Asphyxial cardiac arrest, resuscitation and neurological outcome in a Landrace/Large-White swine model

The vast majority of laboratory studies on animals have focused on ventricular fibrillation (VF) and not on cardiac arrest (CA) resulting from asphyxia. The aim of this study was to develop a clinically relevant animal model in Landrace/Large-White swine of asphyxial CA resuscitated using the European Resuscitation Council guidelines. Survival and 24 h neurological outcome in terms of functional deficit were also evaluated. Asphyxial arrest was induced by clamping the endotracheal tube (ETT) in 10 Landrace/Large-White piglets. After 4 min of untreated arrest, resuscitation was initiated by unclamping the ETT, 100% oxygen mechanical ventilation, 2 min chest compressions and epinephrine administration. Advanced Life Support algorithm was followed. In case of restoration of spontaneous circulation, the animals were supported for one hour and then observed for 23 h. Coronary perfusion pressure was significantly higher in surviving animals (P < 0.001) during cardiopulmonary resuscitation. End-tidal CO(2) was significantly higher in the animals that survived than in non-surviving animals (P = 0.001). All of the animals were severely neurologically impaired 24 h after CA. This refined model of asphyxia CA is easily reproducible and may be used for pharmacological studies in CA.     

Impact of Thermal History on Tolerance of Meloidogyne hapla Second-stage Juveniles to External Freezing

Low temperature induced physiological changes that increased the ability of second-stage juveniles of Meloidogyne hapla to survive external freezing. Second-stage juveniles in polyethylene glycol solution were exposed to -4 , 0, 4, or 24 C, and then their survival was determined after ice-induced freezing of the suspensions at - 4 C for 24 hours. Survival was greatest for juveniles exposed to 4 C before freezing. Some juveniles were killed by exposure to - 4 C before freezing of the suspensions. The percentage of juveniles surviving freezing increased from about 30% to 80% within 12 hours of exposure to 4 C. This tolerance of external freezing was lost during subsequent exposure to 24 C. Longer exposures, of 1 to 15 days, to low temperature did not increase the percentage surviving external freezing, as compared to the 12-hour exposure, but reduced the tolerance of external freezing lost during subsequent exposure to 24 C for 48 hours.     

Effect of biliary obstruction on formation and metabolism of bile acids in rat

The effect of biliary obstruction in the rat on several hydroxylations involved in the formation and metabolism of bile acids was studied. The hydroxylations studied were all catalyzed by the microsomal fraction of liver homogenate fortified with NADPH. The rate of 7α-hydroxylation of cholesterol increased two- to threefold between 24 and 48 hours after ligation of the bile duct and remained at this level the next 48 hours. During the first 24 hours of obstruction the rates of 1 2α-hydroxylation of 7α-hydroxy-4-cholesten-3-one and 7α-hydroxylation of taurodeoxycholic acid decreased but returned to control levels between 24 and 48 hours after operation. The rate of 6β-hydroxylation of lithocholic acid and taurochenodeoxycholic acid increased gradually and reached a plateau between 24 and 48 hours at which time the rate was two to three times faster than in the controls. The increase in 6β-hydroxylase activity was reflected in the pattern of the bile acids excreted in urine. After 48 hours of obstruction β-muricholic acid accounted for 50% or more of the bile acids in urine.     

Aldosterone does not regulate amiloride-sensitive Na(+) transport in the colon of the Australian common brushtail possum,Trichosurus vulpecula

Plasma aldosterone concentrations and the magnitude of amiloride-sensitive Na(+) transport in the proximal and distal colon of newly caught wild possums, and of possums maintained on either low or high Na(+) diets, were determined to evaluate their role in the regulation of salt content of faeces in common brushtail possums. Wild animals had a plasma aldosterone concentration of 439+/-115 pmol l(-1) and high levels of amiloride-sensitive Na(+) transport in both the proximal and distal colon. Animals maintained on a low Na(+) diet for 14 days excreted very little Na(+) in the urine and had an elevated aldosterone concentration (840+/-246 pmol l(-1)), but levels of amiloride-sensitive Na(+) transport in the proximal and distal colon were similar to those in wild animals. Conversely, while provision of a high Na(+) diet (7 days or 14 days) resulted in increased urinary Na(+) excretion and a fall in aldosterone (approximately 250 pmol l(-1)), there was no reduction in the amount of amiloride-sensitive Na(+) transport in either the proximal or distal colon. These data strongly indicate that aldosterone does not regulate amiloride-sensitive Na(+) transport in the colon of possums and that the colon is not involved in the regulation of salt content of the faeces in this species.     

Decreased pCO(2) accumulation by eliminating bicarbonate addition to high cell-density cultures

High-density perfusion cultivation of mammalian cells can result in elevated bioreactor CO(2) partial pressure (pCO(2)), a condition that can negatively influence growth, metabolism, productivity, and protein glycosylation. For BHK cells in a perfusion culture at 20 x 10(6) cells/mL, the bioreactor pCO(2) exceeded 225 mm Hg with approximate contributions of 25% from cellular respiration, 35% from medium NaHCO(3), and 40% from NaHCO(3) added for pH control. Recognizing the limitations to the practicality of gas sparging for CO(2) removal in perfusion systems, a strategy based on CO(2) reduction at the source was investigated. The NaHCO(3) in the medium was replaced with a MOPS-Histidine buffer, while Na(2)CO(3) replaced NaHCO(3) for pH control. These changes resulted in 63-70% pCO(2) reductions in multiple 15 L perfusion bioreactors, and were reproducible at the manufacturing-scale. Bioreactor pCO(2) values after these modifications were in the 68-85 mm Hg range, pCO(2) reductions consistent with those theoretically expected. Low bioreactor pCO(2) was accompanied by both 68-123% increased growth rates and 58-92% increased specific productivity. Bioreactor pCO(2) reduction and the resulting positive implications for cell growth and productivity were brought about by process changes that were readily implemented and robust. This philosophy of pCO(2) reduction at the source through medium and base modification should be readily applicable to large-scale fed-batch cultivation of mammalian cells.     

Metabolic and hormonal response to short term fasting after endurance training in the rat

The metabolic and hormonal response to short term fasting was studied after endurance exercise training. Rats were kept running on a motor driven rodent treadmill 5 days/wk for periods up to 1 h/day for 6 wk. Trained and untrained rats were then fasted for 24 h and 48 h. Liver and muscle glycogen, blood glucose, lactate, beta OH butyrate, glycerol, plasma insulin, testosterone and corticosterone were measured in fed and fasted trained and untrained rats. 48 h fasted trained rats show a lower level of blood lactate (1.08 +/- 0.05 vs 1.33 +/- 0.08 mmol/l-1 of blood glycerol (1 +/- 0.11 vs 0.84 +/- 0.08 mmol/l-1), and of muscle glycogen. There is a significant increase in plasma corticosterone in 48 h fasted trained rats from fed values. Plasma testosterone decreases during fasting, the values are higher in trained rats. Plasma insulin decreases during fasting without any difference between the two groups. These results show higher lipolysis, and decreased glycogenolysis in trained animals during 48 h fasting. The difference between the groups in steroid hormone response could reduce neoglucogenesis and muscle proteolysis in trained animals.     

Electromyographic study of uterine activity in the castrated red fox (Vulpes vulpes L.) treated with oestradiol and progesterone (author's transl)]

Effect of oestradiol and progesterone on the electromyographic activity (EMG) of the uterus is studied in 6 groups of 2 previously castrated vixens (A, B, C, D, E, F). The animals of gropu A are treated daily with intramuscular injections of oestradiol benzoate alone or oestradiol and progesterone together. These hormones are also given to the group F, oestradiol by a subcutaneous tablet and progesterone intramuscularly. The other females only receive a silastic implant of oestrogen (groups B, C, D, E). Electrical activity is daily recorded during the various treatments, in unanaesthetized animals, by means of platinum electrodes permanently implanted in the uterus. Plasma oestradiol concentrations in peripheral blood are determined in groups A and B. The results show that : 1. OEstradiol induces rhythmic EMG activity composed of bursts of action potentials (Fig. 2). It appears after a delay of 1 to 3 days following the beginning of treatment, except in the animals of group E, treated with a 25 mg oestradiol implant (6 days). Then, EMG activity gradually increases, and the frequency of bursts is at a maximum within 24 to 48 hours. Except in group E, it exceeds 30 per 10 minutes and the amplitude of potentials sometimes reachs 1 mV.     

Intestinal transport following transfer to increased salinity in an anadromous fish (Oncorhynchus mykiss)

The ability to transition from freshwater to seawater environments is an intrinsic requirement of the life history of some fish species, including the anadromous rainbow trout (Oncorhynchus mykiss). The differences between hyper- and hypoosmoregulation are developed quickly (in hours to days), and at all scales, from gene expression to organ function. In this study, intestinal ion and water transport was examined in O. mykiss following acute transfer from freshwater (FW) to 70% seawater (SW). Plasma [Mg2+] increased at 24h post-transfer but recovered by 72 h. In the intestinal fluids, total CO? was found to increase with SW exposure/acclimation, while [Na+] decreased after 24h of SW exposure. Overall, in vitro experiments demonstrated the importance of base secretion to epithelial water uptake, and suggested that the primary physiological adjustments occurred 24-72 h after acute SW transfer. The mRNA expression of ion transporters important for intestinal osmoregulation and maintenance of acid-base balance was also investigated. A Na+/H+ exchanger (NHE2) and anion exchanger (SLC26a6) were hypothesized to be involved in the transport of acid-base equivalents, Na+, and Cl?, but were not uniformly expressed across tissue samples, and expression, where present, did not change following salinity transfer. NHE1, however, was expressed in all examined tissues (gill, kidney, anterior intestine, and pyloric cecae), but exhibited no changes in expression following acute salinity transfer.     

Prolonged whole-body cold water immersion: fluid and ion shifts

To characterize fluid and ion shifts during prolonged whole-body immersion, 16 divers wearing dry suits completed four whole-body immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 msw. One immersion was conducted at 1000 (AM) and one at 2200 (PM) so that diurnal variations could be evaluated. Fifty-four hours separated the immersions, which lasted up to 6 h; 9 days separated each air saturation dive. Blood was collected before and after immersion; urine was collected for 12 h before, during, and after immersion for a total of 24 h. Plasma volume decreased significantly and to the same extent (approximately 17%) during both AM and PM immersions. Urine flow increased by 236.1 +/- 38.7 and 296.3 +/- 52.0%, urinary excretion of Na increased by 290.4 +/- 89.0 and 329.5 +/- 77.0%, K by 245.0 +/- 73.4 and 215.5 +/- 44.6%, Ca by 211.0 +/- 31.4 and 241.1 +/- 50.4%, Mg by 201.4 +/- 45.9 and 165.3 +/- 287%, and Zn by 427.8 +/- 93.7 and 301.9 +/- 75.4% during AM and PM immersions, respectively, compared with preimmersion. Urine flow and K excretion were significantly higher during the AM than PM. In summary, when subjects are immersed in cold water for prolonged periods, combined with a slow rate of body cooling afforded by thermal protection and enforced intermittent exercise, there is diuresis, decreased plasma volume, and increased excretions of Na, K, Ca, Mg, and Zn.     

Differential effects of DOCA on renal and gastrointestinal handling of sodium and potassium in pigs

Young, male pigs eating standard pig chow, ad libitum, received approximately 170 mEq Na and 290 mEq K per day. Electrolyte intake, urinary and fecal electrolyte output, and plasma electrolyte levels were determined daily in 12 deoxycorticosterone acetate (DOCA)-treated pigs and in 6 control pigs. Daily Na and K balances (dietary intake - urinary + fecal output) were calculated. DOCA caused a reduction in urinary Na output from 1.53 mEq/kg/day to 0.57 mEq/kg/day during the first 48 hr following implantation. Escape from the renal sodium retaining effect of DOCA was complete within 3 days, with urinary Na output returning to pre-DOCA levels. Fecal Na output decreased from 0.65 mEq/kg/day during the preimplant period to 0.13 mEq/kg/day during the postimplant period. No escape from GI Na retention occurred by Day 15. Plasma Na rose to significantly higher levels by Day 15. Sodium balance was significantly elevated in DOCA-treated pigs for that first 48 hr postimplant. Urinary K output decreased from 3.50 mEq/kg/day to 1.74 mEq/kg/day during the first 2 days, but returned toward preimplant levels by Day 4. Fecal K output was increased for the first week, and thereafter returned to preimplant levels. Plasma K fell from 3.9 to 2.9 mEq/liter by Day 15. Potassium balance fell slightly in both experimental and control animals. No significant differences in potassium balance were present between the two groups. The control pigs showed no significant changes in plasma electrolyte concentration or in electrolyte balance. It is concluded that DOCA has differential effects on renal and gastrointestinal handling of electrolytes and that DOCA may induce an intracellular shift of potassium in pigs.     

Influence of age and starvation on pO2, pCO2 and haematocrit values in the rat.

The author determined the effect of acute starvation on the arterial pO2 and pCO2 value (analysed on a micro-Astrup apparatus) in rats of different ages; in infant rats, this was done by separating them from the female and the nest for 24 hours. Arterial blood was obtained by incising the tail artery. It was found that the pO2 value in rat arterial blood rose signficantly during ontogenesis. At 10 and 14 days the mean pO2 value was 68 torr, while at 25 days and in adult rats it was 92-95 torr. No marked changes were found in CO2 during ontogenesis (the mild drop was not statistically significant). In 10- and 14-day-old rats, 24 hours' starvation caused a significant decrease in pO2. In older rats, deprivation of food and water did not significantly affect the pO2; in the arterial blood. The arterial blood pCO2 was not influenced by starvation. The development of the haematocrit values in mixed blood (obtained by decapitation) during ontogenesis was in agreement with findings in the literature, i.e. a drors' complete starvation produced no change in the haematocrit values in 5- and 10-day-old rats, but a marked increase was recorded in older rats.     

Body mass change during altered gravity: spaceflight, centrifugation, and return to 1 G

To assess the effect of gravity on growth, immature rats (130-200 g) were studied during chronic altered gravity exposure and while transitioning between gravity fields. Body mass gain of rats (n = 12) exposed to 14 days of microgravity (spaceflight) was evaluated and compared to mass gain of 1 G controls. Spaceflight did not affect mass gain. Six rats exposed to 1 G following spaceflight, when compared to controls, experienced a significant (0 < 0.05) post-flight mass loss over 48 h of 13 g. Over subsequent days, however, this loss was compensated for, and no difference from 1 G controls was noted after 5 days. Exposure to hypergravity (2 G) for 16 days was evaluated [(n = 6/group): Centrifuge (C); On Center Control (OCC); Centrifuge Control (CC)]. Body mass of centrifuged and OCC rats was reduced within 24 h, with OCCs regaining control mass within 13 days. The mass difference (44 g) in centrifuged animals persisted, however, with no subsequent difference in rate of mass gain between centrifuged animals and controls over Days 3-16 (3.7 +/- 0.1 vs. 3.9 +/- 0.1 g/day, respectively). Transitioning from 2 G to 1 G resulted in a mass increase within 48 hours for centrifuged animals. Over Days 3-16 at 1 G, the rate of gain for centrifuged animals continued to increase (3.1 +/- 0.1 g/day compared to 2.1 +/- 0.1 g/day for controls); differences from control, however, were still noted on Day 16. Transitioning to an increase in a gravity field causes acute losses in body mass. In hypergravity, the acute reduction in body mass persists but the rate of mass gain is normal. Animals returning to 1 G, after acute changes, adjust to attain control mass.     

Affinity chromatography for human Na+, K+-ATPase inhibitors in plasma and urine

Semi-purified dog kidney Na+,K+-ATPase cross-linked with ovalbumin was used in batch-wise affinity chromatography for the detection of endogenous Na+,K+-ATPase inhibitor in human plasma and urine. Ammonium acetate 1 M washed off the endogenous inhibitor from the immobilized enzyme. The inhibitory activity of the eluate from hypertensive plasma and urine was significantly higher (p less than 0.0025, n = 5 and p less than 0.005, n = 6 respectively) than that of normotensive. This latter was correlated with the ability of plasma from the same subjects to compete with ouabain binding to erythrocytes. Plasma and urine extracts inhibited the activity of Na+, K+-ATPase in a dose-dependent manner as ouabain does and were shown to contain 3 or 4 active compounds by high pressure liquid chromatography. The activity of some of these compounds was lost after peptidase treatment. These data support the heterogeneity of endogenous inhibitors of Na+,K+-ATPase activity in plasma and urine.     

Release of prostaglandin F2α during the bovine peripartal period

Progesterone, estrone and 15-keto-13,14-dihydro-PGF_2α levels were determined in the peripheral blood circulation during the peripartal period in 12 cows. Plasma concentrations of progesterone showed a gradual and continuous decrease during the last 60 days before parturition. This gradual decrease was followed by an abrupt decline in the progesterone concentration occurring 24–48 hours before delivery. The plasma levels of estrone started to increase about 30 days prior to parturition with high concentrations attained during the last days of pregnancy. After delivery the estrone content decreased to baseline levels. Increased levels of the PGF_2α metabolite were recorded 24–48 hours before parturition. These increased PGF_2α metabolite levels occurred before or in conjunction with prepartum luteolysis. Prostaglandin metabolite levels remained high during parturition and returned to baseline 10–20 days after delivery.     

Effects of acute intravenous aldosterone administration on Na(+), K(+), and water excretion in the horse.

The effect of a temporary increase in plasma aldosterone concentration on Na(+), K(+), and water balance was investigated in four horses. Aldosterone was injected intravenously for 6 h at 20-min intervals (total 5.4 microg/kg body wt). Samples were taken for 24 h before, during, and for 48 h after the treatment. Aldosterone treatment reduced the Na(+) loss via urine and feces by 99 and 72%, respectively, later followed by a marked increase in Na(+) excretion by both pathways. During the first 6 h after the treatment, fecal K(+) excretion was elevated, and the plasma K(+) concentration was lowered. Fluid was retained throughout the treatment period and for 12-15 h thereafter. In a second experiment, exercise was performed once after aldosterone treatment and once without prior treatment. Sweat samples were collected, and the composition was not altered after treatment. It was concluded that acute aldosterone injections reduce Na(+) losses in both feces and urine but not in sweat. In addition, the feces was shown to be the main excretion pathway of aldosterone.     

Pravastatin immunomodulates IL-6 and C-reactive protein, but not IL-1 and TNF-alpha, in cardio-pulmonary bypass

BACKGROUND: While statins are increasingly used in cardiopulmonary bypass (CPB), the anti-inflammatory effects of individual statins, within the context of various treatment regimes, need further examination. The present study evaluates the anti-inflammatory effectiveness of the short-term, preoperative and intensive postoperative use of pravastatin in CPB. METHOD: Forty three patients undergoing CPB were enrolled in a randomized, prospective clinical study. One group (n = 21), received pravastatin, the other (n = 22) did not. Patients in the pravastatin group received one dose of 40 mg per day for nine days, starting 48 hours before CPB, with an additional dose of 40 mg one hour after surgery. Plasma levels of selected inflammatory mediators were measured at baseline and tracked systematically. RESULTS: Pravastatin reduced postoperative interleukin-6 (IL-6) levels significantly at 24 and 48 hours, and at seven days. Mean +/- SD values, for treated versus untreated patients were: at 24 hours, 159.5 +/- 58.5 versus 251.2 +/- 53.0 pg/mL (p < 0.001); at 48 hours, 81.9 +/- 31.5 versus 194.2 +/- 56.3 pg/mL (p < 0.001); and at seven days, 16.4 +/- 7.2 versus 30.8 +/- 12.6 (p < 0.001). C-reactive protein (CRP) decreased significantly on the seventh postoperative day, when plasma levels were 3.6 +/- 1.1 in the treated patients versus 8.2 +/- 2.1 mg/dL in the controls (p < 0.001). No changes in plasma IL-1 and TNF-alpha were found during entire study. CONCLUSIONS: Pravastatin induced a precocious modulation of IL-6 expression and a later reduction of plasma CRP levels. Pravastatin;s effects on the expression of these pivotal inflammatory mediators strongly support its well-timed use in CPB.     

Association of Sepsis-Related Mortality with Early Increase of TIMP-1/MMP-9 Ratio

Objective

Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and non-surviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions.

Methods

Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality.

Results

We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p<0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8.

Conclusions

The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis outcome.     

Glomerular filtration rate and blood pressure monitoring in awake baboons

Minimally invasive techniques were used to collect urine with an external catheter together with automated intermittent monitoring of arterial blood pressure in awake male baboons. Using endogenous creatinine, 24-hour creatinine clearances were measured for 2 to 3 consecutive days in four intact and in four uninephrectomized baboons. Despite large differences in urinary volume and sodium excretion, reproducibility of 24-hour creatinine clearances was within 15% in 15 of 19 studies obtained from 6 of 8 animals. Arterial blood pressure was monitored intermittently at 30 to 60 minute intervals over 24 hours with a Dinamap monitor and recorder. Mean blood pressure averaged 71 +/- 4.4 to 89 +/- 5.5 mm Hg in different animals. Blood pressure tended to be lower at night than during the day. In separate studies using 15 to 60 minute urine collection periods, inulin clearance was compared in awake and in anesthetized animals with endogenous or exogenous creatinine clearance measured simultaneously. The clearance of creatinine systematically exceeded the clearance of inulin, even in intact animals with a normal serum creatinine. The creatinine-to-inulin clearance ratio averaged 1.16 +/- 0.03 at a serum concentration of 0.7 to 0.8 mg/dl; 1.27 +/- 0.03 at a serum creatinine of 1.0 to 1.1 mg/dl and 1.56 +/- 0.04 at a serum creatinine greater than 10 mg/dl. All values exceed unity significantly (p less than 0.001). Thus, renal function, including inulin clearance, can be measured in awake baboons. Duplicate or triplicate 24-hour urine collections are needed to assess the reliability of creatinine excretion. However, creatinine clearance overestimates glomerular filtration rate, as it does in humans.     

Effects of eugenol and derivatives on Biomphalaria glabrata

Biomphalaria glabrata snails and egg-masses were exposed, for six to twenty-four hours to concentrations of 1, 10, 100 and 1000 ppm of Eugenol, O-methyleugenol, O-benzyleugenol and dehydrodieugenol. Only at 10 ppm O-benzyleugenol enhanced mortality of snails and egg-masses. The other substances showed ovicidal and molluscicidal activity only at 100 and 1000 ppm concentrations, causing a significant cardiac frequency reduction in snails after 6 to 24 hours of exposure as well as perduring low cardiac rates until 24 hours afterwards. Two specimen exposed to 100 ppm O-methyleugenol presented anesthetic effect and extrusion of copulator and urethral organs. No schistosomicide or anesthetic effects were observed in mice experimentally infected with Schistosoma mansoni and treated during 5 days with oral doses of 150 mg/kg of Eugenol, O-methyleugenol and O-benzyleugenol.     

Free fatty acid mobilization in the development of cerium-induced fatty liver

Following cerium injection to female rats: (1) Plasma free fatty acids (FFA) concentration increases during the first 24 hours, then remains constant up to 48 hours. (2) Adipose tissue lipolytic activity increases tremendously during the first 12 hours (+380%), maintaining high values throughout the study (48hrs). These modifications are followed by a time-dependent increase of total liver lipids consisting mainly of triglycerides and to a less extent of cholesterol. (3) Adrenalectomy prevented the development of cerium-induced fatty liver: plasma FFA and lipolysis failed to increase in adrenalectomized cerium-treated animals. Thus, our study demonstrates the involvement of adrenergic stimulation of adipose tissue lipase as an obligatory step in the development of cerium-induced fatty liver.