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Aim of the study: Syzygium aromaticum has been reported to possess aphrodisiac, stomachic, carminative, antispasmodic and anti-cataract properties in traditional ayurvedic medicine. The current study determined the efficacy of S. aromaticum alcoholic extract in the prevention of diabetic retinopathy in rats with type 2 diabetes. Materials and Methods: Type 2 diabetes was induced in neonatal rats with streptozotocin. The effect of S. aromaticum alcoholic extract in different doses on glycemic parameters, lenticular changes, vessel diameter, antioxidant enzymes, inflammatory markers and thickness basement membrane of retinal capillaries was assessed with electron microscopy. The results of the treatment groups was compared with that of the diabetes control group. Results: The treatment of diabetic rats with S. aromaticum alcoholic extract at different doses significantly reduced blood glucose, glycated hemoglobin, lenticular changes, vessel diameter, inflammatory markers and thickness of basement membrane of retinal capillaries and antioxidant enzymes status. Conclusion: S. aromaticum alcoholic extract may be used strategically to prevent diabetic retinopathy.

Pearl millet breeding programs can use this heterotic group information on seed and restorer parents to generate new series of pearl millet hybrids having higher yields than the existing hybrids. Five hundred and eighty hybrid parents, 320 R- and 260 B-lines, derived from 6 pearl millet breeding programs in India, genotyped following RAD-GBS (about 0.9 million SNPs) clustered into 12 R- and 7 B-line groups. With few exceptions, hybrid parents of all the breeding programs were found distributed across all the marker-based groups suggesting good diversity in these programs. Three hundred and twenty hybrids generated using 37 (22 R and 15 B) representative parents, evaluated for grain yield at four locations in India, showed significant differences in yield, heterosis, and combining ability. Across all the hybrids, mean mid- and better-parent heterosis for grain yield was 84.0% and 60.5%, respectively. Groups G12 B × G12 R and G10 B × G12 R had highest heterosis of about 10% over best check hybrid Pioneer 86M86. The parents involved in heterotic hybrids were mainly from the groups G4R, G10B, G12B, G12R, and G13B. Based on the heterotic performance and combining ability of groups, 2 B-line (HGB-1 and HGB-2) and 2 R-line (HGR-1 and HGR-2) heterotic groups were identified. Hybrids from HGB-1 × HGR-1 and HGB-2 × HGR-1 showed grain yield heterosis of 10.6 and 9.3%, respectively, over best hybrid check. Results indicated that parental groups can be formed first by molecular markers, which may not predict the best hybrid combination, but it can reveal a practical value of assigning existing and new hybrid pearl millet parental lines into heterotic groups to develop high-yielding hybrids from the different heterotic groups.

The primary aim of this study was to assess the complication rate after elective scrotal surgery for benign conditions, following the observation that a higher than expected number of patients were requiring intervention for complications of their surgery. The secondary aim was to assess how different risk factors affected the complication rate, therefore identifying areas for improvement in clinical practice.All patients from April 2008 to September 2013 who underwent an elective hydrocele repair, epididymal cyst excision or epididymectomy at a UK district general hospital were included. Patient notes were reviewed and risk factors for surgery and postoperative complications recorded.In total, 222 patients were included. The overall complication rate was 27.4%. Complications included haematoma (9.0%), infection (5.0%), recurrence of swelling (7.2%) and chronic pain (0.2%). The only risk factor to have a significant relationship to complication rate was a body mass index of 30 kg/m² or greater (χ² = 6.698, p = 0.010).The most common complications after scrotal surgery for benign conditions were haematoma formation, infection and recurrence or persistence of swelling. The only risk factor identified as having a potentially adverse effect on complication rate was a raised body mass index of 30 or greater.

Cadmium, a major metal constituent of tobacco smoke, elicits synergistic enhancement of cell transformation when combined with benzo[a]pyrene (BP) or other PAHs. The mechanism underlying this synergism is not clearly understood. We observed that (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), an ultimate carcinogen of BP, induces apoptosis in promotion sensitive mouse epidermal JB6 Cl41 cells at non-cytotoxic concentrations. BPDE also activates AP-1 several folds in AP-1 reporter JB6 cells. Cadmium at non-cytotoxic concentrations inhibits both AP-1 activation and apoptosis in response to BPDE. Since AP-1 is known to be involved in stress-induced apoptosis we investigated whether inhibition of AP-1 by cadmium has any role in the inhibition of BPDE-induced apoptosis. MAP kinases (particularly ERKs, p38 and JNKs) are known to have important role in DNA damage-induced AP-1 activation. We observed that ERK and JNK, but not p38 MAP kinase, are involved in BPDE-induced AP-1 activation. Effect of cadmium on MAP kinases and the effect of inhibition of above three MAP kinases on BPDE-induced AP-1 activation and apoptosis indicate that AP-1 is probably not involved in BPDE-induced apoptosis. Cadmium up-regulates BPDE-activated ERKs and ERK inhibition by U0126 relieves cadmium-mediated inhibition of BPDE-induced apoptosis. We suggest that cadmium inhibits BPDE-induced apoptosis not involving AP-1 but probably through a different mechanism by up-regulating ERK which is known to promote cell survival.

Cardiovascular disease is a major cause of death and thus a great deal of effort has been made in salvaging the diseased myocardium. Although various factors have been identified as possible causes of different cardiac diseases such as heart failure and ischemic heart disease, there is a real need to elucidate their role for the better understanding of the cardiac disease pathology and formulation of strategies for developing newer therapeutic interventions. In view of the intimate involvement of different types of proteases in maintaining cellular structure, the role of proteases in various cardiac diseases has become the focus of recent research. Proteases are present in the cytosol as well as are localized in a number of subcellular organelles in the cell. These are known to use extracellular matrix, cytoskeletal, sarcolemmal, sarcoplasmic reticular, mitochondrial and myofibrillar proteins as substrates. Work from different laboratories using a wide variety of techniques has shown that the activation of proteases causes alterations of a number of specific proteins leading to subcellular remodeling and cardiac dysfunction. Inhibition of protease action by different drugs and agents, therefore, has a clinical relevance and is expected to form a part of new treatment paradigm for improving heart function. This review examines the biochemistry and localization of some of the proteases in the cardiac tissue in addition to identification of the sites of action of some protease inhibitors. (Mol Cell Biochem 263: 241-256, 2004).

The typical antipsychotic drug haloperidol causes vacuous chewing movements (VCM) in rats, which are representative of early-Parkinsonian symptoms or later-onset extrapyramidal side effects of tardive dyskinesia (TD) in humans. Haloperidol (HP) has been hypothesized to potentiate increases in oxidative stress or free radical-mediated levels of toxic metabolites in rat striatum while simultaneous upregulating dopamine (DA)-D2 receptors leading to presumed DA supersensitivity. Alpha(α)-Phenyl-N-tert-butylnitrone (PBN) is an antioxidant used to combat oxidative stress and measure increases in PBN spin-adduct activity. Thus, the aim of this study was to investigate whether VCMs are related to upregulation of DA-D2 receptors or to increased levels of free radicals produced during oxidative stress, and whether PBN had any protective effects. Rats received daily chronic (28 day) i.p. injections of saline, haloperidol (2 mg/kg), PBN (150 mg/kg), or haloperidol + PBN. The VCM model was used to measure extrapyramidal side effects of drug treatments. Electron spin resonance (ESR) spectroscopy was performed to compare concentrations of free radical species in rats receiving injections of HP + PBN. To examine the upregulation of DA-D2 receptors, binding assays were carried out to assess the increase in DA-D2 receptor numbers with respect to VCMs following treatment of rats injected with HP, PBN, and HP + PBN. Results of these experiments show that HP-induced VCMs in rats results from increases in oxidative cellular events and may not be related to increases in striatal DA-D2 receptors. Synapse 54:156–163, 2004. © 2004 Wiley-Liss, Inc.

PGI is a housekeeping gene encoding phosphoglucose isomerase (PGI) a glycolytic enzyme that also functions as a cytokine (autocrine motility factor (AMF)/neuroleukin/maturation factor) upon secretion from the cell and binding to its 78 kDa seven-transmembrane domain receptor (gp78/AMF-R). PGI contains a CXXC motif, characteristic of redox proteins and possibly evolutionarily related to the CC and CXC motif of the chemokine gene family. Using site-directed mutagenesis, single- and double-deletion (CXC, CC) mutants were created by deleting amino acids 331 and 332 of human PGI, respectively. The mutant proteins lost their enzymatic activity; however, neither of the deletions augmented the proteins’ binding affinity to the receptor and all maintained cytokine function. The results demonstrate that the enzymatic activity of PGI is not essential for either receptor binding or cytokine function of human PGI.

Ozone (O(3)) is a significant component of atmospheric air pollution and produces detrimental effects in the lung. Although the mechanism of O(3)-induced lung inflammation and injury is unclear, the increased release of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) by lung cells following O(3) exposure may shed some light on this subject. To investigate the role of TNF-alpha in the O(3)-induced pulmonary insult, we intraperitoneally injected rats with either rabbit preimmune serum or rabbit antirat TNF-alpha 1 h prior to O(3) exposure. Approximately 12 h after the end of O(3) exposure the animals were sacrificed, the lungs lavaged, and tissue samples collected for expression of cytokine genes relevant to inflammation. The bronchoalveolar lavage fluid (BALF) was analyzed for albumin as a marker of pulmonary epithelial permeability changes and for fibronectin for its role in lung injury and repair. The lavage cells were collected, counted, and identified to quantitate the inflammatory response. Ozone exposure resulted in a significant increase in BALF albumin and fibronectin as compared to air-exposed controls and a significant increase in BALF polymorphonuclear leukocytes (PMNs). Antibody treatment produced a significant decrease in BALF albumin and PMNs as compared to O(3)-exposed rats given preimmune serum. Antibody treatment did not affect the BALF fibronectin concentration or the total cell count in the BAL. Tissue analysis for gene arrays revealed an activation of IL-1alpha, IL-6, and IL-10 in animals exposed to O(3). The gene expression was downregulated in animals treated with anti-TNF-alpha antibody prior to O(3) exposure. The results suggest a central role for TNF-alpha in the mechanistic pathways critical to lung inflammation. The significance of TNF-alpha in the inflammation and epithelial injury produced by ozone exposure reflects its overall contribution through modulation of other cytokines.

Patients evaluated for chest pain with angiographically normal coronary arteries are usually labelled syndrome X. A portion of these patients may not have a cardiac cause for their symptoms. The authors aimed to study a subset within this group who showed the phenom enon of slow coronary flow (SCF) as evidenced by a slow antegrade progression of the dye on the coronary arteriogram to see if this could be used as a marker of myocardial ischemia. This observational study included 207 patients being evaluated for suspected coronary artery disease and found to have normal coronary angiograms. SCF was seen in 49 of these patients (23.7%) while the remaining 158 (76.3%) had normal coronary flow (NCF), as detected by the corrected thrombosis in myocardial infarction (TIMI) frame count method (TIMI frame count more than 2 SD of normal). Forty of the 49 patients (82%) in the SCF group had classical angina as compared with only 51 of the 158 patients (32%) in the NCF group (p The authors conclude that SCF patients constitute a definite subset within the wide spectrum of syndrome X and that the phenomenon of SCF could be used as a marker for myocardial ischemia.

The effects of ozone (O3) on airway epithelia, inflammation, and expression of inflammatory stimuli were investigated to delineate the mechanisms of inflammatory reactions relevant to lung injury. Because the airway responses to O3 develop gradually, this investigation included a time-sequence analysis. Rats exposed for 3 h to 1 ppm O3 were studied at 4-h intervals up to 20 h postexposure. Bronchoalveolar lavage fluid (BAL) was analyzed for albumin as an indicator of increased permeability, polymorphonuclear leukocytes (PMNs) to assess the inflammatory status, macrophage inflammatory protein-2 (MIP-2, an inflammatory chemokine), and cell adhesion molecules for their role in inflammation and PMN functions. The time-related increase in albumin was matched by a similar significant increase for PMNs, MIP-2, and intercellular adhesion molecule-1 (ICAM-1). However, no marked change occurred for beta-2 integrin (CD-18) and leukotriene B4 (LTB4). The results establish a temporal correlation of epithelial permeability with changes in inflammatory activity and stimuli responsible for PMN recruitment in the lung. The observations of elevated MIP-2 and ICAM-1 levels are consistent with their role in injury and inflammation. An early expression of MIP-2 mRNA in BAL cells, that is, immediately post O3 exposure, and the peak increase in BAL MIP-2 levels 4 h later support the chemotactic role of MIP-2 in PMN recruitment at 4- and 12-h time points. The rapid drop in MIP-2 and ICAM-1 levels appears to signal the termination of inflammatory cell recruitment, which is accompanied by an onset of recovery.

The deleterious effects of ozone (O3), an oxidant air pollutant, in the lung are dependent on dose and exposure duration and generally evolve with time postexposure. This study characterized the time sequence of epithelial injury and fibronectin expression in the lungs of rats exposed to O3. Bronchoalveolar lavage (BAL) fluid was analyzed for alkaline phosphatase and total protein as markers of epithelial injury and increased permeability, and fibronectin for its role in inflammation and lung injury. The results revealed a time-related increase in total protein in the BAL fluid following a 3-h exposure of rats to 1 ppm O3. The increased protein concentrations peaked at 12 h and then declined, but remained significantly higher than control at 24 h postexposure. A similar time-related significant increase also occurred for BAL fibronectin and alkaline phosphatase activity. However, the return of alkaline phosphatase levels to baseline prior to a comparable reduction in protein levels suggests repair of injured cells, but a delay in the formation of epithelial junctions that limit the transfer of serum proteins to air spaces. By cytochemistry, alkaline phosphatase activity was detected in association with lung type II epithelial cells and in BAL polymorphonuclear leukocytes (PMNs), but not in macrophages. While a significant increase in cytochemically detectable alkaline phosphatase resulted from the increase in PMN number following O3 exposure, mononuclear cells constituted the primary cell type responsible for fibronectin mRNA upregulation. While the cytochemical observations support the role of inflammatory cells in the injury process, the comparability of temporal changes in BAL protein, fibronectin, and alkaline phosphatase suggests a mechanistic role for fibronectin in lung injury.

We report three cases of angina-like chest pain with documented ST segment elevation and slow coronary flow in the absence of any significant obstructive coronary artery disease and no evidence of any major epicardial coronary arterial spasm.

This study investigated the relationship of fibronectin expression and induction of pulmonary inflammation by ozone (O3). Rats were exposed to 0.8 parts/million O3to induce lung inflammation. A second inflammatory stimulus, rabbit serum, was applied intratracheally to augment O3-induced inflammation. Bronchoalveolar lavage fluid (BALF) and lung tissues were analyzed for fibronectin protein and mRNA expression. Blood plasma was analyzed to investigate the potential of a minimally invasive procedure in predicting lung inflammation and fibronectin levels. Significant increases in the levels of fibronectin protein in the BALF and lung tissue after O3exposure were further enhanced by pretreatment with normal serum. An increase in fibronectin mRNA following O3exposure was also enhanced by serum pretreatment, which by itself had no effect on lung fibronectin mRNA expression. Plasma fibronectin levels were comparable in air-PBS and O3-PBS groups but increased in the O3-serum group. The results suggest leakage of fibronectin from blood plasma into the lung following intratracheal application of rabbit serum and upregulation of local synthesis following O3exposure.

The aim of this study was to test whether galectin-3 is present in human corneal epithelium and whether lipopolysaccharide (LPS) purified from Pseudomonas aeruginosa ATCC 19660 binds to this animal lectin and/or to another human corneal epithelial protein(s) (HCEP) and to confirm which component of LPS (inner or outer core or lipid A) is important in bacterial binding by using the eye in organ culture. LPS isolated and purified from P. aeruginosa ATCC 19660 and a commercial LPS (serotype 10) differed in polyacrylamide gel analysis but bound similarly to blotted HCEP. Binding was determined to be a receptor-ligand type of interaction by the solid-phase assay, because it was both specific and saturable. Several LPS binding proteins in HCEP were identified by an overlay method. Western blotting with antibody against galectin-3 revealed the presence of this protein in both freshly isolated and cultured transformed human corneal epithelium. Binding inhibition assays showed that antibody specific for the outer core region of LPS and an anti-galectin antibody significantly inhibited bacterial binding in vitro. These data provide further evidence that LPS is an important adhesin of P. aeruginosa, that it binds to protein receptor molecules in HCEP, that one of the LPS binding proteins is galectin-3, and that the outer core portion of the molecule appears to be critical for LPS binding to the eye.

A polyclonal antibody (pAb) against gangliotetraosylceramide (asialo GM1), a glycolipid to which bacterial pili and LPS bind, and a mAb against a 66 kDa pilus-binding protein purified from adult mouse corneal epithelium were used to determine if antibodies against host receptors for bacterial adhesins could inhibit bacterial binding to wounded corneal epithelium and protect ocularly challenged mice from corneal perforation when topically applied. Bacteria were mixed with anti-66 kDa mAb, a mixture of anti-asialo GM1 pAb and anti-66 kDa mAb, an irrelevant control mAb (anti-human histocompatibility Ag HLA-DR5) or PBS prior to application to scarified corneas in organ culture. The combination of the two antibodies or the anti-66 kDa mAb alone was effective in reducing bacterial adherence compared with either PBS or the antibody control. To determine if these antibodies were protective in vivo, corneas of C57BL/6J mice were scarified and inoculated with Pseudomonas aeruginosa. Eyes were treated topically with anti-asialo GM1 pAb, anti-66 kDa mAb, a mixture of the two or control mouse serum. More serum-treated corneas perforated compared to corneas from any other group (Por = 0.005) by 30 days postinfection. Treatment with a combination of the two antibodies resulted in significantly less corneal pathology 30 days p.i. when compared to any other treatment (Por = 0.005). These data provide evidence that antibodies against host corneal receptors significantly inhibit bacterial binding in vitro and when applied topically in vivo, lessen the severity of ocular disease characteristic of P. aeruginosa keratitis.

A two-unit cold standby system with an expert repairman and his assistant is examined. If the expert repairman is busy in repairing a failed unit and at that time the second unit fails, the assistant repairman repairs the latter unit. The assistant repairman needs or does not need instructions for doing repair with probability p and q, respectively. Using a regenerative point technique, various measures of system effectiveness are obtained.

A considerable body of literature“[1-17] has been published on various aspects of the solid-state reduction of ilmenite (FeTiO3) using various reductants. All these investigations were limited up to 1200 °C. The present investigation describes the reduction behavior of two ilmenite concentrates produced by Westralian Sands Limited (WSL) and Western Mineral Sands (WMS) with Collie coal at 1240 °C. These materials were from Australia and were supplied by Tioxide International Limited, United Kingdom. The chemical analyses of these materials, given in Table I, were provided with the materials. The unmilled concentrates were sieved, and the size fraction of 104 to 152 μm, which accounted for ≈70 pct of the original material, was used for the experiments. The Collie coal was crushed and sieved to produce particles of the same size fraction. The purpose of this investigation is to study the effect of temperature higher than 1200 °C on the kinetics of the reduction and the formation of various phases after reduction.

Viscosities (η) of PbO-SiO2 melts that contained 25.0 to 48.8 mole pct SiO2 were measured at temperatures 928 to 1273 K by a rotating cylinder method. The data were analyzed in terms of the conventional polymer theory. The results followed Arrhenius behavior in the different temperature ranges despite the general belief of non-Arrhenius behavior of viscosity in slag melts. The calculated activation energies were a function of temperature and composition of the melts. The activation energies for viscous flow, in general, at above approximately 850 °C were lower than those below 850 °C and varied between 25 and 150 kJ per mole.

The effect of long-term (72 h) treatment with dopamine D1 receptor agonists, SKF 38393 and dopamine on D1 dopamine receptor and G-protein (Gs alpha) was investigated in SK-N-MC neuroblastoma cells. The prolonged treatment of cells with 10 microM SKF 38393 or 10 microM dopamine resulted in a decrease in dopamine D1 receptor by 41 and 81%, respectively, as measured by specific antagonist [3H]SCH 23390 binding. Similarly, the prolonged treatment of SK-N-MC cells with 10 microM SKF 38393 or 10 microM dopamine resulted in a reduction of the level of Gs alpha subunit of G-protein. The results indicate that agonist-induced down-regulation of D1 dopamine receptor may also modulate G-proteins.

Laboratory column studies are done to investigate the variation of drainable porosity in relation to water table depth. Corresponding functional relationships are developed between drainable porosity and water table depth. The Boussinesq equation for non–steady-state ground-water flow is adapted and suitably modified by incorporating the variable drainable porosity function. The modified equation is solved using the extrapolated Crank-Nicolson difference scheme for predicting water table depth in relation to space and time. A sand-tank model experiment is done to find observed values of water table fluctuations. The prediction from the modified Boussinesq equation is compared with observed data. It is discovered that incorporating variable drainable porosity in the computation increases the accuracy of the prediction at all distances from the drain compared with using a constant value for drainable porosity. It is also discovered that water table predictions from the modified Boussinesq equation varied with observed data. This is attributed to lag time between the initiation of the drain outflow and response in water table drawdown in mathematical computation.

Anti-tumor potential of root extracts of Calotropis procera: methanolic extract (CM), hexane extract (CH), aqueous extract (CW) and ethylacetate extract (CE) and its possible mechanism against Hep2 cancer cells has been investigated. Cellular proliferation activities were assayed by tetrazolium bromide (MTT) colorimetry. Morphological changes of cancer cells were observed under inverted microscope and cell cycle parameters were determined by flow cytometry following propidium iodide staining. Treatment with the extracts at various doses of 1, 5, 10 and 25 microg/ml revealed that CM, CH and CE possessed cytotoxicity, whereas CW did not have cytotoxic effect. CE (10 microg/ml) showed strongest cytotoxic effect (96.3%) on Hep2 at 48 hr following treatment, whereas CM and CH showed cytotoxicity of 72.7 and 60.5%, respectively. Extract-treated cells exhibited typical morphological changes of apoptosis. Results of flow cytometric analysis clearly demonstrated that root extracts initiated apoptosis of Hep2 cells through cell cycle arrest at S phase, thus preventing cells from entering G2/M phase. Results of the study indicate that the root extracts of C. procera inhibit the proliferation of Hep2 cells via apoptotic and cell cycle disruption based mechanisms.

llmenite concentrates were heated in argon and oxygen in the temperature range 700 °C to 1000 °C to study the behavior of the pseudorutile phase and other changes which occur. Pseudorutile does not persist in argon or oxygen in the temperature range studied. In argon at 700 °C, pseudorutile decomposes into hematite and rutile, while at 1000 °C, it combines with ilmenite to form ferrous-ferritic pseudobrookite solid solution. A new phase “Fe2O3-2TiO2” was identified as an intermediate product during the heating of ilmenite or pseudorutile in oxygen. This compound decomposes into hematite and rutile below 800 °C and to pseudobrookite and rutile above 800 °C. The sequence of reactions during the heating of ilmenite and pseudorutile in oxygen is proposed.

The clinical and pathologic features of progressive renal disease in 4 patients with Down's syndrome are described. All patients were male, between 20 and 30 years of age at the time of clinical presentation. Three out of 4 had proteinuria, and 2 had hematuria. Serologic tests for hepatitis B virus infection and antinuclear antibodies performed in 2 patients were negative. Examination of renal tissue from biopsy and/or from autopsy revealed mesangiocapillary glomerulonephritis (MCGN), type 1. While an increased incidence of congenital heart disease and acute leukemias has been documented in Down's syndrome, an association with MCGN has not been reported previously to our knowledge. This probably represents a form of idiopathic MCGN and may be related to the long survival of these individuals.

Cadmium, a major metal constituent of tobacco smoke, elicits synergistic enhancement of cell transformation when combined with benzo[a]pyrene (BP) or other polynuclear aromatic hydrocarbons (PAHs). The mechanism underlying this synergism is not clearly understood. Present study demonstrates that (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), an ultimate carcinogen of BP, induces apoptosis in human leukemic HL-60 cells and others, and cadmium at non-cytotoxic concentration inhibits BPDE-induced apoptosis. We observed that BPDE treatment also activates all three MAP kinases e.g. ERK1/2, p38 and JNK in HL-60 cells, and inhibition of BPDE-induced apoptosis by cadmium is associated with down-regulation of pro-apoptotic bax induction/caspase-9 activation and up-regulation of ERK phosphorylation, whereas p38 MAP kinase and c-Jun phosphorylation (indicative of JNK activation) remain unaffected. Inhibition of ERKs by prior treatment of cells with 10muM U0126 relieves cadmium-mediated inhibition of apoptosis/bax induction/caspase-9 activation. Our results suggest that cadmium inhibits BPDE-induced apoptosis by modulating apoptotic signaling through up-regulation of ERK, which is known to promote cell survival.

To determine the biological behaviour of very large superficial bladder tumours (pTa, pT1) and evaluate the impact of the initial tumour weight on long-term prognosis.Of 1569 patients who presented with bladder tumours over a 10-year period, 1070 of the tumours were superficial. Fifty-nine patients had very large tumours (resected weightor= 15 g). Case notes were analysed to determine recurrence, progression and survival. Median follow-up was 60 months (range 1-156 months). Histological slides were reviewed for all tumours initially reported as pT1 to determine the presence of uninvolved muscle. Statistical analysis was performed using the Kaplan-Meier method to calculate progression and survival estimates.The overall progression and recurrence rates for very large superficial bladder tumours were 18% and 68%, respectively. The progression rates for Ta, T1, G1, G2 and G3 tumours were 4%, 28%, 0%, 20% and 50%, respectively, with highest progression rates being seen for pT1G2 and pT1G3 tumours. The progression rate was significantly influenced by initial stage (p=0.01) and grade (p=0.03). Tumour weight did not affect either recurrence, progression or cause-specific survival. There were no differences in progression and survival rates in patients with tumour weights of 15-30 and30 g (p=0.80 and 0.07, respectively). The review of histology slides of T1 tumours showed that 7/10 cases (70%) with progression had no muscle or an inadequate amount of muscle for definitive staging. Upper urinary tract tumours were seen in only two patients (3.4%).Large size is not an adverse prognostic factor for patients with a superficial bladder tumour. However, these cases are difficult to stage. In view of the high rates of progression and disease-specific mortality, we recommend that very large pT1G2 bladder tumours should be considered as high-risk tumours and targeted for aggressive treatment, including early re-resection, to rule out any occult invasive disease.

A new concept has been developed for the production of zinc from zinc and complex zinc concentrates. It is a two-stage process involving oxidation of zinc sulfide to oxide and dissolution into slag and the fuming of zinc from the slag by injecting carbonaceous materials into it to produce zinc vapors which can be subsequently condensed in a lead-splash condenser such as those used in the Imperial Smelting Process (ISP). In this paper, the effects of the quantity of air, temperature, and concentrate feed rate have been discussed on the production of zinc-rich slag, which is the first stage of the proposed process.

An ilmenite concentrate was heat treated in argon for 1, 2.5, 5 and 10 hours at 1000°C. The heat-treated samples were reduced with coal isothermally at 1000 and 1050°C and the reduction paths were determined using thermogravimetry. X-ray diffraction and optical microscopy were used to identify the phases before and after heat treatment, and the morphology of the iron produced. Preheating in argon homogenized the structure of the concentrate and increased the rate of its subsequent reduction. However, the morphology of the iron was less suitable for its physical separation from the titanium oxides. The addition of ferric chloride to the ilmenite-coal mixture helped in speeding up the reaction.

Menopause is a pro-atherogenic state with a sharp rise in the incidence of coronary artery disease. This pilot study was designed as an equivalence randomized clinical trial to explore the potential of LycoRed (containing 2000 microg lycopene) as an alternative to hormone replacement therapy (HRT) for the prevention of coronary artery disease in postmenopausal women.Forty-one healthy postmenopausal women were randomly allocated to receive either continuous combined HRT (n = 21) or LycoRed (n = 20) for six months. Serum lipid profile, marker of lipid peroxidation (malondialdehyde), and the level of endogenous antioxidant (glutathione) were measured at the baseline, and 3 and 6 months after the intervention in both groups.At 6 months, HRT resulted in a significant decrease in total cholesterol (TC) level by 23.5%, low-density lipoproteins (LDL) by 19.6%, and an increase in high-density lipoproteins (HDL) by 38.9%. The LycoRed group showed similar changes in TC (-24.2%), LDL (-14.9%) and HDL (+26.1%). Triglyceride levels showed a smaller though significant increase at 6 months, but not at 3 months, in both groups. There was no significant change in the very LDL (VLDL) level in either group. Malondialdehyde levels decreased significantly by 16.3% and 13.3%, whereas glutathione levels increased significantly by 5.9% and 12.5% in HRT and LycoRed groups, respectively.Both HRT and LycoRed had a favorable effect on serum lipids and oxidative stress markers which were comparable. LycoRed can be used as an alternative to HRT to reduce the risk of atherosclerosis in postmenopausal women.

An analogue of the highly potent γ-lactam Pro-Leu-Gly-NH 2 peptidomimetic, 3( R )-[(2( S )-pyrrolidinylcarbonyl) amino]-2-oxo-1-pyrrolidineacetamide ( 2 ), 4( R )-[[2( S )-pyrrolidinylcarbonyl]amino]-2-oxo-1-pyrrolidineacetamide ( 3 ), in which the lactam carbonyl moiety has been placed in a different position with respect to the 3-amino group was synthesized. Also, a series of analogues of 2 , compounds 4 – 6 , were synthesized in which each of the amide bonds of 2 were systematically replaced with a reduced amide bond surrogate. The analogues were tested for their ability to enhance the binding of [ 3 H] N -propylnorapomorphine to dopamine receptors in a functional in vitro assay utilizing bovine striatal membranes. Peptidomimetic 3 was shown to be more potent than 2 , while 4 and 5 were significantly less effective than 2 . Peptidomimetic 6 had a pharmacological profile similar to that of 2 .

γ-Lactam peptidomimetic 2 of Pro-Leu-Gly-NH2 (PLG) was substituted at the 3-position with isobutyl, butyl, and benzyl moieties to give the PLG peptidomimetics 3−5, respectively. These compounds were synthesized to test the hypothesis that attaching a hydrophobic moiety to the lactam ring to mimic the isobutyl side chain of the leucyl residue of PLG would increase the dopamine receptor modulating activity of such peptidomimetics. These peptidomimetics were tested for their ability to enhance the binding of [3H]-N-propylnorapomorphine to dopamine receptors isolated from bovine striatal membranes. The rank order of effectiveness of the 3-substituent was benzyl > n-butyl > isobutyl > H.

Lens epithelial cells are the metabolic unit of the lens and antioxidant enzymes are mainly concentrated here. The purpose of this study was to maintain human lens epithelial cells (HLEC) in culture and examine the status of antioxidant enzymes (glutathione peroxidase (GSHPx), catalase (CAT), glutathione-S-transferase (GST)), lipid peroxidation product malondialdehyde (MDA) and glutathione (GSH) levels in these cells under normal as well as hypergalactosemic (30 mM galactose) conditions. Further, effect of pyruvate, a physiological antioxidant has also been evaluated on these parameters. For conducting experiments, anterior capsule specimens obtained from fresh cadaver eyes from eye bank were cultured in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 20% fetal calf serum. Upon confluency, the cells were subcultured in three separate flasks containing DMEM alone (normal group), DMEM + 30 mM D-galactose (control group), DMEM + 30 mM D-galactose + 5 mM pyruvate (test group) and incubated for 24 or 72 h. These cells were observed under the phase contrast microscope for any morphological changes and harvested for the estimation of various antioxidant parameters. Our results show significant weakened antioxidant defense in HLEC when incubated in the presence of galactose as compared to normal. Addition of pyruvate significantly modulated levels of GSH, MDA, GSHPx, CAT and GST.

The hallmark of tumor metastasis is the dissemination of cells from the primary growth site to distant organs. Autocrine motility factor (AMF), a tumor-associated C-X-X-C cytokine, the ligand for a unique 78 kDa seven transmembrane receptor, is a potent simulator of cell motility, a process that is a prerequisite for tumor progression and metastasis. Because little is known about AMF-dependent signaling, we sought to study whether AMF signaling involves family members of the Rho-like GTPases. AMF stimulation of human melanoma cells resulted in stress-fiber formation, concomitant with up-regulation and activation of both RhoA and Rac1 expression with no apparent changes in the expression level or activation state of Cdc42. Treatment of the cells with C3 exoenzyme before AMF stimulation inhibited both the formation of stress-fiber-like structures and the activation of RhoA. In addition, both c-Jun NH(2)-terminal kinase 1 and c-Jun NH(2)-terminal kinase 2 were simultaneously activated by AMF, supporting the notion that they are involved in the signaling pathway of RhoA. We thus conclude that AMF signaling shares a similar pathway to previously established paracrine factors signaling involving cytoskeletal rearrangement and morphological alterations mediated by the small RhoA-like GTPases.

Ozone (O3), an oxidant air pollutant, is capable of producing pulmonary inflammation and injury. Exposure to O3 results in the release of inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) by alveolar macrophages. In addition, O3 exposure results in an increased expression of the inducible isoform of nitric oxide synthetase (iNOS). Interleukin-10 (IL-10) is an anti-inflammatory cytokine which inhibits the synthesis of TNF-alpha and IL-1 by macrophages and decreases the expression of iNOS. To test the protective properties of IL-10 in vivo, on the pulmonary injury induced by O3 exposure, we intratracheally instilled rat recombinant IL-10 1 h prior to O3 exposure (0.8 ppm x 3 h). Approximately 10-12 h following exposure, the animals were sacrificed and the bronchoalveolar lavage fluid (BALF) collected. The quantification of albumin, protein and fibronectin in the BALF provided a means of assessing pulmonary injury while the analysis of the BALF cells reflected the inflammatory response. Ozone exposure resulted in a significant (P

Modified 9Cr-1Mo ferritic steel has a wide range of special applications, due to its high strength and oxidation resistance behavior. Recently laser irradiation has been found to improve significantly its air oxidation resistance at temperatures above 700 o C. Detailed surface characterization by X-ray photoelectron (XPS) and Auger electron (AES) spectroscopy of the oxidation films has now been undertaken with a view to acquiring an understanding of this phenomenon

The goal of this study was to test whether bacterial exoproducts, such as elastase or alkaline protease contribute to the initial binding of Pseudomonas aeruginosa to mouse corneal epithelium. Each protease, purified from P. aeruginosa, when applied exogenously at concentrations of either 25 or 50 ng ml-1, elevated binding of Pseudomonas to mouse cornea in organ culture. Polyclonal antibodies against bacterial alkaline protease, but not elastase, interfered with bacterial binding and reduced significantly the number of organisms bound to cornea in an organ culture binding inhibition assay. Zymographic analysis of conditioned media from additional organ culture experiments showed that the P. aeruginosa strain used, which is highly virulent in cornea in vivo, secretes detectable levels of alkaline protease, but not elastase in vitro and that secretion was enhanced if the corneal epithelium was wounded. Lastly, how alkaline protease enhanced bacterial binding to the corneal epithelium of the organ cultured eye was examined. Data from this study suggest that exposure of lipase-sensitivity epithelial receptors represents at least one mechanism.

Soluble human corneal epithelial proteins (hcep) to which P. aeruginosa pili bind were identified and characterized using gel electrophoresis and Western blotting techniques. Pilus binding proteins were identified using nitrocellulose membrane blots of one dimensional polyacrylamide gels (1-D-SDS-PAGE) of solubilized hcep and a pilus overlay assay. Five major proteins of approximate molecular weights21, 38, 45, 66, 97 (a doublet) kilodaltons (kDa) and two additional proteins of97 kDa bound pili using an overlay assay and immunoblotting with the monoclonal antibody (MAb) XLR-3, specific for pili. Several of these pili binding proteins were confirmed as single proteins using a similar pilus overlay assay and blotted proteins from two-dimensional polyacrylamide gels (2-D-SDS-PAGE) of hcep. A solid-phase binding assay confirmed that pili binding to hcep was specific, competitive and saturable. The importance of the carbohydrate portions of corneal pili binding proteins was assessed by preincubation of 1-D gel blots of hcep or dot blots of selected eluted pilus binding proteins (21, 38, 45, 66 and 97 kDa) with periodic acid. Mild periodate oxidation of blots before pilus overlay assay completely abolished pili binding. The role of glycosylation of proteins also was assessed using 1-D blots of hcep or dot blots of eluted pilus binding proteins. These blots were preincubated with different lectins before incubation with pili in the pilus overlay assay. Of several lectins examined, only sConA, which recognizes terminal mannose residues, prevented pili binding in the pilus overlay assay. These studies provide evidence that several human corneal epithelial glycosylated proteins provide receptor sites for bacterial pili binding, and that the binding of pili to these proteins is specific, competitive and saturable. They also show that the carbohydrate mannose functions as an integral component of hcep pili binding receptors.

This study investigated which adhesins of Pseudomonas aeruginosa interact with the glycolipid asialo GM1, using solid-phase binding and thin-layer chromatography assays. Radioiodinated pili and flagella contaminated with lipopolysaccharide (LPS) bound to the glycolipid. When LPS was reduced to acceptable levels in pilus and flagellum samples, only pili specifically bound to the glycolipid. Commercial, radiolabeled LPS as well as whole bacteria of strain ATCC 19660 also bound to asialo GM1. Binding was specific, competitive, and saturable. Organ cultures of whole mouse eyes and scanning electron microscopy techniques were used also, and strain ATCC 19660 was inhibited from corneal binding by exogenous pili or commercial LPS and inhibition was concentration dependent for both. Binding of radiolabeled strain ATCC 19660 bacteria to neutral lipids extracted from bovine corneal epithelial tissue showed that the bacteria bound to a glycolipid which migrated at a position similar to that of an asialo GM1 standard and that the glycolipid stained positively with an antibody specific for asialo GM1. The data provide evidence that pili (reduced LPS) and LPS of P. aeruginosa bind to asialo GM1 glycolipid and that the glycolipid is not restricted to the mouse cornea.

Chronic administration of typical neuroleptic drugs, such as haloperidol, causes the supersensitivity of brain dopamine D2 receptor in striatum and limbic regions, while the atypical neuroleptic clozapine does not. In order to understand the mechanism of their action at a molecular level, studies were carried out to assess the effects of chronic treatment of these drugs on the levels of G-proteins in the rat striatum using the Western blot method. Results of the present study demonstrate that the treatment with haloperidol or clozapine, respectively, down-regulate or up-regulate the levels of G proteins. Quantitative immunoblotting, using site-directed specific antisera, demonstrated that chronic treatment with haloperidol down-regulates Gi alpha, Gs alpha, and beta subunits while chronic treatment with clozapine upregulates Gi alpha, Gs alpha, and beta subunits. Neither of these drugs has any effect on the levels of Go alpha.

In a nonhemophilic 72-year-old man, a persistent degenerative hemarthrosis of the shoulder joint was associated with a complete tear of the rotator cuff. Extensive, rusty synovial pigmentation and hyperplasia (hemosiderotic synovitis) mimicking pigmented villonodular synovitis (PVS) were noted at surgery. Spontaneous hemarthrosis of the shoulder includes rapid onset of severe pain, limitation of movement, subsequent appearance of a bruise on the affected shoulder and arm, and radiological evidence of joint degeneration. Hemosiderotic synovitis results from chronic intraarticular bleeding. With the breakdown of trapped hemoglobin, iron-containing hemosiderin is stored in synovial tissue producing rusty discoloration and proliferative reaction. The classic cytoarchitecture of PVS has additional subsynovial nodular proliferation of mononuclear cells. Hemarthrosis may produce significant structural alteration of joints. Its prompt recognition and the awareness of underlying causes should lead to earlier diagnosis, appropriate therapy, less joint destruction, and better outcomes.