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Biomedical subjects

R Agarwal

Publications and source records attributed to R Agarwal.

At least 253 records · Page 14Linked to original sources
PubMed1995

Inhibition of 12-O-tetradecanoylphorbol-13-acetate and other skin tumor-promoter-caused induction of epidermal interleukin-1 alpha mRNA and protein expression in SENCAR mice by green tea polyphenols.

Recent studies have shown that topical application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to murine skin results in increased expression of the highly inflammatory cytokine interleukin (IL)-1 alpha in the epidermis. This has led to the suggestion that IL-1 alpha directly or indirectly mediates the inflammatory and hyperplastic responses elicited by TPA and possibly by other skin tumor promoters. In the current study, we investigated the effect of skin application of a polyphenolic fraction isolated from green tea (GTP) to SENCAR mice on skin tumor-promoter-caused induction of cutaneous edema and hyperplasia, and IL-1 alpha mRNA expression. Pretreatment of the skin with GTP 30 min before that of anthralin, benzoyl peroxide, mezerein, and TPA resulted in a significant (p < 0.05) inhibition of cutaneous edema and epidermal hyperplasia caused by each of these tumor promoters. Northern blot analysis indicated that topical application of TPA, anthralin, mezerein, or benzoyl peroxide to SENCAR mice resulted in an increased expression of epidermal IL-1 alpha mRNA. Pretreatment of the skin with GTP or individual epicatechin derivatives (ECDs) present therein, 30 min before that of TPA, resulted in a significant inhibition of enhanced expression of epidermal IL-1 alpha mRNA caused by skin application of TPA. These inhibitory effects were found to be dependent on the dose of GTP. Among four epicatechin derivatives present in GTP, (-)-epicatechin-3-gallate and (-)-epigallocatechin-3-gallate were more effective than (-)-epigallocatechin and (-)-epicatechin in affording this inhibition. Preapplication of GTP was also found to afford inhibition against anthralin-, benzoyl peroxide-, and mezerein-caused increased expression of epidermal IL-1 alpha mRNA and protein. Our study suggests that the inhibition of tumor-promoter-induced IL-1 alpha mRNA and protein expression in mouse epidermis by green tea in combination with other inhibitory effects may be responsible for the anti-tumor-promoting and anti-inflammatory effects of GTP.

Animals↗
PubMed1995

Protection against ultraviolet-B radiation-induced local and systemic suppression of contact hypersensitivity and edema responses in C3H/HeN mice by green tea polyphenols.

Exposure of skin to UV radiation can cause diverse biological effects, including induction of inflammation, alteration in cutaneous immune cells and impairment of contact hypersensitivity (CHS) responses. Our laboratory has demonstrated that oral feeding as well as topical application of a polyphenolic fraction isolated from green tea (GTP) affords protection against the carcinogenic effects of UVB (280-320 nm) radiation. In this study, we investigated whether GTP could protect against UVB-induced immunosuppression and cutaneous inflammatory responses in C3H mice. Immunosuppression was assessed by contact sensitization with 2,4-dinitrofluorobenzene applied to UVB-irradiated skin (local suppression) or to a distant site (systemic suppression), while double skin-fold swelling was used as the measure of UVB-induced inflammation. Topical application of GTP (1-6 mg/animal), 30 min prior to or 30 min after exposure to a single dose of UVB (2 kJ/m2) resulted in significant protection against local (25-90%) and systemic suppression (23-95%) of CHS and inflammation in mouse dorsal skin (70-80%). These protective effects were dependent on the dose of GTP employed; increasing the dose (1-6 mg/animal) resulted in an increased protective effect (25-93%). The protective effects were also dependent on the dose of UVB (2-32 kJ/m2). Among the four major epicatechin derivatives present in GTP, (-)-epigallocatechin-3-gallate, the major constituent in GTP, was found to be the most effective in affording protection against UVB-caused CHS and inflammatory responses. Our study suggests that green tea, specifically polyphenols present therein, may be useful against inflammatory dermatoses and immunosuppression caused by solar radiation.

Animals↗
PubMed1995

Intracoronary stent placement in thrombus containing vein graft lesions.

Intracoronary stents are traditionally considered to be contraindicated in presence of thrombus. However recent advances in stent deployment technique have reduced the risk of stent thrombosis. We report the placement of a stent in a thrombus laden saphenous vein graft to the posterior descending artery. Three months later the stent site was patent with severe stenosis with thrombus in another graft which was also stented. Intracoronary stents should be considered in patients with complex lesion even in presence of intraluminal thrombus.

Angioplasty, Balloon, Coronary↗
PubMed1994

Inhibition of spontaneous and photo-enhanced lipid peroxidation in mouse epidermal microsomes by epicatechin derivatives from green tea.

In recent years green tea has been shown to afford protection against chemical- and photo-carcinogenesis in several animal tumor bioassay systems. It has been suggested that the wide range of anticarcinogenic properties of green tea may be due to the antioxidant effect of epicatechins present therein. In this study, we assessed whether these epicatechin derivatives (ECDs)--namely (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin (EC) inhibit spontaneous and photo-enhanced lipid peroxidation (LPO) in mouse epidermal microsomes. Our data indicate that significant inhibition (significance levels for P, < 0.05 to < 0.0001) was evident by EGCG, EGC and ECG in Fe3+/ADP supported LPO. Interestingly each of these epicatechin derivatives was also effective in inhibiting photo-enhanced LPO generated by incubating epidermal microsomes in the presence of silicon phthalocyanine and 650 nm irradiation. However, at equimolar basis, EGCG, which is also the major constituent in GTP, showed maximum inhibitory effects compared to other ECDs. Taken together, our results provide the direct evidence for the antioxidant property of ECDs, and suggest that such an effect may contribute towards anticarcinogenic (specifically anti-skin tumor) promoting effects of green tea.

Animals↗
PubMed1994

Evidence for multiple inducible cytochrome P450 isozymes in SENCAR mouse skin by pyridine.

Pyridine, an amphipathic solvent, is widely used in industry and is also a constituent of tobacco and its smoke. Since, in addition to inhalation and ingestion, pyridine is also readily absorbed through skin, we assessed the effect of skin application of pyridine on monooxygenase activities and cytochrome P450 (CYP) isozymes and CYP mRNA levels in the skin of SENCAR mice. Compared to controls, a single topical application of pyridine (30 or 50 mg/100 g body weight) resulted in induction of cutaneous 7-ethoxyresorufin O-deethylase, 7-pentoxyresorufin O-depentylase, and erythromycin N-demethylase activities. Pyridine treatment also resulted in an increase in reactivity with monoclonal antibodies directed against CYP 1A1, 2B1 and 3A. In Northern blot analysis, treatment of pyridine also showed a significant increase in mRNA for Cyp1a-1 in the skin. These data indicate that murine skin contains multiple inducible CYP isozymes, and that pyridine results in the induction of at least three families of CYP in murine skin.

Animals↗
PubMed1994

Pathophysiology of potassium absorption and secretion by the human intestine.

When normal people ingest 90 mEq/day of K+ in their diet, they absorb about 90% of intake (81 mEq) and excrete an equivalent amount of K+ in the urine. Normal fecal K+ excretion averages about 9 mEq/day. The vast majority of intestinal K+ absorption occurs in the small intestine; the contribution of the normal colon to net K+ absorption and secretion is trivial. K+ is absorbed or secreted mainly by passive mechanisms; the rectum and perhaps the sigmoid colon have the capacity to actively secrete K+, but the quantitative and physiological significance of this active secretion is uncertain. Hyperaldosteronism increases fecal K+ excretion by about 3 mEq/day in people with otherwise normal intestinal tracts. Cation exchange resin by mouth can increase fecal K+ excretion to 40 mEq/day. The absorptive mechanisms of K+ are not disturbed by diarrhea per se, but fecal K+ losses are increased in diarrheal diseases by unabsorbed anions (which obligate K+), by electrochemical gradients secondary to active chloride secretion, and probably by secondary hyperaldosteronism. In diarrhea, total body K+ can be reduced by two mechanisms: loss of muscle mass because of malnutrition and reduced net absorption of K+; only the latter causes hypokalemia. Balance studies in patients with diarrhea are exceedingly rare, but available data emphasize an important role for dietary K+ intake, renal K+ excretion, and fecal K+ losses in determining whether or not a patient develops hypokalemia. The paradoxical negative K+ balance induced by ureterosigmoid anastomosis is described. The concept that fecal K+ excretion is markedly elevated in patients with uremia as an intestinal adaptation to prevent hyperkalemia is analyzed; we conclude that the data do not convincingly show the existence of a major intestinal adaptive response to chronic renal failure.

Adaptation, Physiological↗
PubMed1994

Chemical and enzyme-catalysed synthesis of quinoline arene hydrates.

Arene hydrates of quinoline have been synthesized by enzyme-catalysed benzylic and allylic hydroxylation of dihydroquinolines in growing cultures of the fungus Mortierella isabellina and in liver microsomal preparations. A preference for allylic hydroxylation was generally observed in eukaryotic systems. Evidence of epoxidation of dihydroarenes by both the fungal and animal enzyme systems was also obtained. The chemical synthesis of these arene hydrates (5-hydroxy-5,6-dihydroquinoline, 6-hydroxy-5,6-dihydroquinoline, 7-hydroxy-7,8-dihydroxyquinoline, and 8-hydroxy-7,8-dihydroquinoline) from the corresponding hydroxy-5,6,7,8-tetrahydroquinolines, has also been accomplished.

Animals↗
PubMed1994

The post-transurethral resection of prostate syndrome: therapeutic proposals.

Absorption of large volumes of irrigation fluid during transurethral resection of the prostate (TURP) can produce hyponatremia, coma, blindness, and cardiorespiratory depression. This has been termed the "post-TURP syndrome." The pathophysiology and management of this syndrome are controversial. A case of severe post-TURP syndrome due to the absorption of hypotonic glycine irrigant is reported. This patient developed severe hyponatremia, slight hypo-osmolality, hyperglycinemia, hyperserinemia, hyperammonemia, and hypocalcemia. He became comatose, profoundly hypotensive, bradycardic, and transiently blind. Because of this combination of severe biochemical, neurologic, and hemodynamic abnormalities, we elected to treat this patient with hemodialysis. The biochemical and clinical manifestations resolved completely. The pathophysiology and treatment of this disorder are discussed and a role for hemodialysis is suggested.

Aged↗
PubMed1994

Heterogeneity in gentamicin clearance between high-efficiency hemodialyzers.

Gentamicin is frequently prescribed for treatment of gram-negative infections in patients on dialysis. The amino-glycoside is renally excreted; therefore, dosage modifications are required in patients on hemodialysis. The introduction of short-duration dialysis using high-efficiency hemodialyzers requires that the dialysance of gentamicin be re-examined. We recently demonstrated that high-efficiency dialyzers have a superior gentamicin clearance as compared with conventional dialyzers. In this study we examined the dialysance of gentamicin in two high-efficiency dialyzers using a randomized, controlled, cross-over design. Despite a comparable amount of dialysis (Kt/V urea), rate of dialysis (K/V urea), and ultrafiltration, there were significant differences noted in gentamicin removal between the high-efficiency cuprammonium rayon and polysulfone dialyzers. Furthermore, the amount of dialysis (Kt/V urea) could predict the fractional gentamicin clearance for the TAF 175L dialyzer (Terumo Corp, Somerset, NJ) and may be useful in the initial planning of gentamicin therapy. In addition, since gentamicin is a middle molecule (molecular weight, 500 to 2,000 d), the study suggests a superior middle molecule clearance of cuprammonium rayon dialyzer compared with a high-efficiency polysulfone dialyzer. The substantial heterogeneity in gentamicin clearance, even between dialyzers of the same class, emphasizes the importance of monitoring drug levels in hemodialysis patients receiving this drug.

Adult↗
PubMed1994

Inhibitory effect of silymarin, an anti-hepatotoxic flavonoid, on 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity and mRNA in SENCAR mice.

In recent years, considerable emphasis has been placed on identifying new cancer chemopreventive agents which could be useful for human populations. Silymarin, an anti-oxidant flavonoid isolated from artichoke, has been shown to possess significant activity against hepatotoxicity and other pharmacological and physiological disorders. Since many antioxidants inhibit tumor promotion, and because ornithine decarboxylase (ODC) is a well known biochemical marker of tumor promotion, we assessed the effect of skin application of silymarin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal ODC activity and ODC mRNA levels in SENCAR mice. Application of silymarin at doses of 0.5-18 mg (1-37 mumol)/mouse prior to that of TPA (2.5 micrograms) treatment resulted in significant inhibition of TPA-induced epidermal ODC activity in a dose- and time-dependent manner. Northern blot analysis revealed that topical application of silymarin at the dose of 2 mg/mouse resulted in almost complete inhibition of TPA-induced epidermal ODC mRNA. In other studies, silymarin also showed significant inhibition of epidermal ODC activity induced by several other tumor promoters, including free radical-generating compounds. Our data suggest that silymarin could be a useful anti-tumor promoting agent capable of ameliorating the tumor promoting effects of a wide range of tumor promoters.

Animals↗
PubMed1994

Green tea and skin--anticarcinogenic effects.

Because of its special aroma, green tea is a popular beverage consumed by some human populations worldwide. In recent years, many laboratory studies have shown that in a variety of animal tumor bioassay systems the administration of green tea, specifically the polyphenolic fraction isolated from green tea leaves (green tea polyphenols), affords protection against cancer induction. In mouse skin tumor bioassay systems, topical application of green tea polyphenols to skin has been shown to result in protection against a) 3-methylcholanthrene-induced skin tumorigenicity, b) 7,12-dimethylbenz(a)anthracene (DMBA)-induced skin tumor initiation, c) 12-O-tetradecanoylphorbol-13-acetate and other tumor promoters caused tumor promotion in DMBA-initiated skin, and d) benzoyl peroxide- and 4-nitroquinoline N-oxide caused enhanced malignant progression of nonmalignant lesions. Green tea extract has also been shown to cause partial regression of established skin papillomas in mouse. Similarly, chronic oral feeding of green tea polyphenols or water extract of green tea has also been shown to result in the protection against both chemical carcinogen- and ultraviolet B radiation-induced skin tumorigenicity. Collectively these data suggest that green tea possesses significant chemopreventive effect against each stage of carcinogenesis, and that it may be useful against inflammatory responses associated with the exposure of skin to chemical tumor promoters as well as to solar radiation. Available data regarding the mechanism by which green tea affords these diversified effects is discussed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Ras p21 farnesylation in ultraviolet B radiation-induced tumors in the skin of SKH-1 hairless mice.

Cutaneous exposure to solar ultraviolet B (UVB) radiation is well recognized as the major cause of skin cancer in humans; however, the precise molecular mechanisms whereby UVB mediates carcinogenesis remains unclear. The involvement of activated ras oncogenes has been demonstrated extensively in both animal and human skin cancers. Activated ras oncogenes encode mutated ras p21 that exist in the guanosine triphosphate-bound active state and, following localization to the inner side of the plasma membrane, cause cellular transformation. This membrane association requires three post-translational modifications occurring at the C-terminus of the ras p21. The farnesylation of p21 by a cytosolic enzyme known as farnesyltransferase (FTase) is the critical step that triggers biologic functions of the ras p21. In this study, FTase activity was found to be substantially higher (approximately threefold) in UVB radiation-induced tumors in SKH-1 hairless mice compared to epidermis from controls. Western blot analysis showed significantly higher levels of Ha-ras p21 in both cytosolic and membrane fractions prepared from tumors compared to epidermis. Pan ras antibody against mutated p21 at codon 12 showed very strong reactivity for ras val-12p21 in tumors but not in normal epidermis, suggesting a gly to val substitution at 12th position in ras p21 in UVB-induced tumors. Our data indicate that enhanced FTase activity and the processing of overexpressed p21 in UVB-induced tumors are correlated, and predict the role of point mutation at the 12th codon of the ras oncogene during photocarcinogenesis in mice.

Alkyl and Aryl Transferases↗
PubMed1994

Multiple cytochrome P450 isozymes in murine skin: induction of P450 1A, 2B, 2E, and 3A by dexamethasone.

Cytochrome P450s (P450s) are a supergene family of enzymes responsible for the metabolism of a wide range of endogenous and foreign compounds. P450 isozymes possess overlapping substrate specificity. Systemic administration of dexamethasone, a widely used topical agent in dermatologic practice, to animals is known to result in the induction of multiple P450 isozymes in liver. In this study the effect of topical application of dexamethasone to mice on P450-dependent monooxygenase activities, expression of P450 isozymes, and P450 mRNA levels in skin was assessed. The treatment of mice with dexamethasone resulted in significant induction of 7-ethoxyresorufin O-deethylase (2.3 times), 7-pentoxyresorufin O-depentylase (19.2 times), para-nitrophenol hydroxylase (7.5 times), and erythromycin N-demethylase (2.2 times) activities; the monooxygenases catalyzed preferentially by P450 isozymes 1A1, 2B1, 2E1, and 3A, respectively. Immunoblot analysis of cutaneous microsomes, employing antibodies directed against purified P450s 1A1/2, 2B1/2, 2E1, and 3A, showed that dexamethasone treatment results in an increased immunoreactivity (1.8-13.9 times). In immunohistochemical staining of skin with antibody against P4502B1/2, topical application of dexamethasone resulted in an increased reactivity towards microsomal protein in the suprabasal layer of the epidermis and with the cells of the hair follicles. Whereas constitutive expression of mRNAs for CYP1A1 and CYP2E1 was evident in murine skin, any change in the levels of these mRNAs following treatment with dexamethasone was not apparent. The results of our study indicate that the application of dexamethasone to murine skin results in the induction of several families of P450 isozymes, suggesting that murine skin contains multiple inducible P450 isozymes capable of participating in the metabolism of a wide range of xenobiotics and endogenous compounds.

Administration, Topical↗