The strength of the relationship between functional connectivity

The strength of the relationship between functional connectivity and selleck products cognitive control did not differ between groups. These results indicate that SUD is associated with abnormal interactions between subcortical areas that process reward (nucleus accumbens) and cortical areas that govern cognitive-behavioral control. Hum Brain Mapp 35:4282-4292, 2014. (C) 2014 Wiley Periodicals, Inc.”
“Background. Although mycophenolate mofetil (MMF) is recommended at a fixed dose, there is increasing interest in controlled-dose (CD) MMF based on therapeutic drug monitoring. We systematically evaluated published randomized controlled trials (RCTs) on the efficacy and safety of CD

versus fixed-dose MMF for kidney transplant recipients. Methods. The electronic databases Medline, Embase, and Cochrane Library (up to June 2012) were searched to identify relevant RCTs. Two reviewers independently applied the study selection criteria, examined the study quality, and extracted

the data. Dichotomous measures were expressed as relative risk (RR) and continuous outcomes were expressed as weighted mean difference, both with 95% confidence intervals (CIs). All statistical analyses were performed using Review Manager 5.1.6. Results. Four RCTs met our selection criteria and included 1755 de novo recipients. The differences between CD and fixed-dose MMF in treatment failure (RR, 0.95; 95% CI, 0.82-1.10; P=0.52), serum creatinine clearance (weighted mean difference, GSK1210151A 2.46; 95% CI, -1.15 to 6.07; P=0.18), total gastrointestinal

adverse events (RR, 1.23; 95% CI, 0.65-2.35; P=0.53), diarrhea (RR, 1.08; Autophagy Compound Library 95% CI, 0.92-1.25; P=0.35), anemia (RR, 1.24; 95% CI, 0.95-1.64; P=0.12), leukopenia (RR, 1.12; 95% CI, 0.93-1.35; P=0.25), thrombocytopenia (RR, 0.80; 95% CI, 0.47-1.36; P=0.41), and malignancy (RR, 0.61; 95% CI, 0.27-1.38; P=0.23) were not statistically significant. Furthermore, total infections were more frequent in the CD group (36.0% vs. 30.9%; RR, 1.16; 95% CI, 1.03-1.30; P=0.01). Conclusions. Based on current evidence, CD MMF administration cannot be recommended as routine practice for kidney transplant recipients. Therapeutic drug monitoring for MMF may be targeted toward high-risk recipients, who should be identified in future studies.”
“The formation of mossy lithium and lithium dendrites so far prevents the use of lithium metal anodes in lithium ion batteries. To develop solutions for this problem (e.g., electrolyte additives), operando measurement techniques are required to monitor mossy lithium and dendrite formation during electrochemical cycling. Here we present a novel battery cell design that enables operando electron paramagnetic resonance (EPR) spectroscopy.

The outcomes of patients with deep remission were compared with t

The outcomes of patients with deep remission were compared with those of patients with only the absence of mucosal ulceration or only clinical remission. RESULTS: Rates of deep

remission were 16% in patients given adalimumab vs 10% in those given placebo (P =.34) at week 12, and 19% vs 0% (P smaller than .001) at week 52. Rates of deep remission were greatest among patients who received adalimumab and had CD for 2 years or less (33% at weeks ABT-737 cost 12 and 52). At week 52, patients who achieved deep remission at week 12 required significantly fewer adalimumab treatment adjustments, hospitalizations, and CD-related surgeries; had significantly less activity impairment; and had better quality of life and physical function compared with patients not achieving deep remission. Deep remission generally was associated with better outcomes than only an absence of mucosal ulceration; outcomes of patients with deep remission vs only clinical remission were similar. Deep remission was associated with estimated total cost savings of $ 10,360 (from weeks 12 through https://www.selleckchem.com/products/gsk126.html 52) compared with lack of deep remission. CONCLUSIONS: In an exploratory study of patients with moderate to severe ileocolonic CD who received

adalimumab induction and maintenance therapy, patients achieving deep remission appeared to have better 1-year outcomes than those not achieving deep remission. These findings should be validated in large, prospective trials.”
“Genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms (SNPs) associated with the development of common diseases. However, it is clear that genetic risk factors of common diseases are heterogeneous among human populations. Therefore, we developed a database of genomic polymorphisms that are reproducibly associated with disease susceptibilities, drug responses and other traits for each Blebbistatin human population: ‘VarySysDB Disease Edition’ (VaDE; ext-link-type=”uri” xlink:href=”http://bmi-tokai.jp/VaDE/”

xlink:type=”simple” bigger than http://bmi-tokai.jp/VaDE/). SNP-trait association data were obtained from the National Human Genome Research Institute GWAS (NHGRI GWAS) catalog and RAvariome, and we added detailed information of sample populations by curating original papers. In addition, we collected and curated original papers, and registered the detailed information of SNP-trait associations in VaDE. Then, we evaluated reproducibility of associations in each population by counting the number of significantly associated studies. VaDE provides literature-based SNP-trait association data and functional genomic region annotation for SNP functional research. SNP functional annotation data included experimental data of the ENCODE project, H-InvDB transcripts and the 1000 Genome Project. A user-friendly web interface was developed to assist quick search, easy download and fast swapping among viewers.

These deposits could be confirmed by anatomical dissection of the

These deposits could be confirmed by anatomical dissection of the device and by SEM. Device

2 showed no signs of clot formation in MDCT using the same VRT settings. It was demonstrated that MDCT with VRT is able to detect thrombotic Selleck Rabusertib deposits in ECMO devices under ex vivo conditions. MDCT allows direct visualization of the actual thrombus load of a used ECMO device as well as the quantification of the thrombus volume and could, therefore, play a significant role in better understanding the oxygenator thrombosis in modern ECMO treatment.”
“A novel nitridosilicate phosphor, BaSi7N10:Eu2+, was synthesized via the nitridation of Ba1-xEuxSi alloy. Oxide impurities in the product can be significantly reduced by the use of alloy precursor to obtain a single phase product. The synthesized BaSi7N10:Eu2+ absorbs strongly in the UV-part of the electromagnetic spectrum and exhibits bluish-green light with a peak wavelength

at 475 nm. When temperature is increasing, its emission intensity is decreasing with the broadening full widths at half maximum (FWHM). Interestingly, the afterglow emission of Eu2+ (4f(6)5d(1)- bigger than 4f(7)) could be observed after switching off the 280 nm excitation source, which to the best of our knowledge is found for the first time. This simple, inexpensive and high-yield synthesis route has a significant potential to be applied to other nitrides. (C) 2013 Elsevier www.selleckchem.com/products/SB-525334.html B.V. All rights reserved.”
“Background: Genetic polymorphisms, gender and age all influence the risk of developing chronic neuropathic pain following peripheral nerve injury (PNI). It is known that there are significant inter-strain differences in pain hypersensitivity in strains of mice after PNI. In response to PNI, one of the earliest events is thought to be the disruption of the blood-spinal cord barrier (BSCB). The study of BSCB

integrity after PNI may lead to a better understanding of the mechanisms 3-MA ic50 that contribute to chronic pain. Results: Here we used in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to establish a timecourse for BSCB permeability following PNI, produced by performing a spared nerve injury (SNI). From this longitudinal study, we found that the SNI group had a significant increase in BSCB permeability over time throughout the entire spinal cord. The BSCB opening had a delayed onset and the increase in permeability was transient, returning to control levels just over one day after the surgery. We also examined inter-strain differences in BSCB permeability using five mouse strains (B10, C57BL/6J, CD-1, A/J and BALB/c) that spanned the range of pain hypersensitivity. We found a significant increase in BSCB permeability in the SNI group that was dependent on strain but that did not correlate with the reported strain differences in PNI-induced tactile hypersensitivity.

Compound 1 is, monoclinic, space group C2/c, with a = 20 0784(7),

Compound 1 is, monoclinic, space group C2/c, with a = 20.0784(7), b = 9.0316(3), c = 23.0980(8) angstrom, beta = 98.3930(10), V = 4143.7(2) angstrom(3), with Z = 8 for d(calc) = 1.338 Mg/m(3). The analog 2 is, Triclinic, space group P-1, with a = 8.9353(18), b = 10.466(2), c = 14.679(3)

angstrom, beta = 73.60(3), V = 1268.1(4) angstrom(3), with Z = 2 for d(calc) = 1.533 Mg/m(3). X-ray analysis reveals that both glycoluril derivatives bearing two free syn-urea NH groups and two ureidyl C=O, assemble the same one-dimensional chains in the solid-state running parallel to the [110], [1-10] and [010] directions via N-H center dot center dot center dot O hydrogen bonds.”
“This study has developed a new method, near infrared fluorescent bridge polymerase chain reaction (NIRF-bPCR), for analyzing transcription MK-0518 supplier factor (TF) activity. This method was first used to detect the activity of purified nuclear factor kappa B (NF-kappa B) p50. The results demonstrated that this method could quantitatively detect the activity of p50 protein at less than 115 ng (similar to 2320 fmol), and the detection limit reached as little

as 6.94 ng (similar to 140 fmol) of p50 protein. This method was then used to detect TF activity in cell extracts. RG-7112 concentration The results revealed that this method could specifically detect NF-kappa B activity in HeLa cell nuclear extracts. Finally, this method was used to detect the activities of multiple TFs in this website a protein

sample. The results showed that this method could detect the activities of six TFs NF-kappa B, AP-1, TFIID, CREB, NF-E2, and p53-in the TNF alpha-induced and -uninduced HeLa cell nuclear extracts. Calculation of the fold induction of six TFs revealed that NF-kappa B, CREB, and AP1 were activated by TNF alpha induction in HeLa cells, in agreement with the detection results of other methods. Therefore, this study provides a new tool for analyzing TF activity. This study also revealed that NIRF-bPCR may be used as a new method for detecting DNA molecules. (C) 2013 Elsevier Inc. All rights reserved.”
“The expression and the role of renin angiotensin aldosterone system (RAAS) components on regulation of cell volume and water transport on vertebrates and invertebrates were reviewed. The presence of these components even in simple organisms like leeches and their relevance for the control of cellular volume and water transport supports the view that the expression of these components, at cellular level, is an acquisition which was preserved throughout evolution. (C) 2014 Elsevier Inc. All rights reserved.”
“Employers may be loath to fund vaccination programs without understanding the economic consequences. We developed a decision analytic computational simulation model including dynamic transmission elements that estimated the cost-benefit of employer-sponsored workplace vaccination from the employer’s perspective.

Patients undergoing HIPEC were most often white, English speaking

Patients undergoing HIPEC were most often white, English speaking, and privately insured; had a higher mean income; and had traveled Y27632 the greatest distances on average to access surgical care.”
“The angiogenesis inhibitor histidine-rich glycoprotein (HRG) constitutes one of several examples of molecules regulating both angiogenesis and hemostasis. The antiangiogenic properties of HRG

are mediated via its proteolytically released histidine- and proline-rich (His/Pro-rich) domain. Using a combination of immunohistochemistry and mass spectrometry, we here provide biochemical evidence for the presence of a proteolytic peptide, corresponding to the antiangiogenic domain of HRG, in vivo in human tissue. This finding supports a role for HRG as an endogenous regulator of angiogenesis. Interestingly, the His/Pro-rich peptide bound to the vessel wall in tissue from cancer patients but not to the vasculature AZD8055 in tissue from healthy persons. Moreover, the His/Pro-rich peptide was found in close association with platelets. Relesate from in vitro-activated platelets promoted binding

of the His/Pro-rich domain of HRG to endothelial cells, an effect mediated by Zn(2+). Previous studies have shown that zinc-dependent binding of the His/Pro-rich domain of HRG to heparan sulfate on endothelial cells is required for inhibition of angiogenesis. We describe a novel mechanism to increase the local concentration and activity of an angiogenesis inhibitor, which may reflect a host response to counteract angiogenesis check details during pathologic conditions. Our finding that tumor angiogenesis is elevated in HRG-deficient mice supports this conclusion. (Mol Cancer Res 2009;7(11): 1792-802)”
“Background Cancer survival has improved in the past 20 years, affecting the long-term risk of mood disorders. We assessed whether depression and anxiety are more common

in long-term survivors of cancer compared with their spouses and with healthy controls.\n\nMethods We systematically searched Medline, PsycINFO, Embase, Science Direct, Ingenta Select, Ovid, and Wiley Interscience for reports about the prevalence of mood disorders in patients diagnosed with cancer at least 2 years previously. We also searched the records of the International Psycho-oncology Society and for reports that cited relevant references. Three investigators independently extracted primary data. We did a random-effects meta-analysis of the prevalences of depression and anxiety in cancer patients compared with spouses and healthy controls.\n\nFindings Our search returned 144 results, 43 were included in the main analysis: for comparisons with healthy controls, 16 assessed depression and ten assessed anxiety; of the comparisons with spouses, 12 assessed depression and five assessed anxiety. The prevalence of depression was 11.6% (95% CI 7.7-16.2) in the pooled sample of 51 381 cancer survivors and 10.2% (8.0-12.6) in 217 630 healthy controls (pooled relative risk [RR] 1.11, 95% CI 0.

Interobserver variability was assessed by using 400 randomly sele

Interobserver variability was assessed by using 400 randomly selected clinical records.\n\nResults: Data on pregnancy complications and maternal anthropometric parameters were successfully recovered. Agreement between the questionnaire and records in family history data was fair, particularly for cardiovascular disease [k = 0.27; 95% confidence interval Selleck AC220 (95%CI): 0.23-0.32]. The highest agreement was observed for personal history of diabetes (k = 0.82;

95%CI 0.70-0.93), while agreement for hypertension was moderate (k = 0.60; 95%CI 0.50-0.69). Discrepancies in prepregnancy body mass index classes were observed in 10.3% women. Data were highly consistent between the two reviewers, with the highest agreement found for gestational diabetes (k = 1.00) and birth weight (99.5% concordance).\n\nConclusion: Data from the medical records and questionnaire were concordant with regard to pregnancy and well-known risk factors. The low interobserver variability did

not threaten the precision of our data. (C) 2010 SESPAS. Published by Elsevier Espana, S.L. All rights reserved.”
“Background: Carcinoid tumors are low grade, malignant, neuroendocrine neoplasms. Although rare, they represent the most common primary bronchial tumours in childhood. The aim of our study was to analyse the long-term survival and surgical treatment outcome in our young patients operated for carcinoid tumour.\n\nPatients: selleckchem We retrospectively reviewed the data of 15 paediatric patients who underwent surgery at our Institution. There were I I male and 4 female patients with a median age of 15 years (range 8-18). All carcinoids were centrally located and symptomatic.\n\nResults: We performed 10 (66.7%) parenchyma-saving procedures (5 sleeve lobectomies, 3 sleeve resections of the main bronchus, 2 bronchoplasties associated with lung resection) and 5 (33.3%) standard resections (3 bilobectomies and 2 lobectomies). There were 13 typical and 2 atypical carcinoids. Three patients (20%) had nodal metastases. There were no surgery-related deaths or complications. At long-term follow-up all patients www.selleckchem.com/MEK.html presented

with regular growth and all but one are alive. Two (13.3%) patients needed re-operation.\n\nConclusions: Results suggest that, in experienced and skilled hands, conservative procedures are the treatment of choice for the management of paediatric bronchial carcinoids. Relapses can be successfully treated with re-operation and they can occur even after many years, underlining the importance of long-term follow-up.”
“Objective To prospectively compare norfloxacin (N) with trimethoprim-sulfamethoxazole (T-S) in preventing infection in cirrhotic patients. Methods Cirrhotic patients at high risk of spontaneous bacterial peritonitis (SBP) were recruited and assigned N (400 mg daily) or T-S (160/800 mg daily). Patients were followed up for 12 months. The primary end-point was the incidence of infection.

Malnutrition is a major contributor to the double burden of disea

Malnutrition is a major contributor to the double burden of disease in South African children and adolescents.”
“Plant infection by a virus is a complex process influenced by virus-encoded factors and host components which support replication and movement. Critical factors for a successful tobamovirus infection are the viral movement protein (MP) and the host pectin methylesterase (PME), an important plant counterpart that cooperates with MP to sustain viral spread. The activity of PME is modulated by endogenous protein inhibitors (pectin methylesterase inhibitors, PMEIs). PMEIs are targeted to the extracellular matrix and typically inhibit plant PMEs by forming a specific

and stable stoichiometric 1:1 complex. Histone Methyltransf inhibitor PMEIs Navitoclax cost counteract the action of plant PMEs and therefore may affect plant susceptibility to virus. To test this hypothesis, we overexpressed genes encoding two well-characterized PMEIs in tobacco and Arabidopsis plants. Here, we report that, in tobacco plants constitutively expressing a PMEI from Actinidia chinensis (AcPMEI), systemic movement of Tobacco mosaic virus (TMV) is limited and viral symptoms are reduced. A delayed movement of Turnip vein clearing virus (TVCV) and a reduced susceptibility to the virus were also observed in Arabidopsis plants overexpressing AtPMEI-2. Our

results provide evidence that PMEIs are able to limit tobamovirus movement and to reduce plant susceptibility to the virus.”
“Myo-inositol-1,2,3,4,5,6-hexakisphosphate (InsP6), also known as phytic acid, accumulates in large

quantities in plant seeds, serving as a phosphorus reservoir, but is an GW786034 inhibitor animal antinutrient and an important source of water pollution. Here, we report that Gle1 (GLFG lethal 1) in conjunction with InsP6 functions as an activator of the ATPase/RNA helicase LOS4 (low expression of osmotically responsive genes 4), which is involved in mRNA export in plants, supporting the Gle1-InsP6-Dbp5 (LOS4 homolog) paradigm proposed in yeast. Interestingly, plant Gle1 proteins have modifications in several key residues of the InsP6 binding pocket, which reduce the basicity of the surface charge. Arabidopsis thaliana Gle1 variants containing mutations that increase the basic charge of the InsP6 binding surface show increased sensitivity to InsP6 concentrations for the stimulation of LOS4 ATPase activity in vitro. Expression of the Gle1 variants with enhanced InsP6 sensitivity rescues the mRNA export defect of the ipk1 (inositol 1,3,4,5,6-pentakisphosphate 2-kinase) InsP6-deficient mutant and, furthermore, significantly improves vegetative growth, seed yield, and seed performance of the mutant. These results suggest that Gle1 is an important factor responsible for mediating InsP6 functions in plant growth and reproduction and that Gle1 variants with increased InsP6 sensitivity may be useful for engineering high-yielding low-phytate crops.

Here, the apc5(CA) mutant background is used to study a previousl

Here, the apc5(CA) mutant background is used to study a previously uncharacterized functional antagonistic genetic interaction between Gcn5 and Hda1 that is not detected in APC5 cells.\n\nResults: Using Northerns, Westerns, reverse transcriptase PCR (rtPCR), chromatin immunoprecipitation (ChIP), and mutant phenotype suppression analysis, we observed that Hda1 and Gcn5 appear to compete for recruitment to promoters. We observed that the presence of Hda1 can partially occlude the binding of Gcn5 to the same promoter. Occlusion of Gcn5 recruitment to these promoters involved Hda1 and Tup1. Using PD98059 cost sequential ChIP we show that Hda1 and Tup1 likely form complexes at these promoters,

and that complex formation can be increased by deleting GCN5.\n\nConclusions: Our data suggests large Gcn5 and Hda1 containing complexes may compete for space on promoters that utilize the Ssn6/Tup1 repressor complex. We predict that in apc5(CA) cells the accumulation BI 6727 of an APC target may compensate for the loss of both GCN5 and HDA1.”
“Fatigue crack initiation in ductile alloys like austenitic stainless steels is mainly due to the occurrence of localized deformation in persistent slip bands (PSB). The presence of PSB is classically related to the orientation of the surface grains. In fact, the local fields in a grain does not depend on the local orientation only. The aim of the present paper is to investigate the consequences

of this observation, and to propose an analysis, where the neighborhood of the grain also plays a significant role. The study is made on a 316 stainless steel. Finite element computations using a crystal plasticity model are performed to simulate an aggregate submitted to a cyclic tension compression loading. Various configurations

of grain orientations (“clusters”) are studied at the free surface of the aggregate. A statistical selleck screening library analysis of the results is carried out to extract significant information concerning the local strain and stress fields, including the most critical arrangements of grain orientations. The introduction of local fields in classical fatigue life prediction models provides an explanation of the experimental scatter. (C) 2010 Elsevier Ltd. All rights reserved.”
“The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces marked suppression of the primary humoral immune response in virtually every animal species evaluated thus far. In addition, epidemiological studies performed in areas of dioxin contamination have identified an association between TCDD exposure and an increased incidence of non-Hodgkin’s lymphoma (NHL). Recent studies using an in vitro CD40 ligand model of human B cell differentiation have shown that TCDD impairs both B cell activation and differentiation. The present study extends these findings by identifying B cell lymphoma-6 [BCL-6] as a putative cellular target for deregulation by TCDD, which may contribute to suppression of B cell function as well as NHL.

The conjugate addition reactions proceeded smoothly in the presen

The conjugate addition reactions proceeded smoothly in the presence of 5 mol % of the chiral strontium catalyst, at room temperature, to afford the desired Flavopiridol molecular weight adducts in high yields and excellent enantioselectivities. This method provides an. efficient approach to the preparation of building blocks possessing various functional groups and possible sites for further functionalization.”
“Objective:

There are numerous challenges to successfully integrating palliative care in the intensive care unit. Our primary goal was to describe and compare the quality of palliative care delivered in an intensive care unit as rated by physicians and nurses working in that intensive care unit.\n\nDesign: Multisite study using self-report questionnaires.\n\nSetting: Thirteen hospitals throughout the United States.\n\nParticipants: Convenience

sample of 188 physicians working in critical care (attending physicians, critical care fellows, resident physicians) and 289 critical care nurses.\n\nMeasurements and Main Results: Clinicians provided overall ratings of the care delivered by either nurses or physicians in their intensive care unit for each of seven domains Captisol inhibitor of intensive care unit palliative care using a 0-10 scale (0 indicating the worst possible and 10 indicating the best possible care). Analyses included descriptive statistics to characterize measurement characteristics of the ten items, paired Wilcoxon tests comparing item ratings for the domain of symptom management with all other item ratings, and regression analyses assessing differences in ratings within and between clinical disciplines. We used p < .001 to denote statistical significance to address multiple comparisons. The ten items demonstrated good content validity with few missing responses or ceiling or floor effects. Items receiving the lowest ratings assessed spiritual

support for families, emotional support for intensive care unit clinicians, and palliative-care education for intensive care unit clinicians. All but two items were rated significantly lower than the item assessing symptom management (p < .001). Nurses rated nursing https://www.selleckchem.com/products/PF-2341066.html care significantly higher (p < .001) than physicians rated physician care in five domains. In addition, although nurses and physicians gave comparable ratings to palliative care delivered by nurses, nurses’ and physicians’ ratings of physician care were significantly different with nurse ratings of this care lower than physician ratings on all but one domain.\n\nConclusion: Our study supports the content validity of the ten overall rating items and supports the need for improvement in several aspects of palliative care, including spiritual support for families, emotional support for clinicians, and clinician education about palliative care in the intensive care unit. Furthermore, our findings provide some preliminary support for surveying intensive care unit clinicians as one way to assess the quality of palliative care in the intensive care unit.

Methods 306 patients were interviewed Demographic, socioecon

\n\nMethods 306 patients were interviewed. Demographic, socioeconomic, physical, mental health and post-ED referrals were examined. Logistic regression was used to identify factors independently associated with a repeat ED visit, OR and 95% CI are presented. Log likelihood ratio tests were used

to test for interactions.\n\nResults ED revisits were reported by 37% of this elderly population. Independent risk Z-DEVD-FMK cell line factors for a repeat ED visit were previous hospital admission OR 3.78 (95% CI 2.53 to 5.65), anxiety OR 1.13 (95% CI 1.04 to 1.22), being part of a vulnerable social network OR 2.32 (95% CI 1.12 to 4.81), whereas a unit increase in physical inability as measured by the Nottingham Health Profile had a week association OR 1.01 (95% CI 1.00 to 1.02). There were no significant interactions between social networks and the other health-related variables (p>0.05). In patients directly discharged from ED, 48% (71/148) had no documented referrals made to community services, of which 18% (27/148) were repeat ED attendees.\n\nConclusion ED act as an important safety net for older people regardless of economic or demographic backgrounds. Appropriate assessment Ricolinostat nmr and referral are an essential part of this safety role.”
“The objective of this study was to

determine the pharmacokinetic parameters of orally administered terbinafine hydrochloride based on 3, 7, and 15 mg/kg single- as well as multiple-dosage trials in order to calculate dosing requirements for potential treatment of aspergillosis in African penguins selleck screening library (Spheniscus demersus). Ten adult African penguins were used in each of these trials, with a 2-wk washout period

between trials. Mean plasma concentrations of terbinafine peaked in approximately 4 hrs at 0.11 +/- 0.017 mu g/ml (mean +/- SD) following administration of 3 mg/kg terbinafine, while 7 mg/kg and 15 mg/kg dosages resulted in peak plasma concentrations of 0.37 +/- 0.105 and 0.33 +/- 0.054 mu g/ml, respectively. The volume of distribution increased with increasing dosages, being 37 +/- 28.5, 40 +/- 28.1, and 52 +/- 18.6 mg/L for 3, 7, and 15 mg/kg doses, respectively. The mean half-life was biphasic with initial terminal half-life (t(1/2)) values of 9.9 +/- 4.5, 17.2 +/- 4.9 and 16.9 +/- 5.4 hrs, for 3, 7, and 15 mg/kg doses, respectively. A rapid first elimination phase was followed by a slower second phase, and final elimination was estimated to be 136 +/- 9.7 and 131 +/- 9.9 hrs, for 7 and 15 mg/kg doses, respectively. Linearity was demonstrated for area under the curve but not for peak plasma concentrations for the three dosages used. Calculations based on pharmacokinetic parameter values indicate that a 15 mg/kg terbinafine q24h dosage regimen would result in steady-state trough plasma concentrations above the minimum inhibitory concentration (0.8-1.