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Biomedical subjects

S C Agarwal

Publications and source records attributed to S C Agarwal.

At least 19 recordsLinked to original sources

Production of L-phenylacetylcarbinol by free and immobilized yeast cells.

Production of L-phenylacetylcarbinol (L-PAC) through biotransformation of benzaldehyde by free and immobilized cells of the yeast Saccharomyces cerevisiae has been attempted. L-PAC production was found to be maximum (0.4 microliter/ml) when anaerobically grown free cells were used as biocatalyst during aerobic biotransformation for two hours with magnetically stirred bioreactor. Growth under oxygen limited conditions led to accumulation of higher amount of pyruvate decarboxylase enzyme and co-substrate, pyruvate, resulting in higher L-PAC formation. L-PAC yield was low when biotransformations were carried out anaerobically either for aerobically or anaerobically grown free cells. Free cells were found to be more efficient biocatalyst for L-PAC production, as compared with the immobilized cells, with the investigated benzaldehyde concentration (0.3% v/v) and cell density (17.5% w/v). The study has explored and indicated the possibility of optimizing the yield of L-PAC by growing the yeast cells under oxygen limited condition for suitable aerobic mode of benzaldehyde biotransformation.

Acetone↗

Bone quantity and quality in past populations.

BACKGROUND: The study of osteoporosis in past populations offers valuable insight into the patterns and prevalence of the disease in both the past and in the present. METHODS AND RESULTS: A review is made of different paleopathological studies better to understand bone loss in past populations and to examine the contribution such studies can make to our knowledge of osteoporosis in modern populations. The review includes studies of bone mass in past populations from different geographic regions. Nutritionally based hypotheses, traditionally used to explain bone loss in past populations, are reviewed and assessed against the current clinical and epidemiological findings. In general, the various studies have revealed different degrees of low bone mass in past populations; however, the pattern of bone loss and fragility seen in age-related and postmenopausal osteoporosis today is not evident in the past. Bone loss in earlier populations is often found in both sexes, whereas significant bone loss in females occurs often among the young-age categories. In addition, a prevalence of osteoporotic fracture is absent. CONCLUSIONS: We suggest that, despite influences that may have reduced bone mass in past populations, a protection of bone quality may have occurred, reducing the likelihood of bone fragility and fracture typically seen in modern osteoporotics. It seems evident that, although reduced bone mass may be prevalent in past history, clinically recognized osteoporosis is not.

Bone Density↗

Synthesis and characterization of adducts of alachlor and 2-chloro-N-(2,6-diethylphenyl)acetamide with 2'-deoxyguanosine, thymidine, and their 3'-monophosphates.

Adducts of the preemergence herbicide 2-chloro-N-(methoxymethyl)-N-(2,6-diethylphenyl)-acetamide (alachlor) and 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) with 2'-deoxyguanosine, thymidine, 2'-deoxyguanosine 3'-monophosphate, and thymidine 3'-monophosphate have been synthesized and characterized. Under mildly basic conditions alachlor and CDEPA form N-1 adducts with 2'-deoxyguanosine and N-3 adducts with thymidine as a result of chlorine displacement. In addition, alachlor formed an N-7 adduct with 2'-deoxyguanosine, 7-[[(N-(methoxymethyl)-N-(2,6-diethylphenyl)carbamoyl]methyl]guani ne. N-1 adducts of alachlor and CDEPA with 2'-deoxyguanosine 3'-monophosphate and N-3 adducts with thymidine 3'-monophosphate are also described. In addition to spectroscopic data, structural proof included the dephosphorylation of each nucleotide adduct to its corresponding nucleoside adduct by nuclease P1. Alachlor and alachlor adducts but not CDEPA and CDEPA adducts exhibited rotational isomerism as evidenced by proton and 13C NMR studies. These rotamers were attributed to hindered rotation about the shortened N-carbonyl bond. Computational methods employing molecular mechanics and quantum mechanics were used to characterize the structures and energies of these rotamers to account for the patterns of duplicate NMR resonances observed.

Acetamides↗

Morphological transformation and DNA adduct formation by dibenz[a,h]anthracene and its metabolites in C3H10T1/2CL8 cells.

The major routes of metabolic activation of dibenz[a,h]-anthracene (DBA) have been studied in transformable C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts in culture. The morphological transforming activities of three potential intermediates formed by metabolism of DBA by C3H10T1/2 cells, trans-3,4-dihydroxy-3,4-dihydro-DBA-(DBA-3,4-diol), trans-dihydroxy-3,4-dihydro-DBA-anti-1,2-oxide (DBA-3,4-diol-1,2-oxide) and DBA-5,6-oxide were determined. DBA-3,4-diol-1,2-oxide was a strong morphological transforming agent giving a mean of 73% dishes with Type II or III foci and 1.63 Type II and III foci per dish at 0.5 microgram/ml. DBA-3,4-diol produced a mean of 42% dishes with Type II or III foci and 0.81 Type II and III foci per dish at 2.5 micrograms/ml. DBA gave a mean of 24% dishes with Type II or III foci and 0.29 Type II and III foci per dish at 2.5 micrograms/ml. DBA-5,6-oxide was found to be inactive. DNA adducts of DBA, DBA-3,4-diol, DBA-3,4-diol-1,2-oxide, DBA-1,4/2,3-tetrol and DBA-5,6-oxide in C3H10T1/2 cells were analyzed by 32P-postlabeling method. DBA gave 11 adducts, nine of which were observed in the DNA of cells treated with DBA-3,4-diol and seven from cells treated with DBA-3,4-diol-1,2-oxide. Two of these adducts that appear in each of the treatment groups have been identified as the product of the interaction of DBA-3,4-diol-1,2-oxide with 2'-deoxyguanosine. Furthermore, there is evidence for DBA-DNA adducts in cells treated with DBA, DBA-3,4-diol and DBA-3,4-diol-1,2-oxide arising from metabolism to (+,-)-trans,trans-3,4,10,11-tetrahydroxy-3,4,10,11-tetrahydro-DBA (DBA-3,4,10,11-bis-diol). These results are based on co-migration of C3H10T1/2 DNA adducts with skin DNA adducts formed after topical treatment of mice with DBA-3,4,10,11-bis-diol. In C3H10T1/2 cells, DBA is metabolically activated through DBA-3,4-diol, which is further activated via the DBA-3,4-diol-1,2-oxide and DBA-3,4,10,11-bis-diol pathways. No evidence is provided for the metabolism of DBA by the K-region pathway.

Animals↗

Quantitative analysis of the metabolism of 9,10-dihydrobenzo[a]pyrene by induced rat liver microsomes.

The ability of reduced polycyclic aromatic hydrocarbons to be converted to their fully aromatic forms by the microsomal cytochrome P-450 mixed-function oxidases may assist in the explanation of the mutagenic and tumorigenic activities of these agents. The metabolic conversion of 9,10-dihydrobenzo[a]pyrene (9,10-DHB[a]P) to benzo[a]pyrene (B[a]P) and 9- and/or 10-hydroxy-9,10-DHB[a]P (OH-9,10-DHB[a]P) was quantitatively measured. In beta-naphthoflavone-induced rat liver microsomes, 9,10-DHB[a]P was metabolized to B[a]P with a specific activity of 1.51 nmol B[a]P formed/min/mg microsomal protein. The formation of B[a]P was directly related to incubation time and microsomal protein concentration. Similarly, 9,10-DHB[a]P was converted to OH-9,10-DHB[a]P with a specific activity of 4.48 nmol OH-9,10-DHB[a]P formed/min/mg microsomal protein. Its formation was directly related to incubation time and microsomal protein concentration. The possibility of OH-9,10-DHB[a]P as a metabolic intermediate to B[a]P is discussed.

Animals↗

Reaction of cyclopenta[c,d]pyrene-3,4-epoxide with DNA and deoxynucleotides.

Cyclopenta[c,d]pyrene (CPP) is a widespread polycyclic aromatic hydrocarbon with potent mutagenic and carcinogenic activity. The trans isomer of 3,4-dihydro-3,4-dihydroxy-cyclopenta[c,d]pyrene has been shown to be the major metabolic product of CPP in rat, mouse or human microsomal systems, as well as in peroxyl radical-generating systems, indicating the preferential formation of its obligatory precursor, CPP-3,4-epoxide. The direct mutagenicity of CPP-3,4-epoxide, the inactivity of 3,4-dihydro-CPP and the DNA adduct forming capacity of CPP in vivo has prompted analysis of the DNA adducts produced by CPP-3,4-epoxide to provide information pertaining to: (i) the role this postulated major ultimate mutagenic metabolite may play in the formation of DNA adducts in vivo; (ii) the base selectivity of CPP-3,4-epoxide DNA adducts; and (iii) the role of CPP-3,4-epoxide in the mutagenicity/carcinogenicity of CPP. CPP-3,4-epoxide was reacted with calf thymus DNA, dGp, dAp, dTp, dCp, poly dG-dC, poly dA-dT and poly dG. Adducts were analyzed by the butanol-enhanced version of 32P-postlabeling. Four major and at least three minor adducts formed with DNA in vitro, which were further analyzed for their base selectivity. A similar spectrum of adducts was exhibited by dGp, poly dG-dC and poly dG. dCp, dTp, and dAp formed one, two, and four adducts respectively. The relative binding in adducts per 10(7) nucleotides was in the following descending order: dGp (6000), poly dG-dC (5800), dTp (5300), dAp (4800), calf thymus DNA (3800), poly dA-dT (2300), poly dG (2600) and dCp (20). Adducts derived from either dGp, poly dG-dC or poly dG co-migrated with the DNA adducts in three solvent systems, indicating that CPP-3,4-epoxide forms DNA adducts almost exclusively with deoxyguanosine.

Adenine Nucleotides↗

DNA adducts of the antitumor agent diaziquone.

We have studied adduct formation of the antineoplastic agent diaziquone (AZQ; NSC 182986) with DNA and nucleotides in vitro. The aziridine moieties of AZQ can be expected to interact covalently with DNA which, in turn, presumably elicits the antitumor activity. We analyzed AZQ-DNA adducts by a modified 32P-postlabeling assay involving purification of the nuclease P1-enriched labeled adducts by high-salt C18 reversed-phase thin-layer chromatography and separation of the eluted adducts on a polyethyleneimine-cellulose layer using non-urea salt solutions. Modification of calf thymus DNA with AZQ produced two major (22% and 40%) and at least eight minor adducts. At equal concentrations of AZQ and DNA (1 micrograms/microliters each), peak binding was observed in about 2 h [1926 +/- 378 (SD) fmol/micrograms of DNA] with the binding levels remaining practically unchanged through 4 h. However, incubation for 24 h resulted in over 40% decline, indicating adduct instability. AZQ was found to be highly reactive in vitro as evidenced by its substantial binding (49 +/- 14 fmol/micrograms of DNA) even at a DNA:AZQ ratio of 100:1. When incubated with mononucleotides, AZQ reacted extensively with adenine, guanine, and cytosine but only slightly with thymine. Cochromatography of the modified DNA and nucleotides revealed that one of the major adducts and several minor adducts were guanine derived. The aziridine rings of AZQ were found to be the main reactive sites as its monoaminoalcohol derivative showed as much DNA reactivity as did the parent compound, but no activity was observed when both aziridine groups were hydrolyzed to diaminoalcohols. The improved 32P-postlabeling assay seems capable of detecting relatively polar adducts such as those formed with AZQ at a level of one adduct/10(9) nucleotides.

Animals↗

Synthesis of a novel fluorinated benzo[a]pyrene: 4,5-difluorobenzo[a]pyrene.

The synthesis of 4,5-difluorobenzo[a]pyrene, as a fluorinated probe to investigate the involvement of the K-region in the further metabolic activation of benzo[a]pyrene metabolites, is described. Benzo[a]pyrene-4,5-dione obtained from 2,3-dichloro-5,6-dicyano-1,4-benzoquinone oxidation of cis-4,5-dihydro-4,5-dihydroxybenzo[a]pyrene was fluorinated with dimethylaminosulfur trifluoride to give 4H,5H,4,4,5,5,-tetra-fluorobenzo[a]pyrene. Defluorination using lithium aluminum hydride in tetrahydrofuran gave 4,5,-difluorobenzo[a]pyrene.

Benzo(a)pyrene↗

Mutagenicity and alkylating activity of the aqueous chlorination products of humic acid and their molecular weight fractions.

Fluka humic acid used as a model substrate in these studies was analysed for elemental and the oxygen-containing functional groups. It was chlorinated at C:Cl molar ratios of 1:1 and 1:0.3 and subsequently separated into molecular weight fractions by ultrafiltration. The freeze-dried, chlorinated humic acid and the respective molecular weight fractions were analyzed for TOC, TOX, alkylating activity using 4-(p-nitrobenzyl)pyridine and mutagenicity by the Ames/Salmonella/microsome assay with strains TA-98 and TA-100. Results indicated that predominantly non-volatile, direct-acting mutagenic and/or alkylating agents were formed during humic acid chlorination and that these agents were unevenly distributed among the various molecular weight fractions. Formation of mutagenic and alkylating agents were highly dependent upon level of chlorination and total organic carbon. Higher levels of mutagenic and alkylating activities were produced with increasing concentration of chlorine in the range of 0.4-1.2 chlorine equivalents per mole of carbon. However, both these activities in the freeze-dried, chlorinated humic acid solutions containing the non-volatiles or the fresh solutions decreased gradually with increasing pH and storage time, apparently due to degradation and hydrolysis of some of the components.

Alkylating Agents↗

Evaluation of specific immunoglobulin E by enzyme-linked immunosorbent assay in hydatid disease.

The diagnostic significance of elevated hydatid-specific immunoglobulin E (IgE) as measured by enzyme-linked immunosorbent assay (ELISA) was evaluated against hydatid-specific IgG ELISA and Casoni's intradermal test in surgically proven cases of hydatidosis. A specific IgE ELISA did not correlate with IgG ELISA or Casoni's intradermal test, although its recorded sensitivity was 87%. The specific IgE ELISA was at the same time false-positive in 57.14% of the cases because of its cross-reactions with cases of ascariasis and taeniasis, unlike Casoni's intradermal test and specific IgG ELISA. It is suggested that, in a helminth-infested population, the determination of specific IgE levels is not better than Casoni's intradermal or specific IgG ELISA tests.

Antibodies, Helminth↗

Comparative evaluation of enzyme-linked immunosorbent assay for the diagnosis of pulmonary echinococcosis.

An enzyme-linked immunosorbent assay was done for the detection of immunoglobulin G and M (IgG and IgM) antibodies to Echinococcus granulosus in surgically proved cases of hydatidosis, especially pulmonary hydatidosis, by use of human hydatid cyst fluid antigen and soluble scolex antigen. This assay was compared with the following standardized techniques: the indirect hemagglutination test, the indirect immunofluorescent antibody test, and Casoni's intradermal test. The enzyme-linked immunosorbent assay, with either of the antigens (human hydatid cyst fluid or soluble scolex antigen), was more sensitive and specific than the other techniques in diagnosing cases of hydatidosis, especially hydatid disease of the lung.

Antigens, Helminth↗

Effect of serotonin on T lymphocyte proliferation in vitro in healthy individuals.

The direct effect of different concentrations of serotonin on T lymphocyte proliferation in vitro was seen in 20 normal individuals. It has been observed that the neurotransmitter had a suppressive effect on mitogen-induced lymphocyte proliferation. This study shows that the effect of serotonin on the immune system is direct.

Cells, Cultured↗

Childhood malignancies of the eye and orbit in northern Nigeria.

One hundred four histologically proven malignant tumors of the eye and orbit in children seen in Guinness Eye Clinic, Kaduna, Nigeria between 1975 and 1982 are presented. Retinoblastoma and Burkitt's lymphoma account for the majority of the tumors. The data are compared with those from Ibadan, Nigeria. Burkitt's lymphoma occurs less frequently in Kaduna, whereas the incidence of retinoblastoma is almost the same. Chloroma, which was not seen in Ibadan, accounted for 2.9% of the current series. Factors that may be contributory to the observed differences are discussed.

Adolescent↗