Periodontitis and Diabetes: Complication or Predictor.

Recent studies indicate that periodontal health influences systemic health and that this has also been considered as a bidirectional relationship for several systemic conditions. This is particularly evident for the inter-relationship between periodontal disease and diabetes mellitus (DM). This relationship between the health of periodontium and DM provides an example of a viz. association. Whereby, there is always possibility that a systemic disease predisposes the individual to oral infections, and, once the oral infection is established, it exacerbates the systemic disease through its pathogenesis and its disease cycle incorporating other organs as oral cavity is also a part of a human body. There are also associations between periodontal disease and systemic conditions such as cardiovascular problems, osteoporosis, obesity, and pancreatic disease. Hence, emphasis should now be placed on treating chronic periodontal diseases as a means of deteriorating systemic diseases. Now-a-day periodontitis has been considered as the sixth complication of DM.

A comparative 2D QSAR study on a series of hydroxamic acid-based histone deacetylase inhibitors vis-à-vis comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA).

A quantitative structure-activity relationship (QSAR) study was performed on a series of indole amide analogues reported by Dai et al. [Bioorg Med Chem Lett (2003), 13, 1897-1901] to act as histone deacetylase (HDAC) inhibitors. The multiple regression analysis (MRA) revealed a model showing the significant dependence of the activity on molar refractivity (MR) and global topological charge index (GTCI) of the compounds, suggesting that inhibition of the HDAC by this series of compounds might involve the dispersion interaction with the receptor, where charge transfer between pairs of atoms might greatly help to polarize the molecule. The MRA results were then compared with those obtained by Guo et al. [Bioorg Med Chem (2005), 13, 5424-5434] by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). It was found that MRA gave as good results and had as good predictive ability as CoMFA and CoMSIA. Besides, MRA was also able to throw the light on the physicochemical properties of the molecules that were involved in drug-receptor interactions, while CoMFA and CoMSIA could not. The dispersion interaction between the molecule and the active site of the receptor is suggested to be the main interaction.

A quantitative structure-activity relationship (QSAR) study on a few series of potent, highly selective inhibitors of nitric oxide synthase.

QSAR study was performed on a series of 1,2-dihydro-4-quinazolinamines, 4,5-dialkylsubstituted-2-imino-1,3-thiazolidine derivatives and 4,5-disubstituted-1,3-oxazolidin-2-imine derivatives studied by Tinker et al. [J Med Chem (2003), 46, 913-916], Ueda et al. [Bioorg Med Chem (2004) 12, 4101-4116] and Ueda et al. [Bioorg Med Chem Lett (2004) 14, 313-316], respectively, as potent, highly selective inhibitors of inducible nitric oxide synthase (iNOS). The iNOS inhibition activity of the whole series of compounds was analyzed in relation to the physicochemical and molecular properties of the compounds. The QSAR analysis revealed that the inhibition potency of the compounds was controlled by a topological parameter 1v (Kier’s first order valence molecular connectivity index), density (D), surface tension (St) and length (steric parameter) of a substituent. This suggested that the drug-receptor interaction predominantly involved the dispersion interaction, but the bulky molecule would face steric problem because of which the molecule may not completely fit in active sites of the receptor and thus may not have the optimum interaction.

A QSAR study on a series of thiourea derivatives acting as anti-hepatitis C virus agents.

A quantitative structure-activity relationship (QSAR) study was performed on a large series of thiourea derivatives reported by Kang et al. [Bioorg Med Chem Lett (2009), 19, 1950-55 & 6063-68], acting as anti-hepatitis C virus (anti-HCV) agents. The activity of the compounds was found to be significantly correlated with their hydrophobic property and three indicator variables I1, I2 and I3, the first two specifying a negative effect of an alkyl and an aromatic group, respectively on their R-moiety and the third one specifying a negative effect of their Ar-moiety having a nitrogen-containing heterocyclic ring. The whole set containing 85 compounds was divided into two subsets: the training set and the test set containing 61 and 24 compounds, respectively. For the training set, the correlation coefficient (r) and the square of cross-validated correlation coefficient (r2cv) were found to be 0.926 and 0.83, respectively. The correlation obtained suggested that anti-HCV activity of the compounds would depend on their hydrophobic property, conformational flexibility and the steric effects of an alkyl or an aromatic group on the R-moiety. This suggested that the molecules might have significant hydrophobic interactions with the receptor which might be aided by their conformational flexibility, but hindered sterically by an alkyl or an aromatic group on their R-moiety. Using the correlation obtained, some new compounds having activity higher (>8.0) than the most active compound in the existing series were predicted.

A QSAR and molecular modeling study on a series of 3, 4-dihydro-1-isoquinolinamines and thienopyridines acting as nitric oxide synthase inhibitors.

A quantitative structure-activity relationship (QSAR) and molecular modeling study were performed on a series of 3,4-dihyro-1-isoquinolinamines and thienopyridines reported by Beaton et al. [Beaton et al. (2001) Bioorg Med Chem Lett 11, 1023-1026, 1027-1030] as potent, highly selective inhibitors of two isoforms of nitric oxide synthase (NOS) — neuronal NOS (nNOS) and endothelial NOS (eNOS), in order to find the physicochemical properties that governed their activity and the mode of interaction with the receptors, so that still more potent compounds in the series could be suggested. A multiple regression analysis revealed that nNOS and eNOS inhibition potency of these compounds could be controlled by their hydrophobic property and molar refractivity, respectively. Thus, nNOS and eNOS inhibition was indicated to involve the hydrophobic interaction and steric effects, respectively, suggesting some structural differences of the two isoforms of NOS. Based on the correlations obtained, some new, more potent compounds belonging to the series were predicted. These compounds were then docked into the receptors to see their interactions and find out the docking scores. The docked structures of two representative compounds, whose interaction energies with nNOS and eNOS, respectively were found to be the lowest, were given as an example to exhibit the possible orientation of the compounds to interact with the receptors.

A QSAR study on a series of N-methyl pyrimidones acting as HIV integrase inhibitors.

A quantitative structure-activity relationship (QSAR) study has been performed on integrase (IN) inhibition activity of a large series of N-methyl pyrimidones [Gardelli et al. (2007) J Med Chem 50, 4953-4975)] having varying heterocyclic ring substitution at 2-position of pyrimidone ring. The activity is found to be significantly correlated with surface tension and molar volume of the molecules. The whole series of compounds is divided into two subsets: a training set and a test set. A significant correlation is obtained for the training set, which is then used to predict the activity of compounds in the test set. The predicted activities of compounds in the test set are found to be very close to their observed activities. The predicting ability of the correlation obtained is judged by leave-one-out jackknife procedure. The correlation shows the effective role of the surface tension and molar volume of the molecules. From the correlation obtained, the integrase inhibition activities are predicted for some new prospective compounds.

Prophylactic Antiemetic Therapy with Ondansetron, Granisetron and Metoclopramide in Patients Undergoing Laparoscopic Cholecystectomy Under GA.

The aim of the present study was to compare the antiemetic effect of intravenous Granisetron, Ondansetron & Metoclopramide in a randomized blinded study for prophylaxis of post operative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy under general anaesthesia. 60 patients (ASA I & II) undergoing laparoscopic cholecystectomy under general anaesthesia were randomly allocated into three equal groups (n=20). Emetic episodes in first 24 hours were recorded and compared in different study groups. Results were analyzed. Minimal emetic episodes were observed in early post-operative period (1-12hrs) in patients who had received intravenous granisetron in comparison to ondansetron and metoclopramide. However, after 12 hours emesis free periods were statistically insignificant between group A and B while patients in group C had no antiemetic effect.

Recanalization of a single functioning kidney.

For patients with renal artery stenosis, percutaneous transluminal angioplasty is generally the treatment of choice. This report describes the case of an elderly lady with type III aortoarteritis whose right renal artery was successfully recalized and stented. There was satisfactory improvement in renal function and blood pressure post-procedure, and at one-month follow-up.

Pulmonary Resections - Jammu Experience

Ten year registry of patients who underwent pulmonary resections at CTVS section of Govt Medical College Jammu is being presented. The cohort consisted of 94 patients operated between1994-2004. Males outnumbered females in this series Most number (30/94) of patients presented in the 4th decade. Etiology wise, Infective lung diseases were the leading causes leading to pulmonary resections, this included bronchiectasts with 32/94, chronic empyema in6/94 and middle lobe syndrome in one patient. Lung tumors were the causative factors in 20 and post tuberculosis destroyed lung in 17 cases. Two patients presented with intralobar lung sequestrations and one each with pulmonary blastoma and teratoma. The spectrum of resections included right pneumonectomy in19/94 followed by right and left lower lobectomies in 18 each. Thirteen patients underwent left pneumonectomy, 7 bilobectomy and 4 lingulectomy respectively. The mortality in our series was 6/94,20 patients had wound infection, 9 had bronchopleural fistula and 3 postoperative space infections.3 patients were reexplored because of hemorrhage in immediate postoperative period. Diagnostic video assisted thoracoscopy has been started and was employed in 6 patients.

Mortality and morbidity of acute ST segment elevation myocardial infarction in the current era.

BACKGROUND: The mortality rate of acute myocardial infarction has come down considerably in the past three decades. In view of paucity of literature on this issue, present study was done to find out the in-hospital mortality and 30-day event rate in patients with acute ST segment elevation myocardial infarction presenting to a tertiary care hospital in India. METHODS AND RESULTS: Consecutive patients (n=1320) with the diagnosis of acute ST segment elevation myocardial infarction admitted in our institution were included in this study. The in-hospital mortality and 30-day event rates (mortality, reinfarction, recurrent angina and heart failure) were analyzed. The mean age of study population was 56+/-13 years. There were 1106 (83.8%) males and 214 (16.2%) females; 569 (43.1%) patients were smokers, 504 (38.2%) patients had hypertension, 531 (40.2%) patients were diabetic and 154 (11.7%) patients had past history of myocardial infarction. Anterior wall infarction was present in 752 (57%) patients, 517 (39.1%) patients had inferior wall infarction, 324 (62.7%) patients had associated right ventricular or posterior wall infarction and 51 (3.9%) patients had antero-inferior infarction; 1093 patients (82.8%) received thrombolytic therapy while 227 patients were not thrombolyzed due to various reasons. Of the total 1320 patients, 223 (16.9%) patients died during in-hospital stay while 1097 patients were discharged from the hospital in stable condition after a mean stay of 5.3+/-3.4 days. Thirty-day event rates of death, reinfarction and recurrent angina following hospital discharge was 18.8% (134/715 patients) and 36 (5%) patients presented with heart failure. CONCLUSIONS: The in-hospital mortality rate of acute ST segment elevation myocardial infarction in a tertiary care hospital is 16.9%, which is higher compared to reports from the West.

Prevalence of coronary artery disease in patients with rheumatic heart disease in the current era.

BACKGROUND: This study was undertaken to determine the prevalence of coronary artery disease in patients with rheumatic heart disease undergoing valve surgery. METHODS AND RESULTS: Consecutive patients with rheumatic heart disease (n=376) who were above the age of 40 years, and scheduled for valve surgery underwent diagnostic coronary angiogram to delineate coronary arteries. The patients were divided into three groups based on valve involvement (mitral valve, aortic valve, and combined aortic and mitral valve). Significant coronary artery disease was considered to be present if one or more coronaries showed 50% or more luminal stenosis. There were 287 (76.3%) males and 89 (23.7%) females. The mean age of the study population was 51.2+/-8.2 years. Eighty-nine (23.8%) patients had typical chest pain, 116 (30.6%) patients had atypical chest pain and 171 (45.5%) patients had no chest pain. Hypertension was noted in 88 (23.4%) patients, 65 (17.3%) patients had diabetes, 98 (26.1%) patients were smoker, and 66 (17.6%) patients had dyslipidemia, and 15 (4.0%) patients gave past history of myocardial infarction. Of the total 376 patients, 46 (12.2%) patients were found to have significant coronary artery disease. In patients with mitral vale disease the prevalence was 13.5% (13/96), while it was 15.3% (19/124) in patients with aortic valve disease and 9% (14/156) in those with combined mitral and aortic valve disease. CONCLUSIONS: Our results suggest that the overall prevalence of coronary artery disease in a group of patients with rheumatic heart disease undergoing valve surgery in the current era is 12.2%. This prevalence is much lower than the figures reported earlier in the Western literature.

Heart failure: what proportion of patients satisfy the electrocardiographic criteria for cardiac resynchronization therapy?

BACKGROUND: Cardiac resynchronization therapy has emerged as a new therapeutic modality for patients with congestive cardiac failure and associated intraventricular conduction delay. The purpose of this study was to find out what proportion of Indian patients with congestive heart failure may be candidates for cardiac resynchronization therapy based on electrocardiographic characteristics. METHODS AND RESULTS: One hundred twenty-one consecutive patients with congestive cardiac failure due to various etiologies whose left ventricular ejection fraction was less than 40% were included in the study. Standard 12-lead electrocardiogram was recorded in all the patients, and various parameters (rhythm, conduction, QRS axis, chamber enlargement, chamber hypertrophy, and the presence of Q waves) were analyzed. The study population comprised 82 male (67.8%) and 39 female (32.2%) patients with a mean age of 53 +/- 13 years. Thirty-nine patients (32.2%) had NYHA class I-II symptoms, and 82 (67.8%) had NYHA class III-IV symptoms. The mean QRS duration was 111 +/- 27 ms. Bundle branch block was seen in 43 patients (35.5%), of whom 30 (24.8%) had left bundle branch block, and 13 (10.7%) had right bundle branch block. Of the 30 patients who had left bundle branch block, 19 (15.7%) had a QRS duration of between 120 and 149 ms, and 11 (9%) had a QRS duration > or = 150 ms. In the latter group, 7 patients (5.8%) were in NYHA classes III and IV. As the clinical severity of heart failure increased, the mean QRS duration also increased, but this increment was not statistically significant. CONCLUSIONS: Based on our data, it can be estimated that of the patients with heart failure who attend a tertiary care center, 2 5% of patients present with left bundle branch block. If we use the criteria for NYHA class III and IV congestive cardiac failure with QRS duration of > or = 150 ms in patients with left bundle branch block, 6% of patients are likely to need cardiac resynchronization therapy.

Utility of N-terminal pro-brain natriuretic peptide for the diagnosis of heart failure.

BACKGROUND: The goal of this study was to evaluate the utility of plasma N-terminal pro-brain natriuretic peptide for the diagnosis of heart failure in patients presenting with shortness of breath. METHODS AND RESULTS: We measured plasma levels of N-terminal pro-brain natriuretic peptide in 119 patients presenting with shortness of breath. The patients were divided into two groups based on the Framingham criteria and echocardiographic results--those with heart failure and those not in heart failure. Plasma levels of N-terminal pro-brain natriuretic peptide were compared in the two groups. The mean N-terminal pro-brain natriuretic peptide concentration in patients with heart failure (n=73) was higher than that in those not in heart failure (389+/-148 fmol/ml v. 142+/-54 fmol/ml, p<0.001). N-terminal pro-brain natriuretic peptide values increased significantly as the functional severity of heart failure increased (p<0.001). The mean N-terminal pro-brain natriuretic peptide levels were 261+/-34 fmol/ml for patients in New York Heart Association functional class I, 300+/-161 fmol/ml for patients in New York Heart Association functional class II, 427+/-103 fmol/ml for patients in New York Heart Association functional class III and 528+/-170 fmol/ml for patients in New York Heart Association functional class IV. Using a cut-off value of 200 fmol/ml, the sensitivity of N-terminal pro-brain natriuretic peptide was 97%, specificity was 89% and accuracy for differentiating heart failure from other causes of shortness of breath was 93%. CONCLUSIONS: Our results suggest that N-terminal pro-brain natriuretic peptide can be reliably used for the diagnosis of heart failure in an outpatient setting, and this will improve the ability of clinicians to differentiate patients with shortness of breath due to heart failure from those with other causes of shortness of breath.