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Biomedical subjects

S Ramakrishnan

Publications and source records attributed to S Ramakrishnan.

At least 37 records · Page 2Linked to original sources
PubMed2004

Management of root lesion nematode, Pratylenchus delattrei in crossandra using oil cakes.

Selected oil cakes, neem, castor and mahua, were tried independently and in combination with a chemical nematicide (carbofuran 3G) for the management of Pratylenchus delattrei in crossandra under glass house conditions. The neem oil cake was effective compared to other oil cakes used and there was a synergistic effect when the neemcake was coupled with carbofuran 3G in the management of Pratylenchus delattrei. The treatment resulted in better establishment of seedlings, and with increased plant bio-mass and flower yield.

Acanthaceae↗
PubMed2004

VEGF-DT385 toxin conjugate inhibits mammary adenocarcinoma development in a transgenic mouse model of spontaneous tumorigenesis.

Previous experiments have shown that a vascular endothelial growth factor (VEGF)-DT385 toxin conjugate inhibits endothelial cell proliferation, angiogenesis and solid tumor growth in a xenotransplant model system. Here, we report that VEGF-DT385 toxin conjugate effectively inhibits spontaneous tumorigenesis. The C3(1)/SV40 TAg transgenic mouse model of mammary gland carcinogenesis was used to determine the effectiveness of VEGF-DT385 toxin conjugate in delaying the onset of disease and the development of solid tumors. Animals were treated daily with conjugate for a period of 7 days. Therapy was initiated at week 14 of development before any visible adenocarcinomas were evident. Treatment of mice with VEGF-DT385 toxin conjugate significantly delayed the onset of tumorigenesis and inhibited solid tumor growth by more than 92%. Furthermore, conjugate treated animals showed less than twice the number of tumor nodules when compared to control mice. Finally, this vascular targeting agent significantly increased survival time of animals by 5 weeks. VEGF-DT385 toxin conjugate resulted in temporary weight loss and no long-lasting toxicity was seen. More importantly, using this established tumor model, VEGF-DT385 toxin conjugate appeared to be as effective as a similar treatment schedule with recombinant human endostatin. Our results suggest that VEGF-DT385 toxin conjugate is a potent inhibitor of mammary adenocarcinoma growth and might be useful in breast cancer therapy.

Adenocarcinoma↗
PubMed2004

Assessment of patient pain at colonoscopy: are nurses better than endoscopists?

The pain that patients recollect having experienced at colonoscopy is likely to influence uptake of the procedure. We used visual analogue scales to assess recollected pain shortly before discharge, and compared these scores with assessments by the endoscopist and the attending nurse. Data were complete for 426 procedures (90%). The mean perceived pain score for patients was 3.2, for endoscopists 2.8 and for nurses 3.1. On multivariate analysis, the endoscopists' assessments of pain had little predictive value over and above those of nurses, whereas nurses' assessments remained significant when adjusted for endoscopists' assessments. Nurses were more accurate than endoscopists in gauging the pain of colonoscopy. This may be because endoscopists are focused on the video monitor while nurses are focused on the patient. More active use of nurses' assessments might help keep pain to a minimum.

Adolescent↗
PubMed2004

Determination of carbonyl group content in plasma proteins as a useful marker to assess impairment in antioxidant defense in patients with Eales' disease.

PURPOSE: Formation of protein carbonyl groups is considered an early biomarker for the oxidant/antioxidant barrier impairment in various inflammatory diseases. We evaluated the intensity of free radical reactions in patients with Eales' disease, an idiopathic inflammatory condition of the retina. METHODS: Twenty patients with Eales' disease in active vasculitis stage, 15 patients with Eales' disease in healed vasculitis stage and 20 healthy control subjects were recruited for the study. Plasma protein carbonyl groups,plasma glutathione (GSH) superoxide dismutase (SOD) activity and thiobarbituric acid reactive substances (TBARS) were determined in erythrocytes. RESULTS: Plasma protein carbonyl content was elevated by a factor of 3.5 and 1.8 respectively in active and healed vasculitis stages. The increase of carbonyl group content in active and healed stage of patients with Eales' disease correlated with diminished SOD activity and GSH content. There was also increased accumulation of TBARS in active and healed vasculitis stages of Eales' disease, and this correlated with diminished SOD activity. CONCLUSION: Our results showed that protein carbonyl group content increases with severity of Eales' disease. The increase in carbonyl content correlated with diminished antioxidant status. This confirms an earlier report that free radical mediated tissue damage occurs in Eales' disease. The determination of protein carbonyl content may be used as a simple biomarker to monitor the efficacy of antioxidant supplementation in controlling retinal vasculitis in patients with Eales' disease.

Adult↗
PubMed2003

Determination of critical micelle concentration by hyper-rayleigh scattering.

The critical micelle concentration (CMC) of several surfactants that contain an NLO chromophore, either at the hydrocarbon tail, or at the hydrophilic headgroup, or even as a counterion, was determined by hyper-Rayleigh scattering (HRS). In all cases, the HRS signal exhibited a similar variation with surfactant concentration, wherein the CMC is inferred from a rather unprecedented drop in the signal intensity. This drop is attributed to the formation of small pre-micellar aggregates, whose concentrations become negligible above CMC. In addition, a probe molecule, which upon protonation yielded a species with significantly enhanced HRS intensity, was developed and its utility for the determination of the CMC of simple fatty acids was demonstrated.

Journal Article↗
PubMed2002

A randomized controlled trial to evaluate the slow-acting symptom-modifying effects of colchicine in osteoarthritis of the knee: a preliminary report.

OBJECTIVE: To determine if colchicine added to nimesulide may have a beneficial effect on osteoarthritis (OA) of the knee. METHODS: Colchicine 0.5 mg twice daily or placebo was added to nimesulide (a nonsteroidal antiinflammatory drug) in 36 patients with OA of the knee in a randomized, double-blind, placebo-controlled trial over a 5-month period. RESULTS: The 30% improvement rate at 20 weeks was higher in the colchicine group than in the control group receiving placebo, as measured by total Western Ontario and McMaster University Osteoarthritis scores (57.9% versus 23.5%) and visual analog scale for index knee pain (52.6% versus 17.6%) (primary measures of response). The significance persisted on combined analysis by Mantel-Haenszel test (P = 0.062). Comparison of means also showed significant improvement in the colchicine group versus the control group in a multivariate analysis performed using T(2) test (P = 0.0115). CONCLUSION: Among patients with OA of the knee, the group receiving colchicine plus nimesulide exhibited significantly greater symptomatic benefit at 20 weeks than did the control group receiving nimesulide plus placebo.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Gene therapy of murine solid tumors with T cells transduced with a retroviral vascular endothelial growth factor--immunotoxin target gene.

Solid tumor growth can be inhibited by targeting its neovasculature with vascular endothelial growth factor (VEGF)-toxin fusion proteins (FPs), but these agents have been limited by their inability to localize at the tumor site. In this study, we devised a gene therapy approach intended to deliver VEGF-toxin directly to tumor. Antigen-specific cytotoxic T lymphocytes (CTLs) served as vehicles to deliver a retroviral VEGF-toxin fusion protein to its specific leukemia cell target in vivo. A retroviral vector was constructed for gene therapy with VEGF positioned downstream of its 27-amino acid leader sequence, which promoted secretion of a catalytic immunotoxin containing either truncated diphtheria toxin or Pseudomonas exotoxin A. VEGF was chosen on the basis of the expression of VEGF receptor on endothelial cells in the tumor neovasculature. The VEGF FP was first expressed and secreted by mammalian NIH 3T3 cells. Intracellular expression of both VEGF and toxin was verified by immunofluorescence. In vitro, supernatants collected from transfected cells specifically inhibited the growth of VEGF receptor-expressing human umbilical vein endothelial cells (HUVECs), but not a control cell line. In vivo findings correlated with in vitro findings. A retroviral vector containing the target gene and a nerve growth factor receptor (NGFR) reporter gene was used to transiently transduce T15, a CD8(+) CTL line that specifically recognizes C1498, a lethal C57BL/6 myeloid tumor. Transduced T15 cells injected intravenously significantly inhibited the growth of subcutaneous tumor, whereas nontransduced controls did not. Together, these data indicate that gene therapy of T cells with retrovirus containing a VEGF-immunotoxin target gene may be a valid means of inhibiting a broad range of solid tumors dependent on angiogenesis.

Animals↗
PubMed2002

A randomized controlled trial to evaluate the slow-acting symptom modifying effects of a regimen containing colchicine in a subset of patients with osteoarthritis of the knee.

OBJECTIVE: As crystals may contribute to inflammation in osteoarthritis (OA), it is hypothesized that colchicine may have symptom/disease modifying effects in OA. The objective of this study was to evaluate the symptomatic benefit of addition of colchicine to a regimen of intraarticular steroids and piroxicam in patients with knee OA with inflammation. DESIGN: 39 patients with OA of the knee with persisting inflammation, despite at least 2 weeks of piroxicam, were subjected to intraarticular steroid injection and randomly assigned to receive colchicine 0.5 mg twice daily or placebo in a randomized, double blind, placebo-controlled trial over 5 months. RESULTS: VAS for index knee pain (VAS-pain) and total KGMC score (a modified WOMAC index) at 16 and 20 weeks were significantly better in the colchicine group than the corresponding scores in controls. The benefit persisted on multivariate analysis at 16 weeks (Hotellings T(2)=18.6, F(5,33)=3.3154, P=0.015). The proportion of patients who had 30% or greater response at 16 weeks was significantly higher in the colchicine group in VAS-pain (69% vs 15%) and total KGMC scores (74% vs 45%) and the significance persisted on combined analysis using Mantel-Haenszel test (M-H Risk=5.9, 95% C.I.: 2.08 to 16.73). At 20 weeks, benefit of colchicine therapy was seen on pooled analysis only (M-H risk=3.71, 95% C.I.: 1.07=8.02). CONCLUSION: The addition of colchicine produced significantly greater symptomatic benefit at 16 and 20 weeks than intraarticular steroid and piroxicam alone in patients with knee OA with inflammation.

Analysis of Variance↗
PubMed2002

Immunolocalization and quantification of advanced glycation end products in retinal neovascular membranes and serum: a possible role in ocular neovascularization.

PURPOSE: Earlier studies have revealed the association of advanced glycation end products (AGE) with the pathogenesis of various micro and macro vascular complications. The purpose of the present study is to localize AGEs, namely carboxy methyl lysine (CML-AGE) and methyl glyoxal-derived AGEs (MG-AGE), in retinal neovascular membranes and to quantify them in serum samples. METHODS: Surgically excised retinal neovascular membranes and serum samples obtained from patients with diabetic retinopathy, Eales' disease and nondiabetics were studied. Immunolocalization of AGEs namely CML-AGE and MG-derived AGEs was done using avidin biotin complex method and quantification was done by enzyme linked immunosorbent assay (ELISA). RESULTS: CML-AGE immunoreactivity was detected in all cases of Eales' disease and 61% cases of diabetic retinopathy and none in idiopathic epiretinal membrane (ERM). MG-AGE immunoreactivity was observed in approximately 15% of diabetic retinopathy and none in Eales' disease and and idiopathic ERM. Quantification of AGEs in serum samples revealed statistically significant increased levels of MG-AGE in diabetes, in relation to nondiabetics with idiopathic ERM and CML-AGE in Eales' disease, in relation to diabetics and nondiabetics with idiopathic ERM. CONCLUSION: Results from this study suggest that AGEs formed through glycation and glycoxidation may play an important role in the development of retinal neovascularization. The immunoreactivity of CML-AGEs in neovascular membrane and its increased levels in serum suggest that inspite of the normoglycemic status, glycoxidation and lipid peroxidation due to oxidative stress may trigger retinal neovascularization in Eales' disease, while MG-AGEs in diabetic membrane and serum suggest the role of glycation. Thus the mechanism of neovascularization in different pathological conditions could be different.

Adolescent↗
PubMed2001

Purification and characterization of a novel 88 kDa protein from serum and vitreous of patients with Eales' disease.

Eales' disease is a perivasculitis that affects the peripheral retina of young adults and results in recurrent vitreous hemorrhage. Although increased oxidative stress and decreased antioxidant defense have been reported to be associated with Eales' disease, the exact cause for the disease and its pathogenesis are not known. Here is reported the identification, purification and characterization of a new protein from the serum and vitreous of patients with Eales' disease. This protein was purified using preparative electrophoresis and HPLC. The purified protein had a retention time of 9.2 min in RP HPLC. Its molecular weight as determined by gel permeation chromatography was 88 kDa hence, it was termed as 88 kDa protein. Alcian blue and Schiffs staining revealed 88 kDa protein to be a glycoprotein. Proteins purified from both serum and vitreous exhibited anti lipid peroxidation effect on erythrocyte when added during in vitro assay of thiobarbuteric acid reactive substances (TBARS). In addition to this property the protein also has Fe(2+)sequestering effect. The anti TBARS activity of 88 kDa protein was completely inhibited by 0.1 m M concentration of parachlromercuric benzoate (PCMB) and 5,5' dithiobis(2-nitrobenzoic acid) DTNB. The total thiol content (cysteine) of the purified 88 kDa protein was found to be 8% by mass. Eighty eight kDa protein from both the sources namely vitreous and serum are immunologically identical when studied using polyclonal antibodies raised in goat against purified serum protein. The N terminal sequence of 88 kDa protein by automated Edman's degradation chemistry is A D D P N S L S P S A F A E A L A L L R D S X L A R F V. The protein and DNA data base search revealed no match to 88 kDa protein and hence this was considered as unique protein. Further knowledge on the in vivo function of 88 kDa protein is very important to understand its role in the pathogenesis of Eales' disease.

Amino Acid Sequence↗
PubMed2001

Morphine sulfate inhibits hypoxia-induced vascular endothelial growth factor expression in endothelial cells and cardiac myocytes.

Vascular endothelial growth factor (VEGF) is an angiogenic mitogen, specific for endothelial cells. Hypoxia-induced VEGF in endothelial cells and cardiomyocytes leads to autocrine and paracrine stimulation, respectively. During myocardial ischemia, VEGF is upregulated in the endothelium and myocardium, and may mediate angiogenesis. Morphine sulfate is commonly used in pain relief for patients with acute myocardial infarction. We investigated the effect of morphine sulfate on VEGF expression in cultured endothelial cells and cardiac myocytes subjected to hypoxia. Enzyme-linked immunosorbent assays showed that morphine sulfate significantly inhibited hypoxia-induced VEGF expression in mouse heart microvascular endothelial cells (SMHEC4), primary cultures of human umbilical vein endothelial cells (HUVECs) and in primary cultures of rat cardiac myocytes (P<0.05). Real time reverse transcriptase polymerase chain reaction showed that morphine treatment (100 ng/ml) of hypoxic HUVECs resulted in a significant reduction in mRNA levels of VEGF(121) and VEGF(165) isoforms. Transfection of HUVECs with a human VEGF promoter-luciferase construct showed that hypoxia-induced transcriptional activation of VEGF was markedly inhibited by morphine sulfate (P<0.05). Phosphatidyl inositol-3 kinase and protein kinase C-mediated activation of the VEGF promoter was also inhibited by morphine. The opioid antagonist naloxone significantly reversed the inhibitory effects of morphine in endothelial cells suggesting the involvement of opioid receptors. Our results show that the inhibitory effects of morphine on hypoxia-induced VEGF expression in endothelial cells and cardiac myocytes can lead to a decrease in the autocrine and paracrine stimulation and hence limit neovascularization of the ischemic myocardium.

Animals↗
PubMed2001

Beneficial role of amino acids in mitigating cytoskeletal actin glycation and improving F-actin content: in vitro.

AIMS: The actin filaments present in circulating leukocytes facilitate their passage through microvenules and capillaries by helping in their deformability. Decreased deformability of granulocytes is now known to cause occlusion of the retinal microcapillaries leading to hypoxia and the subsequent development of diabetic retinopathy. Structural and functional loss of proteins, due to non-enzymatic glycation and glycoxidation, has been reported to cause diabetic pathogenesis. As amino acids have been earlier reported to have antidiabetic properties, the present study involves the investigation of the susceptibility of the cytoskeletal actin to glycation and its mitigation by free amino acids. This study also involves quantifying F-actin in cultured mononuclear cells obtained from diabetic and normal healthy volunteers and on the effect of glucose and free amino acids on F-actin content. METHODS: Commercial non-muscle actin and actin immuno-pre-cipitated from granulocytes obtained from (a) normal healthy human volunteers and (b) patients with type 2 diabetes mellitus were subjected to glycation studies using [U] (14)C glucose. The effect of free amino acids, as antiglycating agents, was determined using various concentrations of lysine, arginine, alanine, aspartic acid and glutamic acid. F-actin content in cultured mononuclear cells was estimated by flow cytometry using fluorescein isothiocynate (FITC)-Phalloidin. RESULTS: Commercial actin at physiological conditions of pH and temperature was found to undergo non-enzymatic glycation. The extent of in vitro glycation was significantly low (P<0.001) in actin isolated from patients with type2 diabetes when compared to the non-diabetic group, suggesting an increased in vitro structural modification of actin in patients with diabetes. All the free amino acids tested were found to have varying degrees of antiglycating effect. The F-actin content in the intact mononuclear cells obtained from diabetic patients was found to be low when compared with normal healthy volunteers (P<0.001). Similarly the F-actin content was significantly low when the normal mononuclear cells were incubated with glucose. This effect was reversed upon the addition of free amino acids to the incubation mixture. CONCLUSIONS: Free amino acids can play a positive role in improving leukocyte deformability by mitigating cytoskeletal actin glycation and improving F-actin content.

Actins↗
PubMed2001

Oncology thinking cap: scaffolded use of a simulation to learn clinical trial design.

BACKGROUND: Physicians often are called on to participate in and interpret clinical trials, but their training in this area may not provide them with the inquiry skills that are needed. Simulations have the potential to be a promising tool for helping medical students learn the skills involved in clinical trial design. However, simulations may be complex and require additional scaffolding to support learning. DESCRIPTION: The goal of this study was to teach aspects of cancer clinical trial design through the scaffolded use of a simulation, the Oncology Thinking Cap. The software-based scaffolding provided guidance in designing the trial. Subsequently, the simulation allowed students to run the designed trial, which produces detailed patient histories. This feedback then could be used to redesign the trial. EVALUATION: Twenty-four 4th-year medical students were asked to design a clinical trial in advance, on paper, to test a new anticancer drug. Student groups then designed and simulated running the clinical trial assisted by the software environment. Instructional effectiveness was measured using a pretest-posttest design that included having students (a) write a group research proposal and (b) individually critique a flawed proposal. At the group level (N = 6 groups), students demonstrated a 34% increase in the number of elements of a clinical trial that they included in their research proposals. At the individual level (N = 24), students improved by 48% in their critiques of flawed proposals. CONCLUSIONS: Scaffolding embedded in the simulator is a promising approach to helping students learn about clinical trial design.

Antineoplastic Agents↗