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Biomedical subjects

R Sudha

Publications and source records attributed to R Sudha.

At least 19 recordsLinked to original sources

Effect of esmolol on oxidant status and antioxidant activity in acute myocardial infarction.

AIMS AND OBJECTIVES: The role of oxygen free radicals in reperfusion injury to the heart in myocardial infarction (MI) has been postulated. In this study, the clinical and antioxidant effects of esmolol, an ultra-short acting beta blocker in patients of acute MI was studied. MATERIAL AND METHODS: This was a randomized, double-blind, controlled, prospective study. Total 30 patients with acute MI were included. All patients were thrombolysed with streptokinase. Fifteen of these patients were randomly selected to receive esmolol while other 15 patients served as controls. The parameters compared at 0, 2 and 24 hours between the esmolol group and the controls were--malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX). RESULTS: Patients with MI had 5.16 times higher MDA level at 0 hours (20.34 +/- 6.12 nmol/ml vs. 3.94 +/- 0.70 nmol/ml, p < 0.0001) than MDA level in normal healthy population. At 2 hours, patients with MI had 5.71 times higher MDA level compared to normal healthy population (22.51 +/- 5.51 nmol/ml vs. 3.94 +/- 0.70 nmol/ml, p < 0.0001). A statistically significant difference in MDA levels at 2 and 24 hours was observed in MI patients given esmolol (mean change 2.06 +/- 5.39 nmol/ml vs. -4.47 +/- 6.93 nmol/ml, p = 0.009). Esmolol infusion also caused significant difference in GPX level at 2 hours compared to controls (23.79 + 14.68 U/gm Hb vs 38.3 +/- 8.95 U/gm Hb, p = 0.003). CONCLUSION: Free radical levels are raised in patients with MI which may contribute to reperfusion injury. The antioxidant action of esmolol was clearly observed by significant difference in MDA level and GPX sparing effect. Large scale clinical trials may establish conclusively role of beta blockers as antioxidants as adjuvant to thrombolytic therapy in MI.

Adrenergic beta-Antagonists↗

Structural effects on the formation of proton and alkali metal ion adducts of apolar, neutral peptides: electrospray ionization mass spectrometry and Ab initio theoretical studies.

Apolar, neutral peptides have been shown to ionize extremely well under the conditions used for electrospray ionization mass spectrometry (ESIMS). Peptides for which the conformations have been independently determined in solution and in crystals have been examined by ESIMS. Studies of peptide helices ranging from 7 to 18 residues reveal that shorter helices yield exclusively singly charged ions, while in larger helices multiply charged species are detectable. Multiple sites for protonation/metallation are introduced in the helix by proline insertion or by changing the chirality in the residue. The preferred site of cation binding to helices may be the C-terminus end, where three free CO groups are available for chelation. Ab initio and DFT calculations at several levels have been carried out for the binding of H+, Li+, Na+, and K+ to CHO-(Gly)3)-OMe. The results reveal that metallation in helices is favoured by chelation to carbonyl groups at the C-terminus, while protonation involved two carbonyl groups and thus favour a 10-membered cyclic hydrogen-bonded structure. In -strands, metallation/protonation occurs at isolated carbonyl groups. Collision induced fragmentation of hydrophobic peptides under ESI conditions reveals that helix fragmentation occurs predominantly from the C-terminus, while in -hairpins cleavage occurs simultaneously at multiple sites.

Amino Acids, Neutral↗

Gramicidin S: a peptide model for protein glycation and reversal of glycation using nucleophilic amines.

Nonenzymatic glycation of proteins has been implicated in various diabetic complications and age-related disorders. Proteins undergo glycation at the N-terminus or at the epsilon-amino group of lysine residues. Glycation of proteins proceeds through the stages of Schiff base formation, conversion to ketoamine product and advanced glycation end products. Gramicidin S, which has two ornithine residues, was used as a model system to study the various stages of glycation of proteins using electrospray ionization mass spectrometry. The proximity of two ornithine residues in the peptide favors the glycation reaction. Formation of advanced glycation end products and diglycation on ornithine residues in gramicidin S were observed. The formation of Schiff base adduct is reversible, whereas the Amadori rearrangement to the ketoamine product is irreversible. Nucleophilic amines and hydrazines can deglycate the Schiff base adduct of glucose with peptides and proteins. Hydroxylamine, isonicotinic acid hydrazide and aminoguanidine effectively removed glucose from the Schiff base adduct of gramicidin S. Hydroxylamine is more effective in deglycating the adduct compared with isonicotinic acid hydrazide and aminoguanidine. The observation that the hydrazines are effective in deglycating the Schiff base adduct even in the presence of high concentrations of glucose, may have a possible therapeutic application in preventing complications of diabetes mellitus. Hydrazines may be used to distinguish between the Schiff base and the ketoamine products formed at the initial stages of glycation.

Glycation End Products, Advanced↗

Natal and neonatal teeth : a report of four cases.

Natal and Neonatal teeth although not unique anomalies, are observed in infants at birth or during the first 30 days of life. Here, the report of our four cases, in which the bilateral mandibular posterior natal teeth, which stands out to be a rare condition is presented. Etiological, clinical, histological features, complications and treatment modalities are discussed.

Female↗

A role for the alpha 113 (GH1) amino acid residue in the polymerization of sickle hemoglobin. Evaluation of its inhibitory strength and interaction linkage with two fiber contact sites (alpha 16/23) located in the AB region of the alpha-chain.

A cluster of amino acid residues located in the AB-GH region of the alpha-chain are shown in intra-double strand axial interactions of the hemoglobin S (HbS) polymer. However, alphaLeu-113 (GH1) located in the periphery is not implicated in any interactions by either crystal structure or models of the fiber, and its role in HbS polymerization has not been explored by solution experiments. We have constructed HbS Twin Peaks (betaGlu-6-->Val, alphaLeu-113-->His) to ascertain the hitherto unknown role of the alpha113 site in the polymerization process. The structural and functional behavior of HbS Twin Peaks was comparable with HbS. HbS Twin Peaks polymerized with a slower rate compared with HbS, and its polymer solubility (C(sat)) was found to be about 1.8-fold higher than HbS. To further authenticate the participation of the alpha113 site in the polymerization process as well as to evaluate its relative inhibitory strength, we constructed HbS tetramers in which the alpha113 mutation was coupled individually with two established fiber contact sites (alpha16 and alpha23) located in the AB region of the alpha-chain: HbS(alphaLys-16-->Gln, alphaLeu-113-->His), HbS(alphaGlu-23-->Gln, alphaLeu-113-->His). The single mutants at alpha16/alpha23 sites were also engineered as controls. The C(sat) values of the HbS point mutants involving sites alpha16 or alpha23 were higher than HbS but markedly lower as compared with HbS Twin Peaks. In contrast, C(sat) values of both double mutants were comparable with or higher than that of HbS Twin Peaks. The demonstration of the inhibitory effect of alpha113 mutation alone or in combination with other sites, in quantitative terms, unequivocally establishes a role for this site in HbS gelation. These results have implications for development of a more accurate model of the fiber that could serve as a blueprint for therapeutic intervention.

Dimerization↗

Spermidine as a potential biosynthetic precursor to the 1,5-diazabicyclo[4:3:o]nonene residue in the efrapeptins.

Efrapeptins are a group of microheterogeneous polypeptide antibiotics produced by the fungus Tolypocladium niveum, which are potent inhibitors of mitochondrial F1-ATPase. Efrapeptins contain an unusual 1,5-diazabicyclo[4:3:0]nonene (DBN) residue at the C-terminus. This study is driven by the hypothesis that the DBN residue could, in principle, arise by oxidative cyclization of a spermidine moiety. Electrospray ionization mass spectrometry of the peptide antibiotics 'elvapeptins' from T niveum establishes the presence of a C-terminal spermidine residue. Conversion of elvapeptins to efrapeptins by CuCl/pyridine demonstrates the transformation of the spermidine residue to the 1,5-diazabicyclo[4:3:0]nonene system by oxidative cyclization.

Amino Acid Sequence↗

Lot quality assurance sampling for monitoring immunization coverage in Madras City.

OBJECTIVE: To explore the usefulness of Lot Quality Assurance Sampling (LQAS) to identify divisions in a city that had immunization coverage levels of 80% for any of the four EPI vaccines. METHODS: Only 43 divisions were considered for the study, the stratification factor being the death rate. The hypothesis that 80% coverage is 'unacceptable' was stipulated. Critical value (the number of unimmunized children) was chosen as 3. A simple random sample of 36 children in the age-group 12-23 months was taken from each selected division. Since sampling frames of children were not available, a simple random sample of 36 households was selected. Immunization status of each child was assessed by interviewing the child's mother/guardian. If the number of unimmunized children exceeded 3, then the division was regarded having coverage level 80% and rejected. RESULTS: The coverage was classified as unacceptable(i. e., below 80%) in 19 divisions for Polio and DPT vaccines, in 26 divisions for Measles vaccine and in 4 divisions for BCG vaccine. The average time spent for undertaking the LQAS survey was 6 man-days per division. CONCLUSION: This study demonstrated the utility of the LQAS technique in identifying 'unsatisfactory' pockets in Madras City, when the overall coverage was satisfactory. The technique will have greater application with an increase in the number of large units (cities/districts) having an overall coverage of 90% or more.

Health Care Surveys↗

Randomised controlled field trial of two antenatal care packages in rural south India.

A randomised community intervention trial was undertaken in 12 subcentres in Karur health unit district, Tamil Nadu, to compare the efficacy of two antenatal care packages. A newly recommended 'high-risk' strategy package and a uniform package recommended by the Tamil Nadu Government were each implemented in 4 randomly selected subcentres by the study team, and the latter was also delivered by routine health services in the 4 remaining subcentres. Analyses were based on 294 pregnant women on the high-risk package (HR), 242 on the Tamil Nadu Government (TNG) package and 335 women in the control series. The HR package reduced the differences between the high-risk women and the others in mean haemoglobin and the percentages with preventable neonatal morbidity and low birth weight, and consequently the overall outcome was better in the HR series than in the TNG series. Finally, the results with the TNG package were better when it was implemented by the study team than by the routine health services, in terms of preventable maternal morbidity and preventable perinatal morbidity, but there was no impact on birth weight.

Birth Weight↗

Long-term follow-up results after plain balloon coronary angioplasty.

Between September 1987 and June 1992, 571 patients of coronary artery disease underwent percutaneous transluminal coronary angioplasty in our institute. Their ages ranged from 31-82 years (mean 51 +/- 9) and majority (88.3%) were males. At baseline, 318 (55.7%) patients had chronic stable angina, 184 (32.2%) unstable angina, and 57 (10%) underwent PTCA for recurrence of angina in the post-infarction period. Single vessel angioplasty was performed in 406 (71.1%), two-vessel angioplasty in 121 (21.2%) and three or more vessels were dilated in 44 (7.7%). The procedure was successful in 524 (91.8%) patients. Follow-up was available in 438 (83.6%) patients, and ranged from 78 to 135 months (mean 89 +/- 29) with all the patients completing at least 60 months of follow-up. Using Kaplan-Meier statistical analysis, event-free survival (freedom from repeat percutaneous transluminal coronary angioplasty, myocardial infarction, coronary artery bypass surgery, or death) was 72.5 percent at three, 68.0 percent at five, 61.8 percent at seven and 55.6 percent at 10 years of follow-up. Freedom from major adverse cardiac events (myocardial infarction, coronary artery bypass surgery or death) was 88.3, 85.8, 82.0 and 75.4 percent at 3, 5, 7 and 10 years, respectively. Overall survival was 97.4 and 95.2 percent, respectively at 5 and 10 years. Subgroup analysis for all major events was done between males and females, diabetics and non-diabetics, previous history or absence of myocardial infarction, stable versus unstable angina and single versus multivessel disease. Event-free survival rates were compared between the groups using log rank test. On follow-up, the need for surgical revascularisation was more in males compared to females although statistically insignificant, and in patients with unstable angina compared to stable angina (p < 0.02). Similarly, freedom from major adverse cardiac events was significantly better in females compared to males (p < 0.05) and in stable versus unstable angina (p < 0.01). Event-free survival (repeat percutaneous transluminal coronary angioplasty, myocardial infarction, coronary artery bypass surgery, death) was also significantly better in patients with stable angina (p < 0.02). The other outcomes were comparable in all the subgroups. In conclusion, plain balloon angioplasty provides excellent long-term results in patients with coronary artery disease in terms of reduction in major adverse cardiovascular events and need for subsequent revascularisation.

Adult↗

Amlodipine monotherapy in chronic stable angina.

The efficacy and safety of amlodipine was evaluated in 20 patients with stable exertional angina. Patients with > or = 3 anginal attacks per week in the placebo run-in phase were admitted into a 4 weeks active treatment phase. Amlodipine was administered at a starting dose of 5 mg once daily at bed time, which could be adjusted after 2 weeks to 10 mg once daily if the patient continued to have even a single anginal attack/week. Four weeks of treatment with amlodipine produced a significant (p < 0.05) reduction from baseline in both the mean (+/- SE) number of anginal attacks/week (from 13.3 +/- 1.5 to 1.6 +/- 0.5) and the mean (+/- SE) number of isosorbide dinitrate tablets consumed per week (12.1 +/- 1.5 to 2.6 +/- 0.8). Eighty three percent of patients required an increase in dose to 10 mg daily. No significant change in heart rate, blood pressure, ECG and laboratory results were observed. One patient was withdrawn because of deteriorating angina and sinus tachycardia secondary to beta blocker withdrawal. Worsening of ankle odema was reported in 2 (10%) patients, which was tolerated and disappeared on completing therapy. Thus amlodipine is safe and effective when used as monotherapy in the treatment of chronic stable angina.

Adult↗

Amlodipine monotherapy in mild to moderate hypertension.

The efficacy and safety of amlodipine was evaluated in 20 patients of mild to moderate hypertension in a single blind, placebo controlled, noncomparative study. Patients with a baseline diastolic blood pressure of > 90 and < 115 mmHg while on placebo were admitted to a 4 week active treatment phase. Amlodipine produced a significant (p < 0.05) reduction in mean systolic (177 mmHg to 145 mmHg) and diastolic blood pressure (106 mmHg to 84 mmHg) after 4 weeks treatment in all patients. 95% of the patients had their diastolic blood pressure reduced to < or = 90 mmHg by the end of the study period. There was no significant change in heart rate or in the laboratory parameters with amlodipine therapy. Seven patients reported mild to moderate adverse events which did not require discontinuation of therapy. This combination of efficacy and tolerability, together with convenience of once daily dosing, should ensure the usefulness of amlodipine in the treatment of hypertension.

Adult↗

A clinico-hematological study of iron deficiency anemia and its correlation with hyperviscosity symptoms in cyanotic congenital heart disease.

The present study was carried out in 33 cases of cyanotic congenital heart disease (CCHD) to determine the prevalence of iron deficiency anemia (IDA) and its correlation to hyperviscosity symptoms in terms of hematocrit levels. Furthermore, the study was aimed at assessing the response to low dose iron therapy (60 mg of elemental iron once daily) in relieving symptoms of hyperviscosity. All these cases were evaluated for presence of symptoms of hyperviscosity and later subjected to various hematological & biochemical parameters of iron deficiency anemia including hemoglobin (Hb), pack cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), serum iron, total iron binding capacity respectively. Results showed presence of IDA in 6/33 cases (18.2%) and hyperviscosity symptoms in 10/33 cases (30.3%). Amongst the group with symptoms of hyperviscosity, in the subset having IDA these symptoms were observed at PCV levels of 0.52 L/L to 0.58 L/L in contrast to the subset not deficient in iron where the symptoms occurred at a PCV 0.68 L/L. Relief of symptoms of hyperviscosity was evident with a minimal rise of mean hemoglobin by 2.1 gm/dl. It was concluded that IDA was not an uncommon finding in CCHD cases and that it leads to symptoms of hyperviscosity at a level of PCV much lower than those known to produce these symptoms. Finally low dose iron therapy was found effective in relieving the symptoms of hyperviscosity.

Adolescent↗