Biomedical subjects

S Pandey

Publications and source records attributed to S Pandey.

At least 19 recordsLinked to original sources

PubMed2003

Predictors of gastrointestinal bleeding in acute intracerebral haemorrhage.

BACKGROUND: Gastrointestinal (GI) haemorrhage is an important and sometimes serious complication in critically ill neurological patients who suffered from stroke and head injury and those in intensive care. There is no study evaluating frequency, severity and risk factors of GI haemorrhage in patients with primary intracerebral haemorrhage (ICH). AIMS: To evaluate the frequency, severity and predictors of GI haemorrhage in patients with ICH. METHODS: In a prospective hospital-based study, consecutive CT-proven ICH patients within 10 days of the ictus were included. The patients with history of peptic ulcer, GI haemorrhage, liver and kidney disease, bleeding diathesis and those on antiplatelet, anticoagulant or nonsteroidal antiinflammatory drugs (NSAIDS) were excluded. A detailed neurological evaluation was carried out. Glasgow coma scale (GCS) was used for assessment of consciousness level and Canadian neurological scale (CNS) for severity of stroke. The haematomas were classified into small (<20 ml), medium (20-40 ml) and large (>40 ml). The occurrence of GI haemorrhage during 14 days of ictus was considered due to ICH. To evaluate the predictors of GI haemorrhage, various clinical and CT scan findings were evaluated by univariate followed by multivariate logistic regression analysis. RESULTS: Fifty-one patients with ICH were included whose age ranged between 30 and 80 years and 14 were female. The mean GCS score was 8.9 (3-15) and CNS score was 2.2 (2-4). Haematoma was small (<20 ml) in 11 patients and medium (20-40 ml) and large (>40 ml) in 20 patients each. Evidences of septicemia were present in 20 patients. Gastric haemorrhage (GH) was noted in 15 patients which was more than 40 ml in 4 patients and one of these patients needed blood transfusion. On univariate analysis, the size of haematoma, septicemia, motor signs on the nonhemiplegic side and pupillary asymmetry were significantly related to GI haemorrhage. On multivariate analysis, the best set of predictors of gastric haemorrhage included size of haematoma, septicemia and GCS score. CONCLUSION: GI haemorrhage is more likely present in patients with larger haematoma having septicemia. Our study highlights the importance of septicemia, which is an important and modifiable risk factor for GI bleeding in ICH patients.

Cerebral Hemorrhage↗

PubMed2003

Oxidative stress-induced apoptosis in dividing fibroblasts involves activation of p38 MAP kinase and over-expression of Bax: resistance of quiescent cells to oxidative stress.

Oxidative stress has been postulated to be involved in aging and age-related degenerative diseases. Cell death as a result of oxidative stress plays an important role in the age related diseases. Using human diploid fibroblasts (HDF) as model to study the mechanism of cell death induced by oxidative stress, a condition was standardized to induce apoptosis in the early passage sub-confluent HDFs by a brief exposure of cells to 250 microM hydrogen peroxide. It was observed that p38 MAP kinase (MAPK) was activated soon after the treatment followed by over-expression of Bax protein in cells undergoing apoptosis. An interesting finding of the present study is that the confluent, quiescent HDFs were resistant to cell death under identical condition of oxidative stress. The contact-inhibited quiescent HDFs exhibited increased glutathione level following H(2)O(2)-treatment, did not activate p38 MAP kinase, or over-express Bax, and were resistant to cell death. These findings indicated that there was a correlation between the cell cycle and sensitivity to oxidative stress. This is the first report to our knowledge that describes a relationship between the quiescence state and anti-oxidative defense. Furthermore, our results also suggest that the p38MAPK activation-Bax expression pathway might be involved in apoptosis induced by oxidative stress.

Antioxidants↗

PubMed2003

Primary squamous carcinomatous ureteric stricture of a solitary kidney with spontaneous intraperitoneal urinary extravasation.

We report a very rare case of a carcinoma of the ureter occurring in association with contralateral renal agenesis. Owing to this association, the patient had a unique presentation with urinary ascites and anuria. He was initially managed by retrograde ureteral stenting and supportive measures for renal failure. Thereafter, once the renal parameters became normal, distal ureterectomy and Boari flap reconstruction were performed. Although most patients with ureteral tumours present with advanced disease, the disease was localized in our patient, as the absence of the contralateral kidney resulted in an early presentation.

Carcinoma, Squamous Cell↗

PubMed2003

Correlation of lead and cadmium in human seminal plasma with seminal vesicle and prostatic markers.

The objective of this study was to investigate the correlation between lead and cadmium with seminal vesicle and prostatic markers. Semen samples categorized into fertile and infertile were evaluated for the presence of lead and cadmium and biochemical markers in the seminal plasma. Associations between lead and fructose, acid phosphatase and gamma-glutamyl transpeptidase (gamma-GT) were observed. However, no such relationships were noticed for cadmium. It is concluded that lead may be one of the pollutants indirectly affecting semen quality by altering the functions of accessory sex glands.

Adult↗

PubMed2003

[Non-biodegradable drug-sustained capsular ring for prevention of secondary cataract. Part I: In vitro evaluation].

PURPOSE: The appearance of secondary cataract constitutes the most common complication of cataract surgery since the advent of phacoemulsification. Prevention is today one of the most crucial challenges of research in ophthalmology. We have developed a drug-sustained capsular ring releasing 5-fluorouracil (5-FU). This system aims to combine mechanical and pharmacological properties with the ability to interfere on the lens epithelial cellular processes of secondary cataract. This first article will report on the in vitro evaluation of this system. MATERIALS AND METHOD: Development of a hydrogel that can serve as a mechanical support and as a release of an active agent requires a comparative trial of multiple hydrophobic products providing rigidity to the ring and of hydrophilic products providing the ability to release a drug. The choice of 5-FU as a non-proliferate agent was based on its well-known pharmacological properties and its wide use in ophthalmology. Evaluation comprised adjustment of the adequate copolymer, then of the loading phase, and finally assessment of 5-FU release. The mechanical characteristics and cytocompatibility of the ring were also assessed. RESULTS: The characteristics of drug release differed depending on the water content and resulting volume of the copolymer. The pharmaceutical and mechanical testing led to selecting the HPMA-MMA combination (75:25). However, a burst effect within the first 2 hours was observed in all cases. That limit was eliminated by creating a biodegradable surface coating of Poly Lactid-co-Glycolid (PLG 50:50) that could provide a positive barrier effect against migration and a controlled continual release of 0.25 microg/h extended to 9 days. Mechanical tests of tension, compression, and traction showed the crucial influence of the ring's hydration state. The cytocompatibility study showed no evidence of cellular toxicity. DISCUSSION/CONCLUSIONS: The synthesized copolymer is able to release a constant, regular and safe rate of 5-FU, higher than CI50 over a period of 9 days for a cell proliferation phase of 3-5 days. We adjusted the ring associating the mechanical properties and the ability to release 5-FU, allowing further evaluation on animal models, the subject of the second part of this report.

Biocompatible Materials↗

PubMed2003

[Nonbiodegradable drug-sustained capsular ring for prevention of secondary cataract. Part II: In vivo evaluation].

PURPOSE: The appearance of a secondary cataract constitutes the most common complication of cataract surgery since the advent of phacoemulsification. Prevention is today one of the crucial challenges of research in ophthalmology. We have developed a drug-sustained capsular ring releasing 5-fluorouracil (5-FU). This system targets the goal of combining advantageous mechanical and pharmacological properties with the ability to interfere on the epithelial cellular processes of secondary cataract. This paper presents the results of animal evaluation. MATERIAL AND METHODS: The study first developed the in vitro delivery system as a preliminary step to the animal in vivo approach. After a pilot study conducted on micro pigs, lens extraction was performed on the right eye of 22 female albino rabbits. The four study groups included: group 1 (6 animals) as a control group receiving only phacoemulsification; group 2 (6 animals) receiving phacoemulsification and the implantation of a nonsustained capsular tension ring; and group 3 (6 animals) receiving a drug-sustained ring. Group 4 (4 animals), implanted with a 5-FU-sustained ring, was reserved for staged samples of aqueous humor for kinetic determination of active agent release. RESULTS: Clinical evaluation based on biomicroscopy and histology showed a lesser reaction of secondary cataract in eyes with the ring. Compared to group 1, central posterior capsular opacification appeared significantly lower in density and surface in groups 2 and 3. No intraocular toxicity was observed. The poor sensitivity of the 5-FU detection method (high-performance chromatography) impaired pharmacokinetic evaluation. DISCUSSION CONCLUSIONS: The decrease in secondary cataract reaction in cases of implanted capsular ring demonstrated the advantages of its mechanical effect. However, the benefit of an additive pharmacological action related to the release of 5-FU could not be proved. Nevertheless, the theoretical concept of a drug-sustained delivery system seems attractive and thus calls for evaluation of other potential modulators of cell behavior.

Animals↗

PubMed2001

Vascular attack by 5,6-dimethylxanthenone-4-acetic acid combined with B7.1 (CD80)-mediated immunotherapy overcomes immune resistance and leads to the eradication of large tumors and multiple tumor foci.

The promise of cancer immunotherapy is that it will not only eradicate primary tumors but will generate systemic antitumor immunity capable of destroying distant metastases. A major problem that must first be surmounted relates to the immune resistance of large tumors. Here we reveal that immune resistance can be overcome by combining immunotherapy with a concerted attack on the tumor vasculature. The functionally related antitumor drugs 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and flavone acetic acid (FAA), which cause tumor vasculature collapse and tumor necrosis, were used to attack the tumor vasculature, whereas the T-cell costimulator B7.1 (CD80), which costimulates T-cell proliferation via the CD28 pathway, was used to stimulate antitumor immunity. The injection of cDNA (60-180 microg) encoding B7.1 into large EL-4 tumors (0.8 cm in diameter) established in C57BL/6 mice, followed 24 h later by i.p. administration of either DMXAA (25 mg/kg) or FAA (300 mg/kg), resulted in complete tumor eradication within 2-6 weeks. In contrast, monotherapies were ineffective. Both vascular attack and B7.1 immunotherapy led to up-regulation of heat shock protein 70 on stressed and dying tumor cells, potentially augmenting immunotherapy. Remarkably, large tumors took on the appearance of a wound that rapidly ameliorated, leaving perfectly healed skin. Combined therapy was mediated by CD8+ T cells and natural killer cells, accompanied by heightened and prolonged antitumor cytolytic activity (P < 0.001), and by a marked increase in tumor cell apoptosis. Cured animals completely rejected a challenge of 1 x 10(7) parental EL-4 tumor cells but not a challenge of 1 x 10(4) Lewis lung carcinoma cells, demonstrating that antitumor immunity was tumor specific. Adoptive transfer of 2 x 10(8) splenocytes from treated mice into recipients bearing established (0.8 cm in diameter) tumors resulted in rapid and complete tumor rejection within 3 weeks. Although DMXAA and B7.1 monotherapies are complicated by a narrow range of effective doses, combined therapy was less dosage dependent. Thus, a broad range of amounts of B7.1 cDNA were effective in combination with 25 mg/kg DMXAA. In contrast, DMXAA, which has a very narrow range of high active doses, was effective at a low dose (18 mg/kg) when administered with a large amount (180 microg) of B7.1 cDNA. Importantly, combinational therapy generated heightened antitumor immunity, such that gene transfer of B7.1 into one tumor, followed by systemic DMXAA treatment, led to the complete rejection of multiple untreated tumor nodules established in the opposing flank. These findings have important implications for the future direction and utility of cancer immunotherapies aimed at harnessing patients' immune responses to their own tumors.

Animals↗

PubMed2001

Effects of fluorescent probe structure on the dynamics at cysteine-34 within bovine serum albumin: evidence for probe-dependent modulation of the cybotactic region.

We have prepared a series of bovine serum albumins (BSA) that have been site-selectively labeled at cysteine-34 with one of four different sulfhydryl-selective boron dipyrromethene difluoride (BODIPY) fluorescent probes (BODIPY FL IA, BODIPY FL C(1) IA, BODIPY 530/550 IA, and BODIPY 493/503 MB). We determine how the choice of extrinsic probe structure dictates the recovered BSA-BODIPY dynamics under thermal (10-80 degrees C) and chemical (0-5M guanidine hydrochloride) denaturation conditions. The results of these experiments show that the global protein dynamics are sensed equally by each fluorescent probe; however, the probe itself influences the local probe dynamics within the cybotactic region that surrounds cysteine-34. Thus, it seems inappropriate to think of these extrinsic fluorescent probes as passive, nonparticipatory viewers of local protein dynamics.

Animals↗

PubMed2001

Effect of endosulfan on antioxidants of freshwater fish Channa punctatus Bloch: 1. Protection against lipid peroxidation in liver by copper preexposure.

Effect of a single exposure of endosulfan (5 ppb) on catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), and reduced glutathione (GSH) of liver, kidney, and gill of a freshwater fish (Channa punctatus Bloch) were evaluated after 24 h of treatment. Endosulfan exposure resulted in a significant induction (p < 0.05-0.001) of GPx, GST activity, and GSH levels in all the organs. However, CAT activity was found to be significantly decreased (p < 0.01-0.001). Lipid peroxidation (LPO) values were also determined in liver, kidney, and gill and a significant increase in LPO values (p < 0.05-0.01) was observed in all the organs. We also investigated whether preexposure to low concentration of copper (10 ppb) for 4 weeks has any protective effect against endosulfan-induced oxidative damage. In copper-acclimatized endosulfan-exposed fish, a significant decrease in GPx (p < 0.001), GST (p < 0.05), GSH (p < 0.001) levels, and LPO (p < 0.01) was observed in the liver, whereas CAT activity was increased significantly (p < 0.001). However, kidney and gill did not show any significant alterations in antioxidant levels. The results of this study demonstrate that endosulfan induces peroxidative damage in liver, kidney, and gill in response to which levels of antioxidant were modulated. However, when fish preacclimatized to copper were exposed to endosulfan, protection against oxidative damage was observed only in the liver. It is proposed that measurement of antioxidants in fish tissues may prove to be useful in biomonitoring of exposure to aquatic pollutants.

Animals↗

PubMed2001

Acute renal failure due to bilateral matrix renal calculi--a diagnostic dilemma.

We report an unusual case of acute renal failure caused by bilateral matrix calculi. The difficulties in diagnosing the cause of renal failure and the management of the case are discussed. Matrix calculi are rare causes of acute renal failure. Being radiolucent they can be elusive and systematic investigation and a diligent search are required for correct diagnosis and appropriate treatment.

Acute Kidney Injury↗

PubMed2001

Zea mays CCaMK: autophosphorylation-dependent substrate phosphorylation and down-regulation by red light.

The role of protein kinases has been extensively studied in various signal transduction pathways and they are one of the most important components that link the signal perception to the final response. However, not many studies have been reported, especially from the plant systems, that show the regulation pattern of the kinase itself under different conditions. A calcium/calmodulin-dependent protein kinase has already been purified and characterized from etiolated maize coleoptiles. In this paper a detailed study of how the kinase itself is regulated at the autophosphorylation level is provided. Evidence is also given that the autophosphorylation of kinase effects its activity towards substrate phosphorylation. It is further shown that the kinase is an important component of the light signalling pathway as the level of the kinase itself decreases by red light irradiation.

Amino Acids↗

PubMed2001

Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice.

Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs in spite of its toxic side effects including immunotoxicity, hematotoxicity, mutagenicity and a host of others. The present study was undertaken to assess the protective effects of total aqueous extract of a medicinal plant, Indian gooseberry (Emblica officinalis Gaertn.) in mice treated with CP. These protective effects were studied on immunological parameters and kidney and liver antioxidants. Plant extract treatment at a dose of 100 mg/kg body weight per os (p.o.) for 10 days resulted in the modulation of these parameters in normal as well as CP (50 mg/kg)-treated animals. Plant extract in particular was very effective in reducing CP-induced suppression of humoral immunity. Plant extract treatment in normal animals modulated certain antioxidants of kidney and liver. In CP-exposed animals, plant pretreatment provided protection to antioxidants of kidney. Not only were the reduced glutathione levels significantly (p<0.001) increased but plant extract treatment resulted in restoration of antioxidant enzymes in CP-treated animals. It is suggested that E. officinalis or its medicinal preparations may prove to be useful as a component of combination therapy in cancer patients under CP treatment regimen.

Adjuvants, Immunologic↗

PubMed2000

Linkage and redox isomerism in ruthenium complexes of catecholate, semiquinone, and o-acylphenolate ligands derived from 1,2-dihydroxy-9,10-anthracenedione (alizarin) and related species: syntheses, characterizations, and photophysics.

The complexes Ru(CO)2L2(AL-2H) (AL = alizarin; L = PPh3, PCyc3, PBu3, P(m-NaSO3C6H4)3), Ru(CO)(dppe)(PBu3)(AL-2H), and RuH(CO)L2(AL-H) (L = PPh3, PCyc3), and Ru(CO)2L2(AR-2H) (AR = anthrarobin; L = PBu3) were prepared by reactions of Ru3(CO)12, L, and AL, and the complexes RuH(CO)(PPh3)2(AL-H), RuH(CO)(PPh3)2(QN-H) (QN = quinizarin), and RuH(CO)(PPh3)2(LQN-H) (LQN = leucoquinizarin) are prepared by reactions of RuH2(CO)(PPh3)3 with AL or QN. The AL-2H and AR-2H ligands act as 1,2-catecholates, whereas the AL-H, QN-H, LQN-H ligands are 1,9-o-acylphenolate ligands. RuH(CO)(PPh3)2(AL-H) is characterized by X-ray crystallography. The electrochemistry of these complexes is examined, and the semiquinone complexes [Ru(CO)2L2(AL-2H)]+ (L = PPh3, PCyc3, PBu3) and [Ru(CO)(dppe)(PBu3)(AL-2H)]+ are generated by chemical oxidation and were characterized by EPR and IR spectroscopy. The photophysical properties are also reported.

Anthraquinones↗

PubMed2000

Extending the reach of immunoassays to optically dense specimens by using two-photon excited fluorescence polarization.

Fluorescence anisotropy/polarization measurements represent a powerful tool for quantifying biomolecule/ligand complexation. These types of measurements are also at the heart of a wide variety of commercial homogeneous fluoroimmunoassays. In this note, we demonstrate the power of two-photon excited fluorescence anisotropy (2-PEFA) measurements as a tool for quantifying hapten/antibody association in the presence of a strongly absorbing, nonfluorescent dye. The results of these experiments show that 2-PEFA measurements are intrinsically more sensitive when compared to traditional one-photon excited fluorescence anisotropy (1-PEFA) strategies and 2-PEFA-based measurements allow one to perform accurate hapten/antibody binding measurements in strongly absorbing samples directly under conditions where 1-PEFA measurements fail completely. Overall, the 2-PEFA approach offers significant advantages when compared to traditional 1-PEFA methods especially in strongly absorbing samples. 2-PEFA also opens the door to perform more rapid and reliable polarization/anisotropy-based measurements with minimal sample preparation.

Fluorescence Polarization Immunoassay↗

PubMed2000

Effects of ethanol volume percent on fluorescein-labeled spinach apo- and holocalmodulin.

We report the effects of EtOH volume percent (0-70%) on spinach apo- and holocalmodulin that have been site-selectively labeled with fluorescein (F). In these experiments, calmodulin (CaM) has one F reporter group attached to Cys-26, and this site is located immediately adjacent to one of the four primary Ca(2+)-binding sites (EF hands). The optimum analytical CaM-F sensitivity to Ca2+ occurs between approximately 10 and 30% EtOH. Our results also show that added EtOH causes changes in CaM and these changes are surprisingly different for apo- and holo-CaM. Apo-CaM-F appears to lose one of its two waters of hydration at approximately 20% EtOH and retains one water of hydration between approximately 20 and 70% EtOH. In apo-CaM-F, the semiangle that describes the range over which the fluorescein reporter group can precess remains essentially constant (42 +/- 2 degrees) between 0 and 70% EtOH. This shows that the fluorescein reporter group precessional freedom in apo-CaM-F is not affected significantly by EtOH. Holo-CaM-F also appears to lose one water of hydration at approximately 20-30% EtOH but then appears to denature as the EtOH volume percent increases. The fluorescein reporter group semiangle within holo-CaM-F decreases from 43 +/- 1 degrees in neat aqueous buffer to 36 +/- 1 degrees at 70% EtOH. This shows that holo-CaM-F is less nativelike and the EF hand "closes down" about the fluorescein reporter group in holo-CaM-F as the EtOH volume percent increases.

Apoproteins↗

PubMed2000

Role of polyamines and ethylene as modulators of plant senescence.

Under optimal conditions of growth, senescence, a terminal phase of development, sets in after a certain physiological age. It is a dynamic and closely regulated developmental process which involves an array of changes at both physiological and biochemical levels including gene expression. A large number of biotic and abiotic factors accelerate the process. Convincing evidence suggests the involvement of polyamines (PAs) and ethylene in this process. Although the biosynthetic pathways of both PAs and ethylene are interrelated, S-adenosylmethionine (SAM) being a common precursor, their physiological functions are distinct and at times antagonistic, particularly during leaf and flower senescence and also during fruit ripening. This provides an effective means for regulation of their biosynthesis and also to understand the mechanism by which the balance between the two can be established for manipulating the senescence process. The present article deals with current advances in the knowledge of the interrelationship between ethylene and PAs during senescence which may open up new vistas of investigation for the future.

Adenosylmethionine Decarboxylase↗

PubMed2000

Caspase-dependent and independent cell death in rat hepatoma 5123tc cells.

The objective of this study was to establish whether apoptosis in 5123tc rat hepatoma cells required the caspase-3 dependent pathway. Apoptosis was induced by either growth factor deprivation or treatment with a topoisomerase II inhibitor, VM26, in the absence or presence of caspase inhibitors (DEVD-fmk, z-VAD-fmk and BAF). The results indicated that, although these inhibitors at 10 microM concentration completely blocked caspase-3 activity, they had no effect on either the rate of cell death or on any other apoptotic features, e.g., chromatin condensation, DNA fragmentation, protein cleavage, suggesting that caspase-3 was not required to mediate nuclear destruction in these hepatoma cells. At higher concentrations, up to 100 microM, z-VAD-fmk and BAF, but not DEVD-fmk, did block apoptosis, however, they also caused cell swelling and membrane permeabilization, which are the hallmarks of necrotic cell death. Clearly, high concentrations of these inhibitors must have interfered non-specifically with other metabolic pathways, e.g., z-VAD-fmk at a high concentration blocked protein phosphorylation, and caused cell death by a different mechanism.

Amino Acid Chloromethyl Ketones↗

PubMed2000

Tactual recognition of cognitive stimuli: roles of hemisphere and lobe.

Four groups of focal brain-damaged patients, involving left and right hemisphere damage with or without the involvement of parietal lobe, and a control group of general medical patients, were required (a) dichaptically to perceive two cognitive stimuli (letter letter, figure figure, or letter figure), and (b) haptically match the target stimulus from a set of test stimuli. The number of trials taken to match the target stimulus correctly was the dependent measure. The significant main effect of lobe suggested that the parietal lobe is the primary locus for tactual recognition. All interaction effects involving lobe were nonsignificant. The main effect of hemisphere was nonsignificant, although the interaction of hemisphere x lobe was significant. Left and right hemisphere damaged patients required more trials to recognize "letter" and "figure", respectively.

Adult↗