Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Recovery phases”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed1994

Extrasynaptic effects of GABA (gamma-aminobutyric acid) agonists on myelinated axons of peripheral nerve.

Effects of the inhibitory neurotransmitter, GABA (gamma-aminobutyric acid) on the excitability of myelinated fibers of isolated amphibian sciatic nerves and their dorsal and ventral spinal roots have been compared with those of a GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), and the GABAB agonist baclofen. Graded, prolonged increases in the amplitude of A-fiber half-maximal compound action potentials of Rana ballenderi sciatic nerves were evoked by GABA (Rmax = 49%, EC50 = 0.1 mM); responses to THIP were smaller (Rmax = 34%, EC50 = 1.1 mM) and with a different, distinctly biphasic recovery phase. In studies of Rana catesbeiana nerves and their attached spinal roots, excitability increases produced in fibers of the ventral roots by GABA were smaller than those of the dorsal roots. Peak changes evoked by THIP in both roots were similar to the effects of GABA on the ventral root; however, THIP's ventral root response showed much less sensitivity and was followed by a rapid recovery phase, undershoot, and secondary, prolonged enhancement. Bicuculline methiodide antagonized agonist-induced increases, and revealed the presence of significant decreases in excitability of the ventral root fibers at concentrations of GABA or THIP < 3 mM. Baclofen evoked inconsistent changes in the excitability of whole nerve and root fibers; small increases occurred with lower doses and secondary, delayed decreases with higher doses. The high concentration (> or = 0.1 mM) of the active isomer needed to cause a small response suggests a limited contribution and (or) presence of GABAB receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed2000

Induced hsp70 is in small, cytoplasmic complexes in a cell culture model of renal ischemia: a comparative study with heat shock.

A number of clinical conditions are known to result in the induction of heat shock proteins, but detailed studies on stress response have focused mostly on heat shock as a model. We have analyzed the induction and intracellular distribution of heat shock proteins in a reversible adenosine triphosphate (ATP) depletion model of renal ischemia. Two Hsp70 homologues, Hsp70 in the cytoplasm and BiP in the endoplasmic reticulum (ER) lumen, were found significantly induced during the recovery phase of ATP depletion. Other members of the heat shock protein family, such as Hsp90, constitutive Hsc70, and a related protein Hop60, were not induced. The induction of stress proteins on ATP depletion differed from that after heat shock in the kinds of proteins elaborated, their induction kinetics, and their intracellular distributions. Biochemical fractionation and indirect immunofluorescence experiments indicated that Hsp70 was predominantly cytoplasmic in the recovery phase of ischemia-like stress. Velocity sedimentation on sucrose gradients showed that induced Hsp70 sedimented as small, soluble complexes, ranging in size from 4S20,w to 8S20,w. The results suggest a role for induced Hsp70 that may be different from one of protecting aggregated proteins as under heat shock and emphasize the need for their characterization in other clinical conditions that result in stress response.

Adenosine Triphosphate↗
PubMed1992

P amylase is always greater than S in spot urine of normal subjects. Diagnostic implications.

Single random samples of urine were collected from 50 control subjects; 27 patients with chronic pancreatitis; 19 with acute pancreatitis; 6 with acute on chronic pancreatitis; five in the recovery phase of acute attack; four patients with pseudocysts. Salivary (S) and pancreatic (P) amylase values were measured by cellulose acetate electrophoresis. The P amylase values always exceeded those of S amylase in the control specimens. In acute pancreatitis, both the lower and upper levels of total and P amylase were considerably higher than in the controls, and these high values tended to return to normal during the recovery phase of acute pancreatitis. The S amylase values were often very low or undetectable during the acute phase. Values for P amylase exceeded control values in patients with pseudocysts even in the presence of chronic pancreatitis. In chronic calcific pancreatitis, S amylase was higher than P amylase. We conclude that P amylase is always greater than S amylase in normal urine specimens, and a change in this pattern may be helpful in diagnosing various forms of pancreatitis.

Amylases↗
PubMed2002

Invasive pulmonary aspergillosis resulting in respiratory failure during neutrophil recovery from postchemotherapy neutropenia in three patients with acute leukaemia.

Respiratory failure is a severe complication of invasive pulmonary aspergillosis (IPA). Its pathogenesis is not well understood. We herein describe three cases of subacute respiratory failure that occurred during the recovery phase of neutropenia following induction chemotherapy for acute leukaemia with IPA. In each case, severe neutropenia (19-85 days), high-grade fever, severe anaemia, the use of granulocyte-colony-stimulating factor and increasing infusion volume were noted. As the neutrophil count was recovering, the shadows on the chest X-ray expanded with progressing hypoxia. We should pay attention to the respiratory failure during the recovery phase of neutropenia in patients with IPA.

Acute Disease↗
PubMed2006

Molecular properties of rhodopsin and rod function.

Signal transduction in rod cells begins with photon absorption by rhodopsin and leads to the generation of an electrical response. The response profile is determined by the molecular properties of the phototransduction components. To examine how the molecular properties of rhodopsin correlate with the rod-response profile, we have generated a knock-in mouse with rhodopsin replaced by its E122Q mutant, which exhibits properties different from those of wild-type (WT) rhodopsin. Knock-in mouse rods with E122Q rhodopsin exhibited a photosensitivity about 70% of WT. Correspondingly, their single-photon response had an amplitude about 80% of WT, and a rate of decline from peak about 1.3 times of WT. The overall 30% lower photosensitivity of mutant rods can be explained by a lower pigment photosensitivity (0.9) and the smaller single-photon response (0.8). The slower decline of the response, however, did not correlate with the 10-fold shorter lifetime of the meta-II state of E122Q rhodopsin. This shorter lifetime became evident in the recovery phase of rod cells only when arrestin was absent. Simulation analysis of the photoresponse profile indicated that the slower decline and the smaller amplitude of the single-photon response can both be explained by the shift in the meta-I/meta-II equilibrium of E122Q rhodopsin toward meta-I. The difference in meta-III lifetime between WT and E122Q mutant became obvious in the recovery phase of the dark current after moderate photobleaching of rod cells. Thus, the present study clearly reveals how the molecular properties of rhodopsin affect the amplitude, shape, and kinetics of the rod response.

Animals↗
PubMed1997

Electromyographic analysis of muscle fatigue in anterior cruciate ligament deficient knees.

The aim of this study was to detect possible differences in muscle fatigue and recovery of knee flexor and extensor muscles in patients with a deficient anterior cruciate ligament compared with patients with a normal anterior cruciate ligament. Surface electromyography of 15 patients with anterior cruciate ligament deficiency was performed while the muscles were under 80% of maximum isometric contraction, and after 1, 2, 3, and 5 minutes of rest. During the first 60 seconds of contraction, all muscles recorded significantly decreased mean power frequency and increased amplitude. The rate of decrease of mean power frequency was significantly greater in the injured quadriceps and normal hamstrings. All muscles except two recovered to the initial mean power frequency level after 1 minute of rest. All but two muscles in the injured and normal limb recorded an overshoot of mean power frequency during the recovery phase. This overshoot phenomenon also was seen for some muscles in the amplitude analysis. The findings confirm the fatigue state in all the muscles, suggest recruitment of more Type II fibers as the muscle fatigues, and show the physiologic adaptation of the quadriceps and hamstrings to anterior cruciate ligament insufficiency. The current study indirectly shows a dissociation between low intramuscular pH and mean power frequency during the recovery phase. It also indirectly suggests that the atrophied thigh muscles have fiber type composition similar to that of the normal side.

Adaptation, Physiological↗
PubMed1996

Interleukin-6 and its soluble receptor during acute meningococcal infections: effect of plasma or whole blood exchange.

OBJECTIVES: To determine the pattern of the soluble interleukin (IL)-6 receptor during acute meningococcal infections and recovery phase, and to measure the effect of plasma or whole blood exchange on the plasma concentrations of these mediators. DESIGN: Prospective, descriptive patient study. SETTING: University hospital intensive care unit. PATIENTS: Patients with bacteriologically proven meningococcal infections were entered in the study. Three group were formed: a) patients with meningitis without shock (group A); b) patients with meningitis and shock (group B); and c) patients with shock only (group C). INTERVENTIONS: Part (n = 9) of the patients with shock underwent plasma or whole blood exchange. MEASUREMENTS AND MAIN RESULTS: Serum concentrations of interleukin-6 and soluble IL-6 receptors were determined sequentially during the acute and recovery phases. Peak concentrations of IL-6 were highest in group C, followed by group B and group A. Soluble IL-6 receptor concentrations showed an opposite pattern and were all below normal. Soluble IL-6 receptor concentrations were negatively correlated with the IL-6 concentrations. During recovery, IL-6 rapidly decreased and soluble IL-6 receptors increased to supranormal concentrations, after which concentrations returned to normal. Plasma or whole blood exchange did not significantly influence IL-6 concentrations but did increase the soluble IL-6 receptor concentration directly after an exchange session followed by a rapid decrease. CONCLUSIONS: Soluble IL-6 receptor concentrations are low in acute meningococcal infections. Plasma or whole blood exchange temporarily increases these concentrations. It needs to be determined whether the effect of this therapy is beneficial to the patient.

Acute Disease↗
PubMed2005

FT-IR Study of the influence of Tribulus terrestris on Mercury intoxicated mice, Mus musculus liver.

FT-IR spectra of liver tissue isolated from mice, Mus musculus, have been recorded in the region of 4000 - 400 cm-1 for normal, mercury treated and recovery phase. In this study, the total protein content was found to be decreased in the liver tissues after treatment with median-lethal dose of mercuric chloride. The marked fall in the level of bio-chemical constituent in the tissue due to metal exposure indicates the rapid initiation of the breakdown of the bio-chemical constituents to meet the energy demand during toxic stress. During the recovery phase, the decreased levels of bio-chemical constituents are restored to near normal level. Methanol fractions of Tribulus terrestris fruit extract was administrated on mercury intoxicated mice for 15 days. After the administration, the mercury-intoxicated animals slowly recovered from the adverse effect of mercury poisoning with the help of plant bio-formulations. The results are discussed in detail.

Animals↗
PubMed2000

Involvement of extracellular signal-regulated protein kinase in gliosis induced during recovery from metabolic inhibition.

Brain reperfusion may be of particular importance in the etiology of periventricular leukomalacia, of which the common findings are gliosis and ventricular dilatation. To investigate the mechanism of this pathogenesis, we used a metabolic inhibition (MI) model using cyanide plus deoxyglucose treatment of cultured glia isolated from fetal rat brain and examined the activity of extracellular signal-regulated protein kinase (ERK) during MI and also during the recovery from MI of 30 min. ERK activation was stimulated during MI and the recovery from MI. The time course and extent of activation of ERK during MI and the recovery from MI, however, were distinctly different. Activation of ERK was stimulated within 5 min of MI and declined thereafter. Activation of ERK was sustained during the recovery phase from MI and the extent of the activation was much greater than that during MI. Pretreatment with EGTA to eliminate extracellular Ca(2+), or with APV, an NMDA receptor antagonist, to inhibit Ca(2+) influx through the NMDA receptor, attenuated the activation of ERK. Moreover, pretreatment with PMA to downregulate PKC abolished the activation of ERK. PD98059, an inhibitor of ERK kinase, attenuated the cell proliferation induced by MI followed by recovery from MI. These results suggest that ERK is involved in gliosis during the recovery phase from MI and may play a role in the etiology of periventricular leukomalacia.

2-Amino-5-phosphonovalerate↗
PubMed1975

Effect ofO-(beta-hydroxyethyl)rutoside on intestinal tract cells following partial body irradiation.

In the present study the influence of O-(beta-hydroxyethyl)-rutoside (HR) on the intestinal cells of irradiated mice was investigated. The mitotic activity in the duodenum after irradiation of the abdomen with 800 and 1200 R was shown to be significantly increased during the recovery phase after application of HR. The number of irradiation induced stem cell pycnoses was markedly reduced by HR in the case of both radiation doses. The initially decreased incorporation rate of H3-thymidine was found to increase more rapidly during the first few hours after irradiation in animals pretreated with HR than in those untreated. Cytogenesis of goblet cells, in the duodenum proved to be favourably influenced by HR. During the recovery phase the values were found to be above those observed in the control group and in the untreated animals. The mitosis free interval in the rectal cells immediately after irradiation proved to be shortened in the pretreated animals and the re-increase of the mitotic activity was found to be accelerated. The number of cell pycnoses was also markedly reduced after application of HR, while the incorporation rate of H3-thymidine was accelerated. The radiosensitivity of the goblet cells was not influenced by HR. Disorders in differentiation of the muciferous cells were observed in both test groups.

Abdomen↗
PubMed1997

Feeding mechanism and functional morphology of the jaws of the lemon shark Negaprion brevirostris (Chondrichthyes, Carcharhinidae)

This study tests the hypothesis that preparatory, expansive, compressive and recovery phases of biting behavior known for aquatically feeding anamniotes are conserved among extant elasmobranch fishes. The feeding mechanism of the lemon shark Negaprionbrevirostris is examined by anatomical dissection, electromyography and high-speed video analysis. Three types of feeding events are differentiated during feeding: (1) food ingestion primarily by ram feeding; (2) food manipulation; and (3) hydraulic transport of the food by suction. All feeding events are composed of the expansive, compressive and recovery phases common to aquatically feeding teleost fishes, salamanders and turtles. A preparatory phase is occasionally observed during ingestion bites, and there is no fast opening phase characteristic of some aquatically feeding vertebrates. During the compressive phase, palatoquadrate protrusion accounts for 26% of the gape distance during jaw closure and is concurrent with muscle activity in the dorsal and ventral preorbitalis and the levator palatoquadrati. Hydraulic transport events are shorter in duration than ram ingestion bites. Prey ingestion, manipulation and hydraulic transport events are all found to have a common series of kinematic and motor components. Individual sharks are capable of varying the duration and to a lesser extent the onset of muscle activity and, consequently, can vary their biting behavior. We propose a model for the feeding mechanism in carcharhinid sharks, including upper jaw protrusion. This study represents the first electromyographic and kinematic analysis of the feeding mechanism and behavior of an elasmobranch.

Journal Article↗
PubMed2001

Increased noradrenaline release from rat preoptic area during and after sevoflurane and isoflurane anesthesia.

PURPOSE: To study the effects of sevoflurane and isoflurane on noradrenaline release from the rat preoptic area (POA). METHOD: Sixteen male Wistar rats were studied. A microdialysis probe with a 2 mm long semipermeable membrane was implanted in the POA. Dialysates were collected at intervals often minutes. After obtaining five control samples for 50 min, 30 min inhalation of 3% sevoflurane or 1.8% isoflurane was performed. After cessation of the inhalation, five more samples were obtained for 50 min as recovery phase. Noradrenaline (NA) concentration in the dialysates was measured by high pressure liquid chromatography with an electrochemical detector. RESULTS: Both sevoflurane and isoflurane caused marked increases in NA release from the rat POA (sevoflurane 233% at 20 min, isoflurane 357% at ten minutes after the start of inhalation). The marked NA releases were also observed during the emergence from sevoflurane and isoflurane anesthesia (sevoflurane 269% at 20 min, isoflurane 368% at ten minutes in the recovery phase). CONCLUSION: This study suggests that enhanced release of NA in the POA during sevoflurane and isoflurane may explain the excitatory phase observed during the peri-anesthetic period with these agents.

Anesthesia↗
PubMed1995

Gastroesophageal reflux-induced bronchoconstriction. Is microaspiration a factor?

STUDY OBJECTIVE: To evaluate the role of microaspiration in gastroesophageal reflux-induced bronchoconstriction. DESIGN: Prospective study blinded to the subject. SETTING: Outpatient laboratory of a 908-bed university hospital. PARTICIPANTS: Thirty nonsmoking adults divided into two groups: asthmatics with reflux (AR), 20; and subjects with gastroesophageal reflux (R), 10. INTERVENTIONS: Dual esophageal pH probe placed. Esophageal infusions of normal saline solution, 0.1N hydrochloric acid, then normal saline solution, each lasting 18 min, were followed by two 20-min recovery periods. Subjects remained in the supine position throughout. Spirometry and specific airway resistance (SRaw) performed at baseline, after each esophageal infusion and recovery period. Proximal esophageal acid exposure, a requirement for microaspiration, was assessed by the proximal esophageal pH probe. RESULTS: Peak expiratory flow rate (PEF) decreased with esophageal acid in the AR group and did not recover immediately despite esophageal acid clearance with a significant main effect of subject groups (p < 0.021) by repeated measures analysis of covariance. This decrease in PEF was not associated with the presence of proximal esophageal acid exposure (p = 0.618). Specific airway resistance increased in the AR group with esophageal acid and worsened despite acid clearance, especially during the second recovery phase, with a significant phase (p < 0.009) and group by treatment effect (p < 0.009). The presence of proximal esophageal acid exposure was not associated with this deterioration in SRaw (p = 1.0). CONCLUSIONS: Esophageal acid infusions given in the supine position caused a decrease in PEF and an increase in SRaw in the asthma with reflux group, which did not improve despite acid clearance. These responses were not dependent on proximal esophageal acid exposure. Also, SRaw continued to worsen during the recovery phase in the AR group, which may represent a delayed bronchoconstrictor effect. These data suggest that microaspiration does not play a significant role in esophageal acid-induced bronchoconstriction.

Adult↗
PubMed2002

Brain-derived neurotrophic factor in patients with multiple sclerosis.

UNLABELLED: The aim of the present research was to verify the production of BDNF by peripheral blood mononuclear cells (PBMCs), unstimulated and stimulated with phytohemagglutinin (PHA), anti-OKT3 Ab and myelin basic protein (MBP), in 35 patients affected by multiple sclerosis (MS), 20 with relapsing-remitting (R-R) MS and 15 with secondary progressive (SP) MS. Seven R-R MS patients were assessed during the attack, in the subsequent recovery phase and also 3 months after relapse. The production of BDNF by PBMCs was also evaluated in 20 age- and sex-matched control subjects. Levels of BDNF were also determined in CSF of both patient groups and 20 control subjects. RESULTS: Levels of BDNF (pg/ml) in the supernatants of unstimulated and PHA-, anti-OKT3 Ab- and MBP-stimulated PBMCs in patients with R-R MS were significantly higher during relapse and in the recovery phase compared with values detected in the stable phase of the disease. Significantly lower BDNF values were found in unstimulated and stimulated PBMC supernatants of patients with SP MS compared to control subjects. This reduction was greater in patients with a 1-point increase in the EDSS score in the last 6 months compared with that in patients without a progression of the disability score. Reduction in the levels of BDNF was also confirmed in the CSF of SP MS patients compared with R-R MS patients assessed during a stable phase of the disease and control subjects. DISCUSSION: On the basis of recent experimental findings, a neuroprotective effect of BDNF produced by inflammatory cells can be hypothesized during relapses in MS. This can favor remyelination. The reduced production of BDNF by PBMCs of patients with SP MS can contribute to the progression of demyelinating disease and axonal loss in this form.

Adult↗
PubMed1995

Effects of lowered cytoplasmic calcium concentration and light on the responses of salamander rod photoreceptors.

1. In order to study the interactions between cytoplasmic calcium concentration ([Ca2+]i) and light in modulating the responses of rod photoreceptors, [Ca2+]i was held at different levels by manipulating Ca2+ fluxes across the outer segment membrane. 2. If [Ca2+]i was reduced by the removal of external Ca2+ in the continued presence of Na+, and then held near this reduced level by exposure to 0 Ca(2+)-0 Na+ solution, the onset of the recovery phase of the response to a bright flash delivered just before the return to Ringer solution was accelerated, much as is the case during light adaptation, provided that precautions were taken to minimize Na+ influx. 3. If the rod was first allowed to adapt to steady light, [Ca2+]i held near the appropriate light-adapted level by superfusion with 0 Ca(2+)-0 Mg(2+)-0 Na+ solution and the light extinguished, the onset of the recovery phase of the bright flash response varied with the original background intensity in the same way as in the continued presence of steady light. These results indicate that reduction of [Ca2+]i is sufficient to induce this manifestation of light adaptation in darkness. 4. When [Ca2+]i was held at a reduced level in darkness, not only was the sensitivity to dim flashes reduced, but the response rising phase was also delayed and its amplitude increased supralinearly with flash intensity, neither of which changes is seen during light adaptation. However, similar changes in response kinetics resulted when [Ca2+]i was held near its normal dark level and the phosphodiesterase was partially inhibited by 3-isobuty-1-methylxanthine (IBMX), suggesting that they arose indirectly from an elevated cyclic GMP concentration rather than from a direct effect of Ca2+. 5. If [Ca2+]i was held near the normal dark level and bright steady light presented, the circulating current was completely suppressed. Partial inhibition of the phosphodiesterase by superfusion with 0 Ca(2+)-0 Na+ solution including IBMX resulted in restoration of the circulating current. Dim flash responses recorded under these conditions exhibited kinetics similar to those recorded in 0 Ca(2+)-0 Na+ solution in darkness, in contrast to the response acceleration seen when [Ca2+]i was held near the appropriate light-adapted level. These results indicate that the kinetics of the flash response depend on [Ca2+]i rather than on the steady light intensity.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Ursodeoxycholate-induced changes in hepatic Na+-H+ exchange and biliary HCO3- excretion.

Ursodeoxycholate (UDC)-induced HCO3- -rich choleresis may be due to activation of sinusoidal Na+-H+ exchange followed by an increase in intracellular pH (pHi) and HCO3- excretion via canalicular Cl- -HCO3- exchange. To test this hypothesis, we studied the effect of UDC and tauroursodeoxycholate (TUDC) on net H+ efflux from perfused rat livers and pHi in isolated hepatocytes in the presence and absence of amiloride. UDC-induced increases in biliary HCO3- concentration and excretion were inhibited by amiloride. However, these increases were temporally associated with an initial decline in H+ efflux and pHi followed by a gradual recovery toward base line. The initial decline in H+ efflux was associated with a rapid uptake of UDC. Amiloride inhibited only the recovery phases of H+ efflux and pHi. TUDC increased amiloride-sensitive H+ efflux without affecting biliary [HCO3-] and decreased pHi in the presence but not in the absence of amiloride. Amiloride decreased TUDC-induced choleresis and HCO3- excretion most likely by decreasing TUDC excretion. TUDC decreased biliary [Cl-] and increased hepatic O2 uptake more than UDC. We conclude that a rapid influx of UDC in the protonated form decreases pHi and net H+ efflux initially. The recovery phase is due to Na+-H+ exchange activated by decreased pHi and possibly by UDC and increased cellular respiration. TUDC indirectly stimulates Na+-H+ exchange most likely by increasing cellular respiration. UDC-induced HCO3- -rich choleresis, which is observed at a time when both net H+ efflux and pHi are less than control values, is unlikely to be due to a direct activation of Na+-H+ exchange.

Amiloride↗
PubMed2006

Dynamic deformation and recovery response of red blood cells to a cyclically reversing shear flow: Effects of frequency of cyclically reversing shear flow and shear stress level.

Dynamic deformation and recovery responses of red blood cells (RBCs) to a cyclically reversing shear flow generated in a 30-microm clearance, with the peak shear stress of 53, 108, 161, and 274 Pa at the frequency of 1, 2, 3, and 5 Hz, respectively, were studied. The RBCs' time-varying velocity varied after the glass plate velocity without any time lag, whereas the L/W change, where L and W were the major and minor axes of RBCs' ellipsoidal shape, exhibited a rapid increase and gradual decay during the deformation and recovery phase. The time of minimum L/W occurrence lagged behind the zero-velocity time of the glass plate (zero stress), and the delay time normalized to the one-cycle duration remained constant at 8.0%. The elongation of RBCs at zero stress time became larger with the reversing frequency. A simple mechanical model consisting of an elastic linear element during a rapid elongation period and a parallel combination of elements such as a spring and dashpot during the nonlinear recovery phase was suggested. The dynamic response behavior of RBCs under a cyclically reversing shear flow was different from the conventional shape change where a steplike force was applied to and completely released from the RBCs.

Blood Flow Velocity↗
PubMed1992

Nuclear magnetic resonance spectroscopy and pattern recognition analysis of the biochemical processes associated with the progression of and recovery from nephrotoxic lesions in the rat induced by mercury(II) chloride and 2-bromoethanamine.

Nephrotoxic lesions were induced in Fischer 344 rats using HgCl2, a proximal tubular toxin, and 2-bromoethanamine (BEA), a medullary toxin. Biochemical effects of these toxins on urinary composition were observed by high resolution 1H NMR spectroscopy over 9 days after dosing. The onset of, progression of, and recovery from the induced toxic lesions were also followed histopathologically and related to the perturbed urinary biochemistry. Urinary concentrations of 20 endogenous substances were measured simultaneously by NMR at eight time points, to provide a time-related 20-dimensional description of the urinary biochemistry for each rat. Principal components analysis and nonlinear mapping were used to reduce the biochemical parameter spaces for each rat to two or three dimensions for display and classification purposes. An investigation of alternative data-presentation methods was made, and taking interanimal means of the map coordinates at each time point yielded a novel type of metabolic trajectory diagram with which the biochemical abnormalities associated with the HgCl2 and BEA lesions could be related to the progression and recovery phases of the toxic lesions. The time-course trajectories showed characteristically different paths for each toxin. These trajectories allowed the time points at which there were maximum metabolic differences to be determined and provided the visualization of net movements of the treatment group populations in time in relation to interanimal variation. Control animal urine samples subjected to this analysis showed simple clustering, with no evidence of metabolic trajectory. The trajectory for BEA showed different routes for onset of and recovery from toxicity, whereas for HgCl2 the outward trajectory (onset) mapped a space similar to the inward trajectory (recovery phase). This suggests that the NMR-detectable biochemical abnormalities after mercury toxicity mainly reflect the proportions of functional cells lining the nephron, whereas the biochemical abnormalities associated with renal medullary insult probably relate to functional integrity. An examination has been made for those metabolites that are most responsible for defining the trajectories, i.e., the discrimination of renal cortical and medullary toxicity from each other and from controls. These discriminatory metabolites (using paired t test, p < 0.001) included valine, taurine, trimethylamine N-oxide, and glucose for HgCl2 and acetate, methylamine, dimethylamine, lactate, and creatine for BEA, whereas citrate, succinate, N-acetyl resonances from as yet unidentified metabolites, hippurate, alanine, and 2-oxoglutarate played an important role in defining the biochemically perturbed trajectory of both toxins.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗