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Biomedical subjects

R Agarwal

Publications and source records attributed to R Agarwal.

At least 325 records · Page 18Linked to original sources
PubMed1991

Metabolism of benzo[a]pyrene by human melanocytes in culture.

Benzo[a]pyrene (B[a]P) is a ubiquitous environmental pollutant and known skin carcinogen. In the present study, in vitro addition of [3H]B[a]P to normal human melanocytes in culture, isolated from adult human skin, resulted in the metabolism of [3H]B[a]P both intracellularly and extracellularly. HPLC analysis showed that [3H]B[a]P-9,10- and 7,8-diol were the major intracellular and extracellular metabolites followed by 3,6-quinone, 9-hydroxy and 3-hydroxy metabolites. Significant amounts of the [3H]B[a]P metabolites were found to be present in the sonicated cell suspension and culture medium as the glucuronide and sulfate conjugates. In total 37.3% of the [3H]B[a]P added in the culture medium was metabolized by melanocytes, of which 21.1% was quantified as the intracellular and 16.2% as the extracellular metabolites. Our data show that human melanocytes are capable of metabolizing B[a]P.

Benzo(a)pyrene↗
PubMed1991

All-trans retinoic acid protects against conversion of chemically induced and ultraviolet B radiation-induced skin papillomas to carcinomas.

It is becoming increasingly clear that cutaneous carcinogenesis in murine skin is a stepwise process comprising of initiation, promotion and progression. Most of the papillomas induced by an initiation-promotion protocol regress, while a few of them progress to malignant carcinomas. Progression of benign tumors into malignant cancer is critical since the latter lesions are capable of metastatic spread and eventual death. Inhibitors of the conversion process are therefore likely to be useful as cancer chemopreventive agents. All-trans retinoic acid (RA) is a known regulator of cellular proliferation and differentiation, and a known inhibitor of tumor promotion in murine skin. In this study we assessed the effect of topical application of RA on conversion of benign skin papillomas to malignant carcinomas. Papillomas were induced in SENCAR mice by topical application of 7,12-dimethylbenz[a]anthracene (DMBA) as tumor initiator followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) as tumor promoter. In SKH-1 hairless mice papillomas were induced by thrice weekly exposure to ultraviolet B (UVB) radiation. At 18 (DMBA/TPA group) and 25 (UVB group) weeks papilloma yield stabilized and no new tumors developed. Beginning at the 20th week (DMBA/TPA group) and at the 27th week (UVB group), malignant conversion was achieved by twice weekly topical application of TPA or free radical-generating compounds benzoyl peroxide (BPO), 2,2-azobis(2-amidinopropane) (ABP) and tert-butyl peroxybenzoate (BPB). Application of RA (10 micrograms/animal) 1 h prior to skin application of TPA, BPO, ABP or BPB afforded significant protection (up to 70%) only against malignant conversion mediated by free radical-generating compounds in both chemically induced and UVB-induced benign skin papillomas. On the other hand, preapplication of RA was less effective in the suppression of spontaneous malignant conversion in vehicle-treated animals. These results suggest that, in addition to their anti-tumor promoting effects, retinoids may also act as anti-carcinogens by inhibiting the process of malignant conversion induced by free radical-generating compounds.

Animals↗
PubMed1991

Inhibition of mutagenicity in Salmonella typhimurium and skin tumor initiating and tumor promoting activities in SENCAR mice by glycyrrhetinic acid: comparison of 18 alpha- and 18 beta-stereoisomers.

Licorice has been used as medicine and as sweetening agent in food products. The major water-soluble constituent of licorice is glycyrrhizin (GL), an oleanane triterpenoide, which is known to be partly hydrolyzed by glucuronidase to its aglycone glycyrrhetinic acid (GA) which exists in 18 alpha (alpha-GA) and 18 beta (beta-GA) stereoisomeric forms. In this study alpha-GA and beta-GA were found to inhibit the mutagenicity of benzo[a]pyrene (B[a]P), 2-aminofluorene and aflatoxin B1 in Salmonella typhimurium TA98 and TA100. beta-GA was more effective than alpha-GA as an antimutagen. In the two-stage skin tumorigenesis protocol using 7,12-dimethylbenz[a]anthracene (DMBA) as the tumor initiating agent followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate as tumor promoter, pretreatment of SENCAR mice with alpha-GA or beta-GA resulted in significant protection against tumor initiation as well as tumor promotion. As an anti-tumor initiating agent, beta-GA was found to be more effective than alpha-GA. Similarly, topical application of beta-GA was found to be more effective than alpha-GA in inhibiting the binding of both [3H]B[a]P and [3H]DMBA to epidermal DNA. However, as an anti-tumor promoter, alpha-GA and beta-GA showed comparable effects. Our results suggest that both alpha-GA and beta-GA possess substantial anti-skin tumor initiating and anti-skin tumor promoting activities.

Animals↗
PubMed1991

Protection against ultraviolet B radiation-induced photocarcinogenesis in hairless mice by green tea polyphenols.

Our recent studies have shown that polyphenols present in green tea (GTP) possess significant antigenotoxic activity and afford protection against polycyclic aromatic hydrocarbon-induced skin tumor initiation in mice. In this study we assessed the effect of oral feeding and topical application of GTP on ultraviolet B (UVB) radiation-induced skin carcinogenesis in female SKH-1 hairless mice. Chronic oral feeding of GTP (0.1%, w/v) in drinking water resulted in significantly (P less than 0.01) lower tumor yield (percent of animals with tumors and number of tumors per mouse) and extended TDT50 (P less than 0.05), as compared to animals receiving normal drinking water. Topical application of GTP before UVB irradiation also afforded protection against photocarcinogenesis; however, the protective response was lower than that observed by oral feeding of GTP in drinking water. These results, in conjunction with our prior publications, suggest that consumption of green tea may reduce the risk of some forms of human cancer induced by both physical and chemical environmental carcinogens.

Animals↗
PubMed1991

Piezoelectric effect in renal calculi.

The piezoelectric effect is investigated for the first time in renal calculi in vitro. The kidney stones are shaped from solid samples as well as from stones crushed into powder and pressed into tablets. Presence of alpha quartz in the renal calculi is investigated by an X-ray technique and the presence of this constituent also helps to explain the piezoelectric effect in the renal calculi. The dielectric and piezoelectric parameters are studied in detail.

Electric Conductivity↗
PubMed1991

Stress-generated electric potential in renal stones due to ultrasound [43.35.Cg, 43.80.Cs, 62.20.Dc].

The presence of renal calculi in the kidney causes discomfort and pain to the patients and so removal of such stones is thus important. These days, nonsurgical and noninvasive techniques are used for this purpose. In this laboratory, an ultrasonic kidney stone disintegrator is being developed. In order to know design parameters for such instrument, various physical and mechanical properties of renal calculi, have been studied. During the course of ultrasonic studies in kidney stones, "stress-generated electric potential" has been observed. The in vitro samples of the kidney stones were obtained from local hospitals in Delhi. The stones were sliced into a regular shape of 1 x 1 cm. An ultrasonic field at 2.5 and 5.5 MHz was applied to the samples normal incidence to one surface. On the two surfaces parallel to the ultrasonic beam, two electrodes were applied and an electric potential was measured across these electrodes. This stress-generated potential was measured with the help of an electrometer, and varied from 0.50 to 3.0 mV and 3.10 to 12.50 mV at the two frequencies, respectively. This investigation shows that the renal calculi exhibit a stress-generated electric voltage due to their piezoelectric property.

Electric Conductivity↗
PubMed1991

A phase I study of recombinant human interferon-alpha 2a or human lymphoblastoid interferon-alpha n1 and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma.

To determine the safety, maximum tolerated dose, and preliminary efficacy of concomitant interferon-alpha and zidovudine therapy in AIDS-related Kaposi's sarcoma (KS), 56 patients with biopsy-proven KS and documented human immunodeficiency virus type 1 (HIV) infection were enrolled into a phase I study. Interferon-alpha was given intramuscularly at a dose of 9, 18, or 27 mu once a day and zidovudine was administered as 100 or 200 mg every 4 h for 8 weeks followed by a 48-week maintenance period. The major toxicities were anemia, neutropenia, and hepatotoxicity. Neutropenia was dose limiting with 1,200 mg of zidovudine/day and the lowest dose of interferon-alpha (9 mu/day). Hepatotoxicity was dose limiting with 27 mu of interferon and 600 mg of zidovudine/day. Cumulative dose-related anemia or neutropenia was not seen during long-term follow-up. The maximum tolerated doses for the combination were defined as 18 mu daily for interferon-alpha and 600 mg daily for zidovudine. Variable changes in CD4 lymphocytes occurred during the first 8 weeks of therapy. At higher doses of the combination, sustained increases in median CD4 lymphocyte numbers were noted (p less than 0.001). In HIV antigenemic patients, progressive antigen suppression was seen with increasing doses of the combination (p less than 0.005). The overall antitumor response rate was 47%. Tumor regression was associated with better survival benefits (p less than 0.001) and a pretreatment CD4 cell count greater than or equal to 200 cells/mm3 (p = 0.01). In conclusion, intermediate doses of interferon-alpha and lower doses of zidovudine appear to be relatively well tolerated and associated with disease improvement, including survival benefits.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A possible role of caesium radiations in the control of propagation of hookworm.

Faeces charcoal mixtures containing eggs of sheep hookworm, Haemonchus contortus were exposed to caesium radiations (23 r to 1656 r) from 1st to 7th day of incubation. Each plate was exposed only once. A dose related inhibition of transformation of eggs to infective larvae was observed. The maximum effect was observed on 2nd day of incubation. The radiation has maximum effect on the 1st stage larvae followed by 2nd stage. The 3rd stage or ineffective larvae are relatively resistant to the effect of radiation.

Animals↗
PubMed1991

Photodynamic therapy of murine skin tumors using Photofrin-II.

Photodynamic therapy (PDT) is a new experimental cancer therapy in which a photosensitizing chemical that selectively localizes within tumors is given to a tumor-bearing individual and the tumor is then irradiated by wavelengths within the visible spectrum of the photosensitizer. The only photosensitizer currently approved for human clinical trials is Photofrin-II (Pf-II). In most preclinical studies, the effectiveness of Pf-II has been assessed in implanted tumor models rather than in systems in which tumors are grown in their own connective tissue matrix. In this study, the pharmacokinetics, tumor ablation capability and cutaneous photosensitizing capacity of Pf-II were assessed in mice bearing chemically induced or ultraviolet B radiation (UVB)-induced benign skin neoplasms. Intraperitoneal administration of Pf-II (5 mg/kg body weight) to tumor-bearing animals showed maximum tumor: normal skin ratio of the photosensitizer at 72 h. When SENCAR mice bearing chemically induced tumors were irradiated with visible light corresponding to the absorption spectrum of the photosensitizer, up to 89% ablation in tumor volume at 20 d post-irradiation was observed. Animals treated with Pf-II and exposed to visible light showed significant cutaneous photosensitization for at least 6 d after-irradiation. Treatment of SKH-1 hairless mice bearing UVB-induced cutaneous neoplasms with Pf-II exhibited similar pharmacokinetics, skin tumor ablation effects and cutaneous photosensitivity. Our data indicate that Pf-II has significant activity towards the ablation of murine skin benign tumors grown in their own tissue matrix, suggesting that such a murine skin tumor model system could be valuable in evaluating the photodynamic effects of newly developed photosensitizers.

Animals↗
PubMed1991

Dielectric properties of kidney stones as electro-ceramics.

Dielectric properties of kidney stones in processed form are studied in a frequency range of 1 kHz-10 MHz. The samples under test are in the form of discs of the stones. The dielectric properties are found to be highly dependent on the frequency, and as expected, similar to those of conventional electro-ceramics and other such bio-materials, due to presence of alpha-quartz in the calculi.

Electric Conductivity↗
PubMed1991

Central hyperthermic effect of arsenic in rabbits.

Hyperthermic effect of arsenic was investigated in rabbits. Injections of arsenic trioxide (0.0001 to 0.1 micrograms) into a lateral cerebral ventricle of the rabbit evoked a dose-dependent hyperthermia, respiratory stimulation and peripheral vasodilatation. Heat loss through respiratory stimulation and peripheral vasodilatation appeared responsible for the long latent period and the slight hypothermia sometimes obtained during this period as these effects followed the same time course. These effects were centrally mediated as demonstrated by the lack of efficacy of the same doses by the intravenous route. The hyperthermic effect of arsenic was antagonized by the sulphydryl donator, dimercaprol, the a-adrenoceptor blocking agent-phenoxybenzamine and the PG-synthesis inhibitor-aspirin. Multiple sites, for antagonistic effects of these substances can be explained by the action of arsenic in inactivating sulphydryl containing enzymes which are many and catalyze diverse biochemical reactions.

Animals↗
PubMed1990

Evidence for the involvement of singlet oxygen in the photodestruction by chloroaluminum phthalocyanine tetrasulfonate.

In recent years, choloroaluminum phthalocyanine tetrasulfonate (A1PCTS) has been shown to be a promising photosensitizer for the photodynamic therapy (PDT) of cancer. Although its mechanism of photodynamic action is not well defined, A1PCTS is going to be under clinical trials of PDT. In this study, in vitro addition of A1PCTS to a suspension of rat epidermal microsomes followed by irradiation with red light (approximately 675 nm) resulted in significant destruction of cytochrome P-450 and associated monooxygenase activities. The photodestructive effect was dependent on both the dose of A1PCTS and the duration of light exposure. Studies using various quenchers of reactive oxygen species showed that only scavengers of singlet oxygen such as histidine, 2,5-dimethylfuran, beta-carotene and sodium azide afforded substantial protection against photodestruction. Our data indicate the direct involvement of singlet oxygen in the A1PCTS-mediated photodestructive process.

Aluminum↗
PubMed1990

MgADP-induced changes in the structure of myosin S1 near the ATPase-related thiol SH1 probed by cross-linking.

The structural consequences of MgADP binding at the vicinity of the ATPase-related thiol SH1 (Cys-707) have been examined by subjecting myosin subfragment 1, premodified at SH2 (Cys-697) with N-ethylmaleimide (NEM), to reaction with the bifunctional reagent p-phenylenedimaleimide (pPDM) in the presence and absence of MgADP. By monitoring the changes in the Ca2(+)-ATPase activity as a function of reaction time, it appears that the reagent rapidly modifies SH1 irrespective of whether MgADP is present or not. In the absence of nucleotide, only extremely low levels of cross-linking to the 50-kDa middle segment of S1 can be detected, while in the presence of MgADP substantial cross-linking to this segment is observed. A similar cross-link is also formed if MgADP is added subsequent to the reaction of the SH2-NEM-pre-modified S1 with pPDM in the absence of nucleotide. Isolation of the labeled tryptic peptide from the cross-linked adduct formed with [14C]pPDM, and subsequent partial sequence analyses, indicates that the cross-link is made from SH1 to Cys-522. Moreover, it appears that this cross-link results in the trapping of MgADP in this S1 species. These data suggest that the binding of MgADP results in a change in the structure of S1 in the vicinity of the SH1 thiol relative to the 50-kDa "domain" which enables Cys-522 to adopt the appropriate configuration to enable it to be cross-linked to SH1 by pPDM.

Adenosine Diphosphate↗
PubMed1990

Studies of proto-oncogene expression in the chronic and blastic phases of chronic myelogenous leukemia.

Chronic and blastic phase chronic myelogenous leukaemia cells have been studied by northern and Southern blot analysis. DNA from matched chronic and blastic phase cells obtained from the same patient demonstrated that the rearrangement site within the breakpoint cluster region did not change at the time of blastic crisis. A search for a mutation in a controlling region of the first exon of c-myc also failed to demonstrate any new abnormality at the time of blastic crisis. While some differences in the transcript levels for several genes (c-myc, p53, histone H3, MRS) were detected, these differences could be ascribed to differences in the proportions of immature cells during the chronic and blastic phases. The data suggested that the c-myc transcripts in blastic phase cells and in immature chronic phase cells differ in that the latter contain some c-myc transcripts that are not polyadenylated. Differences in c-myc transcript half-life could contribute to the differences in the behaviour of chronic phase and blastic phase immature cells.

Blast Crisis↗
PubMed1990

Mechanical and ultrasonic parameters of kidney stones.

The mechanical and ultrasonic parameters of kidney stones have been measured in vitro. The techniques used for these measurements are briefly described and the data are presented. It was found that the mechanical crushing strength correlates with the acoustic velocity in the calculi, which in turn is a function of the stones' chemical deposition. It was shown that the crushing strength increased exponentially with velocity in the range from approximately 22 kg/mm2 to approximately 100 kg/mm2. The corresponding ultrasonic velocity in the stones varied between approximately 2,200 m/sec to about 3,000 m/sec. It is suggested that these data could be used to determine the desirable characteristics of a piezoelectric lithotripter.

Biophysical Phenomena↗
PubMed1990

Proximal versus distal carcinoma of the stomach. A clinicoendoscopic study.

During the period 1978 to 1988, 4619 upper gastrointestinal fibreoptic panendoscopies were carried out. There were 106 (2.2%) histologically confirmed cases of carcinoma of the stomach. The annual incidence was 9.6. The peak incidence was in the fifth decade. The mean age of these patients was 49.4 years and the male: female ratio was 3.6:1. The most frequent symptoms were weight loss (81%) and anorexia (72.9%). Dysphagia was present in 30% of patients. Thirty two percent of patients had proximal carcinoma, 63.2% had distal carcinoma and in 4.7% the whole stomach was involved. Patients with distal carcinoma had a longer history (P less than 0.01) and were more likely to present with weight loss (P less than 0.001), anorexia (P less than 0.005), abdominal pain (P less than 0.05) and abdominal lump (P less than 0.05), compared to proximal carcinomas. Dysphagia was, however, more likely to be present in patients with proximal carcinomas (P less than 0.001).

Adult↗