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Biomedical subjects

N Agrawal

Publications and source records attributed to N Agrawal.

At least 19 recordsLinked to original sources

Laparoscopic feeding jejunostomy in esophagogastric cancer.

BACKGROUND: Patients with esophagogastric malignancies often require nutritional supplementation in the perioperative period, especially in the setting where neoadjuvant therapy may delay tumor resection. A simple technique is described here that can be performed at the time of staging laparoscopy and that has not been described before. RESULTS: Forty-three patients treated over a 4-year period who had a laparoscopic feeding jejunostomy placed at the time of staging laparoscopy were reviewed. Of these, 35 had preoperative chemotherapy according to a modified MRC OEO2 protocol. In the period between staging and eventual resection, 32% required immediate feeding, and in 14% of those who were thought not to need feeding it later became necessary. More patients gained weight or had a rise in albumin in the group that had jejunal feeding (p < 0.05). The mean time to surgery was 10 weeks. There were no conversions to an open procedure, nor were there any laparotomies for tube-related complications. Dislodgement was recorded in 6 patients; blockage, in 4. In most of these cases a simple bedside replacement of the tube was all that was required. Mean time in the operating room for each procedure was 44 minutes. CONCLUSIONS: Laparoscopic percutaneous feeding jejunostomy is a safe and simple technique that adds little to the morbidity and cost of managing patients with esophagogastric cancers. It facilitates optimization of nutrition in the perioperative period for these patients, especially in those receiving preoperative chemotherapy.

Adult↗

Laryngeal cancer after topical mitomycin C application.

Mitomycin C is part of the mitomycin group of antibiotics and has found use in medicine in the treatment of various cancers, including those of the head and neck. In recent years, it has gained popularity as a topical treatment to prevent scar formation in the larynx and choanae in paediatric and adult inflammatory processes. Also, this alkylating agent is potentially a potent carcinogen. We report the first case in the world literature of laryngeal carcinoma in a non-smoking adult, which may have been induced by topical mitomycin C application to a glottic web. We discuss the mechanism of action of this drug, and we advise caution on its use for benign laryngeal pathologies.

Administration, Topical↗

Diplectanids infesting the gills of the barramundi Lates calcarifer (Bloch) (Perciformes: Centropomidae), with the proposal of Laticola n. g. (Monogenoidea: Diplectanidae).

Four species of the Monogenoidea, Laticola lingaoensis n. sp., L. latesi (Tripathi, 1957) n. comb. [previously Pseudorhabdosynochus latesi (Tripathi, 1957) Kritsky & Beverley-Burton, 1986], L. paralatesi (Nagibina, 1976) n. comb. [previously Diplectanum paralatesi Nagibina, 1976] and Diplectanum penangi Liang & Leong, 1991, are reported from the gills of Lates calcarifer (Centropomidae) from the South China Sea (new geographical records for L. latesi and D. penangi). Collections from off Bathurst Island, Northern Territory, Australia, represent a new geographic record for L. paralatesi; Chilka Lake, Orissa, India, is established as the type-locality for L. latesi. Laticola n. g. (Diplectanidae) is proposed for species with a spoon-shaped copulatory organ with two to four concentric incomplete ridges in the base. Laticola lingaoensis, the type-species of Laticola, is described, and L. latesi and L. paralatesi are redescribed based on specimens from the South China Sea. Pseudorhabdosynochus monosquamodiscusi Balasuriya & Leong, 1995 and Pseudorhabdosynochus yangjiangenesis Wu & Li, 2005 are considered junior subjective synonyms of L. latesi and L. paralatesi, respectively.

Animals↗

Radiation-induced in vitro phototoxic potential of some fluoroquinolones.

Photosensitizing drugs that can damage cellular biomolecules is a matter of concern. Lomefloxacin, norfloxacin, ofloxacin, and enoxacin (broad-spectrum antibiotics of fluoroquinolone group) are used for the treatment of Gram-positive and Gram-negative bacterial infections. Phototoxicity and possible mechanism of their action was assessed under the exposure of ambient levels of UV-A, UV-B, and sunlight at a concentration generally used in the treatment of various diseases. Singlet oxygen (1O2), superoxide anion radical (O2.-) generation, DNA damage, and lipid peroxidation in human blood were studied. All the fluoroquinolones tested in this study produced 1O2 and O2.- under exposure to UV-A, UV-B, and sunlight depending on the concentrations (0 to 60 microg/mL) of the drugs. Enoxacin showed a higher yield of 1O2 and O2.- than other drugs. These materials also degraded deoxyguanosine and induced lipid peroxidation in vitro under exposure to UV-A, UV-B, and sunlight (depending on the dose of radiation). The formation of the reactive oxygen species (ROS) by the photoexcited drugs may be considered as a possible mechanism of their action.

Anti-Bacterial Agents↗

The routine use of intra-operative ultrasound in patients with colorectal cancer improves the detection of hepatic metastases.

INTRODUCTION: Up to one fifth of patients with carcinoma of the colon have occult liver metastases at the time of presentation. Intra-operative hepatic ultrasonography might improve disease staging. We report the use of intra-operative ultrasonography (IOUS) in routine clinical practice over a five-year period. METHOD: Seventy-six patients with colorectal carcinoma (F 21, M 55) of median age 67 years (range 43-89 years) for whom full data were available had IOUS at the time of colonic resection. All patients had had a computerized tomography (CT), magnetic resonance imaging (MRI) or ultrasonography (USS). RESULTS: Of 76 patients, 10 had a Dukes A, 32 had a Dukes B and 34 a Dukes C carcinoma. In 20 patients IOUS detected lesions not seen on pre-operative scanning including 11 metastases (one suitable for resection), seven benign hepatic cysts and two were benign hepatic nodules. Forty-nine patients have remained free of disease and 25 have died with systemic disease (mean survival 10 months, range 2-24 months). In the seven patients diagnosed as having hepatic cysts at IOUS two have died of systemic disease. The remaining patients (n=12) who died with systemic disease had a negative IOUS. CONCLUSION: IOUS increases diagnostic yield but a significant proportion of patients with occult hepatic metastases are not detected. IOUS improves disease staging in some patients refining the indications for adjuvant therapy and enhancing the estimate of prognosis and improving decision-making.

Adult↗

Endosulfan degradation by a Rhodococcus strain isolated from earthworm gut.

A Rhodococcus MTCC 6716 bacterial strain was isolated apparently for the first time from the gut microflora of an Indian earthworm (Metaphire posthuma). Endosulfan was used as a carbon source by the strain and degraded it up to 92.58% within 15 days. Furthermore, the isolated strain of the bacterium did not produce the persistent form of the toxic metabolite endosulfan sulfate. This strain exhibits luxury growth in minimal medium with high concentrations of endosulfan (80 microg mL(-1)). Degradation of the endosulfan occurred simultaneously with bacterial growth and an increase in chloride ion (87.1%) in the growth medium, suggesting nearly complete degradation of the insecticide. This strain is able to tolerate 45 degrees C and retain its degradation potential even under sunlight exposure. Since endosulfan is used worldwide for pest control and its residues have been retained for long periods in soil, water, and agricultural products, the strain isolated by us is valuable for bioremediation of endosulfan-contaminated soil and water.

Animals↗

Morphological and metabolic alterations in duckweed (Spirodela polyrhiza) on long-term low-level chronic UV-B exposure.

Laboratory grown duckweed (Spirodela polyrhiza) plants were exposed to 0.72 and 1.44J of UV-B radiation daily for 7 days at 0.4mW/cm(2) intensity. Chlorosis and necrosis were observed along with depletion in protein, pigments (chlorophyll, pheophytin, carotenoids, phycoerythrin, phycocyanin, and flavoxanthin), biomass, root length, and frond size in UV-B-exposed plants. The study confirms morphological and metabolic alterations leading to reduction in the productivity of duckweed following long-term exposure to UV-B radiation.

Araceae↗

Reduced incidence of upper gastrointestinal ulcer complications with the COX-2 selective inhibitor, valdecoxib.

AIM: In a predefined analysis, data were pooled from eight blinded, randomized, controlled trials, and separately from three long-term, open-label trials to determine the rate of upper gastrointestinal ulcer complications with the cyclo-oxygenase-2 selective inhibitor, valdecoxib, vs. non-selective non-steroidal anti-inflammatory drugs. METHODS: In randomized, controlled trials, 7434 osteoarthritis and rheumatoid arthritis patients received placebo (n = 973), valdecoxib 5-80 mg daily (n = 4362), or a non-selective non-steroidal anti-inflammatory drug (naproxen, ibuprofen or diclofenac; n = 2099) for 12-26 weeks. In long-term, open-label trials, 2871 patients received valdecoxib 10-80 mg daily for up to 1 year. All potential events were reviewed by a blinded, independent review committee based on a priori definitions of ulcer complications (perforations, obstructions, bleeds). RESULTS: In randomized, controlled trials, 19 of 955 potential events were adjudicated to be ulcer complications. Valdecoxib was associated with a significantly lower ulcer complication rate than non-selective non-steroidal anti-inflammatory drugs (0.68% vs. 1.96%, all patients; 0.29% vs. 2.08%, non-aspirin users; P < 0.05). In long-term, open-label trials, seven of 310 potential events were adjudicated to be ulcer complications; the annualized incidence for valdecoxib was 0.39% (seven of 1791 patient-years) for all patients and 0.2% (three of 1472 patient-years) for non-aspirin users. CONCLUSIONS: Valdecoxib, including above recommended doses, is associated with a significantly lower rate of upper gastrointestinal ulcer complications than therapeutic doses of non-selective non-steroidal anti-inflammatory drugs.

Adult↗

Role of multidetector CT virtual bronchoscopy in the evaluation of post-tracheostomy tracheal stenosis--a preliminary study.

AIM: To study the technique and utility of virtual bronchoscopy (virtual reality endobronchial simulation, VRES) as a tool to evaluate post-tracheostomy tracheal stenoses and to correlate the findings of virtual and invasive bronchoscopy and to follow-up treated lesions or those currently under treatment that were initially diagnosed with VRES. METHODOLOGY: This prospective study comprised nine patients in the age group 13 to 65 years presenting with breathlessness and stridor following one or multiple tracheostomies. They underwent plain CT using a multidetector CT (MDCT) scanner (Siemens Volume Zoom) using narrow (1 mm) collimation. These thin slice images were post-processed using an Irix-based workstation with a 'Fly-Through' endoscopy application. These patients also underwent a rigid (three patients) or fiberoptic (six patients) bronchoscopy. RESULTS: Of the nine patients that underwent VRES, five were found to have stenoses, three had obstructing granulation tissue, one had an obstructing membrane and one had synechiae. The invasive bronchoscopic findings supported the VRES diagnosis in all but one case of stenosis, one of granulation tissue and the case with synechiae. Membranes and synechiae were relatively difficult to diagnose without the corresponding axial and multiplanar images. VRES achieved a higher sensitivity, while invasive bronchoscopy a higher specificity. CONCLUSIONS: VRES proved to be comparable to invasive bronchoscopy in the depiction of post-tracheostomy tracheal stenoses, with a notable advantage in critical stenoses in that the airway distal to the stenosis could be assessed with VRES but not with invasive bronchoscopy. A preliminary VRES was found to be of assistance in the selection of patients for the more invasive therapeutic procedures such as laser ablation of granulation tissue and its follow-up.

Adolescent↗

Simultaneous determination of unlabeled and carbon-13-labeled etoricoxib, a new cyclooxygenase-2 inhibitor, in human plasma using HPLC-MS/MS.

A method for the simultaneous determination of etoricoxib and its carbon-13 analog ((13)C(6)-etoricoxib) from human plasma has been developed and used to support bioavailability studies. Plasma samples (0.5 mL) were extracted by using a 3M Empore 96-well plate (C(8)) and the resulting extracts were analyzed by using a PE-Sciex API-3000 HPLC-MS/MS with a heated nebulizer interface (500 degrees C). The method was validated with two different calibration curve ranges, one for etoricoxib (5 to 2500 ng/mL) determined in the presence of lower concentrations of (13)C(6)-etoricoxib (0.5 to 250 ng/mL), and a second curve for the quantitation of similar concentrations of both etoricoxib and (13)C(6)-etoricoxib (0.5 to 250 ng/mL). Extraction recoveries of etoricoxib, (13)C(6)-etoricoxib, and a methylated internal standard were >70% over the range of concentrations included in both calibration curves. Intraday precision and accuracy for the quantitation of etoricoxib were 7.8% relative standard deviation (RSD) or less and within 3.4% respectively over the range of 5 to 2500 ng/mL, and 10.8% RSD or less and within 4 % respectively over the range of 0.5 to 250 ng/mL. Within-batch precision and accuracy for the quantitation of (13)C(6)-etoricoxib over the range of 0.5 to 250 ng/mL were 8.3% RSD or less and within 2.3%, respectively. The validated assay was used in support of human clinical trials.

Carbon Isotopes↗

Persistent sodium channel activity mediates subthreshold membrane potential oscillations and low-threshold spikes in rat entorhinal cortex layer V neurons.

Entorhinal cortex layer V occupies a critical position in temporal lobe circuitry since, on the one hand, it serves as the main conduit for the flow of information out of the hippocampal formation back to the neocortex and, on the other, it closes a hippocampal-entorhinal loop by projecting upon the superficial cell layers that give rise to the perforant path. Recent in vitro electrophysiological studies have shown that rat entorhinal cortex layer V cells are endowed with the ability to generate subthreshold oscillations and all-or-none, low-threshold depolarizing potentials. In the present study, by applying current-clamp, voltage-clamp and single-channel recording techniques in rat slices and dissociated neurons, we investigated whether entorhinal cortex layer V cells express a persistent sodium current and sustained sodium channel activity to evaluate the contribution of this activity to the subthreshold behavior of the cells. Sharp-electrode recording in slices demonstrated that layer V cells display tetrodotoxin-sensitive inward rectification in the depolarizing direction, suggesting that a persistent sodium current is present in the cells. Subthreshold oscillations and low-threshold regenerative events were also abolished by tetrodotoxin, suggesting that their generation also requires the activation of such a low-threshold sodium current. The presence of a persistent sodium current was confirmed in whole-cell voltage-clamp experiments, which revealed that its activation "threshold" was negative by about 10mV to that of the transient sodium current. Furthermore, stationary noise analysis and cell-attached, patch-clamp recordings indicated that whole-cell persistent sodium currents were mediated by persistent sodium channel activity, consisting of relatively high-conductance ( approximately 18pS) sustained openings. The presence of a persistent sodium current in entorhinal cortex layer V cells can cause the generation of oscillatory behavior, bursting activity and sustained discharge; this might be implicated in the encoding of memories in which the entorhinal cortex participates but, under pathological situations, may also contribute to epileptogenesis and neurodegeneration.

Action Potentials↗

Spatial regulation of DELTA expression mediates NOTCH signalling for segmentation of Drosophila legs.

The Notch (N) signalling pathway is recruited for segregation of cell fates in a number of Drosophila tissue types. We show here that N dependent segmentation of Drosophila legs is regulated by a dynamic pattern of expression of its ligand, DELTA (DL). During third larval instar and early stages of pupation, high levels of DL expression is seen in stripes of cells in the leg imaginal discs which later form the proximal borders of leg joints. These domains also displayed heightened Dl enhancer activity. During subsequent stages of pupation, following segmentation of the leg primordium, DL expression becomes uniform throughout these segments barring the joints. We further show that regulatory Dl mutations or mis-expression of DL abolish leg segmentation. Domains of N signalling for segmentation of legs of flies are thus set up by a stringent spatial regulation of expression of its ligand at the segment border. Further, a comparable role of DL in antennal development reveals a common paradigm of DL-N signalling for segmentation of appendages in flies.

Animals↗

Role of human liver cytochrome P4503A in the metabolism of etoricoxib, a novel cyclooxygenase-2 selective inhibitor.

Etoricoxib, a potent and selective cyclooxygenase-2 inhibitor, was shown to be metabolized via 6'-methylhydroxylation (M2 formation) when incubated with NADPH-fortified human liver microsomes. In agreement with in vivo data, 1'-N'-oxidation was a relatively minor pathway. Over the etoricoxib concentration range studied (1-1300 microM), the rate of hydroxylation conformed to saturable Michaelis-Menten kinetics (apparent K(m) = 186 +/- 84.3 microM; V(max) = 0.76 +/- 0.45 nmol/min/mg of protein; mean +/- S.D., n = 3 livers) and yielded a V(max)/K(m) ratio of 2.4 to 7.3 microl/min/mg. This in vitro V(max)/K(m) ratio was scaled, with respect to yield of liver microsomal protein and liver weight, to obtain estimates of M2 formation clearance (3.1-9.7 ml/min/kg of b.wt.) that agreed favorably with in vivo results (8.3 ml/min/kg of b.wt.) following i.v. administration of [(14)C]etoricoxib to healthy male subjects. Cytochrome P450 (P450) reaction phenotyping studies-using P450 form selective chemical inhibitors, immunoinhibitory antibodies, recombinant P450s, and correlation analysis with microsomes prepared from a bank of human livers-revealed that the 6'-methyl hydroxylation of etoricoxib was catalyzed largely (approximately 60%) by member(s) of the CYP3A subfamily. By comparison, CYP2C9 (approximately 10%), CYP2D6 (approximately 10%), CYP1A2 (approximately 10%), and possibly CYP2C19 played an ancillary role. Moreover, etoricoxib (0.1-100 microM) was found to be a relatively weak inhibitor (IC(50) > 100 microM) of multiple P450s (CYP1A2, CYP2D6, CYP3A, CYP2E1, CYP2C9, and CYP2C19) in human liver microsomes.

Animals↗

Evaluation of oxidative stress before and after haemodialysis in chronic renal failure.

OBJECTIVE: To evaluate the oxidative stress before and after haemodialysis in chronic renal failure patients. METHODS: A prospective study comprising of 22 patients of CRF who have to receive their first haemodialysis. All patients were subjected to standard four hours haemodialysis. The parameters of oxidative stress i.e. erythrocyte malonaldehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) were measured before and after haemodialysis. RESULTS: The value of mean erythrocyte MDA (9.40 +/- 3.36 mumol/L) and SOD (617 +/- 64.33 units/ml) were significantly higher in patients of CRF before haemodialysis than in controls (p < 0.001). The mean GSH levels were significantly lower (451 +/- 63.91 micrograms/ml) in patients than in controls before haemodialysis (p < 0.001). After haemodialysis MDA levels further increased (12.27 +/- 4.38 mumol/L), SOD levels decreased (458 +/- 69.58 EU/ml) and GSH levels further decreased (396 +/- 41.41 micrograms/ml) (p < 0.001). CONCLUSIONS: There was an evidence of oxidative stress in patients of CRF before haemodialysis which increased further after haemodialysis, the mechanisms of which is not delineated. The procedural factors may be contributing in the increased oxidative stress after haemodialysis.

Adult↗

Negative regulation of dorsoventral signaling by the homeotic gene Ultrabithorax during haltere development in Drosophila.

Growth and patterning during Drosophila wing development are mediated by signaling from its dorsoventral (D/V) organizer. In the metathorax, wing development is essentially suppressed by the homeotic selector gene Ultrabithorax (Ubx) to mediate development of a pair of tiny balancing organs, the halteres. Here we show that expression of Ubx in the haltere D/V boundary down-regulates its D/V organizer signaling compared to that of the wing D/V boundary. Somatic loss of Ubx from the haltere D/V boundary thus results in the formation of a wing-type D/V organizer in the haltere field. Long-distance signaling from this organizer was analyzed by assaying the ability of a Ubx(-) clone induced in the haltere D/V boundary to effect homeotic transformation of capitellum cells away from the boundary. The clonally restored wing D/V organizer in mosaic halteres not only enhanced the homeotic transformation of Ubx(-) cells in the capitellum but also caused homeotic transformation of even Ubx(+) cells in a genetic background known to induce excessive cell proliferation in the imaginal discs. In addition to demonstrating a non-cell-autonomous role for Ubx during haltere development, these results reveal distinct spatial roles of Ubx during maintenance of cell fate and patterning in the halteres.

Animals↗