the end of some experiments to assay hydroxy radical (OH). Our results demonstrated reduction of local blood flow in cold-exposed leg, indicating development of ischemia. Creatine kinase and lactage dehydrogenase were increased during rewarming in conjunction with hydroxyl radical formation, phospholipid breakdown, and lipid peroxidation. Treatment with superoxide dismutase and catalase reduced OH formation, prevented phospholipid degradation, and decreased creatine kinase, lactate dehydrogenase, and malonaldehyde formation. These results indicate that rewarming of cooled tissue is associated with "rewarming injury" similar to "reperfusion injury", and that oxygen-derived free radicals play a significant role in the pathophysiology of such injury.
Animals↗
Quantitative analysis of nuclear area variation in benign and malignant breast fine needle aspirates.
The measurement of nuclear area was carried out in 30 benign and 32 malignant breast lumps using Omnicon Alpha 500 Image Analyzer. The mean nuclear area of duct cells in malignant group was greater (157.6 +/- 58.64 sq.microns with a peak around 140 sq.microns) and more heterogenous within and amongst cases than observed in duct cells from most of the cases of fibroadenoma (85.05 ae 14.2 sq.microns with a peak around 80 sq.microns). Taking into consideration 110 sq.microns as a differentiating limit, a significant difference was observed between benign and malignant conditions (p). Similarly taking 118 sq.microns as differentiating limit duct cell carcinomas could be divided into two groups i.e. 9(28.1%) cases of small nuclear type with a range of 80-118 sq.microns and 23(71.9%) cases of large nuclear type with a range of 118-320 sq microns .6(18.8%) cases with small nuclei had an overlap with fibroadenoma. Although 13(72.2%) cases of large nuclear type carcinomas had lymph node metastasis as against 4(44.4%) in small nuclear group, the difference was not statistically significant.
Adenofibroma↗
Reduction of infarct size by systemic amino acid supplementation during reperfusion.
The amino acids aspartate and glutamate, in combination, were evaluated as a means of reducing infarct size and improving cardiac function during reperfusion in an intact pig having an acute anteroseptal infarct. Three groups of 6 pigs each were randomly studied in a blinded manner: control (no amino acids), aspartate/glutamate 3 mmol/L, and aspartate/glutamate 13 mmol/L. The left anterior descending coronary artery was occluded distal to its first diagonal branch for 60 minutes followed by reperfusion for 6 hours. Aspartate and glutamate were administered systemically immediately before reperfusion. The following parameters were measured: infarct size and percent area at risk, global metabolic function, global and regional myocardial function, and tissue parameters of metabolic function. The results clearly showed a significant decrease in infarct size from 60% of the area at risk in control pigs to 37% in both 3 mmol/L and 13 mmol/L amino acid groups. Cardiac output, coronary blood flow, and global oxygen consumption were not significantly affected by the use of amino acids relative to the control group. Global left ventricular mechanical function was also not adversely affected by the infarct and was not altered by amino acid administration. Regional function, however, was significantly decreased by occlusion of the left anterior descending coronary artery in all groups to near 20% and only significantly recovered to 64% in the 13 mmol/L amino acid group. Adenosine triphosphate and acetyl coenzyme A measurements documented significant increases in the 13 mmol/L amino acid group relative to the control group. The conclusions of this study strongly support aspartate/glutamate supplementation for stunned, reperfused myocardium. It is apparent that the effect of amino acid supplementation on glycolysis is directly translated into improved regional function and reduced infarct size.
Animals↗
Preconditioning the heart by repeated stunning improves myocardial salvage.
Repeated regional ischemia of short duration followed by reperfusion leads to preconditioning of the myocardium. Left anterior descending coronary artery (LAD) occlusion was applied for 5 minutes and then released for 10 minutes. This was repeated four times by using an intact pig model. LAD occlusion was then continuously applied for 1 hour. Myocardial function, high energy phosphates, and membrane phospholipids were compared with a control (nonstunned) group over a 6-hour reperfusion period. Stunning itself produced no significant change in regional function, total phospholipids, or free fatty acids (FFA). However, regional function, adenosine triphosphate, and creatine phosphate were significantly (p less than 0.05) reduced over control. After 60 minutes of ischemia, regional function was significantly improved by preconditioning that persisted throughout reperfusion (p less than 0.01). This was associated with an 11% mean decrease in infarct size (p less than 0.05). Adenosine triphosphate was significantly preserved during ischemia in the preconditioned hearts, and this preservation persisted throughout reperfusion (p less than 0.05). Total phospholipids were not affected by ischemia in either group. However, during reperfusion both groups demonstrated a 15-20% decrease in phospholipid levels at 1 hour, with only the stunned group showing a progressive increase at 3 and 6 hours (p less than 0.05). Examination of FFA during reperfusion demonstrated a profound increase in only the unstunned animals (p less than 0.05), correlating with the decreased level of membrane phospholipids noted in this group. In conclusion, repeated stunning predisposes the heart to recovery after regional ischemia. This results in improved mechanical function, increased high-energy phosphate stores, and decreased infarct size.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
Improved early detection of recurrence in prostatic carcinoma following hormonal therapy. Combined use of palpation and fine needle aspiration cytology.
Fifty-nine hormonally treated prostatic carcinoma patients were prospectively followed by rectal examination and fine needle aspiration cytology at six-month intervals for periods ranging from six to one hundred twenty months (median follow-up 48 mos). The cytologic findings and clinical impressions were divided into four or five categories, respectively, ranging from benign to clearly malignant. Cytologic material and clinical descriptions suitable for evaluation were available for 306 follow-up examinations. Of these, 209 were cytologically benign (including 191 without and 18 with clinical evidence of malignancy). The remaining 97 examinations showed cytologic evidence of malignancy of which 50 were clinically apparent (51.5%). While the correlation of clinical and cytologic findings was good (91.4%) in cases with no evidence of disease activity, our findings indicate that many recurrences which are occult to clinical examination may be detected by cytologic examination.
Aged↗
Risk factors related to biological behaviour of precancerous lesions of the uterine cervix.
In a study of factors related to cervical carcinogenesis, a cohort of 1,107 cervical dysplasia along with 1,077 controls matched for age and parity were followed up prospectively. During the follow up 75 dysplasia cases progressed to carcinoma in situ. The overall rate of progression of dysplasia to malignancy was observed to be 15.7% at the end of 108 months of follow-up. The analysis of progression rates in relation to various factors revealed significantly higher progression rates for initially higher grade of dysplastic lesions, and early age at consummation of marriage (ACM). The other factors, such as religion, literacy status of the patient, number of pregnancies, presence of cervical erosion, history of fetal loss and positivity to HSV-II antibodies, did not reveal statistical significance. The case-control comparison for detection of HPV 16/18 by in situ hybridisation revealed the presence of HPV 16/18 sequences in 67.3% of the dysplasia subjects progressed to carcinoma in situ while 27.3% of precancerous cases regressed to normalcy. The difference was found to be statistically significant (P less than 0.001).
Adult↗
Polymorphonuclear leucocytes as potential source of free radicals in the ischaemic-reperfused myocardium.
The feasibility of polymorphonuclear leucocytes as a potential source of free radicals during reperfusion of ischaemic myocardium was evaluated. Isolated rat heart was perfused in the presence of f-Met-Leu-Phe-activated and normal polymorphonuclear leucocytes for 30 min. To judge the degree of cellular injury which might result from activated polymorphonuclear leucocytes during perfusion, isolated hearts were also perfused with superoxide anions, hydroxyl radicals, and hypochlorous acid-generating systems in the absence or presence of their corresponding scavengers, superoxide dismutase plus catalase, dimethylthiourea, and allopurinol, respectively. Activated polymorphonuclear leucocytes stimulated the release of lactate dehydrogenase, a biological marker of cellular injury, and malondialdehyde, a presumptive marker for lipid peroxidation; increased tissue injury, as evidenced by morphologic examinations using light and electron microscopy; decreased dry/wet ratios of heart, signifying oedema formation; and reduced myocardial adenosine triphosphate and creatine phosphate content as well as coronary flow, indicating decreased myocardial performance. These biological, physiological, and morphologic parameters were reversed significantly, but not completely, by treating the heart with scavengers, superoxide dismutase plus catalase or allopurinol, but were reversed completely by simultaneous treatment with superoxide dismutase, catalase, and allopurinol. Comparable results were obtained when the hearts were treated with each of these free radical-generating systems and their corresponding scavengers. Generation of free radicals was confirmed either by cytochrome c reduction or by examining the chemiluminescence response using a luminometer. These results indicate that activated polymorphonuclear leucocytes can cause myocardial cellular injury equivalent to the damage caused by free radicals and oxidants which are present in an ischaemic-reperfused heart, suggesting that polymorphonuclear leucocytes may be a potential source of free radicals in the reperfused heart.
Animals↗
Prevention of myocardial reperfusion injury in experimental coronary revascularization following ischemic arrest by a novel antiinflammatory drug, ONO-3144.
The cardioprotective effects of a novel antiinflammatory drug, ONO-3144 (ONO), on ischemic-reperfused myocardium were investigated using an in situ pig heart model. Heart was subjected to 2 h of regional ischemia, with the final 1 h having superimposed global cardioplegic arrest followed by 1 h of reperfusion. ONO (20 microM) was administered after the arrest at the onset of reperfusion. Left ventricular developed pressure (LVDP), maximum rate of rise of left ventricular pressure (LV dp/dt), and left ventricular end-diastolic pressure (LVEDP) were measured under isovolumic conditions to assess cardiac contractility and compliance. ONO improved LVDP and LV dp/dt, and reduced LVEDP after 60 min of reperfusion compared to control. This drug also improved segment shortening and end-diastolic length significantly after 15 and 60 min of reperfusion. Slight improvements in oxygen consumption and creatine kinase (CK) release were also noted. In addition, ONO reduced lipid peroxidation and thromboxane formation but enhanced the production of prostaglandins. In vitro studied demonstrated ONO to be effective scavengers for both hydroxyl (OH.) and hypohalite (OCL.) radicals. The results suggest that myocardial reperfusion injury that developed after ischemic arrest was reduced significantly by ONO. This drug inhibited such injury, probably by directly scavenging potentially harmful radicals such as OH. and OCI., which are generated in ischemic-reperfused myocardium.
Animals↗
Role of iron on membrane phospholipid breakdown in ischemic-reperfused rat heart.
Oxygen-derived free radicals have been implicated in causing degradation of myocardial membrane phospholipids associated with ischemia and reperfusion. Since iron is known to catalyze the hydroxyl radical formation responsible for cellular injury, this study was designed to relate the role of iron with phospholipid breakdown in ischemic-reperfused heart. Isolated rat heart perfused by the Langendorff technique was subjected to 30 min of normothermic ischemia followed by 30 min of reperfusion. The experimental group received 0.6 mM deferoxamine, an iron chelator, before reperfusion of ischemic myocardium. Deacylation and reacylation of membrane phospholipids were monitored by using [14C]arachidonic acid (AA), whereas the de novo phospholipid synthesis was evaluated by using [3H]glycerol in the perfusate. In the deferoxamine group, the loss of [14C]phosphatidylcholine (PC) and the corresponding accumulation of isotopic lysophosphoglycerides as well as AA was significantly lower compared with the control. The incorporation of radioactivity for [14C]AA and [3H]glycerol into phospholipids was significantly increased in the treated group compared with the untreated group. In addition, decreased malonaldehyde formation and lactate dehydrogenase release, a higher recovery of high-energy phosphate compounds, and myocardial contractility were noticed in the deferoxamine-treated hearts. These results indicated that postischemic administration of an iron chelator such as deferoxamine can preserve membrane phospholipids and reduce myocardial dysfunction associated with reperfusion of ischemic heart.
Acylation↗
Protective role of intracoronary fatty acid binding protein in ischemic and reperfused myocardium.
In this study, fatty acid binding protein was used to protect an ischemic heart from reperfusion injury. Isolated rat heart was preperfused in the presence of 1.4 microM liposome-bound fatty acid binding protein for 15 minutes, followed by 30 minutes of ischemia and 30 minutes of reperfusion. Our results indicated better preservation of myocardial high-energy phosphate compounds (including ATP and creatine phosphate), reduced creatine kinase and lactate dehydrogenase release from the heart, and improved coronary flow in hearts treated with fatty acid binding protein compared with untreated controls. Fatty acid binding protein enhanced reacylation of arachidonic acid into phospholipids, thereby preserving membrane phospholipids and reducing free fatty acid contents during ischemia and reperfusion. In addition, fatty acid binding protein-bound long-chain free fatty acids and their thioesters as well as carnitine esters were increased in the cytosolic compartment of the heart. These results suggest that fatty acid binding protein may be used as a possible therapeutic agent to improve myocardial function during reperfusion of ischemic heart.
Animals↗
Microphotometric DNA analysis in moderate dysplasia of the uterine cervix. Correlation to the progression and regression of the lesion.
Nuclear DNA content was determined by microphotometry in 27 cases of moderate dysplasia of the uterine cervix. All these cases were followed from one to ten years to study the biological behavior of moderate dysplasia in relation to cervical carcinogenesis. Ten of them showed progression to carcinoma in situ during a period of one to six years (median 34.8 months) and 17 cases showed regression to inflammation and normalcy during a period of one to ten years (median 44.2 months). DNA analysis was performed both on initial cervical smear and on representative smears collected during follow-up. Amongst ten cases which progressed to malignancy, nine had aneuploid DNA pattern and one had polyploid DNA pattern throughout the follow-up period. Amongst 17 cases which regressed to inflammation, 11 had euploid and six polyploid DNA pattern. The observation that moderate dysplasia with aneuploid DNA value often develops into carcinoma in situ in contrast to dysplasia with euploid or polyploid DNA value strengthens the conception that DNA aneuploidy may be considered as 'high risk indicator' for cervical precancerous lesions.
Adult↗
Burkitt's type lymphoma as a jaw tumour in old age: diagnosed by fine needle aspiration cytology.
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Biopsy, Needle↗
Tuberculous lymphadenitis: correlation of cellular components and necrosis in lymph-node aspirate with A.F.B. positivity and bacillary count.
Cytomorphologic features of tuberculous lymphadenitis cases as observed in lymph-node aspirates were analysed and correlated with AFB positivity and bacillary count. Cytologic features were categorized under three major groups, viz. epithelioid granuloma without necrosis, epithelioid granuloma with necrosis and necrosis without epithelioid granulomas. These three major groups showed a distinct trend in respect of their cellular constituents. While cases with appreciable lymphocytic and multinucleated giant cells component showed a significant decreasing trend, cases with neutrophilic infiltration showed an increasing trend (P less than 0.001). In the above three groups, 9.1 percent, 64.7 percent and 77.4 percent respectively showed AFB positivity, the difference being highly significant (P less than 0.001). All 14 cases with very high bacillary count (greater than 50 bacilli per 500 oil immersion field) were associated with necrosis and 71.4% of them neutrophilic infiltration. A univariate analysis revealed that in presence of lymphocytes, epithelioid cells and Langhan's giant cells, AFB positivity was significantly lower while the picture was just the reverse in presence of necrosis and neutrophilic infiltration (P less than 0.001). The odd's rations for all these variables were highly significant (P less than 0.001). However, a multivariate regression analysis revealed that necrosis was the only independent contributing factor towards AFB positivity.
Adolescent↗
The effects of an iron chelator on cellular injury induced by vascular stasis caused by hypothermia.
Rewarming of a cooled rabbit leg was associated with the generation of oxygen-derived free radicals, shown to be instrumental for tissue injury occurring during rewarming. The present study used a compound that, by its ability to bind with free iron, can remove hydroxyl radical (OH.) from tissue. Deferoxamine reduced tissue injury during cooling and rewarming, as evidenced by its ability to decrease tissue release of lactic acid dehydrogenase and creatine kinase. Deferoxamine also reduced the formation of OH. and lipid peroxidation during the rewarming phase. This compound did not have any effect on the arterial blood flow pattern, which uniformly decreased during cooling and was restored during rewarming. The results of this study indicate the efficacy of deferoxamine in reducing cellular injury associated with cold and rewarming and further suggest a role for oxygen-derived free radicals in the pathophysiology of cold-rewarming injury.
Animals↗
Microphotometric nuclear DNA analysis in cervical dysplasia of the uterine cervix: its relation to the progression to malignancy and regression to normalcy.
The present study was attempted to reveal the predictive value of DNA ploidy pattern of uterine cervical dysplasia cases in relation to cervical carcinogenesis. Microphotometric nuclear DNA analysis using Feulgen stain was carried out in 310 cervical smears of 80 dysplasia cases consisting of 53 cases which progressed to malignancy and 27 cases which regressed to inflammation or normalcy during their follow-up periods. Aneuploid DNA pattern was observed in initial as well as follow-up smears in 69.8% of cases of the progressive group, and in 7.4% of cases of the regressive group. This difference is statistically highly significant (chi 2 27.88, p less than 0.001). In the progressive group, an aneuploid DNA value was observed in 40.0% of mild dysplasia, 71.9% of moderate dysplasia and 90.9% of severe dysplasia. In the regressive group, DNA aneuploidy was observed in only 9.1% of moderate dysplasia. This difference is statistically significant. These findings indicate that an aneuploid DNA value is a risk indicator for malignant potential of dysplasia cases.
Adult↗
Nervous system involvement in Burkitt's lymphoma.
A patient with Burkitt's lymphoma who had nervous system involvement at multiple levels is presented because of the rarity of this condition in India. A high index of suspicion and a rapidly evolving multiple neuraxial involvement led to the diagnosis.
Adult↗