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1.
Indian Heart J ; 75(5): 370-375, 2023.
Article in English | MEDLINE | ID: mdl-37652199

ABSTRACT

OBJECTIVES: The presentation and outcomes of acute decompensated heart failure (ADHF) during COVID times (June 2020 to Dec 2020) were compared with the historical control during the same period in 2019. METHODS: Data of 4806 consecutive patients of acute HF admitted in 22 centres in the country were collected during this period. The admission patterns, aetiology, outcomes, prescription of guideline-directed medical therapy (GDMT) and interventions were analysed in this retrospective study. RESULTS: Admissions for acute heart failure during the pandemic period in 2020 decreased by 20% compared to the corresponding six-month period in 2019, with numbers dropping from 2675 to 2131. However, no difference in the epidemiology was seen. The mean age of presentation in 2019 was 61.75 (±13.7) years, and 59.97 (±14.6) years in 2020. There was a significant decrease in the mean age of presentation (p = 0.001). Also. the proportion of male patients decreased significantly from 68.67% to 65.84% (p = 0.037). The in-hospital mortality for acute heart failure did not differ significantly between 2019 and 2020 (4.19% and 4.,97%) respectively (p = 0.19). The proportion of patients with HFrEF did not change in 2020 compared to 2019 (76.82% vs 75.74%, respectively). The average duration of hospital stay was 6.5 days. CONCLUSION: The outcomes of ADHF patients admitted during the Covid pandemic did not differ significantly. The length of hospital stay remained the same. The study highlighted the sub-optimal use of GDMT, though slightly improving over the last few years.


Subject(s)
COVID-19 , Heart Failure , Humans , Male , Middle Aged , Aged , Heart Failure/epidemiology , Heart Failure/therapy , Retrospective Studies , Stroke Volume , COVID-19/epidemiology , Hospitalization
2.
Indian Heart J ; 75(4): 243-250, 2023.
Article in English | MEDLINE | ID: mdl-37230465

ABSTRACT

OBJECTIVE: To find out differences in the presentation, management and outcomes of COVID-19 infected STEMI patients compared to age and sex-matched non-infected STEMI patients treated during the same period. METHODS: This was a retrospective multicentre observational registry in which we collected data of COVID-19 positive STEMI patients from selected tertiary care hospitals across India. For every COVID-19 positive STEMI patient, two age and sex-matched COVID-19 negative STEMI patients were enrolled as control. The primary endpoint was a composite of in-hospital mortality, re-infarction, heart failure, and stroke. RESULTS: 410 COVID-19 positive STEMI cases were compared with 799 COVID-19 negative STEMI cases. The composite of death/reinfarction/stroke/heart failure was significantly higher among the COVID-19 positive STEMI patients compared with COVID-19 negative STEMI cases (27.1% vs 20.7% p value = 0.01); though mortality rate did not differ significantly (8.0% vs 5.8% p value = 0.13). Significantly lower proportion of COVID-19 positive STEMI patients received reperfusion treatment and primary PCI (60.7% vs 71.1% p value=< 0.001 and 15.4% vs 23.4% p value = 0.001 respectively). Rate of systematic early PCI (pharmaco-invasive treatment) was significantly lower in the COVID-19 positive group compared with COVID-19 negative group. There was no difference in the prevalence of high thrombus burden (14.5% and 12.0% p value = 0.55 among COVID-19 positive and negative patients respectively) CONCLUSIONS: In this large registry of STEMI patients, we did not find significant excess in in-hospital mortality among COVID-19 co-infected patients compared with non-infected patients despite lower rate of primary PCI and reperfusion treatment, though composite of in-hospital mortality, re-infarction, stroke and heart failure was higher.


Subject(s)
COVID-19 , Heart Failure , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Stroke , Humans , COVID-19/epidemiology , Heart Failure/etiology , Percutaneous Coronary Intervention/adverse effects , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/epidemiology , ST Elevation Myocardial Infarction/therapy , Stroke/etiology , Treatment Outcome , Retrospective Studies
3.
J Environ Manage ; 340: 117850, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37105106

ABSTRACT

This study establishes the suitability of cellulosic fibers derived from Canna indica waste biomass for utilization as a reinforcement in natural fiber polymeric composites. The waste biomass was harvested from constructed wetlands engaged in the treatment of municipal wastewater from a gated community. The extracted Canna indica (CI) fibers were studied for their physicochemical, mechanical, structural, crystallographic, and thermal characteristics and proposed as a potential alternative to synthetic fiber. The CI fibers contained a relatively higher amount of cellulose (60 wt%) and a low wax fraction (0.5 wt%) - which is advantageous for its gainful utilization as a reinforcement. The CI fibers were thermally stable up to 237 °C and have an average fiber length, diameter, and density of 4.3 mm, 842 µm, and 0.75 g/cm3, respectively. The mean maximum tensile strength and Young's modulus were found to be 113 ± 6.82 MPa and 0.8 ± 7.91 GPa, respectively. The nano-indentation test displayed the nano hardness and modulus as 0.3 ± 0.6 GPa and 1.62 ± 0.2 GPa, respectively. The crystallographic properties of CI fibers consisted of an 87.45% crystallinity index and 3.2 nm crystallite size. The morphological attributes of CI fibers showed rough surfaces and shallow cavities on the surfaces of the fibers suggesting the suitability for its utilization as a reinforcement. It is argued that this technological approach can potentially achieve circular economy through valorization of Canna indica biomass harvested from natural wastewater treatment plants.


Subject(s)
Polymers , Wetlands , Biomass , Cellulose/chemistry , Tensile Strength
4.
Sci Rep ; 10(1): 15438, 2020 09 22.
Article in English | MEDLINE | ID: mdl-32963308

ABSTRACT

The Indian black clam Villorita cyprinoides (Family: Cyrenidae), an extractive commercially exploited species with aquaculture importance contributing more than 70% of clam fishery in India, is endemic to the Indian peninsula. Currently, there is very sparse information, especially on the molecular data of Villorita. The present study aims to provide a comprehensive knowledge of mitogenome architecture and assess the phylogenetic status of Cyrenidae. This has resulted in reporting the first complete mitogenome of V. cyprinoides using next-generation sequencing technology. The A+T circular mitogenome was 15,880 bp long, exhibiting 13 protein-coding genes (PCGs) including ATP8 (absent in several bivalves), 22 transfer RNA, and two ribosomal RNA genes residing in the heavy strand in a clockwise orientation and a gene order akin to Corbicula fluminea. The molecular phylogeny inferred from a concatenated multi-gene sequence [14 mitochondrial (12 PCGs, rrnS and rrnL) and two nuclear genes (Histone H3, 18S rRNA)] from 47 representative species of superorder Imparidentia, clustered V. cyprinoides and Cyrenid clams to a single clade supporting the monophyly of Cyrenidae. The subsequent mitochondrial gene order analysis substantiates the close relationship of V. cyprinoides and C. fluminea, analogous to phylogenetic output. The multilocus tree topology calibrated with verified fossil data deciphered the origin and diversification of Cyrenid clams during late Triassic-early Jurassic. The data derived from this study shall contribute remarkably for further insights on cryptic species identification, molecular characterization of bivalve mitogenomes and mitochondrial evolutionary history of genus Villorita. Moreover, complete mitogenome can aid in potential marker development for assessing the genetic health of black clam populations.


Subject(s)
Biological Evolution , Bivalvia/genetics , DNA, Mitochondrial/analysis , Genes, Mitochondrial , Genome, Mitochondrial , Phylogeny , Animals , DNA, Mitochondrial/genetics , Gene Order , Gene Rearrangement , High-Throughput Nucleotide Sequencing
5.
J Invertebr Pathol ; 159: 113-120, 2018 11.
Article in English | MEDLINE | ID: mdl-30291866

ABSTRACT

Parasites of the genus Perkinsus predominantly infect bivalves, and two species among them, P. olseni and P. marinus, are notifiable to OIE. P. olseni infections are known to cause extensive damage to wild as well as farmed bivalves globally with enormous implications to its fishery. Consequent to the initiation of a surveillance programme for aquatic animal diseases in India, Perkinsus infections were observed in many species of bivalves. The present paper describes P. olseni infections in the short neck yellow clam, Paphia malabarica from the southwest coast of India. Diagnosis of the parasite was carried out using Ray's Fluid Thioglycollate Medium culture, histology, in-situ hybridisation and molecular taxonomy. Pathology of infection and development of zoospores is also described. This forms the first report of a P. olseni infection in P. malabarica. High prevalence and intensity of infection of Perkinsus in clams raises concerns, as clam reserves in this geographical area sustain fisheries and the livelihoods of local fishing communities.


Subject(s)
Bivalvia/parasitology , Shellfish/parasitology , Animals , Eukaryota , India , Prevalence
6.
Parasitol Res ; 116(11): 3131-3149, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28965237

ABSTRACT

A new species of acanthocephalan infecting marine and brackish water fishes from the south-west coast of India is described. The parasite belongs to the genus Tenuiproboscis, and the fish hosts include Lutjanus argentimaculatus, L. ehrenbergii, Siganus javus, Epinephelus malabaricus, E. coioides, Scatophagus argus, Parascolopsis aspinosa, Caranx ignobilis, Gerres filamentosus and Lates calcarifer. The parasite inhabits mid- and hindgut regions and is characterised by an elongated, cylindrical, bulbous and posteriorly tapering metasoma and a claviform proboscis having 14-15 rows of 14-15 hooks each. Females larger than males, measured 3898.16-10,318.00 µm (6430.00 ± 1417.30) in length and 458.93-1435.68 µm (929.81 ± 250.39) in width. Males measured 3234.89-8644.20 µm (5729.50 ± 1176.60) in length and 388.30-1584.61 µm (795.88 ± 184.12) in width. Parasites recovered from different host species showed morphological/morphometric variations. However, principal component analysis (PCA) revealed significant overlapping of characters indicating their similarities. Proboscis profiling based on variations in size and position of hooks also yielded similar results. Further, in molecular phylogenetic analysis, parasites from different fish hosts formed a monophyletic clade with strong bootstrap support, again indicating their conspecific nature. These morphological/morphometric variations can be ascribed to differences in host species. Morphology and morphometrics in combination with PCA, proboscis profiling and molecular analysis suggest the present acanthocephalan parasite is different from other described species of Tenuiproboscis. Hence, it is considered as a new species and named T. keralensis n. sp. Prevalence, intensity and abundance of the parasite in different hosts are also discussed.


Subject(s)
Acanthocephala , Fish Diseases/parasitology , Perciformes/parasitology , Acanthocephala/classification , Acanthocephala/genetics , Acanthocephala/isolation & purification , Animals , Female , Gastrointestinal Tract/parasitology , Helminthiasis, Animal/parasitology , India , Male , Phylogeny , Saline Waters
8.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(4): 2700-9, 2016 07.
Article in English | MEDLINE | ID: mdl-26065848

ABSTRACT

Lobsters constitute low-volume high-value crustacean fishery resource along Indian coast. For the conservation and management of this declining resource, accurate identification of species and larvae is essential. The objectives of this work were to generate species-specific molecular signatures of 11 commercially important species of lobsters of families Palinuridae and Scyllaridae and to reconstruct a phylogeny to clarify the evolutionary relationships among genera and species included in this study. Partial sequences were generated for all the candidate species from sampling sites along the Indian coast using markers like Cytochrome oxidase I (COI), 16SrRNA, 12SrRNA, and 18SrRNA genes, and analyzed. The genetic identities of widely distributed Thenus species along the Indian coast to be Thenus unimaculatus and the sub-species of Panulirus homarus to be P. homarus homarus were confirmed. Phylogeny reconstruction using the individual gene and concatenated mtDNA data set were carried out. The overall results suggested independent monophyly of Scyllaridae and Stridentes of Palinuridae. The interspecific divergence was found to be highest for the 12SrRNA compared with other genes. Significant incongruence between mtDNA and nuclear 18SrRNA gene tree topologies was observed. The results hinted an earlier origin for Palinuridae compared with Scyllaridae. The DNA sequence data generated from this study will aid in the correct identification of lobster larvae and will find application in research related to larval transport and distribution.


Subject(s)
Genome, Mitochondrial/genetics , Palinuridae/genetics , Animals , DNA, Mitochondrial/genetics , Palinuridae/classification , Phylogeny , RNA, Ribosomal/genetics
10.
Int J Dermatol ; 36(12): 923-5, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9466199

ABSTRACT

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe, idiosyncratic, exfoliative disease of the skin and mucous membranes. The treatment of this condition is controversial. High-dose corticosteroid therapy has been the most commonly advocated treatment, but, more recently, this has changed to a no-steroid protocol. These conflicting treatments prompted us to evaluate retrospectively our protocol. METHODS: The patients admitted to the hospital from 1989 to 1995 with a clinical diagnosis of TEN were included in the study. These patients were given systemic steroids, prophylactic antibiotic, and supportive measures. RESULTS: The patients belonged to both sexes with an average age of 34 years. The average area of involvement was 85.62%. All the patients made an uneventful recovery without any evidence of sepsis. CONCLUSIONS: Treatment with systemic steroids is useful in the management of TEN, and there is no need for a burn care center.


Subject(s)
Stevens-Johnson Syndrome/drug therapy , Adolescent , Adult , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Child , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Female , Humans , India/epidemiology , Male , Middle Aged , Retrospective Studies , Stevens-Johnson Syndrome/epidemiology , Stevens-Johnson Syndrome/pathology , Treatment Outcome
11.
Article in English | MEDLINE | ID: mdl-20948136

ABSTRACT

Necrobiotic xanthogranuloma is a subset of inflammatory form of normolipaemic xanthomas. Because of its characteristic clinical and histopathological findings necrobiotic xanthogranuloma may be regarded as a specific marker of paraproteinaemia.

12.
Article in English | MEDLINE | ID: mdl-20952899

ABSTRACT

A number of skin diseases are described in association with HIV infection/AIDS. In the present study the frequency of various skin manifestations among HIV infected / AIDS patients are noted. Generalised pruritus and dry skin were the common manifestations encountered. There was a significant absence of Kaposi's sarcoma, multi-dermatomal herpes zoster and oral hairy leukoplakia. A prominent hyperpigmented band on finger nails was seen.

13.
Article in English | MEDLINE | ID: mdl-20952932

ABSTRACT

Proteus syndrome is a hamartomatous disorder characterised by focal overgrowths that can involve any structure of the body. An eleven-year-old girl with Proteus syndrome has been described with clitoromegaly.

14.
Article in English | MEDLINE | ID: mdl-20952998

ABSTRACT

A case of leishmaniasis of lip without any involvement of other parts of the body in a 36 year-old-male is described.

15.
Carcinogenesis ; 8(11): 1679-84, 1987 Nov.
Article in English | MEDLINE | ID: mdl-3664959

ABSTRACT

In prior studies with neonatal rats we have suggested that nitrated polycyclic aromatic hydrocarbons (NPAH) are 3-methylcholanthrene (3-MC) type of inducers of cytochrome P-450. These observations have been extended by studying the effect of fluoranthene (FL) and its nitrated derivative, 3-nitrofluoranthene (3-NF) and a mixture of nitrated fluoranthenes (NFs) on the induction of hepatic and pulmonary monooxygenase activities in adult rats. We have characterized the effect of these compounds on hepatic cytochrome P-450 isozyme(s) using immunoblot analysis. The administration of 3-NF and NFs to rats resulted in highly significant induction (1.9- to 5.8-fold) of hepatic and pulmonary aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin-O-deethylase (ERD) activities. FL was either ineffective or much less effective in inducing these enzyme activities. The enzyme induction response to these compounds occurred in the following order: NFs greater than 3-NF greater than FL. SDS-PAGE of hepatic microsomes prepared from FL-, 3-NF- and NFs-treated animals revealed a higher content of protein migrating in the P-450 region. Characterization of isozymes of P-450 was carried out by Western blot analysis with highly specific monoclonal antibodies (MAb) raised against 3-MC-specific P-450 (MAb 1-7-1) and phenobarbital-specific P-450 (MAb-2-66-3) isozymes. Hepatic microsomes prepared from 3-NF- and NFs-treated rats showed two distinct immunoprecipitin bands with MAb 1-7-1 whereas microsomes prepared from FL-treated animals showed a sharp band with MAb 2-66-3. MAb 1-7-1 significantly inhibited (approximately 80%) AHH activity induced by 3-NF and NFs. On the other hand FL-induced AHH activity was only moderately (approximately 30%) inhibited by MAb 1-7-1 whereas higher inhibition (approximately 60%) was observed with MAb 2-66-3. Analysis of BP metabolites by h.p.l.c. revealed enhanced production of metabolites by liver microsomes from 3-NF- and NFs-treated animals. The formation of BP 7,8-diol was 1.8- to 2.4-fold increased following treatment of animals with 3-NF and NFs respectively. Addition of MAb 1-7-1 to a microsomal mixture from 3-NF- and NFs-treated rats inhibited the formation of BP phenols (60-75%) and BP 7,8 diol (52-60%). These inhibitory effects were not observed with microsomes prepared from FL-treated rats. These studies suggest that NFs induce specific monooxygenases in liver and that they are inducers of P-450 isozymes c and d.


Subject(s)
Antibodies, Monoclonal/immunology , Carcinogens/pharmacology , Fluorenes/pharmacology , Oxygenases/biosynthesis , Animals , Aryl Hydrocarbon Hydroxylases/biosynthesis , Benzo(a)pyrene/metabolism , Chromatography, High Pressure Liquid , Cytochrome P-450 Enzyme System , Electrophoresis, Polyacrylamide Gel , Enzyme Induction/drug effects , Liver/enzymology , Lung/enzymology , Male , Mice , Mice, Inbred BALB C , Rats , Rats, Inbred Strains
16.
Cancer Res ; 47(3): 767-73, 1987 Feb 01.
Article in English | MEDLINE | ID: mdl-3802081

ABSTRACT

Naturally occurring plant phenols such as tannic acid, quercetin, myricetin, and anthraflavic acid are known to inhibit the mutagenicity of several bay-region diol-epoxides of polycyclic aromatic hydrocarbons (PAHs). The binding of bay-region diol-epoxides of PAHs to target tissue DNA is thought to be essential for the initiation of cancer by these compounds. In this study we investigated the effect of these plant phenols on PAH-DNA adduct formation in the epidermis and lung of SENCAR mice. In vitro addition of tannic acid, quercetin, myricetin, and anthraflavic acid (25 microM) to an incubation system containing epidermal microsomes prepared from either control or 3-methylcholanthrene-pretreated mice inhibited benzo(a)pyrene binding to calf thymus DNA by 63-64, 38-43, 36-37, and 27-33%, respectively. A single topical application of tannic acid, quercetin, myricetin, and anthraflavic acid at a dose of 400 mumol/kg body weight resulted in the inhibition of [3H]benzo(a)pyrene binding to epidermal DNA (48-73%) and protein (51-63%). The same dose of these plant phenols (400 mumol/kg) caused even greater inhibition of (+/-)-[3H]-7 beta,8 alpha-dihydroxy-7,8-dihydrobenzo(a)pyrene and [3H]-7,12-dimethybenz(a)anthracene binding to epidermal DNA and protein. The formation of (+)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene-deoxyguanosine adducts was substantially diminished in both epidermis (62-86%) and lungs (38-84%). These results indicate that tannic acid, quercetin, myricetin, and anthraflavic acid are potent inhibitors of carcinogen binding to epidermal and lung DNA and suggest that these plant phenols could prove useful in modifying the risk of tumor induction by PAHs such as benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene in these two tissues.


Subject(s)
Lung/metabolism , Phenols/pharmacology , Polycyclic Compounds/metabolism , Skin/metabolism , Animals , Anthraquinones/pharmacology , Benzo(a)pyrene/metabolism , DNA/metabolism , Female , Flavonoids/pharmacology , Hydrolyzable Tannins/pharmacology , Kinetics , Lung/drug effects , Mice , Mice, Inbred Strains , Microsomes/drug effects , Microsomes/metabolism , Plants , Quercetin/pharmacology , Skin/drug effects
17.
Cancer Lett ; 33(3): 287-94, 1986 Dec.
Article in English | MEDLINE | ID: mdl-3100019

ABSTRACT

The levels of benzo[a]pyrene diol epoxide-I-deoxyguanosine (BPDE-I-dG) adduct formation in epidermis and lung of SENCAR mice following the topical application of benzo[a]pyrene (BP) alone, crude coal tar (CCT) alone, and the two combined were determined in an enzyme linked immunosorbent (ELISA) assay using monoclonal antibodies. Topical application of two doses of BP (20 micrograms) at 72-h intervals, with sacrifice 24 h later resulted in the formation of 197 fmol and 205 fmol BPDE-I-dG adducts per mg DNA in epidermis and lung, respectively. Topical application of 0.5 ml CCT alone resulted in the formation of 278 fmol and 410 fmol BPDE-I-dG adducts per mg DNA in epidermis and lung, respectively. Simultaneous topical application of 20 micrograms BP and CCT (0.1-0.5 ml) resulted in substantially lower BPDE-I-dG adducts in the epidermis as well as in the lung. Our results suggest that CCT may contain inhibitors of carcinogen-DNA adduct formation and that topical application of CCT produces greater effects on DNA-adduct formation in lung than in epidermis. Thus the cancer-causing potency of the polycyclic aromatic hydrocarbons (PAHs) in CCT may be reduced by other anticarcinogenic constituents present in CCT and systemic absorption of carcinogenic PAHs in CCT applied to skin might have tumorigenic effects in other tissues.


Subject(s)
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/metabolism , Coal Tar/toxicity , DNA Adducts , DNA/metabolism , Dihydroxydihydrobenzopyrenes/metabolism , Epidermis/metabolism , Lung/metabolism , Administration, Topical , Animals , Benzo(a)pyrene/metabolism , Coal Tar/analysis , Deoxyguanosine/metabolism , Male , Mice , Skin Neoplasms/chemically induced
18.
Toxicol Appl Pharmacol ; 86(1): 33-43, 1986 Oct.
Article in English | MEDLINE | ID: mdl-3490018

ABSTRACT

The effect of a single topical application of several nitroarenes (1-nitropyrene, nitropyrenes mixture, nitrobenzo(ghi)perylene mixture, 3-nitrofluoranthene, nitrofluoranthene mixture, and nitroperylene mixture) and their corresponding parent arenes to neonatal rats on hepatic and cutaneous drug and carcinogen metabolism was studied. Topical application of each nitroarene (10 mg/kg) resulted in significant induction of aryl hydrocarbon hydroxylase (AHH), 7-ethoxyresorufin O-deethylase (ERD), and 7-ethoxycoumarin O-deethylase (ECD) activities in both skin (1.5- to 14.6-fold) and liver (1.3- to 41.9-fold). The induction of these enzymes by each of the nitroarenes was significant when compared to control or to their corresponding parent arenes. Among the nitroarenes studied, 1-nitropyrene was the least effective in inducing enzyme activities. The inducibility in both skin and liver by different nitroarenes tested was in the following order: nitrofluoranthenes mixture greater than 3-nitrofluoranthene greater than nitroperylenes mixture greater than nitrobenzo(ghi)perylenes mixture greater than nitropyrenes mixture greater than 1-nitropyrene. The nitrofluoranthenes mixture and the nitroperylenes mixture were almost as effective as 3-methylcholanthrene (3-MC). Parent arenes were either ineffective or significantly less effective than nitrated arenes in inducing hepatic and/or cutaneous monooxygenase activities. Hepatic and/or cutaneous benzphetamine N-demethylase (BPD), NADPH cytochrome c reductase, NADH ferricyanide reductase activities, and the levels of cytochrome P-450 and cytochrome b5, remained unchanged following treatment with either topically applied nitroarenes or arenes. However, a shift of approximately 1 nm to the blue region in the absorption maximum of hepatic cytochrome P-450 was observed in animals treated with nitroarenes. This shift was not evident in the case of 1-nitropyrene. Analysis of benzo(a)pyrene metabolites by high-pressure liquid chromatography revealed a significant enhancement in the production of metabolites by nitroarene-treated rat skin and liver microsomes. Our studies suggest that nitroarenes are inducers of hepatic and cutaneous monooxygenases in neonatal rats after topical administration and that they resemble the 3-MC type of inducers in this regard.


Subject(s)
Animals, Newborn , Aryl Hydrocarbon Hydroxylases/biosynthesis , Microsomes, Liver/drug effects , Nitro Compounds/toxicity , Oxidoreductases/biosynthesis , Oxygenases/biosynthesis , Polycyclic Compounds/toxicity , Skin/drug effects , 7-Alkoxycoumarin O-Dealkylase , Administration, Topical , Animals , Cytochrome P-450 CYP1A1 , Enzyme Induction , Microsomes, Liver/enzymology , Rats , Rats, Inbred Strains , Skin/enzymology
19.
J Invest Dermatol ; 87(3): 348-53, 1986 Sep.
Article in English | MEDLINE | ID: mdl-3734486

ABSTRACT

The effect of cutaneous exposure to ultraviolet B (UVB) radiation alone, to crude coal tar (CCT) alone, and to the combination of UVB and CCT on the inducibility of the microsomal cytochrome P-450-dependent carcinogen-metabolizing enzyme aryl hydrocarbon hydroxylase (AHH) and other monooxygenases such as 7-ethoxyresorufin O-deethylase (ERD) and 7-ethoxycoumarin O-deethylase (ECD) activities in the skin of neonatal rats was studied. Exposure of the animals to UVB (400-1600 mJ/cm2) alone resulted in a dose-dependent increase in cutaneous enzyme activities. At a UVB dose of 1200 mJ/cm2 increases in AHH, ECD, and ERD were 194%, 115%, and 244%, respectively. A single topical application of CCT (10 ml/kg) 24 h before sacrifice resulted in significant induction of AHH (350%), ECD (921%), and ERD (796%) activities. Treatment of animals with the same dose of CCT followed by UVB exposure resulted in additive and/or synergistic effects on AHH (858%), ECD (1229%), and ERD (1166%) activities in the skin. In contrast, exposure of animals to UVB prior to CCT application had effects no different from those of CCT alone. Epoxide hydrolase and glutathione S-transferase activities in skin from all experimental groups were not different from those of controls. High-pressure liquid chromatographic analysis of the metabolism of benzo[a]pyrene (BP) by cutaneous microsomes prepared from animals treated with UVB alone, CCT alone, and the combination of UVB and CCT revealed increased formation of all the metabolites in each experimental group. The largest increase in metabolite formation occurred in animals receiving CCT followed by UVB exposure. The inducibility of trans-7,8-diol formation by UVB alone and CCT alone was 203% and 435%, respectively, whereas with CCT followed by UVB it was 1065%. The differential responses in AHH activity were found to parallel the capacity of skin microsomal enzymes to enhance the binding of [3H]-BP to DNA. These studies indicate that the sequence of exposure to the components of the Goeckerman regimen in rodents greatly influences metabolic activity in skin. When applied in the same sequence employed in the Goeckerman regimen (CCT followed by UVB exposure) the additive effect upon catalytic activity essential for cancer initiation suggests a possible mechanism for the enhancement of human skin cancer in individuals exposed to this therapeutic regimen.


Subject(s)
Coal Tar/adverse effects , Skin Neoplasms/etiology , Ultraviolet Rays/adverse effects , Animals , Epoxide Hydrolases/metabolism , Glutathione Transferase/metabolism , Microsomes/enzymology , Rats , Rats, Inbred Strains , Skin/enzymology , Skin/ultrastructure , Skin Neoplasms/metabolism
20.
Biochem Biophys Res Commun ; 138(1): 33-9, 1986 Jul 16.
Article in English | MEDLINE | ID: mdl-3091015

ABSTRACT

Human skin grafted onto athymic nude mice maintains its major histological features and may provide a useful system with which to assess the carcinogen interaction with human skin. Significant differences were observed in basal levels of cytochrome P-450 and cytochrome P-448-dependent monooxygenase activities between human grafted and nude mouse epidermis. Topical application of crude coal tar (CCT) to human skin transplanted onto nude mice resulted in 3.9 & 3.5; 3.2 & 2.9 and 1.1 & 1.2 fold increases in mouse and human epidermal aryl hydrocarbon hydroxylase (AHH), ethoxyresorufin deethylase (ERD) and ethoxycoumarin deethylase (ECD) activities, respectively. CCT applied topically to mouse skin resulted in 27.8 & 6.4; 12.8 & 3.3 and 1.7 & 2.6 fold increases in mouse and human epidermal AHH, ERD and ECD activities, respectively. Topical application of coal tar either onto human transplanted skin or to mouse skin also resulted in substantial induction of hepatic and pulmonary AHH and ERD activities. These studies indicate that human skin grafted onto nude mice preserves its metabolic capacity and offers a useful model system with which to assess the effects of polycyclic aromatic hydrocarbons and CCT on cutaneous xenobiotic metabolism in the human population.


Subject(s)
Carcinogens/metabolism , Disease Models, Animal , Skin Neoplasms/chemically induced , Skin/metabolism , 7-Alkoxycoumarin O-Dealkylase , 9,10-Dimethyl-1,2-benzanthracene/metabolism , Administration, Topical , Animals , Aryl Hydrocarbon Hydroxylases/analysis , Coal Tar , Cytochrome P-450 CYP1A1 , Cytochrome P-450 CYP1A2 , Cytochrome P-450 Enzyme System/metabolism , Cytochromes/metabolism , Humans , Lung/enzymology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Oxidoreductases/analysis , Oxygenases/analysis , Polycyclic Compounds/metabolism , Skin Transplantation
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