Discovery of gaseous S2 in Io's Pele plume.

Spectroscopy of Io's Pele plume against Jupiter by the Hubble Space Telescope in October 1999 revealed absorption due to S2 gas, with a column density of 1.0 +/- 0.2 x 10(16) per square centimeter, and probably also SO(2) gas with a column density of 7 +/- 3 x 10(16) per square centimeter. This SO2/S2 ratio (3 to 12) is expected from equilibration with silicate magmas near the quartz-fayalite-magnetite or wüstite-magnetite buffers. Condensed S3 and S4, probable coloring agents in Pele's red plume deposits, may form by polymerization of the S2, which is unstable to ultraviolet photolysis. Diffuse red deposits near other Io volcanoes suggest that venting and polymerization of S2 gas is a widespread feature of Io volcanism.

Fluorescent hydroxyl emissions from Saturn's ring atmosphere.

Just before earth passed through Saturn's ring plane on 10 August 1995, the Hubble Space Telescope Faint Object Spectrograph detected ultraviolet fluorescent emissions from a tenuous atmosphere of OH molecules enveloping the rings. Brightnesses decrease with increasing distance above the rings, implying a scale height of about 0.45 Saturn radii (Rs). A spatial scan 0.28Rs above the A and B rings indicates OH column densities of about 10(13) cm(-2) and number densities of up to 700 cm(-3). Saturn's rings must produce roughly 10(25) to 10(29) OH molecules per second to maintain the observed OH distribution.

HST spectroscopic observations of Jupiter after the collision of comet Shoemaker-Levy 9.

Ultraviolet spectra obtained with the Hubble Space Telescope identified at least 10 molecules and atoms in the perturbed stratosphere near the G impact site, most never before observed in Jupiter. The large mass of sulfur-containing material, more than 10(14) grams in S2 alone, indicates that many of the sulfur-containing molecules S2, CS2, CS, H2S, and S+ may be derived from a sulfur-bearing parent molecule native to Jupiter. If so, the fragment must have penetrated at least as deep as the predicted NH4SH cloud at a pressure of approximately 1 to 2 bars. Stratospheric NH3 was also observed, which is consistent with fragment penetration below the cloud tops. Approximately 10(7) grams of neutral and ionized metals were observed in emission, including Mg II, Mg I, Si I, Fe I, and Fe II. Oxygen-containing molecules were conspicuous by their absence; upper limits for SO2, SO, CO, SiO, and H2O are derived.

Response of the Io plasma torus to comet Shoemaker-Levy 9.

Spectroscopic and imaging observations of the Io plasma torus were made in June and July 1994 in conjunction with the encounter of periodic comet Shoemaker-Levy 9 with Jupiter. Characteristic emissions from sulfur and oxygen ions showed a decline of about 30 percent in the extreme ultraviolet and an increase of about 40 percent in the far ultraviolet relative to preimpact observations. Changes in the extreme ultraviolet may be indicative of small changes in the torus electron temperature as a result of quenching of electrons by dust associated with the comet passage. However, no new emission features indicative of fragment dust within the torus were detected. The characteristic torus morphology seen in ground-based imaging was typical of that observed in the past.

Far-ultraviolet imaging spectroscopy of Io's atmosphere with HST/STIS.

Well-resolved far-ultraviolet spectroscopic images of O I, S I, and previously undetected H ILyman-alpha emission from Io were obtained with the Hubble space telescope imaging spectrograph (STIS). Detected O I and S I lines (1250 to 1500 angstroms) have bright equatorial spots (up to 2.5 kilorayleighs) that shift position with jovian magnetic field orientation; limb glow that is brighter on the hemisphere facing the jovian magnetic equator; and faint diffuse emission extending to approximately 20 Io radii. All O I and S I features brightened by approximately 50 percent in the last two images, concurrently with a ground-based observation of increased iogenic [O I] 6300-angstrom emission. The H ILyman-alpha emission, consisting of a small, approximately 2-kilorayleigh patch near each pole, has a different morphology and time variation.

MAPKs and their relevance to arthritis and inflammation.

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which imbalances in pro- and anti-inflammatory cytokines promote the induction of autoimmunity, inflammation and joint destruction. The importance of inflammatory cytokines in the pathogenesis of RA has been underscored by the success of biologics that act to block the effects of cytokines, such as tumour necrosis factor-alpha, interleukin (IL)-1 or IL-6, in treating disease. Mitogen-activated protein kinases (MAPKs) have been implicated as playing key regulatory roles in the production of these pro-inflammatory cytokines and downstream signalling events leading to joint inflammation and destruction. This article reviews the evidence that MAPKs play important roles in the pathogenesis of RA and discusses their therapeutic potential as drug targets.

Paraproteinemia: blood hyperviscosity and clinical manifestations.

Many of the clinical features of paraproteinemia result from impairment of blood flow through the vascular tree because of blood hyperviscosity. Studies were carried out in 65 patients with serum paraproteins (31 with IgG, 25 with IgM, and 9 with IgA) to examine the relationship between the blood viscosity and the frequency of selected clinical features. The blood and plasma viscosities were measured at low rates of shear. Blood hyperviscosity was present in 91% of the patients and plasma hyperviscosity in 75% of the patients. In each of the three immunoglobulin classes both the blood and plasma viscosities increased logarithmically with the paraprotein concentration being greatest in the case of IgM. In addition, the relationship between the hematocrit and the logarithm of blood viscosity tended to be linear at any given protein concentration. In patients with very high levels of paraprotein the blood viscosity was modified by low hematocrits; the latter was below 30 in 70% of patients in whom the concentration of paraprotein was above 4 g/100 ml. The prevalence of clinical complications involving the retinal circulation, the peripheral vascular system, and the central nervous system increased markedly with increasing blood viscosity, measured at 0.18 S-1. One or more of these regions was affected in greater than 80% of patients with blood viscosity above 60 centipoise and in less than 23% of patients with blood viscosity below 40 centipoise. These observations illustrate the complex relationship between blood viscosity, concentration of paraprotein, immunoglobulin class and hematocrit, and emphasize the importance of measuring the whole blood viscosity at low rates of shear in determining the risk of vascular complications.

Systemic factors contributory to retinal vein occlusion.

This study was undertaken in 79 patients with retinal vein occlusion to assess the different systemic mechanisms contributing to the occlusion, namely, intrinsic vessel disease and abnormalities of the blood constituents and blood viscosity. In 55 patients older than 50 years of age, important associations were hypertension, abnormal results on glucose tolerance test, hyperlipidemia, chronic lung disease, and elevated serum IgA levels. In the 24 patients younger than 50 years of age, male incidence was high and important associations were head injuries, hyperlipidemia, and the use of estrogen-containing preparations. Hyperviscosity and cryofibrinogenemia were prominent in both groups. The pathogenesis of retinal venous occlusion is complex involving interaction between the vessel wall and blood constituents.

The effect of superficial femoral artery occlusion on the outcome of aortofemoral bypass for intermittent claudication.

This study was undertaken to evaluate the effects of untreated superficial femoral artery occlusion in patients undergoing aortofemoral bypass for intermittent claudication. In 56 patients at a mean follow-up time of 3.3 years, graft patency, treadmill walking tolerance, and ankle systolic pressure indices (ASPI) were compared in two groups of limbs: those with a patent superficial femoral artery and those with that vessel occluded. There was a high graft patency rate with no significant difference between the two groups. In limbs with a patent superficial femoral artery, 86% were completely relieved of claudication. However, in limbs with an occluded superficial femoral artery, only 26% were relieved of claudication. In limbs with a patent superficial femoral artery, the mean postoperative ASPI was 0.87 (SE +/- 0.22) compared with 0.61 (SD +/- 0.17) in limbs with an occluded superficial femoral artery. These results indicate that, in patients with combined superficial femoral artery occlusion and aortoiliac disease, revascularizing the deep femoral artery by aortofemoral grafting often does not achieve relief of claudication. There is a need for more effective hemodynamic discrimination of the relative contribution of proximal and distal occlusions.

PTCA in elderly patients: hospital events.

BACKGROUND: Medical treatment of the elderly is changing to include the aggressive management of coronary artery disease with percutaneous transluminal coronary angioplasty. OBJECTIVE: The purpose of this study was to review major hospital events of patients aged 70 years or more, who underwent a first percutaneous transluminal coronary angioplasty. METHODS: A retrospective medical record review was done of 246 consecutive patients of 70 years or more, from January 1985 to December 1988, at a tertiary care community hospital. Adverse events and the factors that influenced outcome were identified. RESULTS: Of 246 patients (age range, 70-85 years, mean = 73.6), 19 died, 4 had a cerebral vascular accident, 11 had a transfusion and 11 underwent coronary artery bypass grafting. Sixteen patients had acute vessel closure and 8 died. Twenty-five patients had one event and 21 patients had more than one. DISCUSSION: The event rate after percutaneous transluminal coronary angioplasty in the elderly is high. CONCLUSIONS: Knowledge of the factors that influence adverse events (diagnostic category, success of procedure, degree of coronary artery disease and age) will assist the critical care team to plan and implement appropriate care.

Effects of 3 analgesic regimens on the perception of pain after removal of femoral artery sheaths.

BACKGROUND: Effective pain management after removal of femoral artery sheaths after percutaneous transluminal coronary angioplasty is highly individualized and requires frequent, accurate assessment and administration of analgesics as needed. OBJECTIVE: To determine which of 3 analgesic regimens is most effective in decreasing patients' perception of pain with the fewest side effects after removal of a femoral artery sheath. SAMPLE: 130 adult who had undergone percutaneous transluminal coronary angioplasty and were in an 8-bed cardiac short-stay unit in a 1400-bed acute care hospital. METHOD: Patients were randomized to receive either intravenous morphine, intravenous fentanyl, subcutaneous lidocaine around the sheath site, or an intravenous placebo before sheath removal. Rescue analgesia (intravenous fentanyl) was made available to all groups. Patients used a visual analog scale to assess pain within 10 minutes before, 1 minute after, and 20 minutes after sheath removal. Pain levels, frequency of side effects, and use of rescue analgesia were compared among groups. RESULTS: Age, sex, number of stents, and frequency of hematomas did not differ significantly among groups. Pain ratings, use of rescue analgesia, and side effects (nausea, vomiting, or vasovagal symptoms) were not significantly different among treatment groups. Ratings of pain were slightly higher immediately after sheath removal in all groups. CONCLUSION: For most patients, removal of femoral artery sheaths and manual compression for hemostasis are relatively pain-free. Pain scores among patients given analgesia with subcutaneous lidocaine, intravenous morphine, or intravenous fentanyl were not significantly different from pain scores among control patients.

Femoral arterial sheath removal after PTCA: a cross-Canada survey.

A cross-sectional survey was conducted to examine current Canadian practices in the nursing and medical management of femoral arterial sheath removal (SR) after PTCA (percutaneous transluminal coronary angioplasty). The purposes of the study were to (a) investigate the roles of the nurses and physicians in SR, (b) assess the length of time arterial sheaths are left in place and patients kept on bedrest, and (c) describe the routine medical protocols used for pain and anticoagulation therapy. Of the 35 hospitals that perform PTCA in Canada, 30 responded to the survey (response rate of 86%). Nurses had primary responsibility for SR in 13% of the sites and shared responsibility with physicians for SR in a further 10% of the institutions. When nurses were trained to remove sheaths, they assumed responsibility for the adjunctive steps to establish hemostasis. One third of hospitals removed sheaths in 4 hours or less; approximately 75% of them removed sheaths in 6 hours or less after PTCA. Patients are kept on bedrest for 6 hours or less following hemostasis in half, and 8 hours or less at three-quarters of the hospitals. Post-PTCA and pre-SR anticoagulant monitoring was used in almost half of the sites. Premedication for SR varied from no premedication to combinations of three intravenous medications plus local anaesthetic. Survey results showed that in almost one quarter of the Canadian institutions where PTCA is performed, nurses play a role in SR. Results also showed that there is no uniformity in post-PTCA SR across Canada and that further research is needed to identify the optimum approach to managing this common cardiovascular procedure.

Epac and the high affinity rolipram binding conformer of PDE4 modulate neurite outgrowth and myelination using an in vitro spinal cord injury model.

BACKGROUND AND PURPOSE: cAMP and pharmacological inhibition of PDE4, which degrades it, are promising therapeutic targets for the treatment of spinal cord injury (SCI). Using our previously described in vitro SCI model, we studied the mechanisms by which cAMP modulators promote neurite outgrowth and myelination using enantiomers of the PDE4-specific inhibitor rolipram and other modulators of downstream signalling effectors. EXPERIMENTAL APPROACH: Rat mixed neural cell myelinating cultures were cut with a scalpel and treated with enantiomers of the PDE4-specific inhibitor rolipram, Epac agonists and PKA antagonists. Neurite outgrowth, density and myelination were assessed by immunocytochemistry and cytokine levels analysed by qPCR. KEY RESULTS: Inhibition of the high-affinity rolipram-binding state (HARBS), rather than the low-affinity rolipram binding state (LARBS) PDE4 conformer promoted neurite outgrowth and myelination. These effects were mediated through the activation of Epac and not through PKA. Expression of the chemokine CXCL10, known to inhibit myelination, was markedly elevated in astrocytes after Rho inhibition and this was blocked by inhibition of Rho kinase or PDE4. CONCLUSIONS AND IMPLICATIONS: PDE4 inhibitors targeted at the HARBS conformer or Epac agonists may provide promising novel targets for the treatment of SCI. Our study demonstrates the differential mechanisms of action of these compounds, as well as the benefit of a combined pharmacological approach and highlighting potential promising targets for the treatment of SCI. These findings need to be confirmed in vivo.

Science potential from a Europa lander.

The prospect of a future soft landing on the surface of Europa is enticing, as it would create science opportunities that could not be achieved through flyby or orbital remote sensing, with direct relevance to Europa's potential habitability. Here, we summarize the science of a Europa lander concept, as developed by our NASA-commissioned Science Definition Team. The science concept concentrates on observations that can best be achieved by in situ examination of Europa from its surface. We discuss the suggested science objectives and investigations for a Europa lander mission, along with a model planning payload of instruments that could address these objectives. The highest priority is active sampling of Europa's non-ice material from at least two different depths (0.5-2 cm and 5-10 cm) to understand its detailed composition and chemistry and the specific nature of salts, any organic materials, and other contaminants. A secondary focus is geophysical prospecting of Europa, through seismology and magnetometry, to probe the satellite's ice shell and ocean. Finally, the surface geology can be characterized in situ at a human scale. A Europa lander could take advantage of the complex radiation environment of the satellite, landing where modeling suggests that radiation is about an order of magnitude less intense than in other regions. However, to choose a landing site that is safe and would yield the maximum science return, thorough reconnaissance of Europa would be required prior to selecting a scientifically optimized landing site.

Hyperosmolarity: effects on nerves and smooth muscle of cutaneous veins.

Helical strips from dogs' saphenous veins were mounted in an organ bath (Krebs-Ringer solution, 37 degrees C) for isometric tension recording. Additional strips were incubated with [7-3H]norepinephrine and mounted for superfusion and isometric tension recording. The perfusate was collected every 2 min for estimation of total radioactivity and for column chromatographic separation of [3H]norepinephrine and its metabolites. Increasing osmolarity by sucrose caused a slow contraction that was maximal at 500-550 mosM and was accompanied by a reduction in total 3H efflux. The contraction was unaffected by a Ca2+-free medium, alpha-adrenegic blockade, and beta-adrenergic stimulaton. It was depressed by cooling (29 degrees C) and by anoxia combined with a glucose-free medium. Contractions elicited by K+ and Ba2+ were augmented by hyperosmolarity, but those caused by sympathetic nerve stimulation, tyramine, and norepinephrine were depressed. The output of [3H]norepinephrine during nerve stimulation was reduced. Thus, the hyperosmolarity causes 1) contraction of vascular smooth muscle, 2) augmentation of the contractile response to K+ and Ba2+, 3) depression of the excitation caused by norepinephrine, and 4) inhibition of the neuronal release of norepinephrine.

Inhibition of adrenergic neurotransmission in canine vascular smooth muscle by histamine: mediation by H2-receptors.

Histamine depressed the contractions of dog saphenous vein strips caused by stimulation of their sympathetic nerves. This was due to a decrease in the release of norepinephrine which appears to be mediated by histamine H2-receptors. The evidence for this is as follows: (1) Contractions of the strips caused by activating the nerve endings electrically or by depolarization with potassium ions were depressed by histamine, whereas contractions caused by tyramine and norepinephrine were either unchanged or augmented. (2) Strips were incubated with norepinephrine[7-3H] and mounted for superfusion and isometric tension recording. The perfusate was collected for estimation of total radioactivity and for column chromatographic separation of norpinephrine and its metabolites. Histamine (0.9 muM) depressed the release of norepinphrine[7-3H] during contractions caused by electric stimulation, whereas the release of radioactive compounds caused by tyramine was unaffected. (3) The depression by histamine of the contractions and the efflux of radioactive compounds caused by electric stimulation were inhibited by an H2-receptor antagonist (metiamide), but were unaffected by an H1-receptor antagonist (pyrilamine). (4) Contractions caused by electric stimulation were inhibited by an H2-receptor agonist (4-methylhistamine) and augmented by an H1-receptor agonist (2-methylhistamine). These findings suggest the possibility that histamine, which is abundant in sympathetic nerves, might have a regulatory role in the release of the neurotransmitter.

Histamine and 5-hydroxytryptamine-inhibition of transmitter release mediated by H2- and 5-hydroxytryptamine receptors.

The vasodilatation caused by histamine and 5-hydroxytryptamine may be due, at least in part, to their inhibitory action on adrenergic neurotransmission. The evidence for this is as follows: 1) contractions of isolated canine vascular strips caused by sympathetic nerve stimulation are depressed by these substances whereas contractions caused by norepinephrine are either unchanged or augmented; 2) histamine and 5-hydroxytryptamine inhibit the release of norepinephrine evoked by sympathetic nerve stimulation of isolated vascular strips previously incubated with the labeled transmitter. This inhibitory effect can be demonstrated using concentrations of the substinces less than those required to affect the smooth muscle cells directly. By contrast, neither histamine nor 5-hydroxytryptamine inhibits the displacement of neuronal norepinephrine by tyramine, suggesting that these substances interfere with the exocytotic process. Additional studies have identified the histamine-H2 receptor as the probable mediator of this prejunctional action of histamine, whereas the nature of the receptor for 5-hydroxytryptamine remains to be clarified.

Blood hyperviscosity in cryoglobulinaemia: temperature sensitivity and correlation with reduced skin blood flow.

Cryoglobulins cause an increase in plasma viscosity and this has been attributed to increased protein-protein interaction. The purpose of the present study was to analyse the interaction between red cells and these proteins by measuring the viscosity of whold blood from 21 patients with cryoglobulinaemia not only at high (73 sec-1) and low (0.18 sec-1) shear rates, but also at different temperatures. At 35 degrees blood hyperviscosity was found in 62% of the patients at the high shear rate, and in 76% of patients at the low shear rate. Cooling of the blood to 25 degrees caused an increase in the blood viscosity which was particularly marked at the low shear rate. The plasma viscosity was significantly increased at both temperatures. The hand blood flow was measured at 32 degrees, 27 degrees and 20 degrees in 12 patients to assess the degree of impairment of the peripheral circulation. The flows were significantly reduced at each temperature and there was an increase in the sensitivity of the flow through this region to local cooling. These findings indicate that in the presence of a cryoglobulin there is an increased viscous resistance, particularly at low flow rates. The temperature and shear rate characteristics of the blood viscosity suggest that cryoglobulins markedly potentiate red cell aggregation. This explains, at lest in part, the high incidence of skin and vascular complications in patients with cryoglobulinaemia and the characteristic localization of these features to exposed peripheral tissues.

The epidemiology of lower limb ischaemia in a new South Wales rural community.

A cross-sectional survey was carried out in the Bangalow Valley on the far north coast of new South Wales to determine the prevalence of lower limb ischaemia. A study was made of 80.2% of the population aged thirty years and over. The presence or absence of peripheral vascular disease was determined by clinical history, clinical examination, and measurement of peripheral arterial pressures with a Doppler ultrasonic velocity detector. Twelve out of 232 (5.2%) males and seven out of 282 (2.5%) females had symptomatic lower limb ischaemia. From these data the predicted incidence of lower limb ischaemia in the sixth and seventh decades in New South Wales is 40/10,000/year in males and 14.5/10,000/year in females. These N.S.W. data re compared with studies in the United Kingdom, the United States of America, and Switzerland, and similarities are noted indicating the universal nature of lower limb atherosclerosis in developed countries.