Effect of insulin on the proliferation of and progesterone production by buffalo granulosa cells in vitro.
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Animals↗
Biomedical subjects
N Bansal
Publications and source records attributed to N Bansal.
Heat-induced changes in intracellular Na+, pH and bioenergetic status in superfused RIF-1 tumour cells determined by 23Na and 31P magnetic resonance spectroscopy.
The acute effects of hyperthermia on intracellular Na+ (Nai+), bioenergetic status and intracellular pH (pHi) were investigated in superfused Radiation Induced Fibrosarcoma-1 (RIF-1) tumour cells using shift-reagent-aided 23Na and 31P nuclear magnetic resonance (NMR) spectroscopy. Hyperthermia at 45 degrees C for 30 min produced a 50% increase in Na, a 0.42 unit decrease in pHi and a 40-45% decrease in NTP/P(i). During post-hyperthermia superfusion at 37 degrees C, pHi and NTP/P(i) recovered to the baseline value, but Na initially decreased and then increased to the hyperthermic level 60 min after heating. Hyperthermia at 42 degrees C caused only a 15-20% increase in Nai+. In the presence of 3 microM 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of the Na+/H+ exchanger, the increase in Nai+ during 45 degrees C hyperthermia was attenuated, suggesting that the heat-induced increase in Nai+ was mainly due to an increase in Na+/H+ anti-porter activity. EIPA did not prevent hyperthermia-induced acidification. This suggests that pHi is controlled by other ion exchange mechanisms in addition to the Na+/H+ exchanger. EIPA increased the thermo-sensitivity of the RIF-1 tumour cells only slightly as measured by cell viability and clonogenic assays. The hyperthermia-induced irreversible increase in Nai+ suggests that changes in transmembrane ion gradients play an important role in cell damage induced by hyperthermia.
Amiloride↗
Noninvasive thermometry using hyperfine-shifted MR signals from paramagnetic lanthanide complexes.
MR thermometry techniques based on the strong water 1H signal provide high spatial and temporal resolution and have shown promise for applications such as laser surgery and RF ablation. However, these techniques have low temperature sensitivity for hyperthermia applications and are greatly influenced by local motion and susceptibility variations. 1H NMR signals from paramagnetic lanthanide complexes of Pr3+, Yb3+ and Tm3+ show up to 300-fold stronger temperature dependence compared to the water 1H signal. In addition, 1H chemical shifts of many of these complexes are insensitive to other factors such as the concentration of the paramagnetic complex, pH, [Ca2+], and the presence of plasma macro-molecules and ions. Applications of lanthanide complexes for temperature measurement in intact animals and the feasibility of mapping temperatures in phantoms have been demonstrated. Among all the lanthanide complexes examined so far, thulium 1, 4, 7, 10-tetramethyl-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetate (TmDOTMA-) appears to be the most attractive for in vivo MR thermometry. The 1H signal from the methyl groups on this complex is relatively intense because of 12 equivalent protons and provides high temperature sensitivity because of the large paramagnetic shifts induced by thulium. The possibility of imaging TmDOTMA2--in intact animals at physiologically safe concentrations has recently been demonstrated. Overall, MR thermometry methods based on hyperfine-shifted MR signals from paramagnetic lanthanide complexes appear promising for animal applications, but further studies relating to acceptable dose and signal-to-noise ratio are necessary before clinical use.
Animals↗
Production of progesterone induced by follicle-stimulating hormone by buffalo (Bubalus bubalis) granulosa cells in vitro.
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Animals↗
Effects of chemotherapy by 1,3-bis(2-chloroethyl)-1-nitrosourea on single-quantum- and triple-quantum-filtered 23Na and 31P nuclear magnetic resonance of the subcutaneously implanted 9L glioma.
The effects of chemotherapy [25 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea administered with a single i.p. injection] on cellular energetics by 31P nuclear magnetic resonance (NMR) spectroscopy, total tissue sodium by single-quantum (SQ) 23Na NMR spectroscopy, and intracellular sodium by triple-quantum-filtered (TQF) 23Na NMR spectroscopy were studied in the s.c. 9L glioma. Animals were studied by NMR 2 days before therapy and 1 and 5 days after therapy. Destructive chemical analysis was also performed 5 days after therapy to validate the origin of changes in SQ and TQF 23Na signals. One day after treatment, there was no significant difference between control and treated tumors in terms of tumor size or 23Na and 31P spectral data. Five days after therapy, treated tumors had 28 +/- 16% (P < 0.1) lower SQ 23Na signal intensity, 46 +/- 20% (P < 0.05) lower TQF 23Na signal intensity, 125 +/- 51% (P < 0.05) higher ATP:Pi ratio, 186 +/- 69% (P < 0.05) higher phosphocreatine:Pi ratio, and 0.17 +/- 0.06 pH units (P < 0.05) higher intracellular pH compared with control tumors. No significant differences in TQF 23Na relaxation times were seen between control and treated tumors at any time point. Destructive chemical analysis showed that the relative extracellular space of control and treated tumors was identical, but the treated tumors had 21 +/- 8% (P < 0.05) lower total tissue Na+ concentration and 60 +/- 24% (P < 0.05) lower intracellular Na+ concentration compared with the controls. The higher phosphocreatine:Pi and ATP:Pi ratios after 1,3-bis(2-chloroethyl)-1-nitrosourea treatment indicate improved bioenergetic status in the surviving tumor cells. The decrease in SQ and multiple-quantum-filtered 23Na signal intensity was largely attributable to a decrease in Na(i)+ because the treatment did not change the relative extracellular space. The improved energy metabolism could decrease the intracellular concentration of Na+ by increasing the activity of Na+-K+-ATPase and decreasing the activity of Na+/H+. Although both 23Na and 31P spectra were consistent with improved cellular metabolism in treated tumors, the 23Na methods may be better suited for monitoring response to therapy because of higher signal:noise ratio and ease of imaging the single 23Na resonance.
Adenosine Triphosphate↗
TmDOTP(5-) as a (23)Na shift reagent for the subcutaneously implanted 9L gliosarcoma in rats.
The use of TmDOTP(5-) as an in vivo (23)Na NMR shift reagent (SR) for subcutaneously implanted 9L gliosarcoma was evaluated. TmDOTP(5-) produced a single sharp extracellular peak after about 50-60 min of infusion, and did not cause any changes in the (31)P resonance areas or chemical shifts, suggesting that the SR is homogeneously distributed in the extracellular space and does not alter tumor bioenergetic status. TmDOTP(5-) and CoEDTA(-) as extracellular space markers gave identical results for relative extracellular space (0.25 +/- 0.03 and 0.25 +/- 0.04, respectively) and intracellular Na(+) concentration (19.3 +/- 4.0 mM and 18.6 +/- 3.9 mM, respectively), indicating that the biodistribution of the SR is the same as the well-accepted extracellular space marker. The in vivo T(1) and T(2) relaxation times of intra- and extracellular Na(+) were also measured. Our results indicate that TmDOTP(5-) promises to be an effective shift reagent and extracellular space marker in the 9L gliosarcoma and perhaps other tumors. Magn Reson Med 45:436-442, 2001.
Animals↗
Triple-quantum-filtered (23)Na NMR spectroscopy of subcutaneously implanted 9l gliosarcoma in the rat in the presence of TmDOTP(5-1).
The utility of triple-quantum (TQ)-filtered (23)Na NMR spectroscopy for discriminating between intra- and extracellular Na(+)(Na(i)(+) and Na(e)(+), respectively) in a solid tumor in vivo was evaluated using TmDOTP(5-) as a (23)Na shift reagent. Infusion of 80 mM TmDOTP(5-) without added Ca(2+) produced baseline-resolved Na(i)(+) and Na(e)(+) peaks in both single-quantum (SQ) and TQ-filtered (23)Na spectra. The Na(i)(+) signal represented 22+/-4% of the SQ spectrum, but 59+/-10% of the TQ-filtered spectrum. Therefore, the Na(i)(+) contribution in TQ-filtered spectra is much higher than in SQ spectra. Both SQ and TQ-filtered Na(i)(+) signals increased by about 75% 1 h after sacrificing the animal. The TQ-filtered relaxation times did not change during this time, indicating that changes observed in TQ-filtered spectra collected with a preparation time of 3 ms represent changes in the concentration of sodium ions contributing to the TQ-filtered signal. Similar experiments were conducted without TmDOTP(5-) to determine changes in the Na(e)(+) signal in the absence of the shift reagent. The changes in total SQ and TQ-filtered signals 1 h after sacrificing the animal showed that the SQ Na(e)(+) signal decreased by approximately 35%, while the TQ-filtered Na(e)(+) signal did not change significantly. This demonstrates that the TQ-filtered (23)Na signal is relatively insensitive to changes in Na(e)(+) content. To our knowledge, this work represents the first evaluation of multiple-quantum-filtered (23)Na spectroscopy to discriminate between intra- and extracellular Na(+) in a solid tumor in vivo.
Animals↗
Enhancement of hyperglycemia-induced acidification of human melanoma xenografts with inhibitors of respiration and ion transport.
RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the selective acidification of a human melanoma xenograft in mice with severe combined immunodeficiency with the induction of hyperglycemia (mean blood glucose level +/- standard error of the mean, 26 mmol/L +/- 1) and the intraperitoneal administration of metaiodobenzylguanidine (MIBG, 30 mg/kg), alpha-cyano-4-hydroxycinnamate (CNCn, 300 mg/kg), lonidamine (100 mg/kg), cariporide (HOE642, 160 mg/kg), or 4.4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS, 50 mg/kg). MATERIALS AND METHODS: The intra- and extracellular pH levels of tumor were estimated from the chemical shifts of inorganic phosphate and 3-aminopropylphosphonate, respectively, with phosphorus-31 nuclear magnetic resonance (MR) spectroscopy. The relative level of steady-state lactate was monitored with hydrogen-1 MR spectroscopy. RESULTS: In small tumors (< or = 8.0 mm), hyperglycemia decreased the intra- and extracellular pH levels by less than 0.2. The combination of hyperglycemia and MIBG decreased the intra- and extracellular pH levels by approximately 0.4 and 0.6, respectively, and lowered the beta-nucleoside triphosphate (NTP)/inorganic phosphate (Pi) ratio of tumor and liver by about 60% and 25%, respectively. The combination of hyperglycemia, MIBG, and CNCn produced a transient decrease in the intracellular pH of about 0.6. The combination of hyperglycemia and lonidamine produced a sustained (>3 hours) 0.8-unit decrease in intracellular pH and an 83% and 100% decrease in PCr/P1 and beta-NTP/P1 ratios, respectively. The combination of hyperglycemia. MIBG, cariporide, and DIDS produced a gradual decrease in intra- and extracellular pH by 1.1 and 1.0, respectively. The relative level of steady-state lactate concentration in tumors increased 10% with hyperglycemia alone, about 20% with MIBG plus hyperglycemia, and increased more than twofold when hyperglycemia was combined with MIBG and CNCn administration. CONCLUSION: These preliminary data suggest that hyperglycemia and combinations of respiratory and ion transport inhibitors can be used to selectively acidify tumors and, thereby, sensitize them to hyperthermnia or other pH-sensitive therapeutic modalities.
3-Iodobenzylguanidine↗
Investigation and control of a cluster of cases of Legionnaires disease in western Sydney.
Three cases of Legionella pneumophila infection were identified in Sydney's west in November 1998. Epidemiological investigations identified an association with one workplace. Environmental sampling revealed that the cooling towers in the workplace, and at 2 other premises within a 1 km radius of the workplace, were positive for L. pneumophila serogroup 1 (LP1) which was indistinguishable from clinical isolates of 2 of the cases on DNA fingerprinting. Our report highlights limitations of the current control program for Legionella in cooling towers, including the finding of unregistered cooling towers, cooling towers positive for LP1 despite satisfactory results on inspection, and cooling towers potentially linked to disease with counts of LP1 below the current protocol requirements for immediate decontamination.
Adult↗
Paralytic rabies following leopard bite.
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Adult↗
Intracellular acidification of human melanoma xenografts by the respiratory inhibitor m-iodobenzylguanidine plus hyperglycemia: a 31P magnetic resonance spectroscopy study.
In vivo 31P magnetic resonance spectroscopy demonstrates that human melanoma xenografts can be significantly acidified by induction of hyperglycemia combined with administration of m-iodobenzylguanidine (MIBG), an inhibitor of mitochondrial respiration. In melanoma xenografts (< or =8 mm diameter), intracellular pH (pHi, measured by the chemical shift of the Pi resonance) and extracellular pH (pHe, measured with 3-aminopropylphosphonate) was reduced by less than 0.2 unit during i.v. infusion of glucose for 40 min. Administration of MIBG (30 mg/kg) under hyperglycemic conditions (26 mM) reduced tumor pHi and pHe by approximately 0.4 (P < 0.001) and approximately 0.6 (P < 0.001) unit, respectively; coincidentally, the nucleoside triphosphates:Pi ratio decreased approximately 60% (P < 0.004) relative to the baseline level. Minimal changes in pHi and pHe and a small decrease in nucleoside triphosphates:Pi ratio (26%, P = 0.2) were observed in liver in response to MIBG plus hyperglycemia. These results suggest that under normoglycemic and hyperglycemic conditions, small human melanoma xenografts (< or =8 mm) may exhibit a relatively high level of oxidative phosphorylation that may be blocked by MIBG. The acidification may result from increased lactate production as a direct effect of MIBG inhibition of respiration in mitochondria of tumor cells, or through indirect systemic effects, which remain to be identified. The synergetic effects of MIBG and hyperglycemia result in significant acidification of the tumor and a decrease in tumor bioenergetic status, and the effects are largely selective for tumors in comparison with normal tissues.
3-Iodobenzylguanidine↗
Effect of exercise on (23)Na MRI and relaxation characteristics of the human calf muscle.
The acute affect of voluntary muscle contractions performed by healthy volunteers was evaluated using (23)Na nuclear magnetic resonance (NMR). Three-dimensional gradient-echo (23)Na images, pulse-acquired spectra, and transverse relaxation times were obtained before and after ankle flexion-extension exercise. The muscle sodium concentration was calculated from (23)Na images using a 40 mM NaCl standard and the measured T(2) values. Before exercise the muscle sodium concentration was 26+/-4 mmole/kg wet weight. This agrees closely with literature values, suggesting that muscle Na(+) is fully NMR visible. The (23)Na image intensity increased by 34%+/-7% in the exercised muscle and diminished with a half-life of 30+/-6 minutes. The pulse-acquired spectra, however, did not show any significant change in muscle signal intensity following exercise, but the relative contribution of the slow T(2) component increased. The calculated sodium concentration also did not change significantly after the exercise. We therefore infer that the changes in (23)Na magnetic resonance imaging (MRI) were due to a change in sodium-macromolecular interaction rather than a change in tissue sodium content. We believe that this report represents the first study of (23)Na MRI of skeletal muscle.
Adult↗
Time-domain quantification of multiple-quantum-filtered (23)Na signal using continuous wavelet transform analysis.
The application of continuous wavelet transform (CWT) analysis technique is presented to analyze multiple-quantum-filtered (MQF) (23)Na magnetic resonance spectroscopy (MRS) data. CWT acts on the free-induction-decay (FID) signal as a time-frequency variable filter. The signal-to-noise ratio (SNR) and frequency resolution of the output filter are locally increased. As a result, MQF equilibrium longitudinal magnetization and the apparent fast and slow transverse relaxation times are accurately estimated. A developed iterative algorithm based on frequency signal detection and components extraction, already proposed, was used to estimate the values of the signal parameters by analyzing simulated time-domain MQF signals and data from an agarose gel. The results obtained were compared to those obtained by measurement of signal height in frequency domain as a function of MQF preparation time and those obtained by a simple time-domain curve fitting. The comparison indicates that the CWT approach provides better results than the other tested methods that are generally used for MQF (23)Na MRS data analysis, especially when the SNR is low. The mean error on the estimated values of the amplitude signal and the apparent fast and slow transverse relaxation times for the simulated data were 2.19, 6. 63, and 16.17% for CWT, signal height in frequency domain, and time-domain curve fitting methods, respectively. Another major advantage of the proposed technique is that it allows quantification of MQF (23)Na signal from a single FID and, thus, reduces the experiment time dramatically.
Magnetic Resonance Spectroscopy↗
Temperature-dependent chemical shift and relaxation times of (23)Na in Na(4)HTm[DOTP].
We describe the characterization of a (23)Na temperature-dependent chemical shift and relaxation rates in the complex, Na(4)HTm[DOTP]. This is the first characterization of a (23)Na temperature-dependent chemical shift in a nonmetallic sample. The (23)Na temperature-dependent chemical shift coefficient is approximately -0. 5 PPM/ degrees C for both an aqueous solution and a 6% agarose gel of this compound. This is 50 times the magnitude of the temperature-dependent chemical shift coefficient of water protons. The relaxation times, T(1), T(2f), and T(2s) increased by 0.1, 0.01, and 0.05 ms/ degrees C, respectively. Applications of these unique properties for designing an MRI technique for monitoring heat deposition in tissue and tissue phantoms are discussed.
Gels↗
Virulence plasmid (pYV)-associated susceptibility of Yersinia enterocolitica to chlorine and heavy metals.
This study was aimed at elucidating the role of virulence plasmid (pYV) in the susceptibility of Yersinia enterocolitica to bactericidal agents such as chlorine and heavy metals. Plasmid-bearing (pYV+) Y. enterocolitica was less susceptible to the antimicrobial action of chlorine and heavy metals compared with the isogenic plasmidless (pYV-) derivative. This difference was, however, observed only with bacteria cultured at 25 degrees C. pYV-associated susceptibility apart, cells cultured at 37 degrees C were also found to be less susceptible to the antimicrobial action of these agents. The results indicate that the susceptibility of Y. enterocolitica to these agents was influenced both by the presence of the virulence plasmid and the temperature at which the cells were cultured.
Cadmium↗
Arsenic and cadmium resistance in environmental isolates of Yersinia enterocolitica and Yersinia intermedia.
Environmental strains of Yersinia enterocolitica representing biotype 1A lack virulence plasmid (pYV) and are regarded as non-pathogenic. Though these occupy a diverse range of environmental niches, nothing is known about their resistance to heavy metals. The minimal inhibitory concentrations (MICs) of various metal ions, namely Ag+, Cu2+, Zn2+, Cd2+, As5+, and As3+, for strains of Yersinia enterocolitica (biotype 1A) and Yersinia intermedia (biotypes 1, 2, and 4), isolated from sewage effluents or pork, were determined. All isolates were resistant (MICs 2.5-5 mM) to Cd2+. The MICs of arsenic varied with bacterial strain and the chemical species of the arsenic used. For the majority of the strains, however, it was between 5-10 mM of Na2HAsO4.7H2O and NaAsO2, and 0.625-2.5 mM of As2O3. Except for one isolate, MICs of Ag+, Cu2+, and Zn2+ for these strains were in the range of 0.3-0.625 mM.
Animals↗
Ethambutol-sugar hybrids as potential inhibitors of mycobacterial cell-wall biosynthesis.
Ethambutol is an established front-line agent for the treatment of tuberculosis, and is also active against Mycobacterium avium infection. However, this agent exhibits toxicity, and is considered to have low potency. The action of ethambutol on the mycobacterial cell wall, particularly the arabinan, and comparison of the structure of ethambutol with several of the cell-wall saccharides, suggested that ethambutol-saccharide hybrids might lead to agents with a more selective mechanism of action. To this end, eight ethambutol-saccharide hybrids were synthesized and screened against M. tuberculosis and several clinical isolates of M. avium.
Antitubercular Agents↗
Multiple quantum filtered 23Na NMR spectroscopy of the isolated, perfused rat liver.
Isolated, perfused rat livers were examined by single-quantum (SQ) and double-quantum-filtered (DQ-filtered) 23Na spectroscopy during prolonged global ischemia and during perfusion with ouabain, low-buffer potassium, or lithium-enriched buffer. Baseline separation of the intracellular (Na(i)+) and extracellular (Na(e)+) sodium resonances using TmDOTP5- allowed a direct comparison of temporal changes in SQ versus DQ-filtered Na(i)+. The SQ Na(i)+ signal increased approximately 150% during the first 15 min of global ischemia and then remained relatively constant over the next 45 min, while the DQ-filtered signal steadily increased approximately 400% over the same 60 min period. In similar experiments in which all perfusate sodium was replaced by lithium, the DQ-filtered Na(i)+ signal increased approximately 180% over a similar period of ischemia. Exposure of livers to ouabain also resulted in larger increases in DQ-filtered versus SQ signal of Na(i)+. The approximately 290% increase in DQ-filtered sodium observed during perfusion of livers with a hypokalemic buffer (1.2 mM K+) could be completely reversed by continued perfusion with a buffer containing normal levels of K+ (4.7 mM). These data suggest that the DQ-filtered Na(i)+ signal of liver does not simply report an increase in [Na(i)+], but may be exquisitely sensitive to other intracellular events initiated by altered physiology.
Animals↗