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Biomedical subjects

P C Mandal

Publications and source records attributed to P C Mandal.

At least 19 recordsLinked to original sources
PubMed1998

Visible radiation effects on flavocytochrome b2 in dilute aqueous solution: a steady-state and laser flash photolysis study.

Irradiation of flavocytochrome b2 by visible radiation at 450 nm in dilute aqueous solution is found to have a devastating effect not only on its activity but also on the important flavin mononucleotide (FMN) constituents. The active site and the substrate binding site are also found to be largely modified on exposure to visible radiation. This has a telling effect on the constituent aromatic amino acids, tryptophan and tyrosine, and therefore justifies the role of FMN as a very potent photosensitizer. Partial unfolding of the irradiated enzyme molecule is also observed. Damage is much greater in deaerated conditions, which indicates that molecular oxygen plays a protecting role in this particular system. The inactivation is mediated through rapid electron transfer from tryptophan and tyrosine to excited flavin, forming flavin semiquinone and tryptophanyl and tyrosinyl radicals, which in turn cause permanent damage at the molecular level.

Absorption↗
PubMed1997

Radiation-induced double-strand modification in calf thymus DNA in the presence of 1,2-dihydroxy-9,10-anthraquinone and its Cu(II) complex.

When cells or DNA is exposed to ionizing radiation, the radicals produced in the irradiated sample will modify the base-pair region of the double strands. Effects of 1,2-dihydroxy-9,10-anthraquinone (DHA) and its Cu(II) complex on the radiation-induced modification of double-strands in calf thymus DNA were studied using ethidium bromide as a fluorescent probe. Our results show that the Cu(II)-DHA complex is more efficient in modifying the base-pair region in double-stranded DNA compared to free DHA.

Animals↗
PubMed1996

Radiosensitization of thymine by copper(II) and nickel(II) complexes of metronidazole.

Aqueous solutions of thymine (10(-3) mol dm(-3)) were irradiated with Co 60 gamma-rays in the absence and presence of metronidazole as well as its Cu(II) and Ni(II) complexes (10(-4) mol dm(-3)) under different conditions. The yields for the loss of thymine and those for the formation of the products of radiolysis were determined by hplc. The degradation of thymine when compared with that in the absence of metronidazole was not significantly altered. However, it increased significantly when the radiolysis of thymine was carried out in the presence of the Cu(II) and Ni(II) complexes of metronidazole. All three compounds were found to promote the formation of thymine glycol although the increase was more significant for the metal complexes than for free metronidazole. The higher radiosensitizing efficiency observed with the metal complexes as compared with that for free metronidazole is due to their higher rate of oxidation of the transient thymine-OH radical adduct. The reduction of the sensitizers results in the formation of the nitro-anion radical which in the case of the Cu(II) complex undergoes intramolecular electron transfer to the metal centre leading to the formation of Cu(I).

Copper↗
PubMed1996

Reactions of OH and eaq- adducts of cytosine and its nucleosides or nucleotides with Cu(II) ions in dilute aqueous solutions: a steady-state and pulse radiolysis study.

The reactions of OH and eaq- adducts of cytosine, cytidine and deoxycytidine in the presence of Cu(II) ions have been studied by product analysis and pulse radiolysis. The product analysis studies show that the degradation of the base is enhanced in N2O-saturated conditions in the presence of Cu(II) ions and the major radiolytic products are Cu(I), cytosine glycols and 5(6)-hydroxycytosine. It is also interesting to note that the yields of Cu(I) are equivalent to cytosine degradation yields, which suggests that the interaction of the OH adducts with Cu(II) ions restricts the radical recombination reactions (known to be the major physicochemical repair process) which partly regenerate the parent cytosine. The rate constants of the reactions of cytosine OH adducts with Cu(II) ions determined by pulse radiolysis lie between 10(7) and 10(8) dm3 mol-1 s-1. The growth in the transient absorption spectra of cytosine OH adducts in the range 330-400 nm, observed in the presence of copper(II) ions in free and complexed state, suggests formation of copper radical adduct which decays by water insertion at the copper-carbon bond to give glycol as the major product. Such copper radical adduct formation was also observed in the case of cytidine and deoxycytidine. The protonated electron adducts (at the hetero atoms) of cytosine, cytidine and deoxycytidine transfer electrons to the Cu(II) ions with rate constants of 10(8) and 10(9) dm3 mol-1 s-1. Here no adduct formation is observed. The steady-state results show that such electron transfer reactions regenerate the parent molecules themselves. Hence such electron transfer reactions do not contribute to enhanced base degradation in the presence of copper ions.

Copper↗
PubMed1995

Radiation-induced inactivation of flavocytochrome b2 in dilute aqueous solution.

Effect of gamma radiation on flavocytochrome b2 in dilute aqueous solution was studied. A study of the effect of the radiolytically produced inorganic free-radical anions such as I2.-, Br2.- and (SCN)2.- on the enzyme activity indicates the involvement of cysteine and tyrosine residues in the catalytic activity of flavocytochrome b2. The changes in kinetic parameters, i.e., Michaelis-Menten constant Km and maximal velocity Vmax, due to irradiation under different conditions suggest that radiation induced enzyme inactivation is the result of destruction of active-site residues as well as modification of the substrate binding site. Fluorescence studies of unirradiated and irradiated enzyme reveal that FMN (flavin mononucleotide) is inaccessible to water radicals.

Bromides↗
PubMed1994

Sequential pathological studies in the udder of goats intramammarily infected with Aspergillus fumigatus.

Intramammary inoculation of goats with Aspergillus fumigatus spores resulted in the development of mastitis with characteristic gross and microscopic lesions. The mastitis and the lesions were restricted to the infected udder halves only and there was no dissemination of infection to other tissues of the body. The experiment was continued for 45 days. Gross changes in the infected udder were observed up to the 45th day post-infection. The lesions, in general, included variable sized abscesses in the first 15 days followed by development of varying sized greyish-white nodules in the infected udders. Microscopic changes consisted of granulomatous reaction with well developed granulomas in the infected udders. Hyphae and spores of Aspergillus fumigatus could be demonstrated in sections of the infected udders up to 45 days after infection. Reisolation of the fungus consistently was achieved up to 45 days. It is concluded that intramammary inoculation of Aspergillus fumigatus spores in goats leads to chronic granulomatous mastitis.

Animals↗
PubMed1993

Sequential pathological studies in goats infected intratracheally with Aspergillus fumigatus.

Intratracheal inoculation of goats with Aspergillus fumigatus spores resulted in the development of characteristic gross and microscopic lesions. The lesions were restricted to lungs and there was no dissemination of infection to other tissues of the body except liver in one goat 16 days after infection. The experiment was continued for 37 days. Gross changes in lungs were observed up to the 24th day post-infection. The lesions, in general, included congestion and oedema in the first 6 days followed by the development of varying greyish-white nodules in the lungs. Microscopic changes consisted of granulomatous reaction with well developed granulomas in lungs. Hyphae and conidiophores with fruiting bodies of Aspergillus fumigatus could be demonstrated in sections up to 24 days of infection. Reisolation of the fungus consistently was achieved up to 24 days. It is concluded that intratracheal inoculation of Aspergillus fumigatus spores in goats leads to pulmonary aspergillosis up to 24 days.

Animals↗
PubMed1993

Tyrosine residues in unirradiated and gamma-irradiated dihydroorotate dehydrogenase: fluorimetric and second-derivative absorption spectrophotometric studies.

The effect of gamma-radiation on tyrosine residues of dihydroorotate dehydrogenase under different conditions was investigated by means of fluorescence spectroscopy and second-derivative spectrophotometry. No change in the fluorescence spectral distribution was observed when unirradiated and irradiated enzyme were denatured in guanidine hydrochloride. However, decreases in fluorescence intensity in irradiated samples indicates a radiation-induced modification of tyrosine residues. The fluorescence intensity at 340 nm decreased exponentially with radiation dose in aerated medium but non-exponentially under argon and nitrous oxide-saturated conditions. The percentage loss of tyrosine fluorescence under different conditions was determined. The number of tyrosine residues left intact following irradiation at a dose for 50% inactivation under different conditions was measured by second-derivative absorption spectrophotometry. The results obtained from both these methods show that the hydroxyl radical is less efficient in inducing radiation damage of tyrosine in aerated conditions compared with that under deoxygenated conditions. This lower efficiency of the hydroxyl radical in aerated medium has been attributed to the protective effect of oxygen and/or the superoxide radical anion.

Cobalt Radioisotopes↗
PubMed1993

Experimental aspergillosis in goats: clinical, haematological and mycological studies.

Thirty-one (including ten lactating) healthy goats were divided into 3 groups viz. intravenous (I/V), intratracheal (I/T) and intramammary (I/M) on the basis of route of inoculation of Aspergillus fumigatus spores. Two animals were kept as control for each group. Clinical aspergillosis developed and was more severe and fatal in consequence in I/V group than those of other groups. Respiratory symptoms appeared and persisted in both I/V and I/T groups. Acute mastitis developed in the right infected udder halves only with a brief and transitory illness in all goats of I/M group and marked discrepancy in size between right inoculated and left uninfected udder halves was observed. Haematological examination revealed significant decrease of haemoglobin concentration and significant increase in both TLC and DLC (neutrophilia) in I/V group but no marked haematological change was observed in I/T and I/M groups. Mycological isolation in pure culture, demonstration of fungus in the impression smears by lactophenol cotton blue staining and in histological sections by PAS and GSM methods were achieved in the lungs, kidneys, heart, liver, spleen and abomasum in I/V group, in the lungs and occasionally in the mediastinal lymph node and liver in I/T group and in the right infected udder halves and their milk/secretions in I/M group.

Animals↗
PubMed1992

Radiation-induced inactivation of dihydroorotate dehydrogenase in dilute aqueous solution.

The inactivation of dihydroorotate dehydrogenase by gamma irradiation in dilute aqueous solution has been investigated. The activity of the enzyme decreased exponentially as a function of the absorbed dose under aerated and nitrous oxide-saturated conditions. The contributions of the individual radical species derived from water radiolysis were estimated from the inactivation results observed under aerated, argon-saturated, and nitrous oxide-saturated conditions. The hydrogen atom and hydroxyl radical were found to be important in enzyme inactivation. The effect of selected inorganic radical anions such as Br.2-, I.2-, and (SCN).2- on the enzyme activity was also studied, and the results implicate the possible involvement of cysteine and tyrosine residues in the catalytic activity of dihydroorotate dehydrogenase. Changes in the kinetic parameters (Michaelis-Menten constant, Km, and maximal velocity, Vmax) due to irradiation under the conditions investigated suggest that radiation-induced inactivation is due to modification of the substrate binding sites and that of the active site residues in the enzyme. Evidence for the reduction of iron-sulfur centers in the enzyme during the inactivation process has been put forward from the difference spectrum of the irradiated dihydroorotate dehydrogenase. It has also been shown by electrophoretic studies that radiation-induced inactivation was not due to any fragmentation of the protein structure or the formation of any intermolecular crosslinking.

Cobalt Radioisotopes↗
PubMed1991

Radiation-induced changes in flavin fluorescence of dihydroorotate dehydrogenase.

The effect of gamma-radiation on the flavin moiety of dihydroorotate dehydrogenase was studied by fluorescence spectroscopy. Irradiation of aerated solutions (0-7 Gy) led to a small increase in fluorescence intensity, but with higher doses a decrease in intensity was observed. The increase in fluorescence intensity after irradiation at low doses may be attributed to protein unfolding, leading to greater exposure of flavin groups and a concomitant increase in separation between the flavin moiety and the iron-sulphur centre. This was confirmed by fluorescence quenching studies using potassium iodide as quencher. The Stern-Volmer constant calculated for iodide quenching indicates a two-fold increase in the fraction of flavin moiety being accessible to the quencher after 6.6 Gy. No spectral change was observed when unirradiated or irradiated enzyme was denatured with guanidine hydrochloride. However, a decrease in fluorescence intensity in the case of irradiated samples indicated a radiation-induced decrease in the flavin fluorophore. The flavin fluorophore loss in dihydroorotate dehydrogenase was also determined using aerated, argon-saturated or nitrous oxide-saturated solutions. H and OH radicals were found to have nearly equal contributions in damaging the flavin moiety of dihydroorotate dehydrogenase.

Cobalt Radioisotopes↗
PubMed1986

Changes of fluorescence spectra of thymine in aqueous solution by radiation.

Aqueous solution of thymine (5 X 10(-4) M, buffered at pH 7.0) was irradiated with 60Co gamma-rays under four different atmospheric conditions. In the presence of t-BuOH-N2, there was little increase in the fluorescence intensity as was previously reported in the radiolysis of cytosine. Under O2 there was also no significant increase differing from the case of cytosine. The fluorescence intensity was found to increase appreciably under N2O but it was less under N2 indicating that OH radical is mainly responsible for the formation of the highly fluorescent products. However, the fluorescence yields under these conditions were much lower in thymine radiolysis than cytosine radiolysis.

Cytosine↗
PubMed1986

Changes of fluorescence spectra of 2'-deoxyadenosine in aqueous solution by radiation.

Aqueous solution of 2'-deoxyadenosine (5 X 10(-4) M, buffered at pH 7.0) was irradiated with 60Co gamma-rays under N2, O2, N2O and t-BuOH-N2 atmospheres in order to compare with adenine radiolysis previously reported. By exposure to radiation, the fluorescence was found to increase more markedly than that from adenine under all conditions of radiolysis. This result indicates that not only base moiety but also sugar moiety participate in the formation of highly fluorescent products. In this 2'-deoxyadenosine radiolysis, both OH and e-aq take part in the formation of such products, but OH predominates over over e-aq when both active species are present, as observed in adenine radiolysis.

Deoxyadenosines↗
PubMed1986

Changes of fluorescence spectra of 2'-deoxyguanosine in aqueous solution by radiation.

Aqueous solution of 2'-deoxyguanosine (5 X 10(-4) M, pH 7.0) was irradiated with 60Co gamma-rays under O2, N2, N2O, and t-BuOH-N2, respectively. A marked increase in fluorescence emission intensity was observed under all atmospheric conditions as was observed in aqueous solutions of adenine and 2'-deoxyadenosine. However, the fluorescence yield from 2'-deoxyguanosine with radiation was lower under O2 and much higher under t-BuOH-N2 than that from 2'-deoxyadenosine though it was not so different both under N2 and N2O. Such high fluorescence yield from 2'-deoxyguanosine especially under t-BuOH-N2 suggests that guanine base has a specific reactivity with hydrated electron or t-butanol radical differing from the other nucleobases.

Dose-Response Relationship, Radiation↗
PubMed1983

Effect of iron (III) ions on the radiosensitivity of uracil.

Aqueous solutions of uracil(U) in the presence of iron(III) were irradiated with 60Co gamma-rays both in the presence and in the absence of dissolved oxygen. The products of radiolysis (uracil dimer, cis- and trans-uracil glycol, hydroxy-dihydrouracil and isobarbituric acid) were separated by means of paper chromatography using n-butanol: water (86:14) as the solvent. Radiolytic reduction of Fe(III) and the formation of Fe(II) were followed spectrophotometrically. In the absence of any additive, G(-U) is approximately 1.3, but with Fe(III) added G(-U) approaches a limiting value of 3.3 and the yield of cis-glycol increases. Radiosensitization by Fe(III) is found to be different from that of oxygen, which results in the yield of cis glycol decreasing and the yields of trans glycol and isobarbituric acid increasing. The mechanisms involved are discussed.

Chromatography, Paper↗