The effects of the forage-to-concentrate ratio on the conversion of digestible energy to metabolizable energy in growing beef steers.

Metabolizable energy (ME) is calculated from digestible energy (DE) using a constant conversion factor of 0.82. Methane and urine energy losses vary across diets and dry matter intake (DMI), suggesting that a static conversion factor fails to describe the biology. To quantify the effects of the forage-to-concentrate ratio (F:C) on the efficiency of conversion of DE to ME, 10 Angus steers were used in a 5 × 5 replicated Latin square. Dry-rolled corn was included in experimental diets at 0%, 22.5%, 45.0%, 67.5%, and 83.8% on a dry matter (DM) basis, resulting in a high F:C (HF:C), intermediate F:C (IF:C), equal F:C (EF:C), low F:C (LF:C), and a very low F:C (VLF:C), respectively. Each experimental period consisted of a 23-d diet adaption followed by 5 d of total fecal and urine collections and a 24-h gas exchange collection. Contrasts were used to test the linear and quadratic effects of the F:C. There was a tendency (P = 0.06) for DMI to increase linearly as F:C decreased. As a result, gross energy intake (GEI) increased linearly (P = 0.04) as F:C decreased. Fecal energy loss expressed as Mcal/d (P = 0.02) or as a proportion of GEI (P < 0.01) decreased as F:C decreased, such that DE (Mcal/d and Mcal/kg) increased linearly (P < 0.01) as F:C decreased. As a proportion of GEI, urine energy decreased linearly (P = 0.03) as F:C decreased. Methane energy loss as a proportion of GEI responded quadratically (P < 0.01), increasing from HF:C to IF:C then decreasing thereafter. The efficiency of DE to ME conversion increased quadratically (P < 0.01) as F:C decreased, ranging from 0.86 to 0.92. Heat production (Mcal) increased linearly (P < 0.04) as F:C decreased but was not different as a proportion of GEI (P ≥ 0.22). As a proportion of GEI, retained energy responded quadratically (P = 0.03), decreasing from HF:C to IF:C and increasing thereafter. DM, organic matter, and neutral detergent fiber digestibility increased linearly (P < 0.01) and starch digestibility decreased linearly (P < 0.01) as the F:C decreased. Total N retained tended to increase linearly as the proportion of concentrate increased in the diet (P = 0.09). In conclusion, the efficiency of conversion of DE to ME increased with decreasing F:C due to decreasing methane and urine energy loss. The relationship between DE and ME is not static, especially when differing F:C.

Indolylkojyl methane analogue IKM5 potentially inhibits invasion of breast cancer cells via attenuation of GRP78.

PURPOSE: More than 90% of the breast cancer deaths occur due to the metastasis of the cancer cells to secondary organ sites. Increased Glucose-regulated protein 78 (GRP78) expression is critical for epithelial-mesenchymal transition (EMT) and invasion in breast cancer resulting in poor patient survival outcomes. Therefore, there is an urgent need of potential inhibitors of GRP78 for the abrogation of invasion and metastasis in breast cancer. METHODS: We investigated the effect of IKM5 (2-(1-(1H-indol-3-yl)octyl)-3-hydroxy-6-(hydroxymethyl)-4H-pyran-4-one) (a novel Indolylkojyl methane analogue) on invasion abilities of human breast cancer cells employing invadopodia formation, Matrigel invasion assays, and mouse models for metastasis. The mechanism underlying the anti-invasive effect of IKM5 was examined through molecular docking, immunoblotting, immunocytochemistry, co-immunoprecipitation analysis, siRNA silencing, and sub-cellular fractionation studies. RESULTS: Treatment with IKM5 at its sub-toxic concentration (200 nM) suppressed invasion and invadopodia formation, and growth factor-induced cell scattering of aggressive human breast cancer MDA-MB-231, MDA-MB-468, and MCF7 cells. IKM5 spontaneously binds to GRP78 (Ki = 1.35 µM) and downregulates its expression along with the EMT markers MMP-2, Twist1, and Vimentin. Furthermore, IKM5 amplified the expression and nuclear translocation of tumor suppressor Par-4 to control NF-kB-mediated pro-EMT activities. Interestingly, IKM5 disrupts the interaction between GRP78 and TIMP-1 by inhibiting GRP78 in a Par-4-dependent manner. Moreover, IKM5 inhibited tumor growth and lung metastasis at a safe dose of 30 mg/kg/body weight. CONCLUSION: Our study warrants IKM5, a potential anticancer agent that can abrogate invasion and metastasis, suggesting its clinical development for the treatment of patients with advanced breast cancer.

Flux and distribution of methane (CH4) in the Gunsan Basin of the southeastern Yellow Sea, off the Western Korea.

The flux and distribution of methane (CH4) was investigated in the seawater column at 14 stations in the Gunsan Basin, the southeastern part of Yellow Sea from 2013 to 2015. Here CH4 is concentrated 2.4-4.7 (3.4 ± 0.7) nM in the surface and 2.5-7.4 (5.2 ± 1.7) nM in the bottom layer. The CH4 saturation ratios ranged from 65.5% to 295.5% (162.6 ± 68.7), comprising the mean sea-to-air CH4 flux of 3.8 to 25.3 (15.6 ± 5.5) µM m-2d-1. Methane concentration was largely different in the upper and the lower seawater layers that is separated by the thermocline of which depth is variable (20-60 m) depending on the time of sampling. The concentration of seawater dissolved CH4 is high between the bottom surface of the thermocline layer and the sea floor. Generally it tends to decrease from the south-westernmost part of the basin toward the west coast of Korea. This distribution pattern of CH4 seems to result from the CH4 supply by decomposition of organic matters produced in the upper seawater layer that is superimposed by the larger supply from the underlying sediment layer especially beneath the thermocline. The latter is manifested by ubiquitous CH4 seeps from the seafloor sediments.

A five-year study of the impact of nitrogen addition on methane uptake in alpine grassland.

It remains unclear how nitrogen (N) deposition affects soil methane (CH4) uptake in semiarid and arid zones. An in situ field experiment was conducted from 2010 to 2014 to systematically study the effect of various N application rates (0, 10, 30, and 90 kg N ha(-1) yr(-1)) on CH4 flux in alpine grassland in the Tianshan Mountains. No significant influence of N addition on CH4 uptake was found. Initially the CH4 uptake rate increased with increasing N application rate by up to 11.5% in 2011 and then there was gradual inhibition by 2014. However, the between-year variability in CH4 uptake was very highly significant with average uptake ranging from 52.9 to 106.6 µg C m(-2) h(-1) and the rate depended largely on seasonal variability in precipitation and temperature. CH4 uptake was positively correlated with soil temperature, air temperature and to a lesser extent with precipitation, and was negatively correlated with soil moisture and NO3(-)-N content. The results indicate that between-year variability in CH4 uptake was impacted by precipitation and temperature and was not sensitive to elevated N deposition in alpine grassland.

Poly-arginine conjugated triarylmethyl radical as intracellular spin label.

Stable triarylmethyl radicals are ideal spin labels used for biomedical electron paramagnetic resonance applications. Previously reported structures exhibit polar charged functions for water solubilization preventing them from crossing the cell membrane. We report the synthesis of a triarylmethyl radical conjugated to poly-arginine peptide allowing intracellular delivery of the paramagnetic label.

Methane attenuates myocardial ischemia injury in rats through anti-oxidative, anti-apoptotic and anti-inflammatory actions.

Myocardial infarction (MI) remains the most frequent cardiovascular disease with high mortality. Recently, methane has been shown protective effects on small intestinal ischemia-reperfusion injury. We hypothesized that methane-rich saline (MS) could protect the myocardium again MI via its anti-oxidative, anti-apoptotic and anti-inflammatory effects. In experiment 1, tetrazolium chloride staining and detection of myocardial enzymes and oxidative and inflammatory parameters were performed at 12h after MI to determine the optimal dose at which intraperitoneal MS exerted the best protective effects on MI. In experiment 2, rats were treated with 10 ml/kg MS. Myocyte apoptosis was detected 72 h after MI, and cardiac function and myocardial remodeling were evaluated 4 weeks after MI. Results showed different dose of MS reduced infarct area, decreased myocardial enzymes, inhibited inflammation and oxidative stress following MI. The optimal dose of MS was 10 mg/kg. Moreover, treatment with 10mg/kg MS for 3 days significantly reduced myocyte apoptosis, improved cardiac function and inhibited myocardial remodeling (reduced anterior wall thickness, attenuated myocyte hypertrophy, and decreased myocardial collagen). MS protects the myocardium of MI rats via its anti-oxidative, anti-inflammatory, anti-apoptotic and anti-remodeling activities. Thus, MS provides a novel and promising strategy for the treatment of ischemic heart diseases.

Analysis of nitromethane from samples exposed in vitro to chloropicrin by stable isotope dilution headspace gas chromatography with mass spectrometry.

Chloropicrin (trichloronitromethane) is a widely used soil fumigant and an old chemical warfare agent. The metabolism of chloropicrin is not well known in mammals but nitromethane has been shown to be one of its main metabolites. Here, a fast and simple headspace gas chromatography with mass spectrometry method was applied for the measurement of nitromethane from aqueous samples. The analytical method was validated using stable isotope labeled internal standard and a small sample volume of 260 µL. No conventional sample preparation steps were needed. The method was accurate (relative standard deviations ≤1.5%) and linear (R(2) = 0.9996) within the concentration range of 0.1-6.0 µg/mL. This method was used to measure nitromethane in in vitro incubations with human and pig liver cell fractions containing enzymes for xenobiotic metabolism, exposed to chloropicrin. The results indicate that the presence of glutathione is necessary for the formation of nitromethane from chloropicrin. Also, nitromethane was formed mostly in liver cytosol fractions, but not in microsomal fractions after the incubation with chloropicrin. Our results suggest that although nitromethane is not the unequivocal biomarker of chloropicrin exposure, this method could be applied for screening the elevated levels in humans after chloropicrin exposure.

Thiophene containing trisubstituted methanes [TRSMs] as identified lead against Mycobacterium tuberculosis.

Triarylmethanes (TRAMs) and thiophene containing trisubstituted methanes (TRSMs) have been reported by us, having potential against Mycobacterium tuberculosis and Mycobacterium fortuitum strains, respectively. Further, extension through synthesis and biological evaluation of novel TRSMs resulted into an identified lead 36 (S006-830) [(diisopropyl-(2-{4-[(4-methoxy-phenyl)- thiophen-2-yl-methyl]-phenoxy}-ethyl)-amine)] with MIC: 1.33 mg/L, non-toxic against Vero C-1008 cell line with selectivity index >10, ex vivo efficacy equivalent to first line TB drugs-isoniazid (INH), rifampicin (RFM) and pyrazinamide (PZA) in the mouse and human macrophages, and lung CFU count of 2.2 × 10(7) (approximately 15 fold lesser than untreated mice, 31 × 10(7)) with efficacies comparable to ethambutol (EMB) (1.27 × 10(7)) and PZA (1.9 × 10(7)). Further, S006-830 also showed potent bactericidal activity against multi-drug resistant and single-drug resistant clinical isolates of M. tuberculosis.

Retention and excretion of inhaled 3H and 14C radiolabeled methane in rats.

A radiological concern for workers at heavy water reactor nuclear facilities is the hazard presented by tritium (H) and C. Radioactive methane is one of many potential H and C containing chemicals to which Nuclear Energy Workers (NEWs) may be exposed. Current dosimetric models for H- and C-methane, recommended by the International Commission on Radiological Protection (ICRP), are based on the assumption that 1% of methane is absorbed following its inhalation. Of this 1%, all H is converted immediately to tritiated water and C is converted immediately to CO2 (50%) and organically bound carbon (50%). In the study, rats were exposed to methane standards (H-methane and C-methane) mixed with breathing air to give a final concentration of 0.27% methane and resulting in final activity concentrations of 4.2 GBq m and 0.88 GBq m for H and C, respectively. This corresponds to exposure estimates of 580 kBq g and 120 kBq g. Simultaneous exposure to H- and C-methane allowed for the direct comparison of the retention of these radionuclides and removed uncertainties concerning their relative uptake and retention. The results demonstrate that the total methane uptake from the inhaled dose was threefold less than the 1% methane uptake predicted by the ICRP dosimetric models for H- and C-methane, with the H concentration being substantially higher than anticipated in the liver. This study provided data suggesting that current ICRP dosimetric methane models overestimate the fraction of H- and C-methane that is absorbed following inhalation and assisted in providing information to better understand the metabolism of inhaled H and C radiolabeled methane.

Point of care testing provides an accurate measurement of creatinine, anion gap, and osmolal gap in ex-vivo whole blood samples with nitromethane.

CONTEXT: Nitromethane interferes with Jaffé measurements of creatinine, potentially mimicking acute kidney injury. OBJECTIVES: We determined the proportional contribution of nitromethane in blood samples to creatinine measured by the Jaffé colorimetric and the point-of-care (POC) reactions and determined whether the difference can reliably estimate the concentration of nitromethane. Additionally, we determined whether the presence of nitromethane interferes with anion/osmolal gaps and ascertained the stability of nitromethane in serum after 7 days. METHODS: Nitromethane was added to whole blood from four healthy volunteers to achieve concentrations of 0, 0.25, 0.5, 1, and 2 mmol/L. The following tests were performed: creatinine (Jaffé and POC), electrolytes (associated with Jaffé and POC), osmolality and nitromethane concentration (gas chromatography [GC]). Remaining samples were refrigerated and reanalyzed using GC at 7 days. Anion and osmolal gaps were calculated. Proportional recovery and degradation of nitromethane were measured using GC. Data were analyzed for agreement with single-factor ANOVA (p = 0.05). RESULTS: Mean creatinine for POC and Jaff methods were 0.93 vs. 0.76 mg/dL, respectively. Jaff creatinine concentrations increased linearly with increasing nitromethane concentrations (R(2) = 1, p = 0.01): measured creatinine (mg/dL) = 7.1*nitromethane (mmol/L) = 0.79. POC creatinine remained unchanged across the range of nitromethane concentrations (p = 0.99). Anion and osmolal gaps also remained unchanged. Nitromethane was reliably identified in all sample concentrations using GC on Day 0. Detection of 0.25 mmol/L nitromethane was not consistently recovered on Day 7. Nitromethane degradation was most pronounced at 2 mmol/L concentrations (81% recovery). CONCLUSIONS: Nitromethane alters apparent concentration of creatinine using the Jaffé reaction in a linear fashion but not when using the POC reaction. Measured difference between Jaffé and POC creatinine may identify the presence and estimate concentration of nitromethane. Presence of nitromethane did not alter the anion or osmolal gap; thus it would not potentially interfere with the diagnosis of co-exposure to a toxic alcohol.

Mitochondria-targeted chemotherapeutics: the rational design of gold(I) N-heterocyclic carbene complexes that are selectively toxic to cancer cells and target protein selenols in preference to thiols.

A family of lipophilic, cationic Au(I) complexes of N-heterocyclic carbenes (NHCs) have been designed as new mitochondria-targeted antitumor agents that combine both selective mitochondrial accumulation and selective thioredoxin reductase inhibition properties within a single molecule. Two-step ligand exchange reactions with cysteine (Cys) and selenocysteine (Sec) occur with release of the NHC ligands. At physiological pH the rate constants for the reactions with Sec are 20- to 80-fold higher than those with Cys. The complexes are selectively toxic to two highly tumorigenic breast cancer cell lines and not to normal breast cells, and the degree of selectivity and potency are optimized by modification of the substituent on the simple imidazolium salt precursor. The lead compound is shown to accumulate in mitochondria of cancer cells, to cause cell death through a mitochondrial apoptotic pathway and to inhibit the activity of thioredoxin reductase (TrxR) but not the closely related and Se-free enzyme glutathione reductase.

Biokinetics of inhaled radioactive methane in rats: a pilot study.

Current dosimetric models for radioactive methane assume 1% of inhaled methane is absorbed, all 3H activity is converted immediately to [3H]H2O, and 14C activity is converted immediately to [14C]CO2 (50%) and organically bound carbon (50%). Results of a pilot study using rats to test these models suggest the models overestimate uptake but underestimate organic fixation of 3H and 14C, especially in liver. Also, the biokinetic properties of organically bound 3H and 14C in liver were markedly different from other tissues. Preliminary dose estimates based on observed uptake and organic fixation of label suggest current methane models likely overestimate radiation doses from radioactive methane by 3- to 10-fold.

Sorption of cobalt and nickel on anaerobic granular sludges: isotherms and sequential extraction.

The objective of this study was to investigate the sorption capacity and the fractionation of sorbed nickel and cobalt onto anaerobic granular sludges. Two different anaerobic granular sludges (non-fed, pH=7) were loaded with nickel and cobalt in adsorption experiments (monometal and competitive conditions). The combination of sequential extraction with the sorption isotherm analysis allowed the assessment of the sorption capacity of individual fractions present in the anaerobic granular sludges. The operational fractionation of the sorbed heavy metals was determined using a modified Tessier sequential extraction procedure. The sorption characteristics of each extracted fraction (exchangeable, carbonates, organic matter/sulfides and residual fractions) fitted well to the Langmuir model. The organic matter/sulfides fraction showed the highest affinity for cobalt and nickel in both sludges investigated compared to the other operationally defined fractions. The presence of iron negatively affected cobalt and nickel accumulation in this organic matter/sulfides fraction. The trace metals-iron sulfide interactions are likely to be the key process in controlling the distribution of cobalt and nickel during sorption onto non-fed methanogenic granules due to the high affinity of iron sulfides towards the metals studied.

Comparative mutagenicity of halomethanes and halonitromethanes in Salmonella TA100: structure-activity analysis and mutation spectra.

Halonitromethanes (HNMs) are a recently identified class of disinfection by-products (DPBs) in drinking water that are mutagenic in Salmonella and potent inducers of DNA strand breaks in mammalian cells. Here we compared the mutagenic potencies of the HNMs to those of their halomethane (HM) homologues by testing all nine HNMs and seven of the nine HMs (minus bromomethane and chloromethane) under the same conditions (the pre-incubation assay) in Salmonella TA100 +/- S9. We also determined the mutation spectra for several DBPs. In the presence of S9, all nine HNMs, but only three HMs, dibromomethane (DBM), dichloromethane (DCM), and bromochloromethane (BCM), were mutagenic. Only two DBPs of each class were mutagenic in the absence of S9. The HNMs were generally more potent mutagens than their HM homologues, and the brominated forms of both classes of DBPs were more mutagenic and cytotoxic than their chlorinated homologues. The HNMs were at least 10 times more cytotoxic than the HMs, and the cytotoxicity rankings in the presence of S9 were similar for the HNMs and the HMs. The addition of a nitro-group to BCM did not change the mutation spectra significantly, with both homologues inducing primarily (55-58%) GC --> AT transitions. The greater cytotoxic and mutagenic activities of the HNMs relative to the HMs are likely due to the greater intrinsic reactivity conferred by the nitro-group. Energy calculations predicted increased reactivity with increasing bromination and greater reactivity of the HNMs versus the HMs (Elumo values were approximately 20 kcal/mol lower for the HNMs compared to their HM homologues). Given that the HNMs also are potent genotoxins in mammalian cells [Environ. Sci. Technol. 38 (2004) 62] and are more mutagenic and 10x more cytotoxic in Salmonella than the HMs, whose levels are regulated in drinking water, further study of their occurrence and potential health effects is warranted.

Influence of plants on the methane emission from sediments.

The previous theory [Chem. Global Change Sci. 3 (2001) 33; Chemosphere 50 (2003) 191] of methane emission is applied to vegetated sediments. The presence of roots in a sediment is taken into account. It is assumed that methane and nitrogen enter a sediment through channels existing in plants and roots. The rate of methane and nitrogen transport through plants and roots is proportional to the difference in concentrations in the layer and on the upper surface. It is established that as the vegetation density increases, the rate of methane transport increases so that with sufficient vegetation density, almost all methane passes to the atmosphere through plants. In this case, the value of bubble emission decreases to zero. The nitrogen transport rate through plants first increases and then decreases with increasing the vegetation density. The theory qualitatively and quantitatively describes the dependence of methane concentration on depth in the presence of plants. A comparison with the available experimental data on dissolved methane concentration and bubble composition indicates satisfactory agreement.

Effect of molecular structure on the selective phototoxicity of triarylmethane dyes towards tumor cells.

In response to transmembrane potentials which are negative on the inner side of both the plasma and mitochondrial membranes, cationic dyes displaying appropriate structural features naturally accumulate in the cytosol and inside the mitochondria. Because enhanced mitochondrial membrane potential is a prevalent tumor cell phenotype, a number of cationic dyes preferentially accrue and are retained for longer periods in the mitochondria of tumor cells as compared to normal cells. The opportunities brought about by this phenomenon in chemo- and photochemotherapy of neoplastic diseases is highlighted by the observation that the phototoxic effects associated with some of the cationic photosensitizers known to accumulate in cell mitochondria are much more pronounced in tumor cells than in normal cells. However, the structural determinants of selective phototoxicity towards tumor cells are not well understood, and the lack of a robust model to describe the relationship between molecular structure and tumor selectivity has prevented mitochondrial targeting from becoming a more dependable therapeutic strategy. In this report we describe how the lipophilic/hydrophilic character of a series of cationic triarylmethane dyes affects the selectivity with which these photosensitizers mediate the destruction of tumor cells. Our results indicated that only the more hydrophilic triarylmethanes show tumor selectivity, presumably because these are the only dyes capable of staining energized mitochondria with a high degree of specificity. The partition of the more lipophilic dyes into a variety of extra-mitochondrial subcellular compartments occurs with comparable efficiencies in tumor and in normal cells, and this less specific subcellular localization precludes tumor selectivity from taking place.

Methane emission from a simulated rice field ecosystem as influenced by hydroquinone and dicyandiamide.

A simple apparatus for collecting methane emission from a simulated rice field ecosystem was formed. With no wheat straw powder amended all treatments with inhibitor(s) had so much lower methane emission during rice growth than the treatment with urea alone (control), which was contrary to methane emission from the cut rice-soil system. Especially for treatments with dicyandiamide (DCD) and with DCD plus hydroquinone (HQ), the total amount of methane emission from the soil system and intact rice-soil system was 68.25-46.64% and 46.89-41.78% of the control, respectively. Hence, DCD, especially in combination with HQ, not only increased methane oxidation in the floodwater-soil interface following application of urea, but also significantly enhanced methane oxidation in rice root rhizosphere, particularly from its tillering to booting stage. Wheat straw powder incorporated into flooded surface layer soil significantly weakened the above-mentioned simulating effects. Regression analysis indicated that methane emission from the rice field ecosystem was related to the turnover of ammonium-N in flooded surface layer soil. Diminishing methane emissions from the rice field ecosystem was significantly beneficial to the growth of rice.

[Methane in cadaver blood--homicide by natural gas or postmortem formation?]. / Methan im Leichenblut--Tötung durch Erdgas oder postmortale Neubildung?

A man had a quarrel with his wife. Suddenly he collapsed and became cyanotic. The woman supposed him to be dead. Because she was afraid of familiar requital, she opened the gas-cock of the cooking-range to pretend a suicide; methane emitted. The autopsy revealed a fresh cardiac infarction. Postmortem chemical analysis established methane in the blood. The question was, whether the methane had any importance for the death. By experimental inhalation of a methane-air-mixture (3%) we could expose, that the methane concentration in postmortem blood didn't have any relevance for the death.

False elevation of serum creatinine following skin absorption of nitromethane complicates the clinical diagnosis of rhabdomyolysis.

A patient had extensive blunt trauma from a high-speed crash in which nitromethane fuel erupted from the fuel tank and soaked into his protective multilayer jumpsuit. The clinical diagnosis was complicated because the absorption of nitromethane fuel through the skin and by inhalation falsely increased the serum creatinine value when a modified Jaffe reaction was used in the laboratory. This spurious value was "unmasked" by the use of an enzymatic method to measure the serum creatinine level. A high serum creatinine value disproportionate to the level of BUN and recent skin exposure to nitromethane were the clinical indications that suggested the differentiation of massive rhabdomyolysis from spurious hypercreatinemia. This spurious value was a confounding factor in the diagnosis of crush syndrome and rhabdomyolysis.

Excess chemical potential of small solutes across water--membrane and water--hexane interfaces.

The excess chemical potentials of five small, structurally related solutes, CH4, CH3F, CH2F2, CHF3, and CF4, across the water-glycerol 1-monooleate bilayer and water-hexane interfaces were calculated at 300, 310, and 340 K using the particle insertion method. The excess chemical potentials of nonpolar molecules (CH4 and CF4) decrease monotonically or nearly monotonically from water to a nonpolar phase. In contrast, for molecules that possess permanent dipole moments (CH3F, CH2F, and CHF3), the excess chemical potentials exhibit an interfacial minimum that arises from superposition of two monotonically and oppositely changing contributions: electrostatic and nonelectrostatic. The nonelectrostatic term, dominated by the reversible work of creating a cavity that accommodates the solute, decreases, whereas the electrostatic term increases across the interface from water to the membrane interior. In water, the dependence of this term on the dipole moment is accurately described by second order perturbation theory. To achieve the same accuracy at the interface, third order terms must also be included. In the interfacial region, the molecular structure of the solvent influences both the excess chemical potential and solute orientations. The excess chemical potential across the interface increases with temperature, but this effect is rather small. Our analysis indicates that a broad range of small, moderately polar molecules should be surface active at the water-membrane and water-oil interfaces. The biological and medical significance of this result, especially in relation to the mechanism of anesthetic action, is discussed.