Relaxation times of choline, creatine and N-acetyl aspartate in human cerebral white matter at 1.5 T

Several studies have investigated the T1 and T2 relaxation time of choline, creatine and N-acetyl aspartate in cerebral white matter in normal human subjects. However, these studies demonstrate a large variation in T1 and T2 values. In the present study, relaxation times of choline, creatine and N-acetyl aspartate were determined in cerebral white matter in 15 control subjects (age 21 +/- 2 y, mean +/- SD) at 1.5 T. Using PRESS, seven or eight data points were obtained to fit the T1 and T2 relaxation curves to, respectively. The mean voxel size was 14 cm3. The T1 relaxation times of choline, creatine and N-acetyl aspartate were 1091 +/- 132 (mean +/- SD), 1363 +/- 137 and 1276 +/- 132 ms. The T2 relaxation times were 352 +/- 52, 219 +/- 29 and 336 +/- 46 ms, respectively.     

Increased seminal plasma lead levels adversely affect the fertility potential of sperm in IVF

BACKGROUND: Lead remains in high levels in the environment and is known to reduce fertility in animal models, but a direct link between lead exposures and human infertility has not yet been established. METHODS: In a prospective, double-blind study of the metal ion levels and sperm function, semen was obtained from partners of 140 consecutive women undergoing their first IVF cycle. Lead in seminal plasma was determined by atomic absorption spectroscopy. Motile sperm populations were assessed for surface receptors for mannose binding, and the ability to undergo premature ('spontaneous'), and free mannose-induced acrosome reactions. Fertile donor (n = 9) sperm were exposed to exogenous lead during capacitating incubations and then assessed for mannose receptor expression and acrosome loss. RESULTS: Lead levels were negatively correlated with IVF rates. Lead levels were negatively correlated to two of the three sperm function biomarkers (mannose receptors, mannose-induced acrosome reactions). Lead levels positively correlated with the spontaneous acrosome reaction. These findings were mimicked by in-vitro exposure of fertile donor sperm to lead. CONCLUSIONS: Multiple sperm parameters are affected as lead levels rise. Increased lead levels may contribute to the production of unexplained male infertility.     

Measurement of venous oxyhaemoglobin saturation in the adult human forearm by near infrared spectroscopy with venous occlusion

Measurement of the oxygenation of the peripheral tissues provides useful information about tissue perfusion. A method is described for the measurement of peripheral venous oxyhaemaglobin saturation (SvO₂) in the adult forearm by a non-invasive technique, near infrared spectroscopy (NIRS) with venous occlusion. A series of studies is performed on healthy adults to compare measurements of forearm SvO₂ made by NIRS with measurements of superficial venous SvO₂ made by co-oximetry, and to study the effect of different optode spacings. There is a significant correlation between forearm SvO₂ measured by NIRS and SvO₂ of superficial venous blood measured by cooximetry (n=19, r=0.7, p<0.0001). Higher values for SvO₂ were obtained using a 2.5 cm spacing than with a 4 cm spacing (mean difference=4.1% (95% Cl 1.4%–6.8%) n=16). This difference is likely to have been due to a more superficial volume of tissue being studied with the closer optode spacing. Peripheral SvO₂ can be measured non-invasively using NIRS with venous occlusion. It may prove to be a useful method to study circulatory disturbances.     

Visualizing metabolic changes in breast-cancer tissue using 1H-NMR spectroscopy and self-organizing maps

In-vitro NMR spectroscopic examinations of tissue extracts can be combined with appropriate pattern-recognition and visualization techniques in order to monitor characteristic metabolic differences between tissue classes. In the present study, such techniques are applied to a set of 88 breast-tissue samples with the intention of identifying typical differences between various tissue classes. The set contains 49 breast-tumor samples of various tumor grades and 39 samples of healthy tissue. The metabolite compositions of the tissue extracts were investigated using a dual extraction technique and high-resolution (1)H-NMR spectroscopy. The spectra of the hydrophilic and the lipophilic compounds were assigned to three groups according to different malignancy grades of the respective tissue samples. The group characteristics were analyzed using the k-nearest-neighbor method and self-organizing-map visualizations. The results show an increase of UDP-hexose, phosphocholine and phosphoethanolamine concentrations according to the tumor grade. Higher concentrations of taurine were detected in the malignant samples. Myo-inositol and glucose content were elevated in control samples compared with malignant tissue. Both compounds also characterized different subgroups in the pool of unaffected tissue samples depending upon fat content or fibrosis. Several lipid metabolites showed a characteristic elevation with high malignancy.     

Fluoropyrimidine chemotherapy in a rat model: comparison of fluorouracil metabolite profiles determined by high-field 19F-NMR spectroscopy of tissues ex vivo with therapy response and toxicity for locoregional vs systemic infusion protocols

A Sprague-Dawley rat model with DS sarcoma transplanted in the thigh was used to compare transcatheter locoregional i.a. and systemic i.v. administration of 5-fluorouracil (FU) at 12 dose-rate schedules: 25, 50 and 100 mg/kg; bolus, 1, 5 and 24 h infusions. In experiment A tumor (62/67 animals) as well as liver and kidney (56/67 animals) were excised 1 h after a single bolus or 1 h infusion or at the end of 5 and 24 h infusions. (19)F-NMR spectroscopy at 11.7 T was used to quantitate FU and its metabolites in ca. 1 g of tissue at 4 degrees C. In experiment B analogous FU treatments were repeated for 5 days (rats 80+11 controls). Tumor volumes vs time, various blood parameters and survival times were recorded, and a log growth rate parameter log GR, a response index RI, and a toxicity index TI were calculated. The i.a. vs i.v. ratios for tumor concentrations of FU and total anabolites (F-Nucl) were >1 for nearly all treatments and increased with infusion time at the higher doses. F-Nucl in tumor correlated linearly with total fluorine concentration (Tot. F range 30-1100 nmol/g) over all treatments (r=0.92, slope=0.45, p<0.0001). For non-bolus i.v. treatments [FU+F-Nucl] decreased linearly with decreasing FU dose rate (r(2)=0.74, zero intercept), while i.a. treatments showed non-linear behavior. For non-bolus treatments the mean log GR per treatment group showed a negative correlation (r=-0.87) with log[F-Nucl]. The most effective non-toxic treatments were 25 mg/kg over 5 or 24 h; the i.a. route was superior to i.v. on the basis of [FU+F-Nucl], RI, the reduction in log GR, and Kaplan-Meier survival statistics. For liver and kidney Tot. F (>83% FU catabolites) reached ca. 3-4 and 6-7 micromol/g, respectively, at the highest dose rates for either route; F-Nucl were detected only for Tot. F>500 nmol/g and increased exponentially as Tot. F increased (toxic treatments). The concentrations of the main catabolite (alpha-fluoro-beta-alanine, FBAL) in tumor did not correlate with Tot. F but rather with FBAL levels in kidney (r=0.90, all treatments), indicating that uptake of liver-derived FBAL from the circulation is the major source of FBAL in tumor.     

Near‐infrared spectroscopy determined brain and muscle oxygenation during exercise with normal and resistive breathing

To elevate effects of carbon dioxide (CO₂) retention by way of an increased respiratory load during submaximal exercise (150 W), the concentration changes of oxy‐ (ΔHbO₂) and deoxy‐haemoglobin (ΔHb) of active muscles and the brain were determined by near‐infrared spectroscopy (NIRS) in eight healthy males. During exercise, pulmonary ventilation increased to 33 (28–40) L min^–1 (median with range) with no effect of a moderate breathing resistance (reduction of the pneumotach diameter from 30 to 14 and 10 mm). The end‐tidal CO₂ pressure (P_ETCO ₂) increased from 45 (42–48) to 48 (46–58) mmHg with a reduction of only 1% in the arterial haemoglobin O₂ saturation (S_aO ₂). During control exercise (normal breathing resistance), muscle and brain ΔHbO₂ were not different from the resting levels, and only the leg muscle ΔHb increased (4 (–2–10) μM , P < 0.05). Moderate resistive breathing increased ΔHbO₂ of the intercostal and vastus lateralis muscles to 6 ± (–5–14) and 1 (–7–9) μM (P < 0.05), respectively, while muscle ΔHb was not affected. Cerebral ΔHbO₂ and ΔHb became elevated to 6 (1–15) and 1 (–1–6) μM by resistive breathing (P < 0.05). Resistive breathing caused an increased concentration of oxygenated haemoglobin in active muscles and in the brain. The results indicate that CO₂ influences blood flow to active skeletal muscle although its effect appears to be smaller than for the brain.     

Assessment of high-energy phosphorus compounds in the rat kidney by in situ31P nuclear magnetic resonance spectroscopy: effect of ischemia and furosemide

Summary ³¹P nuclear magnetic resonance (NMR) spectroscopy of the in situ rat kidney was performed by a surface coil method, and the effects of ischemia and furosemide infusion were assessed.³¹P NMR spectra of the kidney subjected to 30 min of ischemia returned completely to the pre-ischemic level after 60 min of reperfusion. But the³¹P NMR spectra after 60 min of ischemia did not recover, even after 120 min of reperfusion. Levels of -ATP and inorganic phosphate (Pi) decreased and the chemical shift of Pi increased after intravenous infusion of furosemide. This increase in chemical shift might signal an alkalotic change in intracellular pH. Furosemide infusion prior to ischemia is thought to protect the kidney from injury induced by 60 min of warm ischemia. The chemical shift of Pi returned to the pre-ischemic level earlier than -ATP and Pi. In conclusion, according to the findings of³¹P NMR spectroscopy, furosemide infusion prior to ischemia may be effective in protecting the kidney against ischemic injury. But the change in Pi peak and the causes of the dissociation of Pi and -ATP should be examined further.