Identifying Outflow Regions of North American Monsoon Anticyclone-Mediated Meridional Transport of Convectively Influenced Air Masses in the Lower Stratosphere.

We analyzed the effect of the North American monsoon anticyclone (NAMA) on the meridional transport of summertime cross-tropopause convective outflow by applying a trajectory analysis to a climatology of convective overshooting tops (OTs) identified in GOES satellite images, which covers the domain from 29°S to 68°N and from 205°W to 1.25°W for the time period of May to September, 2013. From this analysis, we identify seasonal development of geographically distinct outflow regions of convectively influenced air masses (CIAMs) from the NAMA circulation to the global stratosphere and quantify the associated meridional displacement of CIAMs. We find that prior to the development of the NAMA, the majority of CIAMs exit the study area in a southeastern region between 5°N and 35°N at 45°W (75.5% in May). During July and August, when the NAMA is strongest, two additional outflow regions develop that constitute the majority of outflow: 68.1% in a northeastern region between 35°N and 60°N at 45°W and 13.4% in a southwestern region between 5°N and 35°N at 145°W. The shift in the location of most CIAM outflow from the pre-NAMA southeastern region to NAMA-dependent northeastern and southwestern regions corresponds to a change in average meridional displacement of CIAMs from 3.3° northward in May to 24.5° northward in July and August. Meridional transport of CIAMs through persistent outflow regions from the NAMA circulation to the global stratosphere has the potential to impact global stratospheric composition beyond convective source regions.

Modeling the Effect of Potential Nitric Acid Removal During Convective Injection of Water Vapor Over the Central United States on the Chemical Composition of the Lower Stratosphere.

Tropopause-penetrating convection is a frequent seasonal feature of the Central United States climate. This convection presents the potential for consistent transport of water vapor into the upper troposphere and lower stratosphere (UTLS) through the lofting of ice, which then sublimates. Water vapor enhancements associated with convective ice lofting have been observed in both in situ and satellite measurements. These water vapor enhancements can increase the probability of sulfate aerosol-catalyzed heterogeneous reactions that convert reservoir chlorine (HCl and ClONO2) to free radical chlorine (Cl and ClO) that leads to catalytic ozone loss. In addition to water vapor transport, lofted ice may also scavenge nitric acid and further impact the chlorine activation chemistry of the UTLS. We present a photochemical model that resolves the vertical chemical structure of the UTLS to explore the effect of water vapor enhancements and potential additional nitric acid removal. The model is used to define the response of stratospheric column ozone to the range of convective water vapor transported and the temperature variability of the lower stratosphere currently observed over the Central United States in conjunction with potential nitric acid removal and to scenarios of elevated sulfate aerosol surface area density representative of possible future volcanic eruptions or solar radiation management. We find that the effect of HNO3 removal is dependent on the magnitude of nitric acid removal and has the greatest potential to increase chlorine activation and ozone loss under UTLS conditions that weakly favor the chlorine activation heterogeneous reactions by reducing NOx sources.

Identifying Source Regions and the Distribution of Cross-Tropopause Convective Outflow Over North America During the Warm Season.

We analyzed the interaction between the North American monsoon anticyclone (NAMA) and summertime cross-tropopause convective outflow by applying a trajectory analysis to a climatology of convective overshooting tops (OTs) identified in GOES satellite images, which covers the domain from 29°S to 68°N and from 205 to 1.25°W for the time period of May through September 2013. With this analysis we identified seasonally, geographically, and altitude-dependent variability in NAMA strength and in cross-tropopause convection that control their interaction. We find that the NAMA has the strongest impact on the circulation of convectively influenced air masses in August. Over the entire time period examined the intertropical convergence zone contributes the majority of OTs with a larger fraction of total OTs at 370 K (on average 70%) than at 400 K (on average 52%). During August at 370 K, the convectively influenced air masses within the NAMA circulation, as determined by the trajectory analysis, are primarily sourced from the intertropical convergence zone (monthly average of 66.1%), while at 400 K the Sierra Madres and the Central United States combined constitute the dominant source region (monthly average of 44.1%, compared to 36.6% of the combined Intertropical Convergence Zone regions). When evaluating the impact of cross-tropopause convection on the composition and chemistry of the upper troposphere and lower stratosphere, the effects of the NAMA on both the distribution of convective outflow and the residence time of convectively influenced air masses within the NAMA region must be considered.

Coupling free radical catalysis, climate change, and human health.

We present the chain of mechanisms linking free radical catalytic loss of stratospheric ozone, specifically over the central United States in summer, to increased climate forcing by CO2 and CH4 from fossil fuel use. This case directly engages detailed knowledge, emerging from in situ aircraft observations over the polar regions in winter, defining the temperature and water vapor dependence of the kinetics of heterogeneous catalytic conversion of inorganic chlorine (HCl and ClONO2) to free radical form (ClO). Analysis is placed in the context of irreversible changes to specific subsystems of the climate, most notably coupled feedbacks that link rapid changes in the Arctic with the discovery that convective storms over the central US in summer both suppress temperatures and inject water vapor deep into the stratosphere. This places the lower stratosphere over the US in summer within the same photochemical catalytic domain as the lower stratosphere of the Arctic in winter engaging the risk of amplifying the rate limiting step in the ClO dimer catalytic mechanism by some six orders of magnitude. This transitions the catalytic loss rate of ozone in lower stratosphere over the United States in summer from HOx radical control to ClOx radical control, increasing the overall ozone loss rate by some two orders of magnitude over that of the unperturbed state. Thus we address, through a combination of observations and modeling, the mechanistic foundation defining why stratospheric ozone, vulnerable to increased climate forcing, is one of the most delicate aspects of habitability on the planet.

Transport studies of dual-gated ABC and ABA trilayer graphene: band gap opening and band structure tuning in very large perpendicular electric fields.

We report on the transport properties of ABC and ABA stacked trilayer graphene using dual, locally gated field effect devices. The high efficiency and large breakdown voltage of the HfO(2) top and bottom gates enable independent tuning of the perpendicular electric field and the Fermi level over an unprecedentedly large range. We observe a resistance change of 6 orders of magnitude in the ABC trilayer, which demonstrates the opening of a band gap. Our data suggest that the gap saturates at a large displacement field of D ~ 3 V/nm, in agreement with self-consistent Hartree calculations. In contrast, the ABA trilayer remains metallic even under a large perpendicular electric field. Despite the absence of a band gap, the band structure of the ABA trilayer continues to evolve with increasing D. We observe signatures of two-band conduction at large D fields. Our self-consistent Hartree calculation reproduces many aspects of the experimental data but also points to the need for more sophisticated theory.

14-3-3 protects against stress-induced apoptosis.

Expression of human Bax, a cardinal regulator of mitochondrial membrane permeabilization, causes death in yeast. We screened a human cDNA library for suppressors of Bax-mediated yeast death and identified human 14-3-3ß/α, a protein whose paralogs have numerous chaperone-like functions. Here, we show that, yeast cells expressing human 14-3-3ß/α are able to complement deletion of the endogenous yeast 14-3-3 and confer resistance to a variety of different stresses including cadmium and cycloheximide. The expression of 14-3-3ß/α also conferred resistance to death induced by the target of rapamycin inhibitor rapamycin and by starvation for the amino acid leucine, conditions that induce autophagy. Cell death in response to these autophagic stimuli was also observed in the macroautophagic-deficient atg1Δ and atg7Δ mutants. Furthermore, 14-3-3ß/α retained its ability to protect against the autophagic stimuli in these autophagic-deficient mutants arguing against so called 'autophagic death'. In line, analysis of cell death markers including the accumulation of reactive oxygen species, membrane integrity and cell surface exposure of phosphatidylserine indicated that 14-3-3ß/α serves as a specific inhibitor of apoptosis. Finally, we demonstrate functional conservation of these phenotypes using the yeast homolog of 14-3-3: Bmh1. In sum, cell death in response to multiple stresses can be counteracted by 14-3-3 proteins.

Effects of manure and cultivation on carbon dioxide and nitrous oxide emissions from a corn field under Mediterranean conditions.

The use of organic residues as soil additives is increasing, but, depending on their composition and application methods, these organic amendments can stimulate the emissions of CO(2) and N(2)O. The objective of this study was to quantify the effects of management practices in irrigated sweet corn (Zea mays L.) on CO(2) and N(2)O emissions and to relate emissions to environmental factors. In a 3-yr study, corn residues (CR) and pasteurized chicken manure (PCM) were used as soil amendments compared with no residue (NR) under three management practices: shallow tillage (ST) and no tillage (NT) under consecutive corn crops and ST without crop. Tillage significantly increased (P < 0.05) CO(2) and N(2)O fluxes in residue-amended plots and in NR plots. Carbon dioxide and N(2)O fluxes were correlated with soil NH(4) concentrations and with days since tillage and days since seeding. Fluxes of CO(2) were correlated with soil water content, whereas N(2)O fluxes had higher correlation with air temperature. Annual CO(2) emissions were higher with PCM than with CR and NR (9.7, 2.9, and 2.3 Mg C ha(-1), respectively). Fluxes of N(2)O were 34.4, 0.94, and 0.77 kg N ha(-1) yr(-1) with PCM, CR, and NR, respectively. Annual amounts of CO(2)-C and N(2)O-N emissions from the PCM treatments were 64 and 3% of the applied C and N, respectively. Regardless of cultivation practices, elevated N(2)O emissions were recorded in the PCM treatment. These emissions could negate some of the beneficial effects of PCM on soil properties.

Exposure based waiving: the application of the toxicological threshold of concern (TTC) to inhalation exposure for aerosol ingredients in consumer products.

The inhalation toxicology studies available in the public domain have been reviewed to establish a database for inhalation toxicology and derive thresholds of toxicological concern (TTC) for effects in the respiratory tract and systemically for Cramer class 1 and 3 chemicals. These TTCs can be used as the basis for developing an exposure based waiving (EBW) approach to evaluating the potential for adverse effects from exposure to ingredients in aerosol products, used by consumers. The measurement of consumer exposure in simulated product use is key to the application of an exposure based waiving approach to evaluating potential consumer risk. The detailed exposure evaluation for aerosol ingredients with defined use scenarios, in conjunction with an evaluation of the potential structure activity relationship for toxicity and the TTCs for inhalation exposure could be used to waive undertaking inhalation toxicology studies under REACH. Not all classes of chemicals are suitable for such an approach, but for chemicals with a predictable low potential toxicity, and very low levels of exposure, this approach, could reduce the amount of inhalation toxicology studies required for the implementation of the European REACH legislation. Such an approach is consistent with the concept of developing 'intelligent testing strategies' for REACH.

Prolactin inhibits the apoptosis of chondrocytes induced by serum starvation.

The apoptosis of chondrocytes plays an important role in endochondral bone formation and in cartilage degradation during aging and disease. Prolactin (PRL) is produced in chondrocytes and is known to promote the survival of various cell types. Here we show that articular chondrocytes from rat postpubescent and adult cartilage express the long form of the PRL receptor as revealed by immunohistochemistry of cartilage sections and by RT-PCR and Western blot analyses of the isolated chondrocytes. Furthermore, we demonstrate that PRL inhibits the apoptosis of these same chondrocytes cultured in low-serum. Chondrocyte apoptosis was measured by hypodiploid DNA content determined by flow cytometry and by DNA fragmentation evaluated by the ELISA and the TUNEL methods. The anti-apoptotic effect of PRL was dose-dependent and was prevented by heat inactivation. These data demonstrate that PRL can act as a survival factor for chondrocytes and that it has potential preventive and therapeutic value in arthropathies characterized by cartilage degradation.

16K prolactin induces NF-kappaB activation in pulmonary fibroblasts.

The amino-terminal 16 kDa fragment of prolactin (16K PRL) promotes the expression of the inducible isoform of nitric oxide synthase (iNOS) accompanied by the production of nitric oxide (NO) by rat pulmonary fibroblasts. The present study was designed to elucidate whether the mechanism by which 16K PRL promotes iNOS expression involves the activation of nuclear factor-kappa B (NF-kappaB), a key transcription factor for iNOS induction. 16K PRL stimulated DNA-binding activity of NF-kappaB in pulmonary fibroblasts as demonstrated by gel shift assays. Likewise, fluorescence immunocytochemistry showed that 16K PRL promotes nuclear translocation of the p65 subunit of NF-kappaB. Finally, treatment with 16K PRL induced the degradation of the NF-kappaB inhibitor kappaB-beta (IkappaB-beta), and such degradation was prevented by blocking IkappaB-beta phosphorylation. Altogether, these results show that 16K PRL activates NF-kappaB nuclear translocation via the phosphorylation and degradation of IkappaB-beta. These findings are consistent with NF-kappaB being part of the signal transduction pathway activated by 16K PRL to induce iNOS expression.

Roles of prolactin and related members of the prolactin/growth hormone/placental lactogen family in angiogenesis.

Prolactin, growth hormone and placental lactogen are members of a family of polypeptide hormones which share structural similarities and biological activities. Numerous functions have been attributed to these hormones, among which stand out their recently discovered effects on angiogenesis, the process by which new blood vessels are formed from the pre-existing microvasculature. Prolactin, growth hormone and placental lactogen, along with two non-classical members of the family, proliferin and proliferin-related protein, can act both as circulating hormones and as paracrine/autocrine factors to either stimulate or inhibit various stages of the formation and remodeling of new blood vessels, including endothelial cell proliferation, migration, protease production and apoptosis. Such opposing actions can reside in similar but independent molecules, as is the case of proliferin and proliferin-related protein, which stimulate and inhibit angiogenesis respectively. The potential to exert opposing effects on angiogenesis can also reside within the same molecule as the parent protein can promote angiogenesis (i.e. prolactin, growth hormone and placental lactogen), but after proteolytic processing the resulting peptide fragment acquires anti-angiogenic properties (i.e. 16 kDa prolactin, 16 kDa growth hormone and 16 kDa placental lactogen). The unique properties of the peptide fragments versus the full-length molecules, the regulation of the protease responsible for specific protein cleavage, the selective expression of specific receptors and their associated signal transduction pathways are issues that are being investigated to further establish the precise contribution of these hormones to angiogenesis under both physiological and pathological situations. In this review article, we summarize the known and speculative issues underlying the effects of the prolactin, growth hormone and placental lactogen family of proteins on angiogenesis, and address important remaining enigmas in this field of research.

Regulation of gonadotropin-releasing hormone secretion: insights from GT1 immortal GnRH neurons.

The study of the mammalian GnRH system has been greatly advanced by the development of immortalized cell lines. Of particular relevance are the so-called GT1 cells. Not only do they exhibit many of the known physiologic characteristics of GnRH neurons in situ, but in approximately one decade have yielded new insights regarding the intrinsic physiology of individual cells and networks of GnRH neurons, as well as the nature of central and peripheral signals that directly modulate their function. For instance, valuable information has been generated concerning intrinsic properties of the system such as the inherent pulsatile pattern of secretion displayed by networks of GT1 cells. Concepts regarding feedback regulation and autocrine feedback of GnRH neurons have been dramatically expanded. Likewise, the nature of the receptors and of the proximal and distal signal transduction mechanisms involved in the actions of multiple afferent signals has been identified. Understanding this neuronal system allows a better comprehension of the hypothalamic-pituitary-gonadal axis and of the regulatory influences that ultimately control reproductive competence.

Molecular heterogeneity of prolactin in the plasma of patients with systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) has been associated with high levels of prolactin in the circulation of some patients. Although prolactin stimulates immune responses, the relationship between hyperprolactinemia and the pathophysiology of SLE remains controversial. This study was undertaken to investigate whether circulating bioactive prolactin isoforms are associated with the activity of SLE. METHODS: The molecular heterogeneity of prolactin was studied in the plasma of patients with active and inactive SLE and in healthy volunteers by radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), Nb2-cell bioassay, and immunoprecipitation-Western blots. The specificity of the bioassay determinations was assessed by neutralization of growth-promoting effects with antiserum to human prolactin. RESULTS: Significantly higher prolactin levels were detected by bioassay and by ELISA than by RIA in both subsets of SLE patients and in normal individuals. Plasma prolactin levels in the SLE patients were significantly greater than those in the normal controls when measured by ELISA, but not by RIA or bioassay. The bioassay:ELISA and bioassay:RIA ratios were similar between SLE patients and controls, suggesting that prolactin biopotency was not altered with the disease, and none of the 3 assays detected a difference in prolactin levels between patients with active SLE and those with inactive SLE. However, the prolactin detected in plasma was associated with immunoreactive proteins of 130 kd and 23 kd, and the concentration of the 130-kd prolactin-like species was 10-fold higher in inactive SLE versus active SLE patients. CONCLUSION: Discrepancies among assays substantiate the molecular heterogeneity of circulating prolactin. The prolactin isotype that is found in association with inactive SLE could be of potential use as a marker for the inactive form of the disease and as an index for the efficacy of treatment.

GABA inhibition of immortalized gonadotropin-releasing hormone neuronal excitability involves GABA(A) receptors negatively coupled to cyclic adenosine monophosphate formation.

Gamma-aminobutyric acid (GABA) has been implicated in the regulation of reproduction, particularly in the developmental modulation of gonadotropin-releasing hormone (GnRH) secretion. GnRH neurons are innervated by GABA-containing processes, and the administration of GABA stimulates and inhibits GnRH secretion in vivo and in vitro. We have previously shown that GABA can exert both of these actions in sequence, by acting directly on immortalized GnRH neurons. While the stimulation is the result of a GABA(A) receptor-mediated depolarization of the plasma membrane, the mechanism involved in the delayed inhibition is the subject of the present investigation. GABA (1 nM-10 microM) decreased the intracellular concentration of cyclic adenosine monophosphate (cAMP) in a dose- and time-dependent fashion. This effect was blocked by bicuculline and mimicked by muscimol but not by baclofen. To analyze the effect of GABA on cellular excitability, we used fura-2 loaded GT1-7 cells. Activation of voltage-sensitive calcium channels by high K+-induced depolarization (35 mM) increased [Ca2+]i. GABA (10 microM) and muscimol (10 microM) reduced the amplitude of K+-induced [Ca2+]i transients. This inhibition was blocked by forskolin (20 microM) or 8-Br-cAMP (1 mM). Altogether, these results show that GABA(A) receptors mediate a sustained inhibitory effect of GABA on GnRH neurons, and suggest the involvement of the cAMP pathway decreasing cellular excitability.

Expression of prolactin gene and secretion of prolactin by rat retinal capillary endothelial cells.

PURPOSE: Prolactin fragments inhibit blood vessel formation, whereas anti-prolactin antibodies induce angiogenesis in the cornea. Endothelial cells from brain capillaries and the umbilical vein produce prolactin, and this study was undertaken to determine whether retinal capillary endothelial cells could be a source for prolactin in the eye. METHODS: Primary cultures of rat retinal endothelial cells were investigated for the expression of prolactin mRNA by reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis and by in situ hybridization. The prolactin protein was analyzed by immunocytochemistry, enzyme-linked immunoabsorbent assay, Western blot analysis, and the Nb2-cell bioassay. The effect of prolactin and the 16-kDa prolactin fragment on retinal endothelial cell proliferation was investigated, and the expression of the cloned prolactin receptor was analyzed by RT-PCR and Southern blot analysis. RESULTS: Retinal endothelial cells expressed prolactin mRNA and full-length 23-kDa prolactin. Prolactin was observed in the cytoplasm of cells and in their conditioned medium at levels 300 times those described in endothelial cells from other vessels and species. Exogenous 16-kDa prolactin inhibited rat retinal endothelial cell proliferation, whereas 23-kDa prolactin was inactive. No evidence was obtained for the expression of the cloned prolactin receptor in these cells, but the prolactin receptor was amplified in whole rat retina. CONCLUSIONS: Endothelial cells from the microcirculation of rat retina produce and release prolactin. That the cloned prolactin receptor was not expressed in these cells argues against direct autocrine effects of prolactin. Possible paracrine effects are suggested by the expression of the prolactin receptor in retinal tissue.

Human umbilical vein endothelial cells express multiple prolactin isoforms.

Members of the prolactin (PRL) hormonal family have direct effects on endothelial cell proliferation, migration and tube formation. Moreover, isoforms of PRL may function as autocrine regulators of endothelial cells. Bovine brain capillary endothelial cells (BBCEC) express the PRL gene, while anti-PRL antibodies inhibit BBCEC proliferation. Here, we show the expression of the PRL gene into various PRL isoforms in endothelial cells from the human umbilical vein. Reverse transcription-polymerase chain reaction of total RNA from human umbilical vein endothelial cells (HUVEC) detected the full-length PRL mRNA as well as a 100 bp smaller PRL transcript similar to the one previously reported in BBCEC. HUVEC were positive to PRL immunocytochemistry. In addition, various PRL immunoreactive proteins were detected in HUVEC extracts and HUVEC conditioned media by metabolic labelling immunoprecipitation analysis. These PRL immunorelated proteins had apparent molecular masses of 60, 23, 21, 16 and 14 kDa. In contrast to previous findings in BBCEC, HUVEC conditioned media contained very little PRL bioactivity as determined by the selective bioassay of Nb2 cell proliferation. Moreover, some polyclonal or monoclonal antibodies directed against PRL stimulated HUVEC proliferation, in contrast to the inhibitory effect seen in BBCEC. The present findings extend the previous observations about the expression of PRL gene in endothelial cells from bovine brain capillaries to human cells of the umbilical vein, implicating that endothelium from different types of vessels and species share the expression of PRL gene but may differ in the putative autocrine role of the PRL isoforms expressed.

Proteolytic cleavage confers nitric oxide synthase inducing activity upon prolactin.

Prolactin (PRL), originally associated with milk secretion, is now known to possess a wide variety of biological actions and diverse sites of production beyond the pituitary. Proteolytic cleavage is a common post-translational modification that can either activate precursor proteins or confer upon the peptide fragment unique biological actions not exerted by the parent molecule. Recent studies have demonstrated that the 16-kDa N-terminal proteolytic cleavage product of PRL (16K-PRL) acts as a potent inhibitor of angiogenesis. Despite previous demonstrations of 16K-PRL production in vivo, biological functions beyond its antiangiogenic actions remain unknown. Here we show that 16K-PRL, but not full-length PRL, acts to promote the expression of the inducible isoform of nitric oxide synthase (iNOS) and nitric oxide (*NO) production by pulmonary fibroblasts and alveolar type II cells with potency comparable with the proinflammatory cytokines interleukin-1beta, interferon gamma, and tumor necrosis factor alpha. The differential effect of 16K-PRL versus PRL occurs through a receptor distinct from known PRL receptors. Additionally, pulmonary fibroblasts express the PRL gene and endogenously produce 16K-PRL, suggesting that this pathway may serve both autocrine and paracrine roles in the regulation of *NO production. These results reveal that proteolytic cleavage of PRL confers upon this classical hormone potent iNOS inducing activity, suggesting its role in inflammatory/immune processes.

The action of soybean lipoxygenase-1 on 12-iodo-cis-9-octadecenoic acid: the importance of C11-H bond breaking.

Previous work has demonstrated that the ferric form of soybean lipoxygenase-1 will catalyze an elimination reaction on 12-iodo-cis-9-octadecenoic acid (12-IODE) to produce 9, 11-octadecadienoic acid and iodide ion. Elimination is accompanied by irreversible inactivation of the enzyme on 1 out of 10 turnovers. In the present work, 11,11-dideuterio-12-IODE (D(2)-12-IODE) was synthesized and used to demonstrate that both the elimination reaction and inactivation of the enzyme exhibit very large kinetic isotope effects. The rates with the deuterated compound are so low that the isotope effects are difficult to quantify, but they appear to be comparable to the isotope effects previously observed for the normal reaction catalyzed by lipoxygenase and much larger than can be explained by zero-point energy considerations. ESR spectroscopy was used to demonstrate that 12-IODE can reduce ferric lipoxygenase to the ferrous form, and a large isotope effect on this process was observed with D(2)-12-IODE. It is proposed that the pathway leading to reduction and inactivation by 12-IODE is initiated by homolytic cleavage of the C(11)-H bond. Elimination could be initiated either by homolytic or by heterolytic cleavage of this bond. The results suggest that very large isotope effects may be a general feature of C-H bond cleavages catalyzed by this enzyme.

Isoflurane therapy for status asthmaticus in children: A case series and protocol.

OBJECTIVE: To describe the use of inhaled isoflurane by using a standardized protocol in the treatment of respiratory failure secondary to status asthmaticus in a series of pediatric patients. DESIGN: Case series. SETTING: Pediatric intensive care unit of a tertiary care military medical facility. PATIENTS: Six pediatric patients ranging in age from 14 months to 15 yrs who were treated with isoflurane in our pediatric intensive care unit for status asthmaticus from 1995 to 1998. INTERVENTION: Inhaled isoflurane therapy was initiated by using the treatment protocol after the patients had failed conventional medical management in the treatment of their asthma. MEASUREMENTS AND MAIN RESULTS: All patients tolerated isoflurane therapy well by using our standardized protocol in conjunction with careful hemodynamic monitoring and support. The administration of inhaled isoflurane resulted in measurable improvements in the subject patients, as evidenced by statistically significant decreases in Paco2 and peak inspiratory pressures, as well as a significant increase in pH. All six patients were successfully extubated and were discharged from the hospital without apparent sequelae. CONCLUSIONS: We conclude isoflurane may be a safe, effective treatment modality in the management of status asthmaticus refractory to aggressive medical therapy, although further study is warranted. We emphasize this mode of therapy should be instituted only after traditional treatment modalities have failed and appropriate intensive care support is available.