Modified silver nanowire transparent electrodes with exceptional stability against oxidation.

We report an easy method to prepare thin, flexible and transparent electrodes that show enhanced inertness toward oxidation using modified silver nanowires (Ag NWs). Stabilization is achieved through the adsorption of triphenylphosphine (PPh3) onto the Ag NW hybrid dispersions prior to their 2D organization as transparent electrodes on polyethylene terephtalate (PET) films. After 110 days in air (20 °C) under atmospheric conditions, the transmittance of the PET/Ag NW/PPh3 based films is nearly unchanged, while the transmittance of the PET/Ag NW-based films decreases by about 5%. The sheet resistance increases for both materials as time elapses, but the rate of increase is more than four times slower for films stabilized by PPh3. The improved transmittance and conductivity results in a significantly enhanced stability for the figure of merit σ dc/σ op. This phenomenon is highlighted in highly oxidative nitric acid vapor. The tested stabilized films in such conditions exhibit a decrease to σ dc/σ op of only 38% after 75 min, whereas conventional materials exhibit a relative loss of 71%. In addition, by contrast to other classes of stabilizers, such as polymer or graphene-based encapsulants, PPh3 does not alter the transparency or conductivity of the modified films. While the present films are made by membrane filtration, the stabilization method could be implemented directly in other liquid processes, including industrially scalable ones.

Kinetics of fiber solidification.

Many synthetic or natural fibers are produced via the transformation of a liquid solution into a solid filament, which allows the wet processing of high molecular weight polymers, proteins, or inorganic particles. Synthetic wet-spun fibers are used in our everyday life from clothing to composite reinforcement applications. Spun fibers are also common in nature. Silk solidification results from the coagulation of protein solutions. The chemical phenomena involved in the formation of all these classes of fibers can be quite different but they all share the same fundamental transformation from a liquid to a solid state. The solidification process is critical because it governs the production rate and the strength that fibers can sustain to be drawn and wound. An approach is proposed in this work to investigate the kinetics of fiber solidification. This approach consists in circulating solidifying fibers in the extensional flow of a surrounding liquid. Such as polymers in extensional flows, the fibers break if resultant drag forces exceed the fiber tensile strength. The solidification kinetics of nanotube composite fibers serves as a validation example of this approach. The method could be extended to other systems and advance thereby the science and technology of fiber and textile materials. It is also a way to directly visualize the scission of chain-like systems in extensional flows.

The association between malnutrition and psychological distress in patients with advanced head-and-neck cancer.

OBJECTIVE: Malnutrition and psychological distress are often seen in patients with head-and-neck cancer, but little is known about the interrelationships between those two symptoms. The present study examined the relationship between malnutrition and psychological distress in patients with advanced head-and-neck cancer. METHODS: Using the Patient-Generated Subjective Global Assessment, 99 patients with advanced-stage head-and-neck cancer were screened for nutrition status. The patients were also screened for psychosocial distress (using the Distress Thermometer) and for psychosocial issues (using the Problem Checklist). Any relationship between malnutrition and psychosocial distress was determined by regression and correlation analysis. We also used t-tests to compare distress levels for patients with and without specific nutrition-related symptoms. RESULTS: The study group included 80 men and 19 women [mean age: 58.4 ± 10.9 years (range: 23-85 years)]. The correlation between poorer nutrition status and level of psychological distress was significant r = 0.37 (p < 0.001). Specifically, reduced food intake and symptoms were both positively associated with distress: r = 0.27 and r = 0.29 respectively, both significant at p < 0.01. After controlling for the effects of psychosocial problems and pain, nutrition status remained a significant predictor of distress, explaining 3.8% of the variance in the distress scores of the patients (p < 0.05). CONCLUSIONS: Malnutrition and symptoms were strongly related to distress in patients with advanced head-and-neck cancer. Our results suggest the need for further research into the complex relationship between nutrition status and distress and into the management of both nutrition and distress in cancer care.

Mindfulness-based stress reduction alters brain activity for breast cancer survivors with chronic neuropathic pain: preliminary evidence from resting-state fMRI.

PURPOSE: Breast cancer continues to be the most commonly diagnosed cancer among Canadian women, with as many as 25-60% of women suffering from chronic neuropathic pain (CNP) as a pervasive consequence of treatment. While pharmacological interventions have shown limited efficacy for the management of CNP to date, psychological interventions, such as mindfulness-based stress reduction (MBSR), may be a promising alterative for improving pain-related problems. The purpose of this study was to use brain imaging methods to investigate this potential. METHODS: Resting-state fMRI was used in female breast cancer survivors with CNP before and after an 8-week MBSR course (n = 13) and compared with a waitlist control group (n = 10). RESULTS: Focusing on the default mode network, the most significant results show greater posterior cingulate connectivity with medial prefrontal regions post-MBSR intervention. Moreover, this change in connectivity correlated with reduced pain severity for the MBSR group. CONCLUSIONS: These results provide empirical evidence of a change in the brain following MBSR intervention associated with changes in the subjective experience of pain. IMPLICATIONS FOR CANCER SURVIVORS: This study gives hope for a non-invasive method of easing the struggle of CNP in women following breast cancer treatment.

Colloidal ordering from phase separation in a liquid-crystalline continuous phase

Some binary mixtures exist as a single phase at high temperatures and as two phases at lower temperatures; rapid cooling therefore induces phase separation that proceeds through the initial formation of small particles and subsequent growth and coarsening. In solid and liquid media, this process leads to growing particles with a range of sizes, which eventually separate to form a macroscopically distinct phase. Such behaviour is of particular interest in systems composed of an isotropic fluid and a liquid crystal, where the random distribution of liquid-crystal droplets in an isotropic polymer matrix may give rise to interesting electro-optical properties. Here we report that a binary mixture consisting of an isotropic fluid and a liquid crystal forming the continuous phase does not fully separate into two phases, but self-organizes into highly ordered arrays of monodisperse colloidal droplet chains. We find that the size and spatial organization of the droplets are controlled by the orientational elasticity of the liquid-crystal phase and the defects caused by droplets exceeding a critical size. We expect that our approach to forming monodisperse, spatially ordered droplets in liquid crystals will allow the controlled design of ordered composites that may have useful rheological and optical properties.

Macroscopic fibers and ribbons of oriented carbon nanotubes.

A simple method was used to assemble single-walled carbon nanotubes into indefinitely long ribbons and fibers. The processing consists of dispersing the nanotubes in surfactant solutions, recondensing the nanotubes in the flow of a polymer solution to form a nanotube mesh, and then collating this mesh to a nanotube fiber. Flow-induced alignment may lead to a preferential orientation of the nanotubes in the mesh that has the form of a ribbon. Unlike classical carbon fibers, the nanotube fibers can be strongly bent without breaking. Their obtained elastic modulus is 10 times higher than the modulus of high-quality bucky paper.

Substantial improvement of nanotube processability by freeze-drying.

As-produced carbon nanotubes often contain a fraction of impurities such as metal catalysts, inorganic supports, and carbon by-products. These impurities can be partially removed by using acidic dissolution. The resulting nanotube materials have to be dried to form a powder. The processability of nanotubes subjected to regular (thermal vaporisation) drying is particularly difficult because capillary forces pack and stick the nanotubes irreversibly, which limits their dispersability in polymeric matrices or solvents. We show that this dramatic limitation can be circumvented by using freeze-drying instead of regular-drying during nanotube purification process. In this case, the nanotubes are trapped in frozen water which is then sublimated. As a result the final powder is significantly less compact and, more important, the nanotubes can be easily dispersed with no apparent aggregates, thereby greatly enhancing their processability, e.g., they can be used to make homogeneous composites and fibers. Results from coagulation spinning from water-based dispersions of regularly-dried and freeze-dried nanotubes are compared. We also show that freeze-dried materials, in contrast to regularly-dried materials, can be dissolved in organic polar solvents using alkali-doped nanotubes. High resolution TEM and XRD analysis demonstrate that the nanotube structure and quality are not affected at the nanoscale by freeze-drying treatments.

Vorinostat and Mithramycin A in combination therapy as an interesting strategy for the treatment of Sézary T lymphoma: a transcriptomic approach.

SAHA (vorinostat) is a histone deacetylase inhibitor approved by the USA Food and Drug Administration (FDA) for treating advanced refractory cutaneous T cell lymphomas. As SAHA alters the expression of many genes under control of the Sp1 transcription factor, we examined the effect of its association with the FDA-approved anticancer antibiotic Mithramycin A (MTR, plicamycin), a competitive inhibitor of Sp1 binding to DNA. Sézary syndrome (SS) cells, expanded ex vivo from peripheral blood mononuclear cells of 4 patients, were tested for their sensitivity to the drugs regarding cytotoxicity and differential responsive gene expression. Multivariate statistical methods were used to identify genes whose expression is altered by SAHA, MTR, and the synergist effect of the two drugs. MTR, like SAHA, induced the apoptosis of SS cells, while the two drugs in combination showed clear synergy or potentiation. Expression data stressed a likely important role of additive or synergistic epigenetic modifications in the combined effect of the two drugs, while direct inhibition of Sp1-dependent transcription seemed to have only limited impact. Ontological analysis of modified gene expression suggested that the two drugs, either independently or synergistically, counteracted many intertwined pro-survival pathways deregulated in SS cells, resistance of these tumors to intrinsic and extrinsic apoptosis, abnormal adhesion migration, and invasive properties, as well as immunosuppressive behavior. Our findings provide preliminary clues on the individual and combined effects of SAHA and MTR in SS cells and highlight a potential therapeutic interest of this novel pair of drugs for treatment of SS patients.

Mitotically active cells that generate neurons and astrocytes are present in multiple regions of the adult mouse hippocampus.

Previous studies of the adult hippocampus of rodents and primates have reported neuro- and gliogenesis restricted to the region of the dentate gyrus. In the present study, by employing a prolonged bromodeoxyuridine (BrdU) labeling protocol that attempts to account for cytokinetic changes as an animal ages, we have identified mitotically active cells in multiple regions of the hippocampus, especially in Ammon's horn, of the adult mouse. Immediately following the labeling period, the BrdU-labeled cells did not express known markers for neurons and astrocytes. Subsequent analysis at 3-24 weeks after labeling demonstrated BrdU-labeled neurons and glia in these regions of the hippocampus. Although neuro- and gliogenesis in the adult mammalian hippocampus have been reported previously, these results demonstrate that the phenomenon is not limited to the region of the dentate gyrus, but rather extends into Ammon's horn. Furthermore, it suggests that ongoing cell production, albeit discrete and limited in nature, may be widespread in the adult mammalian central nervous system.

Steroid hormone regulation of vasopressinergic neurotransmission in the central nervous system.

Vasopressinergic neurotransmission is intimately linked to steroid hormone signaling. Both arginine vasopressin (VP) and the extrahypothalamic VP V1a receptors are regulated by steroid hormones. Here, we present work that has been done in our laboratory, investigating mechanisms underlying steroid hormone effects on the expression of both VP and its primary receptor in the brain, the VP V1a receptor. Data on VP receptors, their coupling to second messenger pathways, their localization in brain, and their regulation by peptide exposure are discussed. We also cover the regulation of the V1a receptor by adrenal hormones, and the molecular basis of this effect. Evidence for the existence of other receptors for VP in the brain is presented. Lastly, the regulation of the VP peptide by gonadal hormones is discussed at the transcriptional level in the rodent brain. Finally, the potential significance of the 'cross-talk' between the vasopressinergic system and the steroid hormone system is addressed.

Arginine vasopressin-induced sensitization in brain: facilitated inositol phosphate production without changes in receptor number.

Arginine vasopressin (AVP) has been shown to have a unique sensitization effect whereby repeated injection of AVP into a lateral cerebral ventricle or a mediobasal region of the rat forebrain below the lateral septum and including the anterior hypothalamus referred to as the ventral septal area, causes enhanced motor responses to the ligand. To elucidate possible neuronal mechanisms responsible for AVP sensitization, 1) we determined the dose and the time required for the development and expression of AVP sensitization, and 2) we tested the hypotheses that AVP sensitization may result in a) alteration of septal AVP V1 receptor affinity or number, and/or b) alteration of septal AVP V1 receptor signal transduction (phosphatidylinositol hydrolysis) mechanisms. Our behavioral data show that the magnitude of AVP sensitization varies with dose and time, and the effect is dependent on the time interval between injections, in that an initial intracerebroventricular AVP injection enhances the sensitivity of the animals to the motor effects of similar AVP injections given 6 h to 6 days later but not to injections given hourly or weekly. No changes in septal AVP binding site density and affinity, as measured by [3H]AVP binding to septal synaptic plasma membrane, were found in sensitized animals; [3H]inositol monophosphate stimulation in response to AVP in septal slices, however, was found to be significantly enhanced. This enhanced [3H]inositol monophosphate stimulation appears specific to a V1-type receptor because it was significantly reduced in the presence of the V1 receptor antagonist, d(CH2)5Tyr(Me)AVP, and was not found using oxytocin or the V2 receptor agonist, DDAVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxytocin pretreatment enhances arginine vasopressin-induced motor disturbances and arginine vasopressin-induced phosphoinositol hydrolysis in rat septum: a cross-sensitization phenomenon.

The recent observation that the central oxytocin (OT) receptor has high affinity for both OT and arginine vasopressin (AVP) raises the possibility that it may be involved in some of the central actions of AVP. Repeated intracerebroventricular (icv) injections of AVP in rats evoke an unusual sensitization phenomenon in that a first exposure to the peptide enhances the sensitivity (sensitization) of the brain to a second exposure. This report investigates the possibility that the OT receptor may be involved in the mediation of the phenomenon of sensitization, using OT, a specific OT receptor agonist, [Thr4,Gly7]OT, and a specific OT receptor antagonist, d(CH2)5,[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT (compound 6; cpd 6), as well as a V1 AVP receptor antagonist, d(CH2)5Tyr(Me)AVP. Peptides were injected icv in conscious, adult male Sprague-Dawley rats.(ABSTRACT TRUNCATED AT 250 WORDS)

[3H]arginine vasopressin binding to rat brain: a homogenate and autoradiographic study.

Arginine-vasopressin (AVP) has been implicated as a putative central neurotransmitter or neuromodulator in some brain functions. This study demonstrates binding of [3H]AVP to rat brain homogenates that is pH and temperature dependent, is saturable (Kd = 0.77 nM, Bmax = 0.374 pmol/mg) and reversible. A number of AVP analogues competitively displaced the [3H]AVP binding, indicating that central AVP binding sites may have a resemblance to the peripheral (V1) AVP vasopressor receptor. Homogenate binding occurred predominantly in the microsomal fraction (P3) of the hypothalamus while in the hippocampus and septum binding was predominantly in the synaptosomal fraction (P2). Autoradiographic methods showed displaceable [3H]AVP binding in the lateral septum, amygdala, supraoptic, paraventricular and suprachiasmatic nuclei of the hypothalamus supporting the results of homogenate binding in preparations of these regions.

Autoradiographic localization of binding sites for vasoactive intestinal peptide (VIP) in bovine cerebral arteries.

A substantial body of published evidence indicates that vasoactive intestinal peptide (VIP) may function as a vasodilatory neurotransmitter to cerebral blood vessels via a specific VIP receptor. In the present study in vitro autoradiography utilizing monoiodinated [125I-Tyr10]-VIP demonstrated VIP binding sites in the medial layer of bovine anterior, middle, and posterior cerebral arteries. This observation is consistent with the VIP receptor being localized in vascular smooth muscle components.

Vasopressin-induced motor effects: localization of a sensitive site in the amygdala.

Arginine vasopressin (AVP) induces motor effects when administered into the cerebral ventricles, the ventral septal area (VSA), or the vestibular cerebellum of the rat brain. Because AVP-like immunoreactivity and AVP-binding sites exist in the central medial amygdala (cmeA), and because the amygdala can be kindled to produce motor effects, we hypothesized that the amygdala might play a role in AVP-induced motor effects. This hypothesis was tested by observing motor behavior in response to injection of AVP into the central medial region of the amygdala. Our results demonstrate that an initial injection of AVP into the cmeA caused minor motor effects, including immobility, prostration and ataxia, whereas a similar injection, given 24 h later, caused severe motor effects including barrel rotations and myoclonic/myotonic-like convulsive behavior. A potential receptor basis for the AVP-induced motor and sensitization effects in the cmeA was investigated using AVP analogues. A V1 antagonist, d(CH2)5Tyr(Me)AVP, blocked both the motor and sensitization effects produced by cmeA AVP injection. A V2 receptor agonist, DDAVP, did not affect motor activity upon cmeA injection, but did, however, sensitize animals to subsequent cmeA AVP injection. These results suggest that the cmeA is a sensitive site for AVP-induced motor effects and that these motor effects are sensitized by prior exposure to AVP. While the motor effects observed after cmeA AVP injection are mediated via AVP receptors that resemble the V1 type, the sensitization effect may be mediated via multiple receptor systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasopressin-induced sensitization: involvement of neurohypophyseal peptide receptors.

Rats pretreated with an intracerebroventricular (i.c.v.) injection of 10 pmol of vasopressin or vasopressin analogs, including deamino-D-vasopressin, [pGlu4,Cyt6]vasopressin, [pGlu-Asn-Cys(Cys)]Pro-Leu-Gly-NH2, des-Gly-NH9(2)-vasopressin, Pro-Leu-Gly-NH2, Pro-Arg-Gly-NH2, became markedly hyper-responsive to the motor effects, 24 h later, to a subsequent challenge dose of vasopressin, but not vasopressin-related peptides. A vasopressin V1 receptor antagonist, [d(CH2)1(5),Tyr(Me)2]vasopressin, but not the vasopressin V2 receptor antagonist, [d(CH2)1(5),Tyr(Et)2,Val4]vasopressin, or a more selective vasopressin V2 receptor antagonist, [d(CH2)1(5),D-Ile2,Ile4]vasopressin, or the oxytocin receptor antagonist, [d(CH2)1(5),Tyr(Me)2,Thr4,Orn8,Tyr-NH9(2)]vasotocin ([d(CH2)1(5),Tyr(Me)2,Thr4,Tyr-NH9(2)]OVT), blocked vasopressin and vasopressin analog-induced sensitization. Furthermore, both vasopressin V2 receptor antagonists were found to sensitize the brain to a subsequent vasopressin injection. This vasopressin V2 receptor antagonist-induced sensitization was also blocked by the vasopressin V1 receptor antagonist. Next, we wanted to determine if this sensitization process could involve the release of endogenous vasopressin in the brain as reflected in an amplification of vasopressin mRNA expression. However pretreatment of rats with an i.c.v. vasopressin injection was not associated with an increase in vasopressin mRNA expression in the bed nucleus of the stria terminalis, medial amygdala or the paraventricular nucleus of the hypothalamus when measured 0, 1, 3, 7, 12, or 24 h after the first vasopressin injection. As many vasopressin analogs can induce sensitization, we suggest that a novel type of receptor may be involved in the sensitization process.

The role of vasopressin as an antipyretic in the ventral septal area and its possible involvement in convulsive disorders.

Perfusion of the peptide, arginine vasopressin (AVP), within the ventral septal area (VSA) of the brain of a number of species reduces fever but not normal body temperature. This antipyretic response appears to be mediated by AVP receptors of the V1 subtype. Lesions of the VSA with kainic acid are associated with prolonged and enhanced fevers in rats. A role for endogenous AVP in fever suppression within the VSA comes from several types of experiments: (1) AVP release within the VSA is inversely correlated to fever height; (2) AVP antagonists or antiserum injected into the VSA prolong fever; (3) animals lacking endogenous AVP in the VSA (Brattleboro rat, long-term castrated rat) develop enhanced fevers. Electrical stimulation of the AVP-containing cell bodies of the bed nucleus of the stria terminalis (BST) orthodromically inhibits VSA neurons and also suppresses fever; the latter effect can be abolished with application of a V1 antagonist to the VSA. Iontophoretic studies indicate that AVP inhibits glutamate-stimulated activity of thermoresponsive and other VSA neurons. AVP can also act in the VSA to cause severe motor disturbances; this action is receptor mediated and increases in severity upon sequential exposure to AVP. Because sites of action of the antipyretic and convulsive action of AVP are similar, and because animals lacking brain AVP display reduced convulsive activity, it is possible that AVP, released during fever, could be involved in the genesis of convulsive activity.

The use of silver-stained "comets" to visualize DNA damage and repair in normal and Xeroderma pigmentosum fibroblasts after exposure to simulated solar radiation.

The alkaline and neutral comet assays have been widely used to assess DNA damage and repair in individual cells after in vivo or in vitro exposure to chemical or physical genotoxins. Cells processed under neutral conditions generate comets primarily from DNA double strand breaks, whereas under alkaline conditions, comets arise from DNA single and double strand breaks and alkali-labile lesions. A modified version of the alkaline comet assay, as described here, used silver stain to visualize the comets and a Gelbond base to facilitate the manipulation and processing of samples. To demonstrate how these modifications improve the assay, fibroblasts derived from both normal and Xeroderma pigmentosum (Xp) individuals were exposed to simulated solar radiation and the resulting DNA damage and repair evaluated and compared with results from the relevant literature. Comets from normal fibroblasts reached their maximum length at about an hour after irradiation. Dose-dependent increases in comet length were observed up to at least 360 mJ/cm2. In contrast, comet lengths from repair deficient Xp fibroblasts were shorter than normal cells reflecting their reduced capacity to generate single strand breaks by the excision of DNA dimers. For incubation times of more than 1 h, comet lengths from normal fibroblasts underwent a time-dependent decrease, supporting the contention that this change was related to the ligation step in the DNA repair process. These changes were compatible with the model of DNA damage and repair established by others for ultraviolet radiation.

A priori prediction of tissue:plasma partition coefficients of drugs to facilitate the use of physiologically-based pharmacokinetic models in drug discovery.

The tissue:plasma (P(t:p)) partition coefficients (PCs) are important drug-specific input parameters in physiologically based pharmacokinetic (PBPK) models used to estimate the disposition of drugs in biota. Until now the use of PBPK models in early stages of the drug discovery process was not possible, since the estimation of P(t:p) of new drug candidates by using conventional in vitro and/or in vivo methods is too time and cost intensive. The objectives of the study were (i) to develop and validate two mechanistic equations for predicting a priori the rabbit, rat and mouse P(t:p) of non-adipose and non-excretory tissues (bone, brain, heart, intestine, lung, muscle, skin, spleen) for 65 structurally unrelated drugs and (ii) to evaluate the adequacy of using P(t:p) of muscle as predictors for P(t:p) of other tissues. The first equation predicts P(t:p) at steady state, assuming a homogenous distribution and passive diffusion of drugs in tissues, from a ratio of solubility and macromolecular binding between tissues and plasma. The ratio of solubility was estimated from log vegetable oil:water PCs (K(vo:w)) of drugs and lipid and water levels in tissues and plasma, whereas the ratio of macromolecular binding for drugs was estimated from tissue interstitial fluid-to-plasma concentration ratios of albumin, globulins and lipoproteins. The second equation predicts P(t:p) of drugs residing predominantly in the interstitial space of tissues. Therefore, the fractional volume content of interstitial space in each tissue replaced drug solubilities in the first equation. Following the development of these equations, regression analyses between P(t:p) of muscle and those of the other tissues were examined. The average ratio of predicted-to-experimental P(t:p) values was 1.26 (SD = 1.40, r = 0.90, n = 269), and 85% of the 269 predicted values were within a factor of three of the corresponding literature values obtained under in vivo and in vitro conditions. For predicted and experimental P(t:p), linear relationships (r > 0.9 in most cases) were observed between muscle and other tissues, suggesting that P(t:p) of muscle is a good predictor for the P(t:p) of other tissues. The two previous equations could explain the mechanistic basis of these linear relationships. The practical aim of this study is a worthwhile goal for pharmacokinetic screening of new drug candidates.

Prediction of adipose tissue: plasma partition coefficients for structurally unrelated drugs.

Tissue:plasma (P(t:p)) partition coefficients (PCs) are important parameters describing tissue distribution of drugs. The ultimate goal in early drug discovery is to develop and validate in silico methods for predicting a priori the P(t:p) for each new drug candidate. In this context, tissue composition-based equations have recently been developed and validated for predicting a priori the non-adipose and adipose P(t:p) for neutral organic solvents and pollutants. For ionizable drugs that bind to different degrees to common plasma proteins, only their non-adipose P(t:p) values have been predicted with these equations. The only compound-dependent input parameters for these equations are the lipophilicity parameter, such as olive oil-water PC (K(vo:w)) or n-octanol-water PC (P(o:w)), and/or unbound fraction in plasma (fu(p)) determined under in vitro conditions. Tissue composition-based equations could potentially also be used to predict adipose tissue-plasma PCs (P(at:p)) for ionized drugs. The main objective of the present study was to modify these equations for predicting in vivo P(at:p) (white fat) for 14 structurally unrelated ionized drugs that bind substantially to plasma macromolecules in rats, rabbits, or humans. The second objective was to verify whether K(vo:w) or P(o:w) provides more accurate predictions of in vivo P(at:p) (i.e., to verify whether olive oil or n-octanol is the better surrogate for lipids in adipose tissue). The second objective was supported by comparing in vitro data on P(at:p) with those on olive oil-plasma PC (K(vo:p)) for five drugs. Furthermore, in vivo P(at:p) was not only predicted from K(vo:w) and P(o:w) of the non-ionized species, but also from K*(vo:w) and P*(o:w), taking into account the ionized species in addition. The P(at:p) predicted from K*(vo:w), P*(o:w), and P(o:w) differ from the in vivo P(at:p) by an average factor of 1.17 (SD = 0.44, r = 0.95), 15.0 (SD = 15.7, r = 0.59), and 40.7 (SD = 57.2, r = 0.33), respectively. The in vitro values of K(vo:p) differ from those of P(at:p) by an average factor of 0.86 (SD = 0.16, r = 0.99, n = 5). The results demonstrate that (i) the equation using only data on fu(p) as input and olive oil as lipophilicity surrogate is able to provide accurate predictions of in vivo P(at:p), and (ii) olive oil is a better surrogate of the adipose tissue lipids than n-octanol. The present study is an innovative method for predicting in vivo fat partitioning of drugs in mammals.