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Biomedical subjects

R Rajagopalan

Publications and source records attributed to R Rajagopalan.

At least 19 recordsLinked to original sources
PubMed2006

Occurrence of extended spectrum beta-lactamases among Enterobacteriaceae spp. isolated at a tertiary care institute.

Increasing resistance to third generation cephalosporins has become a cause for concern especially among Enterobacteriaceae that cause nosocomial infections. The prevalence of extended spectrum beta-lactamases (ESBLs) among members of Enterobacteriaceae constitutes a serious threat to current beta-lactam therapy leading to treatment failure and consequent escalation of costs. A detailed study was initiated to identify the occurrence of ESBLs among the Enterobacteriaceae isolates at a tertiary care hospital using the double disk potentiation technique. Antibiogram profiles were determined to commonly used antibiotics and confirmation of ESBLs production was carried out by the disk diffusion assay using ceftazidime and cefotaxime in the presence and absence of clavulanic acid. Our results indicate that the majority of ESBLs were expressed in Escherichia coli.

Anti-Bacterial Agents↗
PubMed2005

Dual PPAR-alpha and -gamma activators derived from novel benzoxazinone containing thiazolidinediones having antidiabetic and hypolipidemic potential.

2,4-Thiazolidinedione derivatives of 1,3-benzoxazinone were synthesized and evaluated for their PPAR-alpha and -gamma dual activation. DRF-2519, a compound obtained through SAR of TZD derivatives of benzoxazinone, has shown potent dual PPAR activation. In ob/ob mice, it showed better efficacy than the comparator molecules. In fat fed rat model, it showed significant improvement in lipid parameters, which was better than fibrates.

Animals↗
PubMed2005

Comparison of pioglitazone with other antidiabetic drugs for associated incidence of liver failure: no evidence of increased risk of liver failure with pioglitazone.

AIM: The aim of this study was to assess the incidence of liver failure in association with antidiabetic treatment using pioglitazone vs. other oral antidiabetic medications. METHODS: The study was a retrospective analysis of claim data from the PharMetrics Patient-Centric Database that had over 1.12 million enrollees with type 2 diabetes. All patients, > or =18 years of age with type 2 diabetes, who had initiated treatment either with a thiazolidinedione (pioglitazone and rosiglitazone), sulfonylurea or metformin were identified and matched on the basis of propensity scores, which served as a proxy for severity of disease. The primary measure of interest was the incidence of liver failure or hepatitis post-index date. In addition to unadjusted comparisons, Cox proportional hazard models were employed to estimate the risk of developing liver failure or hepatitis. RESULTS: There was no significant difference in the 1- and 2-year incidence rates of liver failure or hepatitis (primary and secondary diagnoses) between the pioglitazone monotherapy group and the respective comparator groups. In Cox proportional hazard models controlling for age, pre-index total healthcare costs, Charlson comorbidity index, procedures and a hospitalization or Emergency room (ER) visit for pre-index hyperglycaemia, and pioglitazone were not associated with an increased risk of liver failure or hepatitis, compared to all other defined groups. Furthermore, no primary or secondary diagnosis of liver failure was reported in the pioglitazone group during the follow-up period. CONCLUSIONS: Results of retrospective data analysis demonstrate no evidence of increased risk of liver failure or hepatitis for patients initiating therapy on pioglitazone, compared to other oral antidiabetic agents. Pioglitazone therapy was not associated with an increased risk of liver failure at 2 years relative to other oral antidiabetic therapies.

Administration, Oral↗
PubMed2004

DRF 3188 a novel semi-synthetic analog of andrographolide: cellular response to MCF 7 breast cancer cells.

BACKGROUND: We determined the effect of andrographolide and one of its novel semi-synthetic analog, DRF 3188, on the cell cycle of MCF 7 breast cancer cells. METHODS: The effect of the compounds on cell cycle was determined using FACS and western blot analysis of cell cycle proteins. Hollow fibre assay was used to determine if the compounds had the same effect on the cell cycle in vitro and in vivo. RESULTS: Our results from the in vitro and in vivo experiments show that both the compounds block the cell cycle at the G0-G1 phase through the induction of the cell cycle inhibitor, p27, and the concomitant decrease in the levels of Cdk4. CONCLUSION: The results show that the novel semi-synthetic analog, DRF3188, and andrographolide bring about the anti cancer activity by a similar mechanism.

Animals↗
PubMed2004

Spatially resolved microrheology through a liquid/liquid interface.

We present a light-scattering technique for the measurement of the microrheological properties of viscoelastic liquids in small volumes over a large frequency range (on the order of eight decades). The accuracy of the method for model viscoelastic liquids (polyethylene oxide solutions in water) is demonstrated by comparing the results with conventional mechanical measurements of the loss and storage moduli. Then we show that the method can be used to measure variations in viscoelastic properties in a heterogeneous system by measuring the variation in the moduli with position (and time) across a liquid/liquid interface between a viscoelastic polymer solution and a Newtonian liquid.

Journal Article↗
PubMed2003

Influence of ethylene-oxy spacer group on the activity of linezolid: synthesis of potent antibacterials possessing a thiocarbonyl group.

The influence of an ethylene-oxy spacer element between the heterocycle and the aromatic ring in linezolid is reported. The introduction of such spacer group generated compounds with inferior antibacterial activity. However, the conversion of the acetamide group present in the linezolid analogues to either thiocarbamate or thioacetamide functionality restored the activity. The synthesis of linezolid analogues possessing the ethylene-oxy spacer group along with SAR studies with different heterocycles and preparation of some thiocarbonyl compounds possessing potent antibacterial property are presented.

Acetamides↗
PubMed2003

Biological investigation and structure-activity relationship studies on azadirone from Azadirachta indica A. Juss.

Azadirone 1, a limonoidal constituent of Azadirachta indica is found to possess potent cytotoxic activity against a panel of human cancer cell lines in our in vitro studies. In vitro screening of a number of semi-synthetic analogues of 1 revealed that the alpha,beta-unsaturated enone moiety or its equivalent conjugated system in A-ring, C-7 acetyloxy/chloroacetyloxy or keto group in B-ring and the furan moiety are responsible for the activity of 1 and its analogues. Compound 1 and two of the semi-synthetic analogues 10 and 13 were found to possess good in vivo antitumor activity in modified hollow fiber animal models.

Antineoplastic Agents↗
PubMed2003

Novel 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues as cytotoxic agents.

A series of 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues were synthesized and evaluated for cytotoxic activity against eight human cancer cell lines. Compounds 18, 21, 28, 29, 30 and 31 showed cytotoxic activity with GI(50) values in the range of 2.1-8.1 microM concentration. Among these, compounds 21 and 28 exhibited good pharmacokinetic properties. These compounds were further evaluated for their in vivo efficacy in modified hollow fibre assay (HFA).

Animals↗
PubMed2002

Novel indolo[2,1-b]quinazoline analogues as cytostatic agents: synthesis, biological evaluation and structure-activity relationship.

In our endeavor to design and synthesize novel anticancer agents, a new series of indoloquinazoline compounds were prepared and tested initially for anticancer activity in vitro against a panel of human cancer cell lines. Most of these compounds exhibited cytotoxic activity in in vitro screens. Compounds were selected and further evaluated using a modified Hollow Fiber Assay for their preliminary in vivo activity against 12 cell lines implanted in the subcutaneous and intraperitoneal compartments in mice. The results indicate that these compounds may constitute a new class of anticancer agents.

Animals↗
PubMed2002

Spatially resolved microrheology using localized coherence volumes.

We propose an optical technique, based on dynamic light scattering, for investigating the local rheological response of a complex fluid over a frequency range larger than that provided by standard mechanical instrumentation. The low-coherence radiation used in a fiber optics configuration allows the measurements to be confined to a small volume around a tenth of a picoliter. The ability of the method to accurately measure both loss and storage moduli has been tested using both simple Newtonian liquids and viscoelastic, complex fluids. The possibility to monitor liquid-gel transitions in polymer solutions has also been demonstrated. The unique capability of the technique to localize the measurement volume suggests that this novel approach can be used for three-dimensional mapping of rheological properties in heterogeneous systems.

Journal Article↗
PubMed2002

Antidiabetic and hypolipidemic activity of Helicteres isora in animal models.

Helicteres isora (Sterculiaceae) root juice has been used in the treatment of diabetes by several ethnic groups in different parts of India. A program was initiated to elucidate the scientific basis for the antidiabetic activity of H. isora. Ethanolic extract of H. isora root caused significant reduction in plasma glucose, triglyceride and insulin levels at 300 mg/kg dose after 9 days of administration to insulin resistant and diabetic C57BL/KsJdb/db mice. In normoglycemic and mildly hypertriglyceridemic Swiss albino mice, the extract also showed significant reduction in plasma triglyceride and insulin levels, without affecting plasma glucose level. An ethanolic extract showed activity distinctly different from glybenclamide and acarbose but similar to troglitazone in these models. In high fat fed hamster model, the extract showed significant reduction in plasma lipid levels. In order to identify the active pharmacophore, the ethanolic extract was further subjected to sequential partitioning with low, medium and high polarity solvents, which yielded a semipurified fraction having both euglycemic and lipid-lowering activity. Our study suggests that the extract of H. isora has insulin-sensitizing and hypolipidemic activity and has the potential for use in the treatment of type-2 diabetes.

Animals↗
PubMed2002

Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients.

BACKGROUND: One of the most troublesome features of atopic dermatitis (AD) is its chronic relapsing nature, and there is a lack of published evidence on the best treatment strategy for long-term management of the disease. OBJECTIVE: To compare an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% (twice per week) with its vehicle base in reducing the risk of relapse when added to regular daily emollient in adult and paediatric subjects with stabilized AD. METHODS: Subjects (aged 3 months to 65 years) with moderate or severe AD were enrolled into an open-label Stabilization Phase of up to 4 weeks on daily emollients plus FP twice daily. Those subjects who achieved 'treatment success' (Global Assessment Score </= 2, erythema, pruritus, and papulation/induration/oedema scores </= 1) entered the double-blind Maintenance Phase. They continued with regular emollients and were randomized at a 2 : 1 ratio to either intermittent FP or vehicle, once daily 4 days per week for 4 weeks followed by once daily 2 days per week for 16 weeks. Subjects who relapsed on intermittent FP were discontinued from the study. Those who did not relapse continued for an additional 24 weeks on intermittent dosing for safety monitoring. RESULTS: A total of 372 (247 paediatric, 125 adult) subjects were enrolled into the Stabilization Phase. Of these, 348 (231 children, 117 adults) were randomized into the Maintenance Phase. Analysis of the primary efficacy parameter showed that subjects receiving intermittent FP cream (twice per week), in addition to regular daily emollients in the Maintenance Phase, were 7.7 times less likely to have an AD relapse than subjects receiving intermittent vehicle cream/emollients [Mantel-Haenszel (MH) estimate of the odds ratio, 95% confidence interval (CI) 4.6, 12.8; P < 0.001]. Paediatric subjects were 8.1 times less likely to have an AD relapse (95% CI 4.3, 15.2; P < 0.001) and adult subjects were 7.0 times less likely to have an AD relapse (95% CI 3.0, 16.7; P < 0.001). For subjects receiving intermittent FP cream/emollient, the median time to relapse could not be estimated as the majority remained controlled at 20 weeks. For those receiving intermittent vehicle/emollient, the median time to relapse was 4.7 weeks. For paediatric and adult groups, this was 5.1 and 4.1 weeks, respectively. Median exposure to FP for all subjects was 337 days. There was only one study drug-related adverse event (acne) and there were no reports of skin thinning or atrophy associated with the use of FP cream in paediatric or adult subjects. CONCLUSIONS: In paediatric and adult subjects, once stabilized with regular FP treatment, the risk of relapse of AD can be significantly reduced by extended intermittent dosing with FP cream in addition to regular emollient therapy.

Administration, Topical↗
PubMed2002

PMT13, a pyrimidone analogue of thiazolidinedione improves insulin resistance-associated disorders in animal models of type 2 diabetes.

AIM: To evaluate the antidiabetic and hypolipidaemic potential of a novel thiazolidinedione, PMT13, in different animal models of insulin resistance. METHODS: PPAR transactivation study was performed in HEK293T cells using ligand binding domains of PPARalpha, gamma and delta. Insulin-resistant db/db and ob/ob mice were treated orally with different doses of PMT13 at 0.3-10 mg/kg/day for 15 and 14 days respectively. Zucker fa/fa rats were treated with 3 mg/kg (p.o.) dose of the compound. Plasma glucose, triglyceride, free fatty acid and insulin levels were measured. Liver glucose 6-phosphatase (G6-Ptase) and adipose lipoprotein lipase activity was measured in treated mice. Isolated rat aortic preparations preconstricted with phenylephrine were used to study the vascular relaxation potential of PMT13 in presence of insulin. A 28-day oral toxicity study was performed in Wistar rats. RESULTS: PMT13 showed similar PPARgamma activation as rosiglitazone, but failed to show any activity against PPARalpha or PPARdelta. In obese and diabetic db/db and ob/ob mice, PMT13 showed better reduction in plasma glucose, triglyceride and insulin levels than rosiglitazone and an improvement in glucose tolerance. In insulin-resistant Zucker fa/fa rat model, PMT13 treatment showed better reduction in plasma triglyceride, free fatty acid and insulin levels than that of rosiglitazone. Treated mice showed decreased G6-Ptase activity in liver. The LPL activity was increased in post-heparin plasma and epididymal fat of treated db/db mice. In an isolated, precontracted rat aortic preparation, PMT13 treatment significantly increased insulin-induced relaxation. A 28-day oral toxicity study in rats showed no treatment-related adverse effects. CONCLUSION: Our studies indicate that PMT13 is a potent activator of PPARgamma with antidiabetic, hypolipidaemic and insulin-sensitizing properties. Additionally, PMT13 inhibited liver G6-Ptase activity and increased lipoprotein lipase activity. It showed improvement in insulin-induced vasorelaxation. The compound also showed a good safety margin. Therefore, PMT13 can be a potential drug candidate for future development.

Animals↗
PubMed2001

(-)3-[4-[2-(Phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid [(-)DRF 2725]: a dual PPAR agonist with potent antihyperglycemic and lipid modulating activity.

(-)DRF 2725 (6) is a phenoxazine analogue of phenyl propanoic acid. Compound 6 showed interesting dual activation of PPAR alpha and PPAR gamma. In insulin resistant db/db mice, 6 showed better reduction of plasma glucose and triglyceride levels as compared to rosiglitazone. Compound 6 has also shown good oral bioavailability and impressive pharmacokinetic characteristics. Our study indicates that 6 has great potential as a drug for diabetes and dyslipidemia.

Animals↗
PubMed2001

Gamma ray induced DNA damage in human and mouse leucocytes measured by SCGE-Pro: a software developed for automated image analysis and data processing for Comet assay.

The studies reported in this communication had two major objectives: first to validate the in-house developed SCGE-Pro: a software developed for automated image analysis and data processing for Comet assay using human peripheral blood leucocytes exposed to radiation doses, viz. 2, 4 and 8 Gy, which are known to produce DNA/chromosome damage using alkaline Comet assay. The second objective was to investigate the effect of gamma radiation on DNA damage in mouse peripheral blood leucocytes using identical doses and experimental conditions, e.g. lyses, electrophoretic conditions and duration of electrophoresis which are known to affect tail moment (TM) and tail length (TL) of comets. Human and mouse whole blood samples were irradiated with different doses of gamma rays, e.g. 2, 4 and 8 Gy at a dose rate of 0.668Gy/min between 0 and 4 degrees C in air. After lyses, cells were electrophorased under alkaline conditions at pH 13, washed and stained with propidium iodide. Images of the cells were acquired and analyzed using in-house developed imaging software, SCGE-Pro, for Comet assay. For each comet, total fluorescence, tail fluorescence and tail length were measured. Increase in TM and TL was considered as the criteria of DNA damage. Analysis of data revealed heterogeneity in the response of leucocytes to gamma ray induced DNA damage both in human as well as in mouse. A wide variation in TM and TL was observed in control and irradiated groups of all the three donors. Data were analyzed for statistical significance using one-way ANOVA. Though a small variation in basal level of TM and TL was observed amongst human and mouse controls, the differences were not statistically significant. A dose-dependent increase in TM (P<0.001) and TL (P<0.001) was obtained at all the radiation doses (2-8 Gy) both in human and mouse leucocytes. However, there was a difference in the nature of dose response curves for human and mouse leucocytes. In human leucocytes, a linear increase in TM and TL was observed up to the highest radiation dose of 8 Gy. However, in case of mouse leucocytes, a sharp increase in TM and TL was observed only up to 4 Gy, and there after saturation ensued. In human samples, the dose response of both TM and TL showed best fits with linear model (r(TM)=0.999 and r(TL)=0.999), where as in mouse, the best fit was obtained with Sigmoid (Boltzman) model. From the present data on leucocytes with increase in TM and TL as the criteria of DNA damage, it appears that mouse is relatively more sensitive to radiation damage than humans.

Adult↗
PubMed2001

Effects of allergic dermatosis on health-related quality of life.

Allergic dermatosis is a class of immunologic skin diseases manifested as intense itching, which potentially leads to a cycle of skin pain, damage, and infection. Information collected from clinical samples on health-related quality of life shows that some individuals may suffer from poor-quality sleep, physical and emotional distress, and limitations in social functioning. Although many individual factors may moderate the impact of disease on quality of life, disease severity is consistently linked to amount of limitation. There are only sparse data from population surveys in which participants are not selected based on willingness to join a treatment trial for relief of symptoms. This article presents quality-of-life and disease burden data on 559 persons in a community survey who reported signs and symptoms consistent with allergic dermatosis. Quality of life was assessed using the Dermatology-specific Quality of Life (DSQL) questionnaire. Overall, greater disease severity was associated with higher DSQL scores. Noticeable deficits were reported among those who rated their disease as moderate or severe, especially in terms of physical discomfort, sleep disturbance, and negative self-perceptions and emotions. These complaints correlated significantly with out-of-pocket expenses for lotions and emollients to control skin disease. Despite these complaints, the median number of days from the last primary healthcare visit was 453 days, indicating that many dermatosis sufferers are not accessing expert medical care that could alleviate distress.

Adolescent↗
PubMed2001

Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform.

We have designed, synthesized, and evaluated the efficacy of novel dye-peptide conjugates that are receptor specific. Contrary to the traditional approach of conjugating dyes to large proteins and antibodies, we used small peptide-dye conjugates that target over-expressed receptors on tumors. Despite the fact that the peptide and the dye probe have similar molecular mass, our results demonstrate that the affinity of the peptide for its receptor and the dye fluorescence properties are both retained. The use of small peptides has several advantages over large biomolecules, including ease of synthesis of a variety of compounds for potential combinatorial screening of new targets, reproducibility of high purity compounds, diffusiveness to solid tumors, and the ability to incorporate a variety of functional groups that modify the pharmacokinetics of the peptide-dye conjugates. The efficacy of these new fluorescent optical contrast agents was evaluated in vivo in well-characterized rat tumor lines expressing somatostatin (sst(2)) and bombesin receptors. A simple continuous wave optical imaging system was employed. The resulting optical images clearly show that successful specific tumor targeting was achieved. Thus, we have demonstrated that small peptide-dye conjugates are effective as contrast agents for optical imaging of tumors.

Animals↗