Assessing the Patient Outcomes and Performance of a Cardiothoracic and Vascular Surgery (CTVS) Unit During Its First Two Years in a Tier-2 City in India: A Comprehensive Audit and Analysis.

This detailed article presents a comprehensive overview of the initial two-year experience in establishing a new cardiothoracic vascular surgery (CTVS) facility in a tier-2 city in India. The article discusses various aspects of setting up and operating a specialized healthcare facility. The first two years of developing the CTVS facility were included in the study period. The manpower included one cardiothoracic vascular surgeon, one cardiac anesthesiologist, two perfusionists, and two physician assistants, along with four other ancillary staff to assist in the smooth functioning of the operation theater. The CTVS recovery staff included 15 nursing officers. There was only one modular operation theater reserved for cardiothoracic vascular surgeries, along with a five-bed recovery room (CTVS intensive care unit). One-hundred-seventy-two procedures were done, including 122 open heart surgeries, 36 vascular procedures, and 14 thoracic procedures. The majority of patients were discharged by the seventh day postoperatively. Overall complication and mortality rates were 8% and 4.6%, respectively. This article also discusses relevant hospital policy, challenges faced, and future recommendations for similar endeavors. The findings highlight the successful implementation of the facility and its impact on providing specialized cardiac care to the local population.

Tools for optimising pharmacotherapy in psychiatry (therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests): focus on antidepressants.

Objectives: More than 40 drugs are available to treat affective disorders. Individual selection of the optimal drug and dose is required to attain the highest possible efficacy and acceptable tolerability for every patient.Methods: This review, which includes more than 500 articles selected by 30 experts, combines relevant knowledge on studies investigating the pharmacokinetics, pharmacodynamics and pharmacogenetics of 33 antidepressant drugs and of 4 drugs approved for augmentation in cases of insufficient response to antidepressant monotherapy. Such studies typically measure drug concentrations in blood (i.e. therapeutic drug monitoring) and genotype relevant genetic polymorphisms of enzymes, transporters or receptors involved in drug metabolism or mechanism of action. Imaging studies, primarily positron emission tomography that relates drug concentrations in blood and radioligand binding, are considered to quantify target structure occupancy by the antidepressant drugs in vivo. Results: Evidence is given that in vivo imaging, therapeutic drug monitoring and genotyping and/or phenotyping of drug metabolising enzymes should be an integral part in the development of any new antidepressant drug.Conclusions: To guide antidepressant drug therapy in everyday practice, there are multiple indications such as uncertain adherence, polypharmacy, nonresponse and/or adverse reactions under therapeutically recommended doses, where therapeutic drug monitoring and cytochrome P450 genotyping and/or phenotyping should be applied as valid tools of precision medicine.

CYP and GST polymorphisms and survival in advanced non-small cell lung cancer patients.

UNLABELLED: Several polymorphisms in cytochrome P-450s (CYP)s and Glutathione S-transferases (GST)s have been reported to be associated with survival rates of patients with non-small cell lung cancer (NSCLC) but the studies in this regard are scarce and the results are contradictory. In this study, CYP1A1 (Ile462Val), CYP1B1(Asn453Ser), GST M1, GSTP1 exon 5 (Ile105Val) and exon 6(Ala114Val) and GSTT1 polymorphisms were determined in 138 patients with advanced NSCLC to evaluate their role in survival. Of the studied CYP and GST polymorphisms only GSTP1 exon 6 variant significantly altered (improved) the survival compared to wild type (p=0.036) with median survival of 22.2 months and 16.1 months, respectively. Multivariate analysis also revealed a significant reduction of adjusted hazard ratio of death associated only with the GSTP1 exon 6 variant genotype of 0.45 (95% confidence interval (95% CI), 0.23-0.89, p=0.022). These results show that the GSTP1 exon 6 variant genotype is associated with improved survival in the patients with advanced NSCLC. KEYWORDS: Cytochrome P-450, glutathione S-transferase, non small cell lung cancer, polymorphism, survival.

Comparative effect of N-substituted dehydroamino acids and alpha-tocopherol on rat liver lipid peroxidation activities.

Free radical damage has been associated with a growing number of diseases and conditions, such as autoimmune diseases, neurodegenerative disorders and multiple types of cancer. Some dehydroamino acids and corresponding peptides can function as radical scavengers. In this study the in vitro effects on rat liver lipid peroxidation levels of fourteen N-substituted dehydroamino acid derivatives and alpha-tocopherol were investigated. alpha-Tocopherol is a powerful antioxidant that is beneficial in the treatment of many free radical related diseases. The results indicated that all the compounds showed very good inhibitory effect on the lipid peroxidation compound with alpha-tocopherol at 1 mM concentrations and the inhibition rate was in the range of 70-79 % with the exception of compound 5. At 0.1 mM concentrations compounds 1, 2 and 9 were found more active than alpha-tocopherol. The results confirmed that molecules such as dehydroamino acids which have reactive double bonds can act as a guard in vitro against oxidants.

Synthesis and antimicrobial activity of some new 2-phenyl-N-substituted carboxamido-1H-benzimidazole derivatives.

Some 1H-benzimidazole-carboxamide derivatives were prepared and their antimicrobial activities against Staphyloccus aureus, Escherichia coli and Candida albicans evaluated. Compounds 18, 22, and 25 exhibited the best activity against Candida albicans.

Synthesis and analytical evaluation by voltammetric studies of some new indole-3-propionamide derivatives.

Some biologically important and melatonin-related indole-3-propionamide derivatives were synthesized. The compounds synthesized were analyzed and characterized first by NMR and mass spectrometry and then investigated by analytical voltammetric techniques. Based on this study a simple, rapid and sensitive voltammetric method was developed for the determination of the indole derivatives that are readily oxidized at the carbon-based electrodes. The oxidative behavior of the indole derivatives was studied as a function of pH at a glassy carbon electrode. The characteristics of the corresponding electrode reaction were discussed.

Anti-cancer activity studies of indolalthiohydantoin (PIT) on certain cancer cell lines.

5-(2-Phenyl-3'-indolal)-2-thiohydantoin (PIT) has been evaluated as an anti-cancer compound on several cancer lines organised in to subpanels representing leukemia, melanoma, and cancer of lung, colon, kidney, ovary, breast, prostate and central nervous system by the National Cancer Institute (NCI) anti-cancer drug screen programme. The compound showed inhibitory activity on several cancer cell lines. No information is available on anti-cancer potency of this compound with normal cell lines.

Behaviour of dehydroalanine derivatives under hydrazinolysis conditions. Possible relevance to glycoprotein hydrazinolysis.

Reactions that are relevant to the cleavage, by hydrazinolysis, of O-linked oligosaccharides from glycoproteins were studied using dehydroalanine derivatives as models of the intermediates formed from O-glycosylated serine residues. Conjugate addition of hydrazine followed by cyclisation to form pyrazolidinones, if occurring during glycoprotein hydrazinolysis, could reduce the yield of released oligosaccharide. However, N-acetyldehydroalanine amide derivatives, which modelled the dehydroalanine derivatives believed to be intermediates in the hydrazinolysis of glycoproteins containing O-linked oligosaccharides, underwent conjugate addition but no cyclisation.

Evaluation of anti-HIV activity of 5-(2-phenyl-3'-indolal)-2-thiohydantoin.

The anti-HIV activity of the previously synthesized 5-(2-phenyl-3'-indolal)-2-thiohydantoin I was evaluated. The compound, containing two structural moieties found in highly active anti-HIV agents, exhibited poor activity and rather high cytotoxicity.

Application of the restriction site mutation technique to N-methyl-N-nitrosourea-induced mutations in the rat.

The restriction site mutation (RSM) assay was developed in this laboratory for the detection of point mutations that occur within restriction endonuclease recognition sequences in the genomic DNA of the rat. Mutations were detected and identified in a number of tissues from N-methyl-N-nitrosourea (MNU)-treated rats. Resistant restriction enzyme products were detected in 5 of the 13 restriction endonuclease recognition sequences tested (NcoI, BslI, CfoI, DdeI, and HindIII). These mutations were detected in the p53 tumor suppressor gene and the H-ras protooncogene. No resistant RSM products were detected in any of the samples taken from untreated animals. The MNU-induced mutations were identified as G to A and A to G transitions. Our results describe the first successful application of the RSM assay in detecting induced mutations in the rat and highlight the usefulness of the RSM assay in the analysis of mutagen-induced base changes without the requirement for selection of a mutant phenotype. Given the increasing use of the rat as an animal model in genotoxicity studies, the development of such tests is essential for future genotoxicity investigations.

The inhibitory effect of benzodiazepine derivatives on the bovine lens aldose reductase enzyme.

The aldose reductase enzyme, involved in the sorbitol pathway which is an important mechanism in regulation of mammalian glucose metabolism, has been known to play a significant role in the initiation of diabetic complications. Numerous chemical substances have been prepared in order to improve the pharmacological profile of inhibition of aldose reductase enzyme. In this study, aldose reductase inhibitory activities of several benzodiazepine derivatives were investigated. The enzyme was obtained from bovine lenses via the ammonium sulphate-protein cut method with several steps. It was found that tetrazepam had a significant inhibitor potency among the other benzodiazepine derivatives showing very slight inhibitor activities that are indicated in terms of percent inhibitor potency at 10(-4) M concentration.

Effects of a benzimidazole compound on monooxygenase activities.

A retinoid-type benzimidazole compound (benzimidazole-tetranaphthalene, BITN) was synthesized and its effects on hepatic cytochrome P450 (CYP) dependent ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-depentylase (PROD) enzyme activities were determined in rats in vitro. In vitro addition of BITN in 10(-3) M concentration to the reaction medium caused inhibitions in EROD (94%) and PROD (82%) activities. With the same concentration (10(-3) M) all-trans-retinoic acid (RA) was able to inhibit EROD activity 65% and PROD activity 59% whereas buthylated hydroxytoluen (BHT) inhibited EROD and PROD activities 73% and 62%, respectively. The specific inhibitors of EROD activity (caffeine) and PROD activity (SKF 525A) at 10(-3) M concentration inhibited the corresponding enzymes 33% and 77%, respectively. Thus, these results reveal that the BITN has a stronger inhibitory effect than RA, BHT, caffeine and SKF 525 A on the enzyme activities. Since these enzymes (EROD, CYP 1A1/2 and PROD, CYP2B1) activate polycyclic hydrocarbons, aromatic amines and aliphatic halogenated hydrocarbons to their ultimate mutagenic or carcinogenic forms, and are effective in producing reactive oxygen species such as superoxide, hydroxyl radical and hydrogen peroxide, the new compound, BITN, appears to have a greater anticarcinogenic and antioxidant potential than RA and BHT.

Studies on the synthesis and structure-activity relationships of 5-(3'-indolal)-2-thiohydantoin derivatives as aldose reductase enzyme inhibitors.

A new series of 5-(3'-indolal)-2-thiohydantoin derivatives was synthesized and tested for the ability to inhibit bovine lens aldose reductase (AR) enzyme. The compounds were prepared by condensation of substituted indole-3-aldehyde derivatives with 2-thiohydantoin. The capacity of inhibiting the semi-purified bovine lens enzyme in vitro was observed for several of the compounds tested. One of them was found to be effective in reducing the enzyme activity compared with a corresponding well-known AR inhibitor.

Analysis of the serum paraoxonase/arylesterase polymorphism in a Turkish population.

Human serum paraoxonase is a polymorphic enzyme that is capable of catalyzing the hydrolysis of paraoxon and other organophosphates, some carbamates and certain aromatic carboxylic acid esters. This enzyme is specified by two allelic genes at one autosomal locus (isozymes 'A' and 'B'). The purpose of this study was to examine the paraoxonase activity of 105 Turkish subjects. Paraoxonase activities ranged from 39.6 to 278.2 nmol p-nitrophenol formed per ml of serum per min. Paraoxonase phenotypes could be clearly identified by salt and paraoxonase:arylesterase activity ratio characteristics. The gene frequencies were 0.632 for the low activity allele (A) and 0.368 for the high activity allele (B).