Sequential IV/PO moxifloxacin treatment of patients with severe community-acquired pneumonia.

BACKGROUND: IV/PO moxifloxacin was evaluated in the treatment of hospitalized patients with severe community-acquired pneumonia (CAP). METHODS: Data were pooled from two prospective, randomized studies. In the multinational study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD or IV/ PO amoxicillin clavulanate 1200/625 mg TID +/- IV/PO clarithromycin 500 mg BID. In the North American study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD, IV/ PO alatrofloxacin/trovafloxacin 200 mg QD, or IV/PO levofloxacin 500 mg QD. The primary endpoint was clinical success at the test-to-cure visit. Severe CAP was defined according to the 1993 ATS criteria. RESULTS: In the clinically valid population, clinical success rates were 88% (167/190) for moxifloxacin- and 83% (155/186) for comparator-treated patients (95% CI = -1.9%, 12.2%). Corresponding clinical success rates for the microbiologically valid population were 87% (59/68) and 84% (54/64), respectively (95% CI = 8.6%, 15.0%). A switch from IV to PO therapy was made by day 5 of therapy for 73% of moxifloxacin- vs. 60% of comparator-treated patients (P < 0.01). Clinical success rates were similar in a retrospective analysis using the revised 2001 ATS definition of severe CAP. Mortality rates were 6% (15/241) and 10% (24/238) in the moxifloxacin and comparator treatment groups, respectively. The incidence of drug-related adverse events was similar in both treatment groups. CONCLUSION: Sequential IV/PO moxifloxacin 400 mg QD is as safe and effective as other fluoroquinolones and a beta-lactam/macrolide combination for treating hospitalized patients with severe CAP.

Randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment.

The objective of the present trial was to compare the efficacy, safety, and tolerability of moxifloxacin (400 mg) given intravenously (i.v.) once daily followed by oral moxifloxacin (400 mg) for 7 to 14 days with the efficacy, safety, and tolerability of co-amoxiclav (1.2 g) administered by i.v. infusion three times a day followed by oral co-amoxiclav (625 mg) three times a day, with or without clarithromycin (500 mg) twice daily (i.v. or orally), for 7 to 14 days in adult patients with community-acquired pneumonia requiring initial parenteral therapy. A total of 628 patients were enrolled and assessed by evaluation of their clinical and bacteriological responses 5 to 7 days and 21 to 28 days after administration of the last dose of study medication. Although the trial was designed, on the basis of predefined outcomes, to demonstrate the equivalence of the two regimens, the results showed statistically significant higher clinical success rates (for moxifloxacin, 93.4%, and for comparator regimen, 85.4%; difference [Delta], 8.05%; 95% confidence interval [CI], 2.91 to 13.19%; P = 0.004) and bacteriological success rates (for moxifloxacin, 93.7%, and for comparator regimen, 81.7%; Delta, 12.06%; 95% CI, 1.21 to 22.91%) for patients treated with moxifloxacin. This superiority was seen irrespective of the severity of the pneumonia and whether or not the combination therapy included a macrolide. The time to resolution of fever was also statistically significantly faster for patients who received moxifloxacin (median time, 2 versus 3 days), and the duration of hospital admission was approximately 1 day less for patients who received moxifloxacin. The treatment was converted to oral therapy immediately after the initial mandatory 3-day period of i.v. administration for a larger proportion of patients in the moxifloxacin group than patients in the comparator group (151 [50.2%] versus 57 [17.8%] patients). There were fewer deaths (9 [3.0%] versus 17 [5.3%]) and fewer serious adverse events (38 [12.6%] versus 53 [16.5%]) in the moxifloxacin group than in the comparator group. The rates of drug-related adverse events were comparable in both groups (38.9% in each treatment group). The overall incidence of laboratory abnormalities was similar in both groups. Thus, it is concluded that monotherapy with moxifloxacin is superior to that with a standard combination regimen of a beta-lactam and a beta-lactamase inhibitor, co-amoxiclav, with or without a macrolide, clarithromycin, in the treatment of patients with community-acquired pneumonia admitted to a hospital.

Intrinsic and extrinsic risk factors for anterior cruciate ligament injury in Australian footballers.

The aim of this study was to examine the interaction between intrinsic (player-related) and extrinsic (environment-related) variables as risk factors for anterior cruciate ligament injury in Australian football. Between 1992 and 1999, 100,820 player-match exposures were analyzed for risk of anterior cruciate ligament injury using logistic regression analysis. There were 63 surgically proven noncontact anterior cruciate ligament injuries. The strongest risk factors were a player history of anterior cruciate ligament reconstruction either in the previous 12 months (relative risk [RR], 11.33; 95% confidence interval [CI], 4.02 to 31.91) or before the previous 12 months (RR, 4.44; 95% CI, 2.46 to 8.01). Weather conditions that were associated with dry field conditions--high water evaporation in the month before the match (RR, 2.55; 95% CI, 1.44 to 4.52) and low rainfall in the year before the match (RR, 2.87; 95% CI, 1.30 to 6.32)--were also significantly associated with these injuries. The increased risk of injury in the first 12 months after reconstruction was associated with the reconstructed knee, whereas after 12 months there was an even distribution of new injuries to the reconstructed knee and contralateral knee. A history of anterior cruciate ligament reconstruction is a risk factor for further injury. Weather conditions of high evaporation and low rainfall before matches are associated with noncontact anterior cruciate ligament injury.

Regulated expression of the rat recombinant P2X(3) receptor in stably transfected CHO-K1 tTA cells.

In this report, the regulatable expression by tetracycline of the rat recombinant P2X(3) receptor in stably transfected Chinese hamster ovary (CHO-K1) expressing the tetracycline-controlled transactivator (tTA) is described. cDNA encoding the rat P2X(3)-receptor was subcloned into pTRE (a tetracycline-repressible expression vector) which was used to transfect stably CHO-K1 tTA cells. Using whole cell patch clamp techniques, 100 microM ATP evoked inward currents of 2.9+/-1.6 nA in transfected cells grown in the absence of tetracycline (tet-). The P2X(3) receptor protein was detectable by immunoblot as early as 24 h and protein expression levels continued to increase as much as 192 h following activation of tTA by the removal of the antibiotic. Saturation binding isotherms using [35S]ATP gamma S yielded a pK(d) of 8.2+/-0.1 and a B(max) of 31.9+/-3.5 pmol/mg protein in tet- cell membranes and a pK(d) of 8.1+/-0.1 and a B(max) of 5.8+/-0.8 pmol/mg protein in tet+ cell membranes. The agonist ligands 2MeSATP and alpha beta MeATP displaced the binding of [35S]ATP gamma S in tet- cell membranes with very high affinity, yielding pIC(50) values of 9.4+/-0.2 and 7.5+/-0. 2, respectively. In tet+ cell membrane, displacement of [35S]ATP gamma S by 2MeSATP and alpha beta MeATP was of much lower affinity (pIC(50) values of 7.8 and 6.2, respectively). ATP, ADP and UTP showed similar displacement of [35S]ATP gamma S binding in tet- and tet+ cell membranes. In other experiments, cytosolic Ca(2+) was monitored using the fluorescent indicator, fluo-3. Increases in cytosolic Ca(2+) were elicited by 100 nM alpha beta MeATP in tet- cells while no increases in cytosolic Ca(2+) were detected below 100 microM alpha beta MeATP in either tet+ cells or untransfected cells. These calcium responses to alpha beta MeATP had a pEC(50) of 6.7 and were transient, returning to baseline within 120 s. Suramin produced concentration-dependent, parallel, dextral shifts of E/[A] curves to alpha beta MeATP yielding a pK(B) of 5.6. PPADS produced non-parallel, dextral shifts of E/[A] curves to alpha beta MeATP which were insurmountable. These results show for the first time, expression of a functional, homomeric recombinant rat P2X(3) receptor which is under regulated expression in a stably transfected mammalian cell line.

Rainfall, evaporation and the risk of non-contact anterior cruciate ligament injury in the Australian Football League.

OBJECTIVE: To determine if weather conditions affect the risk of anterior cruciate ligament (ACL) tear in Australian Football. DESIGN: Prospective observational analytic study of football matches. SETTING: The Australian Football League (AFL), a professional competition. PARTICIPANTS: All players in 2280 matches from 1992-1998. MAIN OUTCOME MEASURES: Surgically-proven ACL injury, not involving a direct contact mechanism, during a match; rainfall; water evaporation. RESULTS: 59 ACL injuries not involving direct contact occurred during the study period, more commonly in cities north of Melbourne (chi 2 = 17.0; df = 1; P < 0.001). Senior grade matches (relative risk [RR], 3.03; 95% confidence interval [CI], 1.52-6.03), high water evaporation in the month before the match (RR, 2.80; 95% CI, 1.53-5.10) and low rainfall in the year before the match (RR, 1.93; 95% CI, 1.12-3.34) were significantly associated with these injuries. CONCLUSION: Low water evaporation and high rainfall significantly lower the risk of ACL injuries in AFL footballers. The likely mechanism is a softening of the ground, which lowers shoe-surface traction. Consistent extra watering and covering of grounds during periods of high water evaporation may lower the rate of ACL injuries.

Functional analysis of a voltage-gated sodium channel and its splice variant from rat dorsal root ganglia.

Neurons of the dorsal root ganglia (DRG) express a diversity of voltage-gated sodium channels. From rat DRG we have cloned and functionally expressed a tetrodotoxin-sensitive sodium channel alpha subunit, NaCh6/Scn8a/rPN4, and a splice variant, rPN4a. Primary structure analysis shows NaCh6/Scn8a/rPN4 to be highly homologous (99%) to NaCh6 and most likely represents the same transcript. The splice variation in rPN4a is homologous in sequence and location to that of rat brain I. Tissue distribution analyzed by RT-PCR showed NaCh6/Scn8a/rPN4 to be expressed at its highest levels in rat brain, at moderate levels in spinal cord, and at lower levels in DRG, nodose ganglia, and superior cervical ganglia and to be absent from sciatic nerve, heart, and skeletal muscle. In contrast, rPN4a shows no expression in brain and low-level expression in spinal cord, whereas in DRG its expression is comparable to that of NaCh6/Scn8a/rPN4. Functional analysis of these channels expressed in Xenopus oocytes showed that NaCh6/Scn8a/rPN4 and rPN4a exhibited similar properties, with V(1/2) approximately -100 mV for steady-state inactivation and V(1/2) approximately -40 mV for activation. rPN4a recovered from inactivation significantly faster than NaCh6/Scn8a/rPN4. NaCh6/Scn8a/rPN4 was inhibited by tetrodotoxin with an IC50 approximately 1 nM. Coexpression of the beta1 subunit accelerated inactivation kinetics, but the beta2 subunit was without effect.

Distribution of the tetrodotoxin-resistant sodium channel PN3 in rat sensory neurons in normal and neuropathic conditions.

The novel sodium channel PN3/alpha-SNS, which was cloned from a rat dorsal root ganglion (DRG) cDNA library, is expressed predominantly in small sensory neurons and may contribute to the tetrodotoxin-resistant (TTXR) sodium current that is believed to be associated with central sensitization in chronic neuropathic pain states. To assess further the role of PN3, we have used electrophysiological, in situ hybridization and immunohistochemical methods to monitor changes in TTXR sodium current and the distribution of PN3 in normal and peripheral nerve-injured rats. (1) Whole-cell patch-clamp recordings showed that there were no significant changes in the TTXR and TTX-sensitive sodium current densities of small DRG neurons after chronic constriction injury (CCI) of the sciatic nerve. (2) Additionally, in situ hybridization showed that there was no change in the expression of PN3 mRNA in the DRG up to 14 d after CCI. PN3 mRNA was not detected in sections of brain and spinal cord taken from either normal or nerve-injured rats. (3) In contrast, immunohistochemical studies showed that major changes in the subcellular distribution of PN3 protein were caused by either CCI or complete transection of the sciatic nerve. The intensity of PN3 immunolabeling decreased in small DRG neurons and increased in sciatic nerve axons at the site of injury. The alteration in immunolabeling was attributed to translocation of presynthesized, intracellularly located PN3 protein from neuronal somata to peripheral axons, with subsequent accumulation at the site of injury. The specific subcellular redistribution of PN3 after peripheral nerve injury may be an important factor in establishing peripheral nerve hyperexcitability and resultant neuropathic pain.

[3H]-lifarizine, a high affinity probe for inactivated sodium channels.

1. [3H]-lifarizine bound saturably and reversibly to an apparently homogeneous class of high affinity sites in rat cerebrocortical membranes (Kd = 10.7 +/- 2.9 nM; Bmax = 5.10 +/- 1.43 pmol mg-1 protein). 2. The binding of [3H]-lifarizine was unaffected by sodium channel toxins binding to site 1 (tetrodotoxin), site 3 (alpha-scorpion venom) or site 5 (brevetoxin), Furthermore, lifarizine at concentrations up to 10 microM had no effect on [3H]-saxitoxin (STX) binding to toxin site 1. Lifarizine displaced [3H]-batrachotoxinin-A 20-alpha-benzoate (BTX) binding with moderate affinity (pIC50 7.31 +/- 0.24) indicating an interaction with toxin site 2. However, lifarizine accelerated the dissociation of [3H]-BTX and decreased both the affinity and density of sites labelled by [3H]-BTX, suggesting an allosteric interaction with toxin site 2. 3. The binding of [3H]-lifarizine was voltage-sensitive, binding to membranes with higher affinity than to synaptosomes (pIC50 for cold lifarizine = 7.99 +/- 0.09 in membranes and 6.68 +/- 0.14 in synaptosomes). Depolarization of synaptosomes with 130 mM KCl increased the affinity of lifarizine almost 10 fold (pIC50 = 7.86 +/- 0.25). This suggests that lifarizine binds selectively to inactivated sodium channels which predominate both in the membrane preparation and in the depolarized synaptosomal preparation. 4. There was negligible [3H]-lifarizine and [3H]-BTX binding to solubilized sodium channels, although [3H]-STX binding was retained under these conditions. 5. The potencies of a series of compounds in displacing [3H]-lifarizine from rat cerebrocortical membranes correlated well with their affinities for inactivated sodium channels estimated from whole-cell voltage clamp studies in the mouse neuroblastoma cell line, NIE-115 (r=0.96).6. These results show that [3H]-lifarizine is a high affinity ligand for neuronal sodium channels which potently and selectively labels a site, allosterically linked to toxin binding site 2, associated within activated sodium channels.

Electrophysiological actions of phenytoin on N-methyl-D-aspartate receptor-mediated responses in rat hippocampus in vitro.

1. The effects of the anticonvulsant, phenytoin, have been examined on N-methyl-D-aspartate (NMDA) receptor-mediated population spikes in the CA1 region of the rat hippocampus in vitro. 2. The 'conventional' (AMPA receptor-mediated) CA1 population spike, evoked by electrical stimulation of the Schaffer collateral/commissural pathway, was abolished by 5 min treatment with 5 x 10(-6) M 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), after which superfusion with a nominally Mg(2+)-free Krebs solution (containing 5 x 10(-6) M CNQX) led to the appearance of an epileptiform population spike which was fully developed by 30-40 min. 3. The epileptiform population spike was abolished by the non-competitive NMDA antagonist, dizocilpine (1 x 10(-6) M, 20-30 min) and inhibited by the competitive NMDA receptor antagonist, D-CPP (IC50 for reducing the amplitude of the first spike in the train = 8.3 x 10(-7) M), demonstrating that the response was mediated by activation of NMDA receptors and validating its use as an assay for antagonists acting at the NMDA receptor/channel complex. 4. Phenytoin (0.1, 0.3 and 1 x 10(-4) M applied cumulatively for 30 min at each concentration) failed to inhibit the NMDA receptor-mediated epileptiform population response (n = 7 slices). 5. Phenytoin (3 x 10-6 M to 1 x 10-4M) attenuated the effects of the sodium channel activator,veratridine (2 x 10-6 M), on the CAl population spike amplitude (recorded in normal Krebs solution),indicating that the previously observed lack of effect of phenytoin on the NMDA receptor-mediated response was not due to impaired access of phenytoin to the biophase.6. These data support the conclusion that antagonism of NMDA receptor-mediated events is not a pharmacological property of phenytoin and that such an action is therefore unlikely to contribute to the anticonvulsant activity of this drug.

Actions of the novel neuroprotective agent, lifarizine (RS-87476), on voltage-dependent sodium currents in the neuroblastoma cell line, N1E-115.

1. The actions of the neuroprotective agent, lifarizine (RS-87476-190), on voltage-dependent Na+ currents have been examined in the neuroblastoma cell line, N1E-115, using the whole-cell variant of the patch clamp technique. 2. At a holding potential of -80 mV, lifarizine reduced the peak Na+ current evoked by a 10 ms depolarizing step with an IC50 of 1.3 microM. At holding potentials of -100 and -60 mV the IC50 concentrations of lifarizine were 7.3 microM and 0.3 microM, respectively. 3. At a holding potential of -100 mV, most channels were in the resting state and the IC50 value for inhibition of Na+ current should correspond to the dissociation constant of lifarizine for resting channels (KR). KR was therefore estimated to be 7.3 microM. 4. In the absence of lifarizine, recovery from inactivation following a 20 s depolarization from -100 mV to 0 mV was complete within 2 s. However, in the presence of 3 microM lifarizine recovery took place in a biexponential fashion with time constants of 7 s and 79 s. 5. Lifarizine (1 microM) had no effect on steady-state inactivation curves when conditioning pre-pulses of 1 s duration were used. However, when pre-pulse durations of 1 min were used the curves were shifted to the left by lifarizine by about 10 mV. Analysis of the shifts induced by a range of lifarizine concentrations revealed that the apparent affinity of lifarizine for the inactivated state of the channel (K1) was 0.19 microM. 6. Lifarizine (1 microM) had no effect on chloramine-T-modified Na+ currents, suggesting no significant open channel interaction. 7. Taken together, these data show that lifarizine is a potent voltage-dependent inhibitor of Na+currents in NIE-115 cells and that the voltage-dependence arises from an interaction of the compound with the inactivated state of the channel. The possible contribution of Na+ current inhibition to the neuroprotective actions of lifarizine is discussed.

Action of alpha-dendrotoxin on K+ currents in nerve terminal regions of axons in rat olfactory cortex.

1. In the rat olfactory cortex, unmyelinated axons give rise to synapses en passant. This tissue was used to study the pharmacology of axonal K(+)-currents. Responses were measured from a group of these axons as unclamped field currents, with a polarizable suction electrode. 2. A single stimulus to the axons elicited a tetrodotoxin-sensitive Na(+)-dependent transient K(+)-currents were revealed by positive polarization of the suction electrode and were manifest as a negative current following the Na(+)-component. 3. In the presence of tetraethylammonium (TEA, 5 mM) and Cd2+ (100 microM), the K(+)-component was depressed by 3,4-diaminopyridine (3,4-DAP; 1 to 20 microM; IC50 2.0 +/- 0.4 microM). alpha-Dendrotoxin (DTX; 15-1500 nM) also attenuated the aminopyridine-sensitive component (IC50 93 +/- 4 nM). At the highest DTX concentration, depression of the K(+)-current was incomplete, the residual K+ current being reduced by 3,4-DAP (0.1 to 5 microM). 4. These results indicate the presence of two aminopyridine-sensitive K+ currents in this preparation distinguished by their susceptibility to DTX.

Phorbol ester and lignocaine or pentobarbitone interactions at presynaptic axons.

The interaction between anaesthetics and protein kinase C activation was studied in unclamped field currents from unmyelinated axons which give rise to en passant synapses. Electrical responses could be resolved into Na, K and Ca components revealed by electrode polarisation pretreatment with blockers of K-conductances. In the presence of phorbol dibutyrate, there was an increase in the potency of lignocaine, pentobarbitone and tetrodotoxin: for the Na current, the potency increased by 2.67 +/- 0.64, 2.35 and 2.47 fold respectively. The potentiation does not appear to be any indirect result of changed membrane potential. It is suggested that protein kinase C phosphorylation of membrane channel proteins increases the effectiveness of these substances.

Action of general anaesthetics on unclamped Ca(2+)-mediated currents in unmyelinated axons of rat olfactory cortex.

Na+ and Ca2+ currents were monitored using a suction electrode in unclamped presynaptic axons of rat olfactory cortex pretreated with 0.1 mM 3,4-diaminopyridine and 5 mM tetraethylammonium. The effects of anaesthetics on these currents were compared with tetrodotoxin or cadmium. Ketamine (0.1-1 mM), ether (20-200 mM), diisopropylphenol (0.01-0.5 mM) and lignocaine (0.01-0.2 mmol/l) all depressed both the initial Na+ component and the Ca(2+)-mediated tail of the response. Urethane (5-100 mM), halothane (1-5 mM) and pentobarbitone (0.1-2 mM) showed slight selectivity for the axonal Ca2+ tail. Diisopropylphenol apparently enhanced the Ca2+ tail at low concentrations. The alphaxalone (1-50 microM) depression was very weak. In a few cases the depression may contribute to anaesthesia but with others, high concentrations may contribute to the toxicity of the substances in vivo.

Phorbol dibutyrate enhances local anaesthetic action.

1. Synaptically-evoked field responses were elicited by stimulation of the lateral olfactory tract of rat olfactory cortex slices maintained in vitro. 2. Various concentrations of lignocaine (5-500 microM) were applied to the solution bathing the slices. These produced dose-dependent depressions of the synaptically-evoked potential over the concentration range 20-500 microM. The responses completely recovered on washing out the lignocaine. Similar depressions were also noted for procaine (100-1000 microM). 3. In the 47 slices tested, application of beta-phorbol 12,13-dibutyrate (1 microM) increased the amplitude of the synaptic response (from 0.99 +/- 0.05 to 1.36 +/- 0.06 mV). beta-Phorbol 13-monbutyrate (1 microM) had no effect. 4. In the presence of phorbol dibutyrate the depressant effect of lignocaine was increased: the EC50 changed from 91 +/- 10 to 24 +/- 2 microM (a mean potency increase of 3.47 +/- 0.14). A similar increase in potency for procaine was observed with phorbol dibutyrate (from 264 +/- 23 to 49 +/- 9 microM: a 5.49 +/- 0.82 increase in potency). If the tissue was pre-equilibrated in a concentration of lignocaine which produced a 60-80% depression, addition of phorbol ester caused a complete abolition of the evoked potential. 5. beta-Phorbol 13-monobutyrate (1 microM) had no effect on the potency of lignocaine. 6. The Na and K currents generating the action potential in the presynaptic nerve terminals were unaffected by phorbol dibutyrate. The depressant effect of lignocaine on these currents was not modified by phorbol dibutyrate. The depressant effect of lignocaine on these currents was not modified by phorbol dibutyrate. 7. The potentiation of lignocaine could not be accounted for by membrane depolarization or by nonspecific actions of phorbol dibutyrate, and was distinct from the action on transmitter release. Therefore, it seems likely that protein kinase C activation was responsible for the modified action of lignocaine, although the mechanism for this is unclear.

General anaesthetics and field currents in unclamped, unmyelinated axons of rat olfactory cortex.

1. The effects of seven general anaesthetics and one local anaesthetic having a wide range of physical and chemical properties were studied on nerve terminal Na- and K-mediated currents in slices of olfactory cortex. These currents were measured from the groups of fine unmyelinated axons traversing the surface of the olfactory cortex and which give off synapses en passant. The amplitude of the K-current was visualized by depolarizing the axons via an electrode polarization. 2. The anaesthetics tested were ketamine (0.1-2 mM), pentobarbitone (0.1-5 mM), urethane (5-200 mM), halothane (0.5-5 mM), ether (10-200 mM), alphaxalone (0.001-0.05 mM), diisopropylphenol (0.05-0.5 mM) and lignocaine (0.01-0.5 mM). All had depressant effects on the axonal Na-current (at the higher concentrations tested) and on the K-current (at slightly lower concentrations). The apparent lower potency on the Na-current was considered to be due to a masking of effect as a consequence of the reduction in the K-mediated membrane rectification rather than any real difference in the susceptibilities of the Na and K-currents. 3. Some of the depressant effect of pentobarbitone and alphaxalone was gamma-aminobutyric acid (GABA)-mediated as indicated by the reduced potency in the presence of bicuculline. The actions of ketamine and halothane were unaffected by bicuculline. 4. For some anaesthetics these axonal depressant effects might contribute to general anaesthesia, while for other substances the relatively high concentrations necessary would suggest that this mode of action does not produce effective anaesthesia in vivo.

Improved survival in murine lupus as the result of selenium supplementation.

Selenium is a trace mineral and a required nutrient for animals and humans. Selenium intake appears to be inversely correlated with the risk of developing cancer. Since immunological effects of selenium have been described we studied the capacity of selenium to modify the lupus-like disease of NZB/NZW female mice. Our data indicate that selenium supplementation (sodium selenite 4 parts per million in the drinking water) significantly improves survival in these autoimmune mice: mean survival 55.6 +/- 4.6 weeks (mean +/- s.e.) for treated mice versus 36.1 +/- 1.9 weeks for controls (P less than 0.04). Additionally, selenium supplemented mice had significantly higher natural killer cell activity (P less than 0.001). However, no obvious effects of selenium supplementation on autoantibody production were observed.