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R Agarwal

Publications and source records attributed to R Agarwal.

At least 199 records · Page 11Linked to original sources
PubMed1997

Protective effects of silymarin against photocarcinogenesis in a mouse skin model.

BACKGROUND: Nonmelanoma skin cancer is the most common cancer among humans; solar UV is its major cause. Therefore, it is important to identify agents that can offer protection against this cancer. PURPOSE: We evaluated the protective effects of silymarin, a flavonoid compound isolated from the milk thistle plant, against UVB radiation-induced nonmelanoma skin cancer in mice and delineated the mechanism(s) of its action. METHODS: For long-term studies, three different protocols of treatment were employed, each evaluating protection by silymarin at a different stage of carcinogenesis. Female SKH-1 hairless mice were subjected to 1) UVB-induced tumor initiation followed by phorbol ester-mediated tumor promotion, 2) 7,12-dimethylbenz[a]anthracene-induced tumor initiation followed by UVB-mediated tumor promotion, and 3) UVB-induced complete carcinogenesis. Forty mice were used in each protocol and were divided into control and treatment groups. Silymarin was applied topically at a dose of 9 mg per application before UVB exposure, and its effects on tumor incidence (% of mice with tumors), tumor multiplicity (number of tumors per mouse), and average tumor volume per mouse were evaluated. In short-term studies, the following parameters were measured: formation of sunburn and apoptotic cells, skin edema, epidermal catalase and cyclooxygenase (COX) activities, and enzymatic activity and messenger RNA (mRNA) expression for ornithine decarboxylase (ODC), a frequently observed marker at tumor promotion stage. Fisher's exact test was used to evaluate differences in tumor incidence, two-sample Wilcoxon rank sum test was used for tumor multiplicity and tumor volume, and Student's t test was used for all other measurements. All statistical tests were two-sided. RESULTS: In the protocol with UVB-induced tumor initiation, silymarin treatment reduced tumor incidence from 40% to 20% (P = .30), tumor multiplicity by 67% (P = .10), and tumor volume per mouse by 66% (P = .14). In the protocol with UVB-induced tumor promotion, silymarin treatment reduced tumor incidence from 100% to 60% (P<.003), tumor multiplicity by 78% (P<.0001), and tumor volume per mouse by 90% (P<.003). The effect of silymarin was much more profound in the protocol with UVB-induced complete carcinogenesis, where tumor incidence was reduced from 100% to 25% (P<.0001), tumor multiplicity by 92% (P<.0001), and tumor volume per mouse by 97% (P<.0001). In short-term experiments, silymarin application resulted in statistically significant inhibition in UVB-caused sunburn and apoptotic cell formation, skin edema, depletion of catalase activity, and induction of COX and ODC activities and ODC mRNA expression. CONCLUSIONS AND IMPLICATION: Silymarin can provide substantial protection against different stages of UVB-induced carcinogenesis, possibly via its strong antioxidant properties. Clinical testing of its usefulness is warranted.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Nitric oxide synthase and skin tumor promotion.

Up-regulation of inducible form of nitric oxide (NO)-synthase and increased production of NO has been shown to occur in many pathological conditions associated with inflammatory responses. In this study we show that topical application of skin tumor promoters, which are known to produce inflammatory response, down-regulate the constitutive form of NO-synthase in SENCAR mouse epidermis. The phorbol type of tumor promoters viz 12-0-tetradecanoylphorbol-13-acetate (TPA) and mezerein produced greater inhibitory effects than the non phorbol tumor promoters viz anthralin, n-dodecane, benzoyl peroxide and okadaic acid. Pretreatment of the skin with a polyphenolic fraction isolated from green tea, which possesses strong antioxidant activity, almost completely restored the inhibitory response. We suggest that the constitutive NO-synthase activity may play an important role in tumor promoter-caused oxidative burst during the promotion stage of multistage skin carcinogenesis, and that antioxidants may also target their anti-tumor promoting effect via attenuating the NO-synthase pathway.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Metabolic activation of benzo[g]chrysene in the human mammary carcinoma cell line MCF-7.

Benzo[g]chrysene (BgC) is an environmental pollutant, and recent studies have demonstrated that anti- BgC-11,12-dihydrodiol 13,14-epoxide (anti-BgCDE) is a potent mammary carcinogen in rats. To determine whether BgC can be metabolically activated to anti-BgCDE in human cells, the human mammary carcinoma cell line MCF-7 was treated with BgC and with the racemic trans-3,4- and 11,12-dihydrodiols. The DNA adducts formed in these experiments were examined using 32P-postlabeling, and specific adducts were identified through comparisons with adducts obtained by the reaction of the racemic syn- and anti-BgCDEs with calf thymus DNA and with purine deoxyribonucleoside-3'-phosphates in vitro. It was found that BgC is metabolically activated in MCF-7 cells to form major DNA adducts through both the syn- and anti-11,12-dihydrodiol 13,14-epoxide metabolites. BgC is therefore a potential environmental risk to humans. The major BgC-DNA adducts formed from both the dihydrodiol-epoxide diastereomers were deoxyadenosine adducts. Thus, BgC has DNA-binding properties that are very similar to those of the potent mammary carcinogens 7,12-dimethylbenz[a]anthracene and dibenzo[a,l]pyrene.

Biotransformation↗
PubMed1997

Megalourethra: a report of four cases and review of the literature.

Megalourethra is a rare congenital anomaly characterized by severe dilatation of the penile urethra. Four cases of congenital megalourethra were seen at Sir Padampat Mother and Child Health Institute, Jaipur, during the last 10 years. Three cases of scaphoid megalourethra had no other associated congenital anomalies and were treat-ed successfully without any complications, while one patient with a fusiform megalourethra had severe associated congenital anomalies and died. These cases are reported with a review of the literature.

Child↗
PubMed1997

Heparin absorption across the intestine: effects of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate in rat in situ intestinal instillations and in Caco-2 monolayers.

PURPOSE: The effects of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) on heparin intestinal absorption were studied using rat in situ ileal and colonic instillations and Caco-2 monolayers. METHODS: The flux of heparin was tested in the following groups: i) heparin alone, ii) heparin in the presence of SNAC, iii) heparin in the presence of propylene glycol (PG), and iv) heparin in the presence of SNAC and PG. Heparin absorption was measured by the APTT assay in the in situ models and by the anti-Factor Xa assay in Caco-2. SNAC and [3H]-SNAC fluxes were assessed by HPLC and by scintillation counting respectively. RESULTS: In the rat ileal and colonic in situ instillations SNAC (17-35 mg) promoted heparin absorption in the presence and absence of PG without damaging the tissue. PG alone did not alter heparin absorption in situ, but it amplified the effect of SNAC. In Caco-2, enhanced heparin fluxes were variable in the presence of non-cytotoxic concentrations of SNAC (< 10 mg/ml) and these effects could not be discriminated from those of PG. Papp values for SNAC alone were 2.2 x 10(-5) cm/s and 2.0 x 10(-5) cm/s in the mucosal-to-serosal and serosal-to-mucosal directions respectively, suggesting a substantial passive transcellular flux. Transport of SNAC was significantly reduced in the presence of heparin and/or PG, perhaps indicating physical association between the agents. CONCLUSIONS: SNAC augmented heparin absorption alone and in combination with PG in the rat in situ models without causing toxicity. Caco-2 had limitations for testing increased heparin absorption due to cytotoxic effects of high concentrations of SNAC and PG. However, SNAC itself was well absorbed across Caco-2 and its mechanism of permeation was determined.

Animals↗
PubMed1997

Protection against induction of mouse skin papillomas with low and high risk of conversion to malignancy by green tea polyphenols.

We earlier showed that a polyphenolic fraction isolated from green tea (GTP) affords protection against tumor promotion and tumor progression in SENCAR mouse skin. The present study was designed to further evaluate the protective effect of GTP against the induction and subsequent progression of papillomas to squamous cell carcinomas (SCCs) in experimental protocols where papillomas were developed with a low or high probability of their malignant conversion. Topical application of GTP (6 mg/animal) 30 min prior to that of 12-O-tetradecanoylphorbol-13-acetate (TPA) either once a week for 5 weeks (high risk TPA protocol) or once a week for 20 weeks (low risk TPA protocol) or mezerein (MEZ) twice a week for 20 weeks (high risk MEZ protocol) in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin resulted in significant protection against skin tumor promotion in terms of tumor incidence (32-60%), multiplicity (49-63%) and tumor volume/mouse (73-90%) at the termination of the experiment at 20 weeks. In three separate malignant progression experiments when papilloma yield in DMBA-initiated and TPA or MEZ promoted low and high risk protocols was stabilized at 20 weeks, animals were divided into two subgroups. These animals were either topically treated twice weekly with acetone (0.2 ml/animal, spontaneous malignant conversion group) or with GTP (6 mg/animal in 0.2 ml acetone) for an additional period of 31 weeks. During these treatment regimens, all suspected carcinomas were recorded and each one was verified histopathologically either at the time when tumor-bearing mouse died/moribund or at the termination of the experiment at 51 weeks. GTP resulted in significant protection against the malignant conversion of papillomas to SCC in all the protocols employed. At the termination of the experiment at 51 weeks, these protective effects were evident in terms of mice with carcinomas (35-41%), carcinomas per mouse (47-55%) and percent malignant conversion of papillomas to carcinomas (47-58%). The kinetics of malignant conversion suggest that a subset of papillomas formed in the early phase of tumor promotion in all the protocols had a higher probability of malignant conversion into SCCs because all the positive control groups (acetone treated) produced nearly the same number of carcinomas (33-38 in a group of 20 animals) at the end of the progression period. In the GTP-treated group of animals the number of carcinomas formed was less (14-20 in a group of 20 animals), which shows the ability of GTP to protect against the malignant conversion of papillomas of higher probability of malignant conversion to SCCs. The results of this study suggest that irrespective of the risk involved, GTP may be highly useful in affording protection against skin cancer risk.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Spontaneous double vessel coronary artery dissection. A case report and surgical management.

Spontaneous coronary artery dissection is an uncommon clinical entity, its presentation and management similar to atherosclerotic coronary artery disease. We report on a young adult male who presented with myocardial infarction due to simultaneous dissection of left anterior descending and right coronary artery. He was treated with bilateral interal mammary artery grafts.

Adult↗
PubMed1997

Head-Up Tilt Test (HUTT) in Patients with Episodic Bradycardia and Hypotension Following Percutaneous Coronary Interventions.

We investigated the possible association of post catheterization hypotension/bradycardia and neurocardiogenic syncope. Head up tilt test (HUTT) was performed in 12 consecutive patients (age 32Ð65 years) who developed transient hypotension (systolic blood pressure < 80 mmHg) and/or bradycardia (heart rate < 50/min) with or without syncope following a percutaneous coronary intervention. Ten patients had undergone percutaneous transluminal coronary angioplasty (PTCA) with stent implantation and one each PTCA alone and diagnostic coronary angiography. This event occurred at the time of sheath removal in 7 patients (58%). HUTT was performed with and without intravenous edrophonium (10 mg intravenous). The tilt test was negative in all patients. Post-catheterization hypotension/bradycardia responds promptly to conservative measures and it is unclear whether this is related to neurocardiogenic syncope.

Journal Article↗