Biomedical subjects

S Subramaniam

Publications and source records attributed to S Subramaniam.

At least 91 records · Page 5Linked to original sources

PubMed1997

Knowledge-based design of a soluble bacteriorhodopsin.

Much knowledge has been accrued from high resolution protein structures. This knowledge provides rules and guidelines for the rational design of soluble proteins. We have extracted these rules and applied them to redesigning the structure of bacteriorhodopsin and to creating blueprints for a monomeric, soluble seven-helix bundle protein. Such a protein is likely to have desirable properties, such as ready crystallization, which membrane proteins lack and an internal structure similar to that of the native protein. While preserving residues shown to be necessary for protein function, we made modifications to the rest of the sequence, distributing polar and charged residues over the surface of the protein to achieve an amino acid composition as akin to that of soluble helical proteins as possible. A secondary goal was to increase apolar contacts in the helix intercalation regions of the protein. The scheme used to design the model sequences requires knowledge of the number and orientation of helices and some information about interior contacts, but detailed structural knowledge is not required to use a scheme of this type.

Amino Acid Sequence↗

PubMed1997

Phylogenetic position of Riemerella anatipestifer based on 16S rRNA gene sequences.

Riemerella anatipestifer, the causative agent of septicemia anserum exsudativa (also called new duckling disease), belongs to the family Flavobacteriaceae of gram-negative bacteria. We determined the DNA sequences of the rrs genes encoding the 16S rRNAs of four R. anatipestifer strains by directly sequencing PCR-amplified rrs genes. A sequence similarity analysis confirmed the phylogenetic position of R. anatipestifer in the family Flavobacteriaceae in rRNA superfamily V and allowed fine mapping of R. anatipestifer on a separate rRNA branch comprising the most closely related species, Bergeyella zoohelcum, as well as Chryseobacterium balustinum, Chryseobacterium indologenes, and Chryseobacterium gleum. The sequences of the rrs genes of the four R. anatipestifer strains varied between 0.5 and 1.0%, but all of the strains occupied the same position on the phylogenetic tree. In general, differences in rrs genes were observed among R. anatipestifer strains, even within a given serotype, as shown by restriction fragment length polymorphism of PCR-amplified rrs genes.

Animals↗

PubMed1997

Sub-Tenon's anesthesia and orbicularis oculi function.

BACKGROUND AND OBJECTIVE: To assess the necessary volume of local anesthetic with added hyaluronidase that must be infiltrated to the sub-Tenon's space to achieve complete eyelid akinesia. PATIENTS AND METHODS: Eighty-five consecutive patients were randomly assigned to two groups, receiving either 5 ml or 7 ml of local anesthetic to the sub-Tenon's space. Each patient was assessed clinically at 5 and 10 minutes for orbicularis oculi function. The anesthetic solution consisted of 5 ml of 2% lidocaine, 5 ml of 0.75% bupivacaine hydrochloride, and 1500 IU of hyaluronidase. A top-up of anesthetic infiltration was given in doses of 2 ml if excessive orbicularis muscle function persisted at 10 ml. Routine phacoemulsification surgery was performed, and, if necessary, a top-up of anesthetic was given on the table. RESULTS: Complete eyelid akinesia was achieved in 7.5% (3 of 40) of the patients in the 5-ml group and in 93.3% (42 of 45) of the patients in the 7-ml group (P < .005). There was no effect for 57.5% (23 of 40) of the patients in the 5-ml group and for 2.2% (1 of 45) of the patients in the 7-ml group. A top-up of anesthetic was given in the anesthetic room to 40 patients, 37 of whom were in the 5-ml group, and a Van Lint block of the facial nerves was necessary for 1 patient from the 5-ml group. An on-the-table top-up of anesthesia was necessary for 3 patients (2 from the 5-ml group, 1 from the 7-ml group). CONCLUSIONS: The addition of hyaluronidase promotes diffusion of sub-Tenon's anesthetic, resulting in effective akinesia of the orbicularis oculi. The infiltration of 7 ml of the anesthetic solution significantly improves the rate of eyelid akinesia.

Aged↗

PubMed1996

Modulation of arrestin release in the light-driven regeneration of Rh1 Drosophila rhodopsin.

We report studies of the in vitro regeneration of Rh1 Drosophila rhodopsin using immunochemical and spectroscopic probes for the release of arrestin (49 kDa). Upon illumination of metarhodopsin-containing membrane suspensions isolated from homogenized Drosophila heads, arrestin was released into the aqueous medium. In contrast, no release of arrestin was observed upon illumination of metarhodopsin in lipid/detergent micellar extracts. The spectroscopic changes associated with the transition from metarhodopsin to rhodopsin were, however, similar in membrane suspensions and in micellar extracts. The light-driven release of arrestin was restored in reconstituted liposomes formed by dialysis of detergent from the micellar extracts. We conclude that micellar solubilization of membranes decouples the light-driven release of arrestin from rhodopsin structural changes which are responsible for altering the lambda max of the chromophore. The finding that arrestin release from rhodopsin can be modulated by changes in the local membrane environment provides an opportunity to further characterize the nature of rhodopsin conformational changes during regeneration.

Animals↗

PubMed1996

Modeling the structure of the combining site of an antisweet taste ligand monoclonal antibody NC10.14.

We report the predicted combining site structure of the monoclonal antibody fragment, NC10.14, which is specific for the superpotent sweetener, N-(p-cyanophenyl-N'-(diphenylmethyl) guanidine acetic acid, using computer-aided molecular modeling and experimental methods, such as fluorescence spectroscopy and circular dichroism. This is the first computer-aided modeling study on a lambda-chain antibody fragment. We have also identified the amino acids that are involved in ligand binding. Aromatic residues, L:91(W), L:96(W), and H:100G(Y) are predicted to make van der Waals contacts with the p-cyanophenyl moiety of the ligand. Residue H:56(K) is predicted to provide a counterion for the acetic acid moiety, and H:50(E) provides the negatively charged potential for interaction with the positive guanidinium group. We also make a comparison of the binding site architecture of NC10.14 with that of a related monoclonal antibody fragment NC6.8.

Acetates↗

PubMed1996

Modeling of the D1/D2 proteins and cofactors of the photosystem II reaction center: implications for herbicide and bicarbonate binding.

A three-dimensional model of the photosystem II (PSII) reaction center from the cyanobacterium Synechocystis sp. PCC 6803 was generated based on homology with the anoxygenic purple bacterial photosynthetic reaction centers of Rhodobacter sphaeroides and Rhodopseudomonas viridis, for which the X-ray crystallographic structures are available. The model was constructed with an alignment of D1 and D2 sequences with the L and M subunits of the bacterial reaction center, respectively, and by using as a scaffold the structurally conserved regions (SCRs) from bacterial templates. The structurally variant regions were built using a novel sequence-specific approach of searching for the best-matched protein segments in the Protein Data Bank with the "basic local alignment search tool" (Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ, 1990, J Mol Biol 215:403-410), and imposing the matching conformational preference on the corresponding D1 and D2 regions. The structure thus obtained was refined by energy minimization. The modeled D1 and D2 proteins contain five transmembrane alpha-helices each, with cofactors (4 chlorophylls, 2 pheophytins, 2 plastoquinones, and a non-heme iron) essential for PSII primary photochemistry embedded in them. A beta-carotene, considered important for PSII photoprotection, was also included in the model. Four different possible conformations of the primary electron donor P680 chlorophylls were proposed, one based on the homology with the bacterial template and the other three on existing experimental suggestions in literature. The P680 conformation based on homology was preferred because it has the lowest energy. Redox active tyrosine residues important for P680+ reduction as well as residues important for PSII cofactor binding were analyzed. Residues involved in interprotein interactions in the model were also identified. Herbicide 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) was also modeled in the plastoquinone QB binding niche using the structural information available from a DCMU-binding bacterial reaction center. A bicarbonate anion, known to play a role in PSII, but not in anoxygenic photosynthetic bacteria, was modeled in the non-heme iron site, providing a bidentate ligand to the iron. By modifying the previous hypothesis of Blubaugh and Govindjee (1988, Photosyn Res 19:85-128), we modeled a second bicarbonate and a water molecule in the QB site and we proposed a hypothesis to explain the mechanism of QB protonation mediated by bicarbonate and water. The bicarbonate, stabilized by D1-R257, donates a proton to QB2- through the intermediate of D1-H252; and a water molecule donates another proton to QB2-. Based on the discovery of a "water transport channel" in the bacterial reaction center, an analogous channel for transporting water and bicarbonate is proposed in our PSII model. The putative channel appears to be primarily positively charged near QB and the non-heme iron, in contrast to the polarity distribution in the bacterial water transport channel. The constructed model has been found to be consistent with most existing data.

Amino Acid Sequence↗

PubMed1996

Alteration of pulmonary surfactant proteins in rats chronically exposed to cigarette smoke.

Surfactant proteins (SP) play an important role in enhancing the surface properties of pulmonary surfactant and participate in host-defense mechanism(s) of the lung. Although it is known that cigarette smoking alters both pulmonary surfactant lipid composition and function, its effect on SPs is unknown. The present study was carried out to determine if chronic exposure to cigarette smoke alters pulmonary SPs, namely, SP-A and SP-B, in a rat model. Sprague-Dawley rats were exposed to cigarette smoke in a nose-only exposure system twice a day, every day for 70 weeks. At termination, bronchoalveolar lavage (BAL) fluid and the lung tissues were collected from room control, sham-treated (SH), and smoke-exposed (SM) animals for analyses. The total protein levels in the BAL fluid of SM rats tended to be higher but were not statistically different from those of the SH group. However, the albumin content of BAL fluid in SM rats, measured by quantitative immunoblotting, was significantly higher than in control groups. Compared to control groups, SP-A and SP-B levels in the BAL fluid of SM rats were significantly reduced by 25 and 50%, respectively, when expressed as units per microgram of BAL fluid protein. However, when calculated as total BAL fluid SP recovered per rat, only the SP-B levels of SM rats were significantly different from the control groups. Further analysis by ELISA confirmed the reduced levels of SP-B in SM rats. In contrast to BAL fluid, the lung tissue levels of SP and their respective mRNAs were not significantly different between the control and smoke-exposed groups. These results show a selective reduction in SP-B content on the bronchoalveolar surface following chronic exposure to cigarette smoke and suggest an inhibitory effect of cigarette smoke on surfactant secretory processes and/or a localized destruction of SPs on the bronchoalveolar surface.

Animals↗

PubMed1996

Modification of kainate-induced behavioral and electrographic seizures following inhibition of nitric oxide synthase in mice.

We assessed the effects of N(omega)-nitro-L-arginine-methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), on behavioral and electrographic seizures elicited in mice by convulsant doses of kainate. In Expt. 1, L-NAME dose-dependently potentiated the convulsant effects of kainate (44 mg/kg s.c.), transforming long-latency clonic convulsions into short-latency fits of wild-running, and increased the incidence of kainate-induced mortality. The proconvulsant effects of L-NAME (5 mg/kg i.p.) did not reflect shortened latency to kainate-induced epileptiform afterdischarge recorded via electrodes chronically implanted into the hippocampus, amygdala, frontal cortex or mesencephalic reticular formation (Expt. 2). We also observed a dramatic uncoupling of behavioral and electrographic seizures in mice treated with L-NAME 30 min prior to kainate: 4/6 mice treated with L-NAME failed to express afterdischarge from any of the sites assessed during fits of wild-running. The proconvulsant effects of L-NAME were dependent on the route of administration of kainate, as the inhibitor of NOS failed to alter behavioral (clonic) or electrographic seizures elicited by intrahippocampal kainate (1 nmol, Expt. 3) yet shortened latency to fits of wild-running following i.c.v. kainate (1 nmol, Expt. 4) and reduced the dose of systemic kainate required for either clonic convulsions or wild-running (Expt. 5). The observations that L-NAME potentiates kainate-induced wild-running but not necessarily clonus suggest the involvement of tectopontine mechanisms.

Animals↗

PubMed1996

Factors determining proconvulsant and anticonvulsant effects of inhibitors of nitric oxide synthase in rodents.

Although a majority of studies suggest that inhibitors of nitric oxide synthase (NOS) are proconvulsant, a substantial minority indicate the opposite (i.e. that inhibitors of NOS are anticonvulsant). As a consequence, the role of endogenous nitric oxide (NO) in the expression of seizures is unclear. In the present series of experiments, we therefore assessed factors governing pro- and anticonvulsant effects of inhibitors of NOS. In mice receiving systemic injections of kainate or picrotoxin, we confirmed the hypothesis that the effects of inhibitors of NOS vary with the model of seizure: Whereas 7-nitroindazole (7-NI) reduced the latency and increased the severity of kainate-induced convulsions (Expt. 1), both 7-NI and N(omega)-nitro-L-arginine methyl ester (L-NAME) slightly delayed clonus following the systemic administration of picrotoxin at doses > or = 3.5 mg/kg but not at doses < or = 3.0 mg/kg (Expts. 2-5). Paradoxically, L-NAME but not 7-NI significantly reduced the CD50 of picrotoxin, which was approximately 2 mg/kg in control mice (Expt. 4), revealing inhibitor-specific interactions with the dose of the convulsant. Finally, we determined in rats that the effects of L-NAME on kainate-induced seizures vary as a function of genetic factors: L-NAME significantly potentiated kainate-induced convulsions in Sprague-Dawley rats but not in Wistar rats (Expt. 6).

Animals↗

PubMed1996

Explicit solvent models in protein pKa calculations.

Continuum methods for calculation of protein electrostatics treat buried and ordered water molecules by one of two approximations; either the dielectric constant of regions containing ordered water molecules is equal to the bulk solvent dielectric constant, or it is equal to the protein dielectric constant though no fixed atoms are used to represent water molecules. A method for calculating the titration behavior of individual residues in proteins has been tested on models of hen egg white lysozyme containing various numbers of explicit water molecules. Water molecules were included based on hydrogen bonding, solvent accessibility, and/or proximity to titrating groups in the protein. Inclusion of water molecules significantly alters the calculated titration behavior of individual titrating sites, shifting calculated pKa values by up to 0.5 pH unit. Our results suggest that approximately one water molecule within hydrogen-bonding distance of each charged group should be included in protein electrostatics calculations.

Animals↗

PubMed1996

Solvation, water permeation, and ionic selectivity of a putative model for the pore region of the voltage-gated sodium channel.

This paper describes a molecular dynamics and molecular mechanics study of the solvation and selectivity of the narrow pore and vestibule region of a model-built structure for the voltage-gated sodium channel. The particular structure used was one proposed by Guy and Durell. However, many of the features we saw would likely be shared with other possible models for this channel, such as the one proposed by Lipkind and Fozzard. It was found that the water mobility was reduced in the channel and the water orientations were significantly ordered by the channel environment. Water mobility depended on protein mobility; in a computer experiment in which the protein was artificially frozen, channel water at 300 degrees K was immobilized. Water motions were defined in significant part by a series of discrete moves from one pattern of hydrogen bonding with particular amino acids to another. However, there are so many different hydrogen bonding patterns that a description of the motion in terms of transitions among a small number of discrete states is not appropriate. In the model whose solvation we explored, several charged residues seem to play a particularly significant role in determining solvation and water motions. Based on energy minimization studies, the structure clearly shows selectivity for univalent cations over anions.

Amino Acid Sequence↗

PubMed1996

The residues Leu 93 and Asp 96 act independently in the bacteriorhodopsin photocycle: studies with the leu 93-->Ala, Asp 96-->Asn double mutant.

Previous mutagenesis studies with bacteriorhodopsin have shown that reprotonation of the Schiff's base is the rate-limiting step in the photocycle of the D96N mutant, whereas retinal re-isomerization and return of the protein to the initial state constitute the rate-limiting events in the photocycle of the L93A mutant. Thus, in the D96N mutant, decay of the M intermediate is slowed down by more than 100-fold at pH 7. In the L93A mutant, decay of the O intermediate is slowed down by 250-fold. We report here that in the L93A, D96N double mutant, decay of the M intermediate, as well as the formation and decay of the O intermediate, are slowed down dramatically. The photocycle is completed by the decay of a long-lived O intermediate, as in the L93A mutant. The decay of the M and O intermediates in the double mutant parallels the behavior seen in the single mutants over a wide temperature and pH range, arguing that the observed independence is an intrinsic property of the mutant. The slow decay of the M and O intermediates can be selectively and independently reversed under conditions identical to those used for the corresponding intermediates in the D96N and L93A single mutants. Because the effects of the two individual mutations are preserved in the double mutant and can be independently reversed, we conclude that residues Asp 96 and Leu 93 act independently and at different stages of the bacteriorhodopsin photocycle. These results also show that formation of the O intermediate only requires protonation of the Schiff's base and is independent of the protonation of Asp 96 from the aqueous medium.

Alanine↗

PubMed1996

ABGEN: a knowledge-based automated approach for antibody structure modeling.

Immunoglobulin (Ig) amino acid sequences are highly conserved and often have sequence homology ranging from 70 to 95%. Antigen binding fragments (Fab), variable region fragments (Fv), and single chain Fv (scFv) of more than 50 myeloma proteins and monoclonal antibodies (mAb) have been crystallized and display a high degree of structural similarity. Based on this observation, several homology modeling approaches have been developed for the prediction of Fab and Fv structures prior to their experimental determination. We have extracted features from existing Ig sequences, 44 known Fab and Fv structures to create an automated AntiBody structure GENeration (ABGEN) algorithm for obtaining structural models of antibody fragments. ABGEN utilizes a homology based scaffolding technique, and includes the use of invariant and strictly conserved residues, structural motifs of known Fab, canonical features of hypervariable loops, torsional constraints for residue replacements and key inter-residue interactions. The validity of the ABGEN algorithm has been tested using a five-fold cross validation with the existing Fab structures. Molecular mechanics and dynamics methods have been implemented with ABGEN models to accurately predict two Fab structures of anti-sweetener antibodies prior to crystallographic determinations.

Algorithms↗

PubMed1996

Block of the N-methyl-D-aspartate receptor by remacemide and its des-glycine metabolite.

The anticonvulsant and neuroprotective properties of remacemide [(+/-)-2-amino-N-(1-methyl-1,2-diphenylethyl)acetamide] and its active des-glycine metabolite [(+/-)-1-methyl-1,2-diphenylethylamine] may result in part from blockade of N-methyl-D-aspartate (NMDA) receptors. The blocking actions of the remacemide enantiomers and their des-glycinates were investigated in whole cell voltage-clamp recordings from cultured rat hippocampal neurons and in binding studies with [3H]dizocilpine in rat forebrain membranes. (+/-)-Remacemide caused a rapid and reversible inhibition of NMDA-evoked current; the R(+)- and S(-)-enantiomers were roughly equipotent (IC50 values at -60 mV, 67 and 75 microM, respectively). In contrast, the block by the S(+)- and R(-)-des-glycine analogs was slower, more potent and occurred in a stereoselective fashion (IC50 values, 0.7 and 4 microM). The block by S(+)-des-glycine remacemide was strongly use- and voltage-dependent, and, in addition, could be occluded by Mg++, indicating that it occurs by an open channel mechanism. In contrast, the block by R(+)-remacemide was only partially voltage-dependent, suggesting that it occurs by both channel blocking and nonchannel blocking (allosteric) mechanisms. Support for an allosteric mechanism was obtained in nonequilibrium [3H]dizocilpine binding studies where it was observed that 100 microM R(+)-remacemide slowed the dissociation of the radioligand [whereas 10 microM S(+)-des-glycine remacemide did not]. Neither R(+)-remacemide nor S(+)-des-glycine remacemide inhibited currents evoked by kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate or gamma-aminobutyric acid. We conclude that des-glycine remacemide is a potent and selective channel blocking NMDA receptor antagonist, whereas remacemide is weaker and inhibits NMDA receptors by both channel blocking and nonchannel blocking actions.

Acetamides↗

PubMed1996

A knowledge-based method for protein structure refinement and prediction.

The native conformation of a protein, in a given environment, is determined entirely by the various interatomic interactions dictated by the amino acid sequence (1-3). We describe here a knowledge-based approach for protein structure assessment and prediction. Using a well-defined set of high-resolution protein structures, we have derived statistical potentials, in the form of atom-pairwise distance probability density functions. These provide a description of pairwise interatomic interactions of native proteins. When applied to highly randomized and noisy structures of proteins distinct from the basis set, native-like structures were obtained to very high precision (< or = 2A). The examples tested include proteins of all sizes (from 38 up to 461 amino acids long) and diverse topological structures (alpha, beta and alpha-beta classes). The potentials appear to be sensitive enough to recognize subtle distortions from a native packing structure and in optimization of structures drive them consistently to a higher probability. Therefore they provide a powerful tool for refinement of X-ray and NMR derived structures at arbitrary degrees of initial precision.

Crystallography, X-Ray↗

PubMed1995

Molecular mechanism of protein-retinal coupling in bacteriorhodopsin.

Bacteriorhodopsin is a membrane protein that functions as a light-driven proton pump. Each cycle of proton transport is initiated by the light-induced isomerization of retinal from the all-trans to 13-cis configuration and is completed by the protein-driven reisomerization of retinal to the all-trans configuration. Previous studies have shown that replacement of Leu-93, a residue in close proximity to the 13-methyl group of retinal, by alanine, resulted in a 250-fold increase in the time required to complete each photocycle. Here, we show that the kinetic defect in the photocycle of the Leu-93-->Ala mutant occurs at a stage after the completion of proton transport and can be overcome in the presence of strong background illumination. Time-resolved retinal-extraction experiments demonstrate the continued presence of a 13-cis intermediate in the photocycle of the Leu-93-->Ala mutant well after the completion of proton release and uptake. These results indicate that retinal reisomerization is kinetically the rate-limiting step in the photocycle of this mutant and that the slow thermal reisomerization can be bypassed by the absorption of a second photon. The effects observed for the Leu-93-->Ala mutant are not observed upon replacement of any other residue in van der Waals contact with retinal or upon replacement of Leu-93 by valine. We conclude that the contact between Leu-93 and the 13-methyl group of retinal plays a key role in controlling the rate of protein conformational changes associated with retinal reisomerization and return of the protein to the initial state.

Bacteriorhodopsins↗

PubMed1995

Effect of eugenol on drug-metabolizing enzymes of carbon tetrachloride-intoxicated rat liver.

The chemoprotection extended by eugenol against carbon tetrachloride (CCl4) intoxication was established by studies on drug-metabolizing phase I and phase II enzymes. An overall decrease in drug-metabolizing enzymes, namely NADPH-cytochrome c reductase, NADH-cytochrome reductase, coumarin hydroxylase, 7-ethoxy coumarin-O-deethylase, UDP-glucuronyltransferase and glutathione-S-transferase, was observed with CCl4 intoxication, with a subsequent decrease in cytochrome P450 and cytochrome b5 content. CCl4 caused a significant decrease in microsomal phospholipids and the marker enzymes glucose-6-phosphatase and 5'-nucleotidase, and an increase in thiobarbituric acid reactive substances (TBARS). Simultaneous administration of eugenol with CCl4 inhibited the accumulation of TBARS and the decrease in the microsomal phospholipids and marker enzymes. Further, the chemical onslaught imposed by CCl4 on the drug-metabolizing system was removed successfully by eugenol. Eugenol appears to act as an in vivo antioxidant and as a better inducer of phase II enzymes than phase I enzymes. It is therefore suggested that eugenol could be an interesting basic structure for drug design.

5'-Nucleotidase↗

PubMed1995

Biochemical and biophysical characterization of pulmonary surfactant in rats exposed chronically to cigarette smoke.

The pulmonary surfactant plays an important role in the gas exchange functions of the lungs. Although previous studies suggest that cigarette smoking alters the pulmonary surfactant system in human smokers, the nature of such changes is poorly understood. The aim of the present study was to determine if biochemical and biophysical properties of pulmonary surfactant are affected in rats following chronic exposure to cigarette smoke. Female Sprague-Dawley rats were exposed daily to smoke from the University of Kentucky high tar/high nicotine reference cigarettes, twice a day, for 60 weeks in a nose-only exposure system. Blood carboxyhemoglobin, plasma cotinine, and pulmonary aryl hydrocarbon hydroxylase activity measurements showed that animals effectively inhaled smoke during exposures. At termination, the bronchoalveolar lavage fluids (BALF) and the lung tissues were collected for biochemical and biophysical analyses of surfactant. The total phospholipid content of the BALF and the lung tissues from room control (RC), sham-treated (SH), and smoke-exposed (SM) animals were the same among the different groups. However, disaturated phosphatidylcholine (DSPC) levels in the BALF were significantly decreased in SM rats compared to RC or SH groups. In contrast, the lung tissue DSPC content in SM rats was not significantly different from that of control groups. Phospholipid profile analysis of the BALF also did not reveal any significant differences among other major constituents of surfactant from control and SM animals. The organic extracts of BALF obtained from different animal groups were assessed for surface activity using a Wilhelmy balance. The results showed an increase in surface compressibility and a reduction in respreadability index in SM group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗