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Biomedical subjects

S Basu

Publications and source records attributed to S Basu.

At least 109 records · Page 6Linked to original sources

Propofol (Diprivan-EDTA) counteracts oxidative injury and deterioration of the arterial oxygen tension during experimental septic shock.

PURPOSE: Human septic shock can be replicated in the endotoxaemic pig. Endotoxaemia causes a multitude of events, including reduced PaO(2) and increased lipid peroxidation. This study was designed to evaluate the possible effects of a commonly used anaesthetic drug with known antioxidant properties (propofol) during porcine endotoxaemia. METHODS: Ten pigs were anaesthetised and given a 6 h E. coli endotoxin infusion. The animals received, randomly, a supplementary continuous infusion of propofol emulsion (containing 0.005% EDTA) or the corresponding volume of vehicle (controls). Pathophysiologic responses were determined. Non-enzymatic (by measuring plasma 8-iso-PGF(2 alpha) and enzymatic (by measuring plasma 15-keto-dihydro-PGF(2 alpha)) lipid peroxidations were evaluated. Plasma levels of the endogenous antioxidants alpha- and gamma-tocopherols, were also analysed. RESULTS: Endotoxaemia increased plasma levels of 8-iso-PGF(2 alpha) (1st-4th h) and 15-keto-dihydro-PGF(2 alpha) (1st-4th h) significantly more in controls than in the propofol+endotoxin group. PaO(2) was significantly less affected by endotoxin in the propofol treated animals (2nd-4th h). Mean arterial pressure (4th-6th h) and systemic vascular resistance (6th h) were reduced significantly more by endotoxin among the propofol-treated animals. Vitamin E (alpha-tocopherol) increased in all animals, significantly more in the propofol+endotoxin group (1/2-6th h) than in the control group. CONCLUSIONS: Propofol reduced endotoxin-induced free radical mediated and cyclooxygenase catalysed lipid peroxidation significantly. The implication is that propofol counteracts endotoxin-induced deterioration of PaO(2).

Anesthetics, Intravenous↗

CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin.

Complexes of the heat shock protein gp96 and antigenic peptides are taken up by antigen-presenting cells and presented by MHC class I molecules. In order to explain the unusual efficiency of this process, the uptake of gp96 had been postulated to occur through a receptor, identified recently as CD91. We show here that complexes of peptides with heat shock proteins hsp90, calreticulin, and hsp70 are also taken up by macrophages and dendritic cells and re-presented by MHC class I molecules. All heat shock proteins utilize the CD91 receptor, even though some of the proteins have no homology with each other. Postuptake processing of gp96-chaperoned peptides requires proteasomes and the transporters associated with antigen processing, utilizing the classical endogenous antigen presentation pathway.

Animals↗

Magnetic field effect on the exciplex between all-s-trans- 1,4-diphenylbuta- 1,3-diene and 1,4-dicyanobenzene: a comparative study with other alpha,omega-diphenyl polyenes.

The exciplex between all-s-trans-1,4-diphenylbuta-1,3-diene and 1,4-dicyanobenzene has been studied by steady state fluorescence along with the magnetic field effect (MFE) and compared with the other alpha,omega-diphenyl polyenes. The exciplex formation and magnetic field effect are dictated by the chain length of the polyene rather than the electronic requirement of these phenomena. The wavelength dependence of the MFE confirms the presence of two different charge-transfer complexes.

Butadienes↗

Circulating dopamine level, in lung carcinoma patients, inhibits proliferation and cytotoxicity of CD4+ and CD8+ T cells by D1 dopamine receptors: an in vitro analysis.

Besides cardiovascular and renal functions, the role of dopamine in periphery as an endogenous regulator of immune functions is in the limelight. In human malignancy, depression of T cell functions is known. Interestingly, recent evidences indicate significant elevation of plasma dopamine in malignancy due to stress of the disease process. Therefore, this study evaluates whether this increased plasma dopamine exerts any influence on the proliferation and cytotoxicity of CD4+ and CD8+ T cells. Patients with lung carcinoma were selected for this study due to the high prevalence rate of this kind of cancer in developing countries and also due to strong positive biochemical and psychological criteria of stress in most of the patients. Results showed significant elevation of plasma dopamine (48.6 +/- 5.1 pg/ml) in lung cancer patients than normal controls (10.2 +/- 0.9 pg/ml). In vitro dopamine concentration, simulating the plasma concentration of the patients, significantly inhibited the proliferation and cytotoxicity of T cells of these patients and also of the normal volunteers, in presence of their respective serum. The mechanism has been attributed to be D1 class of dopamine receptor mediated elevation of intracellular cAMP in these cell populations. The results may be of significance in understanding the role of peripheral dopamine as an immunomodulator in human health and diseases.

Adult↗

The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor.

Angiogenesis has an essential role in many important pathological and physiological settings. It has been shown that vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), a potent cytokine expressed by most malignant tumors, has critical roles in vasculogenesis and both physiological and pathological angiogenesis. We report here that at non-toxic levels, the neurotransmitter dopamine strongly and selectively inhibited the vascular permeabilizing and angiogenic activities of VPF/VEGF. Dopamine acted through D2 dopamine receptors to induce endocytosis of VEGF receptor 2, which is critical for promoting angiogenesis, thereby preventing VPF/VEGF binding, receptor phosphorylation and subsequent signaling steps. The action of dopamine was specific for VPF/VEGF and did not affect other mediators of microvascular permeability or endothelial-cell proliferation or migration. These results reveal a new link between the nervous system and angiogenesis and indicate that dopamine and other D2 receptors, already in clinical use for other purposes, might have value in anti-angiogenesis therapy.

Animals↗

A diet containing rapeseed oil-based fats does not increase lipid peroxidation in humans when compared to a diet rich in saturated fatty acids.

OBJECTIVE: To compare the effects of a rapeseed oil-based diet containing an increased proportion of easily oxidised polyunsaturated fatty acids such as alpha-linolenic acid with a diet rich in saturated fatty acids on the degree of lipid peroxidation in the human body. DESIGN: A randomised cross-over study. SUBJECTS AND INTERVENTIONS: Nineteen healthy moderately hyperlipidemic subjects (six women and 13 men, age 50+/-8 y and body mass index (BMI) 24.5+/-2.6 kg/m(2)) were given a rapeseed oil-based diet (RO) and a control diet (SAT) rich in saturated fatty acids during two consecutive 4 week periods separated by a 4 week wash-out period. Biomarkers of lipid peroxidation and antioxidants were analysed in plasma and urine. RESULTS: No significant differences in plasma or urinary levels of free 8-iso-prostaglandin F(2alpha), plasma total 8-iso-prostaglandin F(2alpha) plasma hydroperoxides or plasma malondialdehyde were observed between the RO and SAT diets (P=0.14-0.95). A higher concentration of serum gamma-tocopherol was detected after the RO diet compared to the SAT diet (P<0.001), whereas the serum alpha-tocopherol concentration and plasma antioxidative capacity did not differ between the two test diets. The total cholesterol, LDL cholesterol and LDL/HDL ratio were lower after the RO diet compared to the SAT diet (P<0.001), while HDL cholesterol and total triglyceride levels were similar after the two diets. CONCLUSION: These results suggest that a rapeseed oil-based diet rich in alpha-linolenic acid does not seem to increase the degree of lipid peroxidation in plasma and urine compared to a diet rich in saturated fats. This is possibly due to a sufficient content of antioxidants in the rapeseed oil diet to increase circulating concentrations of antioxidants that may protect unsaturated fatty acids from oxidation. SPONSORSHIP: Swedish Council for Forestry and Agricultural Research and Foundation for Geriatric Research.

Antioxidants↗

Interaction of cytokines and growth factor in the regulation of verotoxin-induced apoptosis in cultured human endothelial cells.

The role of CD77, inflammatory cytokines and endothelial cell growth factor (ECGF) in verotoxin (VT)-induced apoptosis in human umbilical vein endothelial cells (HUVECs) was studied. Apoptosis was detected using annexin V and propidium iodide staining. The expression of CD77 antigen was measured on a FACStar flow cytometer using specific monoclonal antibodies. Our experiments showed that HUVECs had very low initial levels of CD77 and were resistant to VT. Treatment with tumour necrosis factor alpha (TNF-alpha) resulted in a significant upregulation of CD77 expression and sensitized endothelial cells to VT-mediated apoptosis. HUVECs incubated with a combination of cytokines [TNF-alpha and interferon gamma (IFN-gamma), both 500 U/ml] showed more pronounced upregulation of CD77 expression (> sixfold at 48 h) and underwent apoptosis, suggesting that TNF-alpha and IFN-gamma have a synergistic effect on CD77 expression in HUVECs and can induce apoptosis without VT. Cells pretreated with TNF-alpha and IFN-gamma and incubated with VT showed the most pronounced (14-fold) increase in CD77 expression. ECGF had a partial protective effect against cytokine- and VT-induced apoptosis. Taken together, our data suggest that CD77 antigen is involved in the regulation of endothelial cell apoptosis.

Apoptosis↗

F(2)-isoprostane and prostaglandin F(2 alpha)metabolite excretion rate and day to day variation in healthy humans.

Isoprostanes are mainly formed in vivo by a non-enzymatic free radical catalysed oxidation of arachidonic acid. Studies have indicated that a major isoprostane, 8-iso-PGF(2 alpha)in plasma and urine is a reliable biomarker of oxidative stress. Prostaglandins are formed by enzymatic oxidation of arachidonic acid catalysed by cyclooxygenase (COX). 15-Keto-dihydro-PGF(2 alpha), a major metabolite of prostaglandin F(2 alpha)in plasma, and also found in urine, is considered to be a useful biomarker of inflammation. To investigate the excretion pattern and day to day variation of 8-iso-PGF(2 alpha)and 15-keto-dihydro-PGF(2 alpha)in healthy individuals, morning urine samples were collected from 13 volunteers on 10 successive days. The samples were analysed for free 8-iso-PGF(2 alpha)and 15-keto-dihydro-PGF(2 alpha)by radioimmunoassay. The mean excretion rate of 8-iso-PGF(2 alpha)was 0.27+/-0.11 nmol/mmol creatinine (mean+/-SD, n=13) and the coefficient of variation was 42% during the 10 days. The mean excretion rate of 15-keto-dihydro-PGF(2 alpha)was 0.46+/-0.19 nmol/mmol creatinine, giving a coefficient of variation of 41%. The mean values of 8-iso-PGF(2 alpha)were significantly correlated with the mean values of 15-keto-dihydro-PGF(2 alpha)(r=0.68, P=0.01). In conclusion, day to day biological variation in urinary excretion rate of 8-iso-PGF(2 alpha)and 15-keto-dihydro-PGF(2 alpha)should be taken into account in evaluating a clinical study unless a large increase or decrease of these parameters has been obtained.

Adult↗

Unilateral proptosis with thyrotoxicosis resulting from solitary retroorbital soft tissue metastasis from follicular carcinoma thyroid.

Unilateral proptosis can be of neoplastic origin, even if the results of thyroid function tests suggest hyperthyroid disease, and it needs proper investigation with a computed tomographic scan of the orbit. The authors present a case of left-sided proptosis resulting from a metastasis in the retroorbital soft tissue from follicular carcinoma of the thyroid. A nodular goiter involving the left lobe and isthmus was found. The initial thyroid function test values suggested hyperthyroid disease and the patient had clinical signs of toxicity. A computed tomographic scan of the orbit revealed a left-sided retroorbital soft tissue mass, part of which was resected and found be to a metastasis from follicular carcinoma of thyroid. Total thyroidectomy was performed and the patient was treated with I-131 after operation. The proptosis resolved with I-131 treatment.

Carcinoma, Papillary, Follicular↗

Raised levels of F(2)-isoprostanes and prostaglandin F(2alpha) in different rheumatic diseases.

OBJECTIVE: To evaluate oxidative injury and inflammatory status in various rheumatic diseases by measuring the levels of isoprostanes and prostaglandins in serum and synovial fluid. METHODS: The concentrations of 8-iso-PGF(2alpha) (F(2)-isoprostane indicating oxidative injury) and 15-keto-dihydro-PGF(2alpha) (a major metabolite of prostaglandin F(2alpha)) were measured in both serum and synovial fluid aspirated from 26 patients with various arthritic diseases, including rheumatoid arthritis (RA), reactive arthritis (ReA), psoriatic arthritis (PsA), and osteoarthritis (OA). These prostaglandin derivatives were also measured in serum samples collected from 42 healthy control subjects. RESULTS: Overall, serum levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) were much higher in patients with arthritic diseases than in the healthy control subjects. The levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) in synovial fluid aspirated from knee joints were also high and varied among various types of arthritic patients. Although the synovial fluid level of these prostaglandin derivatives was sometimes higher than in the corresponding serum sample, this was not a consistent finding. Overall, there was no correlation between serum and synovial fluid levels of 8-iso-PGF(2alpha), or between serum and synovial fluid levels of 15-keto-dihydro-PGF(2alpha). However, a strong relation was found between the levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha,) in both serum (r(s)=0.53, p<0.001) and synovial fluid (r(s)=0.62, p<0.001). CONCLUSIONS: These data suggest that both free radical mediated oxidative injury and cyclo-oxygenase dependent inflammatory responses are closely correlated in various types of arthritis.

Adult↗

A prospective comparison of echocardiographic wall motion score index and radionuclide ejection fraction in predicting outcome following acute myocardial infarction.

OBJECTIVE: To characterise echocardiographic wall motion score index (WMSI) as a surrogate measure of left ventricular ejection fraction (EF) following acute myocardial infarction (AMI) and to compare its prognostic value with that of EF measured by radionuclide ventriculography (RNV). DESIGN: A prospective study to compare baseline echocardiographic WMSI with RNV EF in consecutive patients thrombolysed for AMI, both performed on the same day before discharge, and their relative prognostic values in predicting cardiac events. SETTING: District general hospital coronary care unit and cardiology department. PATIENTS: 120 consecutive patients free of exclusion criteria thrombolysed for AMI and followed up for a mean (SD) of 13 (10) months. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Correlation coefficients and receiver operating characteristic curve analyses plus cardiac event rates at follow up between RNV EF and echocardiographic WMSI. RESULTS: WMSI correlated well with RNV EF. The best corresponding WMSIs for EFs 45%, 40%, and 35% were 0.6, 0.8, and 1.1, respectively. There were 42 cardiac events during follow up. Although both RNV EF and WMSI were strong univariate predictors of cardiac events, only WMSI independently predicted outcome in a multivariate model. All three WMSI cut offs significantly predicted events, while an RNV EF cut off of </= 45% v > 45% failed to reach significance. CONCLUSIONS: Although both RNV and echocardiographic WMSI strongly predicted cardiac outcome, WMSI, a cheaper and more readily available technique, is more discriminatory, especially in cases of mild left ventricular dysfunction following AMI.

Adult↗

Physiological concentrations of dopamine inhibit the proliferation and cytotoxicity of human CD4+ and CD8+ T cells in vitro: a receptor-mediated mechanism.

OBJECTIVE: Dopamine, a catecholamine neurotransmitter, influences growth and proliferation of lymphocytes. Pharmacological doses of dopamine have been shown to modulate T cell functions significantly, but no information is available on the effect of physiological concentrations of circulating dopamine on CD4+ and CD8+ T cell functions. This information may be of importance since significantly elevated plasma dopamine levels were observed in humans during uncoping stress, and suppression of T cell functions during stress is a well-known phenomenon. However, the mechanism inducing the suppression of T cell functions during stress is not yet clear. In the present investigation, we evaluated the effect of the dopamine level attained in the plasma of individuals with uncoping stress on the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. METHODS: T cell subpopulations were separated by panning. The effect of dopamine on IL-2-induced cell proliferation in vitro was evaluated by [3H]thymidine incorporation and cytotoxicity by 51Cr release, receptors by radioligand binding, cAMP by an assay kit and apoptosis by DNA fragmentation. RESULTS: At these elevated physiological concentrations, dopamine was found to inhibit significantly the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. This dopamine-mediated inhibition of proliferation was more marked on CD8+ T cells than on CD4+ T cells. The underlying mechanism was found to be D1 class of dopamine-receptor-mediated stimulation of intracellular cAMP. CONCLUSION: Results may be of significance to understand the role of peripheral dopamine in human neuroimmune communication in terms of physiological homeostasis in health and disease.

3',5'-Cyclic-AMP Phosphodiesterases↗

Extracellular superoxide dismutase deficiency and atherosclerosis in mice.

Lipoprotein peroxidation in the arterial wall has been implicated in atherogenesis. The superoxide radical is formed in arteries and can induce such oxidation. Extracellular superoxide dismutase (EC-SOD) occurs in high concentration in the vascular wall interstitium, and in this study, we examined the importance of the enzyme in atherogenesis. On an apolipoprotein E-null background, the limited aortic lesions induced by a 1-month atherogenic diet were larger in EC-SOD wild-type mice than in EC-SOD-null mice, whereas there were no differences between the EC-SOD genotypes in the larger lesions seen after 3 months on the diet or after 8 months on normal chow. Despite smaller or equal lesions in the EC-SOD-null mice, their cholesterol levels were somewhat higher. Also, on a wild-type background, there were no effects produced by the absence or presence of EC-SOD on atherogenic diet-induced aortic root lesions. The urinary excretion of the lipid peroxidation biomarker 8-isoprostaglandin F(2alpha) was related to the rates of atherogenesis in the mice but was not influenced by the EC-SOD genotype. Likewise, the EC-SOD status had no effect on the staining for oxidized low density lipoprotein epitopes in aortic root sections. Our findings suggest that EC-SOD has little influence on atherogenesis in mice.

Animals↗

Advances in cancer therapy with plant based natural products.

Natural Products have long been a fertile source of cure for cancer, which is projected to become the major causes of death in this century. However, there is a continuing need for development of new anticancer drugs, drug combinations and chemotherapy strategies, by methodical and scientific exploration of enormous pool of synthetic, biological and natural products. There are at least 250,000 species of plants out of which more than one thousand plants have been found to possess significant anticancer properties. While many molecules obtained from nature have shown wonders, there are a huge number of molecules that still either remains to be trapped or studied in details by the medicinal chemists. The article reviews many such structures and their related chemistry along with the recent advances in understanding mechanism of action and structure-function relationships of nature derived anti-cancer agents at the molecular, cellular and physiological levels. Taxol, one of the most outstanding agents, has been found beneficial in treatment of refractory ovarian, breast and other cancers. Another prominent molecule includes Podophyllotoxin. Synthetic modification of this molecule led to the development of Etoposide, known to be effective for small cell cancers of the lungs and testes. Camptothecin isolated from Camptotheca acuminata also have been extensively studied. Other important molecules discussed include Vincristine, Vinblastine, Colchicine, Ellipticine and Lepachol along with Flavopiridol, a semi-synthetic analogue of the chromone alkaloid Rohitukine from India, a pyridoindole alkaloid from leaves of Ochrosia species and many more. The review also deals with the lesser-known plants of sub-Himalayan region.

Humans↗

Synchronous colonic tumours of dual pathology.

Synchronous colonic tumours of dual pathology are extremely rare. A review of the literature revealed that few cases have been reported to date. Because of their rarity and lack of specific symptoms, preoperative diagnosis is not easy and there is no protocol as yet for the ideal management of these cases. We present such a case which was treated by a combination of surgery and chemotherapy.

Adenocarcinoma↗