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Biomedical subjects

M R Ray

Publications and source records attributed to M R Ray.

At least 19 recordsLinked to original sources

Lycopene.

Oxidative stress is now recognized as an important etiological factor in the causation of several chronic diseases including cancer, cardiovascular diseases, osteoporosis, and diabetes. Antioxidants play an important role in mitigating the damaging effects of oxidative stress on cells. Lycopene, a carotenoid antioxidant, has received considerable scientific interest in recent years. Epidemiological, tissue culture, and animal studies provide convincing evidence supporting the role of lycopene in the prevention of chronic diseases. Human intervention studies are now being conducted to validate epidemiological observations and to understand the mechanisms of action of lycopene in disease prevention. To obtain a better understanding of the role of lycopene in human health, this chapter reviews the most recent information pertaining to its chemistry, bioavailability, metabolism, role in the prevention of prostate cancer and cancer of other target organs, its role in cardiovascular diseases, osteoporosis, hypertension, and male infertility. A discussion of the most relevant molecular markers of cancer is also included as a guide to future researchers in this area. The chapter concludes by reviewing global intake levels of lycopene, suggested levels of intake, and future research directions.

Animals↗

Platelet activation, upregulation of CD11b/ CD18 expression on leukocytes and increase in circulating leukocyte-platelet aggregates in Indian women chronically exposed to biomass smoke.

The majority of households in rural India still rely on unprocessed solid biomass for domestic energy. The aim of this study was to investigate whether chronic exposure to biomass smoke causes activation of leukocytes and the formation of leukocyte-platelet aggregates. We conducted flow cytometric analysis of beta2 Mac-1 integrin (CD11b/CD18) expression on polymorphonuclear leukocytes (PMN) and monocytes, and P-selectin (CD62P) expression on the platelets of 165 women from eastern India, who cook solely with wood, dung and agricultural wastes, and 155 age- and socio-economic condition-matched control subjects, who used relatively cleaner fuel, liquefied petroleum gas (LPG). Leukocyte-platelet aggregates were defined as CD11b-positive PMN and monocytes co-expressing platelet-specific markers CD41 or CD62P. A significant increase in leukocyte-platelet aggregates was found in women who used biomass as cooking fuel. In addition, they showed increased surface expression of CD11b/CD18 in circulating PMN and monocytes and CD62P expression on platelets. The mean fluorescence intensity (MFI) of CD11b on the surface of circulating monocytes and PMN of biomass users increased by 50 and 68%, respectively. Similarly, a 62 and 48% increase in MFI was observed in CD18 expression on the surface of these cells in biomass users. The results show that chronic biomass smoke exposure activates circulating platelets, PMN and monocytes, and increases the number of leukocyte-platelet aggregates, which are considered a risk factor for thrombosis.

Adult↗

Reduction of hematotoxicity and augmentation of antitumor efficacy of cyclophosphamide by dopamine.

Modulatory effects of dopamine (DA) on hematotoxicity and antitumor efficacy of cyclophosphamide (CY) were studied in Swiss mice bearing transplantable Ehrlich ascites carcinoma (EAC). DA was administered i.p. at a dose of 50 mg/kg/day for 5 consecutive days beginning day 3 after tumor transplantation. CY (200 mg/kg i.p.) was injected 24 hour after completion of DA treatment. DA pretreatment reduced the suppressive effects of CY on hemoglobin, RBC, total WBC, neutrophil, platelet, and bone marrow nucleated cell counts. Likewise, DA partially prevented the CY-induced fall in pluripotent (CFU-S12) and lineage-specific stem cells for granulocytes (CFU-C) in bone marrow. Moreover, mice receiving a combination of DA and CY illustrated greater reduction in tumor volume, viable tumor cell count and mitotic index along with upregulation of tumor cell apoptosis than CY-only group. As a result, the former group demonstrated prolonged hosts survival. Thus, DA protected to a great extent the hematopoietic cells of tumor bearing hosts from the suppressive action of CY and concomitantly augmented its antitumor efficacy resulting in improved hosts survival.

Animals↗

Decrease in platelet serotonin level in uterine cervix cancer patients.

Platelet serotonin (5-HT) concentration was measured by HPLC with electrochemical detection in 46 women suffering from cancer of the uterine cervix and 16 matched controls. About 53% reduction (p < 0.05) was recorded in platelet 5-HT level in cancer patients against a control value of 1.29 +/- 0.16 (mean +/- S.E.) nmol per 10(9) platelets. Depletion of intraplatelet 5-HT was positively correlated with clinical stage of the disease although a modest rise (p > 0.05) in platelet 5-HT was observed in patients at stage I. Serotonin release from platelets following activation with thrombin was considerably increased in cancer patients (38.2% compared to 17.4% in controls). The results demonstrate progressive depletion of intraplatelet 5-HT in cervical cancer patients. In addition, their platelets release more 5-HT than the controls upon activation by thrombin.

Biomarkers, Tumor↗

Air pollution in Calcutta elicits adverse pulmonary reaction in children.

BACKGROUND & OBJECTIVE: Pulmonary responses of children chronically exposed to ambient air pollution in Calcutta have been investigated. METHODS: A total number of 153 children from Calcutta and 116 from rural West Bengal in the age group of 6-17 yr were included in this study. Respiratory symptom complex, sputum cytology and micronucleus (MN) count of buccal epithelial cells were evaluated. Blood smears were examined for WBC differential count and RBC morphology. RESULTS: Marked rise in respiratory symptoms (43% in urban vs 14% in rural) and sputum alveolar macrophage (AM) number was observed in urban children compared to their rural counterparts (14.2 +/- 1.4 AM/hpf vs 6.7 +/- 1.4 AM/hpf, mean +/- SE, P < 0.001). The urban group also demonstrated increased numbers of neutrophils, eosinophils and iron-laden AM in their sputum. Besides, buccal epithelial cells of urban children exhibited higher MN frequency than their rural counterparts (0.22 vs 0.17%, P < 0.05). While sputum neutrophilia and eosinophilia suggest inflammatory and allergic lung reactions, elevated MN count is indicative of greater genotoxic effect on the exposed tissues of urban children. Hypochromic red cells in peripheral blood smear was a common finding in both urban and rural groups, but eosinophils and monocytes were present in elevated frequencies in the rural children. INTERPRETATION & CONCLUSION: The study demonstrated that children inhaling grossly polluted air of Calcutta suffer from adverse lung reactions and genetic abnormality in the exposed tissues.

Adolescent↗

Stimulation of megakaryocytopoiesis and platelet production during growth of an experimental lymphoma.

The effect of malignant tumor growth on host's megakaryocytopoiesis and platelet production was studied in mice bearing transplantable Dalton's lymphoma. Tumor growth was paralleled by thrombocytosis, neutrophilia, and anemia. Platelet 51Cr half-life was normal but incorporation of 75Selenomethionine into circulating platelets was significantly enhanced in the tumor bearers suggesting stimulated thrombopoiesis while platelet life span remained unchanged. Megakaryocytes and their precursors, the small acetyl cholinesterase positive cells, were found in increased numbers in the bone marrow (BM) and particularly in the spleen where five to eight-fold rise was observed at the log phase of tumor growth. In addition, a remarkable increase in the number of megakaryocyte progenitors (CFU-MK and MK CFU-S) was observed both in the BM and spleen. Stimulation of these progenitors was more pronounced in the spleen than in the marrow, and the change was noticeable even from the third day of tumor bearing. Therefore, the results suggest that thrombocytosis associated with the growth of this experimental lymphoma was due to accelerated platelet production following stimulated megakaryocytopoiesis especially in the spleen.

Acetylcholinesterase↗

Inhibition of experimental murine tumors by MT81, a new mycotoxin from Penicillium nigricans.

Effects of a new mycotoxin MT81 obtained from the fungal strain Penicillium nigricans on the growth of two transplantable murine tumors and the life span of the hosts were studied. Remarkable decrease in tumor volume and viable tumor cell count was found in both the tumors. Antitumor effect of the compound was more pronounced in Sarcoma 180 (S180) than in Ehrlich ascites carcinoma (EAC). The tumor-inhibitory effect was also manifested by the reduction in mitotic activity and appearance of membrane blebbing and intracytoplasmic vacuoles in the treated tumor cells. MT81 treatment prolonged the life span of the EAC tumor host by 78% and more than 100% in S180 bearing mice. Tumor inhibition by MT81 was followed by improvements in hemoglobin, RBC values and bone marrow cellularity. Thus the results suggest that MT81 has significant antitumor property against experimental murine tumors and it does not adversely affect the hematological profile of the hosts.

Animals↗

Increase in the concentrations of brain serotonin and 5-hydroxyindoleacetic acid during growth of a transplanted murine lymphoma.

The concentrations of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were studied in discrete brain areas of mice bearing transplantable Dalton's lymphoma (DL). Marked rise in 5-HT level (p < 0.05) was observed in serotonin secreting cell rich area--raphe region--as well as in hypothalamus and caudate putamen. High 5-HT level in these discrete areas was maintained throughout the period of tumor growth. Appreciable increase in 5-HT concentration was also observed in midbrain at the late stage (day 15 post-transplantation) of tumor growth. Unlike 5-HT, there was little change in 5-HIAA levels at the early stage (day 7) of tumor growth, and this was followed by a fall in 5-HIAA level around day 10 post-transplantation. However, the concentration of this 5-HT metabolite increased considerably at the late phase of tumor proliferation. The results suggest a close relationship between serotonin level in discrete brain regions and growth of an experimental tumor in mice.

Animals↗

Alterations of brain serotonin during experimental tumor growth in mice.

Concentrations of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were studied in discrete areas of brain and in large intestine of Swiss mice following transplantation of Sarcoma 180 (S 180) ascites tumor. Significant increase in 5-HT levels (2 to 3.5-fold over controls, P < 0.05) was observed in raphe region of the brain throughout the period of tumor growth. Concomitant increase, although of lesser magnitude, was recorded in raphe 5-HIAA content. 5-HT content of hypothalamus, mid brain and caudate putamen, on the other hand, remained relatively unaltered except for an increase at the advanced stage of the disease. While mid brain and hypothalamic 5-HIAA were elevated at the late stage, 5-HIAA values of caudate putamen were normal or slightly reduced during the progression of tumor. Both 5-HT and 5-HIAA levels of the large intestine showed an early decline followed by a modest increase at the late stages. Brain and plasma tryptophan levels were also elevated significantly (P < 0.05) in the tumor hosts. The results suggest a close relationship between increase in serotonin concentrations in the brain, particularly in raphe region, and the progression of S-180 tumor in mice.

Animals↗

Tumor inhibition and hematopoietic stimulation in mice by a synthetic copper-ATP complex.

The hematologic effect of [Cu3(ATP)(2)6H2O]2-, a synthetic copper-ATP complex (Cu-ATP) having antitumor activity, was investigated in normal and Ehrlich ascites carcinoma-bearing mice. Cu-ATP (25 mg/kg) induced appreciable tumor inhibition and prolonged host survival which were accompanied by elevated levels of hemoglobin, platelet and lymphocytes while total WBC count and bone marrow cellularity remained unaffected. In normal mice the compound elicited marrow and splenic hypercellularity with a greater number of granulocyte progenitors and elevated levels of peripheral WBC, RBC and platelets. In addition, the total number of CFU-S of these treated animals was increased and these pluripotent stem cells differentiate preferentially towards granulocyte lineage. The results indicate that Cu-ATP does not adversely affect hematopoiesis while it inhibits tumor growth; on the contrary, it has a stimulatory effect on murine granulocytopoiesis.

Adenosine Triphosphate↗

Stimulation of thrombopoiesis in mice bearing experimental tumors.

Significant increase (p less than 0.05) in circulating platelet counts was observed in a wide spectrum of experimental tumors in mice. The mechanism of this abnormality was investigated in strain A mice bearing a transplantable ascites tumor, Sarcoma 180 (S 180). Thrombocytosis observed in the tumor hosts was not due to prolonged platelet surviva], as 51Cr platelet half-life was normal. On the other hand, stimulation of thrombopoiesis, expressed in terms of platelet 75Selenomethionine (75SeM) incorporation, appeared to be the primary reason for elevated platelet counts in the tumor-bearers. Evaluation of thrombopoietic activity in the femoral marrow and spleen by measuring organ uptake of 75SeM and megakaryocyte counts indicated that tumor-induced stimulation in thrombopoiesis may be attributed to enhancement in splenic activity. Pretreatment of normal mice with tumor ascites or tumor cell-conditioned medium resulted in enhancement in thrombopoiesis. The findings suggest the production of some factor(s) by the tumor cells which probably mediate the stimulation of platelet production in tumor hosts.

Animals↗

Tumor inhibition and hematological improvements by dopamine analog 3,4-dihydroxybenzylamine in mice bearing transplantable carcinoma.

The cancer chemotherapeutic efficacy of 3,4-dihydroxybenzylamine (DHBA), a dopamine analog with reduced neurotoxic effects, was evaluated in strain A mice bearing transplantable Ehrlich's ascites carcinoma. The analog was administered intraperitoneally on day 1 post-transplantation at dose schedules of 50, 100 and 200 mg/kg/day for 7 consecutive days. The results demonstrated a significant inhibition of tumor growth and prolongation of the survival time of EAC tumor bearing mice following DHBA treatment. Diminished activity of the growth-related respiratory enzyme succinate dehydrogenase along with the stimulated activity of the lysosomal enzyme beta-glucuronidase in the DHBA-treated tumor cells indicated inhibition of tumor growth as well as active lysis of the tumor cells. Tumor inhibition was accompanied by marked improvements in hemoglobin concentration. RBC count and bone marrow cellularity. The results demonstrated that DHBA did not adversely affect hematological profile of the host while it inhibited the growth of Ehrlich's ascites carcinoma.

Animals↗

Osmotic fragility, sialic acid content and survival of circulating erythrocytes in anemic tumor-bearing mice.

Effect of tumor growth on the survival of circulating erythrocytes was studied in mice bearing a wide spectrum of experimental tumors. RBC half-life (t1/2), measured by 51Cr-labeling technique, decreased significantly (p less than 0.05) in all the tumor types studied, particularly in transplantable Sarcoma-180 and benzo(a)pyrene-induced primary fibrosarcoma. Changes in erythrocyte morphology like anisopoikilocytosis were also observed in the tumor hosts. Cross-transfusion of 51Cr-labeled RBCs between normal and tumor-bearing animals revealed that both intrinsic and extrinsic factors are responsible for shortened RBC survival. As far as the cellular abnormalities are concerned, the decrease in RBC t1/2 was not attributable to increased osmotic fragility as the cells were observed to be osmotically more resistant. Similarly, membrane sialic acid content was markedly elevated in the tumor hosts, thus the shortened erythrocyte life-span cannot be attributed to decrease in sialic acid content of the erythrocyte membrane.

Anemia↗

Colony-forming ability of pluripotent hematopoietic stem cells in mice following tumor transplantation.

The mechanism of tumor-induced hematological alterations at the level of pluripotent hematopoietic stem cells (CFU-S) was investigated in mice bearing transplantable ascites tumor, Sarcoma 180. Tumor growth for 10 days caused neutrophilic leukocytosis and decline in hemoglobin and RBC values in the peripheral blood, and significant reduction (p less than 0.05) in the concentration as well as absolute number of CFU-S in the femoral marrow but an increment in the spleen. Intraperitoneal administration of cell-free ascitic fluid caused similar alterations of CFU-S in normal mice, but heat-killed tumor cells failed to elicit such response. Tumor cell-conditioned medium when injected into normal mice caused CFU-S alterations in a pattern similar to that of tumor-bearing animals. It is concluded that alterations of CFU-S following tumor transplantation is attributable to tumor growth rather than the presence of dead or necrotic cells in the tumor inoculum. It is likely that tumor cells elaborate some factor(s) which mediate such changes.

Animals↗

Alterations in the number of large granular lymphocytes in patients with carcinoma of the breast and uterine cervix prior to and after radiotherapy.

The relative as well as absolute number of large granular lymphocytes (LGL) in the peripheral blood of patients with carcinomas of the breast and cervix uteri were significantly (p less than 0.05) declined compared to the healthy controls. The reduction in LGL was more pronounced in patients with far advanced carcinoma. Clinical remission following radiotherapy is associated with mild increase in the number of LGL in the blood of both groups of cancer patients.

Adult↗

Erythropoiesis in mice with chemically-induced tumor.

The erythropoietic response of Strain A mice with benzo(a)pyrene-induced fibrosarcoma has been studied. The rate of erythropoiesis, expressed in terms of 59Fe incorporation into circulating erythrocytes, was slightly increased in the fibrosarcomatous mice compared to the matched controls. The femoral marrow of the tumor hosts became hypocellular with reduced number of erythroblasts. The spleen, on the other hand, was hypercellular with an increased number of erythroid progenitor cells. Quantitative assessment of erythropoietic activity in the hematopoietic organs by measuring the 6-hr organ uptake of 59Fe revealed erythropoietic suppression in the marrow but enhancement in the spleen following tumor development. While the number of CFU-s in the femoral marrow of the tumor-bearing animals was slightly increased, marked increase in the concentration as well as absolute number of CFU-s was found in the spleen. Bioassay for erythropoietin revealed appreciable increase in the level of plasma erythropoietin in the tumor-bearing animals.

Animals↗

Erythropoietic alterations in mice bearing a transplantable lymphoma.

Tumor-induced changes in the pattern of erythropoiesis have been studied in A/RB mice bearing a transplantable ascites tumor, DBA lymphoma. The tumor growth was accompanied by diminished erythropoiesis, and the 51Cr-labeled red cell half-life was also decreased. Plasma iron turnover rate of the tumor bearing hosts, however, was increased and the level of erythropoietic stimulating factor (erythropoietin) in the plasma was not reduced. The existence of an inhibitor(s) to erythropoietic activity was unlikely. Comparative study of the erythropoietic activity revealed suppression in the marrow, but an increment in the spleen. The distribution of pluripotent hematopoietic stem cells (CFUs) also paralleled this alteration. However, the degree of ineffective erythropoiesis, determined by in vitro technique, was significantly elevated in the spleen. Possibly, this has reduced the effectiveness of splenic compensatory erythropoiesis.

Animals↗