Search

Background: Overcoming immune suppression is a major barrier to eliciting potent CD8 + T cell responses against cancer. Treatment with anti-CD4 monoclonal antibody is an effective means for eliminating CD4 + Foxp3 + regulatory (Treg) cells in preclinical models and has also demonstrated efficacy in early clinical trials. However, the underlying basis for treatment efficacy, more specifically the implications of codepleting other CD4-expressing cell compartments in tumor-bearing hosts, is not well understood., Methods: Tumor-bearing mice were treated with anti-CD4 versus other therapies that preserve helper T cell function, and the priming, tissue distribution, and maintenance of tumor antigen-specific CD8 T cells were assessed. Antibody blockade and transgenic mouse models were used to determine the mechanisms of CD8 T cell priming. Single-cell RNA-sequencing (scRNAseq) was used to further characterize CD8 T cells that are primed by anti-CD4 therapy and to identify immunosuppressive CD4 T cell subsets in human melanoma following immune checkpoint blockade (ICB)., Results: Comparing anti-CD4 to dual ICB therapy, we show that anti-CD4 facilitates more robust priming of TCF-1 + , IL-2-producing, tumor-specific CD8 + T cells that disseminate to tissues and form memory. By decoupling priming from homeostatic proliferation and associated cytokines, we find that anti-CD4 functions independently of creating homeostatic space for CD8 + T cells. We also show that depletion of CD4-expressing antigen-presenting cell subsets is not required for anti-CD4 efficacy. Instead, robust tumor-specific CD8 + T cell priming and memory generation required the removal of total antigen-specific CD4 + T cells, including both Tregs and CD4 + Foxp3-negative conventional (Tconv) cells. In particular, the elimination of CD4 + Tconv cells was necessary for the accumulation and maturation of conventional type-1 dendritic cells in tumor-draining LNs, which were required for CD8 + T cell priming. Accordingly, anti-CD4 treatment restored CD8 + T cell responses in mice cotreated with dual ICB. scRNAseq of melanoma tumors from patients who received ICB revealed the presence of Tr1 and Treg subsets, as well as CD4 + Tconv subsets that lacked clear transcriptional evidence of helper differentiation., Conclusions: These findings underscore the underappreciated benefit of depleting CD4 + Tconv cells to promote systemic primary and memory CD8 + T cell responses against cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The title compound, [RuCl 2 (C 10 H 14 )(C 21 H 21 O 3 P)], crystallizes with two complex mol-ecules in the asymmetric unit. The Ru II atom has a classical three-legged piano-stool environment being coordinated by a cymene ligand [Ru-centroid = 1.707 (2)/1.704 (2) Å], a tris-(4-meth-oxy-phen-yl)phosphane ligand [Ru-P = 2.3629 (15)/2.3665 (15) Å] and two chloride atoms with the Ru-Cl bonds adopting two distinct values of 2.4068 (16)/2.4167 (16) and 2.4016 (15)/2.4244 (16) Å. The effective cone and solid angles for the phosphane ligands were calculated to be 149.5/150.2° and 25.3/25.6°, respectively. In the crystal, weak C-H⋯Cl/O/π inter-actions are observed. The crystal was refined as a two-component twin., (© Davis and Muller 2021.)

We previously described the expression of CD36 and LPL by breast cancer (BC) cells and tissues and the growth-promoting effect of VLDL observed only in the presence of LPL. We now report a model in which LPL is bound to a heparan sulfate proteoglycan motif on the BC cell surface and acts in concert with the VLDL receptor to internalize VLDLs via receptor-mediated endocytosis. We also demonstrate that gene-expression programs for lipid synthesis versus uptake respond robustly to triglyceride-rich lipoprotein availability. The literature emphasizes de novo FA synthesis and exogenous free FA uptake using CD36 as paramount mechanisms for lipid acquisition by cancer cells. We find that the uptake of intact lipoproteins is also an important mechanism for lipid acquisition and that the relative reliance on lipid synthesis versus uptake varies among BC cell lines and in response to VLDL availability. This metabolic plasticity has important implications for the development of therapies aimed at the lipid dependence of many types of cancer, in that the inhibition of FA synthesis may elicit compensatory upregulation of lipid uptake. Moreover, the mechanism that we have elucidated provides a direct connection between dietary fat and tumor biology.-.

The crystal structures of SeP(o-tol)R 2 , where o-tol is ortho-tolyl (2-methylphenyl) and R is Ph (phenyl), namely (2-methylphenyl)diphenylphosphane selenide, C 19 H 17 PSe, or Cy (cyclohexyl), namely dicyclohexyl(2-methylphenyl)phosphane selenide, C 19 H 29 PSe, were determined to aid in the evaluation of the steric and electronic behaviour of these analogous phosphane compounds. The compounds crystallized in similar monoclinic crystal systems, but are differentiated in their unit cells by a doubling of the number of independent molecules for R = Cy (Z' = 2) and the choice of glide plane by convention. The preferred orientation for the o-tolyl substituent obtained from the X-ray structural analysis is gauche for R = Ph and anti for R = Cy (using the Se-P-C ipso -C ortho torsion angles as reference). Density functional theory (DFT) calculations showed both conformations to be equally probable and indicate that the preferred solid-state conformer is probably due to the minimization of repulsion energies, resulting in a packing arrangement primarily featuring weak C-H...Se interactions and additional C-H...π interactions in the R = Ph structure. A detailed electronic and steric analysis was conducted on both phosphanes using Se-P bond lengths, multinuclear NMR 1 J Se-P coupling constants, theoretical topological evaluation and crystallographic and solid-angle calculations, and compared to selected literature examples. The results indicate that the use of the o-tolyl substituent increases both the electron-donating capability and the steric size, but is also dependent on whether the o-tolyl group adopts a gauche or anti conformation. The single-crystal geometrical data are unable to detect electronic differences between these two structures due to the somewhat large displacement parameters observed for the Se atom in the R = Cy structure.

Objectives: A collar containing 10.0% imidacloprid/4.5% flumethrin (Seresto; Bayer Animal Health) controls flea and tick infestations for 8 months and is effective in preventing transmission of Bartonella henselae and Cytauxzoon felis among cats. The purpose of this study was to compare tolerance of client-owned cats for the 10.0% imidacloprid/4.5% flumethrin collar or a physically identical placebo collar., Methods: A total of 96 client-owned cats were enrolled in the study. Cats that were systemically ill, of hairless breed or declawed in all four limbs were excluded. Cats were randomized by household to wear a placebo collar for 14 days followed by the 10.0% imidacloprid/4.5% flumethrin collar for 14 days or the 10.0% imidacloprid/4.5% flumethrin collar for 28 days. Examinations by a veterinarian were performed on days 0, 14 and 28. Owners recorded daily systemic and local health observations., Results: All but two cats, including one that entrapped the mandible in the collar and one that developed local pyodermatitis (10.0% imidacloprid/4.5% flumethrin collar), completed the 28 day study. The majority of the local lesions or licking associated with the collars occurred in the first 14 days, and licking (but not skin lesions) was more common in cats wearing the 10.0% imidacloprid/4.5% flumethrin collars. No local lesions were reported for placebo cats after switching to the 10.0% imidacloprid/4.5% flumethrin collar, and only one cat wearing the 10.0% imidacloprid/4.5% flumethrin collar had reports of licking after day 14. Housing status, single or multiple cat household, and whether a collar had been worn previously were not associated with side effects., Conclusions and Relevance: Adverse events detected for cats wearing 10.0% imidacloprid/4.5% flumethrin collars were similar to those for cats wearing placebo collars and to cats wearing identification collars in a separate study. The data suggest that most cats originally intolerant of collars become receptive over time., (© The Author(s) 2015.)

Objective: To examine the effects of phentermine combined with a meal replacement program on weight loss and food cravings and to investigate the relationship between food cravings and weight loss., Methods: In a 12-week randomized, double-blind, placebo-controlled clinical trial, 77 adults with obesity received either phentermine or placebo. All participants were provided Medifast ® meal replacements, were instructed to follow the Take Shape for Life ® Optimal Weight 5&1 Plan for weight loss, and received lifestyle coaching in the Habits of Health program. The Food Craving Inventory and the General Food Cravings State and Trait Questionnaires were used to measure food cravings., Results: The phentermine group lost 12.1% of baseline body weight compared with 8.8% in the placebo group. Cravings for all food groups decreased in both groups; however, there was a greater reduction in cravings for fats and sweets in the phentermine group compared with the placebo group. Percent weight loss correlated significantly with reduced total food cravings (r = 0.332, P = 0.009), cravings for sweets (r = 0.412, P < 0.000), and state food cravings (r = 0.320, P = 0.007)., Conclusions: Both phentermine combined with a meal replacement program and meal replacements alone significantly reduced body weight and food cravings; however, the addition of phentermine enhanced these effects., (© 2016 The Obesity Society.)

Brisk fatty acid (FA) production by cancer cells is accommodated by the Warburg effect. Most breast and other cancer cell types are addicted to fatty acids (FA), which they require for membrane phospholipid synthesis, signaling purposes, and energy production. Expression of the enzymes required for FA synthesis is closely linked to each of the major classes of signaling molecules that stimulate BC cell proliferation. This review focuses on the regulation of FA synthesis in BC cells, and the impact of FA, or the lack thereof, on the tumor cell phenotype. Given growing awareness of the impact of dietary fat and obesity on BC biology, we will also examine the less-frequently considered notion that, in addition to de novo FA synthesis, the lipolytic uptake of preformed FA may also be an important mechanism of lipid acquisition. Indeed, it appears that cancer cells may exist at different points along a "lipogenic-lipolytic axis," and FA uptake could thwart attempts to exploit the strict requirement for FA focused solely on inhibition of de novo FA synthesis. Strategies for clinically targeting FA metabolism will be discussed, and the current status of the medicinal chemistry in this area will be assessed. J. Cell. Physiol. 231: 2128-2141, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: This controlled laboratory study was designed to evaluate the efficacy of the 10 % imidacloprid/4.5 % flumethrin collar (Seresto®, Bayer Animal Health) against fleas (Ctenocephalides f. felis) on cats, when compared to fipronil (9.8 %w/w)/(s)-methoprene (11.8 % w/w) topical spot-on formulation (Frontline® Plus for Cats and Kittens, Merial)., Methods: Thirty cats were randomized into three groups of ten animals based on pre-treatment flea counts: Group 1: imidacloprid/flumethrin collar; Group 2: fipronil/(s)-methoprene topical spot-on and Group 3: non-treated controls. The imidacloprid/flumethrin collars were applied one time on Day 0, while the fipronil/(s)-methoprene spot-on was administered every 30 days from Day 0 through Day 210. Cats were infested with 100 fleas on study days 0, 7, 14, 29, 59, 89, 119, 149, 179, 209 and 239. All flea counts were conducted by combing to remove fleas on post-treatment days 2, 8, 15, 30, 60, 90, 120, 150, 180, 210 and 240., Results: The efficacy of the imidacloprid/flumethrin collar ranged from 98.2 to 100 % for eight months. The efficacy of fipronil/(s)-methoprene spot-on ranged from 68.2 to 99.9 %. Efficacy was < 85 % for fipronil/(s)-methoprene on Days 90, 150 and 210. The flea counts in both treatment groups were significantly fewer than those in the non-treated control group at every post-treatment study day (P < 0.0001). In addition, there were significantly fewer fleas in the imidacloprid/flumethrin collar group when compared to the fipronil/(s)-methoprene group on Days 90, 150 and 210 (P < 0.0001)., Conclusions: This study demonstrated that the imidacloprid/flumethrin collar (Seresto®, Bayer Animal Health) maintained excellent ( > 98.2 %) efficacy against fleas on cats for the entire 8 month study. Monthly applications of fipronil/(s)-methoprene (Frontline® Plus for Cats and Kittens, Merial) generally had high, but variable (68.2 to 99.9 %) efficacy over the course of the eight month study. Based on the very high residual efficacy achieved by the imidacloprid/flumethrin collar in this study, veterinarians should expect that this collar will control and eliminate existing flea infestations on cats and in their in-home premises as long as every flea infested host is treated.

This controlled laboratory study demonstrated the residual speed of efficacy of an imidacloprid/flumethrin collar (Seresto(®), Bayer) for the control of ticks (Dermacentor variabilis, Amblyomma americanum) at 6 and 12 hours post-infestation on dogs when compared to oral fluralaner (Bravecto(®), Merck). Dogs were randomised by pre-treatment tick counts: Group 1) imidacloprid 10 % (w/w)/flumethrin 4.5 % (w/w) collar, 2) fluralaner (dosage 25.1 - 49.4 mg/kg), and 3) non-treated controls. Ticks (50/species/dog) were infested on days 3, 14, 21, 28, 42, and 56 followed by 50 D. variabilis on days 70 and 84. Live and dead attached ticks were counted 6 and 12 hours later. Efficacy against both species at 6 and 12 hours for Group 1 was 94 - 100 %. Efficacy for Group 2 against both species at 6 hours was 4 - 69 %; efficacy at 12 hours was 8 - 100 %. Live (attached and non-attached) tick counts at 6 hours in Group 1 were significantly lower (p ≤ 0.05) than counts in Group 2 and 3 on all days. At 12 hours, live counts were significantly lower (p ≤ 0.05) in Group 1 than Group 2 for D. variabilis from days 56 - 84 and for A. americanum from days 28 - 56. There were significantly fewer (p ≤ 0.05) total ticks (total live and dead attached) on dogs in Group 1 compared to Group 2 and 3 at all time points. This study demonstrated that an imidacloprid/flumethrin collar was highly efficacious (94 - 100 %) at repelling and killing ticks on dogs at 6 and 12 hours post-infestation and was more efficacious than fluralaner as early as 6 hours post-infestation on all challenge days.

This randomised controlled laboratory study demonstrated the residual speed of efficacy of an imidacloprid/flumethrin collar (Seresto(®), Bayer) for the control of ticks (Dermacentor variabilis, Amblyomma americanum) at 6 and 12 hours postinfestation on dogs when compared to oral afoxolaner (NexGard(®), Merial). Dogs were randomised by pre-treatment tick counts: Group 1) imidacloprid 10 % (w/w) / flumethrin 4.5 % (w/w) collar, 2) afoxolaner chewable (dosage 3.1 - 6.2 mg/kg), and 3) non-treated controls. Ticks (50/species/dog) were infested on days 3, 14, 21, and 28; live (attached and non-attached) and dead attached ticks were counted 6 and 12 hours later. Efficacy against live D. variabilis at 6 hours for Group 1 was 95 - 100 % and for Group 2 was 38 - 48 %; efficacy at 12 hours for Group 1 was 97 - 100 % and for Group 2 was 27 - 59 %. Efficacy against A. americanum at 6 hours for Group 1 was 94 - 100 % and for Group 2 was < 0 - 38 %; efficacy at 12 hours for Group 1 was 98 - 100 % and for Group 2 was 1 - 40 %. Live and total (total live and dead attached) tick counts in Group 1 against both tick species were significantly lower (p ≤ 0.05) than Group 2 and 3 at all time points. The number of live or total ticks on Group 2 dogs was never significantly lower when compared to the respective number of ticks on Group 3 (controls). This study demonstrated that an imidacloprid/flumethrin collar was highly efficacious (94 - 100 %) at repelling and killing ticks on dogs at 6 and 12 hours post-infestation and was more efficacious than afoxolaner on all challenge days.

A clinical field investigation was conducted to evaluate the safety and efficacy of 10% imidacloprid/2.5% moxidectin for the treatment of ear mites (Otodectes cynotis) in dogs. The study was a multi-centered, blinded, positive controlled, randomized clinical trial conducted under field conditions with privately owned pets. A total of 17 veterinary clinics enrolled cases for the study. An otoscopic examination was performed to confirm the presence of O. cynotis residing in the ear of the dog prior to enrollment. A single-dog household was enrolled in the study if the dog had 5 or more ear mites and an acceptable physical examination. A multi-dog household was eligible if at least one dog in the household had 5 or more mites and all dogs in the household had acceptable physical exams and met the inclusion criteria. Qualified households were randomly assigned to treatments to receive either 10% imidacloprid+2.5% moxidectin topical solution or topical selamectin solution (positive control product) according to a pre-designated enrollment ratio of 2:1, respectively. If more than one dog in a multiple dog household had adequate numbers of ear mites, one dog was randomly selected to represent the household for efficacy evaluation prior to treatment. Treatments were administered twice per label and dose banding directions for each product approximately 28 days apart (Days 0 and 28), by the dog's owner at the study site. All dogs in a household were treated on the same day and with the same product. The owners completed a post-treatment observation form one day after each treatment. Post-treatment otoscopic examinations were performed by the investigators or attending veterinarian on Days 28 and 56. Physical examinations were performed on Days 0 and 56. One hundred and four (104) households were evaluated for efficacy on SD 28, and 102 households were evaluated for efficacy on SD 56. The dogs' ages ranged from 2 months to 16 years. A total of 247 dogs were evaluated for safety. Percent efficacy was based on the percentage of dogs cleared of ear mites. Mite clearance on Day 28 was 71% for the imidacloprid+moxidectin group and 69% for the selamectin group. Mite clearance on Day 56 was 82% for the imidacloprid+moxidectin group and 74% for the selamectin group. No serious adverse events associated with either product were observed during the study. The study demonstrated that 10% imidacloprid+2.5% moxidectin applied using two topical treatments, 28 days apart, was safe and achieved similar efficacy against O. cynotis as selamectin treatments applied and evaluated under the same conditions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Breast tumors often show profound sensitivity to exogenous oxidative stress. Investigational agent 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) induces aryl hydrocarbon receptor (AhR)-mediated DNA damage in certain breast cancer cells. Since AhR agonists often elevate intracellular oxidative stress, we hypothesize that 5F 203 increases reactive oxygen species (ROS) to induce DNA damage, which thwarts breast cancer cell growth. We found that 5F 203 induced single-strand break formation. 5F 203 enhanced oxidative DNA damage that was specific to breast cancer cells sensitive to its cytotoxic actions, as it did not increase oxidative DNA damage or ROS formation in nontumorigenic MCF-10A breast epithelial cells. In contrast, AhR agonist and procarcinogen benzo[a]pyrene and its metabolite, 1,6-benzo[a]pyrene quinone, induced oxidative DNA damage and ROS formation, respectively, in MCF-10A cells. In sensitive breast cancer cells, 5F 203 activated ROS-responsive kinases: c-Jun-N-terminal kinase (JNK) and p38 mitogen activated protein kinase (p38). AhR antagonists (alpha-naphthoflavone, CH223191) or antioxidants (N-acetyl-l-cysteine, EUK-134) attenuated 5F 203-mediated JNK and p38 activation, depending on the cell type. Pharmacological inhibition of AhR, JNK, or p38 attenuated 5F 203-mediated increases in intracellular ROS, apoptosis, and single-strand break formation. 5F 203 induced the expression of cytoglobin, an oxidative stress-responsive gene and a putative tumor suppressor, which was diminished with AhR, JNK, or p38 inhibition. Additionally, 5F 203-mediated increases in ROS production and cytoglobin were suppressed in AHR100 cells (AhR ligand-unresponsive MCF-7 breast cancer cells). Our data demonstrate 5F 203 induces ROS-mediated DNA damage at least in part via AhR, JNK, or p38 activation and modulates the expression of oxidative stress-responsive genes such as cytoglobin to confer its anticancer action.

Background: Bartonella henselae is transmitted amongst cats by Ctenocephalides felis and is associated with multiple clinical syndromes in cats and people. In a previous study, monthly spot-on administration of 10% imidacloprid/1% moxidectin was shown to block transmission of B. henselae amongst cats experimentally exposed to infected C. felis. The purpose of this study was to determine whether application of a flea and tick collar containing 10% imidacloprid and 4.5% flumethrin would lessen C. felis transmission of B. henselae amongst cats for 8 months., Methods: Specific pathogen free cats (n = 19) were housed in three adjoining enclosures that were separated by mesh to allow C. felis to pass among groups but prevent cats in different enclosures from contacting one another. One group of 4 cats was inoculated intravenously with B. henselae and after infection was confirmed in all cats based on positive PCR assay results, the cats were housed in the middle enclosure. The B. henselae infected cat group was flanked by a group of 8 cats that had the collar placed and maintained for the duration of the study and a group of 7 cats that were not treated. Ctenocephalides felis (50 males and 50 females) raised in an insectary were placed on each of the 4 cats in the B. henselae infected group monthly for 7 applications and then every 2 weeks for 4 applications starting the day the collar was applied. Blood was collected from all cats weekly for Bartonella spp. PCR, serology and culture., Results: While side-effects associated with the collars were not noted, persistent fever necessitating enrofloxacin therapy occurred in two of the untreated cats. While B. henselae infection was ultimately confirmed in 4 of 7 of the untreated cats, none of the cats with collars became infected (P = 0.026)., Conclusions: In this study design, use of a collar containing 10% imidacloprid and 4.5% flumethrin was well tolerated and prevented C. felis transmission of B. henselae amongst cats for 8 months.

The asymmetric unit of the title compound, [AuCl(C31H32NP)]·0.25CHCl3, contains two independent complex mol-ecules and half a chloro-form solvent mol-ecule, which is disordered across an inversion center. The Au(I) ions are each coordinated in a slightly distorted linear environment, with P-Au-Cl angles of 177.20 (4) and 178.54 (4)°.

In the title complex, [AuCl(C24H20NOP)], the ligand has N, P and O electron-donating atoms but the Au(I) atom is coordinated only by the 'soft' P atom and an additional Cl atom in an almost linear fashion. Important geometrical parameters include Au-P = 2.2321 (13) Å, Au-Cl = 2.2820 (13) Å and P-Au-Cl = 176.49 (5)°. The furan ring is disordered over two positions in a 0.51 (2):0.49 (2) ratio.

In the title complex, trans-[PtCl2{P(C6H11)2(4-Me2NC6H4)}2]·2CH2Cl2, the Pt(II) atom is located on an inversion centre, resulting in a trans-square-planar geometry. Important geometric parameters are the Pt-P and Pt-Cl bond lengths of 2.3258 (6) and 2.3106 (6) Å, respectively, and the P-Pt-Cl angles of 89.64 (2) and 90.36 (2)°. The effective cone angle for the dicyclo-hex-yl[4-(dimethyl-amino)-phen-yl]phosphane unit was calculated to be 164°. The compound crystallizes with two dichloro-methane solvent mol-ecules; one of which is severely disordered and was treated using the SQUEEZE routine in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155].

The title compound, [PdCl2(C21H12F9P)2]·CH2Cl2, crystallizes with two independent complex molecules (each having the Pd(II) atom situated on an inversion centre) and a dichloro-methane molecule in the asymmetric unit. The independent Pd(II) atoms are in perfectly linear orientations of the ligands in mutually trans positions, but distortions of the Cl-Pd-P angles ranging from 86.151 (19) to 93.849 (19)° are evident. The effective cone angles for the tris-[4-(trifluoro-meth-yl)phen-yl]phosphane ligand were calculated to be 159 and 161°. In the crystal, weak C-H⋯Cl/F inter-actions create a three-dimensional supramolecular network. Loose packing at two of the -CF3 groups resulted in large thermal vibrations which were treated as two-component disorders [occupancy ratios 0.50:0.50 and 0.628 (15):0.372 (15)].

The title compound, [Pd2{P(C10H7)2(C10H6)}2Cl2]·2CH2Cl2, shows cyclo-metalation of one naphthalen-1-yl substituent of each of the phosphane ligands to the Pd dimer in a trans orientation; the complete dimer is generated by a centre of inversion. Two dichloro-methane solvent mol-ecules create C-H⋯Cl inter-actions with the metal complex, generating supermolecular layers in the ab plane. Additional C-H⋯π and π-π [centroid-centroid distances = 3.713 (3), 3.850 (4) and 3.926 (3) Å] inter-actions join these planes into a three-dimensional supermolecular network.

The title compound, P(C10H7)3·0.5CHCl3, was isolated after the unsuccessful reaction of KSeCN and tris-(naphthalen-1-yl)phosphane. The solvent mol-ecule is disordered about an inversion center. The effective cone angle of the phosphine is 203°. In the crystal, weak C-H⋯Cl and C-H⋯π inter-actions are observed.

In the dimeric title compound, [Pd2Cl4{P(C8H9)3}2]·CH2Cl2, the metal complex molecule is situated about an inversion centre and is accompanied by a dichloro-methane solvent mol-ecule situated on a twofold rotation axis. The Pd(II) atom has a slightly distorted square-planar coordination sphere. The effective cone angle for the tris-(3,5-dimethyl-phen-yl)phos-phane ligand was calculated to be 169°. In the crystal, the metal complex and solvent mol-ecules are linked via C-H⋯Cl inter-actions, generating chains along [10-2]. There are also C-H⋯π and weak π-π inter-actions present [centroid-centroid distance = 3.990 (2) Å, plane-plane distance = 3.6352 (15) Å and ring slippage = 1.644 Å], forming of a three-dimensional structure.

The asymmetric unit of the title compound, [RuCl2(C6H6)(C18H27P)]·1.5C6H6, contains one mol-ecule of the Ru(II) complex and one and a half solvent molecules as one of these is located about a centre of inversion. The Ru(II) atom has a classical three-legged piano-stool environment being coordinated by an η(6)-benzene ligand [Ru-centroid = 1.6964 (6) Å], two chloride ligands with an average Ru-Cl bond length of 2.4138 (3) Å and a dicyclo-hexyl-phenyl-phosphane ligand [Ru-P = 2.3786 (3) Å]. The effective cone angle for the phosphane was calculated to be 158°. In the crystal, weak C-H⋯Cl hydrogen bonds link the Ru(II) complexes into centrosymmetric dimers. The crystal packing exhibits intra- and inter-molecular C-H⋯π inter-actions resulting in a zigzag pattern in the [101] direction.

In the title compound, C(17)H(14)NPSe, the P atom has a distorted tetra-hedral environment resulting in an effective cone angle of 163°. In the crystal, C-H⋯Se/N/π inter-actions are observed.

In the title compound, C(20)H(20)NPSe, the P atom lies in a distorted tetra-hedral environment. The Tolman cone angle is 157° indicating steric crowding at this atom. In the crystal, weak C-H⋯Se inter-actions create linked dimeric units and C-H⋯π inter-actions are also observed.

In the title compound, [RuCl(2)(C(6)H(6))(C(19)H(17)P)], the Ru(II) atom has a distorted pseudo-octa-hedral coordination environment with the metrical parameters around the metallic core as Ru-centroid(η(6)-benzene) = 1.6894 (11) Å, Ru-P = 2.3466 (6), Ru-Cl(avg.) = 2.4127 (7) Å; Cl-Ru-Cl = 88.07 (2) and Cl-Ru-P = 82.77 (2), 87.65 (2)°. The effective cone angle for the benzyl-diphenyl-phosphane was calculated to be 143°. In the crystal C-H⋯Cl and C-H⋯π inter-actions are observed.

In the title compound, [Rh(C(5)H(7)O(2)){C(12)H(17)P(C(6)H(11))(2)}(CO)], the Rh(I) atom is coordinated by one carbonyl C, one P and two O atoms, forming a slighlty distorted square-planar configuration.

In the title compound, [Rh(C(5)H(7)O(2))(C(18)H(14)BrP)(CO)], the Rh(I) atom adopts a slightly distorted square-planar geometry involving two O atoms [Rh-O = 2.077 (2) and 2.033 (2) Å] of the acetyl-acetonate ligand, one carbonyl C atom [Rh-C = 1.813 (2) Å] and one P atom [Rh-P = 2.242 (5) Å] of the PPh(2)(2-BrC(6)H(4)) phosphane ligand. Difference electron density maps indicate a disorder of the Br atom over two positions in an approximate 0.95:0.05 ratio. However, this disorder could not be resolved satisfactorily with the present data.

The asymmetric unit of the title compound, [PtCl(2)(C(19)H(17)P)(2)](2)·3CH(2)Cl(2), contains two complex mol-ecules and three dichloro-methane solvent mol-ecules, two of which are disordered over various positions. The Pt(II) complexes reveal a slightly distorted square-planar geometry with average Pt-P and Pt-Cl bond lengthss of 2.252 (8) and 2.363 (8) Å, respectively, and average P-Pt-P and Cl-Pt-Cl angles of 99.17 (8) and 87.1 (7)°, respectively.

The title compound, [Rh(C(5)H(7)O(2))(C(20)H(32)NP)(CO)], features an acetyl-acetonate-chelated Rh(I) cation coordinated by one P [Rh-P = 2.2525 (7) Å], one carbonyl C [Rh-C = 1.792 (3) Å] and two O [Rh-O = 2.0582 (17) and 2.0912 (18) Å] atoms in a slightly distorted square-planar geometry. Mol-ecules are packed in positions of least steric hindrance, with the phosphane ligands positioned above and below the Rh-acetyl-acetonate backbone.

Pegylated liposomal formulations contain lipid conjugated to polyethylene glycol. The disposition of encapsulated drug is dictated by the composition of the liposome, thus altering the pharmacokinetic (PK) profile of the drug. Allometric scaling is based on a power-log relationship between body weight (W) and drug clearance (CL) among mammals and has been used to compare the disposition of nonliposomal drugs across species. The objectives of this study were to use allometric scaling to: (1) compare the disposition of pegylated liposomal drugs across speciesand determine the best scaling model and (2) predict PK parameters of pegylated liposomal drugs in humans. The PK of pegylated liposomal CKD-602 (S-CKD602), doxorubicin (Doxil®), and cisplatin (SPI-077) were compared. PK studies ofS-CKD602, Doxil®, and SPI-077 were performed at the maximum tolerated dose (MTD) in male and female mice, rats, dogs and patients with refractory solid tumors. The allometric equation used to evaluate the relationship between W and CL in each species was CL = a(W)(m) (a = empirical coefficient; m = allometric exponent). Substitution of physiological variables other than body weight, such as factors representative of the mononuclear phagocyte system (MPS) were evaluated. Dedrick Plots and Maximum Life-Span Potential (MLP) were used to determine scaling feasibility. Standard allometry demonstrated a relationship between clearance of S-CKD602, Doxil®, and SPI-077 and body, spleen, liver, and kidney weights, total monocyte count, and spleen and liver blood flow. However, using scaling to predict CL of these agents in humans often resulted in differences >30%. Despite a strong correlation between body weight and MPS-associated variables with CL among preclinical species, the use of the equations did not predict CL. Thus, new methods of allometric scaling and measures of MPS function need to be developed.

Canine heartworm infection has been associated with glomerular disease and proteinuria. We hypothesized that proteinuria, likely due to glomerular damage, would also be found in cats experimentally and naturally infected with Dirofilaria immitis. Two populations of cats were evaluated, including 80 that were each experimentally infected with 60 infective heartworm larvae as part of a drug safety study, and 31 that were naturally infected with D. immitis. Each had a control population with which to be compared. In the experimentally infected group, we evaluated urine from 64 cats. Ten of these cats were shown to have microalbuminuria 8 months post infection. No cat refractory to infection with larvae and no cats from the control group demonstrated microalbuminuria. All 10 microalbuminuric cats were shown to have significant proteinuria, as measured by the urine protein:creatinine ratio. There was a subtle, but significant, association between worm burden and proteinuria, and although the presence of adult heartworms was required for the development of proteinuria, both microfilaremic and amicrofilaremic cats were affected. Neither the presence of circulating heartworm antibodies and antigen nor the presence of antigenuria predicted the development of proteinuria. Both heavily infected cats (5-25 adult heartworms) and cats with worm burdens compatible with natural infections (1-4 adult heartworms) developed proteinuria, and the relative numbers of cats so affected were similar between heavily and more lightly infected cats. Naturally infected cats, for which only dipstick protein determinations were available, were shown to have a significantly greater incidence of proteinuria (90% vs 35%) than did those in an age- and gender-matched control population. Additionally, the proteinuria in heartworm-infected cats was 3- to 5-fold greater in severity. We conclude that cats infected with mature adult heartworms are at risk for developing proteinuria and that this is recognized relatively soon after infection. While heavier infections may predispose cats to developing proteinuria, this complication is seen in naturally infected cats and experimental cats with worm burdens similar to those seen in natural infections (i.e., "clinically appropriate" worm burdens). The clinical relevance of heartworm-associated proteinuria is yet to be determined., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Medical examiner and coroner reports are a rich source of data for epidemiologic research. To maximize the utility of this information, medicolegal death investigation data need to be electronically coded. In order to determine the best option for coding, we evaluated four different options (Current Procedural Terminology [CPT], International Classification of Disease [ICD] coding, Systematized Nomenclature of Medicine Clinical Terms [SNOMED CT], and an in-house system), then conducted internal and external needs assessments to determine which system best met the needs of a centralized, statewide medical examiner's office. Although all four systems offer distinct advantages and disadvantages, SNOMED CT is the most accurate for coding pathologic diagnoses, with ICD-10 the best option for classifying the cause of death. For New Mexico's Office of the Medical Investigator, the most feasible coding option is an upgrade of an in-house coding system, followed by linkage to ICD codes for cause of death from the New Mexico Bureau of Vital Records and Health Statistics, and ideally, SNOMED classification of pathologic diagnoses.

The safety of heartworm preventives in heartworm-positive cats has traditionally been evaluated using adult Dirofilaria immitis removed from infected dogs and surgically implanted into the cats. An alternate study model uses infective larvae to establish adult infections in cats. Unfortunately, the number of adult worms resulting from the latter method varies widely from none to more than 30, both unacceptable for studies of natural heartworm infection and for studies evaluating product safety in heartworm-infected cats. We sought to determine infection severity in experimental infections via echocardiography to reduce the chances of enrolling uninfected and heavily infected cats into a study. Eighty adult cats were each inoculated with 60 infective D. immitis larvae and maintained for 8 months to allow for the development of adult worms. Antigen and antibody testing, as well as echocardiographic imaging, were performed to confirm and estimate adult worm burdens. Approximately 8 and 12 months post-infection, echocardiographic examination was performed to confirm and enumerate adult D. immitis populations in the cardiovascular system. Worm burdens were stratified as 0, 1-3, 4-11, and > 11 adults, with 0 being considered uninfected and more than 11 considered too heavily infected to be relevant for anthelmintic studies. Cats with clinically relevant infections (1-10 adults) subsequently received multiple treatments with the investigational drug, and worm burdens were confirmed by necropsy 30 days following the final treatment. Worm burden estimated with echocardiography correlated well, but not precisely, with post-mortem counts (p < 0.001, r2 = 0.67). Echocardiography under-, over-, and exactly estimated heartworm burden 53%, 27%, and 22% of the time, respectively. Although the correct category (0-4) was determined by echocardiography in only 54% of cats, positive cats were distinguished from negative cats 88% of the time and the heaviest infections (> 11) were correctly categorized 95% of the time. Both false negative and false positive results were observed. We conclude that echocardiography is useful for detecting mature experimental heartworm infections, identifying cats that have rejected mature infection, and detecting very heavy heartworm burdens, but it is only moderately accurate in classifying lesser burdens. While echocardiography cannot be relied upon to consistently determine the exact heartworm burden in experimentally infected cats, it is useful in stratifying worm burdens for anthelmintic safety studies.

The jets of icy particles and water vapor issuing from the south pole of Enceladus are evidence for activity driven by some geophysical energy source. The vapor has also been shown to contain simple organic compounds, and the south polar terrain is bathed in excess heat coming from below. The source of the ice and vapor, and the mechanisms that accelerate the material into space, remain obscure. However, it is possible that a liquid water environment exists beneath the south polar cap, which may be conducive to life. Several theories for the origin of life on Earth would apply to Enceladus. These are (1) origin in an organic-rich mixture, (2) origin in the redox gradient of a submarine vent, and (3) panspermia. There are three microbial ecosystems on Earth that do not rely on sunlight, oxygen, or organics produced at the surface and, thus, provide analogues for possible ecologies on Enceladus. Two of these ecosystems are found deep in volcanic rock, and the primary productivity is based on the consumption by methanogens of hydrogen produced by rock reactions with water. The third ecosystem is found deep below the surface in South Africa and is based on sulfur-reducing bacteria consuming hydrogen and sulfate, both of which are ultimately produced by radioactive decay. Methane has been detected in the plume of Enceladus and may be biological in origin. An indicator of biological origin may be the ratio of non-methane hydrocarbons to methane, which is very low (0.001) for biological sources but is higher (0.1-0.01) for nonbiological sources. Thus, Cassini's instruments may detect plausible evidence for life by analysis of hydrocarbons in the plume during close encounters.

Internationally, there are countless initiatives to build National Healthcare Information Networks (NHIN) that electronically interconnect healthcare organizations by enhancing and integrating current information technology (IT) capabilities. The realization of such NHINs will enable the simple and immediate exchange of appropriate and vital clinical data among participating organizations. In order for institutions to accurately and automatically exchange information, the electronic clinical documents must make use of established clinical codes, such as those of SNOMED-CT, LOINC and ICD-9 CM. However, there does not exist one universally accepted coding scheme that encapsulates all pertinent clinical information for the purposes of patient care, clinical research and population heatlh reporting. In this paper, we propose a combination of methods and standards that target the harmonization of clinical terminologies and encourage sustainable, interoperable infrastructure for healthcare.

Sixteen controlled laboratory studies, involving 420 kittens and cats, were conducted to evaluate the efficacy and safety of topically applied formulations of imidacloprid and moxidectin for the prevention of feline heartworm disease, treatment of flea infestations and treatment and control of intestinal nematodes. Unit-dose applicators and the dosing schedule used in these studies were designed to provide a minimum of 10mg imidacloprid and 1mg moxidectin/kg. Treatments were applied topically by parting the hair at the base of the skull and applying the solution on the skin. Imidacloprid treatment alone did not display activity against Dirofilaria immitis or intestinal nematodes and moxidectin treatment alone provided little or no activity against adult Ctenocephalides felis infestations. The formulation containing 10% imidacloprid and 1% moxidectin was 100% efficacious against the development of adult D. immitis infections when cats were treated 30 days after inoculation with third-stage larvae. A single treatment with this formulation also provided 88.4-100% control of adult C. felis for 35 days. Imidacloprid/moxidectin was 100% efficacious against adult Toxocara cati and 91.0-98.3% efficacious against immature adults and fourth-stage T. cati larvae. The formulation provided 98.8-100% efficacy against adult Ancylostoma and immature adults and third-stage A. tubaeforme larvae. Monthly topical application with 10% imidacloprid/1% moxidectin is convenient, efficacious and safe for the prevention of feline heartworm disease, treatment of flea infestation and for the treatment and control of intestinal nematode infections of cats.

Two controlled, blinded and randomized multi-site clinical field studies evaluated the efficacy and safety of emodepside/praziquantel spot-on in the treatment of gastrointestinal nematode and cestode infections in cats. In a study conducted in Europe, faecal egg count reductions of >98% for all nematode eggs and eggs of Toxocara cati, respectively, were observed in cats treated with emodepside/praziquantel spot-on (Profender, Bayer AG, Leverkusen, Germany). For a positive-control product containing selamectin (Stronghold) reductions of >95% were observed. A 100% reduction of faecal eggs and proglottids was observed in cats treated with emodepside/praziquantel spot-on that were infected with cestodes. In a study conducted in North America, cats were treated with either emodepside/praziquantel spot-on plus a placebo tablet or a combination of two control products containing, respectively, selamectin (Revolution) and epsiprantel (Cestex). Faecal egg count reduction for eggs of T. cati was >99% for both treatments. For faecal eggs and proglottids of Dipylidium caninum reductions of >99 and >97% were recorded for cats treated with emodepside/praziquantel spot-on and the control group, respectively. No adverse reactions were observed in the European study, and only mild ones of short duration in a few cats from both treatment groups of the North American study. The two studies demonstrated that emodepside/praziquantel spot-on is highly efficacious and safe under field conditions.

A topically applied formulation containing 10% imidacloprid+1% moxidectin (Advocate/Advantage multi) has been developed for monthly application to cats for the prevention of feline heartworm (HW) disease caused by Dirofilaria immitis; and for the treatment and control of flea infestations, ear mite infestations, and intestinal nematode infections. A study model was designed to evaluate the safety of this product in cats harboring adult D. immitis infections. Eighty adult cats (40 males/40 females) were each inoculated with 60 third-stage D. immitis larvae on test day (TD) 1. On TD 243-245 echocardiographic imaging was performed on each cat to confirm and estimate the number of adult D. immitis residing in the cardiovascular system. A total of 35 cats were subsequently eligible for safety evaluation based on inclusion criteria. Four treatment groups were established and randomly selected for treatment: imidacloprid+moxidectin solution at the label dose (n=9) (group 1), imidacloprid+moxidectin solution at 5x the Iabel dose (n=9) (group 2), 6% selamectin topical solution (Revolution) at the label dose (positive control, n=8) (group 3), and topical treatment with placebo (negative control, n=9) (group 4). All cats were treated on TD 250. Treatments for groups 1, 3, and 4 were repeated on TDs 278 and 306. Group 2 cats were euthanized and examined for adult D. immitis on TD 288. All other cats were euthanized and examined for adult D. immitis on TD 334. No adverse events attributable to treatment with the test articles were observed during the study. The geometric mean numbers of adult D. immitis recovered at necropsy from treatment groups 1-4 were 2.9, 3.2., 4.0, and 2.7, respectively. There were no statistically significant differences in the comparison of adult D. immitis recovered at necropsy (ANOVA overall group effect P-value of 0.5356). The results of this study demonstrate that imidacloprid+moxidectin topical solution can be used safely in cats heavily infected with adult D. immitis.

We examined the effects of 5 microg/ml ponazuril treatment on developing tachyzoites of Neospora caninum and merozoites of Sarcocystis neurona to better determine the mode of action of this anticoccidial drug. Both parasites develop asexually by endogenesis. Neospora caninum was selected for study because it develops by endodyogeny, which results in two tachyzoites being produced internally, and S. neurona was selected because it develops by endopolygeny which results in many merozoites being produced internally. Ponazuril inhibited development of N. caninum after approximately 48 h post-exposure. Treated tachyzoites of N. caninum developed vacuoles and underwent degeneration. Ponazuril also inhibited development of merozoites of S. neurona. Treated merozoites and maturing schizonts of S. neurona developed vacuoles and underwent degeneration. The ability of S. neurona schizonts to undergo cytokinesis was inhibited. Our results are discussed in relation to previous ultrastructural research on endogenesis of tachyzoites of Toxoplasma gondii undergoing endodyogeny which indicated that ponazuril induced multinucleate stage formation and inhibited cytokinesis. Ponazuril is believed to act on the apicoplast and our study demonstrates that this agent may express its inhibitory effects in different phenotypic manners on different apicomplexan parasites. The enzyme/enzyme systems that are the inhibitory target of ponazuril may be different in these apicomplexans, or the results of inhibition may affect different pathways downstream of its initial site of action in these parasites.

Toxoplasma gondii is an important apicomplexan parasite of humans and other warm-blooded animals. Ponazuril is a triazine anticoccidial recently approved for use in horses in the United States. We determined that ponazuril significantly inhibited T. gondii tachyzoite production (P < 0.05) at 5.0, 1.0, or 0.1 microg/ml in African green monkey kidney cells. We used outbred female CD-1 mice to determine the efficacy of ponazuril in preventing and treating acute toxoplasmosis. Each mouse was subcutaneously infected with 1,000 tachyzoites of the RH strain of T. gondii. Mice were weighed daily, and ponazuril was administered orally in a suspension. Mice given 10 or 20 mg/kg body weight ponazuril 1 day before infection and then daily for 10 days were completely protected against acute toxoplasmosis. Relapse did not occur after prophylactic treatments were stopped. Toxoplasma gondii DNA could not be detected in the brains of these mice using polymerase chain reaction (PCR). One hundred percent of mice treated with 10 or 20 mg/kg ponazuril at 3 days after infection and then daily for 10 days were protected from fatal toxoplasmosis. Sixty percent of mice treated with 10 mg/kg ponazuril at 6 days after infection and 100% of mice treated with 20 mg/kg or 50 mg ponazuril 6 days after infection and then daily for 10 days were protected from fatal toxoplasmosis. Relapse did not occur after treatments were stopped. Toxoplasma gondii DNA was detected in the brains of some, but not all, of these mice using PCR. The results demonstrate that ponazuril is effective in preventing and treating toxoplasmosis in mice. It should be further investigated as a safe and effective treatment for this disease in animals.

Toxoplasma gondii is an important apicomplexan parasite of humans and other warm-blooded animals. Ponazuril is a triazine anticoccidial recently approved for use in horses in the United States. We investigated the mode of action of ponazuril against developing RH strain T. gondii tachyzoites in African green monkey kidney cells. Host cells were infected with 2.0 x 10(5) tachyzoites and treated with 5 microg/ml ponazuril. Cultures were fixed and examined by transmission electron microscopy 3 days after treatment. Ponazuril interfered with normal parasite division. This led to the presence of multinucleate schizonts stages. Up to six tachyzoites were observed partially budded from the surface of these schizonts. Large vacuoles developed in these schizonts and they eventually degenerated.

NGF can regulate nitric oxide synthase (NOS) expression and nitric oxide (NO) can modulate NGF-mediated neurotrophic responses. To investigate the role of NO in NGF-activated expression of cholinergic phenotype, PC12 cells were treated with either the nonselective NOS inhibitor L-NAME (N (omega)-nitro-L-arginine methylester) or the inducible NOS selective inhibitor MIU (s-methylisothiourea), and the effect on NGF-stimulated ChAT mRNA levels and ChAT specific activity was determined. NGF increased steady-state levels of mRNA and protein for both inducible and constitutive isozymes of NOS in PC12 cells, and led to enhanced NOS activity and NO production. MIU and, to a lesser extent, L-NAME blocked neurite outgrowth in nerve growth factor (NGF)-treated PC12 cells. Both L-NAME and MIU attenuated NGF-mediated increases in choline transferase (ChAT)-specific activity and prevented the increase in expression of ChAT mRNA normally produced by NGF treatment of PC12 cells. The present study indicates that NO may be involved in the modulation of signal transduction pathways by which NGF leads to increased ChAT gene expression in PC12 cells.

We investigated mechanisms underlying nerve growth factor-mediated morphological differentiation and expression of cholinergic neuronal phenotype. In PC12, but not PC12nnr5 cells, nerve growth factor induces neurite-like outgrowths and enhances cholinergic phenotype; stable expression of TrkA receptors in nnr5 cells (called B5P cells) restores morphological differentiation but not expression of choline acetyltransferase. Transfection with an AP-1 luciferase reporter gene revealed that PC12 but not B5P cells expressed nerve growth factor-induced functional AP-1 activity. RT-PCR analysis of nerve growth factor-mediated changes in AP-1 transcription factors showed rapid increases in c-fos and junB mRNA in PC12 and B5P cells, while increases in c-jun were small. Using DNA-protein gel shift assays we determined that nerve growth factor stimulates AP-1 binding in both PC12 and B5P cells, and identified c-Fos, FosB, Fra-1, Fra-2, c-Jun, JunB and JunD in AP-1 complexes. In Fos/Jun functional luciferase reporter assays, nerve growth factor stimulated phosphorylation of c-Fos in both PC12 and B5P cells, but phosphorylation of c-Jun only in PC12, and not in B5P cells. These data indicate that mechanisms relating to AP-1 transcription factor complexes underlying nerve growth factor-mediated enhancement of cholinergic gene expression may differ from those required for morphological differentiation.

Choline acetyltransferase, the enzyme that synthesizes the transmitter acetylcholine in cholinergic neurons, is a substrate for protein kinase C. In the present study, we used mass spectrometry to identify serine 440 in recombinant human 69-kDa choline acetyltransferase as a protein kinase C phosphorylation site, and site-directed mutagenesis to determine that phosphorylation of this residue is involved in regulation of the enzyme's catalytic activity and binding to subcellular membranes. Incubation of HEK293 cells stably expressing wild-type 69-kDa choline acetyltransferase with the protein kinase C activator phorbol 12-myristate 13-acetate showed time- and dose-related increases in specific activity of the enzyme; in control and phorbol ester-treated cells, the enzyme was distributed predominantly in cytoplasm (about 88%) with the remainder (about 12%) bound to cellular membranes. Mutation of serine 440 to alanine resulted in localization of the enzyme entirely in cytoplasm, and this was unchanged by phorbol ester treatment. Furthermore, activation of mutant enzyme in phorbol ester-treated HEK293 cells was about 50% that observed for wild-type enzyme. Incubation of immunoaffinity purified wild-type and mutant choline acetyltransferase with protein kinase C under phosphorylating conditions led to incorporation of [(32)P]phosphate, with radiolabeling of mutant enzyme being about one-half that of wild-type, indicating that another residue is phosphorylated by protein kinase C. Acetylcholine synthesis in HEK293 cells expressing wild-type choline acetyltransferase, but not mutant enzyme, was increased by about 17% by phorbol ester treatment.

The human natural blind spot is usually filled in based on the contextual information. When two sufficiently different images are presented to the two eyes, observers typically perceive an alternation between the two images (binocular rivalry). Both the filling-in process and binocular rivalry have been the subject of considerable research. This study investigates whether filled information in one eye's natural blind spot can contribute to binocular rivalry. A radial grating (D=12 degrees ) was presented to one eye, centered on the natural blind spot. Observers perceived a complete figure in monocular view; the blind spot area was filled-in based on the surrounding information. Simultaneously, a circular grating smaller than the blind spot (D=4 degrees ), was presented to the fellow eye in the region corresponding to the other eye's blind spot. The amount of rivalry as indexed by how often the smaller circular grating remained visible was measured. The results suggest that the filled information in the area of the blind spot does contribute to the rivalry process.