Biomedical subjects

J Peeling

Publications and source records attributed to J Peeling.

At least 55 records · Page 3Linked to original sources

PubMed1996

23Na nuclear magnetic resonance spectral changes during and after forebrain ischemia in hypoglycemic, normoglycemic, and hyperglycemic rats.

BACKGROUND AND PURPOSE: The severity of brain injury in animal models of forebrain ischemia increases with blood glucose level. During ischemia, energy failure is slower and maintenance of ion gradients is prolonged as the level of glycemia increases. It is not clear how the level of glycemia influences recovery of ion homeostasis on reperfusion. It has been shown that changes in the intensity of the multiple-quantum 23Na nuclear magnetic resonance (NMR) signals reflect changes in intracellular Na+ levels. We have used 23Na NMR spectroscopy to evaluate the influence of the level of glycemia on changes in Na+ concentration during and after forebrain ischemia in rats. METHODS: Single-quantum (SQ) and double-quantum (DQ) 23Na NMR spectra were measured before and during 10-minute forebrain ischemia and during reperfusion in hypoglycemic, normoglycemic, and hyperglycemic rats. RESULTS: The DQ 23Na NMR signal increased to 210% of preischemia intensity in all rats, but a delay in this increase was observed in normoglycemic and hyperglycemic animals. The rate of the DQ 23Na NMR signal increase was fastest in hypoglycemic (apparent first-order rate constant 0.673 +/- 0.046 min-1, P < .002 compared with normoglycemic animals) and slowest in hyperglycemic (0.285 +/- 0.024 min-1, P < .03) rats. During reperfusion, the signal intensity recovered rapidly in hypoglycemic (0.385 +/- 0.050 min-1) and normoglycemic (0.464 +/- 0.047 min-1) rats, whereas in hyperglycemic animals recovery was slow (0.108 +/- 0.044 min-1, P < .0001 compared with normoglycemic animals). The SQ 23Na NMR signal intensity increased to 117% of preischemia level in hypoglycemic (P < .05 compared with normoglycemic animals) and to 107% in normoglycemic and hyperglycemic animals during reperfusion. CONCLUSIONS: The slower increase in the 23Na DQ NMR signal intensity during forebrain ischemia in rats with higher blood glucose levels suggests that Na+ homeostasis is maintained longer in these animals. On reperfusion, the slower recovery of the DQ 23Na NMR signal intensity in hyperglycemic animals likely indicates a slower recovery of Na+ homeostasis, perhaps contributing to the increased neuronal injury after cerebral ischemia in hyperglycemic animals.

Animals↗

PubMed1994

Ischemia-induced cellular redistribution of the astrocytic gap junctional protein connexin43 in rat brain.

The distribution and levels of the astrocytic gap junction protein, connexin43 (Cx43) was analyzed in various regions of brain as a function of time after neuronal loss and consequent reactive gliosis induced by bilateral carotid occlusion in rats. In the striatum 2 days after induction of ischemia, immunostaining intensity for Cx43 increased in animals exhibiting mild to moderate striatal damage, whereas areas of reduced staining surrounded by elevated levels of Cx43 immunoreactivity were observed in animals with severe ischemic damage. Immunolabelling of glial cell bodies was evident in ischemic, but not normal, striatum. Similar, though less dramatic, changes were seen at 7 days post-ischemia. Compared with the fine punctate pattern of Cx43 staining seen in normal striatum, ischemic striatal areas contained large aggregates of punctate profiles. In the hippocampus, increased immunostaining was seen at 2 and 7 days post-ischemia and, unlike normal hippocampus, neurons in the CA3 pyramidal cell layer were surrounded by a network of Cx43-immunoreactive puncta at the latter survival time. Immuno-EM analysis of ischemic tissue revealed numerous immunolabelled gap junctions among astrocytic processes in the vicinity of degenerating neurons and elevated levels of intracellular Cx43 immunoreactivity in astrocytic processes and cell bodies. No differences in protein levels or phosphorylation states of Cx43 were detected in either hippocampus or striatum by Western blot analyses of ischemic and control tissue. These results suggest that astrocytes respond to an ischemic insult by reorganizing their gap junctions, that the qualitative nature of their response is dependent on the severity of neuronal damage or loss, and that a pool of Cx43 normally undetectable by immunohistochemistry may contribute to the ischemia-induced elevations of immunolabelling for this protein.

Animals↗

PubMed1994

Hydrogen ion compartmentation during and following cerebral ischemia evaluated by 31P NMR spectroscopy.

Two peaks were observed in the inorganic phosphate region in 31P NMR spectra obtained during and shortly after incomplete forebrain ischemia induced in rats under normoglycemic conditions. Pre-ischemia, a single Pi peak was observed at a chemical shift of 2.5 ppm (pH 7.2). This peak shifted upfield to 1.6 ppm (pH 6.5) and, following reperfusion, returned to its pre-ischemia value. During ischemia and for a short time following reperfusion, a second, smaller peak was observed which we assigned to a second pool of inorganic phosphate. The data support the proposal by Kraig and coworkers of pH compartmentation between neurons and glia during and following transient forebrain ischemia.

Animals↗

PubMed1993

Metabolic changes associated with altering blood glucose levels in short duration forebrain ischemia.

31P nuclear magnetic resonance spectroscopy was used to follow changes in cerebral pH and high-energy phosphate metabolites during forebrain ischemia in hypo-, normo- and hyperglycemic rats, and during reperfusion in animals in which the blood glucose level was altered post-ischemia. Pre-ischemia, no differences in the levels of inorganic phosphate (Pi) and adenosine triphosphate (ATP) relative to phosphocreatine (PCr) or in tissue pH between blood glucose groups were observed. During ischemia, the decrease in tissue pH was found to be dependent on the pre-ischemic blood glucose concentration, being greatest in hyperglycemic and least in hypoglycemic animals. The increase of Pi, a consequence of the hydrolysis of high-energy phosphate metabolites, also depended on the blood glucose concentration, being greatest in hypoglycemic and least in hyperglycemic animals. ATP and PCr decreased more rapidly in hypoglycemic rats compared to normo- or hyperglycemic animals, which showed no differences in the rates of depletion. Post-ischemic hyperglycemia resulted in delayed recovery of tissue pH in all groups and of PCr and ATP in animals hyperglycemic throughout the experiment. Insulin administration immediately following ischemia increased the rate of recovery of pH, ATP and PCr in hyperglycemic animals. ATP remained significantly below pre-ischemia level in all subgroups at 1 h post-ischemic, while PCr was lower than it was pre-ischemia only in those subgroups hyperglycemic prior to and/or following ischemia. In animals maintained severely hypoglycemic throughout the experiment, erratic blood pressure and cerebral energy failure during the reperfusion interval were observed.

Adenosine Triphosphate↗

PubMed1993

Ischemic neocortical protection with U74006F--a dose-response curve.

A dose-response curve for the lipid peroxidation inhibitor U74006F was established in a rat forebrain ischemia model. Transient forebrain ischemia was induced by bilateral carotid occlusion plus controlled hypotension (50 mmHg) for 10 min. U74006F was administered at doses of 0.3, 1, 3, 7, or 10 mg/kg 30 min prior to ischemia. Control animals received vehicle (0.02 M citrate buffer in 0.8% NaCl). Brains were perfusion-fixed on day 7 post-ischemia for histopathological examination. For both the hippocampus and striatum, neuronal injury was not significantly different between groups. Within the neocortex ischemic neuronal injury was significantly less (P < 0.05) in the 7 mg/kg U74006F-treated group compared to the control, 1 mg/kg, or 3 mg/kg U74006F-treated groups.

Animals↗

PubMed1993

Failure of 2'-deoxycoformycin to protect against transient forebrain ischemia in rat.

We determined whether 2'-deoxycoformycin (DCF), a potent highly specific inhibitor of adenosine deaminase (ADA), protected against transient forebrain ischemic neuronal injury in rat. Anesthetized male Sprague-Dawley rats received i.p. injections of either saline, 0.5 mg/kg or 5 mg/kg DCF 2 h before undergoing a 10-min forebrain ischemic insult induced by bilateral carotid artery occlusion with concomitant hypotension. Rat brain sections taken 7 days post-ischemia showed damage mostly in the CA1 region of the hippocampus. Quantification of neuronal injury showed no significant differences between saline- or DCF-treated rats. These results indicate that, contrary to previous reports, DCF does not protect against the neuronal damage that follows forebrain ischemia in rat.

Animals↗

PubMed1993

Cerebral metabolic and histological effects of thioacetamide-induced liver failure.

Acute liver failure was induced in rats by successive administrations of thioacetamide over 3 days. At progressing stages of hepatic encephalopathy (HE), brains were fixed with microwave irradiation for analysis of metabolite levels or with formaldehyde for histopathological analysis. Metabolite levels were determined using 1H-nuclear magnetic resonance spectroscopy of perchloric acid extracts of the frontal cortex, parietal or occipital cortex, hippocampus, striatum, brain stem, and cerebellum. After thioacetamide treatment, thioacetamide and its metabolites were detected in the brains at levels that did not correlate with the stage of HE. No changes were observed in the levels of N-acetylaspartate, alanine, gamma-aminobutyric acid, aspartate, or inositol in any brain region after thioacetamide treatment. HE was accompanied by elevated glutamine, glucose, and lactate throughout the brain. At all stages of HE, taurine was decreased in the neocortex and hippocampus, and glutamate and choline compounds were decreased in the frontal cortex. None of the metabolite changes showed progression with the stage of HE. Progressing HE was accompanied by increasing neuronal injury in layer III of the neocortex, in the Purkinje cells of the cerebellum, and in the hippocampus, particularly in the CA4 sector. The similarity of this distribution of injury to that associated with excitotoxic injury suggests that metabolic abnormalities after acute hepatic failure may give rise to adverse effects at excitatory (glutamatergic) neuronal receptors, leading to neuronal injury and clinical symptoms of progressing encephalopathy in this model. However, neuronal injury and the presence of thioacetamide and its metabolites in the brain raise questions about the validity of thioacetamide-induced liver failure as a model for clinical HE.

Animals↗

PubMed1993

1H magnetic resonance spectroscopy of extracts of human epileptic neocortex and hippocampus.

We used high-resolution 1H magnetic resonance spectroscopy to determine the concentrations of several metabolites (lactate, alanine, N-acetylaspartate [NAA], gamma-aminobutyrate, glutamate, aspartate, creatine, cholines, taurine, inositol, and succinate) in tissue from patients undergoing surgical treatment of intractable epilepsy, and correlated the metabolite profiles with the results of histopathologic analysis of the excised tissue. We found no differences in metabolite levels for tissue from actively spiking or nonspiking neocortical sites in temporal lobe epilepsy patients. In neocortical tissue from patients with chronic localized encephalitis (Rasmussen's encephalitis), the metabolite concentrations varied with the severity and extent of the encephalitis. In tissue showing mild encephalitis and mild histologic abnormalities, the metabolite levels differed little from those found for nonencephalitic neocortical tissue. Tissue showing marked abnormalities and extensive encephalitis had decreased NAA, glutamate, cholines, and inositol. In hippocampal tissue from temporal lobe epilepsy patients, the levels of NAA, glutamate, and aspartate were lower and the levels of alanine, taurine, and inositol were higher than in neocortical tissue from the same patients. The decrease in the levels of NAA and glutamate was greater in gliotic hippocampal tissue. The results suggest that in vivo 1H magnetic resonance spectroscopy may aid in diagnosing the extent of chronic localized encephalitis and the severity of hippocampal gliosis.

Adolescent↗

PubMed1993

Nuclear magnetic resonance study of cerebrospinal fluid from patients with multiple sclerosis.

Proton nuclear magnetic resonance (NMR) spectroscopy was used to examine cerebrospinal fluid (CSF) from patients (n = 30) with actively progressive multiple sclerosis (MS). Metabolite concentrations obtained from the spectra were compared to those determined from the spectra of CSF from control patients (n = 27) with benign spinal disorders. No significant difference was found between the 2 groups for most constituents, including lactate, glutamine, citrate, creatine and creatinine, and glucose. Acetate levels were significantly higher in MS patients, while formate levels were significantly lower, than the controls. There were no significant differences in metabolite concentrations in CSF from early and longstanding MS patients. A peak due to an unidentified compound was found at 2.82 ppm in the spectra of CSF from patients with actively progressive MS, but not in the spectra of CSF from the controls. The peak was not found in spectra of CSF from patients with AIDS dementia complex (n = 9) or Parkinson's disease (n = 5), but it did appear in spectra of CSF from 1 patient with Jakob-Creutzfeldt disease (out of 3 examined) and from 1 patient (out of 7) with Guillain-Barré disease. The unidentified compound is volatile and, from the chemical shift of the observed NMR peak, is probably an N-methyl compound. As such, it may be an intermediate in the cholinoglycine cycle, in which an abnormality has been proposed to exist in MS patients.

Adult↗

PubMed1992

High-resolution 1H NMR spectroscopy studies of extracts of human cerebral neoplasms.

High-resolution 1H NMR spectroscopy has been used to measure the concentrations of metabolites (alanine, N-acetylaspartate, gamma-aminobutyric acid, glutamate, glutamine, aspartate, taurine, glycine, succinate, creatine, cholines, inositol, and glucose) in perchloric acid extracts of human epileptic cortex and brain tumors. All tissue was obtained by surgical biopsy, excised before thermal coagulation, and immediately frozen in liquid nitrogen. Lower levels of N-acetylaspartate and gamma-aminobutyric acid and a shift in the glutamate/glutamine ratio toward glutamine in the tumors reflect neuronal loss. Abnormal glucose metabolism (aerobic glycolysis) in the tumors gives decreased levels of succinate, glutamate, aspartate, glutamine, and creatine and generally increased concentrations of glycine and alanine. Differences in metabolite concentrations that may be of use in differential tumor diagnosis include lower creatine and inositol in meningiomas than in astrocytomas. Lower taurine differentiates benign from malignant astrocytomas. Malignant astrocytomas and metastatic tumors are more regionally heterogeneous than meningiomas or benign astrocytomas. Mannitol, administered perioperatively to all patients from whom tissue was obtained, was observed only in the spectra of extracts of tissue from tumors which enhanced on computerized tomographic imaging.

Adolescent↗

PubMed1992

Mannitol does not affect energy metabolism in forebrain ischemia.

Mannitol has a beneficial effect on ischemic injury following a short-duration forebrain ischemic insult in rats. Using the same animal model, we attempted to show that this effect of mannitol could be traced (via an improvement in cerebral blood flow) to a tempering of the collapse in the high-energy phosphates that occurs during the insult. A 10 min ischemic insult was induced by bilateral carotid artery occlusion followed by a reduction of the blood pressure to 50 mmHg through removal of blood via a tail catheter. 31P NMR spectroscopy was used to monitor the energy state and the pH prior to, during, and after the insult. The studies show that mannitol administered in doses of 0.25 g kg-1 or 1.0 g kg-1 prior to the insult has no significant effect on the high-energy phosphate levels or on the cerebral pH during ischemia, or on their post-ischemia recovery.

Animals↗

PubMed1992

Forebrain ischemia in diabetic and nondiabetic BB rats studied with 31P magnetic resonance spectroscopy.

In spontaneously diabetic BB rats, the effect of chronically maintained blood glucose levels on the degree of energy failure and brain pH change during an ischemic insult, and on subsequent recovery after reperfusion, was studied with in vivo 31P magnetic resonance spectroscopy. Short duration forebrain ischemia (10-min carotid occlusion plus hypotension of 50 mmHg) was induced in diabetic and nondiabetic male BB rats whose blood glucose levels were maintained with insulin. Spectra were obtained in 1-min blocks before, during, and for 1 h after ischemia. Before ischemia, hypoglycemic (blood glucose less than 3 mM) diabetic rats had an increased Pi peak intensity, with no significant pH change, compared with other groups. During ischemia, the rate and extent of hydrolysis of high-energy phosphate metabolites (as measured by an increase in Pi) decreased, and the severity of tissue acidosis increased as preischemia blood glucose concentration increased. Among hyperglycemic BB rats, similar ischemia-induced changes were found for subgroups with blood glucose levels of 13.7 +/- 1.2 and 20.3 +/- 0.6 mM, in keeping with the known decrease in hexose binding sites associated with chronic hyperglycemia. Decline in PCr level during ischemia was not significantly different between groups. With reperfusion, both Pi and pH values rapidly returned to preischemia values. PCr levels, however, did not recover in hyperglycemic diabetic animals, with the degree of residual impairment dependent on the preischemia glucose level. Results suggest that optimal management of diabetes may lessen the degree of injury within the ischemic penumbra in diabetic patients who suffer a stroke.

Analysis of Variance↗

PubMed1992

Magnetic resonance imaging and 31P magnetic resonance spectroscopy study of the effect of temperature on ischemic brain injury.

Transient forebrain ischemia was induced in rats whose brain temperature was 31, 33, 35, 38, or 40 degrees C. The development of regional injury was followed using magnetic resonance (MR) imaging, with the ultimate extent of neuronal injury quantified histopathologically. Animals in the hypothermic groups showed minimal changes in MR images over 4 days; normothermic animals showed intensity enhancement attributed to progressive edema developing in the striatum and, later, in the hippocampus. Ischemia at 40 degrees C resulted in widespread edema formation by 1 day post-ischemia; animals in this group did not survive beyond 30 hours. Histopathological analysis at 4 days (1 day for the hyperthermic group) post-ischemia showed that neuronal damage in the normothermic group was confined to the hippocampus and striatum. Minimal damage was found in the hypothermic groups; damage in the hyperthermic group was severe throughout the forebrain. There were no differences in the pre-ischemia 31P MR spectra for the different groups. During ischemia, the increase in intensity of the Pi peak and the fall in tissue pH increased with temperature in the order hypothermic less than normothermic less than hyperthermic group of animals. Post-ischemia energy recovery was similar in all groups, while pH recovered more rapidly in hypothermic animals.

Animals↗

PubMed1991

The effects of caffeine on ischemic neuronal injury as determined by magnetic resonance imaging and histopathology.

The effects of caffeine on ischemic neuronal injury were determined in rats subjected to forebrain ischemia induced by bilateral carotid occlusion and controlled hypotension (50 mmHg for 10 min). High resolution (100 microns) multi-slice, multi-echo magnetic resonance images were obtained daily for three consecutive days post-operatively in sham-operated rats and in rats that received either saline vehicle (controls), a single i.v. injection of 10 mg/kg caffeine 30 min prior to an ischemic insult (acute caffeine group), or up to 90 mg/kg per day of caffeine for three consecutive weeks prior to an ischemic insult (chronic caffeine group). Rats in the control group exhibited enhanced magnetic resonance image intensity in the striatum 24 h after ischemia which increased in the striatum and also appeared in the hippocampus after 48 h, and which began to resolve in both regions by 72 h post-ischemia. Histopathological analysis of each rat following the final magnetic resonance examination showed that ischemic neuronal injury was strictly confined to the brain regions showing magnetic resonance image changes. Acute caffeine rats showed accelerated changes in the magnetic resonance images, with increased hippocampal intensity appearing at 24 h post-ischemia. Although there was magnetic resonance evidence of accelerated injury, quantitative analysis of the histopathological data at 72 h showed no significant difference in the extent of neuronal injury in any brain region between control-ischemic and acute caffeine rats. Nine out of 11 rats in the chronic caffeine group showed no magnetic resonance image changes over the three study days. Chronic caffeine rats had significantly less neuronal damage in all vulnerable brain regions than either of the other groups of ischemic rats. The accelerated ischemic injury in rats treated with an acute dose of caffeine may occur secondary to antagonism of adenosine receptors, whereas protection from ischemic injury following chronic administration of caffeine may be mediated by up-regulation of adenosine receptors.

Adenosine↗

PubMed1991

Quantitative proton nuclear magnetic resonance of plasma for screening hepatic metabolism during ethanol infusion in cats.

The effects of increasing blood ethanol levels on hepatic metabolism were studied in anesthetized cats whose prior fluid intake contained ethanol for 24 days. A hepatic venous long-circuit technique with an extracorporeal reservoir was used to allow hemodynamic measurements and repeated sampling of arterial, portal, and hepatic venous blood without depletion of blood volume. For ethanol, Vmax was 106 +/- 15 mumol.min-1.100 g-1 liver and Km was 164 +/- 31 microM. A previous study showed that there were no changes in O2 uptake by the liver, suggesting other oxidative processes were suppressed during ethanol metabolism. In this study, proton nuclear magnetic resonance spectroscopy was used to simultaneously screen several plasma metabolites to elucidate other metabolic processes that may be perturbed in the liver during ethanol infusion. Hepatic lactate uptake remained unaltered when ethanol metabolism was less than 0.5 Vmax but was suppressed on an equimolar basis with ethanol metabolism when ethanol metabolism rose above 0.5 Vmax. Thus, lactate oxidation is one process that can be suppressed to allow ethanol oxidation without additional O2 uptake by the liver. In addition, no release of acetate from the liver occurred during ethanol metabolism in these experiments. This surprising finding suggests ethanol metabolism may, under some conditions or in some species, result in fatty acid synthesis rather than acetate release. Eight other major metabolites remained unchanged during ethanol infusion.

Acetates↗

PubMed1991

Effect of U74006F on forebrain ischemia in rats.

We examined the effect of a putative lipid peroxidation inhibitor, the 21-aminosteroid U74006F, on transient forebrain ischemia in rats. Acute-treatment rats received either 3 mg/kg U74006F (n = 7) or carrier vehicle (n = 5) intravenously 30 minutes before ischemia, sustained-treatment rats received the same treatment before ischemia followed by 3 mg/kg U74006F (n = 6) or carrier vehicle (n = 5) intraperitoneally every 6 hours for 48 hours, and control rats (n = 7) received no injection. Coronal magnetic resonance images were obtained daily for 3 days, followed by the histological examination of perfusion-fixed brains. Control rats demonstrated magnetic resonance image changes indicative of neuronal damage in the striatum at 24 hours postischemia, followed by changes in the hippocampus and neocortex at 48 hours. No significant effect of U74006F treatment on striatal or hippocampal injury was demonstrated. However, both the acute and sustained U74006F treatments produced a significant reduction in the severity of neuronal damage in the neocortex (p less than 0.05). Our results suggest that U74006F is of benefit in ameliorating ischemic neuronal injury, particularly in the neocortex, and raise the possibility of regional variability in lipid peroxidation following an ischemic insult.

Animals↗

PubMed1990

Experimental cerebral ischemia studied using nuclear magnetic resonance imaging and spectroscopy.

The effects of short-duration forebrain ischemia on cerebral metabolism in the rat have been studied using several nuclear magnetic resonance (NMR) techniques. In vivo phosphorus-31 (31P) NMR spectroscopy showed that the model produces rapid cerebral energy failure and acidosis. Reperfusion was accompanied by recovery of high-energy metabolites in about 30 minutes, with a slower recovery of pH. Proton (1H) NMR spectra of perchloric acid extracts of selected brain regions showed that levels of alanine and gamma-aminobutyric acid (GABA) were elevated and the level of glutamate was depressed immediately after the ischemic insult, returning to normal by 24 hours. The lactate level remained elevated for up to 7 days after ischemia, suggesting ongoing abnormal mitochondrial function. Postischemic cerebral glucose metabolism was monitored using carbon-13 (13C)-labelled glucose as an NMR probe. Glycolysis was impaired immediately after the ischemic insult, resulting in accumulation of glucose in the tissue and reduced formation of amino acids and tricarboxylic acid cycle intermediates. Glycolysis recovered by 1 hour, but underwent a secondary decrease at 24 hours, the time at which neuronal injury became manifest histologically and physiologically. Nuclear magnetic resonance imaging was used to follow the regional development of tissue injury in selectively vulnerable brain regions. Striatal changes were evident by 24 hours after reperfusion, increasing in intensity and accompanied by hippocampal changes by 48 hours, then becoming less pronounced by 72 hours. Histologic analysis of regional neuronal injury correlated well with the imaging results, establishing NMR imaging as a noninvasive method of visualizing the regional development of ischemic tissue injury.

Animals↗

PubMed1989

1H NMR of plasma for detecting cancer. The effect of trauma on linewidths.

The specificity of detecting cancer using the methyl and methylene linewidths in the 1H NMR spectrum of plasma has been examined for patients with brain tumors. Apparently healthy controls are distinguished from patients with metastatic brain tumors or malignant primary intracranial neoplasms, although the amount of overlap with the latter group precludes the use of the method as a diagnostic tool. Furthermore, patients with benign primary intracranial neoplasms are not distinguished from those with malignant primary brain tumors, and non-tumor neurological patients with traumatic head injury are not distinguished from cancer patients. Surgical treatment of neurological patients results in a significant narrowing of the 1H NMR bands of interest, particularly for patients initially exhibiting broad lines. The narrowing persists for at least 3 weeks. This effect of surgical or other trauma on the 1H NMR linewidths indicates that the method is unsuitable for assessing the efficacy of surgical treatment of cancer.

Blood Chemical Analysis↗