Search

Seafloor methane emissions can affect Earth's climate and ocean chemistry. Vast quantities of methane formed by microbial decomposition of organic matter are locked within gas hydrate and free gas on continental slopes, particularly in large areas with high sediment accumulations such as deep-sea fans. The release of methane in slope environments has frequently been associated with dissociation of gas hydrates near the edge of the gas hydrate stability zone on the upper slope, with discharges in greater water depths less understood. Here we show, using data from the Rio Grande Cone (western South Atlantic), that the intrinsic, gravity-induced downslope collapse of thick slope sediment accumulations creates structures that serve as pathways for gas migration, unlocking methane and causing seafloor emissions via giant gas flares in the water column. The observed emissions in the study region (up to 310 Mg year -1 ) are three times greater than estimates for the entire US North Atlantic margin and reveal the importance of collapsing sediment accumulations for ocean carbon cycling. Similar outgassing systems on the Amazon and Niger fans suggest that gravity tectonics on passive margins is a common yet overlooked mechanism driving massive seafloor methane emissions in sediment-laden continental slopes., (© 2023. The Author(s).)

The symbiont-bearing mixed-layer planktic foraminiferal genera Morozovella and Acarinina were among the most important calcifiers of early Paleogene tropical-subtropical oceans. A marked and permanent switch in the abundance of these genera is known to have occurred at low-latitude sites at the beginning of the Early Eocene Climatic Optimum (EECO), such that the relative abundance of Morozovella permanently and significantly decreased along with a progressive reduction in the number of species; concomitantly, the genus Acarinina almost doubled its abundance and diversified. Here we examine planktic foraminiferal assemblages and stable isotope compositions of their tests at Ocean Drilling Program Site 1051 (northwest Atlantic) to detail the timing of this biotic event, to document its details at the species level, and to test a potential cause: the loss of photosymbionts (bleaching). We also provide stable isotope measurements of bulk carbonate to refine the stratigraphy at Site 1051 and to determine when changes in Morozovella species composition and their test size occurred. We demonstrate that the switch in Morozovella and Acarinina abundance occurred rapidly and in coincidence with a negative carbon isotope excursion known as the J event (~53 Ma), which marks the start of the EECO. We provide evidence of photosymbiont loss after the J event from a size-restricted δ 13 C analysis. However, such inferred bleaching was transitory and also occurred in the acarininids. The geologically rapid switch in planktic foraminiferal genera during the early Eocene was a major evolutionary change within marine biota, but loss of photosymbionts was not the primary causal mechanism.

The start of the Palaeocene/Eocene thermal maximum--a period of exceptional global warming about 55 million years ago--is marked by a prominent negative carbon isotope excursion that reflects a massive input of 13C-depleted ('light') carbon to the ocean-atmosphere system. It is often assumed that this carbon injection initiated the rapid increase in global surface temperatures and environmental change that characterize the climate perturbation, but the exact sequence of events remains uncertain. Here we present chemical and biotic records of environmental change across the Palaeocene/Eocene boundary from two sediment sections in New Jersey that have high sediment accumulation rates. We show that the onsets of environmental change (as recorded by the abundant occurrence ('acme') of the dinoflagellate cyst Apectodinium) and of surface-ocean warming (as evidenced by the palaeothermometer TEX86) preceded the light carbon injection by several thousand years. The onset of the Apectodinium acme also precedes the carbon isotope excursion in sections from the southwest Pacific Ocean and the North Sea, indicating that the early onset of environmental change was not confined to the New Jersey shelf. The lag of approximately 3,000 years between the onset of warming in New Jersey shelf waters and the carbon isotope excursion is consistent with the hypothesis that bottom water warming caused the injection of 13C-depleted carbon by triggering the dissociation of submarine methane hydrates, but the cause of the early warming remains uncertain.

The Palaeocene/Eocene thermal maximum represents a period of rapid, extreme global warming 55 million years ago, superimposed on an already warm world. This warming is associated with a severe shoaling of the ocean calcite compensation depth and a >2.5 per mil negative carbon isotope excursion in marine and soil carbonates. Together these observations indicate a massive release of 13C-depleted carbon and greenhouse-gas-induced warming. Recently, sediments were recovered from the central Arctic Ocean, providing the first opportunity to evaluate the environmental response at the North Pole at this time. Here we present stable hydrogen and carbon isotope measurements of terrestrial-plant- and aquatic-derived n-alkanes that record changes in hydrology, including surface water salinity and precipitation, and the global carbon cycle. Hydrogen isotope records are interpreted as documenting decreased rainout during moisture transport from lower latitudes and increased moisture delivery to the Arctic at the onset of the Palaeocene/Eocene thermal maximum, consistent with predictions of poleward storm track migrations during global warming. The terrestrial-plant carbon isotope excursion (about -4.5 to -6 per mil) is substantially larger than those of marine carbonates. Previously, this offset was explained by the physiological response of plants to increases in surface humidity. But this mechanism is not an effective explanation in this wet Arctic setting, leading us to hypothesize that the true magnitude of the excursion--and associated carbon input--was greater than originally surmised. Greater carbon release and strong hydrological cycle feedbacks may help explain the maintenance of this unprecedented warmth.

The history of the Arctic Ocean during the Cenozoic era (0-65 million years ago) is largely unknown from direct evidence. Here we present a Cenozoic palaeoceanographic record constructed from >400 m of sediment core from a recent drilling expedition to the Lomonosov ridge in the Arctic Ocean. Our record shows a palaeoenvironmental transition from a warm 'greenhouse' world, during the late Palaeocene and early Eocene epochs, to a colder 'icehouse' world influenced by sea ice and icebergs from the middle Eocene epoch to the present. For the most recent approximately 14 Myr, we find sedimentation rates of 1-2 cm per thousand years, in stark contrast to the substantially lower rates proposed in earlier studies; this record of the Neogene reveals cooling of the Arctic that was synchronous with the expansion of Greenland ice (approximately 3.2 Myr ago) and East Antarctic ice (approximately 14 Myr ago). We find evidence for the first occurrence of ice-rafted debris in the middle Eocene epoch (approximately 45 Myr ago), some 35 Myr earlier than previously thought; fresh surface waters were present at approximately 49 Myr ago, before the onset of ice-rafted debris. Also, the temperatures of surface waters during the Palaeocene/Eocene thermal maximum (approximately 55 Myr ago) appear to have been substantially warmer than previously estimated. The revised timing of the earliest Arctic cooling events coincides with those from Antarctica, supporting arguments for bipolar symmetry in climate change.

It has been suggested, on the basis of modern hydrology and fully coupled palaeoclimate simulations, that the warm greenhouse conditions that characterized the early Palaeogene period (55-45 Myr ago) probably induced an intensified hydrological cycle with precipitation exceeding evaporation at high latitudes. Little field evidence, however, has been available to constrain oceanic conditions in the Arctic during this period. Here we analyse Palaeogene sediments obtained during the Arctic Coring Expedition, showing that large quantities of the free-floating fern Azolla grew and reproduced in the Arctic Ocean by the onset of the middle Eocene epoch (approximately 50 Myr ago). The Azolla and accompanying abundant freshwater organic and siliceous microfossils indicate an episodic freshening of Arctic surface waters during an approximately 800,000-year interval. The abundant remains of Azolla that characterize basal middle Eocene marine deposits of all Nordic seas probably represent transported assemblages resulting from freshwater spills from the Arctic Ocean that reached as far south as the North Sea. The termination of the Azolla phase in the Arctic coincides with a local sea surface temperature rise from approximately 10 degrees C to 13 degrees C, pointing to simultaneous increases in salt and heat supply owing to the influx of waters from adjacent oceans. We suggest that onset and termination of the Azolla phase depended on the degree of oceanic exchange between Arctic Ocean and adjacent seas.

The Palaeocene/Eocene thermal maximum, approximately 55 million years ago, was a brief period of widespread, extreme climatic warming, that was associated with massive atmospheric greenhouse gas input. Although aspects of the resulting environmental changes are well documented at low latitudes, no data were available to quantify simultaneous changes in the Arctic region. Here we identify the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence obtained during the Arctic Coring Expedition. We show that sea surface temperatures near the North Pole increased from 18 degrees C to over 23 degrees C during this event. Such warm values imply the absence of ice and thus exclude the influence of ice-albedo feedbacks on this Arctic warming. At the same time, sea level rose while anoxic and euxinic conditions developed in the ocean's bottom waters and photic zone, respectively. Increasing temperature and sea level match expectations based on palaeoclimate model simulations, but the absolute polar temperatures that we derive before, during and after the event are more than 10 degrees C warmer than those model-predicted. This suggests that higher-than-modern greenhouse gas concentrations must have operated in conjunction with other feedback mechanisms--perhaps polar stratospheric clouds or hurricane-induced ocean mixing--to amplify early Palaeogene polar temperatures.

Diverse microbial communities and numerous energy-yielding activities occur in deeply buried sediments of the eastern Pacific Ocean. Distributions of metabolic activities often deviate from the standard model. Rates of activities, cell concentrations, and populations of cultured bacteria vary consistently from one subseafloor environment to another. Net rates of major activities principally rely on electron acceptors and electron donors from the photosynthetic surface world. At open-ocean sites, nitrate and oxygen are supplied to the deepest sedimentary communities through the underlying basaltic aquifer. In turn, these sedimentary communities may supply dissolved electron donors and nutrients to the underlying crustal biosphere.

Background: After inhalation of a glucocorticoid from a meter dose inhaler (MDI), a certain portion of the delivered dose is deposited in the lungs, and the remainder is deposited in the oropharynx., Objective: To examine the absolute bioavailability of flunisolide given orally via metered dose inhaler, and metered dose inhaler with a commercially available spacer device as well as to determine the fraction of drug deposited in the lungs following inhalation., Methods: Twenty-four healthy volunteers were enrolled in the study; twenty-two completed the study. The IRB approved the study protocol, and informed consent was obtained. Volunteers received four treatments: treatment A (MDI), 1.0 mg inhaled flunisolide; treatment B (MDI-S), 1.0 mg inhaled flunisolide with a spacer device; treatment C, 1.0 mg of orally administered flunisolide with 240 mL of water; and treatment D, 1.0 mg intravenous flunisolide by IV push in the antecubital vein over 60 seconds. Plasma and urine flunisolide were quantified by HPLC/mass spectrometry/mass spectrometry., Results: Flunisolide is a corticosteroid with low oral bioavailability (6.7%), which was found to be lower than previously reported. Similar AUCs were observed between the MDI and MDI-S groups, but by using mass balance equations, it appears that more flunisolide was delivered to the lungs in the MDI-S group (410 microg versus 280 microg). Oropharyngeal deposition was an important difference between the two inhaler groups. Approximately an 11-fold reduction in the oropharyngeal deposition of flunisolide through use of the spacer device was observed., Conclusions: Use of a spacer device improved pulmonary delivery of flunisolide by almost 50% and significantly decreased the oropharyngeal exposure to drug.

We examined the effects of estrogen on tumor necrosis factor alpha (TNF-alpha)-induced expression of intracellular adhesion molecule (ICAM-1) and vascular adhesion molecule (VCAM-1) in cultured human bronchial smooth muscle cells (BSMC). Experiments were performed in triplicate in T-75 tissue culture flasks containing normal human BSMC. Four experiments were carried out: untreated BSMC cells (control); TNF-alpha 1000 U/ml stimulation of BSMC; forskolin 5 microM before TNF-alpha stimulation of BSMC; and estradiol 30 microM before TNF-alpha stimulation of BSMC. Cyclic adenosine monophosphate was measured by a commercially available radioimmunoassay kit. Cell expression of ICAM-1 and VCAM-1 was quantified by flow cytometry Incubation of cells with TNF-alpha 1000 U/ml for 24 hours elicited a 27-fold increase in basal expression of ICAM-1 and a 2-fold increase in VCAM-1 (p>0.05). Incubation of BSMC with forskolin 5 microM, for 1 hour before TNF-alpha, decreased TNF-alpha-induced expression of ICAM-1 by 62% and VCAM-1 slightly by 17%. The BSMC incubated with estradiol 30 microM, 1 hour before TNF-alpha, decreased TNF-alpha-induced expression of ICAM-1 by 21%; VCAM-1 remained unchanged (p>0.05). We found a trend toward inhibition of TNF-alpha-stimulated ICAM-1 expression in cultured BSMC with pretreatment with estradiol. However, due to large variability within the cell culture model, statistical significance was not reached.

Lithologic, faunal, seismic, and isotopic evidence from the Blake Nose (subtropical western North Atlantic) links a massive release of biogenic methane approximately 55.5 million years ago to a warming of deep-ocean and high-latitude surface waters, a large perturbation in the combined ocean-atmosphere carbon cycle (the largest of the past 90 million years), a mass extinction event in benthic faunas, and a radiation of mammalian orders. The deposition of a mud clast interval and seismic evidence for slope disturbance are associated with intermediate water warming, massive carbon input to the global exogenic carbon cycle, pelagic carbonate dissolution, a decrease in dissolved oxygen, and a benthic foraminiferal extinction event. These events provide evidence to confirm the gas hydrate dissociation hypothesis and identify the Blake Nose as a site of methane release.

The present study was performed to determine whether genistein could inhibit in vivo LPS-induced alveolar macrophage TNFalpha production and thus reduce the alveolar neutrophil influx following LPS. In vitro incubation with genistein completely inhibited LPS-induced TNFalpha production by alveolar macrophages (AM) from BALB/c mice. Subsequently mice were pretreated with intraperitoneal genistein or vehicle, then received nasal LPS to induce an alveolitis. Genistein was then administered every eight hours for five days following LPS. At 24 hours after LPS, the bronchoalveolar lavage (BAL) TNFalpha and ex vivo TNFalpha production from AM, were lower in the genistein treated animals. As well, total BAL white blood cell (WBC) count was reduced in the genistein as compared to the vehicle-only group. The percent neutrophils and the resolution of neutrophils were similar between genistein and vehicle groups. Therefore, genistein was able to decrease AM TNFalpha production, and was associated with a decrease in BAL WBC count post-LPS.

We attempted to determine the effects of cyclosporine on beta-adrenergic receptors in bovine pulmonary artery smooth muscle cells. Bovine pulmonary artery smooth muscle cells were exposed to cyclosporine at a concentration of 100 ng/ml in culture media for 5 days, and control bovine pulmonary artery smooth muscle cells were exposed to only culture media for the same 5-day period. Beta-adrenergic receptors were measured as total binding capacity (Bmax) by nonlinear least squares fit of the specific binding curve. In a separate experiment beta1- versus beta2-adrenergic receptor subtypes were identified by computer modeling (LIGAND) of 17-19 point CGP20712A-125ICYP competition curves. Cyclosporine significantly (p=0.02) decreased bovine pulmonary artery smooth muscle beta-adrenergic receptor density by 54%+/-7%. The Bmax for control versus treated cells was 38.9+/-18 versus 17.7+/-12 fmol/mg protein, respectively. Subtype determination of beta-receptors revealed 70% or more beta2- and 30% or less beta1-adrenergic receptors. Cyclosporine caused a 54% reduction in overall beta-adrenergic receptor density in bovine pulmonary artery smooth muscle cells. The reduction in Bmax is suspected not to be a result of selective down-regulation of beta1-adrenergic receptors alone. We believe that cyclosporine may also contribute to a decrease in beta2-adrenergic receptors.

Carbonate and organic matter deposited during the latest Paleocene thermal maximum is characterized by a remarkable -2.5% excursion in delta 13C that occurred over approximately 10(4) yr and returned to near initial values in an exponential pattern over approximately 2 x 10(5) yr. It has been hypothesized that this excursion signifies transfer of 1.4 to 2.8 x 10(18) g of CH4 from oceanic hydrates to the combined ocean-atmosphere inorganic carbon reservoir. A scenario with 1.12 x 10(18) g of CH4 is numerically simulated here within the framework of the present-day global carbon cycle to test the plausibility of the hypothesis. We find that (1) the delta 13C of the deep ocean, shallow ocean, and atmosphere decreases by -2.3% over 10(4) yr and returns to initial values in an exponential pattern over approximately 2 x 10(5) yr; (2) the depth of the lysocline shoals by up to 400 m over 10(4) yr, and this rise is most pronounced in one ocean region; and (3) global surface temperature increases by approximately 2 degrees C over 10(4) yr and returns to initial values over approximately 2 x 10(6) yr. The first effect is quantitatively consistent with the geologic record; the latter two effects are qualitatively consistent with observations. Thus, significant CH4 release from oceanic hydrates is a plausible explanation for observed carbon cycle perturbations during the thermal maximum. This conclusion is of broad interest because the flux of CH4 invoked during the maximum is of similar magnitude to that released to the atmosphere from present-day anthropogenic CH4 sources.

This study examined the effect of trovafloxacin (CP-99,219) on the pharmacokinetics and pharmacodynamics of a single dose of theophylline, when administered to steady-state concentrations. Twelve healthy, nonsmoking male volunteers participated. A 450-mg dose of theophylline was administered at 7:00 AM on day 1. On day 4, volunteers received 300 mg of trovafloxacin (CP-99,219) daily in the morning for 7 days. The 450-mg dose of theophylline was repeated on day 8 at 7:00 AM concomitantly with 300 mg of trovafloxacin. Theophylline concentrations in plasma and trovafloxacin in serum were determined using reverse-phase high-performance liquid chromatography. There was no significant difference between the geometric mean values for Cmax of theophylline, 6.42 micrograms/mL and 6.00 micrograms mL on days 1 and 8, respectively. A change (P = 0.032) in the geometric mean of the area under the concentration-time curve extrapolated to infinity (AUC0-infinity) for theophylline was noted for trovafloxacin was administered. Mean terminal phase elimination rate constants (Kes) were reduced (P = 0.001) by 13% after administration of trovafloxacin from day 1 to day 8. In general, changes in theophylline clearance of less than 20% are unlikely to be of clinical significance. In this study, oral administration of trovafloxacin in 300 mg doses to achieve steady-state concentration resulted in an 8.4% increase in the extent of systemic exposure (AUC0-infinity) to theophylline. Assuming that this AUC change is based on oral clearance and not absorption, one would not expect to see clinically significant changes in the pharmacokinetics of theophylline. No pharmacodynamic changes resulted from the pharmacokinetic changes of theophylline.

The development of a criteria-based antimicrobial formulary system for use in a 432-bed university-based tertiary-care hospital is described. A subcommittee of the hospital's pharmacy and therapeutics committee developed prescribing criteria for antimicrobials thought to have a specific place in the treatment of various infections. The criteria were based primarily on patient needs, but when two therapies were thought to have similar effectiveness and similar toxicity profiles, cost became the deciding factor in drug selection. Educational packets were designed to assist physicians in prescribing criteria-based antimicrobials. An antimicrobial order form was also developed. The program was implemented after an extensive orientation and education period; data on antimicrobial use were collected for the first year of the program. Hospitalwide compliance with the criteria was 89%, although compliance in certain departments was poorer. The database was formulated to be both service- and physician-specific for the purposes of reporting and education.

Study Objective: To evaluate the metabolic and cardiopulmonary effects of nebulized albuterol in patients suffering moderate to severe exacerbations of asthma or chronic obstructive pulmonary disease., Design: Open-label, prospective study., Setting: The emergency department of a university medical center., Patients: Ten patients with moderate to severe exacerbation of asthma., Interventions: Each patient received nebulized albuterol 2.5 mg for approximately 10 minutes., Measurements and Main Results: Serum potassium, heart rate and rhythm, blood pressure, and pulmonary function were measured before treatment and every 15 minutes for 2 hours after treatment. Serum potassium concentrations decreased significantly (p < 0.05) within 75 minutes after initiation of treatment, from a baseline value of 4.5 +/- 0.6 mEq/L (range 3.5-5.5 mEq/L) to 3.7 +/- 0.5 mEq/L (range 2.8-4.4 mEq/L) at the end of the collection period (120 minutes). Forced expiratory volume in 1 second significantly increased over time in patients with asthma (p < 0.05). No statistically significant changes in blood pressure, heart rate, or corrected QT intervals occurred. Pre-emergency department use of a beta 2-agonist by metered-dose inhaler was not associated with a decreased serum potassium on admission., Conclusions: Nebulized beta 2-agonists are generally efficacious and safe in patients with acute bronchospasms. However, close monitoring of serum electrolytes, heart rate, and rhythm in patients at risk (elderly, those with pre-existing cardiac disease) is advised before these individuals receive repeat doses by continuous aerosol administration.

Omeprazole is a substituted benzimidazole that has gained widespread use in the treatment of acidic and peptic ulcer disease. Adverse events with the drug are rare and involve mainly the gastrointestinal and central nervous systems. Skin inflammation, urticaria, pruritus, alopecia, and dry skin have been reported in 0.5-1.5% of patients. To date, no published report has linked angioedema with omeprazole. We report a case of a 34-year-old woman with cellulitis, ulcerative erosive esophagitis, and gastric and duodenal ulcers who developed several hypersensitivity reactions characterized by shortness of breath, wheezing, cough, mild angioedema, and total body urticaria and pruritus. These symptoms correlated with the addition of omeprazole to her regimen and the timing of its administration. A previous case report prompted a rechallenge with enteric-coated omeprazole granules removed from the capsule shell. Recurrence of the adverse events suggested an allergy to the drug itself and not the capsule. Angioedema can be a life-threatening allergic reaction requiring immediate treatment. Rechallenge using omeprazole with or without the capsule shell should be done only in a hospital setting where prompt action can be taken in the event of an emergency.