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Biomedical subjects

A Shukla

Publications and source records attributed to A Shukla.

At least 37 records · Page 2Linked to original sources

The removal of heavy metal from aqueous solutions by sawdust adsorption - removal of copper.

Locally available sawdust, a byproduct of the world industry, was found to be a low cost and promising adsorbent for the removal of copper(II) from wastewater. In this work, adsorption of copper on sawdust has been studied by using batch techniques. The equilibrium adsorption level was determined to be a function of the solution pH, contact time, and sorbate concentration. The equilibrium adsorption capacity of sawdust for copper was obtained by using linear Freundlich and Langmuir isotherms. Ion exchange is probably one of the major adsorption mechanisms for binding divalent metal ions to the maple sawdust. The results provide strong evidence to support the hypothesis of adsorption mechanism. It also supplies significant sawdust operation capacity data for engineering design.

Adsorption↗

Ultrafast optical nonlinearity in the quasi-one-dimensional mott insulator Sr2CuO3

We report strong instantaneous photoinduced absorption in the quasi-one-dimensional Mott insulator Sr2CuO3 in the IR spectral region. The observed photoinduced absorption is to an even-parity two-photon state that occurs immediately above the absorption edge. Theoretical calculation based on a two-band extended Hubbard model explains the experimental features and indicates that the strong two-photon absorption is due to a very large dipole coupling between nearly degenerate one- and two-photon states. Room temperature picosecond recovery of the optical transparency suggests the strong potential of Sr2CuO3 for all-optical switching.

Journal Article↗

Tandem mass spectrometric study of 1,3,5-trinitrobenzene molecular ion: an unusual ortho effect involving a hydrogen atom from the aromatic ring

Unimolecular (metastable) and collision-induced dissociation of 1,3, 5-trinitrobenzene molecular ion was studied using linked scans and mass-analyzed ion kinetic energy spectrometry on a hybrid instrument of EBEqQ geometry. An unusual ortho effect leading to the loss of OH radical from the parent molecular ion is observed as a unimolecular dissociation process only in the first-field free region between the ion source and the electric sector, although corresponding dissociation in the ion source is of negligible abundance (<0.1%). This unimolecular process is taken over by other dissociation pathways when the parent ion is collisionally activated, suggesting that this dissociation process occurs only in a very narrow energy window with a rate constant of the order of 2 x 10(5) s(-1). Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

Cadmium-mediated oxidative stress in alveolar epithelial cells induces the expression of gamma-glutamylcysteine synthetase catalytic subunit and glutathione S-transferase alpha and pi isoforms: potential role of activator protein-1.

Exposure of rat alveolar epithelial cells to 10 micromol/L CdCl2 causes time-dependent increases in steady-state mRNA levels of the gamma-glutamylcysteine synthetase catalytic (heavy) subunit (gamma-GCS) and of glutathione S-transferase isoforms (GST-alpha and GST-pi). The expression of gamma-GCS was significantly increased as early as 2 h after addition of cadmium. Maximal induction of gamma-GCS mRNA (approximately 4-fold), at 8 h, was subsequently followed by increases in gamma-GCS activity/protein and glutathione (GSH) levels. Maximal elevations in GST-pi (approximately 2-fold) and GST-alpha (approximately 10-fold) transcripts, at 8 and 24 h, respectively, were also accompanied by enhanced GST activity. Cadmium-induced oxidative stress, assessed by alterations in GSH homeostasis and an accelerated rate of intracellular oxidant production, could constitute early events in the signal transduction pathway mediating these responses. The dimeric transcription factor, activator protein-1 (AP-1), may also play a regulatory role in this process. This association is suggested by transcriptional activation of the immediate-early response genes, c-fos and c-jun, within 15 min after exposure to cadmium and by the enhancement of AP-1 DNA binding activity, involving a c-Jun protein complex, which is maximally induced (approximately 4-fold) by 2 h. These molecular changes likely function together to protect alveolar epithelial cells against cadmium toxicity.

Animals↗

Antioxidant status in delayed healing type of wounds.

This investigation studied the contribution of antioxidants in delaying healing in excision cutaneous wounds (8 mm) in diabetic, aged and immunocompromised animals. Skin levels of catalase, glutathione (GSH), ascorbic acid (AA) and vitamin E in streptozotocin-induced diabetic rat were lower as compared to nondiabetics. The 7-d wound tissue of diabetic rats showed an increased vitamin E level along with depleted GSH content. In aged rats (18 months old), higher levels of skin superoxide dismutase (SOD), glutathione peroxidase (Gpx) and thiobarbituric acid reactive substances (TBARS) and lower levels of catalase and GSH were found as compared to their values in young rats (3-4 months old). The levels of SOD, GPx, catalase, AA, GSH and vitamin E in 7-d wound tissue of aged rats were significantly lower in comparison to those in young rats. However, TBARS were elevated in these wound tissues. The non-wounded skin of immunocompromised (athymic) mice showed lower levels of SOD, catalase, and TBARS and higher GSH and GPx levels in comparison to those present in normal mouse skin. Surprisingly, the analysis of 7-d wound tissue showed higher levels of SOD, catalase, GPx, and GSH and lower TBARS level in athymic mice compared to the wound tissue of normal mice. Thus low levels of antioxidants accompanied by raised levels of markers of free radical damage play a significant role in delaying wound healing in aged rats. In diabetic rats reduced glutathione levels may have a contributory role in delaying the healing process. However, in immunocompromised mice the antioxidant status following injury showed an adapted response.

Aging↗

Regulated exocytosis in immune function: are SNARE-proteins involved?

Inflammation is an important feature in the pathogenesis of most chronic lung diseases. It is characterized by tissue infiltration with various inflammatory cells, including eosinophils, mast cells, basophils, macrophages, neutrophils, T- and B-lymphocytes and dendritic cells (1). In the tissue granulocytes release their toxic granule proteins after being stimulated by soluble mediators released by other inflammatory cells (2). Therefore, it is important to characterize the intracellular mechanisms regulating the transport of the granule contents in inflammatory cells. Intracellular vesicle-traffic in mammalian cells is mediated by transport vesicles that emerge from donor compartments and are specifically targeted to acceptor compartments where they deliver their contents after membrane fusion (3). This traffic leads to three types of fusion: vesicle-intracellular membranes, vesicle-vesicle or vesicle-plasma membrane. The process leading to fusion of vesicle-plasma membrane is called exocytosis, and it delivers proteins to the cell surface (receptors e.g. CD11b, CD18) and exports soluble molecules (mediators e.g. ECP) from the cell. A number of key proteins involved in regulated exocytosis have been identified from inflammatory cells. This review is a brief summary of these proteins and it includes recent results from studies on regulated exocytosis in inflammatory cells.

B-Lymphocytes↗

Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro.

High levels of ambient air pollution are associated with exacerbation of asthma and respiratory morbidity, yet little is known concerning the mechanisms of inflammation and toxicity by components of inhaled particulate matter (PM). Brief inhalation of PM(2.5) (particles of an aerodynamic diameter of < 2.5 microns) (300 microg/m(3) air for 6 h followed by a period of 24 h in clean air) by either C3H/HeJ or C57/BL6 mice caused significant (P </= 0.05) increases in steady-state messenger RNA (mRNA) levels of a number of nuclear factor (NF)-kappaB-associated and/ or -regulated genes, including tumor necrosis factor-alpha and -beta, interleukin-6, interferon-gamma, and transforming growth factor-beta. Lung mRNA levels of lymphotoxin-beta and macrophage migration inhibitory factor were unchanged. In murine C10 alveolar cells and an NF-kappaB-luciferase reporter cell line, exposure to PM(2.5) at noncytotoxic concentrations resulted in increases in transcriptional activation of NF-kappaB-dependent gene expression which were inhibited in the presence of catalase. Early and persistent increases in intracellular oxidants, as measured by flow cytometry and cell imaging using the oxidant probe 2'-7'-dichlorofluoroscin diacetate, were observed in epithelial cells exposed to PM(2.5) and ultrafine carbon black particles. Studies here are the first to show NF-kappaB-related inflammatory and cytokine gene expression after inhalation of PM(2.5) and oxidant-dependent induction of NF-kappaB activity by PM(2.5) in pulmonary epithelial cells.

Air Pollutants↗

Healing potential of Calotropis procera on dermal wounds in Guinea pigs.

Calotropis procera (Asclepiadaceae) is a well known plant in the Ayurvedic system of medicine. Based on its traditional use this plant was selected for evaluation of its wound healing potential. For this purpose four full thickness excisional wounds of 8.0 mm diameter were inflicted on the back of guinea pigs. Topical application of 20 microl of 1.0% sterile solution of the latex of C. procera twice daily was followed for 7 days. The latex significantly augmented the healing process by markedly increasing collagen, DNA and protein synthesis and epithelisation leading to reduction in wound area. Thus the present study provides a scientific rationale for the traditional use of this plant in the management of wound healing.

Animals↗

Characterization of cadmium-induced apoptosis in rat lung epithelial cells: evidence for the participation of oxidant stress.

The mode of cadmium-induced cell death was investigated in a rat lung epithelial cell line. Cells, grown to near confluence, were exposed to 0-30 microM CdCl2 for 0-72 h. Phase contrast microscopy and fluorescent nuclear staining showed that Cd caused morphological alterations in lung epithelial cells that are characteristic of apoptosis. These changes included cell shrinkage, detachment of the cell from its neighbors, cytoplasmic and chromatin condensation, and fragmentation of the nucleus into multiple chromatin bodies surrounded by remnants of the nuclear envelope. Apoptotic DNA degradation was validated and quantitated using a sensitive enzyme-linked immunosorbent assay (ELISA) which measures the amount of histone-bound DNA fragments in the cytosol. Using this technique, a maximum level of apoptosis (5-fold higher than control) was observed in cultures exposed for 48 h to 20 microM CdCl2. The terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling method (TUNEL) was subsequently used to determine the percentage of cells that contained Cd-induced DNA strand breaks. After 48 h, approximately 54% of the cells exposed to 20 microM Cd were TUNEL positive compared to less than 2% for control cells. Although the mechanisms by which Cd initiates apoptosis in these cells are presently not known, reactive oxygen species are likely to play a role. This possibility is supported by the finding that the first morphological features indicative of apoptosis were preceded by the up-regulation of oxidant stress genes (glutathione S-transferase-alpha, gamma-glutamylcysteine synthetase, and metallothionein-1), activation of redox sensitive transcription factors (AP-1 and NF-kappaB), and changes in various forms of glutathione (reduced, oxidized, and protein-bound).

Animals↗

Asiaticoside-induced elevation of antioxidant levels in healing wounds.

Asiaticoside derived from the plant Centella asiatica is known to possess good wound healing activity. Enhanced healing activity has been attributed to increased collagen formation and angiogenesis. Since antioxidants have been reported to play a significant role in the wound healing process we studied the effect of asiaticoside on the levels of certain antioxidants in the wound so as to explore the possible involvement of such a mechanism in the asiaticoside induced wound healing. Asiaticoside application (0.2%, topical) twice daily for 7 days to excision-type cutaneous wounds in rats led to increased enzymatic and non-enzymatic antioxidants, namely superoxide dismutase (35%), catalase (67%), glutathione peroxidase (49%), vitamin E (77%) and ascorbic acid (36%) in newly formed tissues. It also resulted in a several fold decrease in lipid peroxide levels (69%) as measured in terms of thiobarbituric acid reactive substance. However, continued application for 14 days showed no significant difference in these antioxidants compared with their values in vehicle treated wound tissue. It appears from the present study that asiaticosides enhanced induction of antioxidant levels at an initial stage of healing which may be an important contributory factor in the healing properties of this substance.

Animals↗

In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica.

The activity of asiaticoside, isolated from Centella asiatica, has been studied in normal as well as delayed-type wound healing. In guinea pig punch wounds topical applications of 0.2% solution of asiaticoside produced 56% increase in hydroxyproline, 57% increase in tensile strength, increased collagen content and better epithelisation. In streptozotocin diabetic rats, where healing is delayed, topical application of 0.4% solution of asiaticoside over punch wounds increased hydroxyproline content, tensile strength, collagen content and epithelisation thereby facilitating the healing. Asiaticoside was active by the oral route also at 1 mg/kg dose in the guinea pig punch wound model. It promoted angiogenesis in the chick chorioallantoic membrane model at 40 microg/disk concentration. These results indicate that asiaticoside exhibits significant wound healing activity in normal as well as delayed healing models and is the main active constituent of Centella asiatica.

Administration, Oral↗

Nitric oxide inhibits wounds collagen synthesis.

Nitric oxide (NO) is a messenger molecule which regulates many physiological functions like immunity, vascular tone and serves as a neurotransmitter. Although it is known to participate in healing process, its role in collagen synthesis is not clear. Therefore, the present investigation was done to study the role of NO in wound collagen synthesis. Rats received full thickness, circular (8 mm), transdermal wounds which were treated with NO releaser, sodium nitroprusside (SNP, 0.001 100 microM) topically for 5 days. Wound collagen content estimated in terms of hydroxyproline (HP) and confirmed histochemically was decreased significantly by all SNP doses. L-Arginine, a substrate for nitric oxide synthase (NOS) when applied topically decreased collagen content of the wounded tissues. N-Nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NOS, increased wound collagen content significantly as compared to untreated and SNP treated animal wounds when administered intraperitoneally at the doses 3, 10 and 30 mg/kg. Furthermore, histological findings also demonstrated laying down of thick collagen bundles and proliferation of fibroblasts together with prominent angiogenesis in L-NAME treated wound tissues as compared to untreated and SNP treated tissues. N-nitro-D-arginine methyl ester, an inactive isomer, was found to have no effect on wound collagen levels. When L-arginine was administered in L-NAME pretreated rats, it significantly elevated wound HP content. The results indicate that NO plays an important role in regulating the collagen biosynthesis in skin model of a healing wound.

Animals↗

Esophageal-directed pressure support ventilation in normal volunteers.

STUDY OBJECTIVES: To ascertain whether inspiratory pressure support (IPS) can be triggered reliably from and targeted at esophageal pressures (Pes), and to compare the work of breathing and time delay to initiation of inspiratory flow between conventional pressure support and esophageal-directed pressure support (EDPS). DESIGN: Prospective laboratory study. SETTING: University medical school. PATIENTS OR PARTICIPANTS: Five normal volunteers. INTERVENTIONS: IPS at a level to achieve tidal volume of 10 mL/kg, and EDPS with a target Pes of 0 cm H2O via full facemask. MEASUREMENTS AND RESULTS: Pes, airway pressure, and inspiratory flow were measured during spontaneous breathing. Peak Pes and pressure time product (PTP) of Pes were calculated during spontaneous breathing and through linear resistances. Measurements were repeated during IPS and EDPS ventilation. At rest, PTP was 7.56 (+/- 3.6) and peak Pes was -5.8 cm H2O (+/- 1.44). When subjects were breathing through the resistors, PTP increased to 12.4 (+/- 8.1) and 30.3 (+/- 8.9) and peak Pes decreased to -7.2 and -15.3 cm H2O respectively. With facemask IPS, unloaded PTP fell to 1.7 (+/- 1.3) and peak Pes fell to -3.3 cm H2O (+/- 1.3). When ventilated through the highest resistance with IPS, mean PTP increased to 21.9 and peak Pes increased to -11.9 (+/- 4.2) cm H2O relative to baseline. During EDPS with the resistor, PTP fell to 1.5+/-1.1 (p < 0.007) and peak Pes fell to -1.9+/-1.1 cm H2O (p < 0.0001). CONCLUSIONS: It was possible to initiate supported breathing from Pes values. The work performed, as measured by PTP, was lower during EDPS than during either unsupported breathing or conventional IPS.

Feasibility Studies↗

Differential expression of proteins during healing of cutaneous wounds in experimental normal and chronic models.

Recent studies have demonstrated growth factors and other cellular proteins as being important in the healing process. In this study, we have investigated the differential expression of proteins in wound tissues of normal and chronic animal models. Proteins were identified by specific antibodies, partial N-terminal amino acid sequence, and molecular weight homology. In normal wound tissues de novo synthesis of a heat shock protein, platelet derived growth factor (PDGF), and fibroblast growth factor (FGF) was induced within 24 h of skin injury. Proteins resembling vascular endothelial growth factor, receptors for PGDF, FGF, and epidermal growth factor, were synthesized. The elevated synthesis declined to a basal level in 7 to 14 days after skin injury which coincided with healing of wounds. These changes occurred only in wound site tissues but not in distal tissues. In contrast, the chronic wounds presented a different picture. The expressions of these proteins were either delayed or inhibited. This suggested the role of these proteins during normal and chronic wound healing. The proteins which were down regulated in chronic wounds may be used in the management of wounds and exploited as targets for therapeutic development.

Animals↗

Comparison of commonly used clinical indicators of hypovolaemia with gastrointestinal tonometry.

OBJECTIVE: The gastrointestinal tonometer, which allows measurement of gastrointestinal mucosal CO2 and subsequent derivation of gut intramucosal pH (pHi), has been demonstrated to be a sensitive predictor of outcome following major surgery. Current theory suggests that the origin of the low pH may be hypovolaemia. This study was designed to compare the temporal sequence of changes in tonometric readings with invasive blood pressure, stroke volume, heart rate, lactate and arterial blood gas measurements during progressive haemorrhage. DESIGN: Observational healthy volunteer study. SETTING: Intensive care unit at University College London Hospitals. SUBJECTS: Six healthy, medically qualified volunteers. INTERVENTIONS: After obtaining baseline measurements, the subjects were progressively bled 25% (range = 21-31%) of their blood volume over a period of 1 h in two approximately equal aliquots. Equilibration was allowed for 30 min following the bleed, after which further measurements were made and the blood was then retransfused over 30 min. MEASUREMENTS AND MAIN RESULTS: There was no consistent change in any of the haemodynamic variables other than gastric intramucosal CO2:arterial CO2 gap (PiCO2-PaCO2) after removal of the first aliquot of blood, although five of the six subjects also demonstrated a fall in pHi. After removal of the second aliquot of blood, PiCO2-PaCO2 gap and pHi continued to indicate a worsening gastric intramucosal acidosis; stroke volume, as measured by suprasternal Doppler, demonstrated a marked fall, while all other variables measured had not altered consistently or to such a degree as to elicit a clinical response or cause suspicion of a hypovolaemic state. On retransfusion, all variables returned towards baseline. CONCLUSIONS: This study demonstrates the value of tonometry as an early monitor of hypovolaemia and highlights the shortcomings of other more commonly measured clinical variables.

Adult↗

Assessment of exposure to chemical agents and ergonomic stressors in tanneries in Kanpur, India.

In developing countries qualitative assessment of exposure at the workplace may be an essential tool in evaluating hazardous working conditions. This survey reports on qualitative assessment of exposure to chemicals, dust, and ergonomic stressors among 298 workers in 15 tanneries in Kanpur, India. In general, chemical exposure and dermal exposure were highest among beamhouse workers, less for workers involved in dry finishing activities, and lowest for those performing the wet finishing of hides. Dermal exposure was rated as high to very high during beamhouse activities, reflecting direct contact with wet hides and manual handling of hides in soak tanks. Relevant dust exposure was observed only during dry finishing activities. Most workers experienced severe postural load due to working in trunk flexion and rotation for more than 50% of their daily work time. In addition, manual materials handling with loads over 20 kg frequently occurred. The size of the tannery, in general a reflection of state of technology, showed no systematic influence on exposure profiles. The survey suggested that mechanization of material transfer and application of trolleys reduced the work time with trunk flexion and rotation and implied less manual lifting. The presence of local exhaust ventilation in large tanneries seemed to reduce the chemical exposure. This survey has demonstrated the importance of rapid appraisal techniques for evaluating hazardous conditions at the workplace. In developing countries this approach may facilitate occupational hygiene research and practice.

Dust↗