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Biomedical subjects

M Chandra

Publications and source records attributed to M Chandra.

At least 19 recordsLinked to original sources
PubMed2006

Effect of ascorbic acid supplementation on certain oxidative stress parameters in the post reperfusion patients of myocardial infarction.

Reperfusion injury causes oxidative stress thereby resulting in an imbalance between oxidant-antioxidant systems. In the present communication, the effect of ascorbic acid supplementation has been studied on certain oxidant and antioxidant parameters in the blood of the patients with myocardial infarction before and after thrombolysis. In patients after thrombolysis, the activity of antioxidant enzyme, superoxide dismutase, in the blood was found to be significantly reduced where as the activity of the oxidant enzyme, xanthine oxidase, was found to be significantly increased. Malondialdehyde levels, the index of free radical mediated damage, was also found to be significantly elevated in thrombolysed patients compared to the patients before thrombolysis. Supplementation of vitamin C to the post reperfusion patients restored these parameters back to normal or near normal levels.

Ascorbic Acid↗
PubMed2006

Status of some free radical scavenging enzymes in the blood of myocardial infarction patients.

Pro-oxidant and anti-oxidant systems and their levels have significant roles in occlusive vascular diseases. In the present communication, we have measured the levels of some representative anti-oxidant enzymes in the blood of the patients of myocardial infarction after reperfusion and compared them to age and sex matched healthy persons. Our findings show that the activities of anti-oxidant enzymes (viz. SOD, catalase and glutathione reductase) are significantly decreased whereas there is significant increase in the levels of malonaldialdehyde (a marker of free radical-mediated damage) in the patients. The findings point out that ischemic myocardial disorders are associated with excessive free radical generation and free radical-mediated damage of lipids.

Aged↗
PubMed2006

Adenosine deaminase in ischemia reperfusion injury in patients with myocardial infarction.

A comparative study on the levels of erythrocyte adenosine deaminase and lipid peroxidation has been undertaken in patients with myocardial infarction before and after thrombolysis along with matched healthy individuals. Our findings show that adenosine deaminase activity is highly elevated in post-reperfused patients when compared to pre- thrombolysed and healthy persons. Malondialdehyde(MDA) levels are also significantly increased in post-thrombolysed patients. The study reveals an important role of adenosine deaminase in reperfusion injury in patients with myocardial infarction.

Adenosine Deaminase↗
PubMed2005

Oxidative stress parameters in erythrocytes of post-reperfused patients with myocardial infarction.

The effect of reperfusion of patients with myocardial infarction on the levels of some anti-oxidant enzymes, total thiols, malondialdehyde formation in erythrocytes and plasma ascorbate levels have been investigated. Significantly decreased activities of catalase and superoxide dismutase and decreased levels of total thiols in RBC's and ascorbic acid in plasma suggest that reperfusion of the infarcted myocardium leads to oxidative stress conditions wherein anti-oxidant mechanisms become less effective in coping with the oxidative insult. This view is further supported by the observation that in the post reperfused patients there is a highly significant enhancement in the levels of malondialdehyde.

Adult↗
PubMed2004

Luminescent piano-stool complexes incorporating 1-(4-cyanophenyl)imidazole: synthesis, spectral, and structural studies.

Three novel luminescent piano-stool arene ruthenium complexes of general formula [(eta(6)-arene)RuCl(2)(CPI)] (eta(6)-arene = benzene, 1, p-cymene, 2, and hexamethylbenzene, 3; CPI=1-(4-cyanophenyl)imidazole were prepared. The molecular structures of 2 and 3 were determined crystallographically. Reaction of 1-3 with EPh(3) (E = P, As, or Sb) and N-N donor bases such as 2,2'-bipyridine and 1,10-phenanthroline afforded cationic mononuclear complexes of general formula [(eta(6)-arene)RuCl(CPI)(EPh(3))](+) (eta(6)-arene = C(6)H(6), E = P (1a), E = As (1b), E = Sb(1c); eta(6)-arene = C(10)H(14), E = P (2a), E = As (2b), E = Sb (2c); eta(6)-arene = C(6)Me(6), E = P (3a), E = As (3b), E = Sb (3c)) and [(eta(6)-arene)Ru(N-N)(CPI)](2+) (eta(6)-arene = C(6)H(6), N-N = bipy (1d), N-N = phen (1e); eta(6)-arene = C(10)H(14), N-N = bipy (2d), N-N = phen (2e); eta(6)-arene = C(6)Me(6), N-N = bipy (3d), N-N = phen (3e)). Molecular structures of 1a and 2a were also confirmed by X-ray crystallography. Structural studies of the complexes 2, 3, 1a, and 2a supported coordination of CPI through the imidazole nitrogen and the presence of a pendant nitrile group. Structural data also revealed stabilization of crystal packing in the complexes 2, 3, and 2a by C-H...X (X = Cl, F) type inter- and intramolecular interactions and in complex 1a by pi-pi stacking. Moreover, neutral homonuclear bimetallic complexes 2f,g were prepared by using complex 2 as a metallo-ligand, where CPI acts as a bridge between two metal centers. Emission spectra of the mononuclear complexes [(eta(6)-arene)RuCl(2)(CPI)] and its derivatives exhibited intense luminescence when excited in the metal to ligand charge-transfer band.

Journal Article↗
PubMed2002

Prevalence of hypertension in psychiatric disorders.

OBJECTIVE: To study the prevalence of hypertension in our cases with psychiatric disorders and to study if the prevalence is higher in the cases with psychiatric disorders. METHODS: Four hundred twenty two cases with various psychiatric disorders attending the Outpatient Department of Psychiatry of our hospital were studied. Detailed clinical evaluation was done in all the cases. Blood pressure was recorded in the sitting position and mean of three readings was taken. Diagnosis and grading of hypertension was done according to the JNC V recommendations. Psychiatric disorders were diagnosed according to DSM IV criteria. RESULTS: Mean age of the cases was 36.3 years. Prevalence of hypertension in the cases was 7.1%. Prevalence in male and female cases were 7.2% and 7.0%, respectively. Prevalence of hypertension in various age groups was 20-39 years--1.48%, 40-60 years--24.4%, > 60 years--33.3%. CONCLUSION: The overall prevalence of hypertension in our cases with psychiatric disorders was 7.1% which was not higher than the reported prevalence of hypertension in our general population.

Adult↗
PubMed2001

Cardiac troponin T mutations: correlation between the type of mutation and the nature of myofilament dysfunction in transgenic mice.

1. The heterogenic nature of familial hypertrophic cardiomyopathy (FHC) in humans suggests a link between the type of mutation and the nature of patho-physiological alterations in cardiac myocytes. Exactly how FHC-associated mutations in cardiac troponin T (cTnT) lead to impaired cardiac function is unclear. 2. We measured steady-state isometric force and ATPase activity in detergent-skinned cardiac fibre bundles from three transgenic (TG) mouse hearts in which 50, 92 and 6 % of the native cTnT was replaced by the wild type (WT) cTnT, R92Q mutant cTnT (R92Q) and the C-terminal deletion mutant of cTnT (cTnT(DEL)), respectively. 3. Normalized pCa-tension relationships of R92Q and cTnT(DEL) fibres demonstrated a significant increase in sensitivity to Ca2+ at short (2.0 microm) and long (2.3 microm) sarcomere lengths (SL). At short SL, the pCa50 values, representing the midpoint of the pCa-tension relationship, were 5.69 +/- 0.01, 5.96 +/- 0.01 and 5.81 +/- 0.01 for WT, R92Q and cTnT(DEL) fibres, respectively. At long SL, the pCa50 values were 5.81 +/- 0.01, 6.08 +/- 0.01 and 5.95 +/- 0.01 for WT, R92Q and cTnT(DEL) fibres, respectively. 4. The difference in pCa required for half-maximal activation (DeltapCa50) at short and long SL was 0.12 +/- 0.01 for the R92Q (92 %) TG fibres, which is significantly less than the previously reported DeltapCa50 value of 0.29 +/- 0.02 for R92Q (67 %) TG fibres. 5. At short SL, Ca2+-activated maximal tension in both R92Q and cTnT(DEL) fibres decreased significantly (24 and 21 %, respectively; P < 0.005), with no corresponding decrease in Ca2+-activated maximal ATPase activity. Therefore, at short SL, the tension cost in R92Q and cTnT(DEL) fibres increased by 35 and 29 %, respectively (P < 0.001). 6. The fibre bundles reconstituted with the recombinant mutant cTnT(DEL) protein developed only 37 % of the Ca2+-activated maximal force developed by recombinant WT cTnT reconstituted fibre bundles, with no apparent changes in Ca2+ sensitivity. 7. Our data indicate that an important mutation-linked effect on cardiac function is the result of an inefficient use of ATP at the myofilament level. Furthermore, the extent of the mutation-induced dysfunction depends not only on the nature of the mutation, but also on the concentration of the mutant protein in the sarcomere.

Actin Cytoskeleton↗
PubMed2001

Structure of the C-domain of human cardiac troponin C in complex with the Ca2+ sensitizing drug EMD 57033.

Ca(2+) binding to cardiac troponin C (cTnC) triggers contraction in heart muscle. In heart failure, myofilaments response to Ca(2+) are often altered and compounds that sensitize the myofilaments to Ca(2+) possess therapeutic value in this syndrome. One of the most potent and selective Ca(2+) sensitizers is the thiadiazinone derivative EMD 57033, which increases myocardial contractile function both in vivo and in vitro and interacts with cTnC in vitro. We have determined the NMR structure of the 1:1 complex between Ca(2+)-saturated C-domain of human cTnC (cCTnC) and EMD 57033. Favorable hydrophobic interactions between the drug and the protein position EMD 57033 in the hydrophobic cleft of the protein. The drug molecule is orientated such that the chiral group of EMD 57033 fits deep in the hydrophobic pocket and makes several key contacts with the protein. This stereospecific interaction explains why the (-)-enantiomer of EMD 57033 is inactive. Titrations of the cCTnC.EMD 57033 complex with two regions of cardiac troponin I (cTnI(34-71) and cTnI(128-147)) reveal that the drug does not share a common binding epitope with cTnI(128-147) but is completely displaced by cTnI(34-71). These results have important implications for elucidating the mechanism of the Ca(2+) sensitizing effect of EMD 57033 in cardiac muscle contraction.

Calcium↗
PubMed2001

Ocular and orbital cysticercosis.

PURPOSE: To study the demographic factors, clinical diagnosis, results of investigation, modalities of treatment and their outcome in ocular and extraocular cysticercosis. METHOD: A total of 20 patients were recruited for the study. Ultrasonography and computed tomography were done for all the patients. Serial ultrasound was obtained in patients receiving medical treatment. Therapy was individualized according to the location of the cyst. RESULTS: The commonest clinical presentation was proptosis (9 of 20) with restriction of ocular movements, followed by subconjunctival cyst, subretinal cyst, papilloedema, atypical optic neuritis, lid nodule and intraretinal cyst. Ultrasonography was comparable with computed tomographic scan for detection of scolex. Two of the twenty patients had associated cysts in the brain parenchyma. Medical or surgical therapy as indicated, had a satisfactory outcome. CONCLUSION: Cysticerci can lodge themselves in any part of the ocular and extra ocular tissue. Associated brain parenchyma involvement is quite rare. The clinical presentation, treatment and outcome mainly depends on the location of the cyst.

Adolescent↗
PubMed2001

Jet eccentricity: a misleading source of agreement between Doppler/catheter pressure gradients in aortic stenosis.

Characterization of the severity of aortic stenosis relies on accurate measurement of the pressure gradient across the valve and the valve area. Pressure gradients measured by Doppler ultrasound based on the clinical form of the Bernoulli equation often overestimate pressure gradients by catheter as the result of pressure recovery. Doppler techniques measure the velocity of the vena contracta of the stenotic jet. This corresponds to the maximal pressure gradient and the minimal effective valve area. Pressure recovery can be characterized by analysis of the spread of the stenotic jet downstream of the valve as it fills the aorta and should be influenced by the shape of the velocity profile of the decaying jet. In this study, we addressed the hypothesis that the site of complete pressure recovery (the point at which the jet fully expands to the size of the aorta), the effective valve area, and the maximal pressure gradient are affected by jet eccentricity. To accomplish this, we developed a computational model of aortic stenosis that provides detailed velocity and pressure information in the vicinity of the valve. The results show that the width of the eccentric wall jet decreased and maximal velocity increased with greater jet eccentricity. Furthermore, for a constant anatomic area, the effective valve area decreased, the distance to complete pressure recovery increased, and the maximal pressure gradient increased with the degree of eccentricity. Failure to take this into account could fortuitously drive Doppler and catheter measurements toward agreement because the distal pressure sensor will not record the fully recovered pressure. Therefore the pressure gradient across a stenotic valve depends on jet eccentricity. The spread of the wall jet after attachment must be characterized to develop a robust method for the prediction of pressure recovery.

Aortic Valve↗
PubMed2001

Ca(2+) activation of myofilaments from transgenic mouse hearts expressing R92Q mutant cardiac troponin T.

The functional consequences of the R92Q mutation in cardiac troponin T (cTnT), linked to familial hypertrophic cardiomyopathy in humans, are not well understood. We have studied steady- and pre-steady-state mechanical activity of detergent-skinned fiber bundles from a transgenic (TG) mouse model in which 67% of the total cTnT in the heart was replaced by the R92Q mutant cTnT. TG fibers were more sensitive to Ca(2+) than nontransgenic (NTG) fibers [negative logarithm of half maximally activating molar Ca(2+) (pCa(50)) = 5.84 +/- 0.01 and 6.12 +/- 0.01 for NTG and TG fibers, respectively]. The shift in pCa(50) caused by increasing the sarcomere length from 1.9 to 2.3 microm was significantly higher for TG than for NTG fibers (DeltapCa(50) = 0.13 +/- 0.01 and 0.29 +/- 0.02 for NTG and TG fibers, respectively). The relationships between rate of ATP consumption and steady-state isometric tension were linear, and the slopes were the same in NTG and TG fibers. Rate of tension redevelopment was more sensitive to Ca(2+) in TG than in NTG fibers (pCa(50) = 5.71 +/- 0.02 and 6.07 +/- 0.02 for NTG and TG fibers, respectively). We concluded that overall cross-bridge cycling kinetics are not altered by the R92Q mutation but that altered troponin-tropomyosin interactions could be responsible for the increase in myofilament Ca(2+) sensitivity in TG myofilaments.

Acidosis↗
PubMed2001

Transgenic incorporation of skeletal TnT into cardiac myofilaments blunts PKC-mediated depression of force.

Protein kinase C (PKC)-mediated phosphorylation of cardiac troponin I (cTnI) and troponin T (cTnT) has been shown to diminish maximum activation of myofilaments. The functional role of cTnI phosphorylation has been investigated. However, the impact of cTnT phosphorylation on myofilament force is not well studied. We tested the effect of endogenous PKC activation on steady-state tension development and Ca(2+) sensitivity in skinned fiber bundles from transgenic (TG) mouse hearts expressing fast skeletal TnT (fsTnT), which naturally lacks the PKC sites present in cTnT. The 12-O-tetradecanoylphorbol 13-acetate (TPA) treatment induced a 29% (46.1 +/- 2.5 vs. 33.4 +/- 2.6 mN/mm(2)) reduction in maximum tension in the nontransgenic (NTG) preparations (n = 7) and was inhibited with chelerythrine. However, TPA did not induce a change in the maximum tension in the TG preparations (n = 11). TPA induced a small but significant (P < 0.02) increase in Ca(2+) sensitivity (untreated pCa(50) = 5.63 +/- 0.01 vs. treated pCa(50) = 5.72 +/- 0.01) only in TG preparations. In TG preparations, (32)P incorporation was not evident in TnT and was also significantly diminished in cTnI, compared with NTG. Our data indicate that incorporation of fsTnT into the cardiac myofilament lattice blunts PKC-mediated depression of maximum tension. These data also suggest that cTnT may play an important role in amplifying the myofilament depression induced by PKC-mediated phosphorylation of cTnI.

Actin Cytoskeleton↗
PubMed2000

Structural mapping of single cysteine mutants of cardiac troponin I.

The global conformation of cardiac muscle troponin I (cTnI) was investigated with single-cysteine mutants by using a combination of sulfhydryl reactivity and fluorescence resonance energy transfer (FRET) to determine cysteine accessibility and intersite distances. The reactivity was determined with a fluorescent reagent for its reaction with cysteine residues singly located at positions 5, 40, 81, 98, 115, 133, 150, 167, and 192. FRET measurements were made by using the endogenous single Trp-192 as the energy donor and an acceptor probe covalently attached to the cysteines as energy acceptor. The results suggest an open and extended conformation of cTnI with a large curvature in which the cysteines are highly exposed to the solvent. These conformational features are largely retained in the segment between residues 40 and 192 upon phosphorylation at Ser-23 and Ser-24. The sulfhydryl groups of the Cys-133 and Cys-150 of the cTnI incorporated into the binary cTnC-cTnI and fully reconstituted troponin complexes experience large reduced exposure resulting from the binding of Ca(2+) to the regulatory site of cTnC, suggesting that key regions of cTnI involved in activation become highly shielded upon activation. In the cTnC-cTnI complex, every intramolecular distance in the cTnI is lengthened and the overall conformation of the bound cTnI remains elongated with reduced exposure for the cysteines. The global conformation of the troponin C-troponin I complex from cardiac muscle has an elongated shape with constrained flexibility. The highly flexible nature of the N-terminal extension of cTnI is preserved in the complex, suggesting that this segment of cTnI is either not bound or only loosely bound to the C-domain of cTnC.

Amino Acid Substitution↗
PubMed2000

Biological function and site II Ca2+-induced opening of the regulatory domain of skeletal troponin C are impaired by invariant site I or II Glu mutations.

To investigate the roles of site I and II invariant Glu residues 41 and 77 in the functional properties and calcium-induced structural opening of skeletal muscle troponin C (TnC) regulatory domain, we have replaced them by Ala in intact F29W TnC and in wild-type and F29W N domains (TnC residues 1-90). Reconstitution of intact E41A/F29W and E77A/F29W mutants into TnC-depleted muscle skinned fibers showed that Ca(2+)-induced tension is greatly reduced compared with the F29W control. Circular dichroism measurements of wild-type N domain as a function of pCa (= -log[Ca(2+)]) demonstrated that approximately 90% of the total change in molar ellipticity at 222 nm ([theta](222 nm)) could be assigned to site II Ca(2+) binding. With E41A, E77A, and cardiac TnC N domains this [theta](222 nm) change attributable to site II was reduced to < or =40% of that seen with wild type, consistent with their structures remaining closed in +Ca(2+). Furthermore, the Ca(2+)-induced changes in fluorescence, near UV CD, and UV difference spectra observed with intact F29W are largely abolished with E41A/F29W and E77A/F29W TnCs. Taken together, the data indicate that the major structural change in N domain, including the closed to open transition, is triggered by site II Ca(2+) binding, an interpretation relevant to the energetics of the skeletal muscle TnC and cardiac TnC systems.

Alanine↗