Biomedical subjects

N Bansal

Publications and source records attributed to N Bansal.

At least 37 records · Page 2Linked to original sources

PubMed1998

Homologated aza analogs of arabinose as antimycobacterial agents.

A series of hydrolytically-stable aza analogs of arabinofuranose was prepared and evaluated against Mycobacterium tuberculosis and M. avium. The compounds were designed to mimic the putative arabinose donor involved in biogenesis of the essential cell wall polysaccharide, arabinogalactan. Though most compounds displayed little activity in cell culture, one compound showed significant activity in infected macrophage models.

Animals↗

PubMed1998

Temporal characteristics of NMR signals from spin 3/2 nuclei of incompletely disordered systems.

Anisotropic nuclear quadrupole interactions can produce residual quadrupole splitting in the NMR spectra of rapidly moving quadrupolar nuclei in incompletely disordered aqueous heterogeneous systems. Such systems may include hydrated sodium nuclei in biological tissue and biopolymer gels. To describe the NMR signals from such samples, we use a domain model in which each domain is characterized by a quadrupole frequency and a residence time of the nucleus. We show that the signals from each domain after one pulse, the quadrupole echo sequence, and the various multiple quantum filters (MQFs) can be expressed as a linear combination of five different phase coherences. To simulate the effect of various distributions (Pake powder pattern, Gaussian, etc.) of quadrupole frequencies for different domains on the NMR signal, we have written the computer program CORVUS. CORVUS also includes the effects of exchange between different domains using diffusion and random jump models. The results of computer simulations show that the Gaussian and Pake powder pattern quadrupole frequency distributions produce very different phase coherences and observable NMR signals when the exchange rate (1/taue) between different domains is slow. When 1/taue is similar to the root mean square quadrupole frequency (final sigma), the signals from the two distributions are similar. When 1/taue is an order of magnitude greater than final sigma, there is no apparent evidence of quadrupole splitting in the shape of the signal following one pulse, but the residual effects of the quadrupole splitting make a significant contribution to the fast transverse relaxation rate. Therefore, in this case, it is inappropriate to use the observed biexponential relaxation rates to obtain a single correlation time. The quadrupole echo and the various MQF signals contain an echo from the satellite transitions in the presence of quadrupole splitting. The peak of this echo is very sensitive to 1/taue. The time domain analysis of these signals is more direct and less ambiguous than the frequency domain analysis because the echo does not occur at the beginning of data acquisition. The quadrupole echo pulse sequence is the most sensitive detector of residual quadrupole splitting and exchange of sodium ions between different domains. However, if the sample is compartmentalized so that only a fraction of the nuclei have quadrupole splitting, the double quantum magic angle filter (DQ-MA) is more suitable. This is because the DQ-MA signal contains only the contributions from satellite transitions. Use of simulations to analyze signals from various one-pulse, quadrupole echo, and multiple quantum filter pulse sequences can yield information on substrate order and aid in quantitation of multiple quantum filter signals.

Algorithms↗

PubMed1998

Quantitation of intracellular [Na+] in vivo by using TmDOTP5- as an NMR shift reagent and extracellular marker.

A method is presented to measure the absolute concentration of intracellular Na+ ([Na+]i) in vivo by using interleaved 23Na- and 31P-nuclear magnetic resonance (NMR) spectroscopy and TmDOTP5- as shift reagent and chemical marker of tissue extracellular space (ECS). The technique was used to determine [Na+]i and relative ECS in livers of control rats (21 +/- 3 and 0.11 +/- 0.02 mM, respectively) and in rats exposed to carbon tetrachloride (103 +/- 29 and 0.23 +/- 0.03 mM, respectively). The NMR measurements were confirmed independently on excised tissue samples by using atomic absorption spectroscopy. The results confirm that TmDOTP5- can be used as a combined cation shift reagent and ECS marker, thereby allowing quantitation of [Na+]i in vivo by NMR.

Animals↗

PubMed1998

Combining aspirin with angiotensin converting enzyme inhibitors in heart failure: how safe is it?

The above discussion on the interaction of aspirin and ACE inhibitors seems to suggest that aspirin in high doses may have adverse interaction with ACE inhibitors in patients with heart failure but the data obtained is not sufficient or conclusive to recommended omission of aspirin in patients with heart failure. This raises a query in the mind of the physician whether to use a combination or not? The role of aspirin in the early period after myocardial infarction is well established so is the role of ACE inhibitors. Hence in patients with myocardial infarction and preserved left ventricular function it would not be wrong to administer combination of ACE inhibitors and aspirin. Albeit at a lower dose. In patients with large myocardial infarction or heart failure, warfarin may be an option but still needs to be documented in large trials. As suggested long term use of aspirin after infarction is still ambiguous and may be harmful in patients with heart failure with its anticedent side effects. But long term benefits of ACE inhibitors in heart failure are well documented. Hence if a choice has to be made whether to discontinue either of the two drugs it would be preferable to stop the aspirin. To answer the issue of use of aspirin in patients with heart failure it would be essential to conduct a double blind randomized trial comparing known anti-thrombotic treatment, aspirin and anti-coagulants on mortality in patients with heart failure, especially caused by coronary artery disease. Such a trial is underway at the present and till the results are available it should be left to clinical judgement of the physician whether to administer aspirin in patients with heart failure after weighing the benefits versus risk.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Follicular fluid immunoreactive-inhibin concentrations in relation to follicular diameter and estradiol-17 beta, progesterone and testosterone concentrations in individual ovarian follicles in buffalo, Bubalus bubalis.

The objective of this study was to measure the concentrations of immunoreactive inhibin (ir-inhibin) in follicular fluid from individual ovarian follicles and relate them to follicular diameter and follicular fluid concentrations of estradiol-17 beta, progesterone and testosterone in buffalo. Follicular size was measured with an ultrasound machine and follicles were categorized as small (4 to 5 mm diam.), medium (6 to 9 mm diam.) and large (10 mm and above in diam.). Ir-inhibin concentrations varied markedly between and within follicles of same size category. Follicular fluid ir-inhibin concentrations (microgram/ml) were positively related to follicular diameter (R = 0.32, n = 262, P < 0.001) and were significantly higher (P < 0.05) in large (8.32 +/- 0.56) in comparison to medium (7.02 +/- 0.31) follicles which, in turn had inhibin concentrations significantly higher (P < 0.001) than those in small follicles (5.13 +/- 0.48). Ir-inhibin and estradiol-17 beta concentrations were positively related in medium (R = 0.38, n = 128, P < 0.001) and large (R = 0.64, n = 35, P < 0.001) but not in small follicles. There was a negative relationship between ir-inhibin and progesterone concentrations in large follicles (R = 0.46, n = 33, P < 0.01), with no relationship between the two hormones in small and medium follicles. Ir-inhibin was positively related to molar ratios of estradiol-17 beta to progesterone in medium (R = 0.30, n = 124, P < 0.01) and large (R = 0.49, n = 24, P < 0.01) but not in small follicles. There was no relationship between ir-inhibin and testosterone concentrations in follicles of all size categories. The results of the present study suggest that follicular inhibin production is related to follicular size as well as intrafollicular estradiol-17 beta and progesterone concentrations.

Animals↗

PubMed1997

Evaluation of triple quantum-filtered 23Na NMR spectroscopy in the in situ rat liver.

Triple quantum (TQ)-filtered 23Na NMR spectroscopy and the shift reagent, TmDOTP5-, have been used to evaluate the contributions of intra- (Na+i) and extracellular (Na+e) sodium to the TQ-filtered signal in the rat liver, in situ. Na+e contributed significantly to the total TQ-filtered signal in live animals, and the intensity of this signal did not change postmortem. The TQ-filtered Na+i signal increased by approximately 380% over a period of 1 h postmortem, whereas the single quantum (SQ) Na+i increased by 90%. The constancy of the TQ-filtered Na+i signal indicates that changes in total TQ-filtered 23Na signal intensity in liver (without a shift reagent) may accurately reflect changes in TQ-filtered Na+i signal intensity. The large percent increase in the TQ-filtered Na+i signal as compared to the SQ signal suggests that the fraction of Na+i interacting with macromolecules increases after death.

Animals↗

PubMed1996

Regional myocardial oxygen tension: 19F MRI of sequestered perfluorocarbon.

A novel noninvasive method of measuring local myocardial oxygen tension (pO2) in the perfused rat heart using 19F MRI is demonstrated. Tissue pO2 was determined on the basis of the 19F spin-lattice relaxation rate (R1) of perflubron (perfluorooctyl bromide) sequestered in the heart after IV infusion of an emulsion. Spectroscopic measurement of R1 was previously used to measure a global weighted average of oxygen status. 19F MRI now provides 3D spatial resolution indicating local cardiac pO2 under normally perfused, globally ischemic, and regionally ischemic conditions.

Animals↗

PubMed1995

TmDOTP5- as a 23Na shift reagent for the in vivo rat kidney.

Since transmembrane sodium gradient is essential to many cell functions, there is continuing interest in methods that differentiate intracellular and extracellular Na+. In the kidney, shift reagent (SR) aided 23Na magnetic resonance spectroscopy (MRS) has been successfully used only in isolated cells, tubules, and the perfused organ. In this report, we demonstrate for the first time that TmDOTP5- can be used to distinguish Na+ compartments in kidneys in vivo. Infusion of 80 mM TmDOTP5- without added Ca2+ produced three resolved 23Na resonances, which we have assigned to intracellular Na+, vascular Na+, and intraluminal Na+. In comparison, infusion of 400 mM DyTTHA3- produced two broad and unresolved resonances. The 31P spectra of the cellular high energy phosphate metabolites indicate that TmDOTP5- is safe for in vivo applications. Washout studies suggest that this SR displays renal clearance similar to that of MR imaging contrast agents. However, the glomerular filtration rate (GFR) in animals infused with TmDOTP5- was reduced by 49% compared with the GFR in control animals, perhaps due to the hypotensive effects of the SR. We conclude that TmDOTP5- is effectively cleared from the blood of live animals but that a different formulation will be required for clinical application.

Animals↗

PubMed1995

Antineoplastic agents 322. synthesis of combretastatin A-4 prodrugs.

Combretastatin A-4 (1a), the principal cancer cell growth-inhibitory constituent of the Zulu medicinal plant Combretum caffrum, has been undergoing preclinical development. However, the very limited water solubility of this phenol has complicated drug formation. Hence, derivatives of the combretastatin A-4 (1a) 3'-phenol group were prepared for evaluation as possible water-soluble prodrugs. As observed for combretastatin A-4, the sodium salt (1b), potassium salt (1c) and hemisuccinic acid ester (1e) derivatives of phenol 1a were essentially insoluble in water. Indeed, these substances regenerated combretastatin A-4 upon reaction with water. A series of other simple derivatives (1d, 1f-j) proved unsatisfactory in terms of water solubility or stability, or both. The most soluble derivatives evaluated included the ammonium (1l), potassium (1m) and sodium (1n) phosphate salts, where the latter two proved most stable and suitable. Both the potassium (1m) and sodium (1n) phosphate derivatives of combretastatin A-4 were also found to exhibit the requisite biological properties necessary for a useful prodrug. Sodium salt 1n was selected for drug formulation and further pre-clinical development.

Animals↗

PubMed1994

Non-invasive measurement of steady-state vitreous lactate concentration.

The cellular events leading to the proliferation of new preretinal blood vessels into the vitreous are unknown. It has been hypothesized that a metabolic trigger, such as increased lactate concentration, induces ambient growth factors to initiate this neovascularization. However, this hypothesis has not been tested in vivo because non-invasive methods for measuring vitreous lactate concentration have not been available. In this study, we identified lactate as the dominant resonance in normal rabbit vitreous using a water-suppressed, localized proton NMR method; negligible spectral contamination from lipid, alanine and threonine was demonstrated. The steady-state vitreous lactate concentration in vivo was 11.3 +/- 4 mM (mean +/- SD, n = 7 eyes) which was not statistically different (p = 0.498) to the enzymatically determined lactate content in vitreous from a parallel group of animals [12.1 +/- 0.6 mM (n = 6 eyes)]. Non-invasive measurement of steady-state vitreous lactate concentration using localized proton NMR represents the necessary first step in understanding the role of lactate in neovascularization.

Animals↗

PubMed1994

In vivo studies of cellular energy state, pH, and sodium in rat liver after thermal injury.

In vivo 31P- and 23Na-magnetic resonance spectroscopy was used to measure phosphorus metabolites, intracellular pH, cytosolic free Mg2+, and intracellular Na+ in the liver of rats 24 h after 40% total body surface area full-thickness burn injury. Studies were performed during infusion of thulium (III) 1,4,7,10-tetraazacyclododecane N,N',N",N"'-tetra(methylenephosphonate), which served as the Na+ shift agent. Compared with the sham-burn group, there was a significant increase in hepatic intracellular Na+ along with a decrease in intracellular pH and free Mg2+. The ratio of intra- to extra-cellular Na+ increased, indicating a decreased Na+ gradient that may determine the hepatic transmembrane potential difference. Hepatic beta-ATP/P(i) also significantly decreased, which suggests that either ATP utilization is significantly accelerated or ATP synthesis is inhibited after the thermal injury. Of the cations measured (Na+, Mg2+, H+), the change in intracellular Na+ was most dramatic. This study demonstrates that major burn injury may cause profound changes in hepatic bioenergetics and ionic metabolism 24 h after injury and that intracellular Na+ may be a sensitive indicator of hepatic dysfunction 24 h after injury. Because these animals tolerated the shift reagent, thulium (III) 1,4,7,10-tetraazacyclododecane N,N',N",N"'-tetra(methylenephosphonate), nuclear magnetic resonance spectroscopy may prove valuable in monitoring intracellular cations in the liver after major injury.

Animals↗

PubMed1993

Thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) as a 23Na shift reagent for the in vivo rat liver.

The use of thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate (TmDOTP5-) as an in vivo 23Na NMR shift reagent for rat liver was evaluated by collecting interleaved 23Na and 31P spectra. Infusion of 80 mM TmDOTP5- without added Ca2+ produced baseline-resolved peaks from intra- and extracellular sodium without producing any changes in phosphate metabolite resonances or intracellular pH. Several key physiological parameters measured in parallel groups of animals confirmed that liver physiology is largely unaffected by this shift reagent. A direct comparison of TmDOTP5- versus DyTTHA3- showed that after infusion of 5-8 times more DyTTHA3-, the extracellular sodium peak shifted by the same amount as with TmDOTP5-, but the two 23Na resonances were very broad and not resolved. The baseline-resolved peaks with TmDOTP5- allowed us to measure the in vivo T1 and T2 relaxation characteristics of intra- and extracellular Na+. The measured T1, T2s, and T2f values and the relative contributions from the slow and fast T2 components for intracellular Na+ in liver did not differ significantly from the values reported for perfused frog heart. The T1 and T2 relaxation curves of the extracellular Na+ resonances fit a monoexponential function. Analysis of the relative contribution of the fast- and slow-relaxing T2 components from intracellular Na+ resulted in a calculated visibility factor of 69 +/- 4% and the intracellular Na+ concentration calculated from the NMR peak intensity ratio, the measured visibility factor, and literature values of intra- and extracellular volume was 19 mM. These results indicate that TmDOTP5- promises to be quite useful as an in vivo shift reagent for liver and other organs.

Animals↗

PubMed1992

Protein-linked isoprenoid lipids in dexamethasone-treated human lymphoid lines in culture.

Accumulation of isoprenoids was studied in two cell lines derived from acute T-cell leukemia: CEM-C7 cells, whose growth is inhibited by the glucocorticoid dexamethasone, and CEM-C1 cells, which are resistant to this steroid. Isoprenoids were measured by growing the cells in serum-free medium in the presence of lovastatin, which blocks synthesis of mevalonate, and then labeling with exogenous [3H]mevalonolactone. In both cell lines, isoprenoids associated with proteins were detected in cytoplasm, nucleus, and chromatin, and in the chromatin residue that remains after extraction of histone and nonhistone proteins. Differences in labeling were detected after treatment with dexamethasone in the CEM-C7 line, showing a decrease in the cytoplasmic fraction with a corresponding increase in both the nuclear and chromatin fractions as compared with untreated cells. No change was seen in the CEM-C1 line. In both cell lines, 25-30% of the incorporated label was released by treatment with acid or alkali. However, the majority of the label required treatment with methyl iodide for the release of organic-soluble tritiated products. After extraction with chloroform, the lipid fractions contained farnesol, geraniol, dolichols, and possibly nerolidol.

Cell Division↗

PubMed1991

Improved MR imaging in extremely inhomogeneous radio-frequency fields.

An improvement to the method for imaging with extremely inhomogeneous radio-frequency fields is presented which uses a pseudo-noise-modulated selective (PNMS) excitation prepulse to randomize the signal from outside the selected slice. This prepulse reduces the problems that arise from imperfect subtraction involved with the one-dimensional ISIS-type slice selection procedures. The results demonstrate two to three times improvement in the signal-to-noise ratio and reduction in the image artifacts when this prepulse is used.

Computer Simulation↗

PubMed1991

Apoptosis: mode of cell death induced in T cell leukemia lines by dexamethasone and other agents.

Glucocorticoids can mediate the destruction of thymocytes and T cell-derived leukemia cells through a mechanism known as apoptosis. The characteristic feature of apoptosis is fragmentation of DNA at internucleosomal linkers through the activity of a specific endonuclease. In this study, an attempt was made to compare dexamethasone-induced apoptosis in two T cell-derived human leukemia lines (CEM-C1 and CEM-C7) to the cell killing brought about by selected cytotoxic agents. In the CEM-C7 cell line (dexamethasone-sensitive), apoptosis was induced not only by dexamethasone but by actinomycin D, cycloheximide, and 25-OH cholesterol. In the CEM-C1 cell line (dexamethasone-resistant) cycloheximide, 25-OH cholesterol, or cell starvation could induce apoptosis. It appears that in leukemic cells apoptosis may be induced by a variety of unrelated toxic agents and is not limited to glucocorticoids.

Cell Division↗

PubMed1990

Dexamethasone-induced killing of neoplastic cells of lymphoid derivation: lack of early calcium involvement.

The role of calcium influx in dexamethasone-induced fragmentation of DNA was studied in the glucocorticoid-sensitive human lymphoid line of T cell derivation (CEM-C7). Reduction of calcium content in the medium or the use of EGTA increased DNA fragmentation and appeared to slightly enhance the effect of dexamethasone. Incubation of isolated nuclei in the presence of high concentrations of calcium did not bring about significant DNA fragmentation. Calmidazolium, an antagonist of calmodulin dependent reactions did not reduce the sensitivity of CEM-C7 cells to dexamethasone nor did it modify the response to dexamethasone of the resistant CEM-C1 line. It appears that in contrast to rodent thymocytes, massive calcium influx is not per se responsible for the initiation of directed cell killing (apoptosis).

Biological Transport↗

PubMed1990

A novel editing technique for 19F MRI: molecule-specific imaging.

A novel technique is proposed to facilitate the selective imaging of specific molecules from a mixture. The application of the technique presented here demonstrates the ability to selectively produce 19F MR images of either trifluoroacetic acid or the perfluorocarbon emulsion Oxypherol-ET (perfluorotributylamine), when both molecules are present simultaneously. Selective detection is based on the presence of homonuclear J-modulation in one molecule and differential spin-spin relaxation time (T2). Perfluorotributylamine, an A3B2 system, is subject to homonuclear J-modulation, which produces a null signal from the antiphase components of the triplet (A3) when an echo time (TE) = 1/2J is used in a spin-echo image. At this echo time the second molecule, in this example trifluoroacetic acid, a non-coupled spin system, is selectively imaged. At longer echo times, e.g., TE = 1/J there is substantial recovery of the J-modulated signal, which may be solely observed due to T2 decay of the trifluoroacetic acid signal. The method is demonstrated both using phantoms and in vivo.

Fluorine↗

PubMed1989

Comparison of dexamethasone and lovastatin (mevinolin) as growth inhibitors in cultures of T-cell derived human acute leukemia lines (CEM).

Because previous studies have shown that a reduction of cholesterol synthesis is one of the earliest effects of dexamethasone on neoplastic lymphoid cells, a study was made to compare dexamethasone to lovastatin, a specific inhibitor of cholesterol synthesis, which acts on 3-hydroxy-3-methylglutaryl coenzyme A reductase. Two cell lines were used, both derived from human acute T-cell leukemia, one dexamethasone-sensitive (CEM-C7), the other dexamethasone-resistant (CEM-Cl). The results revealed a similar pattern of resistance and sensitivity of both lines to lovastatin, although only the dexamethasone effect was reversed by 1 microM RU 486, the antiglucocorticoid steroid. The cell killing by dexamethasone and lovastatin had the characteristics of apoptosis.

Cell Division↗