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Liver transplantation in exertional heat stroke: a medical dilemma.

BACKGROUND: Exertional heat stroke (EHS) is a life-threatening condition caused by an extreme elevation in core body temperature. Hepatic involvement is one of the hallmarks of heat stroke, affecting nearly all heat stroke patients. It is usually manifested by increased serum levels of liver enzymes, but acute liver failure has also been reported. Liver transplantation has been proposed as a potential treatment in cases of severe liver failure, but there are no unanimous criteria pointing to the right stage in which to conduct the transplantation. CASE PRESENTATION: We report a case of an 18-year old patient who suffered heat-induced liver failure. The patient was referred for orthotopic liver transplantation (OLT) but spontaneously recovered completely with conservative treatment. CONCLUSIONS: This case demonstrates the complexity of the decision for liver transplantation in EHS. The various prognostic criteria of acute hepatic failure and their relevance to EHS are critically reviewed, with an aim to assess their application for such a condition.

Adult↗

R 56865 exerts cardioprotective properties independent of the intracellular Na(+)-overload in the guinea pig heart.

Reducing intracellular Na(+)-accumulation during ischemia exerts cardioprotective effects in reperfusion in a variety of models. Since slowly-inactivating Na(+)-channels may contribute to Na(+)-influx in ischemia, we investigated whether the ischemia-protective properties of R 56865, an inhibitor of slowly inactivating Na(+)-channels, are mediated by inhibition of the ischemic Na(+)-overload. Monitoring intracellular Na(+) (Na(+)(i)) by (23)Na-NMR-spectroscopy revealed a continuous rise of Na(+)(i) during ischemia in the isolated perfused guinea pig heart. Within 30 and 60 min of ischemia, respectively, Na(+)(i) had risen 2.6+/-0.2- and 4.4+/-0.2-fold compared to baseline ( n=6). R 56865 (1 microM) did not influence the time course of the Na(+)(i)-accumulation at any point of the ischemic period. R 56865, however, showed marked cardioprotective properties: in the reperfusion period the agent markedly improved the restoration of left ventricular developed pressure (29.1+/-6.8 mm Hg vs. 2.4+/-2.0 mm Hg), ATP (2.8+/-0.3 mM vs. 1.7+/-0.6 mM) and phosphocreatine (10.9+/-2.2 mM vs. 6.8+/-1.1 mM), furthermore contracture development was reduced. The present study strongly suggests slowly-inactivating Na(+)-channels being at best a minor port of Na(+)-entry in the ischemic guinea pig heart. It clearly demonstrates that the potent cardioprotective properties of R 56865 are unrelated to intracellular sodium homeostasis.

Animals↗

An mGluR2/3 antagonist, MGS0039, exerts antidepressant and anxiolytic effects in behavioral models in rats.

RATIONALE: Abnormalities of glutamatergic neurotransmission have been reportedly observed in psychiatric disorders. Previously, we demonstrated that (1R, 2R, 3R, 5R, 6R)-2-Amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039) is a selective antagonist for group II metabotropic glutamate receptors (mGluR2/3), and that it exerted antidepressant effects in some animal behavioral tests. OBJECTIVES: In the present study, we provide additional evidence that MGS0039 exhibits antidepressant and anxiolytic effects in experimental rodent models, which are predictive of clinical efficacy. METHODS: The learned helplessness (LH) paradigm, which is a common model used to examine the depressive state, was used to assess antidepressant effects of MGS0039. Moreover, anxiolytic effects of MGS0039 were investigated in the conditioned fear stress (CFS) model, which represents emotional abnormality, including anxiety. RESULTS: Intraperitoneal administration of MGS0039 (10 mg/kg) to rats for 7 days elicited a significant reduction in escape failures in the LH paradigm. In addition, rats treated with MGS0039 (2 mg/kg) showed significantly attenuated freezing behavior in a CFS model, indicating the anxiolytic-like potential of MGS0039. CONCLUSIONS: These results suggest that the blockade of mGluR2/3 with MGS0039 may be effective in the treatment of depressive and anxiety disorders.

Animals↗

Grip forces exerted against stationary held objects during gravity changes.

In the present study, grip forces exerted against a stationary held object were recorded during parabolic flights. Such flight maneuvers induce changes of gravity with two periods of hypergravity, associated with a doubling of normal terrestrial gravity, and a 20 s period of microgravity. Accordingly, the object's weight changed from being twice as heavy as normally experienced and weightless. Grip-force recordings demonstrated that force control was seriously disturbed only during the first experience of hyper- and microgravity, with the grip forces being exceedingly high and yielding irregular fluctuations. Thereafter, however, grip force traces were smooth, the force level was scaled to the object's weight under normal and high-G conditions, and the grip force changed in parallel with the weight during the transitions between hyper- and microgravity. In addition, during weightlessness, when virtually no force was necessary to stabilize the object, a low force was established, which obviously represented a reasonable safety margin for preventing possible perturbations. Thus, all relevant aspects of grip-force control observed under normal gravity conditions were preserved during gravity changes induced by parabolic flights. Hence, grip-force control mechanisms were able to cope with hyper- and microgravity, either by incorporating relevant receptor signals, such as those originating from cutaneous mechanoreceptors, or by adequately including perceived gravity signals into control programs. However, the adaptation to the uncommon gravity conditions was not complete following the first experience; finer tuning of the control system to both hyper- and microgravity continued over the measurement interval, presumably with a longer observation period being necessary before a stable performance can be reached.

Adult↗

Transient exposure to PTHrP (107-139) exerts anabolic effects through vascular endothelial growth factor receptor 2 in human osteoblastic cells in vitro.

Intermittent administration of the N-terminal fragment of parathyroid hormone (PTH) and PTH-related protein (PTHrP) induces bone anabolic effects. However, the effects of the C-terminal domain of PTHrP on bone turnover remain controversial. We examined the putative mechanisms whereby this PTHrP domain can affect osteoblastic differentiation, using human osteosarcoma MG-63 cells and osteoblastic cells from human trabecular bone. Intermittent exposure to PTHrP (107-139), within 10-100 nM, for only <or=24 hours during cell growth stimulated alkaline phosphatase (ALP) and Runt homology domain protein (Runx2) activities as well as osteocalcin (OC) and osteoprotegerin (OPG) expression but inhibited receptor activator of nuclear factor kappaB (NF-kappaB) ligand. Continuous exposure to this PTHrP peptide reversed these effects. The stimulatory effects of transient treatment with PTHrP (107-139) on OC mRNA and/or OPG protein expression were unaffected by a neutralizing anti-insulin-like growth factor I antibody or [Asn(10), Leu(11), d-Trp(12)]PTHrP (7-34) in these cells. On the other hand, the former antibody and the latter PTHrP antagonist abrogated the PTHrP (1-36)-induced increase in these osteoblastic products. Transient exposure to PTHrP (107-139), in contrast to PTHrP (1-36), stimulated vascular endothelial growth factor receptor 2 (VEGFR2) mRNA levels in these cells. Moreover, induction of ALP activity as well as OC and OPG expression by PTHrP (107-139) was blunted by SU5614, a permeable tyrosine kinase inhibitor of VEGFR2. Protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) inhibitors abolished the PTHrP (107-139)-stimulated VEGFR2 and OPG mRNA levels in these cells. These results indicate that intermittent exposure to PTHrP (107-139) exerts potential anabolic effects through the PKC/ERK pathway and, subsequently, VEGFR2 upregulation in vitro in human osteoblastic cells.

Alkaline Phosphatase↗

Comparison of the effects exerted by luminal Ca2+ on the sensitivity of the cardiac ryanodine receptor to caffeine and cytosolic Ca2+.

Ca(2+) released from the sarcoplasmic reticulum (SR) via ryanodine receptor type 2 (RYR2) is the key determinant of cardiac contractility. Although activity of RYR2 channels is primary controlled by Ca(2+) entry through the plasma membrane, there is growing evidence that Ca(2+) in the lumen of the SR can also be effectively involved in the regulation of RYR2 channel function. In the present study, we investigated the effect of luminal Ca(2+) on the response of RYR2 channels reconstituted into a planar lipid membrane to caffeine and Ca(2+) added to the cytosolic side of the channel. We performed two sets of experiments when the channel was exposed to either luminal Ba(2+) or Ca(2+). The given ion served also as a charge carrier. Luminal Ca(2+) effectively shifted the EC(50) for caffeine sensitivity to a lower concentration but did not modify the response of RYR2 channels to cytosolic Ca(2+). Importantly, luminal Ca(2+) exerted an effect on channel gating kinetics. Both the open and closed dwell times were considerably prolonged over the whole range (response to caffeine) or the partial range (response to cytosolic Ca(2+)) of open probability. Our results provide strong evidence that an alteration of the gating kinetics is the result of the interaction of luminal Ca(2+) with the luminally located Ca(2+) regulatory sites on the RYR2 channel complex.

Animals↗

The diagnostic value of MRI scans for the diagnosis of chronic exertional compartment syndrome of the lower leg.

OBJECTIVE: A prospective descriptive study to determine the value of magnetic resonance imaging (MRI) as an aid in diagnosing (chronic) exertional compartment syndrome. DESIGN AND PATIENTS: MRI was performed in 21 patients (41 anterior compartments) with chronic compartment syndrome at rest and following physical exercise. Median (T2-weighted) signal intensity on the MRI scan was determined in the anterior and the (superficial) posterior compartment of the lower leg before and after exercise. Postexercise increases in the signal intensity in these two compartments were compared. After fasciotomy, a second MRI scan was performed in 13 patients (25 anterior compartments) on the basis of the same protocol. MR studies were performed in 12 normal controls (24 anterior muscle compartments) on the basis of the same protocol. RESULTS: T2-weighted signal intensity increased by 27.5% (range 13.6-38.6%) following exercise in the anterior compartment of patients with a chronic compartment syndrome. In the posterior compartment this increase amounted to 4.25% (range 0-10.2%). Following fasciotomy, the increase in the anterior compartment was 4.1% (range 1.0-5.2%), while the increase in the posterior compartment amounted to 5.6% (range 0-11.0%), In normal controls, the increase in the anterior compartment was 7.6% (range 0-9. 1%), while in the posterior compartment it was 4.0% (range 0-7.2%). CONCLUSIONS: In patients with a chronic compartment syndrome, the affected (anterior) compartment shows a statistically significant increase in (T2-weighted) signal intensity during exercise compared with both the (superficial) posterior compartment and the anterior compartment of normal controls. This effect disappeared after fasciotomy. In view of the substantial increase in T2-weighted signal intensity, MRI can be used in diagnosing chronic compartment syndrome.

Adolescent↗

A prospective blinded evaluation of exercise thallium-201 SPET in patients with suspected chronic exertional compartment syndrome of the leg.

This study compared the quantitative and qualitative results of leg thallium-201 single-photon emission tomography (SPET) imaging in patients with and without raised intracompartmental pressure associated with exercise-related leg pain. The purpose of this study was to clarify the aetiology of chronic exertional compartment syndrome (CECS), and to investigate the diagnostic applications of 201Tl SPET in CECS. Thirty-four study participants underwent compartment pressure testing (CPT) between March and August 2000. There were 25 positive CPT results (patient group), and nine negative CPT results (control group). All 34 participants underwent scintigraphy. Quantitative and qualitative assessments were performed for the anterolateral and deep posterior compartments of the lower leg. There was no significant difference in either quantitative or qualitative assessments of perfusion between those compartments with and those without CECS. In contrast, a marked effect of exercise type upon compartment perfusion pattern was noted. Results of this study indicate that there is no compartment perfusion deficit in those patients with raised intracompartmental pressure associated with CECS, and suggest a non-ischaemic basis for the pain associated with CECS. They also suggest no role for exercise perfusion scintigraphy in the diagnosis of this syndrome.

Adult↗

Regulating exercise intensity using ratings of perceived exertion during arm and leg ergometry.

The purpose of this investigation was to examine the validity of regulating exercise intensity using ratings of perceived exertion (RPEs) during arm crank and leg cycle exercise at 50 and 70% peak oxygen consumption (VO2peak). Ten men and seven women [26 (1) years old; mean (SE)] participated in this study. Each subject completed a maximal estimation trial and two submaximal exercise bouts (production trials) on both an arm and leg ergometer. During each maximal estimation trial, subjects were asked to give a RPE for each stage of the exercise. RPEs, heart rates (HR), and power outputs (PO) equivalent to 50 and 70% VO2peak for each exercise mode were then estimated from plots of RPE versus oxygen consumption (VO2), HR versus VO2, and PO versus VO2, respectively. During the submaximal trials, subjects were instructed to select workloads on an arm and leg ergometer that produced the previously estimated RPEs. Comparisons were made for VO2, HR, and PO between the estimation and production trials for each mode at each exercise intensity. HR did not differ between the trials at either 50 or 70% VO2peak during arm and leg ergometry. In addition, VO2 and PO did not differ between the trials at either 50 or 70% VO2peak during arm ergometry and at 50% VO2peak during leg ergometry. However, these two parameters were lower (P < 0.05) during the production trial [1.88 (0.15) l x min(-1) and 89.1 (10.1) W, respectively] as compared to the estimation trial [2.08(0.14) l x min(-1) and 102.4 (6.5)W, respectively] during leg ergometry at 70% VO2peak. In conclusion, using RPEs to regulate exercise intensity is physiologically valid during arm ergometry at both 50 and 70% VO2peak and during leg ergometry at 50% VO2peak. However, this prescriptive approach remains questionable during leg cycle exercise at 70% VO2peak.

Adult↗

A comparison of physiological responses and rating of perceived exertion between high-impact and low-impact aerobic dance sessions.

The aim of this study was to compare the exercise intensity and rating of perceived exertion (RPE) of a high-impact (HIP) and a low-impact (LIP) university aerobic dance session. Ten women [mean (SD) age 22.9 (2.6) years] took part in the study. An incremental treadmill test was performed by each subject to determine maximum oxygen consumption (VO2max) and maximum heart rate (HRmax). The measured VO2max [mean (SD)] was 49.0 (7.5) ml x kg(-1) x min(-1). The subjects were randomly assigned to LIP and HIP sessions (i.e. five of the subjects participated in the HIP session first, and the other five participated in the LIP session first). In a laboratory, heart rate, oxygen uptake and RPE were measured throughout each session for each subject. Expired air was collected continuously throughout the sessions using Douglas bags (ten bags over a 30-min period). The sessions consisted of 20 min of aerobic exercise (bags 1-7) followed by 5 min of local muscular endurance exercise (bags 8 and 9) and 5 min of flexibility exercises (bag 10). The mean intensity of the aerobic section of the LIP and HIP sessions was 51.6% and 64.7% VO2max, respectively. Ninety-five percent confidence intervals for the average difference between the HIP and LIP sessions demonstrate that the %VO2max was between 12% and 14% higher for the HIP session. The mean %HRmax for the LIP and HIP sessions was 71.4% and 76.7%, respectively, with the %HRmax in the HIP session being between 5.4% and 7.2% higher on average than that of the LIP session. On average, the RPE for the aerobic section of the HIP session (12.1) was consistently higher than that of the LIP session (11.1). HIP activity has the potential to maintain/improve the aerobic fitness of its participants. According to the literature, the exercise intensity elicited by LIP activity may have a limited training effect for the population utilised in this study, and for some individuals may result in detraining. Conversely, LIP activities may be an appropriate mode of exercise for overweight and unfit individuals.

Adolescent↗

Effect of carbohydrate ingestion and hormonal responses on ratings of perceived exertion during prolonged cycling and running.

This randomized, double-blind, placebo-controlled study was designed to determine the influence of exercise mode, and 6% carbohydrate (C) versus placebo (P) beverage ingestion, on ratings of perceived exertion (RPE) and hormonal regulation to 2.5 h of high-intensity running and cycling (approximately 75% maximum oxygen uptake) by ten triathletes who acted as their own controls. Statistical significance was set at P < or = 0.05. The pattern of change in RPE over time was significantly different between C and P ingestion (P < 0.001) and between running and cycling modes (P = 0.001). The lowest RPE values were seen in the C-cycling sessions and the highest in the P-running sessions. The pattern of change in the respiratory exchange ratio and fat and carbohydrate oxidation rates were significantly different between the C and P conditions but not between the running and cycling modes. C relative to P ingestion (but not exercise mode) was associated with higher plasma levels of glucose and insulin and lower plasma cortisol and growth hormone levels. The pattern of change in plasma levels of catecholamines and lactate did not differ between the C and P conditions. These data indicate that a lower RPE was associated with a higher level of carbohydrate oxidation, higher plasma glucose and insulin levels, and lower plasma cortisol and growth hormone levels during cycle exercise following C supplementation as compared to P feeding. These findings support a physiological link between RPE and carbohydrate substrate availability as well as selected hormonal regulation during cycle exercise.

Adult↗

Simultaneous presence of cAMP and cGMP exert a co-ordinated inhibitory effect on the agonist-evoked Ca2+ signal in pancreatic acinar cells.

The stimulation of the pancreatic acinar cells by physiological secretagogues, such as acetycholine (ACh), activates a well-established intracellular signalling pathway, which involves the generation of Inositol 1,4,5-trisphosphate (InsP3) and the release of Ca2+ from intracellular stores. Caffeine, which inhibits this agonist-evoked Ca2+ response reversibly and competitively also blocks the Ca2+ signal generated by the non-specific activation of the membrane guanine nucleotide-binding proteins (G-proteins). Removal of caffeine is associated with an increase of intracellular [Ca2+] ([Ca2+]i) and the spatial and temporal characteristics of this Ca2+ signal are identical to those of the signal generated by the initial agonist stimulation. Caffeine is also a potent non-specific inhibitor of various cellular phosphodiesterases (PDE) and its inhibitory effect can be reproduced by other PDE inhibitors, chemically related (theophylline) or not (papaverine). Various protocols designed to increase the concentration of either of the major intracellular cyclic nucleotides [adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP)] failed to reproduce the full extent of the caffeine inhibition: at maximal agonist concentration (1 microM ACh) increases of either cAMP or cGMP did not affect the Ca2+ signal, whereas at submaximal doses of agonist (0.1-0.3 microM ACh) they induced partial inhibition. Here we show that only the simultaneous increase of the cellular concentrations of both cyclic nucleotides (either simultaneous or sequential) are effective in mimicking the blocking effect of caffeine and other non-specific PDE inhibitors. These data indicate, thus, that, in addition to other independent intracellular effects, cAMP and cGMP can exert a co-ordinated inhibitory effect of the agonist-evoked Ca2+ signal in pancreatic acinar cells.

Acetylcholine↗

Retinol influences contractile function and exerts an anti-proliferative effect on vascular smooth muscle cells through an endothelium-dependent mechanism.

Rat aortic rings maintained in organ culture for as little as 24 h show significant loss of contractile responsiveness to different agonists. Smooth muscle cells (SMC) in culture quickly de differentiate into a non-contractile phenotype with a marked capacity for proliferation. Rat aortic ring segments cultured in retinol supplemented (10(-6) M) medium showed significantly increased active tension development in response to 80 mM K+ depolarization compared with 7-day cultured control rings. The improvement of contractile performance of the cultured aorta segments in retinol-supplemented media was lost when rings were denuded of endothelium prior to culture, suggesting the endothelial cell layer as the mediator of this effect. Retinol at concentrations up to 10(-5) M was found to have no direct effect on proliferation of cells of the A7r5 SMC. However, retinol was found to augment significantly the growth inhibition of A7r5 cells grown in co-culture with bovine aortic endothelial cells (BAEC). It was further observed that media conditioned with BAEC treated with 10(-6) M retinol expressed SMC growth inhibitory properties compared with media conditioned by untreated BAEC cells or unconditioned media. Examination of cultured rat aortic ring segments by electron microscopy and BAEC cells with phase contrast microscopy revealed that retinol had obvious effects on endothelial cell morphology and ultrastructure. These results indicate that retinol exerts its effects primarily on the endothelium, which in turn secretes stable factors that directly affect SMC proliferation and contractility.

Animals↗

Intra-strain clonal phenotypic variation of Tritrichomonas foetus is related to the cytotoxicity exerted by the parasite to cultured cells.

As observed in most of the investigated trichomonads, a strain of Tritrichomonas foetus includes different parasite subpopulations. Such population diversity might account for important properties such as the ability of the parasite to destroy host cells. The aim of this study was to characterize the cytotoxicity exerted by subpopulations (named as K1, K2, K3, K4 and K5) of an isolate of T. foetus on epithelial cultured cells. The five populations studied here destroyed epithelial monolayers at different rates (from 25% to 55%), even though the cytoadhesion level and whole-cell protease activity were closely related among them. We were also able to detect differences in contact-dependent and contact-independent cytotoxicity mechanisms among the five populations. An extracellular parasite protease had varying activity among the parasite populations. The intensity of contact-independent cytotoxicity was strictly related to the degree of enzyme activation, suggesting that such a protease might be involved in the cytotoxicity mediated by T. foetus.

Animals↗

Platelet-derived growth factor exerts disparate effects on odontoblast differentiation depending on the dimers in rat dental pulp cells.

Platelet-derived growth factor (PDGF) has recently been demonstrated to control the expression of alkaline phosphatase and proteoglycan synthesis of odontoblastic cells in dental pulp tissues. Although PDGF appears to be closely related to dentinogenesis, much about the mode of action of PDGF on odontoblast differentiation remains unclear. In this study, we examined the effects of three PDGF dimers (PDGF AA, AB, and BB) on odontoblastic differentiation of dental pulp cells in long-term mineralized cultures. Dental pulp cells isolated from rat lower incisors were continuously treated with each of PDGF AA, AB, and BB in separate cultures for 20 days. The three PDGF dimers suppressed alkaline phosphatase activity, osteocalcin and calcium content, and the formation of dentin-like nodules. The expression of mRNA for dentin sialoprotein (DSP) in the cells was inhibited by PDGF AA treatment, whereas PDGF AB and BB treatment stimulated the expression of DSP, even though the dentin-like nodule formation was inhibited. Although the effects of PDGF on odontoblastic differentiation varied among the dimers, the cells expressed both PDGF alpha and beta receptors, whose quantities were similar. These results suggest that PDGF exerts diverse effects on odontoblastic differentiation depending on its dimeric form. These in vitro findings explain, at least in part, the in vivo action of PDGF in dentinogenesis during the repair process of damaged dental pulp.

Alkaline Phosphatase↗

Effects of pressure on the skin exerted by clothing on responses of urinary catecholamines and cortisol, heart rate and nocturnal urinary melatonin in humans.

The study investigated how the pressure exerted on the skin by clothing worn while working in the daytime affected the urinary excretion of adrenaline, noradrenaline and cortisol, heart rate, and also melatonin secretion at night. Nine young women (experiment I) and seven young women (experiment II) participated. Participants wore either a 100% cotton jacket (tight clothes, TC) or a 100% cotton T-shirt (loose clothes, LC). Loose-fitting, 100% cotton tank tops and panties were worn as underwear in both the TC and the LC groups. The main results can be summarized as follows: (1) urinary excretion of adrenaline, noradrenaline and cortisol was facilitated, and the amounts of urinary excretion were significantly higher when TC were worn. Heart rate was significantly higher in the TC group; (2) nocturnal urinary melatonin excretion was significantly greater in the TC group. These results are discussed in terms of an enhancement of diurnal sympathetic nervous system activity caused by pressure on the skin produced by tight clothing.

Adult↗

Erythropoietin exerts neuroprotection after acute spinal cord injury in rats: effect on lipid peroxidation and early ultrastructural findings.

Lipid peroxidation has been reported to play an important role in spinal cord injury (SCI). Erythropoietin (EPO) is a hematopoietic growth factor that stimulates proliferation and differentiation of erythroid precursor cells and is also known to exert neurotrophic activity in the central nervous system. The purpose of this study was to investigate the effectiveness of recombinant human EPO in attenuating the severity of experimental SCI. Rats were divided into seven groups. Controls (1) received only laminectomy. The trauma-only group (2) underwent 50-g/cm contusion injury and had no medication. In group 3, 30 mg/kg of methylprednisolone was introduced. The vehicle group (4) received vehicle solution containing human serum albumin, which is a solvent of EPO. Groups 5, 6, and 7 received 100 IU/kg, 1,000 IU/kg, and 5,000 IU/kg of EPO, respectively. All treatments were given as single doses, intraperitoneally, immediately after injury. Thiobarbituric acid-reactive substances were estimated to demonstrate lipid peroxidation, and ultrastructure was evaluated by electron microscopy. The results showed that lipid peroxidation by-products increased after injury. Administration of EPO and methylprednisolone sodium succinate (MPSS) reduced thiobarbituric acid-reactive substances after trauma. The best biochemical results were obtained with 5,000 IU/kg of EPO. Electron microscopic findings showed that EPO protected the spinal cord from injury. Although 1,000 IU/kg and 5,000 IU/kg of EPO inhibited lipid peroxidation better than MPSS, ultrastructural neuroprotection was similar.

Acute Disease↗

Fusiogenic endogenous-retroviral syncytin-1 exerts anti-apoptotic functions in staurosporine-challenged CHO cells.

Fusiogenic glycoprotein syncytin-1, expressed in human placenta, is a promising candidate for acquiring a basic knowledge of placental syncytialization. However, its cellular mode of action is unidentified. We investigated whether syncytin-1 may exert influence on apoptotic processes. Therefore, we incubated CHO cells after stable transfection with syncytin-1 (CHO-52) in the presence or absence of staurosporine (STS), a kinase inhibitor well characterized to induce apoptosis. When testing the phenotype of CHO-52 cells, we could demonstrate that the induction of apoptosis by STS was delayed over a period of up to 24 h. Furthermore, the cell death rate was decreased by approx 75% following transfection of syncytin-1 in CHO-52 compared to mock-treated cells. In detail, after 18h of incubation with 500 nM STS, 64 +/- 2% of CHO-52 cells were viable compared to 16 +/- 1% of CHO-mocks, after 24 h 43 +/- 3% vs 5 +/- 2%, respectively. CHO-52 cells exhibited a lower expression of active caspase 3 and anti-apoptotic Bcl-2 was found to be increased in CHO-52 cells at baseline and following STS treatment. Our study provides first evidence that syncytin-1 serves anti-apoptotic function under certain conditions. A lessened activation of caspase 3 and an increased expression of Bcl-2 are possible mechanisms.

Animals↗