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Biomedical subjects

M N Rao

Publications and source records attributed to M N Rao.

At least 19 recordsLinked to original sources
PubMed2006

Pulmonary zygomycosis in a diabetic patient.

We report a case of pulmonary zygomycosis in an adult male diabetic patient who presented with fever and altered sensorium initially and later developed streaky haemoptysis. Bronchoscopy showed picture of necrotizing pneumonia. Sputum was negative for fungal elements on admission but later bronchial wash and repeat sputum samples were positive by microscopy and culture showed growth of Rhizopus species. Immediately the patient was put on amphotericin B but had a bout of massive haemoptysis and succumbed. A high index of suspicion is needed for an early diagnosis and aggressive treatment of this infection in view of the high mortality rate.

Amphotericin B↗
PubMed2001

Chronic ethanol exposure in rats affects rabs-dependent hepatic trafficking of apolipoprotein E and transferrin.

Because of the important roles of rabs in protein trafficking, we tested whether chronic ethanol exposure affected the trafficking of newly synthesized apolipoprotein E (apoE) or transferrin (O-glycosylated and N-glycosylated proteins, respectively) attached to acylated or prenylated rabs. The in vivo 30-min incorporation ratios of [3H]palmitate:[35S]methionine or [3H]mevalonate:[35S]methionine (relative ratios of rabs acylation or prenylation to total protein or to immunoisolated apoE or transferrin) were measured in various hepatic subcellular organelles of 8 week-ethanol-fed (E) and pair-fed control (C) Wistar-Furth rats. With respect to total protein trafficking, ethanol increased rabs acylation ratio by 136% (P <.01), 69% (P <.05), and 64% (P <.01) in the endoplasmic reticulum (ER), Golgi light fraction (GLF), and Golgi heavy fraction (GHF), respectively, and decreased this ratio by 76% (P <.01) in carrier vesicle fraction 2 (CV2). With respect to apoE trafficking, ethanol increased rabs acylation ratio by 121% in GHF and decreased this ratio by 27% in CV2. Rabs prenylation ratio increased by 21% and 53% in GHF and CV2, respectively, and decreased by 42% in GLF. With respect to transferrin trafficking, ethanol increased rabs acylation ratio by 53% (P <.01) in GHF, with no significant effect in ER, whereas rabs prenylation ratio increased by 26% (P <.05) in ER, with no significant effect in GHF. Therefore, we conclude that ethanol-induced impaired trafficking of newly synthesized O- and N-glycosylated proteins occurs primarily in ER and Golgi and is due to altered lipidation of rabs, possibly rabs 1, 2, or 6 or combinations of these three rabs.

Animals↗
PubMed2001

Alcohol biomarkers: clinical significance and biochemical basis.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Raj Lakshman and Mikihiro Tsutsumi. The presentations were (1) Sialic acid index of apolipoprotein J: A new marker for chronic alcohol consumption, by P. Ghosh and M. R. Lakshman; (2) Microheterogeneity of serum glycoproteins in alcoholics, by M. Tsutsumi and S. Takase; (3) Probing protein-ethanol adducts with combinatorial peptide libraries displayed by filamentous phage, by H. Anni, O. Nikolaeva, and Y. Israel Y; (4) Carbohydrate-deficient transferrin as a marker for heavy alcohol use: What have we learned; Where do we go from here, by R. F. Anton; (5) Sensitivity and specificity of carbohydrate-deficient transferrin in drinking experiments and different patient groups, by O. M. Lesch; (6), Transferrin variants interfere with the measurement of carbohydrate-deficient transferrin, by A. Helender, G. Eriksson, and J-O. Jeppson; and (7) Chronic ethanol on protein trafficking in liver, by P. Marmillot, M. N. Rao, and M. R. Lakshman.

Alcoholism↗
PubMed2000

Effect of dietary omega-3 fatty acids and chronic ethanol consumption on reverse cholesterol transport in rats.

We previously showed that chronic ethanol feeding leads to a decrease of apolipoprotein E (apoE) in high-density lipoprotein (HDL), whereas supplementing this diet with 2.8% of total dietary calories as omega3-fatty acids (omega3FAs) restores HDL-apoE to the control values. Since HDL containing apoE plays a major role in reverse cholesterol transport (RCT), we measured the effects chronic ethanol intake and omega3-FAs on RCT in the present study. Four groups of rats, control normal fat (CN), alcohol-normal fat (AN), control omega3FA fat (CF), and alcohol-omega3FA fat (AF), were fed their respective diets for 8 weeks, after which hepatocytes and HDLs from each group were evaluated for RCT capacity (cholesterol efflux from macrophages and uptake by liver cells). Compared with the control diet (CN), chronic ethanol (AN) feeding inhibited the cholesterol efflux capacity of HDL by 21% (P < .01), whereas omega3FA feeding (2.8% of total dietary calories) stimulated this capacity by 79% (P < .01) and 25% (P < .01) in CF and AF rats, respectively. With respect to cholesterol uptake by the liver, there were no significant 3-way or 4-way interactions between the 4 factors, HDL-alcohol, HDL-fish oil, hepatocyte-alcohol, and hepatocyte-fish oil. The main effects for HDL-alcohol, HDL-fish oil, and hepatocyte-alcohol were all highly significant (P = .0001, .0001, and .007, respectively). There was a significant HDL-alcohol and HDL-fish oil interaction (P = .0001). Hepatocyte-alcohol was not a factor in any 2-way interactions. Our study indicates no evidence of an interaction between the effects of omega3FAs and the effects of alcohol on hepatocytes in terms of RCT function. Thus, feeding as little as 2.8% of the total dietary calories as omega3FA not only restored the impaired RCT function of HDL caused by chronic ethanol intake, but also enhanced by severalfold the ability of HDL to promote RCT even in normal animals.

Administration, Oral↗
PubMed2000

Aminosterols from the dogfish shark Squalus acanthias.

Seven new aminosterols related to squalamine (8) were isolated from the liver of the dogfish shark Squalus acanthias. Their structures (1-7) were determined using spectroscopic methods, including 2D NMR and HRFABMS. These aminosterols possess a relatively invariant cholestane skeleton with a trans AB ring junction, a spermidine or spermine attached equatorially at C3, and a steroidal side-chain that may be sulfated. The structure of the lone spermine conjugate, 7 (MSI-1436), was confirmed by its synthesis from (5alpha,7alpha, 24R)-7-hydroxy-3-ketocholestan-24-yl sulfate. Some members of this family of aminosterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine.

Animals↗
PubMed2000

High-density lipoproteins from human alcoholics exhibit impaired reverse cholesterol transport function.

We have previously shown that chronic alcohol consumption leads to inhibition of sialylation of apolipoprotein E (apo E) that results in its impaired binding to high-density lipoprotein (HDL) molecule. Because apo E plays a major role in reverse cholesterol transport (RCT), we speculated that ethanol-mediated formation of HDL molecules without apo E may affect the RCT process. Therefore, we have investigated whether the RCT function of HDL is affected in chronic alcoholics with or without liver disease compared with nondrinkers. HDL was isolated from fasting plasma of normal subjects, n = 9 (nondrinkers), chronic alcoholics, n = 8 (ALC), and chronic alcoholics with liver disease, n = 6 (ALD). A portion of HDL sample from each subject was evaluated for its cholesterol efflux capacity from [3H]cholesterol oleate preloaded mouse macrophages. The remaining portion of each HDL sample was labeled with [3H]cholesterol oleate and evaluated for its ability to deliver cholesterol to the liver using HepG2 cells in culture. Cholesterol efflux capacity of HDLs was decreased by 83% (P < .0002) in alcoholics without liver disease and by 84% (P < .0006) in alcoholics with liver disease compared with the HDLs from nondrinkers. The capacities of HDLs to deliver cholesterol to the liver were decreased by 54% (P < .005) in alcoholics without liver disease and by 64% (P < .005) in alcoholics with liver disease compared with the HDLs from nondrinkers. The fact that further complications by liver disease in alcoholic subjects did not significantly exacerbate the extent of impairment in RCT function of HDL suggest that alcohol per se is responsible for its deleterious effects on RCT. Significantly, plasma HDL apo E concentration relative to that of apo A1 (apo E/apo A1 ratio) was also decreased by 31% to 32% (P < .0005) in alcoholics without or with liver disease compared with nondrinkers. It is therefore concluded that chronic alcohol consumption adversely affects the RCT function of HDL by altering its association with apo E due to ethanol-induced desialylation of apo E.

Adult↗
PubMed2000

Structure-activity relationships for the inhibition of lipid peroxidation and the scavenging of free radicals by synthetic symmetrical curcumin analogues.

A number of ring substituted analogues of curcumin were synthesized. Their antioxidant properties were studied using three models, inhibition of lipid peroxidation, scavenging of 1,1'-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethyl-benzthiazoline-6-sulphonate radical (ABTS+.). In all the models, the phenolic analogues were more active than the non-phenolic analogues, some of which were inactive. The highest antioxidant activity was obtained when the phenolic group was sterically hindered by the introduction of two methyl groups at the ortho position. This and several other compounds were more active than the standard antioxidants alpha-tocopherol and trolox. This study has demonstrated that the phenolic group is important for the antioxidant activity of curcumin and that the structural features that enhance the antioxidant properties of phenols are optimized in curcumin to a significant extent.

Antioxidants↗
PubMed2000

Inhibition of radiation-induced lipid peroxidation by tetrahydrocurcumin: possible mechanisms by pulse radiolysis.

The antioxidant property of tetrahydrocurcumin (THC), a reduced derivative of curcumin, was examined by its ability to inhibit radiation-induced lipid peroxidation in rat liver microsomes and compared with curcumin. The lipid peroxidation caused by irradiation of N2O-purged and aerated buffered aqueous solutions was found to be inhibited by THC in a dose- and concentration-dependent manner. In order to understand the actual reaction mechanisms involved in the inhibition process, pulse radiolysis investigation of THC with radiolytically produced radicals like hydroxyl, model peroxyl radicals, and azide radicals were done and the transients were detected by kinetic spectrophotometry. The reaction of THC with hydroxyl and azide radicals gave rise to transient absorption in the region 200-400 nm with two peaks at 310 nm and 390 nm. From the spectral properties and kinetics of these radicals, a suitable mechanism is discussed to explain the antioxidant actions of THC.

Animals↗
PubMed1999

Reduction of cisplatin-induced nephrotoxicity by cystone, a polyherbal ayurvedic preparation, in C57BL/6J mice bearing B16F1 melanoma without reducing its antitumor activity.

The effect of cystone, a polyherbal ayurvedic preparation, on the nephrotoxicity and antitumor activity of cisplatin is studied in C57BL/6J mice bearing B16F1 melanoma. Intraperitoneal administration of cisplatin 6 mg/kg, resulted in significant reduction of body weight, elevation of blood urea nitrogen (BUN) and serum creatinine levels on day 5. Cystone was found to protect tumor-bearing mice from cisplatin-induced nephrotoxicity, when given i.p. 1 h before cisplatin. At 1000 mg/kg, it showed 46, 57 and 66% protection on body weight, BUN and serum creatinine levels, respectively. Treatment of cisplatin alone to tumor bearing mice resulted in significant antitumor activity as measured by tumor appearance, tumor volume and tumor weight. Pre-treatment with cystone (1000 mg/kg) did not reduce the antitumor activity of cisplatin. These results suggested that cystone protects against cisplatin-induced nephrotoxicity without interfering with its antitumor activity. The present study has many clinical implications in cisplatin chemotherapy.

Animals↗
PubMed1999

Martian soil component in impact glasses in a Martian meteorite.

Chemical compositions of impact melt glass veins, called Lithology C (Lith C) in Martian meteorite EET79001 were determined by electron microprobe analysis. A large enrichment of S, and significant enrichments of Al, Ca, and Na were observed in Lith C glass compared to Lithology A (Lith A). The S enrichment is due to mixing of plagioclase- enriched Lith A material with Martian soil, either prior to or during impact on Mars. A mixture of 87% Lith A, 7% plagioclase, and 6% Martian soil reproduces the average elemental abundances observed in Lith C. Shock melting of such a mixture of plagioclase-enriched, fine-grained Lith A host rock and Martian soil could yield large excesses of S (observed in this study) and Martian atmospheric noble gases (found by Bogard et al., 1983) in Lith C. These mixing proportions can be used to constrain the elemental abundance of phosphorus in Martian soil.

Aluminum Oxide↗
PubMed1999

Free radical scavenging ability and antioxidant efficiency of curcumin and its substituted analogue.

Free radical reactions of curcumin and its ethoxy substituted derivative (C1) 1,7-bis-(4-hydroxy-3-ethoxy phenyl)-1,6-heptadiene-3,5-dione have been studied using a pulse radiolysis technique in homogeneous aqueous-organic solutions like acetonitrile-water and isopropanol-water mixtures, as well as in neutral TX-100 and cationic CTAB micellar solutions. The phenoxyl radicals of curcumin or C1 were generated by one-electron transfer to several oxidants like N(3)(.), Br(2)(-.), CCl(3)O(2)(.), glutathione radicals which exhibit absorption from a 300-600-nm wavelength region with the maximum at 490-500 nm. Other important properties of the phenoxyl radicals such as extinction coefficient, radical lifetime and their formation and decay rate constants were also determined in these systems. The antioxidant property of curcumin and C1 were estimated in terms of their ability to inhibit the lipid peroxidation in liposomes and also in terms of trolox equivalent antioxidant capacity (TEAC). The results were compared with alpha-tocopherol.

Journal Article↗
PubMed1999

Desialylation of human apolipoprotein E decreases its binding to human high-density lipoprotein and its ability to deliver esterified cholesterol to the liver.

Apolipoprotein E (apoE) plays a significant role in the delivery of high-density lipoprotein (HDL) cholesterol to the liver via the apoB/E receptor. The roles of the apoE sialylation status in its association with HDL and in the reverse cholesterol transport (RCT) function of HDL have not been well defined. Furthermore, long-term ethanol treatment impairs apoE sialylation and leads to its decreased content in HDL. Therefore, we investigated the association of either sialo apoE (SapoE) or desialo apoE (DSapoE) with HDL and its effect on the RCT function of HDL. The dextran sulfate precipitation method showed that [125I]DSapoE binding to HDL was 27.3% (P < .02) to 35.5% (P < .001) lower versus [125I]SapoE. Scatchard analysis of the specific binding data showed that [125I]SapoE had 11.2 times more affinity for HDL than [125I]DSapoE based on size-exclusion chromatography (Kd = 89.7 v 1,010 nmol/L). Similarly, [1251]HDL had 4.5 times more affinity for SapoE compared with DSapoE based on solid-phase binding (Kd = 21.9 v 104.4 nmol/L). Furthermore, esterified cholesterol uptake from reconstituted HDL particles (rHDLs) by HepG2 cells increased over basal uptake up to 153% when rHDLs contained SapoE, versus only 37% with DSapoE. Enzymatic resialylation of DSapoE completely restored its HDL-binding and RCT properties, identical to those of SapoE. It is therefore concluded that desialylation of apoE decreases its binding to plasma HDL, leading to an impaired RCT function.

Apolipoproteins E↗
PubMed1999

Chronic ethanol consumption leads to destabilization of rat liver beta-galactoside alpha2,6-sialyltransferase mRNA.

Chronic ethanol consumption in rats is accompanied by decreased levels of Gal beta1,4GlcNAc alpha2,6-sialyltransferase (2,6-ST) activity in the liver. Our previous studies have shown that there is a concomitant decrease in the levels of 2,6-ST mRNA. In this study, the alteration in the regulation of 2,6-ST expression by chronic ethanol consumption was assessed by Northern hybridization, nuclear run-on experiments, and 2,6-ST mRNA stability studies. 2,6-ST downregulation was found at 4 weeks of feeding an ethanol diet (36% of calories from ethanol) and remained up to 8 weeks. The decrease in 2,6-ST mRNA levels was found to be dose-dependent, with lower dose of ethanol (12% and 24% of total dietary calories from ethanol) being ineffective and the effects being manifested only when 36% of the dietary calories were from ethanol. The effects of chronic ethanol feeding could be completely reversed within 1 week after ethanol consumption was stopped, when 2,6-ST mRNA levels were restored to normal. The downregulation was not sensitive to actinomycin D, indicating that the regulation was not affected at the transcriptional level but at the posttranscriptional level. This was confirmed by nuclear run-on experiments showing that the rate of 2,6-ST mRNA transcription was unaffected by ethanol. Finally, mRNA stability experiments showed that the half-life of 2,6-ST mRNA was reduced 50% in ethanol-fed rat livers compared with control rat livers. Taken together, the results show that 2,6-ST mRNA is regulated at the posttranscriptional level and chronic ethanol intake downregulates 2,6-ST expression by destabilizing its mRNA.

Animals↗
PubMed1999

Purification and characterization of cellular carotenoid-binding protein from mammalian liver.

A cellular carotenoid-binding protein was purified to homogeneity from beta-carotene-fed ferret liver utilizing the following steps: ammonium sulfate precipitation, ion exchange, gel filtration, and affinity chromatography. The final purification was 607-fold. beta-[14C]Carotene copurified with the binding protein throughout the purification procedures. SDS-PAGE of the purified protein showed a single band with an apparent molecular mass of 67 kDa. Scatchard analysis of the specific binding of the purified protein to beta-carotene showed two classes of binding sites; a high-affinity site with an apparent Kd of 56 x 10(-9) M and a low-affinity site with a Kd of 32 x 10(-6) M. The Bmax for beta-carotene binding to the high-affinity site was 1 mol/mol whereas that for the low-affinity site was 145 mol/mol. The absorption spectrum of the complex showed a 32-nm bathochromic shift in lambda max with minor peaks at 460 and 516 nm. Except for alpha-carotene and cryptoxanthin, none of the model carotenoids or retinol competed with beta-carotene binding to the protein. Thus, a specific carotenoid-binding protein of 67 kDa size has been characterized in mammalian liver with a high degree of specificity for binding only carotenoids with at least one unsubstituted beta-ionone ring.

Animals↗
PubMed1999

Alcohol and molecular regulation of protein glycosylation and function.

Chronic alcohol exposure leads to the appearance of carbohydrate-deficient transferrin (CDT), a N-glycosylated protein and sialic acid-deficient apolipoprotein E (apoE), an O-glycosylated protein. We show that chronic ethanol treatment destabilizes sialyltransferase (ST) mRNA resulting in a concomitant decreased steady-state level of ST mRNA. As a result, alcohol markedly decreases the hepatic synthetic rate of ST. This leads to impaired sialylation of transferrin and apoE. Consequently, apoE content in plasma high-density lipoproteins (HDL) is decreased. ApoE plays a significant role in the delivery of HDL cholesterol to the liver via apo B/E receptor, a process called reverse cholesterol transport (RCT). Desialylation of apoE results in its decreased association with HDL. Thus, the dissociation constant of HDL for binding to sialo-apoE is 90 +/- 35 nM, whereas that for desialo-apoE is 1010 +/- 250 nM. More importantly, the uptake of labeled cholesterol by human HepG2 cells is decreased by 30-40% from reconstituted HDL particles (rHDL)-containing desialo-apoE compared to rHDL with sialo-apoE. We conclude that chronic alcohol exposure down-regulates the expression of sialyltransferase genes resulting in impaired sialylation of apoE. This leads to its decreased binding to plasma HDL and thereby, impairs the RCT function of HDL.

Animals↗
PubMed1999

Chronic ethanol increases ganglioside sialidase activity in rat leukocytes, erythrocytes, and brain synaptosomes.

In view of the chronic alcohol-mediated pathological changes in various sialic acid-deficient glycoconjugates and the potential importance of sialidase in the generation of these glycoconjugates in the blood compartment and in the brain, we have investigated the effects of chronic ethanol feeding for 8 weeks on ganglioside sialidase activities in rat blood and brain. Ganglioside sialidase activity in erythrocytes (whether expressed as units/mg of protein or units/ml of blood) was 1.37- to 1.40-fold higher (p < 0.01) in the ethanol-fed group than in the control group. On the other hand, the same ethanol treatment increased sialidase activity in the leukocyte soluble fraction by 2.50- to 2.60-fold (p < 0.01) and by 1.61- to 1.63-fold (p < 0.01) in the leukocyte particulate fraction, compared with the control group. More importantly, most of the blood compartment sialidase activity was localized in the leukocytes particulate fraction (80 to 86% of total blood activity). Similarly, chronic ethanol treatment increased brain synaptosomal sialidase activity (whether expressed as units/gram of brain or units/mg of protein) 2.16- to 2.43-fold (p < 0.01). In contrast, brain lysosomal sialidase was not significantly altered by ethanol treatment, even though the major proportion of the brain sialidase activity was localized in the lysosomes. The proportion of synaptosomal sialidase activity as the percentage of total brain sialidase activity increased markedly from 13% in the control group to 24% in the ethanol group. Thus, chronic ethanol-mediated increases in sialidase activity in the leukocytes and brain synaptosomes could account for alterations in the ganglioside status of the animal and consequent adverse effects of chronic ethanol on behavioral and pathological changes.

Animals↗
PubMed1998

Protective effects of cystone, a polyherbal ayurvedic preparation, on cisplatin-induced renal toxicity in rats.

Cystone, a polyherbal ayurvedic preparation, was found to protect rats partially but significantly against cisplatin-induced renal toxicity, when given intraperitonially 1 h before cisplatin. At 500 and 1000 microg/ml, it also inhibited lipid peroxidation induced by cisplatin in renal cortical slices by 62.7 and 71.6%, respectively. The rats pretreated with cystone (1000 mg/kg i.p.) had significantly lower blood urea nitrogen (BUN) and serum creatinine (33.8 and 0.92 mg/dl, respectively) compared to cisplatin alone (51.5 and 1.41 mg/dl, respectively). The control animals had 17.1 and 0.63 mg/dl, respectively. The cystone treated animals lost 5.63 g body weight compared to 12.5 g for cisplatin alone treated animals on day 5. Renal functions like urine to serum creatinine ratio and creatinine clearance showed significant improvement when cystone was given 1 h before cisplatin. However, cystone did not protect increased excretion of urinary protein and decreased WBC count caused by cisplatin. The present study suggests that the cystone protects kidney against cisplatin-induced toxicity and the protection may be mediated through its ability to inhibit lipid peroxidation.

Animals↗