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Biomedical subjects

R S Varma

Publications and source records attributed to R S Varma.

At least 19 recordsLinked to original sources
PubMed2006

Spontaneous tumour lysis syndrome associated with non-Hodgkin's lymphoma--a case report.

Spontaneous tumour lysis syndrome is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, metabolic acidosis and hypocalcemia, that occur even prior to the treatment of a neoplasm. This rare occurrence was encountered in a patient with non-Hodgkin's lymphoma (NHL), of follicular cell type. Conservative but intensive treatment led to complete resolution. Subsequent chemotherapy was well tolerated.

Acidosis, Lactic↗
PubMed2001

Catalyst-free reactions under solvent-free conditions: microwave-assisted synthesis of heterocyclic hydrazones below the melting points of neat reactants.

The reaction of neat 5- or 8-oxobenzopyran-2(1H)-ones, 1-3, with a variety of aromatic and heteroaromatic hydrazines, 4, is remarkably accelerated upon irradiation in a household microwave oven in the absence of any catalyst, solid support or solvent thus providing an environmentally friendly route to several heterocyclic hydrazones.

Journal Article↗
PubMed2000

Effects of nitric oxide donors on the retinal function measured with electroretinography.

It has been reported that nitric oxide raises c-GMP in the vascular muscle to cause vasodilation and to improve blood flow in the retina. Consequently, a diverse group of potential nitric oxide (NO) donors were synthesized and evaluated for their effectiveness in improving the retinal function after ischemic insult. These compounds include an NO carrier, N-acetyl-S-nitrosoglutathione (RVC-593), several NO donors such as N-nitropyrazole derivatives (RVC-595, RVC-596, RVC-597, RVC-598, and RVC-599) and two fused N-heterocycles, 4H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxides, (RVC-600 and RVC-601). Most of the compounds demonstrated the pharmacological activity in the ophthalmic model, except the pyrazole derivatives (RVC-595, RVC-596 and RVC-599) that bear bulky aromatic substituents at the R2-position.

Animals↗
PubMed1997

Nitric oxide donors: effects of S-nitrosoglutathione and 4-phenyl-3-furoxancarbonitrile on ocular blood flow and retinal function recovery.

It is known that NO is involved in the regulation of intraocular pressure (IOP) and retinal function recovery after ischemia. Thus, S-nitrosoglutathione (RVC-588) and 4-phenyl-3-furoxancarbonitrile (RVC-589) as NO donor and precursor, respectively, were studied in terms of their ability to increase b-wave recovery of electroretinogram (ERG) and ocular blood flow. It was found that RVC-588 increased b-wave amplitude markedly from 28% (control) to 67% (treated) and the blood flow significantly in the retina, choroid, and ciliary body. In the case of RVC-589, the b-wave recovery was significantly increased from 30% (control) to 51% (treated) but was less marked than that of RVC-588. The blood flow in the eye tissues was not significantly increased by RVC-588, but there was a clear tendency to enhance in the retina, choroid and iris. These results indicate that NO can be released effectively from S-nitrosothiols but less significantly from furoxans.

Animals↗
PubMed1995

Hybridization of DNA targets to glass-tethered oligonucleotide probes.

Hybridization of nucleic acids to surface-tethered oligonucleotide probes has numerous potential applications in genome mapping and DNA sequence analysis. In this article, we describe a simple standard protocol for routine preparation of terminal amine-derivatized 9-mer oligonucleotide arrays on ordinary microscope slides and hybridization conditions with DNA target strands of up to several hundred bases in length with good discrimination against mismatches. Additional linker arms separating the glass surface from the probe sequence are not necessary. The technique described here offers a powerful tool for the detection of specific genetic mutations.

Base Sequence↗
PubMed1995

Ocular hypotensive effects of L-arginine and its derivatives and their actions on ocular blood flow.

Effects of L-arginine and some related compounds on the intraocular pressure recovery (IOPR) and ocular blood flow in rabbits had been studied. It was found that L-arginine (RVC-579) and N alpha-benzoyl-L-arginine ethyl ester (RVC-578) delayed the IOPR markedly: The IOPR of the contralateral non-treated eye was delayed to the same extent as the treated eye. The effects of closely related congeners L-(+)-canavanine (RVC-581) and L-homoarginine (RVC-580) on the IOPR were qualitatively similar to RVC-579 and RVC-578 but less effective. RVC-578 was found to increase the blood flow significantly in ciliary body, retina and choroid. On the other hand, NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, reduced the blood flow in choroid at 60 and 120 min after drug administration and did not increase the blood flow in iris, ciliary body and retina. These results indicate that L-arginine and its derivative are capable of lowering the IOP possibly through the formation of nitric oxide to relax the blood vessel and to reduce the IOP as a result.

Animals↗
PubMed1995

Improvement of retinal functions after ischemia with L-arginine and its derivatives.

Retinal ischemia was created by occlusion of rat central retinal artery for 30 minutes. The loss of retinal function was indicated by the loss of b-wave of electroretinogram. The recovery of retinal function after reperfusion of central retinal artery was observed with the gradual recovery of b-wave amplitude to approximately 20% of original b-wave amplitude. When L-arginine (RVC-579) was administered at the time of retina ischemia, the b-wave amplitudes recovered up to 64% of original height and were significantly higher than corresponding controls at 120, 180, and 240 min after ischemia. When the derivative of L-arginine, N alpha-benzoyl-L-arginine ethyl ester (RVC-578), was administered, the b-wave recovery was significantly higher than corresponding controls at 90, 120, 180, and 240 min after ischemia; the recovery reached 51% of the original b-wave value. These results indicate that the L-arginine and its lipophilic derivatives could be used for the treatment of ischemic retinopathy. Since L-arginine is a natural amino acid, it is not expected to produce major side effects, if any, and could pave the way for the development of a safer drug to be used in the clinics. Compounds which increase the formation of NO in vivo, dilate blood vessels. Both L-arginine and RVC-578 can be placed in this category. They may improve effects of retinal ischemia by increasing NO production.

Animals↗
PubMed1994

Effect of some phytogenic agents and synthetic compounds on complement cascade-mediated hemolysis.

A variety of anti-inflammatory compounds obtained from various medicinal plants (phytogenic) as well as some synthetic compounds were tested on the complement cascade in vitro. Bovine erythrocytes were treated with rabbit antibovine red blood cell antibody. Rabbit plasma was diluted with veronal buffer and mixed with erythrocytes in the presence or absence of drugs and incubated. Erythrocytes were pelleted and the absorbance of the supernatant at 412 nm determined. Drugs could be grouped into three categories; (a) those with no effect whatsoever; (b) those which produced definite enhancement of the release of hemoglobin by the complement cascade, and (c) prednisolone, which inhibited the release of hemoglobin by the complement cascade. We suggest that prednisolone and the drugs which had no effect on the complement cascade are safer to use as anti-inflammatory agents, while drugs enhancing the complement cascade may have potential adverse properties.

Animals↗
PubMed1993

Evaluation of vanillic acid analogues as a new class of antifilarial agents.

A number of vanillic acid analogues (1-14) have been synthesised and evaluated against experimental filarial infections using cotton rats (Sigmodon hispidus) infected with Litomosoides carinii, a primary screening model, at a dose of 30 mg/kg, ip for 5 days. Of the 8 compounds tested, 4 (5,7, 11 and 12) exhibited high micro- and macro-filaricidal activity with sterilization of surviving female worms. Compounds 5, 7, 12 showed remarkable adulticidal action (> 80%). Sterilization of the female worms by compounds 11 and 12 was highly significant (80-100%).

Animals↗
PubMed1992

Growth inhibitory effects of bioflavonoids and related compounds on human leukemic CEM-C1 and CEM-C7 cells.

Seven compounds, which included some naturally occurring dietary substances, were tested for their inhibitory effects on growth and metabolism of human leukemic CEM-C1 and CEM-C7 cell lines. Among the active compounds the naturally occurring dietary constituents were found to be the most active. The strongest inhibitory effects were observed with 3',4',5,7-tetrahydroxy-flavone (luteolin) and 4,4'-dihydroxychalcone. 31P-NMR spectra of cells incubated for 24 h with 30 microM of either of these compounds show complete ATP depletion. Also glucose uptake by the cells as measured by 13C-NMR is completely inhibited by these compounds. These results may be relevant to the tumor suppressing activity of bioflavonoids and the role of these compounds in chemoprevention.

Cell Division↗
PubMed1992

Nuclear type II sites and malignant cell proliferation: inhibition by 2,6-bis-benzylidenecyclohexanones.

Methyl-p-hydroxyphenyllactate (MeHPLA) is a bioflavonoid and/or tyrosine metabolite which may regulate cellular growth and proliferation through interactions with nuclear type II sites. Our current studies suggest that type II sites may function as MeHPLA receptors which are localized on the nuclear matrix, and occupancy of this binding site by MeHPLA directly correlates with the inhibition of normal and malignant cell proliferation. This ligand is inactivated by MeHPLA esterase in mammary tumors, resulting in a deficiency in MeHPLA, high quantities of unoccupied type II sites, and uncontrolled cellular proliferation. For these reasons we synthesized 2,6-bis((3,4-dihydroxyphenyl)methylene)-cyclohexanone (BDHPC) and 2,6-bis((3-methoxy-4-hydroxyphenyl)-methylene)cyclohexanone (BMHPC) for assessment as nuclear type II site and cell growth antagonists. These two esterase stable cyclohexanone derivatives, which bind to nuclear type II sites with high affinity (Kd 1-7 nM), mimic MeHPLA as cell growth-regulating agents. Dose-dependent occupancy of type II sites in MCF-7 human cells by BDHPC and BMHPC directly correlated with the inhibition of cell proliferation, and administration of BDHPC by silastic implant inhibited mouse mammary tumor growth in vivo. These findings demonstrate that esterase-stable type II antagonists such as BDHPC and BMHPC inhibit mammary cancer cell proliferation in vitro and in vivo and support earlier studies demonstrating that MeHPLA and functionally related compounds may regulate malignant cell proliferation at the level of this binding site.

Animals↗
PubMed1992

Inhibition of ocular inflammation by chalcone derivatives and prednisolone.

Posterior uveitis was induced by injection of 10 micrograms endotoxin intravitreally into rat eyes and anterior ocular inflammation was induced by injection of 0.75 mg of lens protein intracamerally into rabbit eyes. Four chalcone derivatives, RVC-556 (2'-hydroxychalcone), RVC-574 (2'-hydroxychalcone hydrazone), RVC-574P (2'-hydroxychalcone phenyl hydrazone) and RVC-588 (4,4'-dihydroxy chalcone) were studied along with prednisolone at a dose of 10 mg/kg i.p. t.i.d. for their anti-inflammatory actions. RVC-574 was more active than prednisolone in inhibiting posterior uveitis by 65% and 43%, respectively. RVC-556, RVC-574P, and RVC-588 did not affect the posterior uveitis in rats. On the other hand, anterior ocular inflammation was inhibited by 1% eyedrops of RVC-556, RVC-574P and RVC-588 but not by RVC-574. RVC-556 was more active than; RVC-574P was less active than; and RVC-588 was about equiactive as prednisolone in inhibiting anterior ocular inflammation by 77%, 47%, 69%, and 64%, respectively.

Animals↗
PubMed1990

Methyl p-hydroxyphenyllactate and nuclear type II binding sites in malignant cells: metabolic fate and mammary tumor growth.

Previous studies in our laboratory demonstrated that methyl p-hydroxyphenyllactate (MeHPLA) is an important cell growth-regulating agent which binds to nuclear type II binding sites in normal and malignant cells. Furthermore, this compound is deficient in a variety of rat and mouse mammary tumors and human breast cancer preparations, and this deficiency correlates with the loss of regulatory control. The present studies were performed to examine the metabolic fate of [3H]MeHPLA in mouse mammary tumors. Stable analogs of this compound such as 4,4'-dihydroxy benzylidene acetophenone were also assessed for nuclear type II site binding affinity and their ability to inhibit mammary cancer cell growth and proliferation in vitro and in vivo. The results demonstrate that mouse mammary tumors contain esterase activity which hydrolyzes MeHPLA to p-hydroxyphenyllactic acid, and this was the only major metabolite detected in these tumor preparations in vitro or in vivo. 4,4'-Dihydroxy benzylidene acetophenone, an esterase-stable MeHPLA analog, was found to bind with high affinity to nuclear type II sites but not the estrogen receptor, was capable of occupying type II sites in cultured MCF-7 cells, and inhibited the proliferation of these cells in concentrations which directly correlated with type II binding site occupancy. Similarly, 4,4'-dihydroxy benzylidene acetophenone administration by silastic implant or injection resulted in a dose-dependent inhibition of the growth of transplantable mammary tumors in mice, suggesting that this stable analog mimicks MeHPLA as a cell growth-regulating agent. Taken together, these results suggest esterase hydrolysis of MeHPLA in mammary tumors may result in a deficiency in this compound which correlates with a loss of regulatory control.

Animals↗
PubMed1989

Estrogen regulation of methyl p-hydroxyphenyllactate hydrolysis: correlation with estrogen stimulation of rat uterine growth.

We have recently demonstrated that methyl p-hydroxyphenyllactate (MeHPLA) is the endogenous ligand for nuclear type II binding sites in the rat uterus and other estrogen target and non-target tissues. MeHPLA binds to nuclear type II binding sites with a very high binding affinity (Kd approximately 4-5 nM), blocks uterine growth in vivo, and inhibits MCF-7 human breast cancer cell growth in vitro. Conversely, the free acid (p-hydroxyphenyllactic acid, HPLA) interacts with type II binding sites with a much lower affinity (Kd approximately 200 nM) and does not inhibit estrogen-induced uterine growth in vivo or MCF-7 cell growth in vitro. On the basis of these observations, we suggested that one way that estrogen may override MeHPLA inhibition of rat uterine growth may be to stimulate esterase hydrolysis of MeHPLA to HPLA. The present studies demonstrate that the rat uterus does contain an esterase (mol. wt approximately 50,000) which cleaves MeHPLA to HPLA, and that this enzyme is under estrogen regulation. This conclusion is supported by the observations that MeHPLA esterase activity is increased 2-3-fold above controls within 2-4 h following a single injection of estradiol, and is maintained at high levels for 16-24 h following hormone administration. This sustained elevation of MeHPLA esterase activity correlates with estradiol stimulation of true uterine growth and DNA synthesis.

Animals↗
PubMed1983

Beta-glucuronidase in sera of patients with epileptic seizure activity, diabetes and some other disease states.

As compared to controls and epileptics with controlled seizures, serum beta-glucuronidase enzyme is elevated significantly in epileptics with uncontrolled seizures. The enzyme begins to rise just before the seizure, remains elevated during, and for some time after the seizure and then begins to decline, unless another seizure follows the first seizure. The enzyme is not elevated in controlled diabetes patients without any secondary complications. But the enzyme is also elevated in other pathological conditions which involve increased connective tissue catabolism. However, the enzyme is elevated constantly and all the time in these conditions, in contrast with its elevation in uncontrolled epilepsy only close to the seizures.

Brain↗