Multimodal MRI Longitudinal Assessment of White and Gray Matter in Different SPG Types of Hereditary Spastic Paraparesis.

Hereditary spastic paraplegias (HSP) are a group of genetically and clinically heterogeneous neurologic disorders. Hereby we describe a relatively large group of patients (pts) affected by HSP studied at baseline (31 pts) and at follow-up (mean period 28.9 ± 8.4 months; 23 pts) with multimodal advanced MRI: high-resolution T1 images for voxel-based morphometry (VBM) analysis, magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI). An age-matched healthy control (HC) group underwent the same neuroimaging protocol in a time schedule matched with the HSP patients. At baseline, VBM showed gray matter (GM) reduction in HSP in the right pre-frontal cortex and bilaterally in the thalami. MRS at baseline depicted in HSP patients compared to the HC group reduction of NAA/Cr ratio in the right pre-frontal region, increase of Cho/Cr ratio in the right pre-central regions, and increase of mI/Cr ratio on the left pre-central area. At cross-sectional follow-up analysis and longitudinal evaluation, no VBM and MRS statistically significant results were obtained. Tract-based spatial statistics (TBSS) analysis showed widespread DTI brain white matter (WM) alterations in patients compared to HC at baseline, which are characterized by reduction of fractional anisotropy (FA) and increase of mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity, as confirmed on cross-analysis of the follow-up dataset. A longitudinal analysis with TBSS in HSP patients did not show significant variations, while upon applying region-based analysis we found increased FA and decreased MD and AD in specific brain WM fiber complex during follow-up. The changes were not correlated with the clinical presentation (pure vs complicated HSP), motor function, and motility indexes or history of specific treatments (botulinum toxin). In conclusion, the cross-sectional analysis of the multiparametric MRI data in our HSP patients confirmed the non-prominent involvement of the cortex in the primary motor regions but rather of other more associative areas. On the contrary, DTI demonstrated a widespread involvement of the brain WM, including the primary motor regions, which was confirmed at follow-up. The longitudinal analysis revealed an apparent inversion of tendency when considering the expected evolution of a neurodegenerative process: we detected an increase of FA and a decrease of MD and AD. These time-related modifications may suggest a repair attempt by the residual central WM fibers, which requires confirmation with a larger group of patients and with a longer time interval.

Preserved brain functional plasticity after upper limb task-oriented rehabilitation in progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Limited research has been dedicated to upper limb (UL) rehabilitation in progressive multiple sclerosis (PMS). The objective in this pilot study was to investigate the effect of task-oriented UL rehabilitation in PMS and to perform explorative analyses of the magnetic resonance imaging (MRI) correlates of changes in motor performance. METHODS: Twenty-six PMS patients with mild UL impairment were prospectively enrolled and randomized into two groups: an active treatment group (ATG, n = 13) and a passive treatment group (PTG, n = 13). At baseline and after training, patients underwent MRI scans with structural and functional imaging and were evaluated with the action research arm test, the nine-hole peg test, the ABILHAND scale and the modified fatigue impact scale (MFIS). Measures of motor finger performance were obtained by engineered glove measuring. RESULTS: After rehabilitation, the ATG improved in several finger motor tasks (0.001 ≤ P ≤ 0.03, 0.72 ≤ Cohen's d ≤ 1.22) and showed reduced MFIS scores compared with the PTG (P = 0.03). The ATG showed increased functional connectivity within the cerebellar and thalamic resting state networks compared with the PTG (P < 0.05). Correlations were found between several measures of motor improvement and thalamic and sensorimotor networks (0.87 ≤ r ≤ 0.93, 0.001 ≤ P ≤ 0.03). No changes in cerebral volumes and diffusion tensor imaging derived measures were detected. CONCLUSIONS: Progressive multiple sclerosis patients with mild UL dysfunction benefit from task-oriented UL rehabilitation, which seems to be more efficient than simple passive mobilization. Despite a high burden of disability and brain damage, functional adaptive capacities seem to be preserved, thus providing a rationale for the use of rehabilitative treatments in late PMS.

Simultaneous detection of macroevolutionary patterns in phenotypic means and rate of change with and within phylogenetic trees including extinct species.

Recognizing evolutionary trends in phenotypic means and rates requires the application of phylogenetic comparative methods (PCMs). Most PCMs are unsuited to make full use of fossil information, which is a drawback, given the inclusion of such data improves, and in some cases even corrects, the proper understanding of trait evolution. Here we present a new computer application, written in R, that allows the simultaneous computation of temporal trends in phenotypic mean and evolutionary rate along a phylogeny, and to contrast such patterns among different clades within the tree. By using simulation experiments, we show the new implementation, names search.trend is as powerful as existing PCM tools in discerning macroevolutionary patterns in phenotypic means and rates, but differently from any other PCM allows comparing individual clades to each other, and provides rich information about trait evolution for all lineages in the tree.

Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO)--conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development.

In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3 in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to neuropsychiatric disorders.

Role of tissue factor in feto-maternal development: a xiphos.

In this review, the dual role of tissue factor (TF) in pregnancy is described. On the one hand, TF is required for embryonic and placental development in a successful pregnancy, and on the other hand, pathologic expression of TF can lead to serious pregnancy complications in humans and mice. Human studies show increased TF levels in plasma, amniotic fluid and and/or placentas of abnormal pregnancies affected by miscarriages, preterm birth, or pre-eclampsia. Interestingly, using two mouse models, we found that blood-borne TF plays a crucial role in the pathogenesis of pregnancy complications. TF on neutrophils and monocytes is a critical mediator in trophoblast injury and embryo damage in pregnancy loss induced by antiphospholipid antibodies and in the antibody-independent CBA/J × DBA/2 model of miscarriages. Blockade of TF or genetic diminution prevented pregnancy complications, suggesting that TF may be a good target for therapy in patients with recurrent miscarriages, pregnancy loss, and pre-eclampsia. In addition, statins, which downregulate TF, may constitute a good therapeutic option for women with pregnancy complications. Clinical trials should be conducted to confirm these observations in women.

Tissue factor in antiphospholipid antibody-induced pregnancy loss: a pro-inflammatory molecule.

Fetal loss in patients with antiphospholipid antibodies (aPL) has been ascribed to thrombosis of placental vessels. However, we have shown that inflammation, specifically complement activation with generation of the anaphylotoxin C5a, is an essential mediator of fetal injury. We have analysed the role of tissue factor (TF) in a mouse model of aPL-induced pregnancy loss. TF is the major cellular activator of the coagulation cascade but also has cell signaling activity. Mice that received aPL-IgG showed strong TF staining throughout the decidua and on embryonic debris. This TF staining was not associated with either fibrin staining or thrombi in deciduas. The absence of fibrin deposition and thrombi suggests that TF-dependent activation of coagulation does not mediate aPL-induced pregnancy loss.We found that either blockade of TF with a monoclonal antibody in wild type mice or a genetic reduction of TF prevented aPL-induced inflammation and pregnancy loss indicated a pathogenic role for TF in aPL-induced pregnancy complications. In response to aPL-generated C5a, neutrophils express TF potentiating inflammation in the deciduas and leading to miscarriages. Importantly, we showed that TF in myeloid cells, but not fetal-derived cells (trophoblasts), was associated with fetal injury, suggesting that the site for pathologic TF expression is neutrophils. We found that TF expression in neutrophils contributes to respiratory burst and subsequent trophoblast injury and pregnancy loss induced by aPL. The identification of TF, acting as an important pro-inflammatory mediator in aPL-induced fetal injury, provides a new target for therapy to prevent pregnancy loss in the aPL syndrome.

Activation of complement mediates antiphospholipid antibody-induced pregnancy loss.

Although it is clear that the specific antigenic reactivity of antiphospholipid (aPL) antibodies is critical to their effect, the pathogenic mechanisms that result in injury in vivo are incompletely understood. We hyphothesized that aPL antibodies targeted to the placenta activate complement locally, generating split products that mediate placental injury and lead to foetal loss and growth retardation. To test this hypothesis, we used a murine model of APS in which pregnant mice are injected with human IgG containing aPL antibodies. Mice treated with inhibitors of complement activation and mice deficient in complement components were protected from aPL antibody-induced foetal damage. Although the cause of tissue injury in this disease is probably multifactoral, we have shown that complement activation is an absolute requirement for foetal loss and growth restriction and, therefore, thatthis pathway acts upstream of other important effector mechanisms. Identification of complement activation as a mechanism that is necessary for aPL-induced tissue damage and definition ofthe complement components necessary to trigger such injury is likely to lead to a better understanding of the pathogenesis of vascular and tissue injury in SLE and to new and improved treatments.

[Emergence and postoperative course after anesthesia with sevoflurane versus propofol]. / Risveglio e decorso postoperatorio dopo anestesia con sevoflurano versus anestesia con propofol.

BACKGROUND: To compare the postoperative period, with particular regard to occurrence of adverse effects at the time of emergence from anaesthesia, recovery parameters, any post-surgical analgesia requirements and laboratory tests changes in 80 ASA I and II patients undergoing sevoflurane or propofol anaesthesia for elective extracavity surgery. DESIGN: A prospective randomized clinical trial. METHODS: Patients were randomly allocated into two groups: in the first group, thiopentone was administered for induction of anaesthesia and sevoflurane for maintenance; the second group received propofol either for induction of anaesthesia and maintenance. All patients received vecuronium for neuromuscular blockade and fentanyl as needed. At the end of surgery, the occurrence of adverse effects, recovery parameters, time of discharge from recovery area, any post-surgical analgesia requirements, time of walking resumption and any laboratory tests changes were recorded. RESULTS: In the sevoflurane group times of discharges from recovery area were significantly faster. In both groups total bilirubin increase was recorded until 72 hours after the end of anaesthesia. CONCLUSIONS: Significant differences of postoperative adverse effects and laboratory tests changes were not recorded in both groups of anaesthetics.

Randomized trial of salbutamol via metered-dose inhaler with spacer versus nebulizer for acute wheezing in children less than 2 years of age.

The aim of this study was to compare the efficacy of salbutamol delivered via a metered-dose inhaler with a spacer and facial mask (MDI-S) vs. a nebulizer (NEB) for the treatment of acute exacerbations of wheezing in children. In a single-blind, prospective, randomized clinical trial, 123 outpatients (1-24 months of age), presenting with "moderate to severe" wheezing, were seen in the emergency department. Children were randomly assigned to one of two salbutamol treatment groups. In the first hour, the MDI-S group received 2 puffs (100 microg/puff) every 10 min for 5 doses, and the NEB group received 0.25 mg/kg every 13 min for 3 doses. If the clinical score was >5 at the end of the first hour, the patients received another hour of the same treatment and also betamethasone (0.5 mg/kg intramuscular). On enrollment and after the first and the second hour of treatment each child had a validated clinical score assigned by a blinded investigator. There were no differences at the time of admission to the emergency department between groups in clinical score or demographic data. Success (clinical score 0.05). We conclude that in this study population, children less than 2 years of age with moderate-severe exacerbations of wheezing responded faster to salbutamol delivered by MDI with a spacer and facial mask than to salbutamol delivered by nebulizer.

Relation between pulse oximetry and clinical score in children with acute wheezing less than 24 months of age.

The aim of this study was to determine the relation between transcutaneous hemoglobin oxygen saturation, measured by pulse oximetry (SpO2), and clinical score values in 138 infants (mean+/-SD, 6.6+/-5.5 months of age) with acute wheezing episodes presenting in a primary care outpatient setting. A single investigator evaluated the severity of the acute wheezing episodes by assigning a clinical score and was unaware of the SpO2 values. Another investigator measured SpO2 values on all subjects. The mean (+/-SD) SpO2 value was 98.2+/-1.1% for children with clinical scores of 2-5 (n = 32); 95.4+/-1.5% for those with scores of 6-7 (n = 82), and 92.9+/-2% for children with scores of 8-10 (n = 24), (P < 0.001 by Bonferroni's multiple comparison, when all two-way comparisons were done for each pair of results). The clinical score showed a good correlation with SpO2 (r = -0.76; 95% CI, -0.83 to -0.68). We conclude that if pulse oximetry is not available, it is advisable to include oxygen in the therapy of wheezy infants with clinical scores values >8.

Verapamil protection against mercuric chloride-induced renal glomerular injury in rats.

We have examined the effects of the calcium channel blocker verapamil on the renal glomerular structural damage produced by mercuric chloride in rats. Verapamil (75 micrograms/kg body wt iv) was administered 30 min prior to mercuric chloride injection (HgCl2, 5 mg/kg body wt sc). Verapamil prevented the glomerular proteinuria observed in HgCl2-treated rats. Isolated glomeruli from mercury-treated rats 1 h after injection presented a diminished cross-sectional area as compared with control glomeruli (control [micron2], 26,310 +/- 2545; HgCl2 [micron2], 18,474 +/- 1828) and increased glomerular calcium content (control, 23 +/- 6 nmol/mg protein; HgCl2, 43 +/- 7 nmol/mg protein). Verapamil pretreatment prevented glomerular cross-sectional area (GCSA) diminution and glomerular calcium content rise (GCSA [micron2] Vp + Hg, 28,281 +/- 4654, Ca2+ [nmol/mg protein] Vp + Hg, 18 +/- 5). Renal sections prepared for immunohistochemical detection and histochemical analysis showed increased deposits of fibronectin and lipids and enhanced cellularity in glomerular structures from HgCl2-treated rats. Renal sections from animals pretreated with verapamil showed fibronectin and lipid contents not different from control sections and their histological studies did not show any changes when compared with control. Verapamil pretreatment also protected glomeruli from enhanced leukocyte content (myeloperoxidase activity/mg protein): control, 59 +/- 7; HgCl2, 134 +/- 10; Vp + Hg, 79 +/- 11). HgCl2 also contracts GCSA in vitro; Vp prevented this GCSA diminution. The results described in this study indicate that mercuric chloride nephrotoxicity may be associated not only with changes in renal glomerular haemodynamics, but also with a direct effect on glomerular cells.

Early manifestations of nephropathy in alloxan-treated rats.

An early stage of diabetic nephropathy was studied. Rat renal function was evaluated by clearance techniques, 7 or 15 days after alloxan administration (groups A7 and A15). Significant diminutions of glomerular filtration rate (inulin clearance) and p-aminohippurate clearance were observed in alloxan-treated rats. Diabetic animals presented glucosuria and enhanced water excretion. A natriuretic response was only observed in A15-rats. Arterial pressure increased along time, and enlarged lipid deposits in glomeruli and vessels of A7-kidney sections were observed. Thus, a vascular compromise at this time was suggested. To better characterize the set up of the renal dysfunction, other studies were performed in A7-group. Urinary protein excretion remained unchanged while a higher level of glycosylation of urinary proteins was observed in A7-rats. Histological studies revealed a normal general morphology in kidneys from diabetic rats. Immunohistochemical analysis in renal sections showed enlarged deposits of fibronectin in glomeruli and interstitium of alloxan-treated rats. Higher myeloperoxidase activity was observed in renal cortex from diabetic animals indicating leukocytes infiltration. These results indicated that 7 days after hyperglycemia induction, the animals presented a renal dysfunction characterized by hemodynamic alterations associated with vascular and glomerular structural impairments, without modifications in tubular function. The higher level of protein glycosylation and the inflammatory process at this early stage could be responsible for the beginning of diabetic nephropathy.

[Anesthesia with sevoflurane vs propofol in elective extracavity surgery]. / Anestesia con sevoflurano vs propofol nella chirurgia d'elezione extracavitaria.

OBJECTIVE: To compare the cardiovascular effects and recovery characteristics of sevoflurane and propofol anesthesia in 80 ASA I and II patients undergoing elective extracavity surgery expected to last at least one hour. DESIGN: A prospective randomized clinical trial. METHODS: After meperidine and atropine premedication, the patients were randomly allocated into two groups: in the sevoflurane group thiopentone was administered for induction of anesthesia and sevoflurane for maintenance; the propofol group received propofol either for induction of anesthesia or maintenance. All patients received N2O, vecuronium, artificial ventilation and fentanyl as needed. Vital parameters were monitored during anesthesia and two hours later. Recovery times were recorded after anesthesia. Statistical analysis was performed with SAS (Statistical Analysis System). RESULTS: In the sevoflurane group, heart rate and diastolic pressure were slightly higher than in the propofol group. Recovery time was faster after sevoflurane anesthesia.

Effects of clenbuterol as a repartitioning agent on beta-adrenoceptor concentrations in heart, bronchi and brain of veal calves.

The effects induced by dietary clenbuterol (20 micrograms kg-1 body weight day-1 for 40 days) on beta-adrenergic receptor (beta-AR) subtypes in the heart, bronchial smooth muscles and the CNS of veal calves were investigated using a binding method. Clenbuterol exposure caused a significant (P < 0.05, P < 0.01, P < 0.001) decrease in beta 1-AR and beta 2-AR in both cardiac atria and ventricles of treated animals (excluding the beta 2-AR of the right atrium). Similarly, a significant (P < 0.01, P < 0.001) down-regulation of beta-AR subtypes in bronchial smooth muscles of treated calves was observed. In the CNS (cerebral cortex, hippocampus, hypothalamus and cerebellum) the down-regulation was limited to beta 2-AR, with the exception of the hippocampus in which both beta 1-AR and beta 2-AR concentrations were significantly (P < 0.05; P < 0.01) reduced. Scatchard analysis of the binding of the beta-AR antagonist, (-) [3H]CGP 12177, revealed that the down-regulation of beta-AR was not associated with any modification in binding affinity, as Kd values were unaffected by clenbuterol treatment. Data obtained indicated that prolonged clenbuterol exposure induced a remarkable beta-AR down-regulation in the heart, bronchi and brain of veal calves.

Osteitis caused by bacille Calmette-Guérin vaccination: an emergent problem in Chile?

SETTING: Osteitis caused by bacille Calmette-Guérin (BCGOST) vaccination has not been described in Latin American countries. OBJECTIVE: To evaluate the incidence, clinical features and prognosis of patients with BCGOST in one of the most populated areas of Santiago, Chile. DESIGN: A retrospective analysis of medical records kept over twenty years (1976-1995). RESULTS: In ten children (four in the last five years), diagnostic criteria of BCGOST were fulfilled. Six were boys, the mean age was 11 months (range 6.5-21), symptoms were present with a mean of 31 days (range 15-60) before diagnosis and the sites of predilection of osteitis were the lower extremity (8/10 cases). Culture was positive in one case, and nine patients had typical histopathological lesions (two with acid-fast bacilli). All had normal chest X-ray. Mantoux testing was performed in four cases (mean 21.5 mm, range 16-28). None of the ten patients had a history of underlying immunodeficiency. In this area BCG coverage was 90.2 +/- 9.7% of all newborn infants, and the annual risk of tuberculosis infection was 24.6/100,000 population per year. CONCLUSION: Our study demonstrated an estimated incidence for BCGOST in this area of 3.2/100,000 vaccinated newborns. Based on the epidemiological situation of tuberculosis in Chile (29.5/100,000), universal BCG vaccination in newborns should be encouraged.

Glomerular compromise in mercuric chloride-induced nephrotoxicity.

We have examined the effects of mercuric chloride on renal glomerular structure. Isolated glomeruli from mercury-treated rats (HgCl2, 5 mg/kg body wt, s.c.) 1 hour post injection presented a diminished cross-sectional area as compared with control glomeruli [control (micron2) = 26,310 +/- 2,545, HgCl2 (micron2) = 18,474 +/- 1,828] and higher glomerular calcium content (control = 23 +/- 6 nmoles/mg prot, HgCl2 = 43 +/- 7 nmoles/mg prot). Renal sections prepared for immunohistochemical and histochemical analysis showed larger deposits of fibronectin and lipids and enhanced cellularity in glomerular structures from HgCl2-treated rats. Moreover, mieloperoxidase activity measured in isolated glomeruli were also increased as compared with control preparations [MPO (U/mg prot): control = 59 +/- 7, HgCl2 = 134 +/- 10]. When the animals were studied 24 hours post HgCl2 injection, glomerular cross-sectional area values were not different from control values (25,276 +/- 1,983 micron2), while calcium contents were higher than values observed 1 hour after treatment (92 +/- 9 nmoles/mg prot). A similar pattern was observed in fibronectin deposits. Hypercellularity in glomerular structures and the higher mieloperoxidase levels were maintained at this time (MPO HgCl2-rats 24 h = 148 +/- 31 U/mg prot). The effects observed in this study are consistent with an inflammatory response in the glomerular structure of HgCl2-treated rats that could explain the altered renal function described in previous reports in our laboratory.

[Evaluation of the synergism between ketorolac and morphine in the treatment of postoperative pain]. / Valutazione del sinergismo tra ketorolac e morfina nel trattamento del dolore postoperatorio.

BACKGROUND: The aim of the study is to determine what concentration of ketorolac and morphine administered together i.v. achieve best synergic effect between NSAID antiinflammatory and opioids analgesic properties. DESIGN: Randomized comparative study was carried out on 180 patients, ASA II-IV, undergoing major general surgery, in an University Clinic. METHODS: Postoperative pain therapy by i.v. PCA: group 1 morphine 0.75 mg.ml + ketorolac 0.75 mg.ml; group 2 morphine 0.50 mg.ml + ketorolac 1.50 mg.ml; group 3 morphine 0.25 mg.ml + ketorolac 1.50 mg.ml; in saline solution. Initial bolus: 2 ml. Continuous infusion 1.5 ml.h. Demand bolus: 0.2 ml. Lockout time: 30 minutes. Evaluations included: pain intensity (T0, T3, T18); total amount of infused drugs (T18); number of valid demands and attempts (T18); amount of autoadministered analgesic drugs in percent of highest available amount (T18); side effects (T18); patient's judgment. DATA ANALYSIS: ANOVA and Student's "t"-test. RESULTS: A statistically significant reduction of pain intensity was found after 3 and 18 hours in the three groups, no differences were found among the groups. Group 2 required an amount of autoadministered drugs significantly lower than other groups. Rare side effects. Patient's judgment was generally positive. CONCLUSIONS: Results suggest a greater synergetic effect between morphine and ketorolac in concentrations used in group 2.

Mercuric chloride effects on rat renal redox enzymes activities: SOD protection.

This study was done to determine the effect of mercuric chloride treatment on the redox cycle enzymes in rat kidney ex-vivo. Glutathione peroxidase (GSH-Px) and catalase (Cat) activities were measured in kidney homogenates from rats with different nonprotein sulfhydrils levels and different mercury content. The results indicated that GSH-Px activity was enhanced in mercury-treated rats in direct relationship with kidney mercury content, whereas Cat activity was increased in the presence of the highest mercury kidney content obtained. Superoxide dismutase (SOD) was administered to rats prior to mercury chloride injection and renal function, development of lipid peroxidation and renal glutathione level were measured 1 h later. Renal function, renal glutathione, and renal lipid peroxidation production were maintained similar to control values. Moreover, SOD pretreatment also protected kidney from mercuric chloride histological alterations observed 24 h post mercury treatment. Thus, an inhibition of renal redox cycle enzymes "in vivo," did not appear to be an important determinant of the increased lipid peroxidation observed during mercuric chloride nephrotoxicity.

Evidence for renal ischaemia as a cause of mercuric chloride nephrotoxicity.

The present study was undertaken to investigate if the source of oxidative stress and the renal injury produced by mercuric chloride could be renal ischaemia. Verapamil Vp was used because it was described that calcium channel blockers protect cells from nephrotoxicants and from ischaemia. Vp (75 micrograms/kg, i.v.; 30 min before HgCl2 injection) prevented mercuric chloride renal injury observed 1 h post-HgCl2 injection as measured by clearance techniques. Vp also prevented the diminution of non-protein-sulfhydryls (NPSH) and the increased lipid peroxidation (LPO) induced by HgCl2 in renal tissue. Hg2+ toxicokinetic alterations were not observed in Vp plus HgCl2 treated rats, nor was Vp ability found as a free radical scavenger in renal tissue homogenates. The results described in this study give some evidence for the role of renal ischaemia in the production of oxidative stress, generating LPO and functional and morphological renal injury described in mercuric chloride treated rats.