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Biomedical subjects

A Shukla

Publications and source records attributed to A Shukla.

At least 19 recordsLinked to original sources
PubMed2006

Alkylcyanoacrylate nanocapsules prepared from mini-emulsions: a comparison with the conventional approach.

Polyalkylcyanoacrylate nanocapsules are being prepared using two different types of o/w-emulsions: a conventional emulsion generated by intensive stirring with a home-made device and a mini-emulsion produced by the action of ultrasonic dispersion, using the alkylcyanoacrylate monomer as a hydrophobic agent. The emulsions and the resulting nanocapsule dispersions are compared using various methods of physical characterization. The formation of solid capsules is indicated by solid state NMR spectra and atomic force microscopy. Differences between the results of both synthetic approaches are found in terms of particle size distribution, zeta potential and tendency towards particle agglomeration. Capsules prepared by ultrasound via the mini-emulsion pathway tend to be smaller and more monodisperse. Their zeta potential is negative with larger absolute values as compared to capsules obtained from conventional emulsions, leading to stronger repulsive interactions and a higher stability against capsule agglomeration.

Cyanoacrylates↗
PubMed2004

Endothelial cells as mechanical transducers: enzymatic activity and network formation under cyclic strain.

Although it is established that endothelial cells can respond to external mechanical cues (e.g., alignment in the direction of fluid shear stress), the extent to which mechanical stress and strain applied via the endothelial cell substrate impact biomolecular and cellular processes is not well-understood. This issue is particularly important in the context of inflammation, vascular remodeling, and cancer progression, as each of these processes occurs concurrently with localized increases in strain and marked changes in molecules secreted by adjacent cells. Here, we systematically vary the level and duration of cyclic tensile strain applied to human dermal microvascular and bovine capillary endothelial cells via substrate deflection, and then correlate these cues with the secretion of extracellular matrix-degrading enzymes and a morphological transition from confluent monolayers to well-defined multicellular networks that resemble capillary tube-like structures. For a constant chemical environment, we find that super-physiological mechanical strain stimulates both endothelial cell secretion of latent matrix metalloprotease-2 and multicellular networks in a time- and strain-dependent manner. These results demonstrate coupling between the mechanical and biochemical states of microvascular endothelial cells, and indicate that elevated local stress may directly impact new capillary growth (angiogenesis) toward growing tumors and at capillary wall defect sites.

Animals↗
PubMed2003

In vivo release of oxytetracycline from a biodegradable controlled-release gel injected subcutaneously in Japanese quail (Coturnix coturnix japonica).

A long-acting, biodegradable, controlled-release formulation of oxytetracycline (CR-OTC) was evaluated in 18 adult Japanese quail (Coturnix coturnix japonica) following a single subcutaneous (s.c.) injection. Prior to characterizing the release of oxytetracycline (OTC) from the CR-OTC, the pharmacokinetic parameters of intravenously (i.v.) administered OTC were determined. Concentrations of free OTC were measured using a bioassay. The plasma concentration-time profile of OTC after a single i.v. injection at 20 mg/kg was best fit to an open two-compartmental model, with the following pharmacokinetic parameters: area under the curve (AUC) = 36.72 mg. h/L, terminal elimination half-life = 2.34 h, clearance (Cl) = 0.545 L/kg/h. Plasma [OTC] was >1.0 micro g/mL for at least 4 h following i.v. injection. The CR-OTC gel was well tolerated at a dosage of 1500 mg/kg s.c. Plasma [OTC] rose to >1.0 micro g/mL within 24 h; it remained >1.0 micro g/mL for at least 10 days in all birds sampled at that time point (n = 9) and for at least 18 days in two of nine birds. Using a deconvolution technique, it was determined that approximately 54.8% of the administered OTC was released from the CR-OTC over the 45-day observation period. This long-acting, biodegradable controlled-release OTC formulation may have potential for the treatment of chlamydophila infections and other OTC-sensitive bacteria in Japanese quail, however further studies are necessary to determine its safety and clinical application.

Animals↗
PubMed2002

Electronic interactions in the expanded metal compound Li-NH3.

Inelastic x-ray scattering was used to measure the plasmon as a function of electron density in liquid lithium ammonia as well as the low temperature solid phase. As the electronic density is lowered, electronic correlation effects cause the random-phase approximation (RPA) to break down, requiring more advanced theoretical treatments. The deviation from RPA becomes greatest at the lowest electronic densities. We also see evidence for decreased electronic screening as shown by an increase in the strength of the pseudopotential at lower concentrations. Plasmon behavior in the solid is similar to that of the heavier alkali metals, but surprisingly different than in the liquid.

Journal Article↗
PubMed2002

New spectroscopy solves an old puzzle: the Kondo scale in heavy fermions.

Resonant inelastic x-ray scattering (RIXS) yields clear evidence of spectroscopic Kondo scales in heavy fermions. In YbInCu4 and YbAgCu4 RIXS probes the Yb2+ component of the hybrid ground state and the temperature dependence of the Yb 4f occupation. We report a sudden valence change at a phase transition in YbInCu4, but a continuous temperature dependence in YbAgCu4, consistent with the predictions of the Anderson impurity model, for a Kondo temperature T(K) = 70 K. These results solve a long-standing controversy and establish RIXS as a quantitative probe of the electronic structure of strongly correlated electron systems.

Journal Article↗
PubMed2002

Anomalous dispersion of longitudinal optical phonons in Nd(1.86)Ce(0.14)CuO(4+delta) determined by inelastic x-ray scattering.

The phonon dispersions of Nd(1.86)Ce(0.14)CuO(4+delta) along the [xi,0,0] direction have been determined by inelastic x-ray scattering. Compared to the undoped parent compound, the two highest longitudinal phonon branches, associated with the Cu-O bond stretching and out-of-plane oxygen vibration, are shifted to lower energies. Moreover, an anomalous softening of the bond-stretching band is observed at about q = (0.2,0,0). These signatures provide evidence for strong electron-phonon coupling in this electron-doped high-temperature superconductor.

Journal Article↗
PubMed2002

Bioconversion of 3 beta-acetoxypregna-5,16-diene-20-one to androsta-1,4-diene-3,17-dione by mixed bacterial culture.

AIMS: To isolate a bacterium capable of degrading 3 beta-acetoxypregna-5,16-diene-20-one (16-DPA) to androsta-1,4-diene-3,17-dione (ADD) and to decipher the biodegradation pathway. METHODS AND RESULTS: Isolation on mineral salt agar containing 16-DPA as sole carbon source yielded two bacteria identified as Pseudomonas diminuta and Comamonas acidovorons. These bacteria failed to degrade 16-DPA individually in pure cultures but converted 16-DPA to ADD in a mixed culture. The intermediates accumulated during the bioconversion were identified as pregna-4,16-diene-3,20-dione and pregna-1,4,16-triene-3,20-dione. CONCLUSIONS: The degradation pattern of 16-DPA by mixed bacterial culture revealed the reaction sequence as (i) cleavage of C-3 acetyl function, (ii) dehydrogenation at C-1 and C-2 positions and (iii) cleavage of C-17 side-chain. SIGNIFICANCE AND IMPACT OF THE STUDY: The present work opens a new approach towards the production of a female sex hormone precursor and elucidates the biodegradation pathway of 16-DPA by mixed bacterial culture.

Androstadienes↗
PubMed2001

Identification of three new splice variants of the SNARE protein SNAP-23.

SNAP-23 has an important role in protein-trafficking processes in mammalian cells and until yet two isoforms of SNAP-23 (SNAP-23a and SNAP-23b) have been described. In the present report, we have identified the existence of three new SNAP-23 isoforms (named SNAP-23c, SNAP-23d, and SNAP-23e), which arise from alternative splicing. By RT-PCR all five splice variants were shown to be expressed in four different human inflammatory cells (eosinophils, basophils, neutrophils, and peripheral blood mononuclear cells). Transfection of the human basophilic KU-812 cell line with plasmid constructs containing the cDNAs of the five splice variants located SNAP-23a and SNAP-23b primarily in the plasma membrane. The other three splice variants were localized both intracellularly and in the plasma membrane.

Alternative Splicing↗
PubMed2001

The removal of heavy metals from aqueous solutions by sawdust adsorption--removal of lead and comparison of its adsorption with copper.

In this work, sorption of lead on sawdust (SD) has been studied by using batch techniques. Similar to the sorption of copper, the equilibrium sorption levels for lead is a function of the solution pH, contact time, sorbent and sorbate concentration. The equilibrium adsorption capacity of sawdust for lead was measured and extrapolated using linear Freundlich and Langmuir isotherms and compared with that for copper. Metal ions which are bounded to the sawdust could be stripped by acidic solution so that the sawdust can be recycled. Non-equilibrium experiments were done by using glass columns. The results indicate the potentially practical value of this method in industries and also provide strong evidence to support the adsorption mechanism proposed. Even though the focus of this work is on lead, some results from previous study for copper have been incorporated here for sake of comparison.

Adsorption↗
PubMed2001

Silica-induced activation of c-Jun-NH2-terminal amino kinases, protracted expression of the activator protein-1 proto-oncogene, fra-1, and S-phase alterations are mediated via oxidative stress.

Crystalline silica has been classified as a group 1 human carcinogen in the lung. However, its mechanisms of action on pulmonary epithelial cells which give rise to lung cancers are unclear. Using a nontransformed alveolar type II epithelial cell line (C10), we show that alpha-quartz silica causes persistent dose-related increases in phosphorylation of c-Jun-NH2-terminal amino kinases (JNKs) that are inhibited by antioxidants (P < or = 0.05). Increases in activator protein-1 (AP-1) binding to DNA and transactivation of AP-1-dependent gene expression by silica were accompanied by increases in steady-state mRNA levels of the AP-1 family members, c-jun, junB, fra-1, and c-fos at 8 h and elevated mRNA levels of fra-1 at 24 h (P < or = 0.05). Addition of tetramethylthiourea inhibited silica-associated increases infra-1 and proportions of cells in S-phase (P < or = .05). Our findings indicate that silica induces JNK activity, AP-1-dependent gene expression, ie., fra-1, and DNA synthesis via oxidative stress. Moreover, they suggest that silica may act mechanistically as a mitogen or tumor promoter, rather than a genotoxic carcinogen, in the development of lung cancers.

Animals↗
PubMed2001

A new spectrophotometric method for the determination of total and ferric iron in rain water at the ppb level.

A new, simple, selective and sensitive spectrophotometric procedure for the on-site quantification of iron at nano-gram levels in atmospheric precipitations, i.e. rain as sample source is described. It is based on the color reaction of Fe3+ with SCN- ions in the presence of a cationic surfactant, i.e. cetylpyridinium chloride (CPC), in strong HCl solution, and subsequent extraction of the complex with N-octylacetamide into toluene or chloroform. The apparent molar absorptivity of the complex is 2.60 x 10(5) L mol(-1) cm(-1) at lambdamax = 480 nm at an enrichment factor (EF) of 10. The detection limit (causing higher absorbance than the sum of the blank absorbance (0.009) and 3 SD) is 5 ng mL(-1) Fe. Ions commonly associated with iron did not interfere in the present method. The effect of analytical variables, i.e. amount and type of the reagents, acidity, solvent, temperature, dilution, etc., in the determination of iron are discussed. The validity of the present method is checked with GF-AAS. The method has been applied to the determination of iron at the ppb level in rain water samples.

Journal Article↗
PubMed2001

Mode of action of intranasal corticosteroids.

The mode of action of intranasal corticosteroids (INCS) is complex. It is not known whether INCS penetrate the nasal mucosa or act on target cells; however, their low systemic activity supports the concept of local action on nasal mucosa. This local effect can nonetheless influence a variety of inflammatory cells and their mediators such as epithelial cells, lymphocytes, basophils, mast cells, and Langerhans cells. Corticosteroid-induced inhibition of immunoglobulin E-dependent release of histamine is a possible but unproven mode of action. Epithelial cells are an important target for corticosteroids, and INCS concentration is high at the epithelial surface. INCS may combine with the corticosteroid receptors in epithelial cells, which are then expelled into the airway lumen together with the dead epithelial cells or migrating inflammatory cells. A reduced influx of mediator cells may explain some of the effects of INCS on rhinitis symptoms, but it cannot explain all of the effects because INCS also reduce the early-phase sneezing and rhinorrhea after an allergen challenge outside the pollen season. In this situation, the number of surface mast cells/basophils is very low, as it is in the absence of allergic rhinitis. The mechanism by which INCS treatment of allergic rhinitis reduces itching, sneezing, and rhinorrhea, the characteristic symptoms of an early-phase response involving mast cell release of histamine, remains to be determined. Studies should be conducted to characterize the broad range of mechanisms by which INCS produce their therapeutic effects in allergic rhinitis.

Administration, Intranasal↗
PubMed2001

Genetic adaptive neural network to predict biochemical failure after radical prostatectomy: a multi-institutional study.

BACKGROUND AND PURPOSE: Despite many new procedures, radical prostatectomy remains one of the commonest methods of treating clinically localized prostate cancer. Both from the physician's and the patient's point of view, it is important to have objective estimation of the likelihood of recurrence, which forms the foundation for treatment selection for an individual patient. Currently, it is difficult to predict the probability of biochemical recurrence (rising serum prostate specific antigen [PSA] concentration) in an individual patient, and approximately 30% of the patients do experience recurrence. Tools predicting the recurrence will be of immense practical utility in the treatment selection and planning follow up. We have utilized preoperative parameters through a computer based genetic adaptive neural network model to predict recurrence in such patients, which can help primary care physicians and urologists in making management recommendations. PATIENTS AND METHODS: Fourteen hundred patients who underwent radical prostatectomy at participating institutions form the subjects of this study. Demographic data such as age, race, preoperative PSA, systemic biopsy based staging and Gleason scores were used to construct a neural network model. This model simulated the functioning of a trained human mind and learned from the database. Once trained, it was used to predict the outcomes in new patients. RESULTS: The patients in this comprehensive database were representative of the average prostate cancer patients as seen in USA. Their mean age was 68.4 years, the mean PSA concentration before surgery was 11.6 ng/mL, and 67% patients had a Gleason sum of 5 to 7. The mean length of follow-up was 41.5 months. Eighty percent of the cancers were clinical stage T2 and 5% T3. In our series, 64% of patients had pathologically organ-confined cancer, 33% positive margins, and 14% had seminal vesicle invasion. Lymph node positive patients were not included in this series. Progression as judged by serum PSA was noted in 30.6%. With entry of a few routinely used parameters, the model could correctly predict recurrence in 76% of the patients in the validation set. The area under the curve was 0.831. The sensitivity was 85%, the specificity 74%, the positive predictive value 77%, and the negative predictive value of 83%. CONCLUSION: It was possible to predict PSA recurrence with a high accuracy (76%). Physicians desiring objective treatment counseling can use this model, and significant cost savings are anticipated because of appropriate treatment selection and patient-specific follow-up protocols. This technology can be extended to other treatments such as watchful waiting, external-beam radiation, and brachytherapy.

Aged↗
PubMed2001

SNAP-25-associated Hrs-2 protein colocalizes with AQP2 in rat kidney collecting duct principal cells.

The vasopressin-induced trafficking of aquaporin-2 (AQP2) water channels in kidney collecting duct is likely mediated by vesicle-targeting proteins (N-ethylmaleimide-sensitive factor attachment protein receptors). Hrs-2 is an ATPase believed to have a modulatory role in regulated exocytosis. To examine whether Hrs-2 is expressed in rat kidney, we carried out RT-PCR combined with DNA sequence analysis and Northern blotting using a digoxigenin-labeled Hrs-2 RNA probe. RT-PCR and Northern blotting revealed that Hrs-2 mRNA is localized in all zones of rat kidney. The presence of Hrs-2 protein in rat kidney was confirmed by immunoblotting, revealing a 115-kDa protein in kidney and brain membrane fractions corresponding to the expected molecular size of Hrs-2. Immunostaining and confocal laser scanning microscopy of LLC-PK(1) cells (a porcine proximal tubule cell line) transfected with Hrs-2 DNA confirmed the specificity of the antibody and revealed that Hrs-2 is mainly localized in intracellular compartments, including cathepsin D-containing lysosomal/endosomal compartments. The cellular and subcellular localization of Hrs-2 in rat kidney was examined by immunocytochemistry and confocal laser scanning microscopy. Hrs-2 immunoreactivity was observed in collecting duct principal cells, and weaker labeling was detected in other nephron segments. The labeling was predominantly present in intracellular vesicles, but labeling was also observed in the apical plasma membrane domains of some cells. Colabeling with AQP2 revealed colocalization in vesicles and apical plasma membrane domains, suggesting a role for Hrs-2 in regulated AQP2 trafficking.

Adenosine Triphosphatases↗
PubMed2001

A clinico-epidemiological study of organophosphorus poisoning at a rural-based teaching hospital in eastern Nepal.

Thirty-seven patients with severe organophosphorus poisoning (OPP) presented to the emergency ward of BP Koirala Institute of Health Sciences between January 1995 and December 1996. The mean age of patients was 26.9 years. There were 17 (46%) males and 20 (54%) females, with male:female ratio being 1:1.2.Twenty-three (62%) patients were unmarried with 16 (46%) of them students. The most common reason for poisoning was suicide--32 patients (86.5%). The most commonly involved compound was Metacid (methyl-parathion)--23 (62%) patients. Ninety per cent of the patients presented within 2 h of ingestion. All patients were managed with intravenous atropine. Pralidoxime was given to patients with nicotinic symptoms and mechanical ventilation initiated in patients with respiratory distress. The mean dose of atropine used in the first 24 h and during the hospital stay was 30.6 mg and 136.7 mg, respectively. The mean duration of treatment was 5.5 days (range 2-20 days). Two patients developed intermediate syndrome and the overall mortality among hospitalized patients was 8%.

Adolescent↗
PubMed2001

Mumps with cerebellar encephalitis.

A 30 years male patient, having typical symptoms of mumps, presented with acute cerebellar ataxia two days after the onset of parotid enlargement. The neurological symptoms showed complete recovery over the subsequent six weeks, suggestive of para-infectious cerebellar demyelination due to mumps.

Adult↗