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Anti-inflammatory effects of chicanine on murine macrophage by down-regulating LPS-induced inflammatory cytokines in IκBα/MAPK/ERK signaling pathways
Chen, Haixia
Sohn, Johann
Zhang, Likang
Tian, Jingge
Chen, Shuhan
Bjeldanes, Leonard F.
European journal of pharmacology
Schisandra chinensis Baill is a Chinese traditional medicine with multiple pharmacological activities. In this study, chicanine, one of the major lignan compounds of Schiandra chinesis, was investigated for suppressive effects on lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages (RAW 264.7 cells). Chicanine was found to have anti-infammatory properties with the inhibition of nitric oxide (NO) and Prostaglandin E (2) (PGE2) production and nuclear factor-κB (NF-κB) signaling in LPS-stimulated RAW 264.7 cells with no cytotoxic effects. Treatment of RAW 264.7 cells with chicanine down-regulated LPS-induced expression of pro-inflammatory cytokines including TNFα, IL-1β, MCP-1, G-CSF, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). These inhibitory effects were found with the blockage of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 (ERK 1/2), and also IκB-α phosphorylation. These results indicated that anti-inflammatory actions of chicanine in macrophages involved inhibition of LPS-induced TLR4-IκBα/MAPK/ERK signaling pathways.
Chicanine; inflammatory cytokines; IκBα; MAPK; ERK
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Neuroprotective targets through which 6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one (SN79), a sigma receptor ligand, mitigates the effects of methamphetamine in vitro
Kaushal, Nidhi
Robson, Matthew J.
Rosen, Abagail
McCurdy, Christopher R.
Matsumoto, Rae R.
European journal of pharmacology
Exposure to high or repeated doses of methamphetamine can cause hyperthermia and neurotoxicity, which are thought to increase the risk of developing a variety of neurological conditions. Sigma receptor antagonism can prevent methamphetamine-induced hyperthermia and neurotoxicity, but the underlying cellular targets through which the neuroprotection is conveyed remain unknown. Differentiated NG108-15 cells were thus used as a model system to begin elucidating the neuroprotective mechanisms targeted by sigma receptor antagonists to mitigate the effects of methamphetamine. In differentiated NG108-15 cells, methamphetamine caused the generation of reactive oxygen/nitrogen species, an increase in PERK-mediated endoplasmic reticulum stress and the activation of caspase-3, -8 and -9, ultimately resulting in apoptosis at micromolar concentrations, and necrotic cell death at higher concentrations. The sigma receptor antagonist, 6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one (SN79), attenuated methamphetamine-induced increases in reactive oxygen/nitrogen species, activation of caspase-3,-8 and-9 and accompanying cellular toxicity. In contrast, 1,3-di(2-tolyl)-guanidine (DTG), a sigma receptor agonist, shifted the dose response curve of methamphetamine-induced cell death towards the left. To probe the effect of temperature on neurotoxicity, NG108-15 cells maintained at an elevated temperature (40 °C) exhibited a significant and synergistic increase in cell death in response to methamphetamine, compared to cells maintained at a normal cell culture temperature (37 °C). SN79 attenuated the enhanced cell death observed in the methamphetamine-treated cells at 40 °C. Together, the data demonstrate that SN79 reduces methamphetamine-induced reactive oxygen/nitrogen species generation and caspase activation, thereby conveying neuroprotective effects against methamphetamine under regular and elevated temperature conditions.
Apoptosis; Caspase; Methamphetamine; Necrosis; Reactive oxygen species; Sigma receptors
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Sexual dimorphism in rat aortic endothelial function of streptozotocin-induced diabetes: possible involvement of superoxide and nitric oxide production
Han, Xiaoyuan
Zhang, Rui
Anderson, Leigh
Rahimian, Roshanak
European journal of pharmacology
Little is known of the interactions between diabetes and sex on vascular function. The objectives of this study were to investigate whether there were sex differences in rat aortic endothelial function one week after the induction of streptozotocin (STZ)-diabetes, and to examine the potential roles of superoxide and nitric oxide (NO) in this sex-specific effect. Endothelium-dependent vasodilatation to acetylcholine (ACh) was measured in rat aortic rings before and after treatment with MnTMPyP (25 μM), a superoxide dismutase. Contractile responses to phenylephrine (PE) were generated before and after treatment with L-NAME (200 μM), a nitric oxide synthase (NOS) inhibitor. The mRNA expression of NADPH oxidase (Nox) and endothelial nitric oxide synthase (eNOS) were also determined. We demonstrated that 1) STZ-diabetes impaired endothelium-dependent vasodilatation to ACh to a greater extent in female than male aortae, 2) inhibition of superoxide enhanced sensitivity to ACh only in diabetic females, and 3) Nox1 and Nox4 mRNA expression was significantly elevated only in aortic tissue of diabetic females. Furthermore, incubation of aortic rings with L-NAME potentiated PE responses in all groups, but aortae from control females showed a greater potentiation of the PE response after NOS inhibition compared with others. STZ-diabetes reduced the extent of PE potentiation after L-NAME and the aortic eNOS mRNA expression in females to the same levels as seen in males. These data suggest that a decrease in NO, resulting from either decreased eNOS or elevated superoxide, may partially contribute to the predisposition of the female aorta to injury early in diabetes.
Sex difference; diabetes; endothelial dysfunction; nitric oxide; superoxide
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2-methoxyestradiol binding of GPR30 down-regulates angiotensin AT1 receptor
Koganti, Sivaramakrishna
Snyder, Russell
Gumaste, Upendra
Karamyan, Vardan T.
Thekkumkara, Thomas
European journal of pharmacology
Controlling angiotensin AT1 receptor function has been shown to be protective for many pathophysiological disorders. Although estrogen metabolite, 2-methoxyestradiol (2ME2) can down-regulate angiotensin AT1 receptor expression independently of nuclear receptors, no specific cellular targets have been identified. This study was focused on identification and validation of a cellular target responsible for 2ME2-mediated angiotensin AT1 receptor down-regulation in a continuously passaged rat liver epithelial cell line. Cell membranes were isolated and used to determine 2ME2 specific binding. Cell membranes exposed to [3H]2ME2 showed specific saturable binding, which was found to be pertussis toxin (PTx) sensitive. Under similar conditions, G-protein coupled receptor 30 (GPR30) agonist (G1) and antagonist (G15) inhibited 2ME2 specific binding. In these cells GPR30 was found localized to endoplasmic reticulum (ER) membranes. In intact cells, G1 down-regulated angiotensin AT1 receptor expression and this effect was reversed by G15. Furthermore, 2ME2 mediated activation of epidermal growth factor receptor (EGFR) followed by ERK1/2 phosphorylation, an essential signaling step in angiotensin AT1 receptor down-regulation, was abrogated by G15, suggesting that this signal is GPR30 dependent. Additionally, EGF was found to independently down-regulate angiotensin AT1 receptor in an ERK1/2-dependent manner. In summary, our results demonstrate for the first time that 2ME2 down-regulation of angiotensin AT1 receptor is dependent on ER membrane-associated GRP30. Moreover, this effect is facilitated by GPR30 dependent transactivation of EGFR and ERK1/2 phosphorylation. This study provides further understanding of the physiological significance of 2ME2 and its role in modulating angiotensin AT1 receptor expression.
Angiotensin II; angiotensin AT1 receptor; 2-Methoxyestradiol (2ME2); G-Protein coupled receptor 30 (GPR30); MAP-Kinase; Epidermal growth factor receptor (EGFR)
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Mechanism-Driven Phase I Translational Study of Trifluoperazine in Adults with Sickle Cell Disease
Molokie, Robert E.
Wilkie, Diana J.
Wittert, Harriett
Suarez, Marie L.
Yao, Yingwei
Zhao, Zhongsheng
He, Ying
Wang, Zaijie J.
European journal of pharmacology
Recent evidence of neuropathic pain among adults with sickle cell disease (SCD) reveals a need for adjuvant analgesic treatments for these patients. Ca2+/calmodulin protein kinase IIα (CaMKIIα) has a known role in neuropathic pain and trifluoperazine is a potent CaMKIIα inhibitor. The study aim was to determine trifluoperazine's acute effects, primarily on adverse effects and secondarily on pain intensity reduction, in adults with SCD. In a phase I, open-label study of 6 doses of trifluoperazine (0.5, 1, 2, 5, 7.5, 10 mg), we obtained 7-hourly and 24-hour repeated measures of adverse effects, pain intensity, and supplemental opioid analgesics in 18 adults with SCD (18 hemoglobin SS disease, 15 women, average age 35.8 ± 8.9 years, ranged 23-53) each of whom received a single dose. Data were analyzed with descriptive statistics. Subjects reported moderate to severe sedative effects at 7.5 and 10 mg doses, respectively. Eight subjects reported 50% reduction in chronic pain without severe sedation or supplemental opioid analgesics; one of these subjects had dystonia 24.5 hrs after the 10 mg dose. The analgesic effect lasted for at least 24 hrs in 3 subjects. Sedation resolved with caffeine and dystonia resolved with diphenhydramine. Adults with SCD experienced minimal adverse effects at doses under 10 mg. In this molecular mechanism-driven translational study, trifluoperazine shows promise as an analgesic drug that is worthy of further testing in a randomized controlled study of adults with SCD starting at a dose of 1 mg in repeated doses to determine long-term adverse and analgesic effects.
sickle cell disease; neuropathic pain; phase 1 study; safety; trifluoperazine
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Genomic and non-genomic regulation of PGC1 isoforms by estrogen to increase cerebral vascular mitochondrial biogenesis and reactive oxygen species protection
Kemper, Martin F.
Stirone, Chris
Krause, Diana N.
Duckles, Sue P.
Procaccio, Vincent
European journal of pharmacology
We previously found that estrogen exerts a novel protective effect on mitochondria in brain vasculature. Here we demonstrate in rat cerebral blood vessels that 17β-estradiol (estrogen), both in vivo and ex vivo, affects key transcriptional coactivators responsible for mitochondrial regulation. Treatment of ovariectomized rats with estrogen in vivo lowered mRNA levels of peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α) but increased levels of the other PGC-1 isoforms: PGC-1β and PGC-1 related coactivator (PRC). In vessels ex vivo, estrogen decreased protein levels of PGC-1α via activation of phosphatidylinositol 3-kinase (PI3K). Estrogen treatment also increased phosphorylation of forkhead transcription factor, FoxO1, a known pathway for PGC-1α downregulation. In contrast to the decrease in PGC-1α, estrogen increased protein levels of nuclear respiratory factor 1, a known PGC target and mediator of mitochondrial biogenesis. The latter effect of estrogen was independent of PI3K, suggesting a separate mechanism consistent with increased expression of PGC-1β and PRC. We demonstrated increased mitochondrial biogenesis following estrogen treatment in vivo; cerebrovascular levels of mitochondrial transcription factor A and electron transport chain subunits as well as the mitochondrial/ nuclear DNA ratio were increased. We examined a downstream target of PGC-1β, glutamate-cysteine ligase (GCL), the rate-limiting enzyme for glutathione synthesis. In vivo estrogen increased protein levels of both GCL subunits and total glutathione levels. Together these data show estrogen differentially regulates PGC-1 isoforms in brain vasculature, underscoring the importance of these coactivators in adapting mitochondria in specific tissues. By upregulating PGC-1β and/or PRC, estrogen appears to enhance mitochondrial biogenesis, function and reactive oxygen species protection.
Cerebral blood vessels; Estrogen; Glutamate-cysteine ligase; Mitochondria; Peroxisome proliferator-activated; receptor-gamma coactivator-1 (PGC-1); Glutathione
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Quantitative pharmacological analyses of the interaction between flumazenil and midazolam in monkeys discriminating midazolam: determination of the functional half life of flumazenil
Zanettini, Claudio
France, Charles P.
Gerak, Lisa R.
European journal of pharmacology
The duration of action of a drug is commonly estimated using plasma concentration, which is not always practical to obtain or an accurate estimate of functional half life. For example, flumazenil is used clinically to reverse the effects of benzodiazepines like midazolam; however, its elimination can be altered by other drugs, including some benzodiazepines, thereby altering its half life. This study used Schild analyses to characterize antagonism of midazolam by flumazenil and determine the functional half life of flumazenil. Four monkeys discriminated 0.178 mg/kg midazolam while responding under a fixed-ratio 10 schedule of stimulus-shock termination; flumazenil was given at various times before determination of a midazolam dose-effect curve. There was a time-related decrease in the magnitude of shift of the midazolam dose-effect curve as the interval between flumazenil and midazolam increased. The potency of flumazenil, estimated by apparent pA2 values (95% CI), was 7.30 (7.12, 7.49), 7.17 (7.03, 7.31), 6.91 (6.72, 7.10) and 6.80 (6.67, 6.92) at 15, 30, 60 and 120 min after flumazenil administration, respectively. The functional half life of flumazenil, derived from potency estimates, was 57 ± 13 min. Thus, increasing the interval between flumazenil and midazolam causes orderly decreases in flumazenil potency; however, across a broad range of conditions, the qualitative nature of the interaction does not change, as indicated by slopes of Schild plots at all time points that are not different from unity. Differences in potency of flumazenil are therefore due to elimination of flumazenil and not due to pharmacodynamic changes over time.
midazolam; flumazenil; benzodiazepine; drug discrimination; rhesus monkey
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Hemodynamic effects and histamine release elicited by the selective adenosine A3 receptor agonist 2-Cl-IB-MECA in conscious rats
Van Schaick, Erno A.
Jacobson, Kenneth A.
Kim, Hea O.
IJzerman, Adriaan P.
Danhof, Meindert
European journal of pharmacology
The hemodynamic effects of the novel, selective adenosine A3 receptor agonist 2-chloro-N6-(3-iodobenzyl)adenosine-5′-N-methyl-carboxamide (2-Cl-IB-MECA) were investigated in conscious rats. Intravenous administration of 200 μg/kg 2-Cl-IB-MECA resulted in a short-lasting hypotension, which was accompanied by a 50–100-fold increase in plasma histamine concentrations. Administration of a second dose of 2-Cl-IB-MECA did not elicit any hemodynamic effects. Also no histamine release was observed after the second dose. The observation of rapid tachyphylaxis in combination with histamine release suggests that mast cell mediator release plays a key role in the hemodynamic effects of adenosine A3 receptor agonists.
Adenosine A3 receptor; Hemodynamics; Histamine release; Tachyphylaxis; 2-Chloro-N6-(3-iodobenzyl)adenosine-5-N-methylcarboxamide (2-Cl-IB-MECA); Rat, conscious
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Regulation of nausea and vomiting by cannabinoids and the endocannabinoid system
Sharkey, Keith A.
Darmani, Nissar A.
Parker, Linda A.
European journal of pharmacology
Nausea and vomiting (emesis) are important elements in defensive or protective responses that animals use to avoid ingestion or digestion of potentially harmful substances. However, these neurally-mediated responses are at times manifested as symptoms of disease and they are frequently observed as side-effects of a variety of medications, notably those used to treat cancer. Cannabis has long been known to limit or prevent nausea and vomiting from a variety of causes. This has led to extensive investigations that have revealed an important role for cannabinoids and their receptors in the regulation of nausea and emesis. With the discovery of the endocannabinoid system, novel ways to regulate both nausea and vomiting have been discovered that involve the production of endogenous cannabinoids acting centrally. Here we review recent progress in understanding the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system, and we discuss the potential to utilize the endocannabinoid system in the treatment of these frequently debilitating conditions.
Cannabis; serotonin; emesis; brainstem; insular cortex; CB1 receptor; CB2 receptor
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The role of vagal neurocircuits in the regulation of nausea and vomiting
Babic, Tanja
Browning, Kirsteen N.
European journal of pharmacology
Nausea and vomiting are among the most frequently occurring symptoms observed by clinicians. While advances have been made in understanding both the physiological as well as the neurophysiological pathways involved in nausea and vomiting, the final common pathway(s) for emesis have yet to be defined. Regardless of the difficulties in elucidating the precise neurocircuitry involved in nausea and vomiting, it has been accepted for over a century that the locus for these neurocircuits encompasses several structures within the medullary reticular formation of the hindbrain and that the role of vagal neurocircuits in particular are of critical importance. The afferent vagus nerve is responsible for relaying a vast amount of sensory information from thoracic and abdominal organs to the central nervous system. Neurons within the nucleus of the tractus solitarius not only receive these peripheral sensory inputs but have direct or indirect connections with several other hindbrain, midbrain and forebrain structures responsible for the co-ordination of the multiple organ systems. The efferent vagus nerve relays the integrated and co-ordinated output response to several peripheral organs responsible for emesis. The important role of both sensory and motor vagus nerves, and the available nature of peripheral vagal afferent and efferent nerve terminals, provides extensive and readily accessible targets for the development of drugs to combat nausea and vomiting.
Vagus; Brainstem; NTS; DVC
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Pathophysiological and neurochemical mechanisms of postoperative nausea and vomiting
Horn, Charles C.
Wallisch, William J.
Homanics, Gregg E.
Williams, John P.
European journal of pharmacology
Clinical research shows that postoperative nausea and vomiting (PONV) is caused primarily by the use of inhalational anesthesia and opioid analgesics. PONV is also increased by several risk predictors, including a young age, female sex, lack of smoking, and a history of motion sickness. Genetic studies are beginning to shed light on the variability in patient experiences of PONV by assessing polymorphisms of gene targets known to play roles in emesis (serotonin type 3, 5-HT3; opioid; muscarinic; and dopamine type 2, D2, receptors) and the metabolism of antiemetic drugs (e.g., ondansetron). Significant numbers of clinical trials have produced valuable information on pharmacological targets important for controlling PONV (e.g., 5-HT3 and D2), leading to the current multi-modal approach to inhibit multiple sites in this complex neural system. Despite these significant advances, there is still a lack of fundamental knowledge of the mechanisms that drive the hindbrain central pattern generator (emesis) and forebrain pathways (nausea) that produce PONV, particularly the responses to inhalational anesthesia. This gap in knowledge has limited the development of novel effective therapies of PONV. The current review presents the state of knowledge on the biological mechanisms responsible for PONV, summarizing both preclinical and clinical evidence. Finally, potential ways to advance the research of PONV and more recent developments on the study of postdischarge nausea and vomiting (PDNV) are discussed.
Nausea; Vomiting; Emesis; Anesthesia; Surgery; Opioid
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Mucosally-directed adrenergic nerves and sympathomimetic drugs enhance non-intimate adherence of Escherichia coli O157:H7 to porcine cecum and colon
Chen, Chunsheng
Lyte, Mark
Stevens, Mark P.
Vulchanova, Lucy
Brown, David R.
European journal of pharmacology
The sympathetic neurotransmitter norepinephrine has been found to increase mucosal adherence of enterohemorrhagic Escherichia coli O157:H7 in explants of murine cecum and porcine distal colon. In the present study, we tested the hypothesis that norepinephrine augments the initial, loose adherence of this important pathogen to the intestinal mucosa. In mucosal sheets of porcine cecum or proximal, spiral and distal colon mounted in Ussing chambers, norepinephrine (10 µM, contraluminal addition) increased mucosal adherence of wild-type E. coli O157:H7 strain 85–170; in the cecal mucosa, this effect occurred within 15 – 90 min after bacterial inoculation. In addition, norepinephrine transiently increased short-circuit current in cecal and colonic mucosal sheets, a measure of active anion transport. Norepinephrine was effective in promoting cecal adherence of a non-O157 E. coli strain as well as E. coli O157:H7 eae or espA mutant strains that are incapable of intimate mucosal attachment. Nerve fibers immunoreactive for the norepinephrine synthetic enzyme dopamine β-hydroxylase appeared in close proximity to the cecal epithelium, and the norepinephrine reuptake blocker cocaine, like norepinephrine and the selective α2-adrenoceptor agonist UK-14,304, increased E. coli O157:H7 adherence. These results suggest that norepinephrine, acting upon the large bowel mucosa, modulates early, non-intimate adherence of E. coli O157:H7 and probably other mucosa-associated bacteria. Sympathetic nerves innervating the cecocolonic mucosa may link acute stress exposure or psychostimulant abuse with an increased microbial colonization of the intestinal surface. This in turn may alter host susceptibility to enteric infections.
Intimin; Type III secretion system; Mucosa-adherent bacteria; Norepinephrine; Cocaine; Enteric nervous system
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Mediation of neurogenic ion transport by acetylcholine, prostanoids and 5-hydroxytryptamine in porcine ileum
Townsend, DeWayne
Casey, Melissa A.
Brown, David R.
European journal of pharmacology
Enteric neural activity modulates active transepithelial ion transport in the intestine. We investigated the neural circuits mediating neurogenic secretion in mucosal explants from porcine ileum. Transmural electrical stimulation increased short-circuit current, a measure of active ion transport, by 35 ± 2 µA/cm2. The neuronal Na+ channel blocker saxitoxin, the muscarinic cholinergic receptor antagonist atropine, the 5-hydroxytryptamine3 receptor antagonist tropisetron, and the cyclooxygenase inhibitor indomethacin inhibited this response. In addition, tropisetron inhibited the atropine-resistant portion of the response, and both atropine and indomethacin attenuated the saxitoxin-resistant component. Neurogenic secretion in porcine ileum appears to be mediated by tryptaminergic and prostanoid-sensitive cholinergic pathways.
Transmural electrical stimulation; Short-circuit current; 5-hydroxytryptamine 3 receptor; Muscarinic cholinergic receptor; Intestinal mucosa
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Derivation of ligands for the complement C3a receptor from the C-terminus of C5a
Halai, Reena
Bellows-Peterson, Meghan L
Branchett, Will
Smadbeck, James
Kieslich, Chris A
Croker, Daniel E
Cooper, Matthew A
Morikis, Dimitrios
Woodruff, Trent M
Floudas, Christodoulos A
Monk, Peter N
European Journal of Pharmacology
The complement cascade is a highly sophisticated network of proteins that are well regulated and directed in response to invading pathogens or tissue injury. Complement C3a and C5a are key mediators produced by this cascade, and their dysregulation has been linked to a plethora of inflammatory and autoimmune diseases. Consequently, this has stimulated interest in the development of ligands for the receptors for these complement peptides, C3a receptor, and C5a1 (C5aR/CD88). In this study we used computational methods to design novel C5a1 receptor ligands. However, functional screening in human monocyte-derived macrophages using the xCELLigence label-free platform demonstrated altered specificity of our ligands. No agonist/antagonist activity was observed at C5a1, but we instead saw that the ligands were able to partially agonize the closely related complement receptor C3a receptor. This was verified in the presence of C3a receptor antagonist SB 290157 and in a stable cell line expressing either C5a1 or C3a receptor alone. C3a agonism has been suggested to be a potential treatment of acute neutrophil-driven traumatic pathologies, and may have great potential as a therapeutic avenue in this arena.
C3a receptor; C5a1 receptor; Peptide design; In silico sequence selection; Computational optimization; Label-free screening
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Effects of the neurotensin NTS1 receptor agonist PD149163 on visual signal detection in rats
Hillhouse, Todd M.
Prus, Adam J.
European journal of pharmacology
Antipsychotic drugs provide limited efficacy for cognitive impairment in schizophrenia. Recent studies have found that the neurotensin NTS1 receptor agonist and putative atypical antipsychotic drug PD149163 reverses deficits in sensory-gating and novel object recognition, suggesting that this compound may have the potential to improve cognitive functioning in schizophrenia. The present study sought to extend these investigations by evaluating the effects of PD149163 on sustained attention using a visual signal detection operant task in rats. PD149163, the atypical antipsychotic drug clozapine, and the dopamine D2/3 receptor antagonist raclopride all significantly decreased percent "hit" accuracy, while none of these compounds altered "correct rejections" (compared to vehicle control). Clozapine and raclopride significantly increased response latency, while high doses of PD149163 and raclopride significantly increased trial omissions. Nicotine, which was tested as a positive control, significantly improved overall performance in this task and did not affect response latency or trial omissions. The present findings suggest that neurotensin NTS1 receptor agonists, like antipsychotic drugs, may inhibit sustained attention in this task despite having different pharmacological mechanisms of action.
neurotensin; NTS1 receptor; PD149163; antipsychotic; attention; visual signal detection
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Diuretic effects of cannabinoid agonists in mice
Chopda, Girish R
Vemuri, V Kiran
Sharma, Rishi
Thakur, Ganesh A
Makriyannis, Alexandros
Paronis, Carol A
European journal of pharmacology
Cannabinoids both increase urine output and decrease urinary frequency in human subjects. However, these effects have not been systematically evaluated in intact mice, a species commonly used to evaluate the effects of novel cannabinoids. The present studies investigated whether cannabinoid agonists reliably produce diuresis in mice at doses comparable to those that produce other cannabinoid effects and, further, identified the receptors that may mediate these effects. Diuretic effects were measured in male mice over 6 h. In some studies, urine was collected and analyzed for electrolyte measurements. In other studies, agonist injections were preceded by pretreatment with cannabinoid CB1 or CB2 selective antagonists, including a peripherally constrained CB1 antagonist. Companion studies evaluated the antinociceptive effects of the cannabinoid agonists in a warm-water tail-withdrawal assay. Direct-acting cannabinoid CB1 agonists Δ9- tetrahydrocannabinol (THC), WIN 55,212, AM7418 and AM4054, had biphasic effects on diuresis, with peak diuretic effects occurring at lower doses than peak antinociceptive effects. Cannabinoid diuresis was similar to κ-opioid agonist–induced diuresis in terms of maximum effects with only moderate loss of Na+. Antagonism studies indicate that the diuretic effects of cannabinoids are CB1-receptor mediated, with both central and peripheral components. These findings suggest that mice may provide a model for understanding the mixed effects of marijuana on urine output, as described in clinical studies, and aid in the development of targeted cannabinoid based therapies for bladder dysfunction.
cannabinoid; diuresis; Δ9-tetrahydrocannabinol; THC; mice; bladder dysfunction
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Role of mitogen-activated protein kinase phosphatase-1 in corticosteroid insensitivity of chronic oxidant lung injury
Pinart, Mariona
Hussain, Farhana
Shirali, Sima
Li, Feng
Zhu, Jie
Clark, Andrew R.
Ammit, Alaina J.
Chung, Kian Fan
European Journal of Pharmacology
Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and in the induction of corticosteroid (CS) insensitivity. Chronic ozone exposure leads to a model of COPD with lung inflammation and emphysema. Mitogen-activated protein kinase phosphatase-1 (MKP-1) may underlie CS insensitivity in COPD. We determined the role played by MKP-1 by studying the effect of corticosteroids in wild-type C57/BL6J and MKP-1−/− mice after chronic ozone exposure. Mice were exposed to ozone (3 ppm, 3 h) 12 times over 6 weeks. Dexamethasone (0.1 or 2 mg/kg; intraperitoneally) was administered before each exposure. Mice were studied 24 h after final exposure. In ozone-exposed C57/BL6J mice, bronchial hyperresponsiveness (BHR) was not inhibited by both doses of dexamethasone, but in MKP-1−/− mice, there was a small inhibition by high dose dexamethasone (2 mg/kg). There was an increase in mean linear intercept after chronic ozone exposure in both strains which was CS-insensitive. There was lesser inflammation after low dose of dexamethasone in MKP-1−/− mice compared to C57/Bl6J mice. Epithelial and collagen areas were modulated in ozone-exposed MKP-1−/− mice treated with dexamethasone compared to C57/Bl6J mice. MKP-1 regulated the expression of MMP-12, IL-13 and KC induced by ozone but did not alter dexamethasone׳s effects. Bronchial hyperresponsiveness, lung inflammation and emphySEMa after chronic exposure are CS-insensitive, and the contribution of MKP-1 to CS sensitivity in this model was negligible.
Ozone exposure; Emphysema; Lung inflammation; Bronchial hyperresponsiveness; Mitogen-activated protein kinase phosphatase 1 (MKP-1)
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Calanquinone A induces anti-glioblastoma activity through glutathione-involved DNA damage and AMPK activation
Liu, Fan-Lun
Hsu, Jui-Ling
Lee, Yean-Jang
Dong, Yu-Shun
Kung, Fan-Lu
Chen, Ching-Shih
Guh, Jih-Hwa
European journal of pharmacology
Glioblastoma, a highly malignant glioma, is resistant to both radiation and chemotherapy and is an intractable problem in clinical treatment. New therapeutic approaches are in urgent need. Calanquinone A, an herbal constituent, displayed anti-proliferative activity against glioblastoma cells, including A172, T98 and U87. Flow cytometric analysis showed an S phase arrest and a subsequent apoptosis to calanquinone A action. Further identification demonstrated a rapid increase of γH2A.X formation at S phase. The data together with comet tail formation and Chk1 activation indicated DNA damage response. N-acetyl cysteine (an antioxidant and a glutathione precursor) and exogenously applied glutathione, but not trolox (an antioxidant), completely abolished calanquinone A-induced effects. Immunofluorescence assay revealed that calanquinone A decreased the intracellular glutathione levels in both A172 and T98 cells. However, calanquinone A, by itself, did not conjugate glutathione. The data suggested that the decrease of cellular glutathione predominantly contributed to the anticancer mechanism. Furthermore, calanquinone A induced the activation of AMP-activated protein kinase (AMPK) and the inhibition of p70S6K activity. Rhodamine efflux assay showed that calanquinone A did not block efflux activity, indicating that calanquinone A was not a P-glycoprotein substrate. In summary, the data suggest that calanquinone A displays anti-glioblastoma activity through a decrease of cellular glutathione levels that subsequently induces DNA damage stress and AMPK activation, leading to cell cycle arrest at S-phase and apoptotic cell death. Furthermore, calanquinone A does not serve as a P-glycoprotein substrate, suggesting a potential for further development in anti-glioblastoma therapy.
Calanquinone A; Glutathione; DNA damage; AMPK; Glioblastoma
Related Articles
Characterization of serotonin-toxicity syndrome (toxidrome) elicited by 5-hydroxy-L-tryptophan in clorgyline-pretreated rats
Ma, Zhiyuan
Zhang, Gongliang
Jenney, Chris
Krishnamoorthy, Swapna
Tao, Rui
European journal of pharmacology
Patients are at high risk of developing serotonin-toxicity syndrome (toxidrome) when they take multiple serotonergic drugs, particularly co-administered with monoamine oxidase inhibitors or 5-hydroxytryptamine (5-HT) reuptake blockers. The toxidrome can vary from mild to severe. The primary goal of the present study was to understand the relationship between behavioral signs and degrees of toxidrome induced by 5-hydroxy-L-tryptophan (5-HTP) in clorgylinized rats. The severity was obtained by scoring behavioral signs including head shakes, penile erection, forepaw treading, hind limb abduction, Straub tail and tremor. It was found that 5-HTP produced a dose-dependent increase in degrees of the toxidrome. Furthermore, correlation between the toxidrome and changes in body-core temperature (claudqcTcor) was determined. There was hypothermia in the mild toxidrome (claudqcTcor < −1 °C), high hyperthermia in the severe toxidrome (claudqcTcor > +2 °C) and a small change in Tcor in the moderate toxidrome (−1 °C < claudqcTcor < +2 °C). Thus, claudqcTcor in response to drugs can be used to estimate the severity of the toxidrome. The second attempt was to identify the receptors mediating those changes. 5-HT1A receptors were involved in the hypothermic response while 5-HT2A and NMDA receptors mediated head shakes, hyperthermia, forepaw treading and Straub tail. Lastly, antidotal effect of cyproheptadine and (+)-MK-801 was examined. Both drugs blocked hyperthermia and death. However, the effects on mortality became poor when the antidotes were injected 60 min after high hyperthermia had been induced. These findings demonstrate the importance of the time frame using antidotes in the treatment of the 5-HT toxidrome.
Serotonin-toxicity syndrome; head shakes; hyperthermia; hypothermia; 5-HT1A receptor; 5-HT2A receptor
Related Articles
Sphingosine-1-phosphate induced contraction of bladder smooth muscle
Kendig, Derek M.
Matsumoto, Alec K.
Moreland, Robert S.
European journal of pharmacology
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that contracts most smooth muscles. Although S1P has been shown to contract bladder smooth muscle, the mechanism(s) by which S1P initiates contraction has not been extensively investigated. The goal of this study was to determine if S1P-induced force generation and myosin light chain (MLC) phosphorylation are dependent on calcium sensitization pathways mediated by protein kinase C (PKC) and Rho kinase (ROCK) and which S1P receptor is important in this response. Bladder smooth muscle strips from rabbit and rat were mounted for isometric force recording and contracted in response to carbachol or S1P in the presence and absence of an inhibitor of PKC (3 μM Bisindolylmaleimide-1) or ROCK (1 μM H-1172). 10 μM S1P produced approximately 40% of the force generated in response to 110 mM KCl in rabbit bladder smooth muscle. S1P, up to 100 μM, did not produce a response in rat bladder smooth muscle, any response evoked was due to solvent (NaOH). S1P-dependent force development was associated with a concomitant increase in Ser19, but not dual Thr18/Ser19 MLC phosphorylation. Inhibition of PKC decreased force development, whereas inhibition of ROCK abolished S1P-induced force. An inhibitor of the S1P2 receptor, JTE-013, relaxed a S1P-induced contraction; whereas, an agonist with low affinity to the S1P2 receptor, dihydro-S1P, did not elicit a contraction. Our results suggest that S1P contracts rabbit, but not rat, bladder smooth muscle via the S1P2 receptor and is dependent on MLC phosphorylation and myofilament calcium sensitization primarily in response to ROCK activation.
Rho kinase; Protein kinase C; Calcium sensitization; S1P2 Receptor; Myosin light chain phosphorylation
Related Articles
Benzodiazepine-like discriminative stimulus effects of toluene vapor
Shelton, Keith L.
Nicholson, Katherine L.
European journal of pharmacology
In vitro studies show that the abused inhalant toluene affects a number of ligand-gated ion channels. The two most consistently implicated of these are γ-aminobutyric acid type A (GABAA) receptors which are positively modulated by toluene and N-methyl-D-aspartate (NMDA) receptors which are negatively modulated by toluene. Behavioral studies also suggest an interaction of toluene with GABAA and/or NMDA receptors but it is unclear if these receptors underlie the abuse-related intoxicating effects of toluene. Seventeen B6SJLF1/J mice were trained using a two-choice operant drug discrimination procedure to discriminate 10 min of exposure to 2000 ppm toluene vapor from 10 min of exposure to air. The discrimination was acquired in a mean of 65 training sessions. The stimulus effects of 2000 ppm toluene vapor were exposure concentration-dependent but rapidly diminished following the cessation of vapor exposure. The stimulus effects of toluene generalized to the chlorinated hydrocarbon vapor perchloroethylene but not 1,1,2-trichloroethane nor the volatile anesthetic isoflurane. The competitive NMDA antagonist CGS-17955, the uncompetitive antagonist dizocilpine and the glycine-site antagonist L701,324 all failed to substitute for toluene. The classical nonselective benzodiazepines midazolam and chlordiazepoxide produced toluene-like stimulus effects but the alpha 1 subunit preferring positive GABAA modulator zaleplon failed to substitute for toluene. The barbiturates pentobarbital and methohexital and the GABAA-positive modulator neurosteroid allopregnanolone did not substitute for toluene. These data suggest that the stimulus effects of toluene may be at least partially mediated by benzodiazepine-like positive allosteric modulation of GABAA receptors containing alpha 2, 3 or 5 subunits.
drug discrimination; inhalants; toluene; GABA; NMDA
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The 2-Methoxy methyl analogue of salvinorin A attenuates cocaine-induced drug seeking and sucrose reinforcements in rats
Morani, Aashish S.
Ewald, Amy
Prevatt-Smith, Katherine M.
Prisinzano, Thomas E.
Kivell, Bronwyn
European journal of pharmacology
κ opioid receptor activation by traditional arylacetamide agonists and the novel neoclerodane diterpene κ opioid receptor agonist Salvinorin A (Sal A) results in attenuation of cocaine-seeking behavior in pre-clinical models of addiction. However, adverse effects such as sedation, depression and aversion limit their clinical utility. The Sal A analogue, 2-methoxymethyl salvinorin B (MOM Sal B) is a longer acting Sal A analogue with high affinity for κ opioid receptors. In this study, we tested MOM Sal B for its ability to modulate cocaine-seeking behavior in rats. MOM Sal B (0.3 mg/kg) successfully attenuated cocaine-seeking but also attenuated sucrose reinforcement. No change in activity was observed in either cocaine-induced hyperactivity or spontaneous open field activity tests but increased immobility and decreased swimming times in the forced swim test were observed. This study indicates that κ opioid receptor activation by more potent Sal A analogues modulates cocaine-seeking behavior non-selectively without causing sedation, suggesting an improved side effects profile. However, pro-depressive effects are seen, which may limit the therapeutic potential of this compound. Future studies with Sal A analogues having affinities at other opioid receptors are warranted as they have the potential to identify compounds having effective anti-addiction properties.
Cocaine; self-administration; salvinorin A; sucrose reinforcement; locomotion; forced swim test
Related Articles
Similar activity of mecamylamine stereoisomers in vitro and in vivo
Papke, Roger L.
Stokes, Clare
Muldoon, Pretal
Damaj, M. Imad
European journal of pharmacology
A previous characterization of mecamylamine stereoisomers using nicotinic acetylcholine receptors expressed in Xenopus oocytes revealed only small differences between the activity of the R and S forms of mecamylamine. However, that work was limited in the breadth of receptor subtypes tested, especially in regard to the discrimination of high and low sensitivity receptors, which differ in the ratios of alpha and beta subunits. We report new data using subunit concatamers, which produce uniform populations of high-sensitivity or low-sensitivity receptors, as well as alpha2, alpha5, and alpha6-containing receptors, which were not studied previously. Consistent with previous studies, we found that beta4-containing receptors were most sensitive to mecamylamine and that the IC50 values for the inhibition of net charge were lower than for inhibition of peak currents. No large differences were seen between the activities of the mecamylamine isomers. Additionally, a previously reported potentiation of high-sensitivity α4β2 receptors by S-mecamylamine could not be reproduced in the oocyte system, even with mutants that had greatly reduced sensitivity to mecamylamine inhibition or when the selective agonist TC-2559 was used. In vivo studies suggested that the R-isomer might be somewhat more potent than the S isomer at blocking CNS effects of nicotine. Although the potency difference was no more than a factor of two, it is consistent with lower LD50 estimates previously reported for the R isomer. Our results significantly extend knowledge of the nicotinic acetylcholine receptor activity profile of mecamylamine and support the hypothesis that these effects are not strongly stereoisomer selective.
Tourette's syndrome; depression; nicotine addiction; TC-5214; TC-2559
Related Articles
Hippocampal calcium dysregulation at the nexus of diabetes and brain aging
Thibault, Olivier
Anderson, Katie L.
DeMoll, Chris
Brewer, Lawrence D.
Landfield, Philip W.
Porter, Nada M.
European journal of pharmacology
Accumulating evidence is associating disorders of lipid and glucose metabolism, including the overlapping conditions of insulin resistance/metabolic syndrome, obesity and diabetes, with moderate cognitive impairment in normal aging and elevated risk of Alzheimer's disease. It appears that a common feature of these conditions is deficient insulin signaling, likely affecting the brain as well as canonical peripheral target tissues. A number of studies have documented that insulin directly affects brain processes and that reduced insulin signaling results in impaired learning and memory. Several studies have also shown that deficient insulin signaling induces Ca2+ dysregulation in neurons. Because brain aging is associated with substantial Ca2+ dyshomeostasis, it has been proposed that deficient insulin signaling exacerbates or accelerates aging-related Ca2+ dyshomeostasis. However, there have been few studies examining insulin interactions with Ca2+ regulation in aging animals. We have been testing predictions of the Ca2+ dysregulation/diabetes/brain aging hypothesis and have found that insulin and insulin sensitizers (thiazolidinediones) target several hippocampal Ca2+-related processes affected by aging, including larger Ca2+ transients and Ca2+-dependent afterhyperpolarizations, and counteract the effects of aging on those processes. Thus, while additional testing is needed, the results to date are consistent with the view that effects of deficient insulin signaling on brain aging are mediated in part by neuronal Ca2+ dyshomeostasis.
afterhyperpolarization; thiazolidinediones; cognition; imaging; aging; learning
Related Articles
The serotonin-2 receptor modulator, (−)-trans-PAT, decreases voluntary ethanol consumption in rats
Kasper, James
Tikamdas, Rajiv
Kim, Myong Sang
MacFadyen, Kaley
Aramini, Richard
Ladd, Joseph
Bisceglia, Sarah
Booth, Raymond
Peris, Joanna
European journal of pharmacology
Serotonin (5-HT) 5-HT2C receptor agonists have shown promise as novel alcoholism pharmacotherapies, but developing selective agonists has been problematic. Female Sprague Dawley rats were given ethanol in a palatable gel vehicle during operant sessions. 5-HT2C receptor modulators (Ro60-0175, SB242,084, and (−)-trans-PAT) were administered before operant sessions. As a control for the effects of 5-HT2C receptor agonism on caloric intake, drugs were also tested using non-ethanol containing gelatin. Ro60-0175, a 5-HT2 family receptor agonist, decreased both ethanol and vehicle responding while (−)-trans-PAT, a 5-HT2C receptor agonist with 5-HT2A-2B receptor inverse agonist activity, selectively reduced only ethanol responding. The effect of 5-HT2C receptor agonists on self-administration after reinstatement of ethanol after a three week deprivation was also determined. (−)-trans-PAT eliminated increases in ethanol intake following ethanol deprivation whereas Ro60-0175 had no effect. These results emphasize the need for caloric controls and further support the idea that selective modulation of 5-HT2 family receptors is a potential pharmacotherapeutic approach in the treatment of alcoholism.
Ethanol; serotonin 2C receptor; alcoholism; operant self-administration; alcohol deprivation
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text:
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Daily margarita specials! A new flavor on special each week. Read more
2/4.99 margaritas, & they're actually good too!
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subset: commoncrawl


text:
The English Department at CWRU promotes intellectual curiosity, analytical inquiry, and creative thinking about the rich variety of fields in our discipline. Building on the passion our students bring, the Department's faculty encourages the formation of new knowledge through careful examination of both real and imagined worlds.
Our seminars and research explore the craft of poetry, Shakespearean drama, science fiction, the techniques of horror films, the rhetoric of medicine, and the dynamics of novels, plays, short stories and creative non-fiction. Evidence suggests that students wishing to work in one of the fields in our discipline — literature, creative writing, film, journalism, and rhetoric — need not sacrifice passion for practicality.
In addition to serving as a stand-alone major, English complements majors in other disciplines and serves as excellent preparation for law school, medical school, and business school. There is no better place to learn the art of communication, a skill that informs nearly every profession from teaching literature to computer programming. Our smaller class sizes allow individual attention from professors who have published acclaimed books and won awards including the Fulbright, the Guggenheim, and the Pulitzer Prize.
Friday, April 29th
The Adrian-Salomon Awards Event: Lectures by Cara Byrne and Eric Earnhardt
"From The Snowy Day to Goggles!:The Racial Legacy of Ezra Jack Keats' Picture Books," a lecture by Cara Byrne
"The Modern Lyric Refinery: From John Ruskin's Iron to T. S. Eliot's Platinum," a lecture by Eric Earnhardt
Bellflower102. 3:00 p.m.
Date posted: April 1st, 2016
in this issue
Interview with Jeff Morgan /Faculty Notes/Past Faculty: Lemuel Potwin/ Alumni News/England's Impact on a Major/ Schedule of Events
March 2016
Interview with Jeff Morgan (American Comic Poetry)
CWRU: Why does comic poetry make people uncomfortable? …Read more.
Date posted: December 14th, 2015
Dave Lucas is one of forty Cuyahoga County artists who will each receive $15,000 in 2016 through the Creative Workforce Fellowship. Awards are made in the disciplines of craft, dance, design, literature, media arts, music, theatre and visual arts. …Read more.
Date posted: December 11th, 2015
in this issue
WRC and Bellflower Hall /Faculty Notes/EGSA Mentoring/ Alumni News/Letter from the Chair/ Beachy-Quick Reading
The Writing Resource Center and Bellflower Hall
by Kurt Koenigsberger
About the Writing Resource Center
Pardee Hall, in its earlier years. …Read more.
Date posted: December 3rd, 2015
Anisfield-Wolf blogs about our colloquium with Kenneth Warren–"Race, Literature and #BlackLivesMatter":
http://www.anisfield-wolf.org/2015/11/professor-kenneth-warren-visits-cleveland-for-talk-on-race-literature-and-blacklivesmatter/ …Read more.
Date posted: November 9th, 2015
Over the years Case Western Reserve University's benefactors have donated funds to establish endowments for many purposes – scholarships, research, buildings maintenance, and professorships. Typically, the donated funds are invested and only the income is used to support the endowment's purpose. …Read more.
Date posted: September 29th, 2015
in this issue
Letter from the Chair/"What Are You Reading?" /Faculty Notes/NEH Summer Institute/ Alumni News/ASLE Biennial Conference/Coptic Binding/Faculty Timeline/Grad Picnic
June 2015
Letter from the Chair
In another technocratic era, Charles Dickens intimated that calling a horse by its name was getting extremely hard. …Read more.


text:
Now That's a Man Boat!
Shark Boat, Boats Yachts, Cool Boats, Fishing Boats, Paint Job
Cool paint job.....not a car or a bike but sick just the same
Suggested paint job for the in-laws' new fishing boat.
Fantastical Shark Boat | Flickr - Photo Sharing!
F**k Yeah Friday KCCO. Bad ass paint job
Fantastical Shark Boat | by 1GrandPooBah
Shark Boat! OMG that is RAD!!
Shark attack!!Cool boat!!
Shark Boat Wrap
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Power boat.
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İNANILMAZ TEKNE , BİRAZ MOTOR TAKSAYDINIZ BARİ :) go-fast boat with $130,000 worth of outboard motors...each at 250 HP...top speed of about 70 mph.
LOL! A go-fast boat with $130,000 worth of outboard motors...each at 250 HP...top speed of about 70 mph.
inboard+drag+boats | most speed boats involve a boat with a big motor a redneck speedboat
In 2004, Richard Davison, the managing director of Crompton Marine, and his girlfriend, Ellen George, were arrested after Spanish authorities conducting anti-drug smuggling operations seized a number of boats sold by their company and reported them to British customs officials. The two were suspected of using Crompton Marine as a front for supplying high-speed inflatable boats to illegal drug merchants, advertising them as "high-speed, uncatchable craft that have a low radar signature." INXS
Power boat. Couldn't Afford Maintenance with Mercury 2 Strokes; Get Yamaha's, Suzuki's.
Now that a fishing boat. ~ really a drug dealers boat they took.
Bullet Bass Boats MORE POWER
Power boat.from a drugsrunner
My dream boat
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Yachts Boats, Fastest Boats, Boats Yachts, Fire Extinguisher, Barsheff Racing Future
Offshore Powerboat Racing when boats were boats!www.pyrotherm.gr FIRE PROTECTION ΠΥΡΟΣΒΕΣΤΙΚΑ 36 ΧΡΟΝΙΑ ΠΥΡΟΣΒΕΣΤΙΚΑ 36 YEARS IN FIRE PROTECTION FIRE - SECURITY ENGINEERS & CONTRACTORS REFILLING - SERVICE - SALE OF FIRE EXTINGUISHERS www.pyrotherm.gr www.pyrosvestika.com www.fireextinguis... www.pyrosvestires.eu www.pyrosvestires..
Offshore Powerboat Racing when boats were boats! - YouTube
pedrazzini boat design
Boats Yachts, Boats Wooden, Boatbuilding Craftsmanship, Swiss Boatbuilding, Boat Building
Claudio Pedrazzini merges Italian elegance with Swiss boatbuilding craftsmanship to create the perfect motorboat.
Pinned by www.craftculture.co Claudio Pedrazzini merges Italian elegance with Swiss boatbuilding craftsmanship to create the perfect motorboat. #artisan #men
→→→ http://automobilevehiclequote.tumblr.com/post/119676932702/1#09202319 ←←←CLICK the PICTURE or LINK for more! Boatbuilding craftsmanship.
pedrazzini boat design - my great grandfather's name was Pedrazzini. Pretty cool boats...
Claudio Pedrazzini with Swiss boatbuilding craftsmanship to create the perfect boat
Pedrazzini – Boat design that reflects glamorous sophistication @ thebrander.com
The Brander » Pedrazzini – Boat design that reflects glamorous sophistication
OSPREY LONDON loves pedrazzini boat design
Boat building
Beautiful Jeep!
Jeeps Cars Trucks Bikes, Cj7 Jeep, Ass Jeep, Jeep Thing
All the SICKEST Jeep Wrangler porn curated by Wrangler Porn & Gatecrasher Jeep Outfitters.
TJ Jeep Wrangler paint job goal
Awesome Jeep CJ7 paint job
jeep wrangler design
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Bad ass Jeep
Awesome jeep
Riva Boats at the French Riviera
Boats Riva, Wood Boats, Boats Yachts, Wooden Boats, Classic Wooden, Italian Wooden, Riva Boats
There are all kinds of 'cool' - the classic wooden hulled speedboat (Garwood, Riva or Chris Craft).
Riva boats - the nautical equivalent of an Aston Martin - pure class.
Riva Boats at the French Riviera... Nick would be in love :)
So many Riva Boats, so little time...LLA
Riva boats | riva Italian yachts
Chris craft classic wooden boat
Italian wooden speed boats
riva yachts
VW Bus http://caravaning-univers.com/ #accessoire #camping car accessoire #caravane #vw # volkswagen bus
Cars Motorcycles, Volkswagen Kombi, Vw Bus, Vw Camper, Volkswagen Bus
#VW #Camper #QuirkyRides #ClassicCar #cars #motorcycles #cycles
#VW #Camper #QuirkyRides #ClassicCar ____ AKA Dream car of life
VW camper can. There would be one of these on my driveway
VW van ... my dream car ..
(volkswagon camper van).
VW bus and palm trees
Volkswagen Kombi..
Lowrider VW bus
Northrop N9M | Flickr - Photo Sharing!
Military Aircraft, Flickr Photo, Jets Planes, Awesome Airplanes, Planes Trains, Photo Sharing, Air Planes
I've seen this plane fly at the Planes of Fame in Chino, CA where it is kept. Northrop N9M | Flickr - Photo Sharing!
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Follow this panel in the Pintrest and see photos, news and facts about aircraft of all time. Icons, ideas and incredible designs and prototypes as well. Helicopters and rockets included. Siga este painel no Pintrest e fique por dentro de tudo sobre aviões de todos os tempos. Também protótipos, projetos, idéias e aeronaves ícones da aviação militar e civil. Helicópteros e foguetes também. Notícias. Clique na foto para ir ao site! Northrop N9M | Flickr - Photo Sharing!
Northrop N9M | Flickr - Photo Sharing! looks very suspiciously like the German Horton!
Airforce, A 10 Thunderbolt, Military Aircraft, Air Force, Aircraft, A 10 Warthog, Fighter Jets
A-10 Warthog. I can not tell you how many days I spent building this model fighter jet. One of the most wild fighters in the US Arsenal...
A-10 Thunderbolt by Photomatt28, via Flickr-- ♥Get 7-14% cash back shopping your favorite stores Online. Bass Pro Shops, Walmart, Home Depot, Sears, JC Penneys and more. Cash back on gas cards, airline tickets, and motels too! bit.ly/... ♥
A-10 Thunderbolt by Photomatt28, via Flickr-- this would be the plane I would fly if I were a pilot. Badass
→→→ http://automobilevehiclequote.tumblr.com/post/119635227132/2#09251357 ←←←CLICK the PICTURE or LINK for more! A-10 Thunderbolt by Photomatt28, via Flickr-- this would be the plane I would fly if I were a pilot. Badass.
A-10 Thunderbolt What you get when you make the machine gun first and then, ask someone to design an aircraft around it. The gun is longer than the fuselage.
A-10 Thunderbolt, this would be the plane I would fly if I were a pilot.
USAF A-10 Warthog - the tank killer. "Smile when you see the flash!"
The A-10 Warthog,.. sporting its war face...
A-10 Thunderbolt | Flickr - Photo Sharing!
dutch fighter. F-16 Max Level Speed (at altitude) 1,350 mph (2,175 km/h) at 40,000 ft (12,190 m), Mach 2.05
Military Aircraft, Air Force, Airplane, War Planes, Jet Fighter, Fighter Jets
Badass Dutch fighter plane x-post from rpics #eyecandy #badass #dutch #fighter #plane #rpics #photography
Royal Netherlands Air Force (RNLAF), General Dynamics (Lockheed Martin) F-16 Fighting Falcon
Dutch fighter. Who knew they had an Air Force? And such a well-designed/branded one?
♠ The Royal Netherlands Air Force F-16 Demo Team 2014-2015 #Aviation #Military #Jet
Netherlands Air Force. What a paint scheme!
Royal Netherlands Air Force Fighter Plane
Airplane in the sky
dutch fighter Jet
F-16 Jet Fighter
Airborne/rough water boat pics!! - Page 2 - The Hull Truth - Boating and Fishing Forum
Contender Boat
contender boats - Google Search
Le Manoosh, http://nathandearsley.blogspot.com.es/
Helmet Concept, Motorcycle Helmet Design, Motorcycles Helmets, Motorcycle Helmets, Bikes Helmets, Nathandearsley Blogspot, Bike Helmets Design
http://www.motorcyclemaintenancetips.com/motorcyclehelmetchoices.php has some info on motorcycle helmets and how properly select the right one.
http://www.motorcyclemaintenancetips.com/howtocleanamotorcyclehelmet.php MotorcycleMaintenanceTips.com has some info on how to clean a motorcycle helmet and keep it looking new.
Carbon Fiber helmet #helmets #motorcycle #motorcycles #gear #black
Navigator by Nathan Dearsley (http://nathandearsley.blogspot.com)
TAG Heuer Steve McQueen Motorcycle Helmet | iainclaridge.net
Bike helmet that looks like the cog helmet
Carbon Fiber helmet?(concept)
Contender Boats
Contender Boat, Boats Cars, Boats Bigger, Boats Boats, Beautiful Boats
Contender Boats. Heaven on Water
Contender Boats - gimme gimme
A boat
Speedboat, Classic Boats, Boats Yachts, Power Boats, Mf Powerboats, Boats Ships, Crazed Boats
Speed boat racer...this thing would have looked like a stealth bomber today. From another planet.
Berylla riveted aluminium speedboat
Retro Speed boat
32 Things You'd Definitely Buy If You Ever Won The Lottery
it's a boat inside a boat
Speedboat, Superyacht
CRN J'ade http://www.yachtemoceans.com/60m-jade-crn/ #superyacht #megayacht #yacht #crn
Luxury Yacht..I totally want a yacht with a garage for a speed boat on the side.
OMG!! A garage door on a luxury yacht by j'Ade yacht by CRN via One Big Photo
Luxury super Yacht... Soon to be heading to Kata Rocks... www.katarocks.com
This yacht has a garage door for your speed boat... ridiculous! ok jealous.
Luxury Yacht with a garage for a speed boat on the side.
A boat...with a garage for another boat. #yachting
TRANSPORT: Mega yacht with Speedboat
garage door on a luxury yacht
Awesome boat.
Boats Yachts, Luxury Boats, Speed Boats
This is the Hornet G-36 , rebuilt from the original blueprints of a 1934 Speedboat of the same name. Is this a #speed #boat or just a dream?
M :: This is the sleekest boat I have ever seen! What an incredible thing if beauty and the epitome of luxury! #boat
boats#customized cars #sport cars #celebritys sport cars #ferrari vs lamborghini #luxury sports cars| http://luxury-sports-cars-vesta.blogspot.com
boats#customized cars #ferrari vs lamborghini #sport cars #luxury sports cars #celebritys sport cars
Great Boat #ferrari vs lamborghini #sport cars #celebritys sport cars #customized cars #luxury sports cars| http://sportcarcollections124.blogspot.com
would have one of these babies outside of it!! #boats #yachts #lake #beach #house
beautiful boat.
luxury yachting
sexy boat
Walth Boats, manufactured in Holland.
Yachts Boats, Wood Boats, Classic Boats, Boats Manufactured, Wooden Boats, Boats Yachts, Boats Holland, Boats Ships
Walth Boats, manufactured in Holland.. CLICK the PICTURE or check out my BLOG for more: http://automobilevehiclequotes.tumblr.com/#1506301456
Walth 1075 built by Walth Boats Holland twin Ilmor V10
Walth 1075 built by Walth Boats Holland
Luxurious wooden boat.
Classic Wooden Boats
slick wooden boat
wooden boat.
Wood Boats
What a beautiful boat!
Chris Craft, Speedboat, Wood Boats, Wooden Boats
I think this is a classic Chris-Craft boat circa 1950s?? BEAUTIFUL! I want to go to "On Golden Pond!"
#seabuddy re-pin #classicwoodboat Wooden Boat -easy to buy-a nightmare to maintain-what else does he have to do??
classic boat - needs an american flag waving on the back
Classic wood boat-my dream boat and vacation
Wooden Speedboat = Love
Chris-Craft #boat
Wood speed boat
beautiful boat
Wooden Boat -
#cvx20 #carlson #classicglastron #carlson #jet #glastron


text:
DEAR BENNY: We live in a high-rise condominium and the owner or tenant who lives immediately above us is constantly making noise that disturbs us. We believe someone, perhaps a young child, is bouncing a basketball on the floor beginning ...Read More »
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INVESTOR'S CORNER: A strange but true investing tale
Here is a "strange but true" story from my business that I thought might brighten your weekend a bit. Once upon a time, I "got the deed" (took legal ownership, subject to the existing mortgage) to a house in pre-foreclosure. ...Read More »
BERKO: Don't confuse Wall Street with Sesame Street
DEAR MR. BERKO: I bought 100 shares of VimpelCom at $10 in early 2014, and almost two years later, it's $4.25. I was told that VimpelCom's fall in price was related to management's buying favors from government officials. I figured ...
Tagged with: Wall StreetRead More »
KASS: Make sure title is clean in cash sale
DEAR BENNY: I am buying a property for cash. I received a draft of the settlement statement from the title company, but there is no seller information. The seller, an attorney, says she does not want to provide her info ...Read More »
INVESTOR'S CORNER: Negotiation tip: Negative preparation
Legendary sports figures like John Wooden, Michael Jordan, Troy Aikman and Joe Montana were all positive thinkers. But they were also relentlessly realistic. Instead of simply thinking positive and hoping things worked out, these sports stars also took steps to ...Read More »
KASS: Reserves critical for association
DEAR BENNY: I am the accountant for several small community associations, and there is one question I am always asked: Why should we budget for reserves? How much do we need in reserves? Is there any legal requirement as to ...Read More »
BERKO: Monthly income a better choice than lump sum
DEAR MR. BERKO: I'm single and retiring at the end of the year from Alcatel-Lucent. The company has offered me a lump payment of $181,000 or a guaranteed monthly income of $1,020 when I retire. What to do? Three stockbrokers ...Read More »
INVESTOR'S CORNER: What is a 'seller's market'?
Most of us have seen Charlotte in recent times referred to as a very strong "seller's market." But what does this mean to you as a real estate investor? For the answer, we have to look first to simple economics. ...Read More »
KASS: Document apartment before and after
DEAR BENNY: My son recently moved out of an apartment he rented for slightly longer than a year. At the end of the lease, the landlord allowed him to continue on a month-to-month basis. My son told him he would ...
Tagged with: apartmentRead More »
INVESTOR'S CORNER: Further things I learned the hard way in investing
Editor's note: This is the second of a three-part column on pitfalls to avoid in real estate investing. Home inspections One of my mentors when I got started had worked at or owned construction companies for over 30 years. Warren ...Read More »


text:
20X20 cabin
Tiny House, Cabin Bing, Cabins Buildings, 20X20 Cabin, Cabins Lodges Inns Log Homes, Log Cabins, Door Cabin, Cabin Fever
Tiny House in a Landscape
Red Cabin - Bing Images
red door cabin in snow
red door! snow!
20X20 cabin
Winter Cabin, Tiny House, Black House, Winter Homes, Wooden House, Mountain Cabin, Log Houses
I have a thing for black houses with white trim!
a winter home by the style files via Flickr
small lake house.
mountain cabin
Cabin setting
Wooden house
winter cabin
Tiny house.
log house
Barns Cabins, Mountain Cabins, Dream Cabin, Cozy Cabin, Log Cabins, Cabin Snow, Rustic Cabins, Winter Photos
Hiver neige : ❤*❤ j'adore !Cabin blanketed in snow. #Winter Photo by Romain Villa
Love it! I wouldn't mind being snowed in, in this adorable log cabin anytime.
Cabin blanketed in snow. Winter Photo by Romain Villa
Cabin, Snow, Colorado, what more could you want?
Dream cabin in the mountains
A cozy cabin and a fire....
Winter log cabin, Canada
winter mountain cabin
Amazing rustic cabin
Tiny House, Dream House, Dream Home, Wooden House, House Idea
Oak Timber Framed House in Devon, England - - the understated light fixtures mounted on the beams, that might work for us
BARN CONVERSION Designed and Built by Roderick James Architects | Carpenter Oak Designed by Roderick James for himself and his family, the Seagull House features this incredibl...
So many timberframe variants...from simple to complex..: Provide a plane of structure at each timberframe bent, and then span with smaller pieces from bent to bent. The shape of the timberframe provides the support as well as the lateral stability. And then you have a skeletal system that can be infilled with whatever floats your boat (and is appropriate in your climate)...strawbales, light clay straw, cob, adobe, etc. barn conversion in Devon England from www.naturalhomes.org
cabin#Dream Houses #Dream Home| http://wedding-ideas-1720.blogspot.com
Oak Timber Framed House in Devon, England I love the high archway!
Beautiful timber frame. I'd love to relax in a place like this.
Love the grander of the ceiling of this Tiny House
Wooden houses...love timber framing.
Beautiful log cabin
Log Homes, Cabins Cottages, Dream Cabin, Little Cabin, Cozy Cabin, Cabin Life, Log Cabins, Dream Home, Cabin Fever
Cozy cabin the #living room design #luxury house design #modern home design #home designs| http://modern-house-design.hana.lemoncoin.org
one of my fav going away ovenight or weekend with my sweetheart is staying in a cozy cabin.
cabin your own log cabin in Estonia for under 30.000,- € www.estland-service.com
Mt. Hood, #Dream Houses #Dream Home| http://dreamhome844.blogspot.com
Mount Hood cabin ♥ Would love to live in a little cabin.
Cabin Fever | by: [Anne Parker]
Literally my perfect dream home.
My Dream Cabin
Cabin Life
Cabins Cottages, Tiny House, Cabin Eco, Log Cabins, Small House, Cabin Fever, Small Cabins, Tiny Cabins
Tiny cabin www.SELLaBIZ.gr ΠΩΛΗΣΕΙΣ ΕΠΙΧΕΙΡΗΣΕΩΝ ΔΩΡΕΑΝ ΑΓΓΕΛΙΕΣ ΠΩΛΗΣΗΣ ΕΠΙΧΕΙΡΗΣΗΣ BUSINESS FOR SALE FREE OF CHARGE PUBLICATION
Kelly Stuart's Sweet Knoll- all I will ever need. A tiny cabin for me and a love.
Kelly Stuart's Sweet Knoll #small #house
Tiny Cabin / The Green Life <3
Tiny Cabin / Eco Dwelling <3
small house for facade town
Small #Cabin #logcabin #log
Small Cabin sam's house
tiny house
Kids Room, Treehouse, Bunk Bed, Bunkbed, House Idea
I just love this log cabin bunk-bed,this country styled room is would be so cool for a big kids room!
Rustic bunk beds...a must have! I love this! I need a log cabin to go with this!
Rustic Bunk Beds. Would be super cute in a super extravagant tree house!
Rustic Bunk Beds ♡ this is going to be awesome for our future tree house
I just love the log cabin, country styled room or lake house idea!
kids room, log cabin, custom wood bunkbeds builtin
Log cabin bunk beds - a cave in a tree-house
Rustic Bunk Beds. Love this for kids room
Log cabin bunk beds ~indoor treehouse!
Wood Burning Stove, Tiny House, Cozy Cabin, Cabin Idea, Living Room, Woodstove, Wood Stove
This is the perfect small living room in a tiny house in the woods. Would love to build such a place.
Wood stove, wood paneling; Rockwood cabin makeover, daybed by woodstove; upper shelf, soft green curtains
Small living room in a log cabin. More log cabins at quick-garden.co.uk/log-cabins.html
living room plan w/ wood stove doubling as cooking stove---if that makes sense?
This is the perfect small living room in a tiny house in the woods.
wood burning stove for my future blue ridge log cabin
Log cabin interior with wood stove and day bed
Cozy cabin ideas...compact rustic getaway.
Cozy cabin living room
log cabin ideas
Bathroom Sink, Half Bath, Rustic Bathroom, Cabin Idea, Bathroom Idea, House Idea
pics of homemade log cabins | ... Pedestal Sink Shaped Like A Log | The Fun Times Guide to Log Homes
log cabin ideas - or in my case I'd like large beach drift wood and sea blue bathroom. It would look great with beach glass counter..OMG COOL!!!
log cabin ideas - #modern home design #luxury house design #home design ideas| http://cookingguidebrooklyn.blogspot.com
log cabin ideas #home design #modern home design| http://homedesignmarcellatriston.blogspot.com
Stone/granite/slate top with log base ~ rustic bathroom sink
log cabin ideas - bathroom.... for a half bath downstairs
log cabin ideas -Great tiny bathroom idea!
log cabin ideas - bathroom sink
tree trunk & stone sink
log cabin love
Tiny Cabin, Tiny House, Cabins Cottage, Cozy Cabin, Design Blog
Jalopy Cabins Skit Hut Tiny House Interior View - WANT!!! Want that rug or one like it.
tiny log cabin ski hut 3 Tiny Log Cabin by Jalopy Cabins
Jalopy Cabins Skit Hut Tiny House Interior View - WANT!!!
Jalopy Cabins: D-Log Cabin | Busyboo Design Blog
log cabin love - looks like our to be home
Tiny log cabins are so cute! <3
log cabin love- one day
log cabin interior
I would love a log cabin home
Entry Way, Dreamhome, Dream Home, Cabin Dream, Entryway
My dream home would be an incredible modern log home ;)))) like the ones u see in whistler .... Siiigh ;)
Log home doorway. I LOVE this. It reminds me of ski trips in Deer Valley, Utah, where you can stay in the coziest log cabins!
I would love a log cabin home..love this entryway. And the flooring! I could picture looking outside at the snow falling, while a fire burns in the fireplace.
I would love a log cabin this entryway. And the #home decorating before and after #home designs #luxury house design| http://interior-design-513.blogspot.com
Love this entry way into the main part of the log Cabin.
I so want a log cabin! I Love this front door!
Entryway. cozy little log cabin
Log home entryway
cabin loft
Tiny Cabin, Tiny House, Tinyhouse, Small House, Tiny Home
One couple spent one year building this 133-square-foot home #tinyhome #tinyhouse #cozy #DIY #design
tiny house tour.jpg from Christopher Merete's Truly Tiny Home on the Range... amazing what you can do with a very small space
Christopher & Merete's Truly Tiny Home on the Range — House Tour Bookshelf, couch, desk, counter space/storage, space heater, and window inspiration
tiny house tour.jpg http://www.apartmenttherapy.com/christopher-meretes-tiny-home-on-the-range-house-tour-174154
Christopher & Merete's Truly Tiny Home on the Range — House Tour - from The Tiny House Documentary!
Christopher Merete's Truly Tiny Home on the Range — House Tour | Apartment Therapy
The Tiny House Movement....I just really wanna live in a small house like this!!
One day....Christopher & Merete's Truly Tiny Home on the Range — House Tour
tiny cabin interior
log cabin nook
Guest Room, Built In, Kids Bedroom, Kids Room, Builtin, Kidsroom
"These exquisitely carved twin beds traveled across the ocean they now overlook in their current home on a coastal Maine island. The entire log cabin was built in Norway for a U.S. ambassador who wanted to bring a bit of his experience back home."
"These exquisitely carved twin beds traveled across the ocean they now overlook in their current home on a coastal Maine island. The entire log cabin was built in Norway for a U.S. ambassador who wanted to bring a bit of his experience back home. The colorful and ornate built-in sleeping nook brightens the room's expanse of unfinished wood. Everything is connected—the platform flows into the beds' footboards, side rails merge into a shared nightstand..." photography by Brian Vanden Brink
Love these built-in's, kids room, guest room, attic, anything! Looks Great!
amazing twin beds inset in the room, log cabin, great for a guest room
Love this kids room!! #HomeDesign #KidsRoom #RealEstate
log cabin built-ins ...guest room? Love this!
built in children's guest room? Log cabin
more cool kid bedroom ideas
tiny cabin
Tiny Cabin, Garden Shed, Sheds Greenhouses, Potting Sheds, Rustic Garden, Green House, Playhouse
Little rustic garden shed~as perfectly cute as this is~and it's way super cure~I may use it as a bar as much as a potting shed~ok, that's a lie, I'd add a patio on specifically to relax and sip adult beverages <3
Cute and Rustic Garden Sheds on Pinterest | Sheds, Potting Sheds ...
Another garden shed/greenhouse idea. With more windows, of course.
rustic garden shed in Ontario; photo by Flickr user freelancr47
Little rustic garden shed. Would make a cute playhouse!
This tiny cabin would make a great art studio space!
Little rustic garden shed or art studio
Little rustic garden house
little green house
Tiny log cabin...so cute!
Tiny Cabin, Tiny House, Tiny Log Cabin, Guest House, Small House, Tiny Home
Random Tiny Houses « The Tiny #home decorating before and after #interior design #home interior #modern interior design #modern home design
Tiny log cabin. This would be a great idea for a guest house or a little "tree" house for the kids when they have sleep overs. (:
A Log Home.... // ♡ A "GUEST HOUSE" BEHIND THE MAIN HOUSE! [Which I really wish could be our Craft / Artist Studio!!!] ♥A
Tiny log cabin in Taos, New Mexico. I would love this as a guest cottage! http://www.flickr.com/photos/gr00vy/4685367103/in/faves-24137741@N03/ #log #cabin #taos #new #mexico #small #tiny #little #cottage #guest #house
Tiny log cabin in Taos, New Mexico. I would love this as a guest cottage! www.flickr.com/... #log #cabin #taos #new #mexico #small #tiny #little #cottage #guest #house
small unusual homes | Small houses | unique camping/living spaces tree houses
A tiny log home!!! Guest house maybe??
tiny log house
Tiny cabin.
Self-sustainable cabin in maine
Tiny Cabin, Small Cabin, Tiny Homes, Tinyhouse, Tiny Houses, Small Home, Small Houses
I want one! // Small House Style is a web magazine dedicated to all things small home, small house, tiny home, tiny house, prefab, sustainable, design, architecture and modern.
11 Tiny Houses We Love : With a shed roof and corrugated siding, this off-the-grid cabin, beautifully sited on an island off the coast of New England, runs on solar power. A rainwater tank with an instant hot-water heater provides drinking and bathing water, while rolling exterior door panels protect the home in inclement weather. It may be tiny, but this house can stand tall all on its own.
On a tiny island some 20 miles off the coast of Maine, you'll find a tiny cabin. The good news is that you'll also find it on our site. Be sure to tell us what you think of it :-) For more inspiration view the full album on our site at http://theownerbuildernetwork.co/house-hunting/tiny-homes/a-tiny-cabin-in-maine/
Maine Coast Retreat A project 30 years in the making, this tiny off-grid retreat on a coastal island in Maine is almost entirely self-sufficient. Designed and built by Alex Porter for her father, the project features a shed roof and is wrapped in a distinctive blue-grey corrugated... #tinyhouse
Tresa this post is for you and Jason - Build a tiny house to live in while you build your future home then the tiny house can be a mancave! Eschewing excess space and making the most of every inch, these functional-but-small houses prove that bigger is not always better.
Tiny Off-Grid Cabin in Maine is Completely Self-Sustaining | Inhabitat - Sustainable Design Innovation, Eco Architecture, Green Building | Tiny Homes
OFF-GRID Self Sustainable House - inhabitat.com With a Shed Roof and Corrugated Siding, this off-the-grid cabin runs on Solar Power. A Rainwater Tank with an instant hot-water heater provides drinking and bathing water. Rolling Exterior Door Panels protect the home in inclement weather. It may be Tiny, but stand Tall all on its own. http://inhabitat.com/?s=tiny+houses
Some people dream big. I dream small. A small house that is - small space, big views.
small cabin
Cabin House Plan 76163
First Floor Plan of Cabin House Plan 76163
Tiny House, Guest House, Floor Plans, Floorplan, Small House, Cabin Plans, House Plans
Cottage Style House Plan - 1 Beds 1 Baths 320 Sq/Ft Plan #23-2287 Floor Plan - Main Floor Plan - Houseplans.com
Change the two single beds out for a queen bed - perfect granny flat. First Floor Plan of Cabin House Plan 76163
House Plan No.141091 House Plans by WestHomePlanners.com. Nice plan, but for full time living comfort, this house needs the few extra feet that will allow a decent sized closet in the bedroom and a washer dryer space.
Plan W21760DR: Narrow Lot, Vacation, Cottage, Metric, Canadian House Plans & Home Designs
1st level 320 sq.ft. Recreational tiny home or tiny cabin for 2 to 6 people - Wodwinds
Cottage 1 Beds 1 Baths 320 Sq/Ft Plan #23-2287 Main Floor Plan - Houseplans.com
I Just Love Tiny Houses!: Tiny House Layout
320 square foot floorplan.
Another great guest house
Great idea for a tiny cabin. The booth seating offers versatility for guests, as a workspace, and if you were really crafty I bet it could convert to a bed like in a camper.
Small Cabin, Tiny Cabin, Tiny House, Good Ideas, Cabin Ideas, Cabin Inside, Guest House, Guest Cabin
small-cabin-inside My husband would love the booth table. I would put storage under the seats.
small-cabin-inside....table like a pop up camper...can convert into a bed
small-cabin-inside Our table when finished will be very similar to this
Cute small cabin! would make an amazing guest house too!
Cabin Interior, Dinette, Loft
Great idea for a tiny house.
Cabin Ideas
Could we use some of the barn wood to do this in the bathroom...wider shelves, maybe?
Cabin Ideas, Narrowboat Interior, Tiny House, Cabin Kitchens, Rustic Cabin, Rustic Kitchen
cabin#kitchen designs #kitchen decorating before and after #kitchen interior design #modern kitchen design #kitchen design| http://modern-kitchen-design-17.blogspot.com
Small open pantry in this rustic cabin interior
Log cabin pantry/kitchen.
Barn wood rustic kitchen
cabin kitchen storage
narrowboat interior
cabin storage
kitchen idea
Cabin ideas
no shortage on amenities from front porch to interior living area; sweet kitchen, entry mudroom, open concept gathering room with fab fireplace, ladder to additional sleeping space & master bath/bedroom just off the main conversation area :: Family Cabin Retreat :: view 1 of 3
Logcabin, Tiny House, Cozy Cabin, Cabin Loft, Cabin Idea, Rustic Cabin, House Idea
My cozy cabin on the lake in Minnesota!!!
Swaback Partners cabin: loft loft loft
Rustic cabin... love Love LOVE this!
.Looks like Brands cabin. Loft.
.small and cozy cabin. t
Log cabin interior
Tiny house idea
Log cabin loft
cabin ideas


text:
List all words ending with dustrags
Only the word dustrags was found, nothing longer.
Some random words: svaraj tho pya evulsion pya ne dhobi
This is not a dictionary, it's a word game wordfinder.
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Grated Parmesan cheese can get moldy, too
Dear Heloise: Most cheese, even when stored in the refrigerator, will begin to mold after awhile. However, the Parmesan cheese in the shaker-type container, no matter how long it is kept, seems never to develop mold. Does it ever develop mold and it just can't be seen, or does it simply not mold? How long should one keep this cheese for safe consumption? This would seem to be an important question for us all.
– Ray M., via email
Well, Ray, here's what I found, after calling the manufacturer. The cheese will show mold eventually, even if kept under the best refrigerated conditions. So, make sure to consume the cheese within three months after the "Best When Purchased By" date that is stamped on the bottom of the container.
– Heloise
P.S.: I write the date that I open the container on the bottom in black marker. This way, I know when several months have passed and I need to purchase new cheese.
Dear Heloise: I save my grocery-store receipt until the next time I go shopping. I use a magnet to stick it on the side of my refrigerator. This is handy, because I can look at the receipt to see what foods I bought as a reminder that I need to use things before they go bad. Also, if I come across a bad product, I have the receipt, so I can take it back and get a refund.
– Linda C. in Washington
Dear Heloise: I've tried the various "sponge dishes," etc., that are commercially available and have yet to find one that doesn't collect soap scum or leave my sponge smelling of mildew.
To solve the dilemma, I cut vertically into the open end of a plastic, net vegetable bag (potatoes and Brussels sprouts, for example, come in these). I make the cut long enough that I can tie a knot with the two sides and still have a 4-inch opening. I have a heavyweight soap dispenser sitting on the edge of my sink. I tie the net bag around the neck of the soap dispenser so that it hangs into the sink without touching it. I slip my sponge into the open slit of the bag, and it hangs in the sink. The sponge dries quickly after each use.
– Margaret B., via email
Dear Heloise: When I am making cupcakes or muffins, I use a measuring cup to put the batter in the cupcake/muffin tin. No more mess!
– Betty H. in Ohio
Dear Heloise: My daughter loves different juices, but hates that they water down so easily over ice. She began freezing grapes and using them in place of ice cubes. She's tried a few different types of fruit, but grapes certainly work best. Her idea gave me one: using frozen grapes to chill wine! It's worked great!
– Shelby T. in Oregon
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Corning: At least three years until flexible displays
Apple screen glass supplier Corning claims that "it will probably take at least three years before companies start making flexible displays using its new Willow material," according to a report. Corning Glass Technologies president James Clappin said that companies have yet to come up with products that can fully take advantage of Willow glass, which can roll up in a manner similar to newsprint. Recent reports have suggested that Apple could use Willow to create a curved glass display in its rumored iWatch; Apple is said to be experimenting with curved glass designs, but it appears unlikely that Willow will be used in the immediate future. Corning is currently producing Willow glass, and teaching "very big name" customers how to handle it, Clappin said. [via Bloomberg]
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