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Sample records for vivo pth provokes

  1. In vivo PTH provokes apical NHE3 and NaPi2 redistribution and Na-K-ATPase inhibition

    DEFF Research Database (Denmark)

    Zhang, Y; Norian, J M; Magyar, C E

    1999-01-01

    The aim of this study was to test the hypothesis that in vivo administration of parathyroid hormone (PTH) provokes diuresis/natriuresis through redistribution of proximal tubule apical sodium cotransporters (NHE3 and NaPi2) to internal stores and inhibition of basolateral Na-K-ATPase activity and...

  2. Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns

    DEFF Research Database (Denmark)

    Leong, Patrick K K; Yang, Li E; Lin, Harrison W

    2004-01-01

    in renal cortical membranes fractionated on sorbitol density gradients. Aortic clamp-induced acute hypotension (from 100 +/- 3 to 78 +/- 2 mmHg) provoked a 62% decrease in urine output and a significant decrease in volume flow from the proximal tubule detected as a 66% decrease in endogenous lithium......-density membranes enriched in apical markers. PTH at much lower doses (

  3. A PTH-responsive circadian clock operates in ex vivo mouse femur fracture healing site.

    Science.gov (United States)

    Kunimoto, Tatsuya; Okubo, Naoki; Minami, Yoichi; Fujiwara, Hiroyoshi; Hosokawa, Toshihiro; Asada, Maki; Oda, Ryo; Kubo, Toshikazu; Yagita, Kazuhiro

    2016-02-29

    The circadian clock contains clock genes including Bmal1 and Period2, and it maintains an interval rhythm of approximately 24 hours (the circadian rhythm) in various organs including growth plate and articular cartilage. As endochondral ossification is involved not only in growth plate but also in fracture healing, we investigated the circadian clock functions in fracture sites undergoing healing. Our fracture models using external fixation involved femurs of Period2::Luciferase knock-in mice which enables the monitoring of endogenous circadian clock state via bioluminescence. Organ culture was performed by collecting femurs, and fracture sites were observed using bioluminescence imaging systems. Clear bioluminescence rhythms of 24-hour intervals were revealed in fracture healing sites. When parathyroid hormone (PTH) was administered to fractured femurs in organ culture, peak time of Period2::Luciferase activity in fracture sites and growth plates changed, indicating that PTH-responsive circadian clock functions in the mouse femur fracture healing site. While PTH is widely used in treating osteoporosis, many studies have reported that it contributes to improvement of fracture healing. Future studies of the role of this local clock in wound healing may reveal a novel function of the circadian timing mechanism in skeletal cells.

  4. PTH Test

    Science.gov (United States)

    ... diseases that disrupt this feedback loop can cause inappropriate elevations or decreases in calcium and PTH levels ... More Common Questions See Less Common Questions Related Content On This Site Tests: Calcium ; Phosphorus ; Magnesium ; Vitamin ...

  5. Klotho lacks a vitamin D independent physiological role in glucose homeostasis, bone turnover, and steady-state PTH secretion in vivo.

    Directory of Open Access Journals (Sweden)

    René Anour

    Full Text Available Apart from its function as co-receptor for fibroblast growth factor-23 (FGF23, Klotho is thought to regulate insulin signaling, intracellular oxidative stress, and parathyroid hormone (PTH secretion in an FGF23 independent fashion. Here, we crossed Klotho deficient (Kl⁻/⁻ mice with vitamin D receptor (VDR mutant mice to examine further vitamin D independent functions of Klotho. All mice were fed a rescue diet enriched with calcium, phosphorus, and lactose to prevent hyperparathyroidism in VDR mutants, and were killed at 4 weeks of age after double fluorochrome labeling. Kl⁻/⁻ mice displayed hypercalcemia, hyperphosphatemia, dwarfism, organ atrophy, azotemia, pulmonary emphysema, and osteomalacia. In addition, glucose and insulin tolerance tests revealed hypoglycemia and profoundly increased peripheral insulin sensitivity in Kl⁻/⁻ mice. Compound mutants were normocalcemic and normophosphatemic, did not show premature aging or organ atrophy, and were phenocopies of VDR mutant mice in terms of body weight, bone mineral density, bone metabolism, serum calcium, serum phosphate, serum PTH, gene expression in parathyroid glands, as well as urinary calcium and phosphate excretion. Furthermore, ablation of vitamin D signaling in double mutants completely normalized glucose and insulin tolerance, indicating that Klotho has no vitamin D independent effects on insulin signaling. Histomorphometry of pancreas islets showed similar beta cell volume per body weight in all groups of animals. In conclusion, our findings cast doubt on a physiologically relevant vitamin D and Fgf23 independent function of Klotho in the regulation of glucose metabolism, bone turnover, and steady-state PTH secretion in vivo.

  6. Recovery following Thyroxine Treatment Withdrawal, but Not Propylthiouracil, Averts In Vivo and Ex Vivo Thyroxine-Provoked Cardiac Complications in Adult FVB/N Mice

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    Nancy S. Saad

    2017-01-01

    Full Text Available Persistent cardiovascular pathology has been described in hyperthyroid patients even with effective antithyroid treatment. Here, we studied the effect of a well-known antithyroid drug, propylthiouracil (PTU; 20 mg/kg/day, on thyroxine (T4; 500 µg/kg/day-induced increase in blood pressure (BP, cardiac hypertrophy, and altered responses of the contractile myocardium both in vivo and ex vivo after 2 weeks of treatment. Furthermore, the potential recovery through 2 weeks of T4 treatment discontinuation was also investigated. PTU and T4 recovery partially reduced the T4-prompted increase in BP. Alternatively, PTU significantly improved the in vivo left ventricular (LV function with no considerable effects on cardiac hypertrophy or ex vivo right ventricular (RV contractile alterations subsequent to T4 treatment. Conversely, T4 recovery considerably enhanced the T4-provoked cardiac changes both in vivo and ex vivo. Altogether, our data is in agreement with the proposal that hyperthyroidism-induced cardiovascular pathology could persevere even with antithyroid treatments, such as PTU. However, this cannot be generalized and further investigation with different antithyroid treatments should be executed. Moreover, we reveal that recovery following experimental hyperthyroidism could potentially ameliorate cardiac function and decrease the risk for additional cardiac complications, yet, this appears to be model-dependent and should be cautiously construed.

  7. Parathyroid hormone (PTH) blood test

    Science.gov (United States)

    ... gov/ency/article/003690.htm Parathyroid hormone (PTH) blood test To use the sharing features on this page, ... to measure the amount of PTH in your blood. How the Test is Performed A blood sample is needed. How ...

  8. Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.

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    Beatrice Cousin

    Full Text Available BACKGROUND: Normal tissue homeostasis is maintained by dynamic interactions between epithelial cells and their microenvironment. Disrupting this homeostasis can induce aberrant cell proliferation, adhesion, function and migration that might promote malignant behavior. Indeed, aberrant stromal-epithelial interactions contribute to pancreatic ductal adenocarcinoma (PDAC spread and metastasis, and this raises the possibility that novel stroma-targeted therapies represent additional approaches for combating this malignant disease. The aim of the present study was to determine the effect of human stromal cells derived from adipose tissue (ADSC on pancreatic tumor cell proliferation. PRINCIPAL FINDINGS: Co-culturing pancreatic tumor cells with ADSC and ADSC-conditioned medium sampled from different donors inhibited cancer cell viability and proliferation. ADSC-mediated inhibitory effect was further extended to other epithelial cancer-derived cell lines (liver, colon, prostate. ADSC conditioned medium induced cancer cell necrosis following G1-phase arrest, without evidence of apoptosis. In vivo, a single intra-tumoral injection of ADSC in a model of pancreatic adenocarcinoma induced a strong and long-lasting inhibition of tumor growth. CONCLUSION: These data indicate that ADSC strongly inhibit PDAC proliferation, both in vitro and in vivo and induce tumor cell death by altering cell cycle progression. Therefore, ADSC may constitute a potential cell-based therapeutic alternative for the treatment of PDAC for which no effective cure is available.

  9. Experimental Evidence that In Vivo Intracerebral Administration of L-2-Hydroxyglutaric Acid to Neonatal Rats Provokes Disruption of Redox Status and Histopathological Abnormalities in the Brain.

    Science.gov (United States)

    Ribeiro, Rafael Teixeira; Zanatta, Ângela; Amaral, Alexandre Umpierrez; Leipnitz, Guilhian; de Oliveira, Francine Hehn; Seminotti, Bianca; Wajner, Moacir

    2018-02-06

    Tissue accumulation of L-2-hydroxyglutaric acid (L-2-HG) is the biochemical hallmark of L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic inherited disease characterized by neurological symptoms and brain white matter abnormalities whose pathogenesis is not yet well established. L-2-HG was intracerebrally administered to rat pups at postnatal day 1 (P1) to induce a rise of L-2-HG levels in the central nervous system (CNS). Thereafter, we investigated whether L-2-HG in vivo administration could disturb redox homeostasis and induce brain histopathological alterations in the cerebral cortex and striatum of neonatal rats. L-2-HG markedly induced the generation of reactive oxygen species (increase of 2',7'-dichloroflurescein-DCFH-oxidation), lipid peroxidation (increase of malondialdehyde concentrations), and protein oxidation (increase of carbonyl formation and decrease of sulfhydryl content), besides decreasing the antioxidant defenses (reduced glutathione-GSH) and sulfhydryl content in the cerebral cortex. Alterations of the activities of various antioxidant enzymes were also observed in the cerebral cortex and striatum following L-2-HG administration. Furthermore, L-2-HG-induced lipid peroxidation and GSH decrease in the cerebral cortex were prevented by the antioxidant melatonin and by the classical antagonist of NMDA glutamate receptor MK-801, suggesting the involvement of reactive species and of overstimulation of NMDA receptor in these effects. Finally, L-2-HG provoked significant vacuolation and edema particularly in the cerebral cortex with less intense alterations in the striatum that were possibly associated with the unbalanced redox homeostasis caused by this metabolite. Taken together, it is presumed that these pathomechanisms may underlie the neurological symptoms and brain abnormalities observed in the affected patients.

  10. Provoked vestibulodynia: current perspectives

    OpenAIRE

    Henzell,Helen; Berzins,Karen; Langford,Jennifer

    2017-01-01

    Helen Henzell,1,2 Karen Berzins,1,3 Jennifer P Langford4 1Melbourne Sexual Health Centre, Carlton, 2Action Centre, Family Planning Victoria, Melbourne, 3Dermatology/Vulval Conditions Clinic, Mercy Hospital for Women, Heidelberg, 4Clifton Hill Physiotherapy, Clifton Hill, VIC, Australia Abstract: Provoked vestibulodynia (PVD) refers to vulvar pain of at least 3 months duration, localized to the vestibule, provoked by touch and sexual activity and occurring in the absence of a clear identifia...

  11. Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in Klotho-/- mice.

    Directory of Open Access Journals (Sweden)

    Quan Yuan

    Full Text Available Maintenance of normal mineral ion homeostasis is crucial for many biological activities, including proper mineralization of the skeleton. Parathyroid hormone (PTH, Klotho, and FGF23 have been shown to act as key regulators of serum calcium and phosphate homeostasis through a complex feedback mechanism. The phenotypes of Fgf23(-/- and Klotho(-/- (Kl(-/- mice are very similar and include hypercalcemia, hyperphosphatemia, hypervitaminosis D, suppressed PTH levels, and severe osteomalacia/osteoidosis. We recently reported that complete ablation of PTH from Fgf23(-/- mice ameliorated the phenotype in Fgf23(-/-/PTH(-/- mice by suppressing serum vitamin D and calcium levels. The severe osteomalacia in Fgf23(-/- mice, however, persisted, suggesting that a different mechanism is responsible for this mineralization defect. In the current study, we demonstrate that deletion of PTH from Kl(-/- (Kl(-/-/PTH(-/- or DKO mice corrects the abnormal skeletal phenotype. Bone turnover markers are restored to wild-type levels; and, more importantly, the skeletal mineralization defect is completely rescued in Kl(-/-/PTH(-/- mice. Interestingly, the correction of the osteomalacia is accompanied by a reduction in the high levels of osteopontin (Opn in bone and serum. Such a reduction in Opn levels could not be observed in Fgf23(-/-/PTH(-/- mice, and these mice showed sustained osteomalacia. This significant in vivo finding is corroborated by in vitro studies using calvarial osteoblast cultures that show normalized Opn expression and rescued mineralization in Kl(-/-/PTH(-/- mice. Moreover, continuous PTH infusion of Kl(-/- mice significantly increased Opn levels and osteoid volume, and decreased trabecular bone volume. In summary, our results demonstrate for the first time that PTH directly impacts the mineralization disorders and skeletal deformities of Kl(-/-, but not of Fgf23(-/- mice, possibly by regulating Opn expression. These are significant new perceptions into

  12. Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH-induced bone anabolism in mice.

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    Yu, Mingcan; D'Amelio, Patrizia; Tyagi, Abdul Malik; Vaccaro, Chiara; Li, Jau-Yi; Hsu, Emory; Buondonno, Ilaria; Sassi, Francesca; Adams, Jonathan; Weitzmann, M Neale; DiPaolo, Richard; Pacifici, Roberto

    2017-11-20

    Teriparatide is a bone anabolic treatment for osteoporosis, modeled in animals by intermittent PTH (iPTH) administration, but the cellular and molecular mechanisms of action of iPTH are largely unknown. Here, we show that Teriparatide and iPTH cause a ~two-threefold increase in the number of regulatory T cells (Tregs) in humans and mice. Attesting in vivo relevance, blockade of the Treg increase in mice prevents the increase in bone formation and trabecular bone volume and structure induced by iPTH Therefore, increasing the number of Tregs is a pivotal mechanism by which iPTH exerts its bone anabolic activity. Increasing Tregs pharmacologically may represent a novel bone anabolic therapy, while iPTH-induced Treg increase may find applications in inflammatory conditions and transplant medicine. © 2017 The Authors.

  13. Maximizing PTH Anabolic Osteoporosis Therapy

    Science.gov (United States)

    2014-09-01

    rod-like to a plate- like form, and the lower the value, the more plate-like the shape , which is indicative of an increase in bone strength [18]. PTH...serum CTX, perhaps in part a consequence of the enhanced activity of the null osteo- clasts . Despite the multiple lines of evidence suggesting higher...Additionally, c-Fos has multiple and complex roles in regulating osteoblast-derived signals that regulate osteoclastogenesis and mature osteo- clast

  14. Parathyroid-Specific Deletion of Klotho Unravels a Novel Calcineurin-Dependent FGF23 Signaling Pathway That Regulates PTH Secretion

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    Olauson, Hannes; Lindberg, Karolina; Amin, Risul; Sato, Tadatoshi; Jia, Ting; Goetz, Regina; Mohammadi, Moosa; Andersson, Göran; Lanske, Beate; Larsson, Tobias E.

    2013-01-01

    Klotho acts as a co-receptor for and dictates tissue specificity of circulating FGF23. FGF23 inhibits PTH secretion, and reduced Klotho abundance is considered a pathogenic factor in renal secondary hyperparathyroidism. To dissect the role of parathyroid gland resident Klotho in health and disease, we generated mice with a parathyroid-specific Klotho deletion (PTH-KL−/−). PTH-KL−/− mice had a normal gross phenotype and survival; normal serum PTH and calcium; unaltered expression of the PTH gene in parathyroid tissue; and preserved PTH response and sensitivity to acute changes in serum calcium. Their PTH response to intravenous FGF23 delivery or renal failure did not differ compared to their wild-type littermates despite disrupted FGF23-induced activation of the MAPK/ERK pathway. Importantly, calcineurin-NFAT signaling, defined by increased MCIP1 level and nuclear localization of NFATC2, was constitutively activated in PTH-KL−/− mice. Treatment with the calcineurin-inhibitor cyclosporine A abolished FGF23-mediated PTH suppression in PTH-KL−/− mice whereas wild-type mice remained responsive. Similar results were observed in thyro-parathyroid explants ex vivo. Collectively, we present genetic and functional evidence for a novel, Klotho-independent, calcineurin-mediated FGF23 signaling pathway in parathyroid glands that mediates suppression of PTH. The presence of Klotho-independent FGF23 effects in a Klotho-expressing target organ represents a paradigm shift in the conceptualization of FGF23 endocrine action. PMID:24348262

  15. Management of provoked seizure

    Directory of Open Access Journals (Sweden)

    Misra Usha

    2011-01-01

    Full Text Available A provoked seizure may be due to structural damage (resulting from traumatic brain injury, brain tumor, stroke, tuberculosis, or neurocysticercosis or due to metabolic abnormalities (such as alcohol withdrawal and renal or hepatic failure. This article is a part of the Guidelines for Epilepsy in India. This article reviews the problem of provoked seizure and its management and also provides recommendations based on currently available information. Seizure provoked by metabolic disturbances requires correction of the triggering factors. Benzodiazepines are recommended for treatment of seizure due to alcohol withdrawal; gabapentin for seizure seen in porphyria; and antiepileptic drugs (AED, that are not inducer of hepatic enzymes, in the seizures seen in hepatic dysfunction. In severe traumatic brain injury, with or without seizure, phenytoin (PHT may be given for 7 days. In ischemic or hemorrhagic stroke one may individualize the AED therapy. In cerebral venous sinus thrombosis (CVST, AED may be prescribed if there is seizure or computed tomographic (CT abnormalities or focal weakness; the treatment, in these cases, has to be continued for 1 year. Prophylactic AED is not recommended in cases of brain tumor and neurosurgical procedures and if patient is on an AED it can be stopped after 1 week.

  16. Management of provoked seizure.

    Science.gov (United States)

    Misra, Usha Kant; Kalita, Jayantee

    2011-01-01

    A provoked seizure may be due to structural damage (resulting from traumatic brain injury, brain tumor, stroke, tuberculosis, or neurocysticercosis) or due to metabolic abnormalities (such as alcohol withdrawal and renal or hepatic failure). This article is a part of the Guidelines for Epilepsy in India. This article reviews the problem of provoked seizure and its management and also provides recommendations based on currently available information. Seizure provoked by metabolic disturbances requires correction of the triggering factors. Benzodiazepines are recommended for treatment of seizure due to alcohol withdrawal; gabapentin for seizure seen in porphyria; and antiepileptic drugs (AED), that are not inducer of hepatic enzymes, in the seizures seen in hepatic dysfunction. In severe traumatic brain injury, with or without seizure, phenytoin (PHT) may be given for 7 days. In ischemic or hemorrhagic stroke one may individualize the AED therapy. In cerebral venous sinus thrombosis (CVST), AED may be prescribed if there is seizure or computed tomographic (CT) abnormalities or focal weakness; the treatment, in these cases, has to be continued for 1 year. Prophylactic AED is not recommended in cases of brain tumor and neurosurgical procedures and if patient is on an AED it can be stopped after 1 week.

  17. Provoked vestibulodynia: current perspectives.

    Science.gov (United States)

    Henzell, Helen; Berzins, Karen; Langford, Jennifer P

    2017-01-01

    Provoked vestibulodynia (PVD) refers to vulvar pain of at least 3 months duration, localized to the vestibule, provoked by touch and sexual activity and occurring in the absence of a clear identifiable cause. The clinical spectrum ranges from mild with distressing discomfort through to severe and disabling pain. Current understanding is that PVD is one of many chronic pain conditions characterized by sensitization of peripheral and central nociceptive pathways, with pain arising due to dysfunctional neuronal activity in the absence of painful stimuli. Pathophysiology is not well understood but is likely a complex interplay of environmental, genetic, psychological and immune factors. Care is multidisciplinary and follows general principles of chronic pain management with the addition of specific therapy tailored to address pelvic floor overactivity, and sexual and relationship difficulties. More recently, the therapeutic use of placebo is gaining traction in chronic pain research and is a very promising adjunctive therapy. The majority of women with PVD are managed outside of tertiary clinic settings, and care depends on availability and affordability of specialized services; however, much can be done by the primary health provider. PVD is common, and highly treatable, especially with early intervention, but unfortunately, many clinicians are unaware of this condition, and the biggest hurdle for women accessing treatment is obtaining a diagnosis. With treatment, most women can expect significant improvement, often with fairly simple interventions, although some women will benefit from referral to specialized centers. The aims of this article are twofold: firstly, to summarize current literature concerning PVD pathophysiology and management; secondly, to provide a framework for clinicians unfamiliar with vulvar medicine to understand and manage PVD.

  18. Provoked vestibulodynia: current perspectives

    Directory of Open Access Journals (Sweden)

    Henzell H

    2017-09-01

    Full Text Available Helen Henzell,1,2 Karen Berzins,1,3 Jennifer P Langford4 1Melbourne Sexual Health Centre, Carlton, 2Action Centre, Family Planning Victoria, Melbourne, 3Dermatology/Vulval Conditions Clinic, Mercy Hospital for Women, Heidelberg, 4Clifton Hill Physiotherapy, Clifton Hill, VIC, Australia Abstract: Provoked vestibulodynia (PVD refers to vulvar pain of at least 3 months duration, localized to the vestibule, provoked by touch and sexual activity and occurring in the absence of a clear identifiable cause. The clinical spectrum ranges from mild with distressing discomfort through to severe and disabling pain. Current understanding is that PVD is one of many chronic pain conditions characterized by sensitization of peripheral and central nociceptive pathways, with pain arising due to dysfunctional neuronal activity in the absence of painful stimuli. Pathophysiology is not well understood but is likely a complex interplay of environmental, genetic, psychological and immune factors. Care is multidisciplinary and follows general principles of chronic pain management with the addition of specific therapy tailored to address pelvic floor overactivity, and sexual and relationship difficulties. More recently, the therapeutic use of placebo is gaining traction in chronic pain research and is a very promising adjunctive therapy. The majority of women with PVD are managed outside of tertiary clinic settings, and care depends on availability and affordability of specialized services; however, much can be done by the primary health provider. PVD is common, and highly treatable, especially with early intervention, but unfortunately, many clinicians are unaware of this condition, and the biggest hurdle for women accessing treatment is obtaining a diagnosis. With treatment, most women can expect significant improvement, often with fairly simple interventions, although some women will benefit from referral to specialized centers. The aims of this article are twofold

  19. Provoked vestibulodynia: current perspectives

    Science.gov (United States)

    Henzell, Helen; Berzins, Karen; Langford, Jennifer P

    2017-01-01

    Provoked vestibulodynia (PVD) refers to vulvar pain of at least 3 months duration, localized to the vestibule, provoked by touch and sexual activity and occurring in the absence of a clear identifiable cause. The clinical spectrum ranges from mild with distressing discomfort through to severe and disabling pain. Current understanding is that PVD is one of many chronic pain conditions characterized by sensitization of peripheral and central nociceptive pathways, with pain arising due to dysfunctional neuronal activity in the absence of painful stimuli. Pathophysiology is not well understood but is likely a complex interplay of environmental, genetic, psychological and immune factors. Care is multidisciplinary and follows general principles of chronic pain management with the addition of specific therapy tailored to address pelvic floor overactivity, and sexual and relationship difficulties. More recently, the therapeutic use of placebo is gaining traction in chronic pain research and is a very promising adjunctive therapy. The majority of women with PVD are managed outside of tertiary clinic settings, and care depends on availability and affordability of specialized services; however, much can be done by the primary health provider. PVD is common, and highly treatable, especially with early intervention, but unfortunately, many clinicians are unaware of this condition, and the biggest hurdle for women accessing treatment is obtaining a diagnosis. With treatment, most women can expect significant improvement, often with fairly simple interventions, although some women will benefit from referral to specialized centers. The aims of this article are twofold: firstly, to summarize current literature concerning PVD pathophysiology and management; secondly, to provide a framework for clinicians unfamiliar with vulvar medicine to understand and manage PVD. PMID:28979166

  20. Evidence for a role of intracellular stored parathyroid hormone in producing hysteresis of the PTH-calcium relationship in normal humans

    DEFF Research Database (Denmark)

    Schwarz, Peter; Madsen, J C; Rasmussen, A Q

    1998-01-01

    OBJECTIVE: Despite the clear recognition that extracellular ionized calcium controls PTH secretion, there have been suggestions of hysteresis in the relationship between extracellular ionized calcium and PTH during recovery from induced hypo- and hypercalcaemia in vivo in humans. In this study, we...... examined the possibility that release of intracellular stored PTH during induced hypocalcaemia may explain hysteresis. VOLUNTEERS: Eleven volunteers, five women and six men, were recruited to participate in the study. DESIGN: A series of three protocols of repeated induction of hypocalcaemia or sequential...... depot PTH can explain, at least in part, the observed hysteretic PTH-calcium relationship in normal humans....

  1. Pre-clinical studies of toxin-specific Nanobodies: Evidence of in vivo efficacy to prevent fatal disturbances provoked by scorpion envenoming

    Energy Technology Data Exchange (ETDEWEB)

    Hmila, Issam [Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Cosyns, Bernard [Laboratory of In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel (Belgium); Tounsi, Hayfa [Service d' Anatomo-Pathologie, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Roosens, Bram; Caveliers, Vicky [Laboratory of In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel (Belgium); Abderrazek, Rahma Ben [Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Boubaker, Samir [Service d' Anatomo-Pathologie, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Muyldermans, Serge [Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussel (Belgium); Department of Structural Biology, VIB, Brussels (Belgium); El Ayeb, Mohamed [Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Bouhaouala-Zahar, Balkiss, E-mail: balkiss.bouhaouala@pasteur.rns.tn [Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, BP-74, 1002 Tunis (Tunisia); Faculté de Médecine de Tunis, Université de Tunis-El Manar (Tunisia); Lahoutte, Tony [Laboratory of In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel (Belgium)

    2012-10-15

    Scorpions represent a significant threat to humans and animals in various countries throughout the world. Recently, we introduced Nanobodies (Nbs) to combat more efficiently scorpion envenoming and demonstrated the performance of NbAahIF12 and NbAahII10 to neutralize scorpion toxins of Androctonus australis hector venom. A bispecific Nb construct (NbF12-10) comprising these two Nbs is far more protective than the classic Fab′{sub 2} based therapy and is the most efficient antivenom therapy against scorpion sting in preclinical studies. Now we investigate the biodistribution and pharmacokinetics of {sup 99m}Tc labeled Nbs by in vivo imaging in rodents and compared these data with those of the Fab′{sub 2} product (PAS). The pharmacodynamics of the Nbs was investigated in rats by in vivo echocardiography and it is shown that NbF12-10 prevents effectively the hemodynamic disturbances induced by a lethal dose of venom. Moreover, even a late injection of NbF12-10 restores the heart rate and brings the blood pressure to baseline values. Histology confirms that NbF12-10 prevents lung and heart lesions of treated mice after envenoming. In conjunction, in this preclinical study, we provide proof of concept that NbF12-10 prevents effectively the fatal disturbances induced by Androctonus venom, and that the Nanobody based therapeutic has a potential to substitute the classic Fab′{sub 2} based product as immunotherapeutic in scorpion envenoming. Further clinical study using larger cohorts of animals should be considered to confirm the full protecting potential of our NbF12-10. -- Highlights: ► Nanobody therapy prevents the hemodynamic disturbances induced by a lethal dose. ► Late injection of Nanobody restores hemodynamic parameters to baseline values. ► Nanobody therapy prevents lung and heart lesions of treated mice after envenoming. ► Labeled Nanobody and Fab’2 pharmacokinetics curves reach plateau in favour of Nanobody.

  2. Phosphorus overload and PTH induce aortic expression of Runx2 in experimental uraemia.

    Science.gov (United States)

    Graciolli, Fabiana G; Neves, Katia R; dos Reis, Luciene M; Graciolli, Rafael G; Noronha, Irene L; Moysés, Rosa M A; Jorgetti, Vanda

    2009-05-01

    Vascular calcification (VC) is commonly seen in patients with chronic kidney disease (CKD). Elevated levels of phosphate and parathormone (PTH) are considered nontraditional risk factors for VC. It has been shown that, in vitro, phosphate transforms vascular smooth muscle cells (VSMCs) into calcifying cells, evidenced by upregulated expression of runt-related transcription factor 2 (Runx2), whereas PTH is protective against VC. In addition, Runx2 has been detected in calcified arteries of CKD patients. However, the in vivo effect of phosphate and PTH on Runx2 expression remains unknown. Wistar rats were submitted to parathyroidectomy, 5/6 nephrectomy (Nx) and continuous infusion of 1-34 rat PTH (at physiological or supraphysiological rates) or were sham-operated. Diets varied only in phosphate content, which was low (0.2%) or high (1.2%). Biochemical, histological, immunohistochemistry and immunofluorescence analyses were performed. Nephrectomized animals receiving high-PTH infusion presented VC, regardless of the phosphate intake level. However, phosphate overload and normal PTH infusion induced phenotypic changes in VSMCs, as evidenced by upregulated aortic expression of Runx2. High-PTH infusion promoted histological changes in the expression of osteoprotegerin and type I collagen in calcified arteries. Phosphate, by itself is a potential pathogenic factor for VC. It is of note that phosphate overload, even without VC, was associated with overexpression of Runx2 in VSMCs. The mineral imbalance often seen in patients with CKD should be corrected.

  3. Primary hyperparathyroidism: intraoperative PTH-measurements

    DEFF Research Database (Denmark)

    Rolighed, L; Heickendorff, L; Hessov, I

    2004-01-01

    BACKGROUND: With the development of rapid assays and intraoperative measurement of intact parathyroid hormone (PTH), new strategies in the handling of patients with primary hyperparathyroidism (pHPT) have evolved. AIM: The aim of our study was to illustrate the performance of the intraoperative PTH...... positive and cured, 11 patients (8%) were test negative but cured, and 10 patients (7%) were test negative and not cured by the primary operation. Consequently, the sensitivity of the test was 0.92 and the specificity 1.00. CONCLUSIONS: The rapid PTH test used is a reliable predictor of a successful...

  4. Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34.

    Directory of Open Access Journals (Sweden)

    Yongxin Ren

    Full Text Available Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH.Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/- mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/- mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/- mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/- mice compared to vehicle-treated wild-type and Pth(-/- mice.Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.

  5. ZP2307, a novel cyclic PTH(1-17) analog, reversed established osteopenia in adult ovariectomized rats

    DEFF Research Database (Denmark)

    Vääräniemi, Jukka; Morko, Jukka; Peng, ZhiQi

    -17) analog, ZP2307, with a high efficacy and potency on the human PTH receptor in vitro. This study characterized the effects of intermittent treatment with ZP2307 on established osteopenia in adult ovariectomized (OVX) rats. Female Sprague-Dawley rats were ovariectomized at 6 months of age. After 6 weeks......Recombinant human parathyroid hormone (PTH) analogs (1-34) and (1-84) are used as bone anabolic agents in clinical practice. Hitherto, PTH analogs shorter than 28 amino acids have not demonstrated any bone anabolic activity in vivo. Recently, Zealand Pharma A/S has developed a novel, cyclic PTH(1......-34). This study demonstrated that the intermittent treatment with ZP2307, the novel cyclic PTH(1-17) analog, is effective in reversing the established osteopenia in adult OVX rats to normal conditions. Due to its broad dose response relationship, ZP2307 may have a wider therapeutic window and a better safety...

  6. Comparison of Intact PTH and Bio-Intact PTH Assays Among Non-Dialysis Dependent Chronic Kidney Disease Patients.

    Science.gov (United States)

    Einbinder, Yael; Benchetrit, Sydney; Golan, Eliezer; Zitman-Gal, Tali

    2017-09-01

    The third-generation bio-intact parathyroid hormone (PTH) (1-84) assay was designed to overcome problems associated with the detection of C-terminal fragments by the second-generation intact PTH assay. The two assays have been compared primarily among dialysis populations. The present study evaluated the correlations and differences between these two PTH assays among patients with chronic kidney disease (CKD) stages 3 to 5 not yet on dialysis. Blood samples were collected from 98 patients with CKD stages 3 to 5. PTH concentrations were measured simultaneously by using the second-generation - PTH intact-STAT and third-generation bio-intact 1-84 PTH assays. Other serum biomarkers of bone mineral disorders were also assessed. CKD stage was calculated by using the CKD-Epidemiology Collaboration (EPI) formula. Serum bio-intact PTH concentrations were strongly correlated but significantly lower than the intact PTH concentrations (r=0.963, Pbio-intact PTH) positively correlated with urea (r=0.523, r=0.504; P=0.002, respectively), phosphorus (r=0.532, r=0.521; Pbio-intact PTH assay detected significantly lower PTH concentrations compared with intact PTH assay. Additional studies that correlate the diagnosis and management of CKD mineral and bone disorders with bone histomorphometric findings are needed to determine whether bio-intact PTH assay results are better surrogate markers in these early stages of CKD.

  7. Modeling of Oxidized PTH (oxPTH) and Non-oxidized PTH (n-oxPTH) Receptor Binding and Relationship of Oxidized to Non-Oxidized PTH in Children with Chronic Renal Failure, Adult Patients on Hemodialysis and Kidney Transplant Recipients

    DEFF Research Database (Denmark)

    Hocher, Berthold; Oberthür, Dominik; Slowinski, Torsten

    2013-01-01

    Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies i......PTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies. © 2013 S. Karger AG, Basel.......Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies...... in the 1970(s) and 80(s). However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study...

  8. Targeted Over-expression of Dkk1 in Osteoblasts Reduces Bone Mass But Does Not Impair the Anabolic Response to Intermittent PTH Treatment in Mice

    Science.gov (United States)

    Yao, Gang-Qing; Wu, Jian-Jun; Troiano, Nancy; Insogna, Karl.

    2012-01-01

    PTH is a potent anabolic agent but the cellular mechanisms by which it increases bone mass are not fully understood. Dkk1 is an endogenous inhibitor of Wnt signaling and suppresses bone formation in vivo. We sought to determine if Dkk1 and anabolic PTH treatment interact in regulating bone mass. PTH treatment of primary murine osteoblasts for 24 hours reduced Dkk1 expression by 90% as quantified by real-time PCR, while PTH treatment in vivo reduced Dkk1 expression by 30% when give as a single daily subcutaneous dose. To directly determine whether Dkk1 modulates PTH’s anabolic response in vivo, we engineered transgenic (TG) mice expressing murine Dkk1 under the control of the 2.3-kb rat collagen alpha-1 promoter. TG mice had significantly reduced bone mass, which was accompanied by reduced histomorphometric parameters of bone formation (reduced OV/TV, ObS/OS and NOb/TAR). Treatment of TG and wild-type (WT) littermates with 95 ng/g body-weight of human (1–34) PTH daily for 34 days resulted in comparable increases in bone mass at all skeletal sites. Histomorphometric analyses indicated that PTH treatment increased numbers of both osteoblasts and osteoclasts in WT mice but only increased numbers of osteoblasts in TG mice. We conclude that overexpression of Dkk1 does not attenuate the anabolic response to PTH in vivo. PMID:20602130

  9. We want to be provoked

    DEFF Research Database (Denmark)

    Holmgren, Steen

    2001-01-01

    are often considered negative. But new views or knowledge are often provocative. To my opinion this is a good and needed provocation. For-given-taken professional values need to be questioned: as well as the usual roles of residents and professionals in the ongoing regeneration projects. My contribution......The title is a quotation from one of the meetings between residents and professionals during the Holmbladsgade regeneration process. During a discussion of future projects somebody asked what the residents expected from the professionals. We want to be provoked a resident answered. Provocations...

  10. Endogenous PTH Deficiency Impairs Fracture Healing and Impedes the Fracture-Healing Efficacy of Exogenous PTH(1-34)

    Science.gov (United States)

    Feng, Yuxu; Shu, Lei; Cao, Xiaojian; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

    2011-01-01

    Background Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH. Methodology/Principal Findings Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth−/−) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1–4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth−/− mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth−/− mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth−/− mice compared to vehicle-treated wild-type and Pth−/− mice. Conclusions/Significance Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing. PMID:21829585

  11. Risk factors associated with provoked pulmonary embolism.

    Science.gov (United States)

    Gjonbrataj, Endri; Kim, Ji Na; Gjonbrataj, Juarda; Jung, Hye In; Kim, Hyun Jung; Choi, Won-Il

    2017-01-01

    This study aimed to investigate the risk factors associated with provoked pulmonary embolism (PE). This retrospective cohort study included 237 patients with PE. Patients that had transient risk factors at diagnosis were classified as having provoked PE, with the remaining patients being classified as having unprovoked PE. The baseline clinical characteristics and factors associated with coagulation were compared. We evaluated the risk factors associated with provoked PE. Of the 237 PE patients, 73 (30.8%) had provoked PE. The rate of respiratory failure and infection, as well as the disseminated intravascular coagulation score and ratio of right ventricular diameter to left ventricular diameter were significantly higher in patients with provoked PE than in those with unprovoked PE. The protein and activity levels associated with coagulation, including protein C antigen, protein S antigen, protein S activity, anti-thrombin III antigen, and factor VIII, were significantly lower in patients with provoked PE than in those with unprovoked PE. Multivariate analysis showed that infection (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4 to 7.4) and protein S activity (OR, 0.97; 95% CI, 0.95 to 0.99) were significantly associated with provoked PE. Protein S activity and presence of infection were important factors associated with provoked PE. We should pay attention to the presence of infection in patients with provoked PE.

  12. Structure, morphology and corrosion resistance of Ni–Mo+PTh ...

    Indian Academy of Sciences (India)

    Ni–Mo+PTh composite coatings were prepared from nickel–molybdenum galvanic bath with the addition of thiophene (Th) and HClO4 as result of two processes: induced Ni–Mo alloy deposition and PTh polymerization. A scanning electron microscope was used for surface morphology characterization of the coatings.

  13. Control of Bone Anabolism in Response to Mechanical Loading and PTH by Distinct Mechanisms Downstream of the PTH Receptor.

    Science.gov (United States)

    Delgado-Calle, Jesus; Tu, Xiaolin; Pacheco-Costa, Rafael; McAndrews, Kevin; Edwards, Rachel; Pellegrini, Gretel G; Kuhlenschmidt, Kali; Olivos, Naomie; Robling, Alexander; Peacock, Munro; Plotkin, Lilian I; Bellido, Teresita

    2017-03-01

    Osteocytes integrate the responses of bone to mechanical and hormonal stimuli by poorly understood mechanisms. We report here that mice with conditional deletion of the parathyroid hormone (PTH) receptor 1 (Pth1r) in dentin matrix protein 1 (DMP1)-8kb-expressing cells (cKO) exhibit a modest decrease in bone resorption leading to a mild increase in cancellous bone without changes in cortical bone. However, bone resorption in response to endogenous chronic elevation of PTH in growing or adult cKO mice induced by a low calcium diet remained intact, because the increased bone remodeling and bone loss was indistinguishable from that exhibited by control littermates. In contrast, the bone gain and increased bone formation in cancellous and cortical bone induced by daily injections of PTH and the periosteal bone apposition induced by axial ulna loading were markedly reduced in cKO mice compared to controls. Remarkably, however, wild-type (WT) control littermates and transgenic mice overexpressing SOST injected daily with PTH exhibit similar activation of Wnt/β-catenin signaling, increased bone formation, and cancellous and cortical bone gain. Taken together, these findings demonstrate that Pth1r in DMP1-8kb-expressing cells is required to maintain basal levels of bone resorption but is dispensable for the catabolic action of chronic PTH elevation; and it is essential for the anabolic actions of daily PTH injections and mechanical loading. However, downregulation of Sost/sclerostin, previously shown to be required for bone anabolism induced by mechanical loading, is not required for PTH-induced bone gain, showing that other mechanisms downstream of the Pth1r in DMP1-8kb-expressing cells are responsible for the hormonal effect. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  14. Reactive nitrogen species mediate oxidative stress and astrogliosis provoked by in vivo administration of phytanic acid in cerebellum of adolescent rats: A potential contributing pathomechanism of cerebellar injury in peroxisomal disorders.

    Science.gov (United States)

    Borges, C G; Canani, C R; Fernandes, C G; Zanatta, Â; Seminotti, B; Ribeiro, C A J; Leipnitz, G; Vargas, C R; Wajner, M

    2015-09-24

    Phytanic acid (Phyt) accumulates in various peroxisomal diseases including Refsum disease (RD) and Zellweger syndrome (ZS). Since the pathogenesis of the neurological symptoms and especially the cerebellar abnormalities in these disorders are poorly known, we investigated the effects of in vivo intracerebral administration of Phyt on a large spectrum of redox homeostasis parameters in the cerebellum of young rats. Malondialdehyde (MDA) levels, sulfhydryl oxidation, carbonyl content, nitrite and nitrate concentrations, 2',7'-dichlorofluorescein (DCFH) oxidation, total (tGS) and reduced glutathione (GSH) levels and the activities of important antioxidant enzymes were determined at different periods after Phyt administration. Immunohistochemical analysis was also carried out in the cerebellum. Phyt significantly increased MDA and nitric oxide (NO) production and decreased GSH levels, without altering tGS, DCFH oxidation, sulfhydryl oxidation, carbonyl content and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD). Furthermore, immunohistochemical analysis revealed that Phyt caused astrogliosis and protein nitrosative damage in the cerebellum. It was also observed that the NO synthase inhibitor Nω-Nitro-L-arginine methyl ester (L-NAME) prevented the increase of MDA and NO production as well as the decrease of GSH and the immunohistochemical alterations caused by Phyt, strongly suggesting that reactive nitrogen species (RNS) were involved in these effects. The present data provide in vivo solid evidence that Phyt disrupts redox homeostasis and causes astrogliosis in rat cerebellum probably mediated by RNS production. It is therefore presumed that disequilibrium of redox status may contribute at least in part to the cerebellum alterations characteristic of patients affected by RD and other disorders with Phyt accumulation. Copyright © 2015 IBRO. Published by

  15. Structure, morphology and corrosion resistance of Ni–Mo+PTh ...

    Indian Academy of Sciences (India)

    PTh, (2) Mo+4.9%PTh and (3) Ni−21.7%Mo. potential Ni–Mo coatings containing comparable content of. Mo is equal −0.780 V (figure 3). Increase of polythiophene contents in coatings, causes decrease of corrosion current. (table 1). Result of this change of corrosion current is increase of polarization resistance from 18.8 to ...

  16. Metabolic alkalosis transition in renal proximal tubule cells facilitates an increase in CYP27B1, while blunting responsiveness to PTH

    Science.gov (United States)

    Parathyroid hormone (PTH) is the central activator of renal proximal 1-alpha-hydroxylase (CYP27B1), the enzyme responsible for synthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Past studies have documented a disruption of CYP27B1 activity in chronic metabolic acidosis in vivo, while simulated ac...

  17. [Mode of action of parathyroid hormone (PTH) and PTH-related peptide (PTHrP) in target organs].

    Science.gov (United States)

    Ureña, P; Abou Samra, A B; Jüppner, H; Kong, X F; Lee, K; Bringhurst, F R; Segre, G V

    1994-01-01

    Calcium and phosphorus metabolism is mainly regulated by PTH through its actions on kidney and bone. PTHrP, which is associated with the hypercalcemia of malignancy syndrome, binds to and activates the same receptor that PTH does. cDNA clones of PTH/PTHrP receptors from rat osteosarcoma (ROS 17/2.8) and opossum kidney (OK) cells are highly homologous and are members of a novel G protein-linked receptor family that includes calcitonin, glucagon, GLP-1, GHRH, VIP, and secretin receptors. Analysis of the protein sequence predicts a receptor with 7 transmembrane domains, a 155 amino acids (aa) extracellular (EC) N-terminal, and 130aa intracellular C-terminal domaina. The extracellular domain has 6 conserved cysteines and 4 potential glycosylation sites. When transfected in COS cells, both receptors are able to bind PTH and PTHrP active fragments with equal affinity. Likewise, agonists activate both adenylate cyclase and phospholipase C efficiently. The N-terminal EC domain and the first EC loop seem to determine the receptor binding capacity with the agonists. Activation of adenylate cyclase and phospholipase C might involve multiple sites between the 3rd helix and the C-terminal tail. Partial characterization of the rat PTH/PTHrP receptor gene demonstrates the existence of at least 15 exons. The first six transmembrane domains are encoded by separated exons. The PTH/PTHrP receptor mRNA is expressed mainly in kidney and bone, and also is widely expressed in many tissues, but not all. A major 2.3-2.5 kb transcript is observed in all these tissues. Nevertheless, 2 larger transcripts are observed in kidney and liver, and multiple smaller mRNA species are observed in kidney, skin, and testis.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Serum vitamin D and parathormone (PTH) concentrations as ...

    African Journals Online (AJOL)

    Rania Naguib Abdel Mouteleb Abdel Reheem

    2012-10-06

    Oct 6, 2012 ... Abstract Background: Vitamin D is suggested to be an inhibitor of angiogenesis. The degree of severity of diabetic retinopathy (DR) may be related to serum vitamin D concentration. Aim: Investigating vitamin D and parathormone (PTH) concentrations as predictors of the devel- opment and severity of ...

  19. PTH1 receptor is involved in mediating cellular response to long-chain polyunsaturated fatty acids.

    Directory of Open Access Journals (Sweden)

    Jose Candelario

    Full Text Available The molecular pathways by which long chain polyunsaturated fatty acids (LCPUFA influence skeletal health remain elusive. Both LCPUFA and parathyroid hormone type 1 receptor (PTH1R are known to be involved in bone metabolism while any direct link between the two is yet to be established. Here we report that LCPUFA are capable of direct, PTH1R dependent activation of extracellular ligand-regulated kinases (ERK. From a wide range of fatty acids studied, varying in chain length, saturation, and position of double bonds, eicosapentaenoic (EPA and docosahexaenoic fatty acids (DHA caused the highest ERK phosphorylation. Moreover, EPA potentiated the effect of parathyroid hormone (PTH(1-34 in a superagonistic manner. EPA or DHA dependent ERK phosphorylation was inhibited by the PTH1R antagonist and by knockdown of PTH1R. Inhibition of PTH1R downstream signaling molecules, protein kinases A (PKA and C (PKC, reduced EPA and DHA dependent ERK phosphorylation indicating that fatty acids predominantly activate G-protein pathway and not the β-arrestin pathway. Using picosecond time-resolved fluorescence microscopy and a genetically engineered PTH1R sensor (PTH-CC, we detected conformational responses to EPA similar to those caused by PTH(1-34. PTH1R antagonist blocked the EPA induced conformational response of the PTH-CC. Competitive binding studies using fluorescence anisotropy technique showed that EPA and DHA competitively bind to and alter the affinity of PTH1 receptor to PTH(1-34 leading to a superagonistic response. Finally, we showed that EPA stimulates protein kinase B (Akt phosphorylation in a PTH1R-dependent manner and affects the osteoblast survival pathway, by inhibiting glucocorticoid-induced cell death. Our findings demonstrate for the first time that LCPUFAs, EPA and DHA, can activate PTH1R receptor at nanomolar concentrations and consequently provide a putative molecular mechanism for the action of fatty acids in bone.

  20. Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH-1-37

    Directory of Open Access Journals (Sweden)

    Wolf-Georg Forssmann

    2016-08-01

    Full Text Available Background/Aims: Parathyroid hormone (PTH derivatives exert pronounced renal and osteoanabolic properties when given intermittently. The current study was performed to assess the pharmacokinetic and pharmacodynamic properties as well as safety of subcutaneously applied PTH-1-37 after repeated dosing in healthy subjects. Methods: This randomized, double-blind, dose-escalating, placebo and active comparator controlled study was conducted in 33 healthy postmenopausal women. Subjects were allocated to one of five treatment options: 10, 20, or 40 µg PTH-1-37, 20 µg PTH-1-34 or placebo, administered as once daily subcutaneous doses for three days. Plasma drug concentrations and serum levels of endogenous PTH-1-84, and calcium as markers of biological activity were monitored during the treatment. Results: PTH was absorbed rapidly from the subcutaneous tissue with a median tmax of 30 minutes for 20 and 40 µg of PTH-1-37. tmax was 45 minutes for 20 µg PTH-1-34. Elimination half-lives were estimated as 76 ± 34 min and 70 ± 13 min for 20 µg and 40 µg PTH-1-37 (mean ± SD, and 78 ± 34 for 20 µg PTH-1-34. Both PTH fragments (PTH-1-37 and PTH-1-34 increased serum calcium. For PTH-1-37 the effect on serum calcium was dose-dependent. Suppression of endogenous PTH-1-84 was seen after the application of both PTH-1-37 and PTH-1-34. During the study period, the subjects experienced no unexpected or serious adverse events. Conclusions: PTH-1-37 is rapidly absorbed after s.c. injection, has a short plasma elimination half-life, and does not accumulate during multiple dosing. Biological activity was demonstrated by rising serum calcium and decreasing endogenous PTH-1-84 in blood plasma. The study drugs were well tolerated and safe. Our investigation presents data that PTH-1-37 is an excellent drug candidate for intervening with syndromes of dysregulation of calcium metabolism.

  1. Functional characterization and evolution of PTH/PTHrP receptors: insights from the chicken

    Directory of Open Access Journals (Sweden)

    Pinheiro Pedro LC

    2012-07-01

    Full Text Available Abstract Background The parathyroid hormone (PTH-family consists of a group of structurally related factors that regulate calcium and bone homeostasis and are also involved in development of organs such as the heart, mammary gland and immune system. They interact with specific members of family 2 B1 G-protein coupled receptors (GPCRs, which have been characterised in teleosts and mammals. Two PTH/PTHrP receptors, PTH1R and PTH2R exist in mammals and in teleost fish a further receptor PTH3R has also been identified. Recently in chicken, PTH-family members involved in calcium transport were characterized and specific PTHRs are suggested to exist although they have not yet been isolated or functionally characterized. The aim of this study is to further explore the evolution and function of the vertebrate PTH/PTHrP system through the isolation, phylogenetic analysis and functional characterization of the chicken receptors. Results Two PTHRs were isolated in chicken and sequence comparison and phylogenetic analysis indicate that the chicken receptors correspond to PTH1R and PTH3R, which emerged prior to the teleost/tetrapod divergence since they are present in cartilaginous fish. The vertebrate PTH2R receptor and its ligand TIP39 have been lost from bird genomes. Chicken PTH1R and PTH3R have a divergent and widespread tissue expression and are also evident in very early embryonic stages of development. Receptor stimulation studies using HEK293 cells stably expressing the chicken PTH1R and PTH3R and monitoring cAMP production revealed they are activated by chicken 1–34 N-terminal PTH-family peptides in a dose dependent manner. PTH-L and PTHrP were the most effective peptides in activating PTH1R (EC50 = 7.7 nM and EC50 = 22.7 nM, respectively. In contrast, PTH-L (100 nM produced a small cAMP accumulation on activation of PTH3R but PTHrP and PTH (EC50 = 2.5 nM and EC50 = 22.1 nM, respectively readily activated the receptor. PTHr

  2. Roles of Parathyroid Hormone (PTH) Receptor and Reactive Oxygen Species in Hyperlipidemia-Induced PTH(1-34) Resistance in Preosteoblasts.

    Science.gov (United States)

    Li, Xin; Garcia, Jamie; Lu, Jinxiu; Iriana, Sidney; Kalajzic, Ivo; Rowe, David; Demer, Linda; Tintut, Yin

    2013-01-01

    Bioactive lipids initiate inflammatory reactions leading to pathogenesis of atherosclerosis. Evidence shows that they also contribute to bone loss by inhibiting parathyroid hormone receptor (PTH1R) expression and differentiation of osteoblasts. We previously demonstrated that bone anabolic effects of PTH(1-34) are blunted in hyperlipidemic mice and that these PTH effects are restored by antioxidants. However, it is not clear which osteoblastic cell developmental stage is targeted by bioactive lipids. To investigate the effects of hyperlipidemia at the cellular level, hyperlipidemic Ldlr−/− mice were bred with Col3.6GFPtpz mice, in which preosteoblasts/osteoblasts carry a topaz fluorescent label, and with Col2.3GFPcyan mice, in which more mature osteoblasts/osteocytes carry a cyan fluorescent label. Histological analyses of trabecular bone surfaces in femoral as well as calvarial bones showed that intermittent PTH(1-34) increased fluorescence intensity in WT-Tpz mice, but not in Tpz-Ldlr−/− mice. In contrast, PTH(1-34) did not alter fluorescence intensity in femoral cortical envelopes of either WT-Cyan or Ldlr−/−-Cyan mice. To test the mechanism of PTH1R downregulation, preosteoblastic MC3T3-E1 cells were treated with bioactive lipids and the antioxidant Trolox. Results showed that inhibitory effects of PTH1R levels by bioactive lipids were rescued by pretreatment with Trolox. The inhibitory effects on expression of PTH1R as well as on PTH-induced osteoblastic genes were mimicked by xanthine/xanthine oxidase, a known generator of reactive oxygen species. These findings suggest an important role of preosteoblasts as the target development stage and downregulation of PTH receptor expression mediated by intracellular oxidant stress as a mechanism in hyperlipidemia-induced PTH resistance. PMID:24038594

  3. Acute generalized exanthematous pustulosis provoked by furosemide

    Directory of Open Access Journals (Sweden)

    Andżelika Schwann-Majewska

    2015-06-01

    Full Text Available Introduction. Acute generalized exanthematous pustulosis (AGEP is a skin disease characterized by the sudden appearance of generalized pustules, accompanied by elevated body temperature and neutrophilia. Objective. Presentation of a patient with AGEP provoked by furosemide. Case report. We present a case of a 65-year-old patient diagnosed with and treated for generalized pustular eruption, with fever and changes in laboratory tests. Numerous coexisting medical conditions and a great number of frequently changed drugs (ciprofloxacin, allopurinol, folic acid, calcium carbonate, cyclophosphamide, atorvastatin, betaxolol and furosemide hindered identification of the causative factor. Conclusions. On the basis of the medical history and clinical picture, the patient was diagnosed with generalized exanthematous pustulosis induced by furosemide.

  4. Effect of licorice on PTH levels in healthy women.

    Science.gov (United States)

    Mattarello, Mee Jung; Benedini, Stefano; Fiore, Cristina; Camozzi, Valentina; Sartorato, Paola; Luisetto, Giovanni; Armanini, Decio

    2006-05-01

    Licorice has been considered a medicinal plant for thousands of years. Its most common side effect is hypokalemic hypertension, which is secondary to a block of 11beta-hydroxysteroid dehydrogenase type 2 at the level of the kidney, leading to an enhanced mineralocorticoid effect of cortisol. This effect is due to glycyrrhetinic acid, which is the main constituent of the root, but other components are also present, including isoflavans, which have estrogen-like activity, and are thus involved in the modulation of bone metabolism. We investigated nine healthy women 22-26 years old, in the luteal phase of the cycle. They were given 3.5 g of a commercial preparation of licorice (containing 7.6%, w/w of glycyrrhizic acid) daily for 2 months. Plasma renin activity (PRA), aldosterone, cortisol, serum parathyroid hormone (PTH), 1,25-dihydroxy Vitamin D (1,25OHD), 25-hydroxycholecalciferol (25OHD), estradiol, FHS, LH, alkaline phosphatase (ALP), calcium, phosphate and creatinine, urinary calcium and phosphate and mineralometry were measured. PTH, 25OHD and urinary calcium increased significantly from baseline values after 2 months of therapy, while 1,25OHD and ALP did not change during treatment. All these parameters returned to pretreatment levels 1 month after discontinuation of licorice. PRA and aldosterone were depressed during therapy, while blood pressure and plasma cortisol remained unchanged. licorice can increase serum PTH and urinary calcium levels from baseline value in healthy women after only 2 months of treatment. The effect of licorice on calcium metabolism is probably influenced by several components of the root, which show aldosterone-like, estrogen-like and antiandrogen activity.

  5. Hyperventilation provokes symptoms of carpal tunnel syndrome.

    Science.gov (United States)

    Aslam, U; Afzal, S; Syed, Shakir

    2012-01-01

    Hyperventilation causes respiratory alkalosis. The nervous system is more excitable in alkalosis. This phenomenon can be observed as paraesthesia in fingers and toes as well as around the lips in anxious patients breathing rapidly. We wanted to test this phenomenon on already irritable nerves like the median nerve in carpal tunnel syndrome (CTS). We deployed 50 patients who came in to the day case unit for carpal tunnel decompression with electro-physiologically proven diagnosis. We devised a test whereby patients were made to hyperventilate under prescribed conditions and repeated Phalen's test and Tinel's sign for comparison. These were compared with a control group chosen randomly among hospital staff. 86% patients had a positive result which was just behind Phalen's test in sensitivity. It was also 100% specific as there were no false positives. Hyperventilation is a phenomenon which provokes carpal tunnel syndrome. Its clinical value remains to be seen due to cumbersome method and probable patient non-compliance but it is a new discovery. It may be useful in other irritable-nerve-syndromes as a test to add to our available armament. It may be an additional factor or a primary reason for nocturnal paraesthesias in CTS patients.

  6. A fast intraoperative PTH point-of-care assay on the Philips handheld magnotech system.

    Science.gov (United States)

    Jarrige, Veronique; Nieuwenhuis, Jeroen H; van Son, Jacco P H F; Martens, Mike F W C; Vissers, Joost L M

    2011-03-01

    Intraoperative parathyroid hormone (ioPTH) is used during minimally invasive parathyroidectomy (MIP) to predict the success of surgery and should be accurate with a short turnaround time. We developed an ioPTH point-of-care (POC) assay on Philips handheld magnotech system. Magnotech technology is based on magnetically controlled movement of superparamagnetic nanoparticles in stationary sample fluid. During first phase, intact-PTH is captured by magnetic particles coated with anti-N-terminal-PTH antibodies. Subsequently, magnetic particles are collected by magnetic forces at sensor surface coated with anti-C-terminal-PTH antibodies. Unbound/nonspecifically bound particles are pulled away from detection surface, using a second magnetic force. Amount of specifically bound particles is measured using a surface-sensitive optical imaging technique. ioPTH test could be performed with a turnaround time of less than 10 min and could detect low intact-PTH concentrations (picomolar). Integrated cartridge contains a blood separation filter and dry reagents for the assay. The next magnotech ioPTH assay will be the only POC test able to give accurate results in less than 10 min, using 25 μL of whole blood. Thanks to the ease-of-use, magnotech ioPTH could be performed in the operating theater by any member of surgical staff.

  7. Rat parathyroid hormone (rPTH) ELISAs specific for regions (2-7), (22-34) and (40-60) of the rat PTH structure: influence of sex and age.

    Science.gov (United States)

    D'Amour, Pierre; Rousseau, Louise; Hornyak, Stephen; Yang, Zan; Cantor, Tom

    2010-09-15

    Rat (r) PTH ELISAs were used to study the influence of age and sex on rPTH levels and circulating PTH molecular forms separated by HPLC. Standard curves and saturation analysis were undertaken to define epitopes. Rats were sacrificed at approximately 27, 47 and 75days. Relevant biochemical parameters and 25(OH) vitamin D were measured. Differences between sexes were analyzed by Kruskal-Wallis ANOVA, followed by Dunn's test. Epitopes were localized in regions 2-7, 22-34 and 40-60 of rPTH structure for whole (W), total (T) and carboxyl (C) rPTH ELISAs. The W-rPTH assay only detected rPTH(1-84) and N-PTH in circulation while the T-PTH assay further detected large C-rPTH fragments. The C-rPTH assay detected all circulating rPTH molecular forms including smaller C-rPTH fragments. In both sexes, weight (p<0.001), ionized calcium, creatinine, albumin and 25(OH)D values (p<0.001) increased with age, while phosphate and alkaline phosphatase decreased (p<0.001). In male rats, W-rPTH remained unchanged, while T-rPTH rose slightly (p<0.05) and C-rPTH declined by half with time (p<0.001). In female rats, W-rPTH (p<0.05), T-rPTH (p<0.001) and C-rPTH (p<0.01) all increased in older animals. In both sexes, C-rPTH/W-rPTH and C-rPTH/T-rPTH ratios decreased between 25 and 47 days, to rise again between 47 and 75 days. The initial decrease may represent an adaptation to weaning and a change of diet between 25 and 47 days while the rise corresponds to higher calcium and 25(OH)D levels between 47 and 75 days. These changes were more pronounced in female rats, indicating an influence of sex on PTH molecular form secretion or metabolism. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  8. PTH Assays: Understanding What We Have and Forecasting What We Will Have

    Directory of Open Access Journals (Sweden)

    Jose Gilberto H. Vieira

    2012-01-01

    Full Text Available Parathyroid hormone (PTH assays have evolved continuously for the last 50 years. Since the first radioimmunoassay was described in 1963, several assays based on immunological identification have been published (first generation assays. The routine assays used nowadays are immunometric “sandwich-type”. They are based on two different monoclonal antibodies, one amino-terminal and the other carboxyl terminal specific. These second generation assays are widely available and adapted to most of the automation platforms. The specificity of the amino terminal antibody defines if the immunometric assay measures only the bioactive PTH circulating form (including the first amino terminal amino acids or the “intact” PTH, which includes, besides bioactive PTH, other “long” carboxyl-terminal forms, for example, 7–84-PTH. Assays for “intact” PTH are the most commonly available and the potential advantage of the bioactive PTH assays is still debatable. Next generation of assays will be based on different principles, mainly mass spectrometry in samples submitted to a prior purification and fragmentation steps. These assays will provide information about the whole spectra of PTH peptides in circulation, with a significant increase of the information regarding this biologically important peptide hormone.

  9. Intermittent parathyroid hormone (PTH) promotes cementogenesis and alleviates the catabolic effects of mechanical strain in cementoblasts.

    Science.gov (United States)

    Li, Yuyu; Hu, Zhiai; Zhou, Chenchen; Xu, Yang; Huang, Li; Wang, Xin; Zou, Shujuan

    2017-04-20

    External root resorption, commonly starting from cementum, is a severe side effect of orthodontic treatment. In this pathological process and repairing course followed, cementoblasts play a significant role. Previous studies implicated that parathyroid hormone (PTH) could act on committed osteoblast precursors to promote differentiation, and inhibit apoptosis. But little was known about the role of PTH in cementoblasts. The purpose of this study was to investigate the effects of intermittent PTH on cementoblasts and its influence after mechanical strain treatment. Higher levels of cementogenesis- and differentiation-related biomarkers (bone sialoprotein (BSP), osteocalcin (OCN), Collagen type I (COL1) and Osterix (Osx)) were shown in 1-3 cycles of intermittent PTH treated groups than the control group. Additionally, intermittent PTH increased alkaline phosphatase (ALP) activity and mineralized nodules formation, as measured by ALP staining, quantitative ALP assay, Alizarin red S staining and quantitative calcium assay. The morphology of OCCM-30 cells changed after mechanical strain exertion. Expression of BSP, ALP, OCN, osteopontin (OPN) and Osx was restrained after 18 h mechanical strain. Furthermore, intermittent PTH significantly increased the expression of cementogenesis- and differentiation-related biomarkers in mechanical strain treated OCCM-30 cells. Taken together, these data suggested that intermittent PTH promoted cementum formation through activating cementogenesis- and differentiation-related biomarkers, and attenuated the catabolic effects of mechanical strain in immortalized cementoblasts OCCM-30.

  10. Optical and thermal properties of PTh-co-PANI-Ti random copolymer composite for photovoltaic application

    Directory of Open Access Journals (Sweden)

    Sanjay R. Takpire

    2015-12-01

    Full Text Available In thе present work, a polythiophene (PTh-co-polyaniline (PANI-titanium (Ti copolymer has been synthesized as a novel copolymeric composite material for photovoltaic (PV application. The focus of the study was to evaluate optical and thermal properties of the PTh-co-PANI-Ti copolymer containing different types of monomers. The optical conductivity was determined from the UV–VIS spectra that were used to calculate the extinction coefficients. The structure and morphology of composite was analyzed through field emission-electron microscopy (FESEM. The PTh-co-PANI-Ti copolymer composite exhibited significant photovoltaic (PV response to light intensity. J–V analysis showed an increase in conversion efficiency from 0.21 to 1.5 of PTh-co-PANi-Ti with illumination light intensity. PV properties demonstrated that the PTh-co-PANI-Ti exhibited the highest power conversion efficiency ɳ=1.5, with a short circuit current Isc=0.72mA, an open circuit voltage Voc=0.9V and a fill factor FF=0.51. Thermo-gravimetric (TG and differential thermal (DTA analyses were carried out for the thermal stability of the PTh-co-PANI-Ti copolymer composite. The results obtained from the characterization of PTh-co-PANI-Ti showed that many properties of PV action are present in as-synthesized material.

  11. PTH Promotes Bone Anabolism by Stimulating Aerobic Glycolysis via IGF Signaling.

    Science.gov (United States)

    Esen, Emel; Lee, Seung-Yon; Wice, Burton M; Long, Fanxin

    2015-11-01

    Teriparatide, a recombinant peptide corresponding to amino acids 1-34 of human parathyroid hormone (PTH), has been an effective bone anabolic drug for over a decade. However, the mechanism whereby PTH stimulates bone formation remains incompletely understood. Here we report that in cultures of osteoblast-lineage cells, PTH stimulates glucose consumption and lactate production in the presence of oxygen, a hallmark of aerobic glycolysis, also known as Warburg effect. Experiments with radioactively labeled glucose demonstrate that PTH suppresses glucose entry into the tricarboxylic acid cycle (TCA cycle). Mechanistically, the increase in aerobic glycolysis is secondary to insulin-like growth factor (Igf) signaling induced by PTH, whereas the metabolic effect of Igf is dependent on activation of mammalian target of rapamycin complex 2 (mTORC2). Importantly, pharmacological perturbation of glycolysis suppresses the bone anabolic effect of intermittent PTH in the mouse. Thus, stimulation of aerobic glycolysis via Igf signaling contributes to bone anabolism in response to PTH. © 2015 American Society for Bone and Mineral Research.

  12. Higher parathyroid hormone (PTH) concentrations with the Architect PTH assay than with the Elecsys assay in hemodialysis patients, and a simple way to standardize these two methods.

    Science.gov (United States)

    Monge, Marie; Jean, Guillaume; Bacri, Jean-Louis; Lemaitre, Vincent; Masy, Eric; Joly, Dominique; Souberbielle, Jean-Claude

    2009-01-01

    The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend maintaining serum parathyroid hormone (PTH) concentration between 150 and 300 pg/mL in patients with chronic kidney disease (CKD) stage 5. However, a marked inter-method variability in PTH measurement has been reported recently. The aim of this study was to evaluate whether harmonization of the results measured with two commercial kits known to produce significantly different serum PTH concentrations could be reasonably achieved by a simple procedure. The study comprised a total of 216 hemodialyzed patients in whom blood was collected immediately before a dialysis session. The patients were from three dialysis centers, which defined three groups (119, 34, and 63 patients for groups 1, 2, and 3, respectively). PTH was measured by two automated assays, the Elecsys (Roche Diagnostics) and Architect (Abbott Diagnostics) assays, in three different laboratories and with different lots of reagents. We arbitrarily chose the Roche assay as the reference method, because several studies had previously shown that the concentrations measured with this assay were very close to the Allegro assay used in the studies that defined the K/DOQI thresholds. Data are median (interquartile range). The median PTH concentrations were higher (pArchitect assay [238 (140-434) pg/mL] when compared to the Elecsys assay [182 (109-338) pg/mL]. Bland-Altman plots in the three groups showed a similar proportional bias between both kits. The Architect PTH/Elecsys PTH ratios were similar in the three groups [1.30 (1.25-1.35), 1.30 (1.19-1.39), and 1.31 (1.25-1.35)], and the ratio was 1.30 (1.25-1.35) in the cohort (pooling the three groups). In the whole population, 53 patients (24.5%) were classified differently by the two kits according to the K/DOQI cut-off values. We divided the Architect values by 1.3 to obtain "corrected" values. These corrected Architect values were not different to the measured Elecsys values, and the

  13. Transcriptional regulation of BMP2 expression by the PTH-CREB signaling pathway in osteoblasts.

    Directory of Open Access Journals (Sweden)

    Rongrong Zhang

    Full Text Available Intermittent application of parathyroid hormone (PTH has well established anabolic effects on bone mass in rodents and humans. Although transcriptional mechanisms responsible for these effects are not fully understood, it is recognized that transcriptional factor cAMP response element binding protein (CREB mediates PTH signaling in osteoblasts, and that there is a communication between the PTH-CREB pathway and the BMP2 signaling pathway, which is important for osteoblast differentiation and bone formations. These findings, in conjunction with putative cAMP response elements (CREs in the BMP2 promoter, led us to hypothesize that the PTH-CREB pathway could be a positive regulator of BMP2 transcription in osteoblasts. To test this hypothesis, we first demonstrated that PTH signaling activated CREB by phosphorylation in osteoblasts, and that both PTH and CREB were capable of promoting osteoblastic differentiation of primary mouse osteoblast cells and multiple rodent osteoblast cell lines. Importantly, we found that the PTH-CREB signaling pathway functioned as an effective activator of BMP2 expression, as pharmacologic and genetic modulation of PTH-CREB activity significantly affected BMP2 expression levels in these cells. Lastly, through multiple promoter assays, including promoter reporter deletion, mutation, chromatin immunoprecipitation (ChIP, and electrophoretic mobility shift assay (EMSA, we identified a specific CRE in the BMP2 promoter which is responsible for CREB transactivation of the BMP2 gene in osteoblasts. Together, these results demonstrate that the anabolic function of PTH signaling in bone is mediated, at least in part, by CREB transactivation of BMP2 expression in osteoblasts.

  14. Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids.

    Science.gov (United States)

    Sage, Andrew P; Lu, Jinxiu; Atti, Elisa; Tetradis, Sotirios; Ascenzi, Maria-Grazia; Adams, Douglas J; Demer, Linda L; Tintut, Yin

    2011-06-01

    In hyperlipidemia, oxidized lipids accumulate in vascular tissues and trigger atherosclerosis. Such lipids also deposit in bone tissues, where they may promote osteoporosis. We found previously that oxidized lipids attenuate osteogenesis and that parathyroid hormone (PTH) bone anabolism is blunted in hyperlipidemic mice, suggesting that osteoporotic patients with hyperlipidemia may develop resistance to PTH therapy. To determine if oxidized lipids account for this PTH resistance, we blocked lipid oxidation products in hyperlipidemic mice with an ApoA-I mimetic peptide, D-4F, and the bone anabolic response to PTH treatment was assessed. Skeletally immature Ldlr(-/-) mice were placed on a high-fat diet and treated with D-4F peptide and/or with intermittent PTH(1-34) injections. As expected, D-4F attenuated serum lipid oxidation products and tissue lipid deposition induced by the diet. Importantly, D-4F treatment attenuated the adverse effects of dietary hyperlipidemia on PTH anabolism by restoring micro-computed tomographic parameters of bone quality-cortical mineral content, area, and thickness. D-4F significantly reduced serum markers of bone resorption but not bone formation. PTH and D-4F, together but not separately, also promoted bone anabolism in an alternative model of hyperlipidemia, Apoe(-/-) mice. In normolipemic mice, D-4F cotreatment did not further enhance the anabolic effects of PTH, indicating that the mechanism is through its effects on lipids. These findings suggest that oxidized lipids mediate hyperlipidemia-induced PTH resistance in bone through modulation of bone resorption. Copyright © 2011 American Society for Bone and Mineral Research.

  15. Differing effects of PTH 1-34, PTH 1-84 and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis. An 18 month open-labeled observational study using HR-pQCT

    DEFF Research Database (Denmark)

    Hansen, Stinus; Hauge, Ellen Margrethe; Jensen, Jens-Erik Beck

    2012-01-01

    Whereas the beneficial effects of intermittent treatment with parathyroid hormone (PTH) (intact PTH 1-84 or fragment PTH 1-34, teriparatide) on vertebral strength is well documented, treatment may not be equally effective in the peripheral skeleton. We used high resolution peripheral quantitative...... computed tomography (HR-pQCT) to detail effects on compartmental geometry, density and microarchicture as well as finite element (FE) estimated integral strength at the distal radius and tibia in postmenopausal osteoporotic women treated with PTH 1-34 (20 µg sc. daily, n=18) or PTH 1-84 (100 µg sc. daily......, n=20) for 18 month in an open label, non-randomized study. A group of postmenopausal osteoporotic women receiving zoledronic acid (5 mg infusion once yearly, n=33) was also included. Anabolic therapy increased cortical porosity in radius (PTH 1-34 32±37%, PTH 1-84 39±32%, both p...

  16. Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells

    Energy Technology Data Exchange (ETDEWEB)

    Shekhar, Tanmay M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Green, Maja M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Department of Anatomy & Neuroscience, The University of Melbourne, Parkville 3010 (Australia); Rayner, David M.; Miles, Mark A.; Cutts, Suzanne M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Hawkins, Christine J., E-mail: c.hawkins@latrobe.edu.au [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia)

    2015-07-15

    Graphical abstract: - Highlights: • Mutagenicities of anti-cancer drugs were tested using HPRT, γH2AX and comet assays. • TRAIL, doxorubicin and etoposide were more mutagenic than BH3- or Smac-mimetics. • Physiologically achievable levels of the BH3-mimetic ABT-737 were not mutagenic. • High concentrations of ABT-737 provoked mutations via an off-target mechanism. • Even very high concentrations of IAP antagonists were not mutagenic. - Abstract: Chemotherapy and radiotherapy can cause permanent damage to the genomes of surviving cells, provoking severe side effects such as second malignancies in some cancer survivors. Drugs that mimic the activity of death ligands, or antagonise pro-survival proteins of the Bcl-2 or IAP families have yielded encouraging results in animal experiments and early phase clinical trials. Because these agents directly engage apoptosis pathways, rather than damaging DNA to indirectly provoke tumour cell death, we reasoned that they may offer another important advantage over conventional therapies: minimisation or elimination of side effects such as second cancers that result from mutation of surviving normal cells. Disappointingly, however, we previously found that concentrations of death receptor agonists like TRAIL that would be present in vivo in clinical settings provoked DNA damage in surviving cells. In this study, we used cell line model systems to investigate the mutagenic capacity of drugs from two other classes of direct apoptosis-inducing agents: the BH3-mimetic ABT-737 and the IAP antagonists LCL161 and AT-406. Encouragingly, our data suggest that IAP antagonists possess negligible genotoxic activity. Doses of ABT-737 that were required to damage DNA stimulated Bax/Bak-independent signalling and exceeded concentrations detected in the plasma of animals treated with this drug. These findings provide hope that cancer patients treated by BH3-mimetics or IAP antagonists may avoid mutation-related illnesses that afflict

  17. The effect of PTH(1-34) on fracture healing during different loading conditions

    DEFF Research Database (Denmark)

    Ellegaard Larsen, Maria; Kringelbach, Tina; Syberg, Susanne

    2013-01-01

    . Five days before fracture, half of the animals received Botulinum Toxin A injections in the muscles of the fractured leg to induce muscle paralysis (unloaded group), whereas the other half received saline injections (control group). For the following 8 weeks, half of the animals in each group received...... injections of hPTH(1-34) (20 µg/kg/day) and the other half received vehicle treatment. Fracture healing was assessed by radiology, dual-energy X-ray absorptiometry (DXA), histology, and bone strength analysis. We found that unloading reduced callus area significantly, whereas no effects of PTH(1...... and control animals. PTH(1-34) treatment increased ultimate force of the fracture by 63% in both control and unloaded animals and no interaction of the two interventions could be detected. PTH(1-34) was able to stimulate bone formation in normally loaded as well as unloaded intact bone. In conclusion...

  18. Standardisation of a two-site PTH immunoradiometric assay using various solid phase formats.

    Science.gov (United States)

    Prasad, U V; Mohan, R Krishna; Samuel, G; Harinarayan, C V; Sivaprasad, N; Venkatesh, M

    2012-12-01

    Estimation of parathyroid hormone (PTH) levels is important in the management of metabolic bone disorders. Here we describe a simple, sensitive and specific second generation immunoradiometric assay (IRMA) to detect intact PTH levels using different solid phase matrices. Different methods for immobilization of antibodies have also been evaluated. Experiments were carried out with physical adsorption of antibodies, covalent coupling using 2 per cent glutaraldehyde and N,N`carbonyldiimidazole. In all cases, antibodies raised against C-terminal were used as solid phase agent. Detector antibodies were N terminal antibodies that were radio-iodinated with [125] I followed by gel purification. Several of the antibodies coupled to various solid phase matrices were incubated with PTH standards and the detector antibody as well as the commercially available tracer from DiaSorin kit to identify a suitable match pair. The best pair was polyclonal C-terminal PTH antibody along with the kit tracer from DiaSorin with regards to antibody coated to magnetic cellulose particles. Among the various antibodies and the solid phases evaluated, the best assay was obtained with the matched pair of antibodies (70×G67 and 70×G68) from Fitzgerald immobilized on polystyrene tubes. The polyclonal antibody against C-terminal PTH was chosen as the capture antibody and [125] I labelled polyclonal antibody against N-terminal PTH as the tracer. The sample values obtained in the antibody coated tubes were comparable to those obtained using a commercial kit. The results indicated the feasibility of adopting this system for further development into a PTH IRMA for regular production as there is no indigenous kit available for intact PTH.

  19. P12 - PTHC1: A Continuing Cell Line Expressing PTH and Genes Involved in Calcium Homeostasis

    OpenAIRE

    Fabbri, S.; Mazzotta, C.; Ciuffi, S; Mavilia, C.; Galli, G.; Zonefrati, R.; Strigoli, D.; Cavalli, L.; Cavalli, T; Brandi, M.L.

    2010-01-01

    The main organs regulating serum levels of ionised calcium (Ca2+) are the parathyroids, which are composed of two different cell types: chief cells and oxyphil cells. Chief cells, through the calcium sensing receptor (CaSR), are affected by changes in calcium concentration, modifying PTH secretion in proportion to calcium levels. Current understanding of calcium regulation mechanisms connected to PTH and of the signalling pathways involved derive from in vitro studies carried out on primary c...

  20. Thyroid Storm Provoked by Interleukin-2 Therapy for Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Yao-Chung Liu

    2014-06-01

    Full Text Available With the growing use of immunotherapy in the treatment of cancer and autoimmune disease, severe autoimmune thyroid dysfunction may be provoked at an increasing rate. We herein report a 49-year-old male patient experiencing a life- threatening thyroid storm provoked by interleukin-2 (IL-2. This was a case of pulmonary metastasis of melanoma without a previous history of thyroid dysfunction. For the metastatic melanoma, he underwent combined immunochemotherapy including dacarbazine and IL-2. The 3rd course of immunochemotherapy was complicated with a thyroid storm manifested by high fever, tachycardia and even transient cardiac arrest. Fortunately, he recovered eventually from this crisis by immediate resuscitation followed by antithyroid dugs. Our case highlights the rare complication of a thyroid storm provoked by IL-2 treatment. Precaution against autoimmune thyroid dysfunction is required during treatment with IL-2 and probably also other kinds of newly-developed immunotherapy to avoid life-threatening complications.

  1. Resorption controls bone anabolism driven by parathyroid hormone (PTH) receptor signaling in osteocytes.

    Science.gov (United States)

    Rhee, Yumie; Lee, Eun-Young; Lezcano, Virginia; Ronda, Ana C; Condon, Keith W; Allen, Matthew R; Plotkin, Lilian I; Bellido, Teresita

    2013-10-11

    The contribution of remodeling-based bone formation coupled to osteoclast activity versus modeling-based bone formation that occurs independently of resorption, to the anabolic effect of PTH remains unclear. We addressed this question using transgenic mice with activated PTH receptor signaling in osteocytes that exhibit increased bone mass and remodeling, recognized skeletal effects of PTH elevation. Direct inhibition of bone formation was accomplished genetically by overexpressing the Wnt antagonist Sost/sclerostin; and resorption-dependent bone formation was inhibited pharmacologically with the bisphosphonate alendronate. We found that bone formation induced by osteocytic PTH receptor signaling on the periosteal surface depends on Wnt signaling but not on resorption. In contrast, bone formation on the endocortical surface results from a combination of Wnt-driven increased osteoblast number and resorption-dependent osteoblast activity. Moreover, elevated osteoclasts and intracortical/calvarial porosity is exacerbated by overexpressing Sost and reversed by blocking resorption. Furthermore, increased cancellous bone is abolished by Wnt inhibition but further increased by blocking resorption. Thus, resorption induced by PTH receptor signaling in osteocytes is critical for full anabolism in cortical bone, but tempers bone gain in cancellous bone. Dissecting underlying mechanisms of PTH receptor signaling would allow targeting actions in different bone compartments, enhancing the therapeutic potential of the pathway.

  2. Do stages of dentistry training affect anxiety provoking situations ...

    African Journals Online (AJOL)

    ... coping with children were the anxiety provoking situations that showed statistically significant difference in the 3 studied training stages of dentistry. Bonferroni post‑hoc analysis significant difference was in the preclinical and clinical students' pair for getting diagnosis wrong, not developing radiograph properly and coping ...

  3. Foods provoking and alleviating symptoms in gastroparesis: patient experiences.

    Science.gov (United States)

    Wytiaz, Victoria; Homko, Carol; Duffy, Frank; Schey, Ron; Parkman, Henry P

    2015-04-01

    Nutritional counseling for gastroparesis focuses on reduction of meal size, fiber, and fat to control symptoms. The tolerance of gastroparesis patients for particular foods is largely anecdotal. The aim of this study was to identify and characterize foods provoking or alleviating gastroparesis symptoms. Gastroparesis patients completed: (1) Demographic Questionnaire; (2) Patient Assessment of Upper GI Symptoms; (3) Food Toleration and Aversion survey asking patients about experiences when eating certain foods utilizing a scale from -3 (greatly worsening symptoms) to +3 (greatly improving symptoms). Descriptive qualities (acidic, fatty, spicy, roughage-based, bitter, salty, bland, and sweet) were assigned to foods. Forty-five gastroparesis patients participated (39 idiopathic gastroparesis). Foods worsening symptoms included: orange juice, fried chicken, cabbage, oranges, sausage, pizza, peppers, onions, tomato juice, lettuce, coffee, salsa, broccoli, bacon, and roast beef. Saltine crackers, jello, and graham crackers moderately improved symptoms. Twelve additional foods were tolerated by patients (not provoking symptoms): ginger ale, gluten-free foods, tea, sweet potatoes, pretzels, white fish, clear soup, salmon, potatoes, white rice, popsicles, and applesauce. Foods provoking symptoms were generally fatty, acidic, spicy, and roughage-based. The foods shown to be tolerable were generally bland, sweet, salty, and starchy. This study identified specific foods that worsen as well as foods that may help alleviate symptoms of gastroparesis. Foods that provoked symptoms differed in quality from foods that alleviated symptoms or were tolerable. The results of this study illustrate specific examples of foods that aggravate or improve symptoms and provide suggestions for a gastroparesis diet.

  4. Are seizures in the setting of sleep deprivation provoked?

    Science.gov (United States)

    Lawn, Nicholas; Lieblich, Sam; Lee, Judy; Dunne, John

    2014-04-01

    It is generally accepted that sleep deprivation contributes to seizures. However, it is unclear whether a seizure occurring in the setting of sleep deprivation should be considered as provoked or not and whether this is influenced by seizure type and etiology. This information may have an important impact on epilepsy diagnosis and management. We prospectively analyzed the influence of sleep deprivation on the risk of seizure recurrence in patients with first-ever unprovoked seizures and compared the findings with patients with first-ever provoked seizures. Of 1026 patients with first-ever unprovoked seizures, 204 (20%) were associated with sleep deprivation. While the overall likelihood of seizure recurrence was slightly lower in sleep-deprived patients with first-ever seizures (log-rank p=0.03), sleep deprivation was not an independent predictor of seizure recurrence on multivariate analysis. Seizure recurrence following a first-ever unprovoked seizure associated with sleep deprivation was far more likely than for 174 patients with a provoked first-ever seizure (log-rank psleep deprivation should not be regarded as provoked. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Phenomenon of isomorphic provoking responses in cases of limited scleroderma

    Directory of Open Access Journals (Sweden)

    Talnikova Е.Е.

    2015-09-01

    Full Text Available The article presents the historical origin of the term "Koebner phenomenon". The literature data reflect the etiology, pathogenesis and epidemiology of isomorphic mechanisms provoking responses in lichen planus, psoriasis, scleroder-ma, syphilis. Variants of the Koebner phenomenon's classifications are given. The clinical cases of limited scleroderma after mechanical injury are described.

  6. PTH prevents the adverse effects of focal radiation on bone architecture in young rats

    Science.gov (United States)

    Chandra, Abhishek; Lan, Shenghui; Zhu, Ji; Lin, Tiao; Zhang, Xianrong; Siclari, Valerie A.; Altman, Allison R.; Cengel, Keith A.; Liu, X. Sherry; Qin, Ling

    2013-01-01

    Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy. PMID:23466454

  7. Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA

    Directory of Open Access Journals (Sweden)

    Mary C. Hames

    2013-11-01

    Full Text Available Bacterial Pth1 is essential for viability. Pth1 cleaves the ester bond between the peptide and nucleotide of peptidyl-tRNA generated from aborted translation, expression of mini-genes, and short ORFs. We have determined the shape of the Pth1:peptidyl-tRNA complex using small angle neutron scattering. Binding of piperonylpiperazine, a small molecule constituent of a combinatorial synthetic library common to most compounds with inhibitory activity, was mapped to Pth1 via NMR spectroscopy. We also report computational docking results, modeling piperonylpiperazine binding based on chemical shift perturbation mapping. Overall these studies promote Pth1 as a novel antibiotic target, contribute to understanding how Pth1 interacts with its substrate, advance the current model for cleavage, and demonstrate feasibility of small molecule inhibition.

  8. Are PTH levels related to oxidative stress and inflammation in chronic kidney disease patients on hemodialysis?

    Directory of Open Access Journals (Sweden)

    Marcel Jaqueto

    Full Text Available Abstract Introduction: Patients at end stage renal disease have higher levels of inflammation and oxidative stress than the general population. Many factors contribute to these issues, and the parathyroid hormone (PTH is also implicated. Objective: The study was conducted in order to assess the relationship between PTH levels and inflammation and oxidative stress in hemodialysis patients. Methods: Cross-sectional study with patients of two hemodialysis facilities in Londrina, Brazil. Patients with other conditions known to generate oxidative stress and inflammation were excluded. Blood levels of PTH and biochemical parameters of inflammation (interleukins 1 and 6, tumor necrosis factor-alpha and oxidative stress (total plasma antioxidant capacity, malonic dialdehyde, lipid hydroperoxidation, advanced oxidation protein products, quantification of nitric oxide metabolites, and 8-isoprostane were measured before a dialysis session. Then, we made correlation analyses between PTH levels - either as the continuous variable or categorized into tertiles-, and inflammatory and oxidative stress biomarkers. Results: PTH did not show any correlation with the tested inflammation and oxidative stress parameters, nor as continuous variable neither as categorical variable. Conclusion: In this descriptive study, the results suggest that the inflammation and oxidative stress of hemodialysis patients probably arise from mechanisms other than secondary hyperparathyroidism.

  9. Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

    Energy Technology Data Exchange (ETDEWEB)

    Perna, A.F.; Smogorzewski, M.; Massry, S.G.

    1988-12-01

    Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and /sup 45/Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in /sup 45/Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker.

  10. Jansen Metaphyseal Chondrodysplasia due to Heterozygous H223R-PTH1R Mutations With or Without Overt Hypercalcemia

    National Research Council Canada - National Science Library

    Nampoothiri, Sheela; Fernández-Rebollo, Eduardo; Yesodharan, Dhanya; Gardella, Thomas J; Rush, Eric T; Langman, Craig B; Jüppner, Harald

    2016-01-01

    Context: Jansen's metaphyseal chondrodysplasia (JMC) is a rare skeletal dysplasia characterized by abnormal endochondral bone formation and typically severe hypercalcemia despite normal/low levels of PTH...

  11. The Anabolic Effect of PTH on Bone is Attenuated by Simultaneous Glucocorticoid Treatment

    DEFF Research Database (Denmark)

    Oxlund, Hans; Ørtoft, Gitte; Thomsen, Jesper Skovhus

    2006-01-01

    Glucocorticoids (GC) are used for the treatment of a wide spectrum of diseases because of their potent anti-inflammatory and immunosuppressive effects, and they are serious and common causes of secondary osteoporosis. Administration of intermittent parathyroid hormone (PTH) may induce formation...... of new bone and may counteract the bone loss induced by GC treatment. Effects of simultaneous PTH and GC treatment were investigated on bone biomechanics, static and dynamic histomorphometry, and bone metabolism. Twenty-seven-month-old female rats were divided randomly into the following groups: baseline...... injections resulted in a 5-fold increase in cancellous bone volume. At the proximal tibia, PTH induced a pronounced formation of new cancellous bone which originated from the endocortical bone surfaces and from thin trabeculae. Formation and modeling of connections between trabeculae were observed. Similar...

  12. Control of bone mass and remodeling by PTH receptor signaling in osteocytes.

    Directory of Open Access Journals (Sweden)

    Charles A O'Brien

    2008-08-01

    Full Text Available Osteocytes, former osteoblasts buried within bone, are thought to orchestrate skeletal adaptation to mechanical stimuli. However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone resorption and formation. Herein, we demonstrate that transgenic mice expressing a constitutively active PTH receptor exclusively in osteocytes exhibit increased bone mass and bone remodeling, as well as reduced expression of the osteocyte-derived Wnt antagonist sclerostin, increased Wnt signaling, increased osteoclast and osteoblast number, and decreased osteoblast apoptosis. Deletion of the Wnt co-receptor LDL related receptor 5 (LRP5 attenuates the high bone mass phenotype but not the increase in bone remodeling induced by the transgene. These findings demonstrate that PTH receptor signaling in osteocytes increases bone mass and the rate of bone remodeling through LRP5-dependent and -independent mechanisms, respectively.

  13. PTH (1-84) Replacement Therapy in Hypoparathyroidism: Effects on bone metabolism and structure

    DEFF Research Database (Denmark)

    Sikjær, Tanja Tvistholm; Rejnmark, Lars; Tietze, Anna

    Conventional treatment of hypoparathyroidism (hypoPT) with calcium supplements and active vitamin D analogues causes reduced bone turnover and over-mineralized bone. We studied 62 patients with known hypoPT randomized into 2 groups of treatment with either PTH (1–84) 100 µg/d s.c. or placebo....... The effect of PTH (1–84)-treatment in hypoPT is an increased bone turn-over with a decreased vBMD at cortical sites, and an increased vBMD at the trabecular sites, which is related to morphological changes in the bone microstructure with intratrabecular tunnelling and increased cortical porosity....

  14. PTH (1-84) Replacement Therapy in Hypoparathyroidism: Effects on bone metabolism and structure

    DEFF Research Database (Denmark)

    Sikjær, Tanja Tvistholm; Rejnmark, Lars; Tietze, Anna

    2011-01-01

    Conventional treatment of hypoparathyroidism (hypoPT) with calcium supplements and active vitamin D analogues causes reduced bone turnover and over-mineralized bone. We studied 62 patients with known hypoPT randomized into 2 groups of treatment with either PTH (1–84) 100 µg/d s.c. or placebo....... The effect of PTH (1–84)-treatment in hypoPT is an increased bone turn-over with a decreased vBMD at cortical sites, and an increased vBMD at the trabecular sites, which is related to morphological changes in the bone microstructure with intratrabecular tunnelling and increased cortical porosity....

  15. Polynomial representation of the matrix pth root functions and generalized Fibonacci sequences

    OpenAIRE

    Ben Taher, Rajae; Khatabi, Youness,; Rachidi, Mustapha

    2017-01-01

    This study is devoted to the polynomial representation of the matrix pth root functions. The Fibonacci-Hörner decomposition of the matrix powers and some techniques arisen from properties of generalized Fibonacci sequences, notably the Binet formula, serves as a triggering factor to provide explicit formulas for the matrix pth roots. Special cases and illustrative numerical examples are given.; Cette étude est consacrée à la représentation polynomiale de la racine p-ième de matrice. La décomp...

  16. Sequential treatment with basic fibroblast growth factor and PTH is more efficacious than treatment with PTH alone for increasing vertebral bone mass and strength in osteopenic ovariectomized rats

    DEFF Research Database (Denmark)

    Iwaniec, U.T.; Mosekilde, Li.; Mitova-Caneva, N.G.

    2002-01-01

    The study was designed 1) to determine whether treatment with basic fibroblast growth factor (bFGF) and PTH is more efficacious than treatment with PTH alone for increasing bone mass and strength and improving trabecular microarchitecture in osteopenic ovariectomized rats, and 2) to assess whether......) and maintained untreated for 1 yr. Baseline sham and OVX rats were killed at this time (15 months of age). Groups of rats were injected sc with estrogen (10 microg/kg, 4 d/wk), risedronate (5 microg/kg, 2 d/wk), or vehicle. At the end of the second week of antiresorptive treatment, catheters were inserted...... into the jugular veins of all rats, and vehicle or bFGF at a dose of 250 microg/kg was injected daily for 14 d. Three groups of rats were killed at the end of bFGF treatment. The remaining rats were continued on their respective antiresorptive therapy and injected sc with vehicle or synthetic human PTH-(1...

  17. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 is Expressed inOsteoblasts and Regulated by PTH

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Sonali; Mahalingam, Chandrika D.; Das, Varsha [Department of Internal Medicine/Endocrinology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Jamal, Shazia [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Levi, Edi [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Rishi, Arun K. [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States); VA Medical Center, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Datta, Nabanita S., E-mail: ndatta@med.wayne.edu [Department of Internal Medicine/Endocrinology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States)

    2013-07-12

    Highlights: •CARP-1 is identified for the first time in bone cells. •PTH downregulates CARP-1 expression in differentiated osteoblasts. •PTH displaces CARP-1 from nucleus to the cytoplasm in differentiated osteoblasts. •Downregulation of CARP-1 by PTH involves PKA, PKC and P-p38 MAPK pathways. -- Abstract: Bone mass is dependent on osteoblast proliferation, differentiation and life-span of osteoblasts. Parathyroid hormone (PTH) controls osteoblast cell cycle regulatory proteins and suppresses mature osteoblasts apoptosis. Intermittent administration of PTH increases bone mass but the mechanism of action are complex and incompletely understood. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 (aka CCAR1) is a novel transducer of signaling by diverse agents including cell growth and differentiation factors. To gain further insight into the molecular mechanism, we investigated involvement of CARP-1 in PTH signaling in osteoblasts. Immunostaining studies revealed presence of CARP-1 in osteoblasts and osteocytes, while a minimal to absent levels were noted in the chondrocytes of femora from 10 to 12-week old mice. Treatment of 7-day differentiated MC3T3-E1 clone-4 (MC-4) mouse osteoblastic cells and primary calvarial osteoblasts with PTH for 30 min to 5 h followed by Western blot analysis showed 2- to 3-fold down-regulation of CARP-1 protein expression in a dose- and time-dependent manner compared to the respective vehicle treated control cells. H-89, a Protein Kinase A (PKA) inhibitor, suppressed PTH action on CARP-1 protein expression indicating PKA-dependent mechanism. PMA, a Protein Kinase C (PKC) agonist, mimicked PTH action, and the PKC inhibitor, GF109203X, partially blocked PTH-dependent downregulation of CARP-1, implying involvement of PKC. U0126, a Mitogen-Activated Protein Kinase (MAPK) Kinase (MEK) inhibitor, failed to interfere with CARP-1 suppression by PTH. In contrast, SB203580, p38 inhibitor, attenuated PTH down-regulation of CARP-1

  18. Influence of four different PTH methods on the classification of chronic kidney disease patients according to the new KDIGO guideline.

    Science.gov (United States)

    Ten, Boekel Edwin; Van Veen, Merk C; Vervloet, Marc G; Fischer, Johan C; Koopman, Marion G; Van Dam, Bastiaan

    2012-01-01

    Secondary hyperparathyroidism develops frequently with chronic kidney disease (CKD) and is associated with poor outcome. The new CKD-MBD guideline, Kidney Disease: Improving Global Outcomes (KDIGO), recommends a target range for PTH which is based on the locally used, upper reference range limit (URL). We examined the impact of the KDIGO guideline on the classification of dialysis patients in two different hospitals using 4 different intact-PTH assays. Blood samples from 76 consecutive hemodialysis CKD patients were measured for PTH concentration. Classification of the patients was performed according to the previous KDOQI and the KDIGO guideline using the manufacturers' and laboratory determined URLs. Classification of patients based on 3 different PTH methods (Siemens ADVIA Centaur, Siemens Immulite 2000, and Beckman Coulter Unicel DxI) was compared with the classification found in another hospital using the Roche Modular E170 PTH assay. Depending on the PTH assay used, between 9 (12%) to 14 (18%) of the patients were classified differently in the two hospitals if the KDOQI guideline was followed. Application of the KDIGO-PTH target range resulted in a similar or decreased number of differently classified patients if the PTH concentration was measured using the Advia Centaur and Immulite assays. With the Beckman Coulter PTH assay, however, the number of differently KDIGO-classified patients increased if the manufacturers' URL (9.3 pmol/L) was used to calculate the PTH-target range. Application of the laboratory determined URL (7.0 pmol/L) improved concordance in classification, although the number of differently classified patients was still higher than with the other PTH assays. The best concordance in classification for the Beckman Coulter assay was found at a PTH value of 6.0 pmol/L. Regarding the Roche and Siemens assays, no significant difference was found in the classification using the URL either determined by the laboratory or the manufacturers. Compared

  19. All-atom simulation study of protein PTH(1-34) by using the Wang-Landau sampling method

    Science.gov (United States)

    Kim, Seung-Yeon; Kwak, Wooseop

    2014-12-01

    We perform simulations of the N-terminal 34-residue protein fragment PTH(1-34), consisting of 581 atoms, of the 84-residue human parathyroid hormone by using the all-atom ECEPP/3 force field and the Wang-Landau sampling method. Through a massive high-performance computation, the density of states and the partition function Z( T), as a continuous function of T, are obtained for PTH(1-34). From the continuous partition function Z( T), the partition function zeros of PTH(1-34) are evaluated for the first time. From both the specific heat and the partition function zeros, two characteristic transition temperatures are obtained for the all-atom protein PTH(1-34). The higher transition temperature T 1 and the lower transition temperature T 2 of PTH(1-34) can be interpreted as the collapse temperature T θ and the folding temperature T f , respectively.

  20. [The replacement therapy of rPTH(1-84) in established rat model of hypothyroidism].

    Science.gov (United States)

    Ding, Zhiwei; Li, Tiancheng; Liu, Yuhe; Xiao, Shuifang

    2015-12-01

    To investigate the replacement therapy of rPTH(1-84) (recombinant human parathyroid hormone (1-84)) to hypothyroidism in established rat model. Rat model of hypothyroidism was established by resecting parathyroids. A total of 30 rats with removal of parathyroids were divided into 6 groups randomly, 5 in each group, and applied respectively with saline injection (negative control group), calcitriol treatment (positive control group) and quadripartite PTH administration with dose of 20, 40, 80 and 160 µg/kg (experimental groups). Saline and rPTH(1-84) were injected subcutaneously daily. Calcitriol was gavaged once a day. Sham-operation was conducted in 5 rats of negative control group. To verify the authenticity of the rat model with hypothyroidism, the serum was insolated centrifugally from rat blood that was obtained from angular vein at specific time to measure calcium and phosphorus concentration. Urine in 12 hours was collected by metabolic cages and the calcium concentration was measured. After 10-week drug treatment, the experiment was terminated and bilateral femoral bone and L2-5 lumbar vertebra were removed from rats. Bone mineral density (BMD)of bilateral femoral bone and lumbar vertebra was analyzed by dual X-ray absorptiometry (DXA). The concentration of bone alkaline phosphatase (BALP) in serum was determined by radioimmunoassay. The rat model with hypothyroidism was obtained by excising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently. Administration of rPTH(1-84) in the dose of 80 or 160 µg/kg made serum calcium and phosphorus back to normal levels, with no significant difference between the doses (P>0.05). The BMD in each group of rats with rPTH(1-84) administration was increased significantly (Prats of maximum rPTH(1-84) injection group (160 µg/kg) were higher than those of normal control group (Prats treated with calcitriol had normal calcium levels and showed the increase of BMD and phosphorus

  1. Changes in Vitamin D and PTH Metabolism in Incident Pediatric Crohn Disease

    Science.gov (United States)

    Prosnitz, Aaron R.; Leonard, Mary B.; Shults, Justine; Zemel, Babette S.; Hollis, Bruce W.; Denson, Lee A.; Baldassano, Robert N.; Cohen, Aaron B.; Thayu, Meena

    2015-01-01

    Background and Aims Prior studies of vitamin D metabolism in Crohn disease (CD) did not include controls or examine changes following diagnosis. This study examined associations among 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) levels in incident pediatric CD, compared with controls, and following diagnosis. Methods Serum vitamin D and PTH were measured at diagnosis (n = 78), 6, 12, and a median of 43 months (n = 52) later in CD participants, and once in 221 controls. Multivariate regression was used to examine baseline associations, and quasi-least squares regression to assess subsequent changes. Results At diagnosis, 42% of CD participants were 25(OH)D deficient (<20 ng/mL). The odds ratio for deficiency was 2.1 (95% CI 1.1, 3.9; p<0.05) vs. controls, adjusted for age, race, and season. 1,25(OH)2D was lower in CD vs. controls (p<0.05), adjusted for 25(OH)D, tumor necrosis factor–α (TNF-α) and PTH. TNF-α was associated with lower 1,25(OH)2D (p<0.05), and the positive association between PTH and 1,25(OH)2D in controls was absent in CD (interaction p=0.02). Among participants with 25(OH)D <30 ng/mL, CD was associated with lower PTH (p<0.05) vs. controls. Following diagnosis, 25(OH)D and 1,25(OH)2D improved (p<0.001). At the final visit, 3% were 25(OH)D deficient, PTH was no longer low relative to 25(OH)D, and 1,25(OH)2D was significantly elevated (p<0.001), compared with controls. Conclusions Incident CD was associated with 25(OH)D and 1,25(OH)2D deficiency and a relative hypoparathyroidism that resolved following diagnosis. Inflammatory cytokine suppression of PTH and renal 1-α-hyroxylase may contribute to these alterations. PMID:22488969

  2. Are PTH levels related to oxidative stress and inflammation in chronic kidney disease patients on hemodialysis?

    Science.gov (United States)

    Jaqueto, Marcel; Delfino, Vinicius Daher Alvares; Bortolasci, Chiara Cristina; Barbosa, Decio Sabbatini; Morimoto, Helena Kaminami; Frange, Raquel Ferreira Nassar; Ferreira, Larissa França Fontoura; Guimarães, Fernanda Burle Dos Santos

    2016-01-01

    Patients at end stage renal disease have higher levels of inflammation and oxidative stress than the general population. Many factors contribute to these issues, and the parathyroid hormone (PTH) is also implicated. The study was conducted in order to assess the relationship between PTH levels and inflammation and oxidative stress in hemodialysis patients. Cross-sectional study with patients of two hemodialysis facilities in Londrina, Brazil. Patients with other conditions known to generate oxidative stress and inflammation were excluded. Blood levels of PTH and biochemical parameters of inflammation (interleukins 1 and 6, tumor necrosis factor-alpha) and oxidative stress (total plasma antioxidant capacity, malonic dialdehyde, lipid hydroperoxidation, advanced oxidation protein products, quantification of nitric oxide metabolites, and 8-isoprostane) were measured before a dialysis session. Then, we made correlation analyses between PTH levels - either as the continuous variable or categorized into tertiles-, and inflammatory and oxidative stress biomarkers. PTH did not show any correlation with the tested inflammation and oxidative stress parameters, nor as continuous variable neither as categorical variable. In this descriptive study, the results suggest that the inflammation and oxidative stress of hemodialysis patients probably arise from mechanisms other than secondary hyperparathyroidism. Pacientes com doença renal em estágio terminal têm níveis de inflamação e estresse oxidativo maiores do que a população geral. Muitos fatores contribuem para isso, e o hormônio paratireoidiano (PTH) é um deles. Estudo foi realizado para avaliar a relação entre os níveis de PTH e níveis de inflamação e estresse oxidativo em pacientes em hemodiálise. estudo transversal com pacientes de duas unidades de hemodiálise de Londrina, Brasil. Pacientes com condições causadoras de inflamação e estresse oxidativo foram exclusos. Níveis plasmáticos de PTH e par

  3. Do stages of dentistry training affect anxiety provoking situations?

    Science.gov (United States)

    Obarisiagbon, A; Azodo, Cc; Omoaregba, Jo; James, Bo

    2014-11-01

    Undetected and unaddressed anxiety negatively affects performance in clinical learning environments. The aim was to investigate the anxiety provoking situations in clinical dental care delivery among students of preclinical and clinical years and house officers. A 38-item modified Moss and McManus clinical anxiety questionnaire, general health questionnaire-12 (GHQ-12) and the Zung self-rating anxiety scale were the data collection tools. Of the 84 recruited, 79 completed the study giving 94.0% (79/84) response rate. The median age of the participants was 25 years with 50.6% (40/79) being 20-25 years. Gender distribution revealed that males constituted 60.8% (48/79) of the participants. House officers constituted 29.1% (23/79), clinical students 36.7% (29/79), and preclinical students 34.2 (27/79) of the participants. The top anxiety provoking situations using the modified Moss and McManus clinical anxiety questionnaire were extracting wrong tooth 3.24 (1.06), inability to pass examination 3.32 (1.01), achieving examination requirement 3.19 (1.01), fracturing a tooth 3.08 (0.98) and accidental pulp exposure 2.96 (1.04). Getting diagnosis wrong, help in faint episode, not developing radiograph properly and coping with children were the anxiety provoking situations that showed statistically significant difference in the 3 studied training stages of dentistry. Bonferroni post-hoc analysis significant difference was in the preclinical and clinical students' pair for getting diagnosis wrong, not developing radiograph properly and coping with children while house officers/clinical students and house officers/preclinical students' pairs were for help in faint episode. Overall, 2.5% (2/79) had severe, 69.6% (55/79) moderate, 26.6% (21/79) mild clinical anxiety while 1 (1.3%) of the participants expressed no clinical anxiety. Data from this study revealed that the clinical anxiety of moderate severity was prevalent among the studied dental healthcare students. The anxiety-provoking

  4. Critical size defect regeneration by rhPTH-collagen membrane as a new tissue engineering tool.

    Science.gov (United States)

    Missana, Liliana R; Jammal, María V

    2014-12-01

    Recombinant Human Parathyroid Hormone (rhPTH 1-34) administration is an effective treatment to improve bone mass in osteoporosis. The aim of this study was to develop a Tissue Engeenering Tool for bone regeneration. We evaluated the efficacy of a freeze dried rhPTH membrane in calvarial critical size defect (CSD). Forty-four Wistar female rats (body weight 150 ± 50 g) with CSD (5 mm) were divided into four groups: group 1: rhPTH membrane (rhPTHm); group 2: atelocollagen membrane (Cm); group 3: rhPTH and atelocollagen I (CrhPTHm); group 4: without any treatment (CG). All samples were evaluated on the 1st, 3rd, and 6th weeks (weeks) post-surgery by soft X-ray, histological and histometric studies. Soft X-ray results showed a radiolucent image with many irregular radiopaque areas. Histologically, rhPTHm was replaced by reticular bone (7%) since 3rd week, and lamellar bone ossicles (30%) at 6th week. Cm showed bone formation like composite bone type on week 1st, 3rd, and 6th (2%, 44%, and 41%, respectively). With CrhPTHm, bone formation was observed in all periods (2.4%, 48%, and 53%), showing statistical difference with CG in the 3rd and 6th wks (p = 0.03 and 0.01). Our results demonstrated the effectiveness of a new biomaterial called CrhPTHm because its ability to regenerate calvarial CSD. Moreover, the membrane represents a new local intermittent delivery system allowing rhPTH slow release. © 2014 Wiley Periodicals, Inc.

  5. Children's self-speech and self-regulation during a fear-provoking behavioral test.

    NARCIS (Netherlands)

    Prins, P.J.M.

    1986-01-01

    Conducted a behavioral test and a behavioral interview to assess children's spontaneous use of self-speech and self-regulation in a fear-provoking situation. 44 children (aged 8-12 yrs) performed a series of more fear-provoking (e.g., jumping off the high diving board) or less fear-provoking (e.g.,

  6. Teriparatida (PTH[1-34]rh: uma nova perspectiva no tratamento da osteoporose Teriparatide (PTH[1-34]rh: a new perspective in the treatment of osteoporosis

    Directory of Open Access Journals (Sweden)

    Juliana Helena Abreu de Oliveira

    2003-08-01

    Full Text Available No momento, as medicações aprovadas para tratamento da osteoporose agem reduzindo a taxa de perda óssea e diminuindo a reabsorção óssea. A teriparatida é um fragmento recombinante sintético de 34 aminoácidos do hormônio paratireóide humano. A teriparatida se liga ao receptor de PTH da proteína G e estimula a formação e a ação dos osteoblastos, que são as células responsáveis pela formação dos ossos. Assim, a principal diferença entre o tratamento da osteoporose com teriparatida e o tratamento anti-reabsorção é que a teriparatida promove o crescimento de osso novo. Em estudos pré-clínicos, o uso intermitente de PTH foi associado com um aumento significativo da massa óssea gradeada em diversos locais. A exposição intermitente ao PTH durante 4 a 6 semanas em modelos de animais ovariectomizados leva a um aumento da espessura do osso gradeado. Há estudos clínicos que mostram que a teriparatida aumenta significativamente a densidade óssea e diminui a incidência de fraturas osteoporóticas vertebrais e não-vertebrais nas mulheres com osteoporose pós-menopáusica e têm risco alto de fratura, e aumenta a densidade óssea nos homens com osteoporose, tanto hipogonádica como idiopática. A teriparatida é dada por injeção subcutânea diária e foi associada com um mínimo de efeitos colaterais, além de não apresentar interações medicamentosas. Sendo assim, a teriparatida surge como uma abordagem completamente nova no tratamento da osteoporose, estimulando diretamente a formação do osso.Medications currently approved for treatment of osteoporosis act by slowing the rate of bone loss and decreasing bone resorption. Teriparatide is a synthetic recombinant 34-amino-acid fragment of human parathyroid hormone. Teriparatide binds to the G protein PTH receptor and stimulates the action of osteoblasts, which are the cells responsible for bone formation. Thus the main difference between teriparatide and antiresorptive

  7. Monitoring of Cellular Changes in the Bone Marrow following PTH(1-34 Treatment of OVX Rats Using a Portable Stray-Field NMR Scanner

    Directory of Open Access Journals (Sweden)

    Inbar Hillel

    2017-01-01

    Full Text Available Osteoporosis is characterized by reduction in trabecular bone in conjunction with increased marrow cell adiposity. While these changes occur within weeks, monitoring of treatment efficacy as performed by DEXA is sensitive only to long-term changes. MRI is sensitive to bone marrow changes but is less affordable. In a recent study, we have shown that a stray-field NMR can monitor bone marrow cellular changes that are related to osteoporosis. Objectives. To demonstrate sensitivity of a low-field tabletop NMR scanner to bone marrow dynamics following hormonal treatment in rats. Methods. Two-month-old female rats (n=36 were ovariectomized (OVX and dosed for the ensuing 3 or 5 weeks with 20 mg/kg of PTH(1-34. Hind limbs femurs and tibiae were isolated and underwent ex vivo microradiography and histology and NMR relaxometry at 6 weeks (preventive experiment and 11 weeks (therapeutic treatment experiment after OVX. Results. OVX rats developed osteoporotic changes including adipogenic marrow compared to Sham and PTH treated rats. T2 and ADC NMR relaxation coefficients were found to correlate with marrow composition. Conclusions. This study suggests that stray-field NMR, an affordable method that is sensitive to the rapid cellular changes in bone marrow, may have a clinical value in monitoring hormonal treatment for osteoporosis.

  8. Monitoring of Cellular Changes in the Bone Marrow following PTH(1-34) Treatment of OVX Rats Using a Portable Stray-Field NMR Scanner.

    Science.gov (United States)

    Hillel, Inbar; Binderman, Itzhak; Sarda, Yifat; Nevo, Uri

    2017-01-01

    Osteoporosis is characterized by reduction in trabecular bone in conjunction with increased marrow cell adiposity. While these changes occur within weeks, monitoring of treatment efficacy as performed by DEXA is sensitive only to long-term changes. MRI is sensitive to bone marrow changes but is less affordable. In a recent study, we have shown that a stray-field NMR can monitor bone marrow cellular changes that are related to osteoporosis. Objectives. To demonstrate sensitivity of a low-field tabletop NMR scanner to bone marrow dynamics following hormonal treatment in rats. Methods. Two-month-old female rats (n = 36) were ovariectomized (OVX) and dosed for the ensuing 3 or 5 weeks with 20 mg/kg of PTH(1-34). Hind limbs femurs and tibiae were isolated and underwent ex vivo microradiography and histology and NMR relaxometry at 6 weeks (preventive experiment) and 11 weeks (therapeutic treatment experiment) after OVX. Results. OVX rats developed osteoporotic changes including adipogenic marrow compared to Sham and PTH treated rats. T2 and ADC NMR relaxation coefficients were found to correlate with marrow composition. Conclusions. This study suggests that stray-field NMR, an affordable method that is sensitive to the rapid cellular changes in bone marrow, may have a clinical value in monitoring hormonal treatment for osteoporosis.

  9. Focused parathyroidectomy without intra-operative parathormone monitoring: The value of PTH assay in preoperative ultrasound guided fine needle aspiration washout

    Directory of Open Access Journals (Sweden)

    Fatih Kuzu

    2016-03-01

    Conclusions: The higher level of PTH in preoperative ultrasound guided FNA washout is a considerable data to predict the correct localization of HP, particularly in circumstances of greater values than the serum PTH level. However, although its specificity is high, in cases of coexisting nodular thyroid disease, associated additional HP might be missed at focused parathyroidectomy without PTH monitoring, leading to recurrent disease.

  10. Mucosal versus muscle pain sensitivity in provoked vestibulodynia

    Directory of Open Access Journals (Sweden)

    Witzeman K

    2015-08-01

    Full Text Available Kathryn Witzeman,1 Ruby HN Nguyen,2 Alisa Eanes,3 Sawsan As-Sanie,4 Denniz Zolnoun51Department of Obstetrics and Gynecology, Denver Health Medical Center, Denver, CO, 2Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, 3Pelvic Pain Research Unit, Division of Advanced Laparoscopy and Pelvic Pain, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC, 4Department of Obstetrics and Gynecology, Division of Minimally Invasive Gynecologic Surgery, University of Michigan, Ann Arbor, MI, 5Department of Obstetrics and Gynecology and Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, NC, USABackground: An estimated 8.3%–16% of women experience vulvovaginal discomfort during their lifetime. Frequently these patients report provoked pain on contact or with attempted intercourse, commonly referred to as provoked vestibulodynia (PVD. Despite the burden of this condition, little is known about its potential etiologies including pelvic floor muscular dysfunction and mucosal components. This knowledge would be beneficial in developing targeted therapies including physical therapy.Objective: To explore the relative contribution of mucosal versus muscle pain sensitivity on pain report from intercourse among women with PVD.Design: In this proof of concept study, 54 women with PVD underwent a structured examination assessing mucosal and pelvic muscle sensitivity.Methods: We examined three mucosal sites in the upper and lower vestibule. Patients were asked to rate their pain on cotton swab palpation of the mucosa using a 10-point visual analog scale. Muscle pain was assessed using transvaginal application of pressure on right and left puborectalis, and the perineal muscle complex. The Gracely pain scale (0–100 was used to assess the severity of pain with intercourse, with women rating the lowest, average, and highest pain levels; a 100 rating the

  11. Transformation of sweet orange [Citrus sinensis (L.) Osbeck] with pthA-nls for acquiring resistance to citrus canker disease.

    Science.gov (United States)

    Yang, Li; Hu, Chunhua; Li, Na; Zhang, Jiayin; Yan, Jiawen; Deng, Ziniu

    2011-01-01

    The COOH terminal of pthA encoding three nuclear localizing signals (NLS) was amplified by polymerase chain reaction (PCR) from the plasmid of Xanthomonas axonopodis pv. citri, the pathogen of citrus canker disease. Then the sense and antisense strands of the nls were cloned into pBI121 vector. pthA-nls driven by the CaMV35 s promoter was transferred into sweet orange via Agrobacterium -mediated transformation. Successful integration was confirmed by PCR and Southern blotting, and 12 sense-nls (nls (+)) and 9 antisense-nls (nls (-)) transgenic clones were obtained. The expression of nls fragment was analyzed by RT-PCR, Real time q-PCR and Western blotting, in which the specific NLS protein was detected only in nls (+) transgenic clones. In an in vitro assay, when pin-puncture inoculation was performed with 2.5 × 10(7) cfu/ml of bacterial solution, the nls (+) transgenic clones showed no typical lesion development, while typical symptoms were observed in the wild types and the nls (-) transgenic clones. In vivo assay results indicated that the nls (+) transgenic clones showed less disease incidence, in comparison with the wild types and the nls (-) transgenic clones, when pin-puncture inoculation was performed with 10(4)-10(5) cfu/ml. The minimum disease incidence was 23.3% for 'Sucarri' sweet orange and 33.3% for 'Bingtang' sweet orange. When 10(4)-10(7) cfu/ml of pathogen was spray inoculated, the nls (+) transgenic clones did not show any symptom, and even the concentration raised to 10(9) cfu/ml, the disease incidence was 20-80%, while the wild types and the nls (-) transgenic clones had 100% disease development with whatever concentration of inoculum. Two transgenic clones were confirmed to be resistant to citrus canker disease in the repeated inoculation. The results suggested that the transformation of nls sense strands may offer an effective way to acquire resistance to citrus canker disease.

  12. High-energy drinks may provoke aortic dissection.

    Science.gov (United States)

    Jonjev, Zivojin S; Bala, Gustav

    2013-05-01

    High-energy drinks have become extremely popular after Red Bull's promotion at 1987 in Austria and 1997 in the United States. Since then, we witnessed spectacular increase in different brands, caffeine content and market consumption all over the world. However, there are no reports published in the scientific literature related with detrimental side effects after heavy consumption of high-energy drinks. We report a series of three high-risk cardiovascular patients who had aortic dissection (De Bakey type I and II) following significant consumption of high-energy drinks. All of them required emergency surgical procedure and were remaining stable after surgery. We propose that uncontrolled consumption of high-energy drinks, especially in patients with underlying heart disease, could provoke potentially lethal cardiovascular events as well as acute aortic dissection.

  13. [Adulthood atopic dermatitis: epidemiology, clinical symptoms, provoking and prognostic factors].

    Science.gov (United States)

    Pónyai, Györgyi; Temesvári, Erzsébet; Kárpáti, Sarolta

    2007-01-07

    The prevalence of atopic diseases, including allergic rhinitis, asthma bronchiale and atopic dermatitis is increasing both in children and adults at different parts of the world. Atopic dermatitis is a chronic inflammatory skin disease affecting mostly children, but the atopic trait continues, not only for later respiratory allergies, but also for skin symptoms in adulthood. In this form dry skin, flexural lichenification, head and neck dermatitis, hand dermatitis are typical. The exact etiology of atopic dermatitis is unknown, in the background interactions of genetical predisposition, skin barrier defects and immunological and environmental factors can be verified. In the complex approach of atopic dermatitis, a pivotal role is ascribed to the evaluation and possibly the elimination of provoking factors, like gender, family structure, clothing, aero-, alimentary and contact allergens, psychosocial stress, migration, infections, and personal home environment. Authors review clinical manifestations, triggering and prognostic factors of the adulthood atopic dermatitis.

  14. Monitoring of intermittent PTH(1-34) treatment by serum PINP in adult ovariectomized osteopenic rats

    DEFF Research Database (Denmark)

    Halleen, Jussi; Peng, ZhiQi; Fagerlund, Katja

    Procollagen I N-terminal propeptide (PINP) is a sensitive marker of bone formation for monitoring the efficacy of treatment with recombinant human parathyroid hormone (1-34) analog [PTH(1-34)] in osteoporotic patients. Recently, a new immunoassay has been developed for serum PINP in rodents......, allowing measurement of serum PINP in preclinical rodent osteoporosis models. The purpose of this study was to evaluate the use of serum PINP for monitoring intermittent PTH(1-34) treatment in adult ovariectomized (OVX) osteopenic rats. Study groups included a sham-operated control group and an OVX......-operated control group receiving vehicle, and OVX-operated groups receiving daily subcutaneous injections of 1.2, 4.0, 12.0, 40.0 and 120.0 µg/kg human PTH(1-34). Each group contained 12 animals that were 6 months of age at the time of the operations. Dosing was started at 7 weeks after OVX and continued for 6...

  15. PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.

    Science.gov (United States)

    Kir, Serkan; Komaba, Hirotaka; Garcia, Ana P; Economopoulos, Konstantinos P; Liu, Wei; Lanske, Beate; Hodin, Richard A; Spiegelman, Bruce M

    2016-02-09

    Cachexia is a wasting syndrome associated with elevated basal energy expenditure and loss of adipose and muscle tissues. It accompanies many chronic diseases including renal failure and cancer and is an important risk factor for mortality. Our recent work demonstrated that tumor-derived PTHrP drives adipose tissue browning and cachexia. Here, we show that PTH is involved in stimulating a thermogenic gene program in 5/6 nephrectomized mice that suffer from cachexia. Fat-specific knockout of PTHR blocked adipose browning and wasting. Surprisingly, loss of PTHR in fat tissue also preserved muscle mass and improved muscle strength. Similarly, PTHR knockout mice were resistant to cachexia driven by tumors. Our results demonstrate that PTHrP and PTH mediate wasting through a common mechanism involving PTHR, and there exists an unexpected crosstalk mechanism between wasting of fat tissue and skeletal muscle. Targeting the PTH/PTHrP pathway may have therapeutic uses in humans with cachexia. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Solution Structure of Archaeoglobus fulgidis Peptidyl-tRNA Hydrolase(Pth2) Provides Evidence for an Extensive Conserved Family of Pth2 Enzymes in Archaea, Bacteria and Eukaryotes.

    Energy Technology Data Exchange (ETDEWEB)

    Powers, Robert; Mirkovic, Nebojsa; Goldsmith-Fischman, Sharon; Acton, Thomas; Chiang, Yiwen; Huang, Yuanpeng; Ma, LiChung; Rajan, Paranji K.; Cort, John R.; Kennedy, Michael A.; Liu, Jinfeng; Rost, Burkhard; Honig, Barry; Murray, Diana; Montelione, Gaetano

    2005-11-01

    The solution structure of protein AF2095 from the thermophilic archaea Archaeglobus fulgidis, a 123-residue (13.6 kDa) protein, has been determined by NMR methods. The structure of AF2095 is comprised of four a-helices and a mixed b-sheet consisting of four parallel and anti-parallel b-strands, where the a-helices sandwich the b-sheet. Sequence and structural comparison of AF2095 with proteins from Homo sapiens, Methanocaldococcus jannaschii and Sulfolobus solfataricus, reveals that AF2095 is a peptidyl-tRNA hydrolase (Pth2). This structural comparison also identifies putative catalytic residues and a tRNA interaction region for AF2095. The structure of AF2095 is also similar to the structure of protein TA0108 from archaea Thermoplasma acidophilum, which is deposited in the Protein Database but not functionally annotated. The NMR structure of AF2095 has been further leveraged to obtain good quality structural models for 55 other proteins. Although earlier studies have proposed that the Pth2 protein family is restricted to archeal and eukaryotic organisms, the similarity of the AF2095 structure to human Pth2, the conservation of key active-site residues, and the good quality of the resulting homology models demonstrate a large family of homologous Pth2 proteins that are conserved in eukaryotic, archaeal and bacterial organisms, providing novel insights in the evolution of the Pth and Pth2 enzyme families.

  17. Effects of increasing age, dosage, and duration of PTH treatment on BMD increase--a meta-analysis

    DEFF Research Database (Denmark)

    Schwarz, Peter; Jorgensen, Niklas Rye; Mosekilde, Leif

    2012-01-01

    We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present...... were included. By metaregression analysis, we found that the increase in spine BMD (Z-score) after PTH treatment was blunted by increasing age (R (2) = 0.27; 2p = 0.01, slope -0.023 Z-scores per year, 11 studies). By increasing PTH dosage (μg/d), spine BMD increased significantly (2p = 0...

  18. [Glucocorticoid and Bone. The effect of glucocorticoid and PTH in osteoblast apoptosis and differentiation via interleukin 11 expression].

    Science.gov (United States)

    Endo, Itsuro

    2014-09-01

    Intermittent PTH administration stimulates bone formation and counteracts the inhibition of bone formation by glucocorticoid excess. We have previously demonstrated that PTH enhances interleukin (IL) -11 gene transcription by a rapid induction of delta-fosB expression and Smad1/5 phosphorylation. On the other hand, glucocorticoid can suppress osteoblast differentiation and enhance apoptosis of osteoblast cells via down-regulation of IL-11 expression. PTH could reverse glucocorticoid-induced these damage of osteoblast via stimulation of IL-11 expression. Our data also suggested that IL-11 mediates stimulatory and inhibitory signals of osteoblast differentiation by affecting Wnt signaling. These data demonstrates that PTH and glucocorticoid may regulate osteoblast differentiation and apoptosis via their effect on IL-11 expression.

  19. Arterial blood pressure, serum calcium and PTH in elderly men with parathyroid tumors and primary hyperparathyroidism.

    Science.gov (United States)

    Lumachi, Franco; Camozzi, Valentina; Luisetto, Giovanni; Zanella, Simone; Basso, Stefano M M

    2011-11-01

    In patients with parathyroid tumors and primary hyperparathyroidism (PHPT), the relationship between arterial blood pressure (BP) and both serum calcium and parathyroid hormone (PTH) is still unclear. The aim of this study was to investigate whether a correlation exists between BP and the main biochemical parameters in men with confirmed sporadic PHPT due to a solitary parathyroid adenoma. A series of 38 elderly (>64 years) men (median age 69 years, range 65-78 years) were enrolled in the study. Twenty-nine (76.3%) were asymptomatic, while 9 (23.7%) had renal diseases (i.e. renal stones, impaired renal function). The main preoperative biochemical parameters were the following: serum calcium=2.77±0.25 mmol/l, PTH=166.5±157.0 ng/l, alkaline phosphatase (ALP)=107.6±37.0 U/l, and creatinine=82.5±8.1 μmol/l. In each patient, the BP was recorded three times at 2-3 min intervals using an automatic device, and the mean values were recorded. All patients successfully underwent parathyroidectomy. As expected, there was a significant relationship between age and both systolic and diastolic BP (β=0.39, p=0.018; β=0.41, p=0.014, respectively). There was also a correlation between systolic and diastolic BP (β=0.39, p=0.01) and between serum calcium and PTH (β=0.51, p=0.008). A weak relationship (β=0.28, p=0.04) between serum calcium and creatinine was also found. However, no significant relationship between systolic or diastolic BP and serum calcium (β=0.012, p=0.94; β=0.065, p=0.71) or PTH (β=0.08, p=0.65; β=0.17, p=0.32), respectively, was observed. In conclusion, our study confirms that in men with parathyroid tumors and PHPT, the BP values are independent of both serum calcium and PTH levels.

  20. ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats

    DEFF Research Database (Denmark)

    Neerup, Trine Skovlund Ryge; Stahlhut, Martin; Petersen, Jørgen S

    2011-01-01

    Daily injections of human parathyroid hormone (1-34), hPTH(1-34), provide a highly effective treatment option for severe osteoporosis. However, PTH analogs shorter than 28 amino acids do not retain any bone augmenting potential. Here, we present ZP2307 ([Ac₅c¹, Aib³, Leu⁸, Gln¹⁰, Har¹¹, Ala¹², Trp...

  1. PTH1–34 Blocks Radiation-induced Osteoblast Apoptosis by Enhancing DNA Repair through Canonical Wnt Pathway*

    Science.gov (United States)

    Chandra, Abhishek; Lin, Tiao; Zhu, Ji; Tong, Wei; Huo, Yanying; Jia, Haoruo; Zhang, Yejia; Liu, X. Sherry; Cengel, Keith; Xia, Bing; Qin, Ling

    2015-01-01

    Focal radiotherapy for cancer patients has detrimental effects on bones within the radiation field and the primary clinical signs of bone damage include the loss of functional osteoblasts. We reported previously that daily injection of parathyroid hormone (PTH, 1–34) alleviates radiation-induced osteopenia in a preclinical radiotherapy model by improving osteoblast survival. To elucidate the molecular mechanisms, we irradiated osteoblastic UMR 106-01 cells and calvarial organ culture and demonstrated an anti-apoptosis effect of PTH1–34 on these cultures. Inhibitor assay indicated that PTH exerts its radioprotective action mainly through protein kinase A/β-catenin pathway. γ-H2AX foci staining and comet assay revealed that PTH efficiently promotes the repair of DNA double strand breaks (DSBs) in irradiated osteoblasts via activating the β-catenin pathway. Interestingly, Wnt3a alone also blocked cell death and accelerated DNA repair in primary osteoprogenitors, osteoblastic and osteocytic cells after radiation through the canonical signaling. Further investigations revealed that both Wnt3a and PTH increase the amount of Ku70, a core protein for initiating the assembly of DSB repair machinery, in osteoblasts after radiation. Moreover, down-regulation of Ku70 by siRNA abrogated the prosurvival effect of PTH and Wnt3a on irradiated osteoblasts. In summary, our results identify a novel role of PTH and canonical Wnt signaling in regulating DSB repair machinery and apoptosis in osteoblasts and shed light on using PTH1–34 or Wnt agonist as possible therapy for radiation-induced osteoporosis. PMID:25336648

  2. A novel, secreted form of human ADAM 12 (meltrin alpha) provokes myogenesis in vivo

    DEFF Research Database (Denmark)

    Gilpin, B J; Loechel, F; Mattei, M G

    1998-01-01

    , membrane-bound form designated ADAM 12-L (L for long form). These two forms arise by alternative splicing of a single gene located on chromosome 10q26. Northern blotting demonstrated that mRNAs of both forms are abundant in human term placenta and are also present in some tumor cell lines. The ADAM 12-L......The ADAM (A Disintegrin And Metalloprotease) family of cell-surface proteins may have an important role in cellular interactions and in modulating cellular responses. In this report we describe a novel, secreted form of human ADAM 12 (meltrin alpha), designated ADAM 12-S (S for short), and a larger...... transcript can also be detected in normal human adult skeletal, cardiac, and smooth muscle. Human A204 embryonal rhabdomyosarcoma cells that do not differentiate into muscle cells and do not express any form of ADAM 12 were stably transfected with an ADAM 12-S minigene encoding the disintegrin domain...

  3. PTH Test

    Science.gov (United States)

    ... determine the cause of calcium imbalances; to evaluate parathyroid function ; to diagnose and differentiate between primary, secondary, and tertiary hyperparathyroidism ; to diagnose hypoparathyroidism ; during surgery for hyperparathyroidism to confirm removal of the gland(s) causing the ... Required? A blood sample ...

  4. Pain Symptoms in Fibromyalgia Patients with and without Provoked Vulvodynia

    Directory of Open Access Journals (Sweden)

    Anna Ghizzani

    2014-01-01

    Full Text Available Objective. The aim of the study was to compare the pain symptoms of fibromyalgia patients exhibiting (FMS+PVD and not exhibiting (FMS comorbidity with provoked vulvodynia. Study Design. The case control study was performed in 39 patients who had been diagnosed with FMS and accepted to undergo gynaecological examination and in 36 healthy women (C. All patients completed standardized questionnaires for pain intensity, pain area, and psychological functioning. The gynaecological examination included vulvar pain pressure reactivity (Q-tip, pelvic tone assessment (Kegel manoeuver, and a semistructured interview collecting detailed information about pelvic symptoms and sexual function. Results. FMS+PVD patients displayed a higher number of associated symptoms than FMS patients. The vulvar excitability was significantly higher in FMS+PVD than in FMS and in both groups than in Controls. Half of FMS+PVD patients were positive to Kegel manoeuver and displayed higher scores in widespread pain intensity, STAI-Y2, and CESD levels than Kegel negative patients. Conclusions. The study reveals that increased vulvar pain excitability may occur in FMS patients independently of the presence of coital pain. Results suggest that coital pain develops in patients with higher FMS symptoms severity due to the cooperative effects of peripheral and central sensitization mechanisms.

  5. Alteration in the gut microbiota provokes susceptibility to tuberculosis

    Directory of Open Access Journals (Sweden)

    Nargis Khan

    2016-11-01

    Full Text Available AbstractThe microbiota that resides in the gastrointestinal tract provides essential health benefits to the host. In particular, they regulate immune homeostasis. Recently, several evidences indicate that alteration in the gut microbial community can cause infectious and non-infectious diseases. Tuberculosis (TB is the most devastating disease, inflicting mortality and morbidity. It remains unexplored, whether changes in the gut microbiota can provoke or prevent TB. In the current study, we have demonstrated the antibiotics driven changes in the gut microbial composition and their impact on the survival of Mtb in the lungs, liver and spleen of infected mice, compared to those with intact microbiota. Interestingly, dysbiosis of microbes showed significant increase in the bacterial burden in lungs and dissemination of Mtb to spleen and liver. Further, elevation in the number of Tregs and decline in the pool of IFN-γ and TNF-α releasing CD4 T cells was noticed. Interestingly, fecal transplantation in the gut microbiota disrupted animals exhibited improved Th1 immunity and lesser Tregs population. Importantly, these animals displayed reduced severity to Mtb infection. This study for the first time demonstrated the novel role of gut microbes in the susceptibility to TB and its prevention by microbial implants. In future, microbial therapies may help in treating patients suffering from TB.

  6. Loss of receptor activity-modifying protein 2 in mice causes placental dysfunction and alters PTH1R regulation.

    Directory of Open Access Journals (Sweden)

    Mahita Kadmiel

    Full Text Available Receptor activity-modifying protein 2 (Ramp2 is a single-pass transmembrane protein that heterodimerizes with several family B G-protein coupled receptors to alter their function. Ramp2 has been primarily characterized in association with calcitonin receptor-like receptor (Calcrl, CLR, forming the canonical receptor complex for the endocrine peptide adrenomedullin (Adm, AM. However, we previously demonstrated that Ramp2+/- female mice display a constellation of endocrine-related phenotypes that are distinct from those of Adm+/- and Calcrl+/- mice, implying that RAMP2 has physiological functions beyond its canonical complex. Here, we localize Ramp2 expression in the mouse placenta, finding that Ramp2 is robustly expressed in the fetal labyrinth layer, and then characterize the effects of loss of Ramp2 on placental development. Consistent with the expression pattern of Ramp2 in the placenta, Ramp2-/- placentas have a thinner labyrinth layer with significantly fewer trophoblast cells secondary to a reduction in trophoblast proliferation. We also find that absence of Ramp2 leads to failed spiral artery remodeling unaccompanied by changes in the uterine natural killer cell population. Furthermore, we assess changes in gene expression of other RAMP2-associated G-protein coupled receptors (GPCRs, concluding that Ramp2 loss decreases parathyroid hormone 1 receptor (Pthr1 expression and causes a blunted response to systemic parathyroid hormone (PTH administration in mice. Ultimately, these studies provide in vivo evidence of a role for RAMP2 in placental development distinct from the RAMP2-CLR/AM signaling paradigm and identify additional pathways underlying the endocrine and fertility defects of the previously characterized Ramp2 heterozygous adult females.

  7. PTH1-34 Alleviates Radiotherapy-induced Local Bone Loss by Improving Osteoblast and Osteocyte Survival

    Science.gov (United States)

    Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth; Zhu, Ji; Altman, Allison R.; Tseng, Weiju; Zhang, Yejia; Akintoye, Sunday O.; Cengel, Keith; Liu, X. Sherry; Qin, Ling

    2014-01-01

    Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1–34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1–34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1–34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1–34. Furthermore, histological analyses revealed that PTH1–34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage. PMID:24998454

  8. La proteína PthB de Xanthomonas axonopodis pv. manihotis es autoactiva en ensayos de doble hibrido

    Directory of Open Access Journals (Sweden)

    Gil Juliana

    2011-04-01

    Full Text Available La bacteriosis vascular de yuca producida por la bacteria Xanthomonas axonopodis pv. manihotis (Xam es uno de los factores limitantes para la producción de yuca. Dentro de los primeros factores de patogenicidad identificados en esta bacteria se encuentra el gen pthB. La proteína PthB pertenece a la familia de efectores PthA/AvrBs3, que se caracterizan por presentar dominios NLS (Nuclear Localization Signal y un dominio AAD (Acidic Activation Domain, lo cual sugiere que estas proteínas actúan como factores de transcripción. La identificación de las proteínas de yuca que interactúan con PthB permitiría dar luces sobre la función de esta proteína en la patogenicidad de esta bacteria. En este trabajo se clonó pthB en una fusión traduccional con el BD (Binding Domain del factor de transcripción GAL4. Después de transformar este constructo en una cepa de levadura, se observó autoactivación de los genes reporteros, incluso a concentraciones altas de 3-AT. La eliminación del primer, segundo o de los dos NLS y del AAD no eliminaron la capacidad de autoactivación de los genes reporteros mediada por PthB. Estos resultados indican la imposibilidad de su utilización en un tamizaje de una librería de ADNc de yuca para identificar las proteínas que interactúan con PthB.

  9. Cue-Provoked Craving and Nicotine Replacement Therapy in Smoking Cessation

    Science.gov (United States)

    Waters, Andrew J.; Shiffman, Saul; Sayette, Michael A.; Paty, Jean A.; Gwaltney, Chad J.; Balabanis, Mark H.

    2004-01-01

    Cue exposure paradigms have been used to examine reactivity to smoking cues. However, it is not known whether cue-provoked craving is associated with smoking cessation outcomes or whether cue reactivity can be attenuated by nicotine replacement therapy (NRT) in clinical samples. Cue-provoked craving ratings and reaction time responses were…

  10. All-atom simulation study of protein PTH(1-34) by using the Wang-Landau sampling method

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung-Yeon [Korea National University of Transportation, Chungju (Korea, Republic of); Kwak, Woo-Seop [Chosun University, Gwangju (Korea, Republic of)

    2014-12-15

    We perform simulations of the N-terminal 34-residue protein fragment PTH(1-34), consisting of 581 atoms, of the 84-residue human parathyroid hormone by using the all-atom ECEPP/3 force field and the Wang-Landau sampling method. Through a massive high-performance computation, the density of states and the partition function Z(T), as a continuous function of T, are obtained for PTH(1-34). From the continuous partition function Z(T), the partition function zeros of PTH(1-34) are evaluated for the first time. From both the specific heat and the partition function zeros, two characteristic transition temperatures are obtained for the all-atom protein PTH(1-34). The higher transition temperature T{sub 1} and the lower transition temperature T{sub 2} of PTH(1-34) can be interpreted as the collapse temperature T{sub θ} and the folding temperature T{sub f} , respectively.

  11. Comparison between 1alpha(OH)D3 and 1,25(OH)2D3 on the suppression of plasma PTH levels in uremic patients, evaluated by the 'whole' and 'intact' PTH assays

    DEFF Research Database (Denmark)

    Brandi, Lisbet; Egfjord, Martin; Olgaard, Klaus

    2005-01-01

    of plasma Ca2+ and plasma PTH were drawn at 0, 6, 12, 24, 48 and 72 h. The same patient was studied 3 times in a random fashion with an interval of 3 weeks. Further, 7 of the patients were studied after an injection of 6 microg 1,25(OH)2D3 intravenously. RESULTS: No significant changes in plasma Ca2...... 'intact PTH' assays. METHODS: 11 patients on chronic hemodialysis with plasma intact PTH >90 pg/ml were studied. At time zero 10 microg 1,25(OH)2D3 (Calcijex, Abbott, USA), or 10 microg 1alpha(OH)D3 (Etalpha, LEO, Denmark) or 10 ml of isotonic saline was injected as a bolus. Blood samples for analyses......)2D3 than after 1alpha(OH)D3 at 48 (p = 0.016) and 72 h (p times greater than that of 1alpha(OH)D3. The increase...

  12. Low Bone Turnover and Low BMD in Down Syndrome: Effect of Intermittent PTH Treatment

    Science.gov (United States)

    Akel, Nisreen S.; Vander Schilden, Jaclyn; Bacon, Anthony W.; Bracey, John W.; Sowder, Timothy; Skinner, Robert A.; Swain, Frances L.; Hogue, William R.; Leblanc, Donna B.; Gaddy, Dana; Wenger, Galen R.; Suva, Larry J.

    2012-01-01

    Trisomy 21 affects virtually every organ system and results in the complex clinical presentation of Down syndrome (DS). Patterns of differences are now being recognized as patients’ age and these patterns bring about new opportunities for disease prevention and treatment. Low bone mineral density (BMD) has been reported in many studies of males and females with DS yet the specific effects of trisomy 21 on the skeleton remain poorly defined. Therefore we determined the bone phenotype and measured bone turnover markers in the murine DS model Ts65Dn. Male Ts65Dn DS mice are infertile and display a profound low bone mass phenotype that deteriorates with age. The low bone mass was correlated with significantly decreased osteoblast and osteoclast development, decreased bone biochemical markers, a diminished bone formation rate and reduced mechanical strength. The low bone mass observed in 3 month old Ts65Dn mice was significantly increased after 4 weeks of intermittent PTH treatment. These studies provide novel insight into the cause of the profound bone fragility in DS and identify PTH as a potential anabolic agent in the adult low bone mass DS population. PMID:22916188

  13. Does simvastatin stimulate bone formation in vivo?

    Directory of Open Access Journals (Sweden)

    Chorev Michael

    2003-04-01

    Full Text Available Abstract Background Statins, potent compounds that inhibit cholesterol synthesis in the liver have been reported to induce bone formation, both in tissue culture and in rats and mice. To re-examine potential anabolic effects of statins on bone formation, we compared the activity of simvastatin (SVS to the known anabolic effects of PTH in an established model of ovariectomized (OVX Swiss-Webster mice. Methods Mice were ovariectomized at 12 weeks of age (T0, remained untreated for 5 weeks to allow development of osteopenia (T5, followed by treatment for 8 weeks (T13. Whole, trabecular and cortical femoral bone was analyzed by micro-computed tomography (micro CT. Liquid chromatography/mass spectrometry (LC/MS was used to detect the presence of SVS and its active metabolite, simvastatin β-hydroxy acid (SVS-OH in the mouse serum. Results Trabecular BV/TV at T13 was 4.2 fold higher in animals treated with PTH (80 micro-g/kg/day compared to the OVX-vehicle treated group (p in vivo study. Conclusions While PTH demonstrated the expected anabolic effect on bone, SVS failed to stimulate bone formation, despite our verification by LC/MS of the active SVS-OH metabolite in mouse serum. While statins have clear effects on bone formation in vitro, the formulation of existing 'liver-targeted' statins requires further refinement for efficacy in vivo.

  14. Simultaneous control of PTH and CaxP Is sustained over three years of treatment with cinacalcet HCl.

    Science.gov (United States)

    Sprague, Stuart M; Evenepoel, Pieter; Curzi, Mario P; González, Maria Teresa; Husserl, Fred E; Kopyt, Nelson; Sterling, Lulu Ren; Mix, Chris; Wong, Gordon

    2009-09-01

    Chronic kidney disease (CKD) is commonly complicated by secondary hyperparathyroidism (SHPT), leading to increased risk of morbidity and mortality. SHPT is a progressive disease often requiring long-term therapy to control parathyroid hormone (PTH) and mineral imbalances. Vitamin D sterols and phosphate binders, used as traditional therapies to lower PTH and phosphorus, may provide inadequate long-term control for many dialysis patients. Cinacalcet, by simultaneously lowering PTH, calcium, phosphorus, and calcium-phosphorus levels, may maintain PTH and mineral balance in these individuals. However, as with traditional therapies, long-term data are limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENT: Dialysis subjects from at least one of five lead-in studies (double-blind placebo-controlled, including one extension trial) completing up to 52 wk of either cinacalcet or placebo were eligible for this open-label extension study, including an 8-wk dose titration (initiated at 30 mg/d), followed by 24-wk maintenance and up to 132 wk of follow-up. Final efficacy analysis was at week 180. Three hundred thirty-four of 589 enrolled subjects received cinacalcet from the beginning of the lead-in study. Weekly median PTH values were values were < or =55 mg(2)/dl(2) (weeks 4 through 180). Similar results were exhibited in the 255 subjects who initially received placebo. Among the patients exposed to cinacalcet from the beginning of the lead-in study, 3% of subjects exhibited treatment-related serious adverse events. Cinacalcet effectively maintained PTH, Ca and P reductions in dialysis subjects for up to 180 wk.

  15. Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

    Science.gov (United States)

    Evenepoel, Pieter; Curzi, Mario P.; González, Maria Teresa; Husserl, Fred E.; Kopyt, Nelson; Sterling, Lulu Ren; Mix, Chris; Wong, Gordon

    2009-01-01

    Background & objectives: Chronic kidney disease (CKD) is commonly complicated by secondary hyperparathyroidism (SHPT), leading to increased risk of morbidity and mortality. SHPT is a progressive disease often requiring long-term therapy to control parathyroid hormone (PTH) and mineral imbalances. Vitamin D sterols and phosphate binders, used as traditional therapies to lower PTH and phosphorus, may provide inadequate long-term control for many dialysis patients. Cinacalcet, by simultaneously lowering PTH, calcium, phosphorus, and calcium-phosphorus levels, may maintain PTH and mineral balance in these individuals. However, as with traditional therapies, long-term data are limited. Design, setting, participants, & measurement: Dialysis subjects from at least one of five lead-in studies (double-blind placebo-controlled, including one extension trial) completing up to 52 wk of either cinacalcet or placebo were eligible for this open-label extension study, including an 8-wk dose titration (initiated at 30 mg/d), followed by 24-wk maintenance and up to 132 wk of follow-up. Final efficacy analysis was at week 180. Results: Three hundred thirty-four of 589 enrolled subjects received cinacalcet from the beginning of the lead-in study. Weekly median PTH values were ≤300 pg/ml (weeks 16 through 180) and median Ca×P values were ≤55 mg2/dl2 (weeks 4 through 180). Similar results were exhibited in the 255 subjects who initially received placebo. Among the patients exposed to cinacalcet from the beginning of the lead-in study, 3% of subjects exhibited treatment-related serious adverse events. Conclusions: Cinacalcet effectively maintained PTH, Ca and P reductions in dialysis subjects for up to 180 wk. PMID:19696213

  16. [Diagnostic value of PTH total kit for estimation of bone turnover in children with chronic renal failure].

    Science.gov (United States)

    Ziółkowska, Helena; Roszkowska-Blaim, Maria

    2006-01-01

    The aim of the study was to estimate the usefulness of total PTH and 1-84 molecule (CAP) assay in clinical practice. 118 children with chronic renal failure aged 13.8 +/- 4.5 years were examined: 69 on conservative treatment with creatinine clearance 40.7 +/- 20 ml/min/1.73 m2, 31 on peritoneal dialysis and 16 on hemodialysis. In all patients the following parameters were assessed: serum levels of calcium (sCa), phosphorus (sP), PTH intact (PTHs) by chemiluminescence method (Immulite analyzer), total PTH (PTHc) and CAP with Duo PTH Assay (Scantibodies Laboratories, USA). The value of CIP as the difference between total PTH and CAP was calculated. For the evaluation of bone turnover the serum level of osteocalcin (OC) with IRMA, (OsteoRiact, CIS, F) and activity of serum alkaline phosphatase (AP) were determined. The correlations between parameters were calculated by Pearson's correlation coefficient (r). Significant correlation were found between PTHs and PTHc (r=0.84, p=0.0000), CAP (r=0.79, p=0.0000) and CIP. The increase of PTHs, PTHc, CAP, CIP, sP, OC and percentage of CIP were noticed, when parallel increase of creatinine level was found. The negative correlation between creatinine level and CAP/CIP was observed. The similar correlations between level of PTHs, PTHc, CAP and OC level were observed (r=0.55, 0.49 and 0.50 respectively). The assay of total PTH and CAP fragment is not usefull in clinical practice for estimation of bone turnover in children with chronic renal failure.

  17. Identification of Six Novel PTH1R Mutations in Families with a History of Primary Failure of Tooth Eruption

    DEFF Research Database (Denmark)

    Risom, Lotte; Christoffersen, Line Borck; Daugaard-Jensen, Jette

    2013-01-01

    Primary Failure of tooth Eruption (PFE) is a non-syndromic disorder which can be caused by mutations in the parathyroid hormone receptor 1 gene (PTH1R). Traditionally, the disorder has been identified clinically based on post-emergent failure of eruption of permanent molars. However, patients......-26_544-23del and c.989G>T). The latter was validated by transfection of minigenes. The six novel mutations expand the mutation spectrum for PFE from eight to 14 pathogenic mutations. Loss-of-function mutations in PTH1R are also associated with recessively inherited Blomstrand chondrodysplasia. We compiled all...

  18. Teriparatide (PTH 1-34) treatment increases peripheral hematopoietic stem cells in postmenopausal women.

    Science.gov (United States)

    Yu, Elaine W; Kumbhani, Ruchit; Siwila-Sackman, Erica; DeLelys, Michelle; Preffer, Frederic I; Leder, Benjamin Z; Wu, Joy Y

    2014-06-01

    Cells of the osteoblast lineage play an important role in regulating the hematopoietic stem cell (HSC) niche and early B-cell development in animal models, perhaps via parathyroid hormone (PTH)-dependent mechanisms. There are few human clinical studies investigating this phenomenon. We studied the impact of long-term daily teriparatide (PTH 1-34) treatment on cells of the hematopoietic lineage in postmenopausal women. Twenty-three postmenopausal women at high risk of fracture received teriparatide 20 mcg sc daily for 24 months as part of a prospective longitudinal trial. Whole blood measurements were obtained at baseline, 3, 6, 12, and 18 months. Flow cytometry was performed to identify hematopoietic subpopulations, including HSCs (CD34+/CD45(moderate); ISHAGE protocol) and early transitional B cells (CD19+, CD27-, IgD+, CD24[hi], CD38[hi]). Serial measurements of spine and hip bone mineral density (BMD) as well as serum P1NP, osteocalcin, and CTX were also performed. The average age of study subjects was 64 ± 5 years. We found that teriparatide treatment led to an early increase in circulating HSC number of 40% ± 14% (p = 0.004) by month 3, which persisted to month 18 before returning to near baseline by 24 months. There were no significant changes in transitional B cells or total B cells over the course of the study period. In addition, there were no differences in complete blood count profiles as quantified by standard automated flow cytometry. Interestingly, the peak increase in HSC number was inversely associated with increases in bone markers and spine BMD. Daily teriparatide treatment for osteoporosis increases circulating HSCs by 3 to 6 months in postmenopausal women. This may represent a proliferation of marrow HSCs or increased peripheral HSC mobilization. This clinical study establishes the importance of PTH in the regulation of the HSC niche within humans. © 2014 American Society for Bone and Mineral Research. © 2014 American Society for

  19. Relationship between fasting glucose, vitamin D and PTH in early postmenopausal women

    DEFF Research Database (Denmark)

    við Streym, Susanna; Rejnmark, Lars; Vestergaard, Peter

      Abstract Relationship between fasting glucose, vitamin D and PTH in early postmenopausal women Súsanna við Streym Thomsen (1), Lars Rejnmark (1), Peter Vestergaard (1), Christine Brot (2), Pia Eiken (3), Pernille Hermann (4) Leif Mosekilde (1). (1) Department of Medicine and Endocrinology C...... postmenopausal Caucasian women (n=2016) aged 45 to 58 years old. Measurements: Fasting blood glucose was measured after an overnight fast by standard laboratory methods. Serum levels of 25OHD were measured by a competitive assay using rachitic rat binding protein. The fat and lean mass was measured by DXA...... between fasting blood glucose and 25OHD and all studied indices. In a multivariate linear regression analyzing fasting blood glucose was significantly associated with BMI (b=0.038 ±0.007 (SE), 2p

  20. Recent advances in understanding provoked vestibulodynia [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Ahinoam Lev-Sagie

    2016-10-01

    Full Text Available Vulvodynia refers to pain in the vulva of at least 3 months’ duration in the absence of a recognized underlying cause. Provoked, localized vestibulodynia is the term used to describe superficial pain confined to the vulvar vestibule, provoked by touch. This review will focus on provoked vestibulodynia with regard to its suggested causative factors and will discuss the role of inflammation, vulvovaginal infections, mucosal nerve fiber proliferation, hormonal associations, central pain mechanisms, pelvic floor muscle dysfunction, and genetic factors. Clinical observations, epidemiological studies, and data from basic research emphasize the heterogeneity of vulvar pain syndromes. There is a critical need to perform prospective, longitudinal studies that will allow better diagnostic criteria and subgrouping of patients that would lead to improvements in our understanding of provoked vestibulodynia and its treatment.

  1. Vitamin D, PTH, and calcium in relation to survival following prostate cancer.

    Science.gov (United States)

    Brändstedt, Johan; Almquist, Martin; Manjer, Jonas; Malm, Johan

    2016-05-01

    Epidemiological studies suggest that low levels of vitamin D constitute a risk factor for prostate cancer. However, the results are conflicting, perhaps because prostate cancer is a very heterogeneous disease. More recent studies have focused on cancer progression and mortality. Vitamin D is closely related to both calcium metabolism and parathyroid hormone (PTH) levels, and all three factors have been implicated in prostate cancer. We examined the associations between pre-diagnostic serum levels of vitamin D (25OHD), PTH, and calcium and mortality among 943 participants within the Malmö Diet and Cancer Study, who were diagnosed with prostate cancer. The mean time from diagnosis until the end of followup was 9.1 years (SD 4.5), and the mean time from inclusion until end of follow-up was 16.6 years (SD 4.9). The analytes were divided into quartiles, and the risk of death from prostate cancer was analyzed using Cox proportional hazard analysis, yielding hazards ratios (HR) with 95 % confidence intervals. The models were adjusted for season and year of inclusion, age at baseline, age at diagnosis, body mass index (BMI), and tumor characteristics (TNM and Gleason score). We observed a trend toward a lower prostate-specific mortality with 25OHD >85 nmol/L in the unadjusted analysis. This became statistically significantly in the third quartile of 25OHD (85-102 nmol/L) compared to the first (cancer mortality. This study shows that levels of pre-diagnostic vitamin D above 85 nmol/L may improve survival in men with prostate cancer.

  2. Influence of four different PTH methods on the classification of chronic kidney disease patients according to the new KDIGO guideline

    NARCIS (Netherlands)

    ten, Boekel Edwin; van Veen, Merk C.; Vervloet, Marc G.; Fischer, Johan C.; Koopman, Marion G.; van Dam, Bastiaan

    2012-01-01

    Secondary hyperparathyroidism develops frequently with chronic kidney disease (CKD) and is associated with poor outcome. The new CKD-MBD guideline, Kidney Disease: Improving Global Outcomes (KDIGO), recommends a target range for PTH which is based on the locally used, upper reference range limit

  3. Searching the optimal PTH target range in children undergoing peritoneal dialysis: new insights from international cohort studies.

    Science.gov (United States)

    Haffner, Dieter; Schaefer, Franz

    2013-04-01

    The treatment of the mineral and bone disorder associated with chronic kidney disease (CKD-MBD) remains a major challenge in pediatric patients. The principal aims of therapeutic measures are not only to prevent the debilitating skeletal complications and to achieve normal growth but also to preserve long-term cardiovascular health. Serum parathyroid hormone (PTH) levels are used as a surrogate parameter of bone turnover. Whereas it is generally accepted that serum calcium and phosphate levels should be kept within the range for age, current pediatric consensus guidelines differ markedly with respect to the optimal PTH target range and operate on a limited evidence base. Recently, the International Pediatric Dialysis Network (IPPN) established a global registry collecting detailed clinical and biochemical information, including data relevant to CKD-MBD in children on chronic peritoneal dialysis (PD). This review highlights the current evidence basis regarding the optimal PTH target range in pediatric CKD patients, and re-assesses the current guidelines in view of the outcome data collected by the IPPN registry. Based on a comprehensive evaluation of CKD-MBD outcome measures in this global patient cohort, a PTH target range of 1.7-3 times the upper limit of normal (i.e. 100-200 pg/ml) appears reasonable in children undergoing chronic PD.

  4. Feasibility Study of a Standardized Novel Animal Model for Cervical Vertebral Augmentation in Sheep Using a PTH Derivate Bioactive Material

    Directory of Open Access Journals (Sweden)

    Karina Klein

    2014-08-01

    Full Text Available Prophylactic local treatment involving percutaneous vertebral augmentation using bioactive materials is a new treatment strategy in spine surgery in humans for vertebral bodies at risk. Standardized animal models for this procedure are almost non-existent. The purpose of this study was to: (i prove the efficacy of PTH derivate bioactive materials for new bone formation; and (ii create a new, highly standardized cervical vertebral augmentation model in sheep. Three different concentrations of a modified form of parathyroid hormone (PTH covalently bound to a fibrin matrix containing strontium carbonate were used. The same matrix without PTH and shams were used as controls. The bioactive materials were locally injected. Using a ventral surgical approach, a pre-set amount of material was injected under fluoroscopic guidance into the intertrabecular space of three vertebral bodies. Intravital fluorescent dyes were used to demonstrate new bone formation. After an observation period of four months, the animals were sacrificed, and vertebral bodies were processed for µCT, histomorphometry, histology and sequential fluorescence evaluation. Enhanced localized bone activity and new bone formation in the injected area could be determined for all experimental groups in comparison to the matrix alone and sham with the highest values detected for the group with a medium concentration of PTH.

  5. Treatment of postmenopausal women with osteoporosis with PTH(1-84) for 36 months: treatment extension study

    NARCIS (Netherlands)

    Zanchetta, J.R.; Bogado, C.E.; Cisari, C.; Aslanidis, S.; Greisen, H.; Fox, J.; Lems, W.F.

    2010-01-01

    Objective: To determine the safety and efficacy of full-length parathyroid hormone, PTH(184), treatment for up to 36 months by evaluating bone mineral density (BMD) changes, bone histomorphometric indices, and clinical fracture incidence in postmenopausal women with osteoporosis. Background: The TOP

  6. PTH (1–34), but not strontium ranelate counteract loss of trabecular thickness and bone strength in disuse osteopenic rats

    DEFF Research Database (Denmark)

    Brüel, Annemarie; Vegger, Jens Bay; Raffalt, Anders Christer

    2013-01-01

    R in combination could counteract immobilization-induced bone loss in a rat model.Immobilization was induced by injecting 4IU Botox (BTX) into the muscles of the right hind limb. Seventy-two female Wistar rats, 3-months-old, were divided into the following groups: Baseline, Controls, BTX, BTX+PTH, BTX+SrR, and BTX...

  7. Oral Allergy Syndrome in a Child Provoked by Royal Jelly

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    Fantini Paola

    2014-01-01

    Full Text Available Royal jelly has been demonstrated to have several physiological activities. However, in the literature, different reactions induced by royal jelly are reported. We describe a case of seven-year-old child that was referred to our observation for two episodes of oral allergy syndrome (OAS that appeared ten minutes after ingestion of royal jelly. Skin prick test with standard panel of inhalant and food allergens, a prick-to-prick test using the royal jelly’s extract responsible for patient’s reactions, and royal jelly patch test with extemporaneous preparation were performed. The specific IgE by ImmunoCAP System method versus Hymenoptera venom, inhalant allergens, food allergens, and lipid transfer proteins was dosed. According to the positive reactions to royal jelly both by prick-by-prick test and by a first reading patch test, royal jelly immediate hypersensitivity was diagnosed. According to the positive response for almond in both in vivo and in vitro tests we can think of the royal jelly contamination with almond pollen as possible cause of patient’s reaction. Moreover, from the results of specific IgE titers versus Compositae pollens, we have argued the possibility that this case of royal jelly allergy could be explained also by the mechanism of cross-reaction with Compositae pollens.

  8. Comparative study of the effect of PTH (1-84) and strontium ranelate in an experimental model of atrophic nonunion.

    Science.gov (United States)

    Pérez Núñez, M I; Ferreño Blanco, D; Alfonso Fernández, A; Casado de Prado, J A; Sánchez Crespo, M; De la Red Gallego, M; Pascual Carra, A; Rodriguez López, T; Diego Cavia, S; Garcés Zarzalejo, C; Mayorga Fernández, M; Ruiz Martínez, E; Carrascal Vaquero, I; Riancho Moral, J A

    2015-12-01

    This study aimed to set up an experimental model of long bone atrophic nonunion and to explore the potential role of PTH-1-84 (PTH 1-84) and strontium ranelate (SrR). A model of atrophic nonunion was created in Sprague-Dawley rats at the femoral midshaft level. The animals were randomised into four groups. Group A1: control rodents, fracture without bone gap; Group A2: rodents with subtraction osteotomy (non-union model control) treated with saline; Group B: rodents with subtraction osteotomy treated with human-PTH (PTH 1-84); and Group C: rodents with subtraction osteotomy treated with strontium ranelate (SrR). The groups were followed for 12 weeks. X-rays were be obtained at weeks 1, 6 and 12. After sacrificing the animals, we proceeded to the biomechanical study and four point bending tests to evaluate the resistance of the callus and histological study. In second phase, the expression of genes related to osteoblast function was analysed by reverse transcription-quantitative PCR in rats subjected to substraction osteotomy and treated for 2 weeks. The animals were randomised into three groups: Group A2: rodents treated with saline; Group B: rodents treated with PTH 1-84 and Group C: rodents treated with SrR. No significant histological differences were found between animals subjected to subtraction osteotomy and treated with either saline or PTH (p=0.628), but significant difference existed between animals receiving saline or SrR (p=0.005). There were no significant differences in X-ray score between the saline and PTH groups at either 6 or 12 weeks (p=0.33 and 0.36, respectively). On the other hand, better X-ray scores were found in the SrR group (p=0.047 and 0.006 in comparison with saline, at 6 and 12 weeks, respectively). In line with this, biomechanical tests revealed improved results in the SrR group. Gene expression analysis revealed a slightly decreased levels of DKK1, a Wnt pathway inhibitor, in rats treated with SrR. SrR increases has a beneficial

  9. Calcium, phosphorus, PTH and death rates in a large sample of dialysis patients from Latin America. The CORES Study.

    Science.gov (United States)

    Naves-Díaz, Manuel; Passlick-Deetjen, Jutta; Guinsburg, Adrian; Marelli, Cristina; Fernández-Martín, Jose Luis; Rodríguez-Puyol, Diego; Cannata-Andía, Jorge B

    2011-06-01

    Mineral metabolism parameters may play a role in the survival of patients with chronic kidney disease (CKD). In the CORES Study, we analysed the association between calcium, phosphorus and PTH and mortality (all-cause and cardiovascular) in 16 173 haemodialysis (HD) patients over 18 years from six Latin American countries, who underwent haemodialysis up to 54 months. Unadjusted, case-mix-adjusted and time-dependent multivariable-adjusted hazard ratio (HR) of death were calculated for categories of serum albumin-corrected calcium (Ca(Alb)), phosphorus and PTH using as 'reference values' the range in which the lowest death rate was observed. Age, gender, vitamin D treatment, diabetes, vintage, vascular access, weight, blood pressure and laboratory variables (serum albumin, haemoglobin, creatinine, ferritin and Kt/V) were used as confounding variables. Low (10.5 mg/dL) Ca(Alb) increased the HR for all-cause mortality. Low (5.5 mg/dL) increased the HR for both all-cause and cardiovascular mortality. Low phosphorus (500 and >300 pg/mL) PTH increased the HR for both all-cause and cardiovascular mortality. In addition, only phosphorus >6.0 mg/dL increased the HR for cardiovascular hospitalizations. No effect was observed with Ca(Alb) or PTH. In summary, in 16,173 HD patients, elevated and reduced serum levels of albumin-corrected calcium, phosphorus and PTH levels were associated with increments in all-cause mortality. Similar results were obtained when only cardiovascular mortality was analysed.

  10. Mice lacking bone sialoprotein (BSP) lose bone after ovariectomy and display skeletal site-specific response to intermittent PTH treatment.

    Science.gov (United States)

    Wade-Gueye, Ndéye Marième; Boudiffa, Maya; Laroche, Norbert; Vanden-Bossche, Arnaud; Fournier, Carole; Aubin, Jane E; Vico, Laurence; Lafage-Proust, Marie-Hélène; Malaval, Luc

    2010-11-01

    Bone sialoprotein (BSP) belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, whose members play multiple and distinct roles in the development, turnover, and mineralization of bone and dentin. The functions of BSP in bone remodeling are not yet well established. We previously showed that BSP knockout (BSP(-/-)) mice exhibit a higher trabecular bone volume, concomitant with lower bone remodeling, than wild-type (BSP(+/+)) mice. To determine whether bone turnover can be stimulated in the absence of BSP, we subjected BSP(+/+) and BSP(-/-) mice to catabolic [ovariectomy (OVX)] or anabolic (intermittent PTH administration) hormonal challenges. BSP(-/-) mice progressively develop hypocalcemia and high serum PTH between 2 and 4 months of age. Fifteen and 30 d after OVX, microtomography analysis showed a significant decrease of trabecular bone volume in tibiae of both genotypes. Histomorphometric parameters of bone formation and resorption were significantly increased by OVX. PTH treatment resulted in an increase of trabecular thickness and both bone formation and resorption parameters at all skeletal sites in both genotypes and a decrease of trabecular bone volume in tibiae of BSP(+/+) but not BSP(-/-) mice. PTH increased cortical thickness and bone area in BSP(+/+) but not BSP(-/-) mice and stimulated the bone formation rate specifically in the endosteum of BSP(+/+) mice and the periosteum of BSP(-/-) mice. PTH enhanced the expression of RANKL, MEPE, and DMP1 in both genotypes but increased OPG and OPN expression only in BSP(-/-) mice. In conclusion, despite the low basal turnover, both catabolic and anabolic challenges increase bone formation and resorption in BSP(-/-) mice, suggesting that compensatory pathways are operative in the skeleton of BSP-deficient mice. Although up-regulation of one or several other SIBLINGs is a possible mechanism, further studies are needed to analyze the interplay and cross-regulation involved in

  11. Dig1 protects against cell death provoked by glyphosate-based herbicides in human liver cell lines

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    Travert Carine

    2010-10-01

    Full Text Available Abstract Background Worldwide used pesticides containing different adjuvants like Roundup formulations, which are glyphosate-based herbicides, can provoke some in vivo toxicity and in human cells. These pesticides are commonly found in the environment, surface waters and as food residues of Roundup tolerant genetically modified plants. In order to know their effects on cells from liver, a major detoxification organ, we have studied their mechanism of action and possible protection by precise medicinal plant extracts called Dig1. Methods The cytotoxicity pathways of four formulations of glyphosate-based herbicides were studied using human hepatic cell lines HepG2 and Hep3B, known models to study xenobiotic effects. We monitored mitochondrial succinate dehydrogenase activity and caspases 3/7 for cell mortality and protection by Dig1, as well as cytochromes P450 1A1, 1A2, 3A4 and 2C9 and glutathione-S-transferase to approach the mechanism of actions. Results All the four Roundup formulations provoke liver cell death, with adjuvants having stronger effects than glyphosate alone. Hep3B are 3-5 times more sensitive over 48 h. Caspases 3/7 are greatly activated in HepG2 by Roundup at non-cytotoxic levels, and some apoptosis induction by Roundup is possible together with necrosis. CYP3A4 is specifically enhanced by Roundup at doses 400 times less than used in agriculture (2%. CYP1A2 is increased to a lesser extent together with glutathione-S-transferase (GST down-regulation. Dig 1, non cytotoxic and not inducing caspases by itself, is able to prevent Roundup-induced cell death in a time-dependant manner with an important efficiency of up to 89%, within 48 h. In addition, we evidenced that it prevents Caspases 3/7 activation and CYP3A4 enhancement, and not GST reduction, but in turn it slightly inhibited CYP2C9 when added before Roundup. Conclusion Roundup is able to provoke intracellular disruption in hepatic cell lines at different levels, but a

  12. Upregulations of Clcn3 and P-Gp Provoked by Lens Osmotic Expansion in Rat Galactosemic Cataract

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    Lixia Ji

    2017-01-01

    Full Text Available Objective. Lens osmotic expansion, provoked by overactivated aldose reductase (AR, is the most essential event of sugar cataract. Chloride channel 3 (Clcn3 is a volume-sensitive channel, mainly participating in the regulation of cell fundamental volume, and P-glycoprotein (P-gp acts as its modulator. We aim to study whether P-gp and Clcn3 are involved in lens osmotic expansion of galactosemic cataract. Methods and Results. In vitro, lens epithelial cells (LECs were primarily cultured in gradient galactose medium (10–60 mM, more and more vacuoles appeared in LEC cytoplasm, and mRNA and protein levels of AR, P-gp, and Clcn3 were synchronously upregulated along with the increase of galactose concentration. In vivo, we focused on the early stage of rat galactosemic cataract, amount of vacuoles arose from equatorial area and scattered to the whole anterior capsule of lenses from the 3rd day to the 9th day, and mRNA and protein levels of P-gp and Clcn3 reached the peak around the 9th or 12th day. Conclusion. Galactosemia caused the osmotic stress in lenses; it also markedly leads to the upregulations of AR, P-gp, and Clcn3 in LECs, together resulting in obvious osmotic expansion in vitro and in vivo.

  13. Internal derangement as a predictor of provoked pain on mouth opening: A magnetic resonance imaging study

    Science.gov (United States)

    Park, Ha-Na; Kim, Kyoung-A

    2017-01-01

    Purpose This study investigated the relationship between pain and internal derangement in temporomandibular disorder (TMD) patients using magnetic resonance imaging (MRI). Materials and Methods This study analyzed 356 TMD patients (712 temporomandibular joints [TMJs]). The inclusion criteria were the presence of spontaneous or provoked pain on one or both TMJs and having undergone MRI. The patients with provoked pain were divided into 3 groups: pain on palpation, pain on mouth opening, and pain on mastication. MRI was performed using a 1.5-T scanner. T1- and T2-weighted parasagittal and paracoronal images were obtained. According to the findings on the T1-weighted images, another 3 groups were created based on internal derangement: normal, disc displacement with reduction, and disc displacement without reduction. The MRI findings were independently interpreted by 2 experienced oral and maxillofacial radiologists at 2 different times. Statistical analysis was performed by the chi-square test using SPSS (version 12.0; SPSS Inc., Chicago, IL, USA). Results Provoked pain on mouth opening was found to be correlated with internal derangement in TMD patients (Ppain and provoked pain on palpation or mastication were not associated with internal derangement (P>.05). Conclusion These results suggest that internal derangement was a significant predictor of provoked pain on mouth opening. PMID:29279820

  14. Vitamin D, PTH, and calcium and tumor aggressiveness in prostate cancer: a prospective nested case-control study.

    Science.gov (United States)

    Brändstedt, Johan; Almquist, Martin; Ulmert, David; Manjer, Jonas; Malm, Johan

    2016-01-01

    Epidemiological studies suggest that low levels of vitamin D (25OHD) constitute a risk factor for more aggressive prostate cancer. We examined the relationship between pre-diagnostic serum levels of vitamin D, parathyroid hormone (PTH), and calcium and risk of prostate cancer according to tumor aggressiveness. We performed a nested case-control study within the Malmö Diet and Cancer Study on 943 incident prostate cancer cases. Tumor aggressiveness was defined by Gleason score, TNM stage, and serum levels of total prostate-specific antigen. Odds ratios (OR) were calculated for different quartiles of serum levels of 25OHD, PTH, and calcium, and for interactions between them. We found no significant association when comparing aggressive to non-aggressive disease regarding vitamin D, PTH, or calcium. There was a trend toward an increased risk in low-grade tumors, i.e., Gleason score ≤6, and a significant association regarding Gleason score 7 tumors with OR 1.70 (1.09-2.65) in the highest quartile of vitamin D. Stratifying the analysis yielded several significant findings demonstrating a nonspecific interaction between the metabolites. In men with PTH above median, the risk of aggressive prostate cancer was double in the highest vitamin D quartile, OR 2.01 (1.24-3.25), and for non-aggressive cancer 1.82 (1.25-2.66). There was an inverse effect on risk of prostate cancer in men with PTH above median and vitamin D ≤50 nmol/L, OR 0.25 (0.09-0.71) and calcium ≤2.37 mmol/L, OR 0.53 (0.34-0.82) for aggressive cancer. This study showed no significant association when comparing aggressive to non-aggressive disease. There was a possible relationship between vitamin D and low-risk tumors. There were both positive and negative interactions between PTH, calcium, and vitamin D and risk of prostate cancer. These results were similar for low-risk and aggressive cases.

  15. Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model

    Science.gov (United States)

    Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert

    2014-01-01

    Alopecia is a psychologically devastating complication of chemotherapy for which there is currently no effective therapy. PTH-CBD is a collagen-targeted parathyroid hormone analog that has shown promise as a therapy for alopecia disorders. To compare the efficacy of prophylactic versus therapeutic administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle control before or after hair loss developing from three courses of cyclophosphamide chemotherapy (50–150 mg/kg/week). Mice receiving chemotherapy alone developed hair loss and depigmentation over 6–12 months. Mice pretreated with PTH-CBD did not develop these changes and maintained a normal-appearing coat. Mice treated with PTH-CBD after development of hair loss showed a partial recovery. Observations of hair loss were confirmed quantitatively by gray scale analysis. Histological examination showed that in mice receiving chemotherapy alone, there were small, dystrophic hair follicles mostly in the catagen phase. Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH-CBD was effective in both the prevention and the treatment of chemotherapy-induced alopecia in mice, but pretreatment appears to result in a better cosmetic outcome. PTH-CBD shows promise as an agent in the prevention of this complication of chemotherapy and improving the quality of life for cancer patients. PMID:24025564

  16. Histopathological changes of radial artery wall in patients of chronic kidney disease stage 5 undergoing Av fistula formation and their correlation with serum iPTH levels

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    Vidyanand Tripathi

    2015-01-01

    Full Text Available Vascular complications arise in uremic patients in the absence of clinically significant atherosclerotic disease. Elevated serum parathyroid hormone (PTH and abnormal calcium (Ca and phosphorus (P balance have been implicated in vascular damage in chronic kidney disease (CKD patients, but there is lack of histo-pathological studies. Patients with CKD stage 5 and 5D who underwent arterio-venous fistula were included in this study. Baseline and laboratory parameters including assessment of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid, albumin, calcium, phosphorus, intact PTH (iPTH and vitamin D level were documented. The specimens of the arterial wall were obtained during the procedure and were analyzed. Patients were divided into two groups iPTH 400 (Group B. Mean intimal thickness (IT was significantly high in patients of Group B (60.4 ± 24.1 μ m as compared with patients of Group A (37.8 ± 14.9 μm (P = 0.003. Vascular calcification was comparable in both groups. The iPTH level was found to be an independent risk factor for high intima thickness (correlation coefficient 0.653 (P-value <0.01. Patients with high (≥400 pg/mL iPTH have 8.93 times the risk of developing intimal thickness of ≥60 μ m as compared with patients with low (<400 pg/mL iPTH (P-value <0.05, with 95% confidence interval of 1.27, 62.61. The mean IT of the radial artery significantly correlated with the iPTH level, while vascular calcification was independent of the iPTH level. Hyperparathyroidism is an important cause of ongoing vascular damage and may contribute to higher vascular events in CKD patients.

  17. Provokative Elemente einer Didaktik internetgestützter Lehr-Lernarrangements

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    Wolfgang Müskens

    2002-10-01

    Full Text Available Onlinebasiertes kollaboratives Lernen erfordert eine neue Rolle der Lehrenden und damit verbunden auch neue didaktische Methoden. Ausgehend vom Begriff der Provokation wird eine solche Didaktik in Abgrenzung zur Vorstellung eines ausschliesslich selbstgesteuerten Lernens entwickelt. Provokation wird in diesem Zusammenhang als die intendierte Konfrontation eines Lernenden mit einstellungskonträrem Material verstanden. Die Grundlagen der hier vorgestellten Didaktik werden aus einer Vielzahl theoretischer Wurzeln und empirischer Forschungsergebnisse hergeleitet: Es wird auf die Beziehung zum Kompetenzbegriff, zur Systemtheorie, zur Emotionspsychologie, zur Induzierung kognitiver Konflikte, zur Dissonanztheorie und zu Kellys Theorie der persönlichen Konstrukte eingegangen. Als konkrete Methoden der provokativen Didaktik für das E-Learning werden u. a. provokative Statements, das Induzieren einstellungskonträrer Perspektiven und eine an die «Fixed-Role-Therapy» angelehnte Aufgabenstellung diskutiert. Die Methoden der provokativen Didaktik bedeuten eine hochgradige Individualisierung des Lernens und eine Intensivierung des Verhältnisses zwischen Lerner und Lehrendem.

  18. Endogenous PKI gamma limits the duration of the anti-apoptotic effects of PTH and beta-adrenergic agonists in osteoblasts.

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    Chen, Xin; Song, In-Hwan; Dennis, James E; Greenfield, Edward M

    2007-05-01

    PKI gamma knockdown substantially extended the anti-apoptotic effects of PTH and beta-adrenergic agonists, whereas PKI gamma overexpression decreased these effects. Therefore, inhibition of PKI gamma activity may provide a useful co-therapy in combination with intermittent PTH or beta-adrenergic agonists for bone loss in conditions such as osteoporosis. PTH has both catabolic and anabolic effects on bone, which are primarily caused by cAMP/protein kinase A (PKA) signaling and regulation of gene expression. We previously showed that protein kinase inhibitor-gamma (PKI gamma) is required for efficient termination of cAMP/PKA signaling and gene expression after stimulation with PTH or beta-adrenergic agonists. Inhibition of osteoblast apoptosis is thought to be an important, but transient, mechanism partly responsible for the anabolic effects of intermittent PTH. Therefore, we hypothesized that endogenous PKI gamma also terminates the anti-apoptotic effect of PTH. PKI gamma knockdown by antisense transfection or siRNA was used to examine the ability of endogenous PKI gamma to modulate the anti-apoptotic effects of PTH and beta-adrenergic agonists in ROS 17/2.8 cells. Knockdown of PKI gamma substantially extended the anti-apoptotic effects of PTH, whether apoptosis was induced by etoposide or dexamethasone. In contrast, overexpression of PKI gamma decreased the anti-apoptotic effect of PTH pretreatment. This study is also the first demonstration that beta-adrenergic agonists mimic the anti-apoptotic effects of PTH in osteoblasts. Moreover, PKI gamma knockdown also substantially extended this anti-apoptotic effect of beta-adrenergic agonists. Taken together, these results show that endogenous PKI gamma limits the duration of the anti-apoptotic effects of cAMP/PKA signaling in osteoblasts. Because significant individual variability exists in the anabolic responses to PTH therapy in current clinical treatment of osteoporosis, inhibition of PKI gamma activity may provide a

  19. Multiple regression technique for Pth degree polynominals with and without linear cross products

    Science.gov (United States)

    Davis, J. W.

    1973-01-01

    A multiple regression technique was developed by which the nonlinear behavior of specified independent variables can be related to a given dependent variable. The polynomial expression can be of Pth degree and can incorporate N independent variables. Two cases are treated such that mathematical models can be studied both with and without linear cross products. The resulting surface fits can be used to summarize trends for a given phenomenon and provide a mathematical relationship for subsequent analysis. To implement this technique, separate computer programs were developed for the case without linear cross products and for the case incorporating such cross products which evaluate the various constants in the model regression equation. In addition, the significance of the estimated regression equation is considered and the standard deviation, the F statistic, the maximum absolute percent error, and the average of the absolute values of the percent of error evaluated. The computer programs and their manner of utilization are described. Sample problems are included to illustrate the use and capability of the technique which show the output formats and typical plots comparing computer results to each set of input data.

  20. [Sociodemographic Factors Related to Plasma Concentrations of 25-OH Vitamin D and PTH in Cord Blood].

    Science.gov (United States)

    Ortigosa Gómez, Sandra; García-Algar, Oscar; Mur Sierra, Antonio; Ferrer Costa, Roser; Carrascosa Lezcano, Antonio; Yeste Fernández, Diego

    2015-01-01

    Plasma 25(OH)D levels in the newborn are dependent on maternal stores, thus, neonates of vitamin D-deficient mothers present a greater risk of hypocalcaemia, rickets and infections the first year of life. Several studies showing a high prevalence of vitamin D deficiency in pregnant women have been published recently. The aim of the study is to analyze the levels of 25(OH)D in cord blood and determine whether there is a relation with nutritional, socioeconomic and clinical factors of pregnant women and their newborns. Between March and May 2013, 99 pregnant women were recruited in Hospital del Mar (Barcelona), in whom plasma 25(OH)D and PTH levels were measured in cord blood at birth. Clinical history data were collected and a nutritional survey was made on maternal vitamin D and calcium intake and sun exposure. Statistical analysis was performed using SPSS. Comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests, and correction for multiple comparisons using Bonferroni. P value cord blood was 10.4 ± 6 .1 ng/ml. 94% of pregnant women had 25(OH)D levels in cord blood cord blood. The lowest 25(OH D levels were observed in Indo-Pakistani ethnicity, dark phototype and deficient sun exposure.

  1. All five host-range variants of Xanthomonas citri carry one pthA homolog with 17.5 repeats that determines pathogenicity on citrus, but none determine host-range variation.

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    Al-Saadi, Abdulwahid; Reddy, Joseph D; Duan, Yong P; Brunings, Asha M; Yuan, Qiaoping; Gabriel, Dean W

    2007-08-01

    Citrus canker disease is caused by five groups of Xanthomonas citri strains that are distinguished primarily by host range: three from Asia (A, A*, and A(w)) and two that form a phylogenetically distinct clade and originated in South America (B and C). Every X. citri strain carries multiple DNA fragments that hybridize with pthA, which is essential for the pathogenicity of wide-host-range X. citri group A strain 3213. DNA fragments that hybridized with pthA were cloned from a representative strain from all five groups. Each strain carried one and only one pthA homolog that functionally complemented a knockout mutation of pthA in 3213. Every complementing homolog was of identical size to pthA and carried 17.5 nearly identical, direct tandem repeats, including three new genes from narrow-host-range groups C (pthC), A(w) (pthAW), and A* (pthA*). Every noncomplementing paralog was of a different size; one of these was sequenced from group A* (pthA*-2) and was found to have an intact promoter and full-length reading frame but with 15.5 repeats. None of the complementing homologs nor any of the noncomplementing paralogs conferred avirulence to 3213 on grapefruit or suppressed avirulence of a group A* strain on grapefruit. A knockout mutation of pthC in a group C strain resulted in loss of pathogenicity on lime, but the strain was unaffected in ability to elicit an HR on grapefruit. This pthC- mutant was fully complemented by pthA, pthB, or pthC. Analysis of the predicted amino-acid sequences of all functional pthA homologs and nonfunctional paralogs indicated that the specific sequence of the 17th repeat may be essential for pathogenicity of X. citri on citrus.

  2. Intrusions and provoked and spontaneous confabulations on memory tests in Korsakoff's syndrome.

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    Rensen, Yvonne C M; Oosterman, Joukje M; Walvoort, Serge J W; Eling, Paul A T M; Kessels, Roy P C

    2017-03-01

    Intrusions on verbal memory tests have been used as an index for clinical confabulation. Severe memory impairments in combination with executive dysfunction have been suggested to be the underlying mechanism of confabulation, but to date, this relation is unclear. The aim of this study was (a) to examine the relation between (different types of) intrusions and confabulations in a large sample of confabulating patients with Korsakoff's syndrome (KS) and (b) to investigate whether different measures of executive functioning and memory performance are related to provoked and spontaneous confabulation. The Dutch version of the California Verbal Learning Test (CVLT) and various executive function and memory tests were administered to a group of 51 confabulating patients with KS. Professional caregivers rated the severity of provoked and spontaneous confabulation behavior of the patients using the Nijmegen-Venray Confabulation List-20 (NVCL-20). The total number of intrusions on the CVLT was not related to either provoked or spontaneous confabulation scores. None of the CVLT intrusion scores correlated significantly with any of the confabulation scores, but we did find small-to-medium, positive correlations between unrelated intrusions and both provoked confabulations and spontaneous confabulation. Provoked confabulation behavior was associated with executive dysfunction and poorer memory performances. Spontaneous confabulation was not related to performance on measures of executive function and memory. The total number of intrusions on verbal memory tests and clinical confabulations appear to be different phenomena. Only unrelated intrusions produced on the CVLT might possibly be related to confabulations. The production of provoked, but not spontaneous, confabulation is associated with executive dysfunction and memory deficits.

  3. A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism.

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    Marie Courbebaisse

    Full Text Available BACKGROUND: The sodium-hydrogen exchanger regulatory factor 1 (NHERF1 binds to the main renal phosphate transporter NPT2a and to the parathyroid hormone (PTH receptor. We have recently identified mutations in NHERF1 that decrease renal phosphate reabsorption by increasing PTH-induced cAMP production in the renal proximal tubule. METHODS: We compared relevant parameters of phosphate homeostasis in a patient with a previously undescribed mutation in NHERF1 and in control subjects. We expressed the mutant NHERF1 protein in Xenopus Oocytes and in cultured cells to study its effects on phosphate transport and PTH-induced cAMP production. RESULTS: We identified in a patient with inappropriate renal phosphate reabsorption a previously unidentified mutation (E68A located in the PDZ1 domain of NHERF1.We report the consequences of this mutation on NHERF1 function. E68A mutation did not modify cAMP production in the patient. PTH-induced cAMP synthesis and PKC activity were not altered by E68A mutation in renal cells in culture. In contrast to wild-type NHERF1, expression of the E68A mutant in Xenopus oocytes and in human cells failed to increase phosphate transport. Pull down experiments showed that E68A mutant did not interact with NPT2a, which robustly interacted with wild type NHERF1 and previously identified mutants. Biotinylation studies revealed that E68A mutant was unable to increase cell surface expression of NPT2a. CONCLUSIONS: Our results indicate that the PDZ1 domain is critical for NHERF1-NPT2a interaction in humans and for the control of NPT2a expression at the plasma membrane. Thus we have identified a new mechanism of renal phosphate loss and shown that different mutations in NHERF1 can alter renal phosphate reabsorption via distinct mechanisms.

  4. The relationship of PTH Bst BI polymorphism, calciotropic hormone levels, and dental fluorosis of children in China.

    Science.gov (United States)

    Wen, Shibao; Li, Anqi; Cui, Liuxin; Huang, Qi; Chen, Hongyang; Guo, Xiaoyi; Luo, Yixin; Hao, Qianyun; Hou, Jiaxiang; Ba, Yue

    2012-06-01

    The aim of this study was to explore the association of parathyroid hormone (PTH) gene Bst BI polymorphism, calciotropic hormone levels, and dental fluorosis of children. A case-control study was conducted in two counties (Kaifeng and Tongxu) in Henan Province, China in 2005-2006. Two hundred and twenty-five children were recruited and divided into three groups including dental fluorosis group (DFG), non-dental fluorosis group (NDFG) from high fluoride areas, and control group (CG). Urine fluoride content was determined using fluoride ion selective electrode; PTH Bst BI were genotyped using PCR-RFLP; osteocalcin (OC) and calcitonin (CT) levels in serum were detected using radioimmunoassay. Genotype distributions were BB 85.3% (58/68), Bb 14.7% (10/68) for DFG; BB 77.6% (52/67), Bb 22.4% (15/67) for NDFG; and BB 73.3% (66/90), Bb 27.7% (24/90) for CG. No significant difference of Bst BI genotypes was observed among three groups (P > 0.05). Serum OC and urine fluoride of children were both significantly higher in DFG and NDFG than in CG (P 0.05). Serum OC level of children with BB genotype was significantly higher compared to those with Bb genotype in high fluoride areas (P dental fluorosis and PTH Bst BI polymorphism. Serum OC might be a more sensitive biomarker for detecting early stages of dental fluorosis, and further studies are needed.

  5. Mid-term effects of sleeve gastrectomy on calcium metabolism parameters, vitamin D and parathormone (PTH) in morbid obese women.

    Science.gov (United States)

    Ruiz-Tovar, Jaime; Oller, Inmaculada; Tomas, Andres; Llavero, Carolina; Arroyo, Antonio; Calero, Alicia; Martinez-Blasco, Amparo; Calpena, Rafael

    2012-05-01

    Despite routine supplementation of vitamins and minerals after bariatric surgery, an important number of patients suffer from deficiencies. Little is still known about the novel restrictive procedure, sleeve gastrectomy. A retrospective study of 30 morbidly obese patients undergoing a laparoscopic sleeve gastrectomy, between May 2008 and September 2010, was performed. Baseline albumin, ferritin, iron, zinc, calcium, vitamin D, parathormone (PTH), vitamin B12, and folic acid were obtained before operation and postoperative determinations 1, 3, 6, 9, 12, 18, and 24 months after surgery. Before surgery, 96.7% of the patients presented vitamin D deficiency, 20% had elevated PTH, 3.3% hypoalbuminemia, and 3.3% folic acid deficiency. One year after surgery, only one patient (3.3%) presented vitamin D deficiency and had elevated PTH. The rest of parameters were within normal range. The second year after surgery, the results remain similar. A significant difference was obtained when comparing preoperative vitamin D values and postoperative determinations 12 months after surgery (increase of 51.9 ng/dl, 95% confidence interval (CI) (41.8-61.3); p levels. We have demonstrated an inverse correlation between weight loss and vitamin D increase at the third month after surgery.

  6. Effect of chronic elevation of plasma calcium concentration by PTH or vitamin D3on blood pressure and hypotensive activity of nifedipine in rats

    NARCIS (Netherlands)

    Jonkman, F.A.M.; Thoolen, M.J.M.C.; Wilffert, B.

    1984-01-01

    The influence of a chronically elevated total plasma calcium concentration on blood pressure and heart rate was investigated in conscious normotensive rats. The plasma calcium concentration was elevated by continuous subcutaneous infusion with parathormone (PTH) after parathyreoidectomy, and by oral

  7. Aging Periosteal Progenitor Cells have Reduced Regenerative Responsiveness to Bone Injury and to the Anabolic Actions of PTH 1-34 Treatment

    Science.gov (United States)

    Yukata, Kiminori; Xie, Chao; Li, Tian-Fang; Takahata, Masahiko; Hoak, Donna; Kondabolu, Sirish; Zhang, Xinping; Awad, Hani A.; Schwarz, Edward M.; Beck, Christopher A.; Jonason, Jennifer H.; O’Keefe, Regis J.

    2014-01-01

    A stabilized tibia fracture model was used in young (8-week old) and aged (1-year old) mice to define the relative bone regenerative potential and the relative responsiveness of the periosteal progenitor population with aging and PTH 1-34 (PTH) systemic therapy. Bone regeneration was assessed through gene expressions, radiographic imaging, histology/histomorphometry, and biomechanical testing. Radiographs and microCT showed increased calcified callus tissue and enhanced bone healing in young compared to aged mice. A key mechanism involved reduced proliferation, expansion, and differentiation of periosteal progenitor cell populations in aged mice. The experiments showed that PTH increased calcified callus tissue and torsional strength with a greater response in young mice. Histology and quantitative histomorphometry confirmed that PTH increased callus tissue area due primarily to an increase in bone formation, since minimal changes in cartilage and mesenchyme tissue area occurred. Periosteum examined at 3, 5, and 7 days showed that PTH increased cyclin D1 expression, the total number of cells in the periosteum, and width of the periosteal regenerative tissue. Gene expression showed that aging delayed differentiation of both bone and cartilage tissues during fracture healing. PTH resulted in sustained Col10a1 expression consistent with delayed chondrocyte maturation, but otherwise minimally altered cartilage gene expression. In contrast, PTH 1-34 stimulated expression of Runx2 and Osterix, but resulted in reduced Osteocalcin. β-catenin staining was present in mesenchymal chondroprogenitors and chondrocytes in early fracture healing, but was most intense in osteoblastic cells at later times. PTH increased active β-catenin staining in the osteoblast populations of both young and aged mice, but had a lesser effect in cartilage. Altogether the findings show that reduced fracture healing in aging involves decreased proliferation and differentiation of stem cells lining

  8. Personality and Aggressive Behavior under Provoking and Neutral Conditions: A Meta-Analytic Review

    Science.gov (United States)

    Bettencourt, Ann B.; Talley, Amelia; Benjamin, Arlin James; Valentine, Jeffery

    2006-01-01

    The authors conducted a comprehensive review to understand the relation between personality and aggressive behavior, under provoking and nonprovoking conditions. The qualitative review revealed that some personality variables influenced aggressive behavior under both neutral and provocation conditions, whereas others influenced aggressive…

  9. Anisocoria in the dog provoked by a toxic contact with an ornamental plant: Datura stramonium.

    Science.gov (United States)

    Hansen, Philippe; Clerc, Bernard

    2002-12-01

    We report an unusual case of anisocoria in the dog provoked by Datura stramonium, and an experimental clinical assay to reproduce the anisocoria using simple contact with part of the plant in four healthy dogs. Any part of the D. stramonium plant produced anisocoria following simple contact with the eye.

  10. MLA Report on Foreign-Language Education Continues to Provoke Debate

    Science.gov (United States)

    Wasley, Paula

    2008-01-01

    This article reports that, nearly one year after its release, the report on foreign language and higher education issued by an ad hoc committee of the Modern Language Association (MLA) is still provoking discussion about reforms in the teaching of foreign languages and the role of the association in any revamp. The debate continued at a panel held…

  11. What are people afraid of during dental treatment? Anxiety-provoking capacity of 67 stimuli characteristic of the dental setting

    NARCIS (Netherlands)

    Oosterink, F.M.D.; de Jongh, A.; Aartman, I.H.A.

    2008-01-01

    Relatively little is known about the anxiety-provoking capacity of the various objects and situations characteristic of the dental setting. The aims of the current study were to establish a hierarchy of anxiety-provoking capacities of a large set of dental stimuli and to determine the differences in

  12. Correlations between serum intact parathyroid hormone (PTH) and N-terminal-probrain natriuretic peptide levels in elderly patients with chronic heart failure (CHF).

    Science.gov (United States)

    Zhang, Shuang; Hu, Yan; Zhou, Lu; Chen, Xiaojing; Wang, Yan; Wu, Jiayu; He, Huimin; Gao, Yanhong

    2015-01-01

    The aim of this study was to investigate the association between PTH and Nt-proBNP in elderly patients with CHF in an attempt to gain insights into the role of PTH in a community-based cohort of elderly patients with CHF. A total of 182 consecutive CHF patients with follow-up for mortality after 3 years were prospectively studied. Serum levels of intact PTH, Nt-proBNP and biochemical parameters were examined. The enrolled patients were divided into groups by the levels of PTH and New York Heart Association (NYHA) functional classes. A total of 66 (36%) patients had PTH values above the upper limit of the normal range. Serum creatinine (p=0.001), estimated glomerular filtration rate (eGFR) (p=0.001), Nt-proBNP (pCHF-related death was 48.98 pg/ml, with 57.14% sensitivity and 86.24% specificity. The best cut-off point of Nt-proBNP was 480 ng/ml with 76.47% sensitivity and 80.48% specificity. Over a mean follow-up of 3 years, Kaplan-Meier survival curves demonstrate that patients with higher levels of intact PTH had lower survival time, with a hazard ratio of 2.5 (95% CI 1.5-3.9). The study has shown that serum intact PTH level obtained in the elderly patients with CHF is a novel biomarker associated with Nt-proBNP and could provide supplementary information for the diagnosis and prognostic prediction of CHF, especially when it is used in combination with Nt-proBNP. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Recruitment methods in a clinical trial of provoked vulvodynia: Predictors of enrollment.

    Science.gov (United States)

    Bachour, Candi C; Bachmann, Gloria A; Foster, David C; Wan, Jim Y; Rawlinson, Leslie A; Brown, Candace S

    2017-02-01

    Successful recruitment in clinical trials for chronic pain conditions is challenging, especially in women with provoked vulvodynia due to reluctance in discussing pain associated with sexual intercourse. The most successful recruitment methods and the characteristics of women reached with these methods are unknown. To compare the effectiveness and efficiency of four recruitment methods and to determine socioeconomic predictors for successful enrollment in a National Institutes of Health-sponsored multicenter clinical trial evaluating a gabapentin intervention in women with provoked vulvodynia. Recruitment methods utilized mass mailing, media, clinician referrals and community outreach. Effectiveness (number of participants enrolled) and efficiency (proportion screened who enrolled) were determined. Socioeconomic variables including race, educational level, annual household income, relationship status, age, menopausal status and employment status were also evaluated regarding which recruitment strategies were best at targeting specific cohorts. Of 868 potential study participants, 219 were enrolled. The most effective recruitment method in enrolling participants was mass mailing ( p recruitment methods ( p = 0.11). Relative to clinician referral, black women were 13 times as likely to be enrolled through mass mailing (adjusted odds ratio 12.5, 95% confidence interval, 3.6-43.1) as white women. There were no differences in enrollment according to educational level, annual income, relationship status, age, menopausal status, or employment status and recruitment method. In this clinical trial, mass mailing was the most effective recruitment method. Race of participants enrolled in a provoked vulvodynia trial was related to the recruitment method.

  14. Entitled vengeance: A meta-analysis relating narcissism to provoked aggression.

    Science.gov (United States)

    Rasmussen, Kyler

    2016-07-01

    Narcissism has long been used to predict aggressive or vengeful responses to provocations from others. The strength of this relation can, however, vary widely from study to study. Narcissism and revenge were examined in 84 independent samples (N = 11297), along with the moderating role of sample type (i.e., child/adolescent, prisoner, undergraduate, or general samples), type of narcissism measure used (i.e., Narcissistic Personality Inventory, Psychological Entitlement Scale, Short D3, etc.), the nature of the provocation, and the type of provoked aggression examined. Narcissism was positively related to provoked aggression across studies (ρ = .25), but that relation was stronger in child/adolescent samples (ρ = .36) and when measures of entitlement or vulnerable narcissism were employed (ρ = .29). Implications for practical research, as well as neglected areas of research on narcissism and provoked aggression are discussed. Aggr. Behav. 42:362-379, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  15. A case report of successful team approach treatment of provoked vulvodynia

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    Gabrijela Simetinger

    2015-10-01

    Full Text Available AbstractBackground: Vulvodynia has been defined as vulvar discomfort, most often described as burning pain, occurring in the absence of relevant findings or a specific, clinically identifiable, neurologic disorder. Vulvodynia is a genital syndrome of multi-causal origin and requires a team approach. The purpose of the case report of provoked vulvodynia is to show the efficacy of individualized, multifaceted and multidisciplinary therapeutic team approach used by a gynaecologist with special knowledge of sexology and a physiotherapist specialising in treatment of pelvic floor dysfunction. Case report: A 35-year old patient presented with a complaint of genital itching and consequently burning pain which first occurred during sexual intercourse one year previously. Afterwards a gynaecologist with special knowledge of sexology performed a biopsychosocial assessment, broader gynaecological examination and psychoeducation. Diagnosed was provoked vulvodynia. Than she was assessed by the physiotherapist specialising in treatment of pelvic floor dysfunction and treated with TENS. To assess the effectiveness of treatment were used Female Sexual Function Index questionnaire and the visual analogue scale before and after the team approach treatment. Conclusions: In our case individualized, multifaceted and multidisciplinary therapeutic approach proved to be a good choice for treating genital syndrome of provoked vulvodynia of multi-causal origin.

  16. High dose teriparatide (rPTH1-34 therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model.

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    Kohei Nishitani

    Full Text Available Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34 effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20 received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1 Placebo (n = 5; daily saline, 2 Continuous rPTH1-34 (n = 7; 5 μg/kg/day s.c. from day 1-55 post-op, or 3 Delayed rPTH1-34 (n = 8; 5 μg/kg/day s.c. from day 14-28 post-op. Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05. These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR on host bone and graft-host junctions (p<0.05. Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05. Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01. In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia.

  17. VDRA therapy is associated with improved survival in dialysis patients with serum intact PTH ≤ 150 pg/mL: results of the Italian FARO Survey.

    Science.gov (United States)

    Cozzolino, Mario; Brancaccio, Diego; Cannella, Giuseppe; Messa, Piergiorgio; Gesualdo, Loreto; Marangella, Martino; LoDeserto, Cosimo; Pozzato, Marco; Rombolà, Giuseppe; Costanzo, Anna Maria; di Luzio Paparatti, Umberto; Mazzaferro, Sandro

    2012-09-01

    Chronic kidney disease (CKD) patients affected by mineral bone disorders (MBD) have higher rates of all-cause and cardiovascular-related mortality. Approximately, one-third of dialysis patients have low serum parathyroid hormone (PTH) levels (≤ 150 pg/mL). However, the reason why these patients have higher mortality compared to patients with normal PTH levels has not yet been fully elucidated. The FARO study was performed on 2453 Italian patients followed prospectively from 28 dialysis centres over a 2-year period. Data were collected every 6 months and end points included time-to-death cumulative probability in patients with serum intact PTH (iPTH) ≤ 150 pg/mL and the effect of vitamin D receptor activation (VDRA) therapy. Kaplan-Meier curves and proportional hazards regression models stratified by PTH levels (i.e. ≤ 150 and >150 pg/mL) were used to determine cumulative probability of time-to-death and adjusted hazard ratios (HRs) for demographic, clinical and CKD-MBD treatment characteristics. The cumulative probability of death was higher (P < 0.01) for patients with serum iPTH levels ≤ 150 pg/mL [25.1%, 95% confidence interval (CI): 22.1-28.5 at 18 months] versus those with serum iPTH levels within the normal range (18.0%, 95% CI: 16.1-20.1). In a model with time-dependent covariates restricted to time periods when patients had iPTH levels ≤ 150 pg/mL, lower mortality was observed in patients treated with VDRA [i.e. HR = 0.62, 95% CI: 0.42-0.92 for oral or intravenous (IV) calcitriol; HR = 0.18, 95% CI: 0.04-0.8 for IV paricalcitol] versus those not receiving any VDRA (P < 0.01) independently of other variables. Patients who received IV paricalcitol, compared with either oral or IV calcitriol, showed reduced mortality, but this was not statistically significant (HR = 0.3, 95% CI: 0.07-1.31, P = 0.11). Results from this observational study suggest that VDRA therapy was associated with improved survival in dialysis patients, even with low serum iPTH

  18. PTH(1-84) Replacement Therapy in Hypoparathyroidism (HypoPT): a Randomized Controlled Trial on Pharmacokinetics and Dynamic effects Following 24 Weeks of treatment

    DEFF Research Database (Denmark)

    Sikjær, Tanja Tvistholm; Amstrup, Anne Kristine; Rolighed, Lars

    In HypoPT, lack of PTH necessitates treatment with calcium and vitamin D analogues in order to avoid hypocalcemia. To study if replacement with the missing hormone possesses advantages, we randomized 62 patients with HypoPT to 24-wks with a daily SC injection in the thigh of PTH(1-84) 100 μg......, reaching a peak level of median 246 (interquartile range (IQR): 181–396) pg/ml at the first time point of measurement (15 min after injection). Thereafter, PTH levels decreased gradually reaching pre-dosing levels after app. 16h, with a plasma t½ of 4.7 (IQR 4.0–5.8)h. PTH caused significant changes...... in the diurnal rhythms of plasma ionized calcium and 1,25(OH)2D levels (Figure), with rising levels reaching a peak app. 8h following the injection. 4 to 12h following injection, asymptomatic hypercalcemia (>1.32 mmol/l) was present in 41% of PTH treated patients. Despite hypercalcemia, renal excretion...

  19. Influence of Secondary Hyperparathyroidism Induced by Low Dietary Calcium, Vitamin D Deficiency, and Renal Failure on Circulating Rat PTH Molecular Forms

    Directory of Open Access Journals (Sweden)

    Pierre D'Amour

    2011-01-01

    Full Text Available Rats(r with secondary hyperparathyroidism were studied to define the relationship between vitamin D metabolites and rPTH levels measured by 3 different rat ELISAs. Controls and renal failure (RF rats were on a normal diet, while 2 groups on a low-calcium (-Ca or a vitamin D-deficient (-D diet. RF was induced surgically. Mild RF rats had normal calcium and 25(OHD but reduced 1,25(OH2D levels (P<.001 with a 2.5-fold increased in rPTH (P<.001. Severe RF rats and those on a -Ca or -D diet had reduced calcium (P<.01 and 25(OHD levels (P<.05, with rPTH increased by 2 (-Ca diet; P<.05, 4 (-D diet; P<.001, and 20-folds (RF; P<.001 while 1,25(OH2D was high (-Ca diet: P<.001 or low (-D diet, RF: P<.001. 25(OHD and 1,25(OH2D were positively and negatively related on the -Ca and -D diets, respectively. rPTH molecular forms behaved as expected in RF and on -Ca diet, but not on -D diet with more C-rPTH fragments when less were expected. This may be related to the short-time course of this study compared to prior studies.

  20. Influence of Secondary Hyperparathyroidism Induced by Low Dietary Calcium, Vitamin D Deficiency, and Renal Failure on Circulating Rat PTH Molecular Forms.

    Science.gov (United States)

    D'Amour, Pierre; Rousseau, Louise; Hornyak, Stephen; Yang, Zan; Cantor, Tom

    2011-01-01

    Rats(r) with secondary hyperparathyroidism were studied to define the relationship between vitamin D metabolites and rPTH levels measured by 3 different rat ELISAs. Controls and renal failure (RF) rats were on a normal diet, while 2 groups on a low-calcium (-Ca) or a vitamin D-deficient (-D) diet. RF was induced surgically. Mild RF rats had normal calcium and 25(OH)D but reduced 1,25(OH)(2)D levels (P < .001) with a 2.5-fold increased in rPTH (P < .001). Severe RF rats and those on a -Ca or -D diet had reduced calcium (P < .01) and 25(OH)D levels (P < .05), with rPTH increased by 2 (-Ca diet; P < .05), 4 (-D diet; P < .001), and 20-folds (RF; P < .001) while 1,25(OH)(2)D was high (-Ca diet: P < .001) or low (-D diet, RF: P < .001). 25(OH)D and 1,25(OH)(2)D were positively and negatively related on the -Ca and -D diets, respectively. rPTH molecular forms behaved as expected in RF and on -Ca diet, but not on -D diet with more C-rPTH fragments when less were expected. This may be related to the short-time course of this study compared to prior studies.

  1. Evaluating the Role of PTH in Promotion of Chondrosarcoma Cell Proliferation and Invasion by Inhibiting Primary Cilia Expression

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    Wei Xiang

    2014-10-01

    Full Text Available Chondrosarcoma is characterized by secretion of a cartilage-like matrix, with high proliferation ability and metastatic potential. Previous studies have shown that parathyroid hormone-related protein (PTHrP has a close relationship with various tumor types. The objectives of this study were to research the function played by PTHrP in human chondrosarcoma, especially targeting cell proliferation and invasion, and to search for the potential interaction between PTHrP and primary cilia in tumorigenesis. Surgical resection tissues and the human chondrosarcoma cell line SW1353 were used in the scientific research. Cells were stimulated with an optimum concentration of recombinant PTH (1-84, and siRNA was used to interfere with internal PTHrP. Cell proliferation and invasion assays were applied, including MTS-8 cell proliferation assay, Western blot, RT-PCR, Transwell invasion assay, and immunohistochemistry and immunofluorescence assays. A high level of PTHrP expression was found in human chondrosarcoma tissues, and recombinant PTH exhibited positive promotion in tumor cell proliferation and invasion. In the meantime, PTHrP could inhibit the assembly of primary cilia and regulate downstream gene expression. These findings indicate that PTHrP can regulate tumor cell proliferation and invasion ability, possibly through suppression of primary cilia assembly. Thus, restricting PTHrP over-expression is a feasible potential therapeutic method for chondrosarcoma.

  2. Effect of endothelin receptor antagonist on parathyroid gland growth, PTH values and cell proliferation in azotemic rats.

    Science.gov (United States)

    Jara, Aquiles; von Höveling, Andrea; Jara, Ximena; Burgos, M Eugenia; Valdivieso, Andres; Mezzano, Sergio; Felsenfeld, Arnold J

    2006-04-01

    A variety of stimuli are involved in the pathogenesis of parathyroid gland hyperplasia in renal failure. Recently, it was shown that blocking the signal from the endothelin-1 (ET-1) receptor (ET(A)R/ET(B)R) by a non-selective receptor antagonist, bosentan, reduced parathyroid cell proliferation, parathyroid gland hyperplasia and parathyroid hormone (PTH) levels in normal rats on a calcium deficient diet. Our goal was to determine whether in 5/6 nephrectomized (NPX) rats with developing or established hyperparathyroidism, the endothelin receptor blocker, bosentan, reduced the increase in parathyroid cell proliferation, parathyroid gland hyperplasia and PTH values. High (HPD, 1.2%) or normal phosphorus diets (PD) (NPD, 0.6%) were given to 5/6 NPX rats for 15 days (NPX(15)). In each dietary group, one-half the rats were given bosentan (B) i.p. 100 mg/kg/day. The four groups of rats were: (1) NPX(15)-1.2% P; (2) NPX(15)-1.2% P+B; (3) NPX(15)-0.6% P; and (4) NPX(15)-0.6% P+B. In a second study in which hyperparathyroidism was already established in 5/6 NPX rats fed a HPD for 15 days, rats were divided into two groups in which one group was maintained on a HPD and the other group was changed to very low PD (VLPD, rats were given bosentan i.p. 100 mg/kg-day. The four groups of rats were: (1) NPX(30)-1.2% P; (2) NPX(30)-1.2% P+B; (3) NPX(30)-0.05% P and (4) NPX(30)-0.05% P+B. Parathyroid cell proliferation was measured by proliferating cell nuclear antigen (PCNA) staining and ET-1 expression by immunohistochemical techniques. In the study of developing hyperparathyroidism, bosentan reduced ET-1 expression in the parathyroid glands of rats on the NPD and HPD (Prats on the NPD did bosentan result in a reduced increase in parathyroid gland weight (Phyperparathyroidism, in which 5/6 NPX rats were given a HPD for 15 days, bosentan started on day 15 reduced (Prats maintained for 15 additional days on the HPD or the VLPD. On the VLPD, parathyroid gland weight was less (Prats on

  3. A Novel Cyclic PTH(1-17) analog with bone anabolic activity and efficacy sufficient to treat established osteopenia in adult ovariectomized rats

    DEFF Research Database (Denmark)

    Morko, Jukka; Peng, ZhiQi; Vääräniemi, Jukka

    of a novel, cyclic PTH(1-17) analog, ZP2307, on the treatment of established osteopenia in adult ovariectomized (OVX) rats. ZP2307 has been developed at Zealand Pharma A/S. Female Sprague-Dawley rats were ovariectomized at the age of 6 months. After 6 weeks without treatment, the development of metaphyseal...... exacerbated in OVX rats treated with vehicle. Treatment with ZP2307 reversed the development of osteopenia in tibial metaphysis and lumbar vertebra at all doses in a dose-dependent manner, and enhanced bone formation on their trabecular bone surface at the dose of 200.0 µg/kg/d. Treatment with ZP2307 also......, is the shortest PTH analog reported hitherto to exhibit bone anabolic activity and efficacy sufficient to treat established osteopenia in adult OVX rats. Due to its mild efficacy, ZP2307 may be very tolerable and have a broad therapeutic window and a better safety/efficacy profile than the PTH analogs currently...

  4. Effects of add on PTH(1-84) substitution therapy in hypoparathyroidism: results from a double-blind randomised controlled study

    DEFF Research Database (Denmark)

    Sikjær, Tanja Tvistholm; Rejnmark, Lars; Mosekilde, Leif

    Conventional treatment of hypoparathyroidism (hypoPT) with calcium supplements and active vitamin D analoges causes a high renal calcium excretion and over-mineralized bone. We studied 62 patients with known hypoPT randomised to 6 months of treatment with either PTH(1-84) 100 µg/d s.c. or similar...... placebo, administrated as an add-on therapy. Participants have had hypoPT for a mean of 12 (range: 1; 37) yrs. Only 4 subjects had idiopathic hypoPT whereas 58 had acquired hypoPT following surgery. Mean age of subjects was 52±11 yrs and 85% were females. PTH(1-84) maintained p-calcium and p......-phosphate levels within the physiological range. Compared with placebo, participants randomised to PTH (1-84) reduced their daily dose of calcium supplements by 68 % (p1-84) arm were no longer in need of calcium supplements...

  5. PTH(1-34) for Surgical Hypoparathyroidism: A 2 year Prospective, Open-Label Investigation of Efficacy and Quality of Life.

    Science.gov (United States)

    Palermo, Andrea; Santonati, Assunta; Tabacco, Gaia; Bosco, Daniela; Spada, Antonio; Pedone, Claudio; Raggiunti, Bruno; Doris, Tina; Maggi, Daria; Grimaldi, Franco; Manfrini, Sivlia; Vescini, Fabio

    2017-11-01

    Daily PTH(1-34) administrations can reduce the required total daily dose of calcium/calcitriol and restore normocalcemia in refractory hypoparathyroidism. However, most of the PTH(1-34) trials were conducted on small cohorts including subjects with hypoparathyroidism of various etiologies and quality of life(QOL) was not investigated. To investigate the effects of 24 month PTH(1-34) treatment in a homogeneous cohort of adult subjects with postoperative hypoparathyroidism and to evaluate quality of life(QOL) changes. Prospective open-label study. Italian multicentric study. 42 subjects. twice-daily PTH(1-34) 20 mcg sc injection. calcium and vitamin D supplementation requirements, serum calcium, phosphate, urinary calcium excretion (3,6,12,18,24 months). At baseline, 6 and 24 months, QOL was evaluated by the RAND 36-Item Short Form(SF-36) Health Survey covering eight domains of physical and mental health. mean serum calcium concentration significantly increased from baseline to 3 months(7.6±0.6 vs 8.9±1.1mg/dl, P<.001) and remained stable until the end of the study, despite a significant reduction in calcium and vitamin D supplementation. Phosphate levels gradually decreased from baseline to 6 months(4.3±1.1 vs 3.9±0.6 mg/dl, P<.019) remaining stable until 24 months. Serum alkaline phosphatase and calcium excretion gradually increased from baseline to 24 months. Data from SF-36 showed a significant improvement in the mean scores of all 8 domains(P<.001). this is the largest study that demonstrates the efficacy and safety of PTH(1-34) to treat adult patients with post-surgical hypoparathyroidism. For the first time, it has been shown that PTH(1-34) can improve their mental and physical health.

  6. The TAL effector PthA4 interacts with nuclear factors involved in RNA-dependent processes including a HMG protein that selectively binds poly(U RNA.

    Directory of Open Access Journals (Sweden)

    Tiago Antonio de Souza

    Full Text Available Plant pathogenic bacteria utilize an array of effector proteins to cause disease. Among them, transcriptional activator-like (TAL effectors are unusual in the sense that they modulate transcription in the host. Although target genes and DNA specificity of TAL effectors have been elucidated, how TAL proteins control host transcription is poorly understood. Previously, we showed that the Xanthomonas citri TAL effectors, PthAs 2 and 3, preferentially targeted a citrus protein complex associated with transcription control and DNA repair. To extend our knowledge on the mode of action of PthAs, we have identified new protein targets of the PthA4 variant, required to elicit canker on citrus. Here we show that all the PthA4-interacting proteins are DNA and/or RNA-binding factors implicated in chromatin remodeling and repair, gene regulation and mRNA stabilization/modification. The majority of these proteins, including a structural maintenance of chromosomes protein (CsSMC, a translin-associated factor X (CsTRAX, a VirE2-interacting protein (CsVIP2, a high mobility group (CsHMG and two poly(A-binding proteins (CsPABP1 and 2, interacted with each other, suggesting that they assemble into a multiprotein complex. CsHMG was shown to bind DNA and to interact with the invariable leucine-rich repeat region of PthAs. Surprisingly, both CsHMG and PthA4 interacted with PABP1 and 2 and showed selective binding to poly(U RNA, a property that is novel among HMGs and TAL effectors. Given that homologs of CsHMG, CsPABP1, CsPABP2, CsSMC and CsTRAX in other organisms assemble into protein complexes to regulate mRNA stability and translation, we suggest a novel role of TAL effectors in mRNA processing and translational control.

  7. High dose ESAs are associated with high iPTH levels in hemodialysis patients with end-stage kidney disease: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Lan eChen

    2015-11-01

    Full Text Available Objective: Anemia and secondary hyperparathyroidism are the two most common complications associated with chronic kidney disease (CKD. Erythropoiesis-stimulating agents (ESAs are widely used in the management of anemia in hemodialysis patients. A reverse correlation has been established between hyperparathyroidism and hemoglobin levels. The aim of this retrospective study is to evaluate the relationship of high dose ESAs and hyperparathyroidism in hemodialysis patients with anemia. Methods: A total of 240 uremic patients maintained on regular hemodialysis were enrolled into this study. Among them, 142 patients were treated with Epiao® (epoetin-alfa and 98 patients were treated with Recormon® (epoetin-beta. The target hemoglobin concentration was 110-130 g/L. Laboratory measurements including hemoglobin, calcium, phosphorus, albumin, intact-parathyroid hormone (iPTH, serum ferritin and transferrin saturation were collected. Results: Hemoglobin concentration increased as iPTH level decreased by stratification. However, no significant association between anemia and calcium or phosphorus level was found. Patients with iPTH levels within 150-300 pg/mL had the highest levels of hemoglobin, serum ferritin and transferrin saturation. Patients treated with Recormon and Epiao had similar hemoglobin concentrations. However, the dose of Recormon for anemia treatment was significantly less than that the dose of Epiao (P<0.05. The level of iPTH in the Recormon group was significantly lower than in the Epiao group. In patients with hemoglobin levels between 110-130 g/L (P<0.05, iPTH level was found to be significantly lower in patients treated with lower doses of ESAs than in patients treated with higher doses of ESAs, no matter which ESA was used (Recormon or Epiao, P<0.05. Conclusions: The dose of ESAs might be positively associated with iPTH level, suggesting that a reasonable hemoglobin target can be achieved by using the lowest possible ESA dose.

  8. Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

    Science.gov (United States)

    Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

    2017-04-01

    Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. Effectiveness of Cognitive-Behavioral Therapy and Physical Therapy for Provoked Vestibulodynia: A Randomized Pilot Study.

    Science.gov (United States)

    Goldfinger, Corrie; Pukall, Caroline F; Thibault-Gagnon, Stephanie; McLean, Linda; Chamberlain, Susan

    2016-01-01

    Non-medical and non-surgical treatments for provoked vestibulodynia target psychological, sexual, and pelvic floor muscle factors that maintain the condition. The goal of the study was to compare the effects of cognitive-behavioral therapy (CBT) and physical therapy (PT) on pain and psychosexual outcomes in women with provoked vestibulodynia. In a clinical trial, 20 women with provoked vestibulodynia were randomly assigned to receive CBT or comprehensive PT. Participants were assessed before treatment, after treatment, and at 6-month follow-up by gynecologic examination, structured interviews, and standardized questionnaires measuring pain, psychological, and sexual variables. Outcome measurements were based on an adaptation of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials recommendations. The primary outcome was change in intercourse pain intensity. Secondary outcomes included pain during the cotton swab test, pain with various sexual and non-sexual activities, and sexual functioning and negative pain cognitions. The two treatment groups demonstrated significant decreases in vulvar pain during sexual intercourse, with 70% and 80% of participants in the CBT and PT groups demonstrating a moderate clinically important decrease in pain (≥30%) after treatment. Participants in the two groups also had significant improvements in pain during the gynecologic examination, the percentage of painful intercourse attempts, the percentage of activities resulting in pain, and the ability to continue intercourse without stopping because of pain. Psychological outcomes, including pain catastrophizing and perceived control over pain, also showed improvement in the two groups. Significant improvements in sexual functioning were observed only in participants who completed CBT. Few between-group differences were identified other than the PT group showing earlier improvements in some outcomes. Nearly all improvements were maintained at the 6-month

  10. Do psychosexual factors play a role in the etiology of provoked vestibulodynia? A critical review.

    Science.gov (United States)

    Desrochers, Geneviève; Bergeron, Sophie; Landry, Tina; Jodoin, Mélanie

    2008-01-01

    The aim of this review was to critically examine published studies concerning the psychosexual aspects of provoked vestibulodynia. Despite the presence of several methodological limitations, some findings were consistently replicated. Overall, women with vestibulodynia demonstrate impaired sexual functioning, namely, lower levels of sexual desire, arousal, and frequency of intercourse. Childhood physical and sexual abuse represent potential risk factors for the development of this condition. Additionally, specific psychological states such as anxiety, fear of pain, hypervigilance, catastrophizing, and depression, are more frequently reported by these women. More rigorous studies are needed to establish which psychosexual variables may exacerbate and/or maintain vestibulodynia.

  11. Epilepsy provoked by television and video games: safety of 100-Hz screens.

    Science.gov (United States)

    Ricci, S; Vigevano, F; Manfredi, M; Kasteleijn-Nolst Trenité, D G

    1998-03-01

    Television (TV) and video games (VG) can provoke seizures in patients with photosensitive epilepsies. Flicker frequency is the most important factor in screen activation. We tested conventional 50-Hz versus 100-Hz monitors during TV viewing and VG playing in 30 photosensitive subjects, 23 of whom had a history of TV or VG seizures or both. Fifteen subjects' discharges were activated by 50-Hz TV; 17 by 50-Hz VG; and one by a 100-Hz screen. Thus, 100-Hz screens protect against screen activation.

  12. pth moment exponential stability of stochastic memristor-based bidirectional associative memory (BAM) neural networks with time delays.

    Science.gov (United States)

    Wang, Fen; Chen, Yuanlong; Liu, Meichun

    2018-02-01

    Stochastic memristor-based bidirectional associative memory (BAM) neural networks with time delays play an increasingly important role in the design and implementation of neural network systems. Under the framework of Filippov solutions, the issues of the pth moment exponential stability of stochastic memristor-based BAM neural networks are investigated. By using the stochastic stability theory, Itô's differential formula and Young inequality, the criteria are derived. Meanwhile, with Lyapunov approach and Cauchy-Schwarz inequality, we derive some sufficient conditions for the mean square exponential stability of the above systems. The obtained results improve and extend previous works on memristor-based or usual neural networks dynamical systems. Four numerical examples are provided to illustrate the effectiveness of the proposed results. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Synergism between endotoxin priming and exotoxin challenge in provoking severe vascular leakage in rabbit lungs.

    Science.gov (United States)

    Schütte, H; Rosseau, S; Czymek, R; Ermert, L; Walmrath, D; Krämer, H J; Seeger, W; Grimminger, F

    1997-09-01

    Lipopolysaccharides (LPS) of gram-negative bacteria prime rabbit lungs for enhanced thromboxane-mediated vasoconstriction upon subsequent challenge with the exotoxin Escherichia coli hemolysin (HlyA) (Walmrath et al. J. Exp. Med. 1994;180:1437-1443). We investigated the impact of endotoxin priming and subsequent HlyA challenge on lung vascular permeability while maintaining constancy of capillary pressure. Rabbit lungs were perfused in a pressure-controlled mode in the presence of the thromboxane receptor antagonist BM 13.505, with continuous monitoring of flow. Perfusion for 180 min with 10 ng/ml LPS did not provoke vasoconstriction or alteration of capillary filtration coefficient (Kfc) values. HlyA (0.021 hemolytic units/ml) induced thromboxane release and a transient decrease in perfusion flow in the absence of significant changes in Kfc. Similar results were obtained when LPS and HlyA were coapplied simultaneously. However, when the HlyA challenge was undertaken after 180 min of LPS priming, a manifold increase in Kfc values was noted, with concomitant severe lung edema formation, although capillary pressure remained unchanged. Thus, endotoxin primes the lung vasculature to respond with a severe increase in vascular permeability to a subsequent low-dose application of HlyA. Such synergism between endotoxin priming and exotoxin challenge in provoking lung vascular leakage may contribute to the pathogenesis of respiratory failure in sepsis and severe lung infection.

  14. Beer flavor provokes striatal dopamine release in male drinkers: mediation by family history of alcoholism.

    Science.gov (United States)

    Oberlin, Brandon G; Dzemidzic, Mario; Tran, Stella M; Soeurt, Christina M; Albrecht, Daniel S; Yoder, Karmen K; Kareken, David A

    2013-08-01

    Striatal dopamine (DA) is increased by virtually all drugs of abuse, including alcohol. However, drug-associated cues are also known to provoke striatal DA transmission- a phenomenon linked to the motivated behaviors associated with addiction. To our knowledge, no one has tested if alcohol's classically conditioned flavor cues, in the absence of a significant pharmacologic effect, are capable of eliciting striatal DA release in humans. Employing positron emission tomography (PET), we hypothesized that beer's flavor alone can reduce the binding potential (BP) of [(11)C]raclopride (RAC; a reflection of striatal DA release) in the ventral striatum, relative to an appetitive flavor control. Forty-nine men, ranging from social to heavy drinking, mean age 25, with a varied family history of alcoholism underwent two [(11)C]RAC PET scans: one while tasting beer, and one while tasting Gatorade. Relative to the control flavor of Gatorade, beer flavor significantly increased self-reported desire to drink, and reduced [(11)C]RAC BP, indicating that the alcohol-associated flavor cues induced DA release. BP reductions were strongest in subjects with first-degree alcoholic relatives. These results demonstrate that alcohol-conditioned flavor cues can provoke ventral striatal DA release, absent significant pharmacologic effects, and that the response is strongest in subjects with a greater genetic risk for alcoholism. Striatal DA responses to salient alcohol cues may thus be an inherited risk factor for alcoholism.

  15. Effects of Thought Suppression on Provoked Men's Alcohol-Related Physical Aggression in the Laboratory.

    Science.gov (United States)

    Gallagher, Kathryn E; Lisco, Claire G; Parrott, Dominic J; Giancola, Peter R

    2014-01-01

    This study utilized a comprehensive theoretical approach to provide the first data on the impact of thought suppression on provoked men's alcohol-related aggression. A diverse community sample (58% African-American) of males between the ages of 21 and 35 (M = 25.25) were randomly assigned to one of two beverage conditions (i.e., alcohol, no-alcohol control). Following beverage consumption, participants were provoked via reception of electric shocks and a verbal insult from a fictitious male opponent. Participants' physical aggression was measured using a shock-based aggression task. Results indicated that acute alcohol intoxication significantly increased physical aggression among lower, but not higher, thought suppressing men. Results suggest that, under conditions of interpersonal provocation, alcohol intoxication produces a myopic focus on hostile thoughts and angry affect in lower, but not higher, suppression men. This pattern of results provides support for the durability of the alcohol myopia effect and highlights the need for continued examination of alcohol's role in the disruption of protective factors for men's aggression. It is important for research to continue to identify modifiable cognitive variables that influence self-regulation of behavior; however, it is imperative that researchers consider the extent to which these variables withstand alcohol's effects.

  16. Alteração do teor de cálcio no banho de DP para 2,5 mEq/L é eficaz no reestabelecimento dos valores preconizados por diretrizes atuais em pacientes com PTH < 150 pg/dL Low-calcium peritoneal dialysis solution is effective in bringing PTH levels to the range recommended by current guidelines in patients with PTH levels < 150 pg/dL

    Directory of Open Access Journals (Sweden)

    Thyago Proença de Moraes

    2010-09-01

    Full Text Available INTRODUÇÃO/OBJETIVO: A doença óssea adinâmica (DOA é um achado comum em diálise peritoneal (PD e é considerada fator de risco para desenvolvimento de fraturas e doença cardiovascular. Dados do BRAZPD apontam as soluções de cálcio a 3,5 mEq/L presentes na maioria das prescrições no país, que possui quase 9.000 pacientes em PD. É comum o balanço positivo de cálcio com concentrações a 3,5 mEq/L contribuindo para o desenvolvimento de DOA. Diretrizes atuais recomendam um PTHi na DRC V em diálise entre 2 e 9 vezes (150-500 pg/mL o valor máximo da normalidade. O objetivo deste estudo foi avaliar a resposta em 6 meses do PTH-i após a conversão para solução de cálcio a 2,5 mEq/L de pacientes que usavam soluções com cálcio a 3,5 mEq/L e com PTH-i basal INTRODUCTION/OBJECTIVE: Adinamic bone disease (ABD is a common finding in peritoneal dialysis (PD and is associated with higher risk of developing cardiovascular and bone disease. Data from BRAZPD indicates that 3.5 mEq/L calcium PD solutions represents the majority of PD prescriptions in the country. A positive calcium balance can contribute to ABD development. Currently guidelines suggest that PTH-i levels in end stage renal disease should be kept from 150-300 pg/mL. The purpose of this study is to evaluate 6 month PTH-i response after conversion to 2.5 mEq/L calcium PD solution in patients with baseline PTH-i levels < 150 pg/mL. METHODS: Prospective, observational study of all prevalent patients (at least 90 days on therapy on PD of a single Brazilian center from January 2008 to May 2009. Inclusion criteria (1 be in use of a PD solution with 3.5mEq/L of calcium; (2 baseline PTH leves < 150 pg/ mL. According to clinical practice patients could be switched to PD solutions with 2.5 mEq/L of calcium. RESULTS: 35 patients (age 62 ± 17 years were included. Of these 22 were converted to 2.5 mEq/L calcium solutions. Diabetic nephropathy (36% was the main cause of renal disease

  17. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism

    DEFF Research Database (Denmark)

    Nielsen, Morten Frost; Abrahamsen, B; Nielsen, T L

    2010-01-01

    and the effects of vitamin D and parathyroid hormone (PTH) on bone mass, bone markers and metabolic function. Design and Participants  The study population consisted of 783 men aged 20-29 years. Measurements  Bone mineral density (BMD) of the total hip, femoral neck and lumbar spine was measured. dual-energy X...

  18. Update on the efficacy, safety, and adherence to treatment of full length parathyroid hormone, PTH (1-84, in the treatment of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    Luca Pietrogrande

    2009-11-01

    Full Text Available Luca PietrograndeDipartimento di Medicina Chirurgia e Odontoiatria Polo San Paolo, Università degli Studi di Milano, Milan, ItalyAbstract: Full length (1-84 parathyroid hormone (PTH was introduced in Europe as a treatment for postmenopausal osteoporosis in 2006. The efficacy of PTH (1-84 in the prevention of vertebral fractures is very high, and is similar to that of teriparatide. Its action in the prevention of femoral fractures has yet to be fully demonstrated, but the incidence of such fractures in trials was very low, and a decrease in nonvertebral fractures was seen in high-risk patients. The effect on bone mineral density (BMD was clearly demonstrated in the spine and also in the hip. The effects on BMD were evident and increased progressively with treatment until 36 months. After its discontinuation there was a clear decrease in BMD if no antiresorptive treatment was initiated. Increases in bone volumetric density and bone volume in trabecular sites were also reported. Moreover, a bone volume increase was detected in cortical sites. Hypercalcemia and hypercalciuria are frequent consequences of PTH treatment, but rarely have clinical effects and are usually well controlled by reducing calcium and vitamin D supplementation.Keywords: PTH (1-84, full-length parathyroid hormone, osteoporosis treatment

  19. Postmenopausal women treated with combination parathyroid hormone (1-84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and Ibandronate Combination Study (PICS).

    Science.gov (United States)

    Schafer, A L; Burghardt, A J; Sellmeyer, D E; Palermo, L; Shoback, D M; Majumdar, S; Black, D M

    2013-10-01

    In postmenopausal women receiving combination parathyroid hormone (PTH) (1-84) therapy and ibandronate, we evaluated bone microarchitecture and biomechanics using high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical and trabecular changes were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. PTH therapy and bisphosphonates decrease fracture risk in postmenopausal osteoporosis, but their effects on bone microstructure and strength have not been fully characterized, particularly during combination therapy. PTH increases trabecular bone mineral density (BMD) substantially but may decrease cortical BMD, possibly by stimulating intracortical remodeling. We evaluated bone microarchitecture and biomechanics with HR-pQCT at the radius (a nonweight-bearing site) and tibia (weight bearing) in women receiving combination PTH(1-84) and ibandronate. Postmenopausal women with low bone mass (n = 43) were treated with 6 months of PTH(1-84) (100 μg/day), either as one 6- or two 3-month courses, in combination with ibandronate (150 mg/month) over 2 years. HR-pQCT was performed before and after therapy. Because changes in HR-pQCT parameters did not differ between treatment arms, groups were pooled into one cohort for analysis. Trabecular BMD increased at both radius and tibia (p radius (p X-ray absorptiometry, while these parameters did not change at the tibia (p ≤ 0.02 for difference between radius and tibia). In contrast, cortical porosity increased at the tibia (p radius. Stiffness and failure load decreased at the radius (p radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. Our findings support the possibility that weight bearing may optimize the effects of osteoporosis therapy.

  20. Comparative study of the serum measurement of PTH on Roche Cobas e411® versus the Abbott Architect ci8200®.

    Science.gov (United States)

    Bensalah, Mohammed; Bouayadi, Ouardia; Rahmani, Nawal; Lyagoubi, Amina; Lamrabat, Somiya; Choukri, Mohammed

    2017-12-15

    Parathormone (PTH) is the main hormone of phosphocalcic homeostasis. It is synthesized and secreted by the parathyroid glands. PTH has become a routine test in the medical biology laboratory. However, its measurement presents analytical difficulties with the various marketed kits. The aim of this work is to present the results of a comparative study between the PTH measurment on Abbott architect ci8200 and on Roche's Cobas e411 automaton. It is a prospective study carried out for 252 hospitalized patients in the various departments of the University Hospital Center Mohammed VI of Oujda. The "intact" PTH tests were performed on two automata: Abbott Architect ci8200 and Roche Cobas e411. The first uses chemiluminescent microparticle immunoassay. The second uses electrochemiluminiscence sandwich enzyme immunoassay. The agreement of the results between the different techniques was evaluated using the Bland-Altman difference diagram and the Passing-Bablok and Deming regression line (MedCalc software version 14.8.1.0®). By analyzing the diagram of Bland-Altman, we note that the average bias between both methods is of the order of 193.9 pg/mL. As for the equation of the right of Passing-Bablok, it is: Y(Architect) = 3.11 X (Cobas) - 12.26. In conclusion, our study shows a great discrepancy between the results of the PTH assay on the Architect ci8200 versus the Cobas e411, hence the biologist's indisputable role in the control and evaluation of the kits marketed through the various validation tests.

  1. Effects of electrocautery to provoke endovascular thermal injury Efeitos do eletrocautério para provocar lesão térmica endovascular

    Directory of Open Access Journals (Sweden)

    Fabio Henrique Rossi

    2011-10-01

    Full Text Available PURPOSE: To investigate the effects of a new electrocautery device to provoke endovascular venous thermal injury. METHODS: An experimental endovascular electrocautery was placed inside eight ex-vivo bovine saphenous veins models. Each one was divided in eight segments and progressive intensities of electric energy liberated. The macroscopic and microscopic effects were analyzed. RESULTS: Forty bovine saphenous veins segments were studied. The higher the electric energy applied the greater the nuclear picnosis and more intense the cytoplasmatic shrinkage and electrocoagulation effects. CONCLUSION: The experimental endovascular electrocautery device demonstrated to be both capable of inducing the destruction of the intimal layers of the studied vein model and provoke endovascular thermal injury.OBJETIVO: Investigar os efeitos de um modelo experimental de eletrocautério em provocar lesão venosa térmica endovascular. MÉTODOS: O eletrocautério endovascular foi colocado dentro de oito modelos experimentais de veia safena bovina. Cada uma foi dividida em oito segmentos e intensidades progressivas de energia elétrica liberada. Os efeitos macroscópicos e microscópicos foram analisados. RESULTADOS: Foram estudados quarenta segmentos de veia safena bovina. Quanto maior a energia elétrica aplicada pelo eletrocauterizador endovascular maiores foram as alteraçoes de picnose nuclear e mais intensa a retração citoplasmática observada. CONCLUSÃO: O eletrocautério endovascular experimental demonstrou ser capaz de induzir a destruição da camada íntima e provocar lesão térmica endovascular.

  2. Experimental activation of the sphenopalatine ganglion provokes cluster-like attacks in humans

    DEFF Research Database (Denmark)

    Schytz, Henrik W; Barløse, Mads; Guo, Song

    2013-01-01

    BackgroundHigh frequency (HF) stimulation of the sphenopalatine ganglion (SPG) is an emerging abortive treatment for cluster headache (CH) attacks. HF SPG stimulation is thought to exert its effect by physiologically blocking parasympathetic outflow. We hypothesized that low frequency (LF) SPG...... stimulation may activate the SPG, causing increased parasympathetic outflow and thereby provoking cluster attacks in CH patients.MethodsIn a double-blind randomized cross-over study, seven CH patients implanted with an SPG neurostimulator were randomly allocated to receive HF or LF stimulation for 3 min on 2...... separate days. We recorded headache characteristics and autonomic symptoms during and after stimulation.ResultsSix patients completed the study. Three out of six patients (50%) reported ipsilateral cluster-like attacks during or within 30 min of LF SPG stimulation. These cluster-like attacks were all...

  3. Systematic Review of the Effectiveness of Physical Therapy Modalities in Women With Provoked Vestibulodynia.

    Science.gov (United States)

    Morin, Mélanie; Carroll, Marie-Soleil; Bergeron, Sophie

    2017-07-01

    Pelvic floor muscle physical therapy is recommended in clinical guidelines for women with provoked vestibulodynia (PVD). Including isolated or combined treatment modalities, physical therapy is viewed as an effective first-line intervention, yet no systematic review concerning the effectiveness of physical therapy has been conducted. To systematically appraise the current literature on the effectiveness of physical therapy modalities for decreasing pain during intercourse and improving sexual function in women with PVD. A systematic literature search using PubMed, Scopus, CINHAL, and PEDro was conducted until October 2016. Moreover, a manual search from reference lists of included articles was performed. Ongoing trials also were reviewed using clinicaltrial.gov and ISRCTNregistry. Randomized controlled trials, prospective and retrospective cohorts, and case reports evaluating the effect of isolated or combined physical therapy modalities in women with PVD were included in the review. Main outcome measures were pain during intercourse, sexual function, and patient's perceived improvement. The literature search resulted in 43 eligible studies including 7 randomized controlled trials, 20 prospective studies, 5 retrospective studies, 6 case reports, and 6 study protocols. Most studies had a high risk of bias mainly associated with the lack of a comparison group. Another common bias was related to insufficient sample size, non-validated outcomes, non-standardized intervention, and use of other ongoing treatment. The vast majority of studies showed that physical therapy modalities such as biofeedback, dilators, electrical stimulation, education, multimodal physical therapy, and multidisciplinary approaches were effective for decreasing pain during intercourse and improving sexual function. The positive findings for the effectiveness of physical therapy modalities in women with PVD should be investigated further in robust and well-designed randomized controlled trials

  4. Understanding the Uncanny: Both Atypical Features and Category Ambiguity Provoke Aversion toward Humanlike Robots

    Science.gov (United States)

    Strait, Megan K.; Floerke, Victoria A.; Ju, Wendy; Maddox, Keith; Remedios, Jessica D.; Jung, Malte F.; Urry, Heather L.

    2017-01-01

    Robots intended for social contexts are often designed with explicit humanlike attributes in order to facilitate their reception by (and communication with) people. However, observation of an “uncanny valley”—a phenomenon in which highly humanlike entities provoke aversion in human observers—has lead some to caution against this practice. Both of these contrasting perspectives on the anthropomorphic design of social robots find some support in empirical investigations to date. Yet, owing to outstanding empirical limitations and theoretical disputes, the uncanny valley and its implications for human-robot interaction remains poorly understood. We thus explored the relationship between human similarity and people's aversion toward humanlike robots via manipulation of the agents' appearances. To that end, we employed a picture-viewing task (Nagents = 60) to conduct an experimental test (Nparticipants = 72) of the uncanny valley's existence and the visual features that cause certain humanlike robots to be unnerving. Across the levels of human similarity, we further manipulated agent appearance on two dimensions, typicality (prototypic, atypical, and ambiguous) and agent identity (robot, person), and measured participants' aversion using both subjective and behavioral indices. Our findings were as follows: (1) Further substantiating its existence, the data show a clear and consistent uncanny valley in the current design space of humanoid robots. (2) Both category ambiguity, and more so, atypicalities provoke aversive responding, thus shedding light on the visual factors that drive people's discomfort. (3) Use of the Negative Attitudes toward Robots Scale did not reveal any significant relationships between people's pre-existing attitudes toward humanlike robots and their aversive responding—suggesting positive exposure and/or additional experience with robots is unlikely to affect the occurrence of an uncanny valley effect in humanoid robotics. This work

  5. Sexual arousal in women with provoked vestibulodynia: the application of laser Doppler imaging to sexual pain.

    Science.gov (United States)

    Boyer, Stéphanie C; Pukall, Caroline F; Chamberlain, Susan M

    2013-04-01

    Introduction.  Women with provoked vestibulodynia (PVD) report lower sexual arousal than nonaffected women, however, laboratory studies of arousal have reported contradictory results about whether group differences exist in genital and subjective arousal. Aim.  To examine genital and subjective sexual arousal in women with and without PVD. Methods.  Eligible women with and without PVD (N = 42) attended a laboratory session that included an interview, questionnaire completion, and genital imaging. A direct measure of superficial blood flow-laser Doppler imaging-was used to assess vulvar blood flow levels while participants watched three films, including an erotic film. Participants answered questions about their level of sexual arousal before, during, and after the erotic film. Main Outcome Measures.  Average vulvar blood flow levels during the baseline and erotic films, numerical ratings of subjective sexual arousal and anxiety, as well as questionnaire measures of arousal. Results.  There was a significant group difference in genital arousal, whereby the PVD group showed a lower genital response to the erotic film, as well as a significant interaction between baseline blood flow and group membership. Separate group regression analyses demonstrated that baseline blood flow explained a substantial amount of the variance in erotic film blood flow in the control group (70%), while only 27% was explained by this variable in the PVD group. There were no differences in subjective sexual arousal or anxiety between the groups. Across questionnaire measures, women with PVD reported lower sexual arousal than the control group. Conclusions.  The results suggest that women with PVD show lower genital responsiveness than nonaffected women to sexual stimuli in a laboratory setting and that their genital arousal is likely impacted by a number of biopsychosocial factors. Boyer SC, Pukall CF, and Chamberlain SM. Sexual arousal in women with provoked vestibulodynia

  6. Understanding the Uncanny: Both Atypical Features and Category Ambiguity Provoke Aversion toward Humanlike Robots.

    Science.gov (United States)

    Strait, Megan K; Floerke, Victoria A; Ju, Wendy; Maddox, Keith; Remedios, Jessica D; Jung, Malte F; Urry, Heather L

    2017-01-01

    Robots intended for social contexts are often designed with explicit humanlike attributes in order to facilitate their reception by (and communication with) people. However, observation of an "uncanny valley"-a phenomenon in which highly humanlike entities provoke aversion in human observers-has lead some to caution against this practice. Both of these contrasting perspectives on the anthropomorphic design of social robots find some support in empirical investigations to date. Yet, owing to outstanding empirical limitations and theoretical disputes, the uncanny valley and its implications for human-robot interaction remains poorly understood. We thus explored the relationship between human similarity and people's aversion toward humanlike robots via manipulation of the agents' appearances. To that end, we employed a picture-viewing task ( N agents = 60) to conduct an experimental test ( N participants = 72) of the uncanny valley's existence and the visual features that cause certain humanlike robots to be unnerving. Across the levels of human similarity, we further manipulated agent appearance on two dimensions, typicality (prototypic, atypical, and ambiguous) and agent identity (robot, person), and measured participants' aversion using both subjective and behavioral indices. Our findings were as follows: (1) Further substantiating its existence, the data show a clear and consistent uncanny valley in the current design space of humanoid robots. (2) Both category ambiguity, and more so, atypicalities provoke aversive responding, thus shedding light on the visual factors that drive people's discomfort. (3) Use of the Negative Attitudes toward Robots Scale did not reveal any significant relationships between people's pre-existing attitudes toward humanlike robots and their aversive responding-suggesting positive exposure and/or additional experience with robots is unlikely to affect the occurrence of an uncanny valley effect in humanoid robotics. This work furthers

  7. The abdominal compartment syndrome as a second insult during systemic neutrophil priming provokes multiple organ injury.

    Science.gov (United States)

    Rezende-Neto, Joao B; Moore, Ernest E; Masuno, Tomohiko; Moore, Peter K; Johnson, Jeffrey L; Sheppard, Forest R; Cunha-Melo, Jose R; Silliman, Christopher C

    2003-10-01

    In our recent clinical study of damage control laparotomy, the abdominal compartment syndrome (ACS) emerged as an independent risk factor for postinjury multiple organ failure (MOF). We and others have shown previously that the ACS promotes the systemic production of proinflammatory cytokines. Our study objective was to develop a clinically relevant two-event animal model of postinjury MOF using the ACS as a second insult during systemic neutrophil priming to provoke organ dysfunction. Male adult rats underwent hemorrhagic shock (30 mmHg x 45 min) and were resuscitated with crystalloids and shed blood. The timing of postshock systemic neutrophil (PMN) priming was determined by the surface expression of CD11b via flow cytometry. Finding maximal PMN priming at 8 h, but no priming at 2 h (early) and 18 h (late), the ACS (25 mmHg x 60 min) was introduced at these time points. At 24 h postshock, lung injury was assessed by lung elastase concentration and Evans blue dye extravasation in bronchoalveolar lavage. Liver and renal injuries were determined by serum alanine aminotransferase, serum creatinine, and blood urea nitrogen. The ACS during the time of maximal systemic PMN priming (8 h) provoked lung and liver injury, but did not if introduced at 2 or 18 h postshock when there was no evidence of systemic PMN priming. The 24-h mortality of this two-event model was 33%. These findings corroborate the potential for the ACS to promote multiple organ injury when occurring at the time of systemic PMN priming. This clinically relevant two-event animal model of PMN organ injury may be useful in elucidating therapy strategies to prevent postinjury MOF.

  8. Understanding the Uncanny: Both Atypical Features and Category Ambiguity Provoke Aversion toward Humanlike Robots

    Directory of Open Access Journals (Sweden)

    Megan K. Strait

    2017-08-01

    Full Text Available Robots intended for social contexts are often designed with explicit humanlike attributes in order to facilitate their reception by (and communication with people. However, observation of an “uncanny valley”—a phenomenon in which highly humanlike entities provoke aversion in human observers—has lead some to caution against this practice. Both of these contrasting perspectives on the anthropomorphic design of social robots find some support in empirical investigations to date. Yet, owing to outstanding empirical limitations and theoretical disputes, the uncanny valley and its implications for human-robot interaction remains poorly understood. We thus explored the relationship between human similarity and people's aversion toward humanlike robots via manipulation of the agents' appearances. To that end, we employed a picture-viewing task (Nagents = 60 to conduct an experimental test (Nparticipants = 72 of the uncanny valley's existence and the visual features that cause certain humanlike robots to be unnerving. Across the levels of human similarity, we further manipulated agent appearance on two dimensions, typicality (prototypic, atypical, and ambiguous and agent identity (robot, person, and measured participants' aversion using both subjective and behavioral indices. Our findings were as follows: (1 Further substantiating its existence, the data show a clear and consistent uncanny valley in the current design space of humanoid robots. (2 Both category ambiguity, and more so, atypicalities provoke aversive responding, thus shedding light on the visual factors that drive people's discomfort. (3 Use of the Negative Attitudes toward Robots Scale did not reveal any significant relationships between people's pre-existing attitudes toward humanlike robots and their aversive responding—suggesting positive exposure and/or additional experience with robots is unlikely to affect the occurrence of an uncanny valley effect in humanoid robotics

  9. Referred Pain Patterns Provoked on Intra-Pelvic Structures among Women with and without Chronic Pelvic Pain: A Descriptive Study

    Science.gov (United States)

    Butler, Stephen; Peterson, Magnus; Eriksson, Margaretha

    2015-01-01

    Objectives To describe referred pain patterns provoked from intra-pelvic structures in women with chronic pelvic pain (CPP) persisting after childbirth with the purpose to improve diagnostics and give implications for treatment. Materials and Methods In this descriptive and comparative study 36 parous women with CPP were recruited from a physiotherapy department waiting list and by advertisements in newspapers. A control group of 29 parous women without CPP was consecutively assessed for eligibility from a midwifery surgery. Inclusion criterion for CPP was: moderate pain in the sacral region persisting at least six months after childbirth confirmed by pelvic pain provocation tests. Exclusion criteria in groups with and without CPP were: persistent back or pelvic pain with onset prior to pregnancy, previous back surgery and positive neurological signs. Pain was provoked by palpation of 13 predetermined intra-pelvic anatomical landmarks. The referred pain distribution was expressed in pain drawings and described in pain maps and calculated referred pain areas. Results Pain provoked by palpation of the posterior intra-pelvic landmarks was mostly referred to the sacral region and pain provoked by palpation of the ischial and pubic bones was mostly referred to the groin and pubic regions, with or without pain referred down the ipsilateral leg. The average pain distribution area provoked by palpation of all 13 anatomical landmarks was 30.3 mm² (19.2 to 53.7) in women with CPP as compared to 3.2 mm² (1.0 to 5.1) in women without CPP, ppain patterns provoked from intra-pelvic landmarks in women with CPP are consistent with sclerotomal sensory innervation. Magnification of referred pain patterns indicates allodynia and central sensitization. The results suggest that pain mapping can be used to evaluate and confirm the pain experience among women with CPP and contribute to diagnosis. PMID:25793999

  10. Referred pain patterns provoked on intra-pelvic structures among women with and without chronic pelvic pain: a descriptive study.

    Directory of Open Access Journals (Sweden)

    Thomas Torstensson

    Full Text Available To describe referred pain patterns provoked from intra-pelvic structures in women with chronic pelvic pain (CPP persisting after childbirth with the purpose to improve diagnostics and give implications for treatment.In this descriptive and comparative study 36 parous women with CPP were recruited from a physiotherapy department waiting list and by advertisements in newspapers. A control group of 29 parous women without CPP was consecutively assessed for eligibility from a midwifery surgery. Inclusion criterion for CPP was: moderate pain in the sacral region persisting at least six months after childbirth confirmed by pelvic pain provocation tests. Exclusion criteria in groups with and without CPP were: persistent back or pelvic pain with onset prior to pregnancy, previous back surgery and positive neurological signs. Pain was provoked by palpation of 13 predetermined intra-pelvic anatomical landmarks. The referred pain distribution was expressed in pain drawings and described in pain maps and calculated referred pain areas.Pain provoked by palpation of the posterior intra-pelvic landmarks was mostly referred to the sacral region and pain provoked by palpation of the ischial and pubic bones was mostly referred to the groin and pubic regions, with or without pain referred down the ipsilateral leg. The average pain distribution area provoked by palpation of all 13 anatomical landmarks was 30.3 mm² (19.2 to 53.7 in women with CPP as compared to 3.2 mm² (1.0 to 5.1 in women without CPP, p< 0.0001.Referred pain patterns provoked from intra-pelvic landmarks in women with CPP are consistent with sclerotomal sensory innervation. Magnification of referred pain patterns indicates allodynia and central sensitization. The results suggest that pain mapping can be used to evaluate and confirm the pain experience among women with CPP and contribute to diagnosis.

  11. Referred pain patterns provoked on intra-pelvic structures among women with and without chronic pelvic pain: a descriptive study.

    Science.gov (United States)

    Torstensson, Thomas; Butler, Stephen; Lindgren, Anne; Peterson, Magnus; Eriksson, Margaretha; Kristiansson, Per

    2015-01-01

    To describe referred pain patterns provoked from intra-pelvic structures in women with chronic pelvic pain (CPP) persisting after childbirth with the purpose to improve diagnostics and give implications for treatment. In this descriptive and comparative study 36 parous women with CPP were recruited from a physiotherapy department waiting list and by advertisements in newspapers. A control group of 29 parous women without CPP was consecutively assessed for eligibility from a midwifery surgery. Inclusion criterion for CPP was: moderate pain in the sacral region persisting at least six months after childbirth confirmed by pelvic pain provocation tests. Exclusion criteria in groups with and without CPP were: persistent back or pelvic pain with onset prior to pregnancy, previous back surgery and positive neurological signs. Pain was provoked by palpation of 13 predetermined intra-pelvic anatomical landmarks. The referred pain distribution was expressed in pain drawings and described in pain maps and calculated referred pain areas. Pain provoked by palpation of the posterior intra-pelvic landmarks was mostly referred to the sacral region and pain provoked by palpation of the ischial and pubic bones was mostly referred to the groin and pubic regions, with or without pain referred down the ipsilateral leg. The average pain distribution area provoked by palpation of all 13 anatomical landmarks was 30.3 mm² (19.2 to 53.7) in women with CPP as compared to 3.2 mm² (1.0 to 5.1) in women without CPP, ppain patterns provoked from intra-pelvic landmarks in women with CPP are consistent with sclerotomal sensory innervation. Magnification of referred pain patterns indicates allodynia and central sensitization. The results suggest that pain mapping can be used to evaluate and confirm the pain experience among women with CPP and contribute to diagnosis.

  12. PTH 1-34 Ameliorates the Osteopenia and Delayed Healing of Stabilized Tibia Fracture in Mice with Achondroplasia Resulting from Gain-Of-Function Mutation of FGFR3

    Science.gov (United States)

    Chen, Hangang; Sun, Xianding; Yin, Liangjun; Chen, Shuai; Zhu, Ying; Huang, Junlan; Jiang, Wanling; Chen, Bo; Zhang, Ruobin; Chen, Lin; Nie, Mao; Xie, Yangli; Deng, Zhongliang

    2017-01-01

    Bone fracture healing is processed through multiple stages including the cartilaginous callus formation and its transition to bony callus. FGFR3 negatively regulates chondrogenesis and enhances osteogenesis during skeleton development. We previously found in mice carrying gain-of-function mutation of FGFR3 that FGFR3 delays the healing of un-stabilized fracture that heals mainly through endochondral ossification. Since fracture is regularly treated in clinics with rigid fixation, and stabilized fracture is healed largely through intramembranous ossification, we asked whether FGFR3, a key regulator of osteogenesis, also affect the regeneration of stabilized fracture. We found that gain-of-function mutation of FGFR3 inhibits the initiation of chondrogenesis and the subsequent bone formation. We further studied whether PTH1-34 can improve the osteopenia and delayed healing of the stabilized tibia fracture in mice with achondroplasia. Fracture healing was evaluated by radiography, micro-CT, biomechanical tests, histology, and real-time polymerase chain reaction (RT-PCR) analysis. We found that PTH 1-34 can alleviate the decreased bone mass and compromised architecture in ACH mice. Histological analysis revealed that administration of PTH1-34 increased the size of both the total callus and cartilaginous callus at 14 days after the surgery in ACH mice. RT-PCR data suggested that systemic PTH1-34 accelerated the initiation of chondrogenesis and chondrocyte maturation (earlier and higher levels of expression of chondrogenesis related markers) and enhanced the osteogenic differentiation in the fracture callus in ACH mice. These results indicate that the PTH1-34 administration resulted in an enhanced callus formation during bone fracture healing in ACH mice, which is at least in part mediated by an increase of cartilaginous callus at early stage and the promotion of bone formation in bony callus. In summary, in this study we revealed that FGFR3 delays the regeneration of

  13. Heightened Pelvic Floor Muscle Tone and Altered Contractility in Women With Provoked Vestibulodynia.

    Science.gov (United States)

    Morin, Mélanie; Binik, Yitzchak M; Bourbonnais, Daniel; Khalifé, Samir; Ouellet, Stéphane; Bergeron, Sophie

    2017-04-01

    Pelvic floor muscle (PFM) dysfunctions are reported to be involved in provoked vestibulodynia (PVD). Although heightened PFM tone has been suggested, the relative contribution of active and passive components of tone remains misunderstood. Likewise, alterations in PFM contractility have been scarcely studied. To compare PFM tone, including the relative contribution of its active and passive components, and muscular contractility in women with PVD and asymptomatic controls. Fifty-six asymptomatic women and 56 women with PVD participated in the study. The PVD diagnosis was confirmed by a gynecologist based on a standardized examination. PFM function was evaluated using a dynamometric speculum combined with surface electromyography (EMG). PFM general tone was evaluated in static conditions at different vaginal apertures and during repeated dynamic cyclic stretching. The active contribution of tone was characterized using the ratio between EMG in a static position and during stretching and the proportion of women presenting PFM activation during stretching. Contribution of the passive component was evaluated using resting forces, stiffness, and hysteresis in women sustaining a negligible EMG signal during stretching. PFM contractility, such as strength, speed of contraction, coordination, and endurance, also was assessed during voluntary isometric efforts. Greater PFM resting forces and stiffness were found in women with PVD compared with controls, indicating an increased general tone. An increased active component also was found in women with PVD because they presented a superior EMG ratio, and a larger proportion of them presented PFM activation during stretching. Higher passive properties also were found in women with PVD. Women with PVD also showed decreased strength, speed of contraction, coordination, and endurance compared with controls. Findings provide further evidence of the contribution of PFM alterations in the etiology of PVD. These alterations should be

  14. Distúrbios do eixo cálcio-PTH-vitamina D nas doenças hepáticas crônicas

    OpenAIRE

    Moreira, Rodrigo O.; Duarte, Mônica P.C.; Farias, Maria Lucia F.

    2004-01-01

    Distúrbios no eixo cálcio-PTH-vitamina D são freqüentemente associados às doenças hepáticas crônicas (DHC). Já foi demonstrado que pacientes com DHC apresentam uma tendência à diminuição do cálcio e vitamina D, com aumento compensatório do PTH. Embora a diminuição da hidroxilação da vitamina D em 25 (OH) vitamina D fosse considerada o mecanismo principal destas alterações, estudos recentes vêm demonstrando que, mesmo nos estágios avançados de doença, o fígado ainda consegue manter níveis adeq...

  15. Comparison of calcium carbonate and aluminium hydroxide as phosphate binders on biochemical bone markers, PTH(1-84), and bone mineral content in dialysis patients

    DEFF Research Database (Denmark)

    Jespersen, B; Jensen, J D; Nielsen, H K

    1991-01-01

    Bone mineral content, estimated by single-photon absorptiometry of the forearm, serum values of intact parathyroid hormone (PTH(1-84], osteocalcin, alkaline phosphatase, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), and aluminium were determined during treatment with calcium carbonate (CaCO3......% per half-year during CaCO3 treatment (P less than 0.05). Comparing the CaCO3 and Al(OH)3 periods the following differences were found: serum calcium increased during CaCO3 treatment, PTH(1-84) decreased (79% of initial values during CaCO3 versus 196% during Al(OH)3, mean area under curve, P less than...

  16. Monoassociation of SCID mice with Helicobacter muridarum, but not four other enterics, provokes IBD upon receipt of T cells

    NARCIS (Netherlands)

    Jiang, HQ; Kushnir, N; Thurnheer, MC; Bos, NA; Cebra, JJ

    Background & Aims: Recently, a number of animal models for different aspects of inflammatory bowel disease (IBD) have been developed. The aim of this study was to use one of these to determine whether particular, ostensibly innocuous, intestinal bacteria could provoke or exacerbate IBD. Methods:

  17. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism

    DEFF Research Database (Denmark)

    Frost, M; Abrahamsen, B; Nielsen, T L

    2010-01-01

    Although vitamin D and bone metabolism are closely related, few studies have addressed the effects of vitamin D status on bone in men at time of peak bone mass. The objectives of this study were to evaluate the prevalence of vitamin D inadequacy in a cross-sectional study in young men and the eff...... and the effects of vitamin D and parathyroid hormone (PTH) on bone mass, bone markers and metabolic function....

  18. Pelvic floor muscle function in women with provoked vestibulodynia and asymptomatic controls.

    Science.gov (United States)

    Næss, Ingrid; Bø, Kari

    2015-10-01

    The purpose of the present study was to assess vaginal resting pressure (VRP), pelvic floor muscle (PFM) strength and endurance, and surface EMG activity in women with and without provoked vestibulodynia (PVD). This was an assessor-masked comparison study including 70 women. Exclusion criteria were any previous pregnancy and presence of candida. Sensitivity of the vulvar vestibule was rated at three sites with Q-tip pressure measurement and a numerical rating scale for pain. VRP and PFM strength and endurance were measured with a high precision pressure transducer connected to a vaginal balloon. Pelvic floor muscle activity was measured with surface EMG. The independent samples t test was used to analyze differences between groups. The p value was set to VRP: 20.6 cmH2O (SD 7.1) versus controls: 17.3 cmH2O (SD 4.4), p = 0.02. The PVD group had significantly lower muscle activity during a 10-s holding period; PVD: 465.2 μV (SD 218.4), controls: 591.1 μV (SD 277.7), p = 0.04. Young, nulliparous women with PVD had significantly higher VRP, but this finding was not confirmed by vaginal surface EMG.

  19. Acute Administration of Diazepam Provokes Redox Homeostasis Imbalance in the Rat Brain: Prevention by Simvastatin.

    Science.gov (United States)

    Eger, Guilherme André; Ferreira, Vinícius Vialle; Batista, Camila Ribeiro; Bonde, Henrique LuisPetrek; de Lima, Daniela Delwing; Rodrigues, André Felipe; da Cruz, José Geraldo Pereira; Magro, Débora Delwing Dal

    2016-10-01

    We investigated the effects of acute diazepam (DZP) administration on thiobarbituric acid-reactive substance (TBARS) levels, protein carbonyl content, and on the activities of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase in the brain of rats. Additionally, we investigated the antioxidant role of chronic pretreatment with simvastatin on the effects provoked by DZP. Simvastatin was administered (1 or 10 mg/kg by oral gavage) for 30 days. On the 30th day of treatment, groups were randomized and DZP was administered (0.5 or 1.0 mg/kg by intraperitoneal injection). Control groups received saline. Results showed that DZP enhanced TBARS levels and protein carbonyl content and altered enzymatic activity in the brain of rats. Simvastatin prevented most of the alterations caused by DZP on the oxidative stress parameters. Data indicate that DZP administration causes an oxidative imbalance in the brain areas studied; however, in the presence of simvastatin, some of these alterations in oxidative stress were prevented. © 2016 Wiley Periodicals, Inc.

  20. Anodal Transcranial Direct Current Stimulation Provokes Neuroplasticity in Repetitive Mild Traumatic Brain Injury in Rats

    Directory of Open Access Journals (Sweden)

    Ho Jeong Kim

    2017-01-01

    Full Text Available Repetitive mild traumatic brain injury (rmTBI provokes behavioral and cognitive changes. But the study about electrophysiologic findings and managements of rmTBI is limited. In this study, we investigate the effects of anodal transcranial direct current stimulation (tDCS on rmTBI. Thirty-one Sprague Dawley rats were divided into the following groups: sham, rmTBI, and rmTBI treated by tDCS. Animals received closed head mTBI three consecutive times a day. Anodal tDCS was applied to the left motor cortex. We evaluated the motor-evoked potential (MEP and the somatosensory-evoked potential (SEP. T2-weighted magnetic resonance imaging was performed 12 days after rmTBI. After rmTBI, the latency of MEP was prolonged and the amplitude in the right hind limb was reduced in the rmTBI group. The latency of SEP was delayed and the amplitude was decreased after rmTBI in the rmTBI group. In the tDCS group, the amplitude in both hind limbs was increased after tDCS in comparison with the values before rmTBI. Anodal tDCS after rmTBI seems to be a useful tool for promoting transient motor recovery through increasing the synchronicity of cortical firing, and it induces early recovery of consciousness. It can contribute to management of concussion in humans if further study is performed.

  1. [Risk factors for provoking collisions between cyclists and pedestrians in Spain, 1993-2011].

    Science.gov (United States)

    Martínez Ruiz, Virginia; Jiménez Mejías, Eladio; Amezcua Prieto, Carmen; Olmedo Requena, Rocío; Pulido Manzanero, José; Lardelli Claret, Pablo

    2015-09-01

    To identify and quantify the factors depending on pedestrians, cyclists and the environment associated with the risk of causing a collision between a cyclist and a pedestrian in Spain from 1993 to 2011. retrospective case series. 1228 pedestrian-cyclist pairs involved in the same number of collisions in an urban area, only one of whom committed an infraction. Register of Traffic Accidents with Victims, supported by the Spanish Traffic General Directorate. committing an infraction (yes/no), age, sex, helmet use (cyclist), hour, type of day, year, existence of sidewalks, place of the accident, and priority regulated. logistic regression model to estimate the strength of the association between the pedestrian's responsibility and independent variables. The association with the cyclist's responsibility was assessed by reversing the value of the odds ratios obtained. In both groups of users, the risk of causing a collision was higher in extreme ages. Female cyclists had a slightly higher risk than male cyclists, while the use of a helmet had a protective effect. The risk of the pedestrian causing an accident was higher in the absence of sidewalks. Cyclists more frequently provoked accidents in crosswalks. We recommend the implementation of safety campaigns aimed at pedestrians and cyclists, with special attention paid to the youngest and older people. Interventions for correct road use would also be advisable. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  2. Original article Coffee consumption and propensity to experience aggressive feelings in provoking and frustrating situations

    Directory of Open Access Journals (Sweden)

    Anna Zajenkowska

    2015-07-01

    Full Text Available The present study focused on examining whether coffee intake is related to the intensity of aggressive feelings in reaction to various provoking or frustrating situations, along with consideration of sex and culture. Previous studies focused mainly on the dose of caffeine (not the habit of coffee drinking and aggressive behavior. Many of these studies showed a positive relation between the amount of caffeine consumed and aggression, so it was expected that also habitual coffee consumption would be positively related to propensity for aggressive feelings in situ ations of provocation and frustration. Participants from Greece (n = 299 and Poland (n = 300 declared whether they were coffee drinkers (at least 1 mug of coffee per day and completed the Situational Triggers of Aggressive Responses questionnaire. The results showed that in females, coffee drinkers had higher scores in Sensitivity to Provocation (SP and Frustration (SF than nondrinkers, while no differences between drinkers and nondrinkers appeared in males. Moreover, amongst coffee drinkers, females had higher scores in SP and SF than males, while no sex differences were found in nondrinkers. Furthermore, in Poland coffee drinkers had higher SP scores than nondrinkers. Poles also had higher SP scores than Greeks, but only when coffee drinkers were compared.

  3. Post-injection induced seismicity provoked by superposition of different mechanisms.

    Science.gov (United States)

    De Simone, Silvia; Carrera, Jesus; Vilarrasa, Victor

    2017-04-01

    Induced microseismicity is a controversial issue related to fluid injection into deep geological formations. The occurring of felt earthquakes after stopping injection especially generates concern, because the correlation between injection and seismic activity is unclear. Thus, advancing in its understanding is crucial to minimize its occurrence. Here, we perform numerical simulations of hydraulic stimulation of deep geothermal systems to analyze the mechanisms that may induce or trigger co- and post-injection seismicity. Apart from the direct impact of fluid pressure increase, we acknowledge thermal effects due to cooling and stress redistribution due to fault slip. We analyze the effect of these three processes both separately and superimposed. We find that preferential flow through conductive fractures or fault zones provokes pressure and temperature perturbations that result in not only heterogeneous variation of the stress field, but also highly anisotropic variations of the local stress tensor. Anisotropic variations tend to stabilize some fractures, but destabilize others. Moreover, shear slip causes a significant variation of the stress field that enlarges the range of critical fracture orientations. We find that, given the different response times of mechanical, hydraulic and thermal effects, post-injection seismicity may occur on non-critically oriented faults that were originally stable. During injection, such faults become destabilized by thermal and shear slip stress changes, but remain static by the superposition of pressure forcing. However, they become unstable and fail when the pressure forcing dissipates shortly after injection stops abruptly.

  4. Paternal bisphenol a diet changes prefrontal cortex proteome and provokes behavioral dysfunction in male offspring.

    Science.gov (United States)

    Luo, Guangying; Wei, Ruifen; Wang, Shaolin; Wang, Jundong

    2017-10-01

    Relatively little attention has been given paternal effects on next generation. Given that Bisphenol A (BPA), a ubiquitous compound in maternal diet, may disrupt brain development and behavior, we hypothesized that paternal BPA diet (PBD) could affect offspring development. Prefrontal cortex (PFC), a vital brain region, is involved in emotion and social behavior. To test whether PBD could alter developing PFC, we carried out a proteomics approach for PFC in male juvenile offspring that responded to PBD (50 mg BPA/kg diet). We found that PBD altered the expressions of binding immunoglobulin protein (BIP), CCAAT/-enhancer-binding protein homologous protein (CHOP) and B-cell lymphoma-2 (BCL-2), which could reflect endoplasmic reticulum (ER) stress. In addition, downregulation of myelinogenesis genes and myelin basic protein (MBP) could provoke myelin deficiency. Furthermore, PBD significantly increased anxiety-like behavior and impaired social behavior in male offspring. Taken together, these results revealed the alterations of ER stress and myelin destruction related molecules induced by PBD might be a potential mechanism for the behavior deficits in their male offspring. These findings remind us of the importance of paternal effects in the further environmental exposure research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Perception of experimental pain is reduced after provoked waking from rapid eye movement sleep.

    Science.gov (United States)

    Daya, Vivek G; Bentley, Alison J

    2010-06-01

    Patients with chronic pain often complain of pain when they wake at night, but the accuracy of their perception of the pain after waking at night is unknown. While cognitive functions are reduced for a short time after waking from sleep, a situation known as sleep inertia, it is unclear how sleep inertia may affect the perception of pain. We investigated the effects of sleep inertia on the perception of experimentally induced pain. Fourteen male volunteers were exposed to a randomized thermal heat stimulus of 43.1 degrees C 'hot' and 46.5 degrees C 'hurting' during provoked waking from Stage 2 sleep, slow wave sleep and rapid eye movement (REM) sleep. Subjects rated their pain on awakening on a Visual Analogue Scale at 30 s after awakening and each minute thereafter for 5 min. We found no change in pain perception over the 5-min period irrespective of temperature used or sleep stage. However, perceived pain when awoken abruptly from REM sleep was significantly lower than the awake score for both the hot (P = 0.0069) and hurting (P = 0.0025) temperatures. Pain perception when woken from Stage 2 sleep or slow wave sleep was not significantly different from perception when awake. Our findings indicate that sleep inertia reduces pain perception when awoken abruptly from REM. This suggests that patients who wake up in pain either perceive accurately the pain they are experiencing, or at worst underestimate the level of pain if woken from REM sleep.

  6. Home-Schooled Students And Their Teachers: Provoking Curriculum Together Through Child-Driven Learning

    Directory of Open Access Journals (Sweden)

    Karen E. EFFORD

    2017-12-01

    Full Text Available Child-centered and child-driven learning can provoke the creation of curriculum that is responsive to students’ particular learning needs, is engaging and meaningful, and promotes learner agency. Homeschool settings provide opportunities for parent/educators cognizant of child-centered and child-driven curriculum to meet students’ interests, readiness, growth, and educational drive with responses tailored for each unique situation. This learning space can allow for the relationship between the parent/educator and the student to continually revisit and revitalize learning, expanding on shared experience and potentially spanning the developmental years of the student. The lines between educator and student become blurred as the educator is directed by the unique interests and educational needs of each student. Research into the field of homeschooling curriculum can inspire discussion and innovation in more traditional educational settings. In this paper presentation, the authors will discuss the literature on child-centered and child-driven learning. Next, stories from real homeschools illustrating the co-creation of child- centered curriculum by both the educator/parent and student will be shared. Finally, the presenters will kindle a lively conversation with all participants about the role of students and teachers in curriculum creation, student-centered and student-driven learning in homeschools and in public schools, and imagining the possibilities of both contexts.

  7. LA PROTEÍNA PTHB DE Xanthomonas axonopodis pv. Manihotis ES AUTOACTIVA EN ENSAYOS DE DOBLE HÍBRIDO The PthB Protein from Xanthomonas axonopodis pv. Manihotis is an Autoactive in Yeast Two-Hybrid Assays

    Directory of Open Access Journals (Sweden)

    JULIANA GIL

    Full Text Available La bacteriosis vascular de yuca producida por la bacteria Xanthomonas axonopodis pv. manihotis (Xam es una enfermedad limitante para la producción de yuca. Dentro de los primeros factores de patogenicidad identificados en esta bacteria se encuentra el gen PthB. La proteína PthB pertenece a la familia de efectores PthA/AvrBs3, que se caracterizan por presentar dominios NLS (Nuclear Localization Signal y un dominio AAD (Acidic Activation Domain, lo cual sugiere que estas proteínas actúan como factores de transcripción. La identificación de las proteínas de yuca que interactúan con PthB permitiría dar luces sobre la función de esta proteína en la patogenicidad de esta bacteria. En este trabajo se clonó PthB en una fusión traduccional con el BD (Binding Domain del factor de transcripción GAL4. Después de transformar este constructo en una cepa de levadura, se observó autoactivación de los genes reporteros, incluso a concentraciones altas de 3-AT. La eliminación del primer, segundo o de los dos NLS y del AAD no eliminaron la capacidad de autoactivación de los genes reporteros mediada por PthB. Estos resultados indican la imposibilidad de su utilización en un tamizaje de una librería de ADNc de yuca para identificar las proteínas que interactúan con PthB.Cassava bacterial blight disease is caused by the gram-negative bacteria Xanthomonas axonopodis pv. manihotis (Xam, and constitutes one of the most important constraints for cassava production. One of the first determinants of pathogenicity identified in this bacterium is the PthB gene. The PthB protein belongs to the PthA/AvrBs3 family, characterized by the presence of Nuclear Localization Signal (NLS and Acidic Activation (AAD domains, suggesting that these proteins are transcription factors. The identification of cassava proteins interacting with PthB could give insights about the function of this protein in the pathogenicity of this bacterium. In this work we cloned PthB in

  8. Time course of 25(OHD3 vitamin D3 as well as PTH (parathyroid hormone during fracture healing of patients with normal and low bone mineral density (BMD

    Directory of Open Access Journals (Sweden)

    Wöfl Christoph

    2013-01-01

    Full Text Available Abstract Background Until now the exact biochemical processes during healing of metaphyseal fractures of healthy and osteoporotic bone remain unclear. Especially the physiological time courses of 25(OHD3 (Vitamin D as well as PTH (Parathyroid Hormone the most important modulators of calcium and bone homeostasis are not yet examined sufficiently. The purpose of this study was to focus on the time course of these parameters during fracture healing. Methods In the presented study, we analyse the time course of 25(OHD3 and PTH during fracture healing of low BMD level fractures versus normal BMD level fractures in a matched pair analysis. Between March 2007 and February 2009 30 patients older than 50 years of age who had suffered a metaphyseal fracture of the proximal humerus, the distal radius or the proximal femur were included in our study. Osteoporosis was verified by DEXA measuring. The time courses of 25(OHD3 and PTH were examined over an eight week period. Friedmann test, the Wilcoxon signed rank test and the Mann-Withney U test were used as post-hoc tests. A p-value ≤ 0.05 was considered significant. Results Serum levels of 25(OHD3 showed no differences in both groups. In the first phase of fracture healing PTH levels in the low BMD level group remained below those of the normal BMD group in absolute figures. Over all no significant differences between low BMD level bone and normal BMD level bone could be detected in our study. Conclusions The time course of 25(OHD3 and PTH during fracture healing of patients with normal and low bone mineral density were examined for the first time in humans in this setting and allowing molecular biological insights into fracture healing in metaphyseal bones on a molecural level. There were no significant differences between patients with normal and low BMD levels. Hence further studies will be necessary to obtain more detailed insight into fracture healing in order to provide reliable decision criteria for

  9. Cybersickness provoked by head-mounted display affects cutaneous vascular tone, heart rate and reaction time.

    Science.gov (United States)

    Nalivaiko, Eugene; Davis, Simon L; Blackmore, Karen L; Vakulin, Andrew; Nesbitt, Keith V

    2015-11-01

    Evidence from studies of provocative motion indicates that motion sickness is tightly linked to the disturbances of thermoregulation. The major aim of the current study was to determine whether provocative visual stimuli (immersion into the virtual reality simulating rides on a rollercoaster) affect skin temperature that reflects thermoregulatory cutaneous responses, and to test whether such stimuli alter cognitive functions. In 26 healthy young volunteers wearing head-mounted display (Oculus Rift), simulated rides consistently provoked vection and nausea, with a significant difference between the two versions of simulation software (Parrot Coaster and Helix). Basal finger temperature had bimodal distribution, with low-temperature group (n=8) having values of 23-29 °C, and high-temperature group (n=18) having values of 32-36 °C. Effects of cybersickness on finger temperature depended on the basal level of this variable: in subjects from former group it raised by 3-4 °C, while in most subjects from the latter group it either did not change or transiently reduced by 1.5-2 °C. There was no correlation between the magnitude of changes in the finger temperature and nausea score at the end of simulated ride. Provocative visual stimulation caused prolongation of simple reaction time by 20-50 ms; this increase closely correlated with the subjective rating of nausea. Lastly, in subjects who experienced pronounced nausea, heart rate was elevated. We conclude that cybersickness is associated with changes in cutaneous thermoregulatory vascular tone; this further supports the idea of a tight link between motion sickness and thermoregulation. Cybersickness-induced prolongation of reaction time raises obvious concerns regarding the safety of this technology. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Daily associations between partner responses and sexual and relationship satisfaction in couples coping with provoked vestibulodynia.

    Science.gov (United States)

    Rosen, Natalie O; Muise, Amy; Bergeron, Sophie; Delisle, Isabelle; Baxter, Mary Lou

    2015-04-01

    Women with provoked vestibulodynia (PVD) experience a recurrent vulvo-vaginal pain triggered primarily during sexual intercourse. Although affected couples report adverse effects on their sexual and global romantic relationships, few studies have examined interpersonal factors that may influence their sexual and relationship satisfaction. Cross-sectional studies have shown that greater partner solicitous and negative responses and lower facilitative responses are associated with poorer sexual and relationship satisfaction in women with PVD. The aim of this study was to investigate the within-person associations between partner responses to painful intercourse and the sexual and relationship satisfaction of affected couples. In a dyadic daily experience study, 69 women (M(age) = 28.46, SD = 6.66) diagnosed with PVD and their cohabitating male partners (M(age) = 30.29, SD = 8.13) reported on male partner responses, as well as sexual and relationship satisfaction on sexual intercourse days (M = 6.81; SD = 5.40) over 8 weeks. Dependent measures were the (i) Kansas Marital Satisfaction Scale and (ii) Global Measure of Sexual Satisfaction Scale. On sexual intercourse days when women perceived more facilitative partner responses than usual and on days when they perceived lower negative partner responses than usual, they reported higher sexual and relationship satisfaction. On sexual intercourse days when men reported more solicitous responses than usual, both they and their female partners reported lower sexual satisfaction. Interventions aimed at improving the day-to-day sexual and relationship satisfaction of couples with PVD should target increasing facilitative and decreasing negative and solicitous partner responses. © 2015 International Society for Sexual Medicine.

  11. Short pain-provoked head-up tilt test for the confirmation of vasovagal syncope.

    Science.gov (United States)

    Adamec, Ivan; Mišmaš, Antonija; Zaper, Dinka; Junaković, Anamari; Hajnšek, Sanja; Habek, Mario

    2013-06-01

    We investigated a short pain-provoked head-up tilt (PP-HUT) and the Calgary Syncope Symptom Score in a group of patients with clinically diagnosed vasovagal syncope and group of neurological patients without transient loss of consciousness. We included 127 consecutive patients who were investigated in our laboratory. The group 1 included 56 patients who after appropriate investigations were diagnosed with vasovagal syncope. The group 2 included 70 neurological patients without transient loss of consciousness. The subjects were tilted to 70° for a maximum period of 10 min or until symptoms occurred. If there were no symptoms after initial 10 min, a painful stimulus with the insertion of 0.7 mm needle into the dorsum of hand subcutaneously for 30 s was performed with the patient in the tilted for further 5 min. Calgary Syncope Symptom Score was calculated for all patients. In the group 1, significantly higher number of patients had positive results on PP-HUT (36 vs. 6 patients, respectively; p syndrome (3 vs. 1 patient, respectively; p = 0.32) between groups. PP-HUT had sensitivity of 65.9 % (95 % CI 0.49-0.79) and specificity of 89.7 % (95 % CI 0.75-0.97). The CSSS had sensitivity of 58.5 % (95 % CI 0.42-0.73) and specificity of 46.1 % (95 % CI 0.30-0.63). PP-HUT has a higher diagnostic rate than the CSSS and provides a rapid alternative to conventional methods.

  12. GCH1-polymorphism and pain sensitivity among women with provoked vestibulodynia

    Directory of Open Access Journals (Sweden)

    Heddini Ulrika

    2012-09-01

    Full Text Available Abstract Background Provoked vestibulodynia (PVD is a pain disorder localized in the vestibular mucosa. It is the most common cause of dyspareunia among young women and it is associated with general pain hypersensitivity and other chronic pain conditions. Polymorphism in the guanosine triphosphate cyclohydrolase (GCH1 gene has been found to influence general pain sensitivity and the risk of developing a longstanding pain condition. The aim of this study was to investigate GCH1-polymorphism in women with PVD and healthy controls, in correlation to pain sensitivity. Results We found no correlation between the previously defined pain-protective GCH1-SNP combination and the diagnosis of PVD. Nor any correlation with pain sensitivity measured as pressure pain thresholds on the arm, leg and in the vestibule, coital pain scored on a visual analog scale and prevalence of other bodily pain conditions among women with PVD (n = 98 and healthy controls (n = 102. However, among patients with current treatment (n = 36, there was a significant interaction effect of GCH1-gene polymorphism and hormonal contraceptive (HC therapy on coital pain (p = 0.04 as well as on pressure pain thresholds on the arm (p = 0.04. PVD patients carrying the specified SNP combination and using HCs had higher pain sensitivity compared to non-carriers. In non-HC-users, carriers had lower pain sensitivity. Conclusions The results of this study gave no support to the hypothesis that polymorphism in the GCH1-gene contributes to the etiology of PVD. However, among patients currently receiving treatment an interaction effect of the defined SNP combination and use of hormonal contraceptives on pain sensitivity was found. This finding offers a possible explanation to the clinically known fact that some PVD patients improve after cessation of hormonal contraceptives, indicating that PVD patients carrying the defined SNP combination of GCH1 would benefit from this

  13. The recurrent pain and sexual sequelae of provoked vestibulodynia: a perpetuating cycle.

    Science.gov (United States)

    Basson, Rosemary

    2012-08-01

    Optimal management of provoked vestibulodynia (PVD), thought to be the most common form of chronic dyspareunia, is unclear. To integrate recent brain data on chronic pain circuitry with stress-induced neuroendocrine mechanisms in the skin and the stress burden (allostatic load) of women with PVD; to also clarify the typical chronicity and negative sexual sequelae associated with PVD; and then review modulation of pain circuitry by cognitive therapy and mindfulness practice and apply to PVD management. Methods.  Review of scientific publications in the areas of sexual medicine, pain, brain imaging, gynecology, stress response, mindfulness, and cognitive behavioral therapy (CBT). (i) A model of PVD to reflect its etiology, typical chronicity, and the detrimental effects on sexual function; (ii) Interventions of sexual rehabilitation based on principles underlying changes associated with CBT and mindfulness practice. A model emerges which reflects how stress-induced changes of pain amplification (central sensitization), characteristic of chronic pain conditions, may impair sexual response in addition to sexual dysfunction that arises from conscious pain avoidance and/or fear-related inattention to sexual cues. Stress from low self-acceptance may be a major component of the allostatic load present in women with PVD, only to be exacerbated by the sexual dysfunction precipitated by the pain of intercourse. Mindfulness-based CBT appears promising to target both the pain and sexual suffering from PVD. New findings on brain activity associated with recurrent clinical pain, functional brain changes associated with CBT and mindfulness, plus new data on stress systems within the skin along with data on increased stress load in women with PVD, support the use of mindfulness-based CBT for the recurrent pain and sexual suffering from PVD. © 2012 International Society for Sexual Medicine.

  14. Ex vivo

    Science.gov (United States)

    Matsuda, Kant M; Lopes-Calcas, Ana; Honke, Michael L; O'Brien-Moran, Zoe; Buist, Richard; West, Michael; Martin, Melanie

    2017-07-01

    To advance magnetic resonance imaging (MRI) technologies further for in vivo tissue characterization with histopathologic validation, we investigated the feasibility of ex vivo tissue imaging of a surgically removed human brain tumor as a comprehensive approach for radiology-pathology correlation in histoanatomically identical fashion in a rare case of pigmented ganglioglioma with complex paramagnetic properties. Pieces of surgically removed ganglioglioma, containing melanin and hemosiderin pigments, were imaged with a small bore 7-T MRI scanner to obtain T1-, T2-, and T2*-weighted image and diffusion tensor imaging (DTI). Corresponding histopathological slides were prepared for routine hematoxylin and eosin stain and special stains for melanin and iron/hemosiderin to correlate with MRI signal characteristics. Furthermore, mean diffusivity (MD) maps were generated from DTI data and correlated with cellularity using image analysis. While the presence of melanin was difficult to interpret in in vivo MRI with certainty due to concomitant hemosiderin pigments and calcium depositions, ex vivo tissue imaging clearly demonstrated pieces of tissue exhibiting the characteristic MR signal pattern for melanin with pathologic confirmation in a histoanatomically identical location. There was also concordant correlation between MD and cellularity. Although it is still in an initial phase of development, ex vivo tissue imaging is a promising approach, which offers radiology-pathology correlation in a straightforward and comprehensive manner.

  15. Surface electromyography of myopotential oversensing provoked by simultaneous straining and leftward twisting in a patient with an implantable cardioverter defibrillator.

    Science.gov (United States)

    Ajiro, Yoichi; Shiga, Tsuyoshi; Shoda, Morio; Hagiwara, Nobuhisa

    2017-03-01

    An important step in diagnosing myopotential oversensing is to confirm its reproducibility using specific provocation maneuvers. Although most maneuvers involve the co-contraction of many muscles, no attempt has been made to assess relevant muscle activities by electromyography. We describe a case with an implantable cardioverter defibrillator (ICD) whose myopotential oversensing was provoked by simultaneous straining and leftward twisting. Simultaneous recordings from real-time ICD telemetry and myopotentials of the rectus abdominis, oblique abdominis, and diaphragm on electromyography during the provocation maneuvers were conducted. It was shown that all three muscles contracted simultaneously during the provocation maneuvers; the diaphragm activity was the main source of noise oversensing, and the twist itself caused oversensing possibly due to the change in the position of the lead. In conclusion, the electromyographic assessment of relevant muscle activities may be useful in assessing each muscle's role and its contribution to myopotential oversensing, especially in a patient whose myopotential oversensing requires complex maneuvers to be provoked.

  16. Referred pain patterns provoked on intra-pelvic structures among women with and without chronic pelvic pain : a descriptive study

    OpenAIRE

    Torstensson, Thomas; Butler, Stephen; Lindgren, Anne; Peterson, Magnus; Eriksson, Margaretha; Kristiansson, Per

    2015-01-01

    OBJECTIVES: To describe referred pain patterns provoked from intra-pelvic structures in women with chronic pelvic pain (CPP) persisting after childbirth with the purpose to improve diagnostics and give implications for treatment. MATERIALS AND METHODS: In this descriptive and comparative study 36 parous women with CPP were recruited from a physiotherapy department waiting list and by advertisements in newspapers. A control group of 29 parous women without CPP was consecutively assessed for el...

  17. Carnitine Deficiency and Oxidative Stress Provoke Cardiotoxicity in an Ifosfamide-Induced Fanconi Syndrome Rat Model

    Directory of Open Access Journals (Sweden)

    Mohamed M. Sayed-Ahmed

    2010-01-01

    Full Text Available In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day combined with mildronate (MD, 200 mg/kg/day and PLC (250 mg/kg/day, respectively, for 10 successive days. The 4th, 5th and 6th groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day. IFO significantly increased serum creatinine, blood urea nitrogen (BUN, urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB, lactate dehydrogenase (LDH, intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS in cardiac tissues and significantly decreased adenosine triphosphate (ATP and total carnitine and reduced glutathione (GSH content in cardiac tissues. In carnitine

  18. Migration Processes Provoked yy the Break-Up of Yugoslavia and the Agression against Croatia

    Directory of Open Access Journals (Sweden)

    Mirjana Domini

    1999-10-01

    Full Text Available The paper deals with forced migration caused by Serb aggression in areas of Croatia and the neighbouring countries. The first part presents the relevant facts relating to Croatia and important for an understanding of the migration flows (some demographic data as well as the basic guidelines of migration policy, legal regulations and most important problems connected with expellees, refugees and displaced persons. The main elements of contemporary migration movements in Croatia are indicated – migration based on economic causes (traditional migration, migration provoked by crisis and war destruction in former Yugoslavia and migration flows that are difficult to register (mainly clandestine crossings of the border of the Republic of Croatia and the irregular labour market. The author states that the expellee, refugee and displaced persons crisis (with psychological and material repercussions began in 1991 and reached a climax in 1992 when Croatia became one of the most pronounced refugee countries in the world, with refugees accounting for about 15% of its population. As the war crisis shifted, the areas from which intense forced migration to and from Croatia resulted also shifted as did the mechanisms for regulating these forced migrations (dual citizenship, transit visas, accords with "third countries" for accepting refugees and expellees, ways of resolving and caring for the refugee-expellee populations in the Republic of Croatia. The author concludes that even after seven years from the start of the aggression against Croatia, this humanitarian crisis among expellees, refugees and displaced persons has not yet finished, as testified by the new military conflict in Kosovo and by many open questions in regard to the future organisation of states in this crisis area as well as the creation of mechanisms for monitoring potential conflicts. A fundamental idea is expressed throughout the paper – i.e. the notion that now it is maybe more

  19. PTH levels and not serum phosphorus levels are a predictor of the progression of kidney disease in elderly patients with advanced chronic kidney disease.

    Science.gov (United States)

    Toapanta Gaibor, Néstor Gabriel; Nava Pérez, Nathasha Carolina; Martínez Echevers, Yeleine; Montes Delgado, Rafael; Guerrero Riscos, María Ángeles

    At present, there is a high incidence of elderly patients with advanced chronic kidney disease (CKD) and it is important to know the long term progression and the factors that influence it. To analyse the progression of advanced CKD in elderly patients and the influence of bone-mineral metabolism. Retrospective study of 125 patients ≥70years of age with CKD stages 4-5 who started follow-up from January 1, 2007 to December 31, 2008, showing the progression of CKD (measured by the slope of the regression line of the estimated glomerular filtration rate [eGFR] by MDRD-4) over 5years. Progression in the entire group (median and 25th and 75th percentiles): -1.15 (-2.8/0.17) ml/min/1.73m2/year, CKD-4: -1.3 (-2.8/0.03) ml/min/1.73m2/year, CKD-5: -1.03 (-3.0/0.8) ml/min/1.73m2/year; the slope of the regression line was positive in 35 patients (28%: CKD does not progress) and negative in 90 patients (72%: CKD progresses). Negative correlation (Spearman) (slower progression): PTH, albumin/Cr ratio and daily Na excretion (all baseline measurements). No correlation with eGFR, serum P, urinary P excretion, protein intake and intake of P (all baseline measurements). In the linear regression analysis (dependent variable: slope of progression): albuminuria and PTH (both at baseline measurements) influenced this variable independently. Logistic regression (progresses vs. does not progress): PTH, albuminuria and eGFR (all at baseline measurements) influenced significantly. In our group of elderly patients, impairment of renal function is slow, particularly in CKD-5 patients. Albuminuria and PTH at baseline levels are prognostic factors in the evolution of renal function. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  20. In vivo

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    Berkowitz, Bruce A; Lenning, Jacob; Khetarpal, Nikita; Tran, Catherine; Wu, Johnny Y; Berri, Ali M; Dernay, Kristin; Haacke, E Mark; Shafie-Khorassani, Fatema; Podolsky, Robert H; Gant, John C; Maimaiti, Shaniya; Thibault, Olivier; Murphy, Geoffrey G; Bennett, Brian M; Roberts, Robin

    2017-09-01

    Hippocampus oxidative stress is considered pathogenic in neurodegenerative diseases, such as Alzheimer disease (AD), and in neurodevelopmental disorders, such as Angelman syndrome (AS). Yet clinical benefits of antioxidant treatment for these diseases remain unclear because conventional imaging methods are unable to guide management of therapies in specific hippocampus subfields in vivo that underlie abnormal behavior. Excessive production of paramagnetic free radicals in nonhippocampus brain tissue can be measured in vivo as a greater-than-normal 1/ T 1 that is quenchable with antioxidant as measured by quench-assisted (Quest) MRI. Here, we further test this approach in phantoms, and we present proof-of-concept data in models of AD-like and AS hippocampus oxidative stress that also exhibit impaired spatial learning and memory. AD-like models showed an abnormal gradient along the CA1 dorsal-ventral axis of excessive free radical production as measured by Quest MRI, and redox-sensitive calcium dysregulation as measured by manganese-enhanced MRI and electrophysiology. In the AS model, abnormally high free radical levels were observed in dorsal and ventral CA1. Quest MRI is a promising in vivo paradigm for bridging brain subfield oxidative stress and behavior in animal models and in human patients to better manage antioxidant therapy in devastating neurodegenerative and neurodevelopmental diseases.-Berkowitz, B. A., Lenning, J., Khetarpal, N., Tran, C., Wu, J. Y., Berri, A. M., Dernay, K., Haacke, E. M., Shafie-Khorassani, F., Podolsky, R. H., Gant, J. C., Maimaiti, S., Thibault, O., Murphy, G. G., Bennett, B. M., Roberts, R. In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome. © FASEB.

  1. Assessment of vitamin D status in healthy children and adolescents living in Tehran and its relation to iPTH, gender, weight and height.

    Science.gov (United States)

    Razzaghy-Azar, Maryam; Shakiba, Marjan

    2010-01-01

    This study was conducted to determine the frequency of vitamin D deficiency and its correlation with different factors. Three hundred and thirteen healthy children and adolescents (192 females and 121 males aged 8-18 years, mean +/- SD, 12.7 +/- 2.3 years) were enrolled, and measurements of serum 25-hydroxyvitamin D [25(OH)D] (using EIA) and intact parathyroid hormone (iPTH) (using immunoradiometric assay (IRMA)) were conducted. The grades of vitamin D status were defined according to blood level of 25(OH)D as follows: severely deficient or = 12.5 and or = 25 and or = 50 and rickets. Frequency of vitamin D deficiency did not have any significant seasonal variation. Furthermore, vitamin D deficiency was not found to be related to the type or location of the subjects' homes. In this study, subclinical vitamin D deficiency was significantly more prevalent in females, particularly those undergoing puberty. Children who were obese and taller than average, had lower levels of 25(OH)D, and level of 25(OH)D should be maintained > 75 nmol/L in order to prevent PTH rising.

  2. Muscle-bone and fat-bone interactions in regulating bone mass: do PTH and PTHrP play any role?

    Science.gov (United States)

    Datta, Nabanita S

    2014-11-01

    Metabolic bone disease occurs when there is a net loss in bone density. Osteoporosis, the most common metabolic bone disease, is a devastating problem and an increasingly major public health issue. A substantial body of evidence in the elderly population indicates that a relationship exists between the components of body weight and various measures of bone/mass, density, and function. Both muscle and fat contribute to the body's total weight and the intimate associations of muscle, fat, and bone are known. But the close functional interactions between muscle and bone or fat and bone are largely unidentified and have drawn much attention in recent years. Each of these tissues not only responds to afferent signals from traditional hormone systems and the central nervous systems but also secretes factors with important endocrine functions. Studies suggest that during growth, development, and aging, the relationship of muscle and fat with the skeleton possibly governs bone homeostasis and turnover. A better understanding of the endocrine function and the cellular and molecular mechanisms and pathways linking muscle or adipose tissues with bone anabolism and catabolism is a new avenue for novel pathways for anabolic drug discovery. These in turn will likely lead to more rational therapy toward increasingly prevalent disorders like osteoporosis. In this review, some of the recent works on the interaction of bone with muscle and fat are highlighted, and in so doing the role of parathyroid hormone (PTH), and PTH-related peptide (PTHrP) is surveyed.

  3. Circulating insulin-like growth factor binding protein-4 (IGFBP-4) is not regulated by parathyroid hormone and vitamin D in vivo: evidence from children with rickets.

    Science.gov (United States)

    Bereket, Abdullah; Cesur, Yaşar; Özkan, Behzat; Adal, Erdal; Turan, Serap; Onan, Sertaç Hanedan; Döneray, Hakan; Akçay, Teoman; Haklar, Goncagül

    2010-01-01

    Insulin-like growth factor binding protein-4 (IGFBP-4), inhibits IGF actions under a variety of experimental conditions. Parathyroid hormone (PTH), 1.25-hydroxy(OH)vitamin D, IGF-I, IGF-II and transforming growth factor (TGF)-b are the major regulators of IGFBP-4 production in vitro. However, little is known about the in vivo regulation of circulating IGFBP-4 in humans. We measured serum concentrations of calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), PTH, vitamin D, IGF-I, IGFBP-3, and IGFBP-4 in infants (n=22) with nutritional rickets before and after treatment of rickets with vitamin D (300 000 U single dose po). The mean±SD age of the patients was 1.3±1.6 years (range 0.2-3). Serum Ca and P increased, whereas ALP and PTH decreased after treatment (Ca from 6.6±1.4 to 9.5±1.6 mg/dL, P from 3.9±1.4 to 5.4±0.8 mg/dL, ALP from 2590±2630 to 1072±776 IU/mL and PTH from 407±248 to 27.4±20.8 ng/dL, respectively). Vitamin D levels were low (7.8±2.5 ng/mL) and increased after treatment (18.1±4.0 ng/mL, prickets since IGFBP-4 levels did not change after normalization of PTH with vitamin D treatment.

  4. Role of actinically provoked systemic elastolysis in polymyalgic vascular disease. A study based on serum fluorescence and haptoglobin

    Energy Technology Data Exchange (ETDEWEB)

    O' Brien, J.P.; Argyle, J.C.

    This study of cutaneous elastic tissue and serum fluorescence supports the hypothesis that widespread destruction and resorption of elastic tissue (elastolysis) occurs in the temporal arteritis/polymyalgia rheumatica syndrome. A systemic elastolysis of this nature may be provoked by actinic (radiant) damage to the exposed elastic tissues in the skin and superficial arteries, the archetype of such injury being seen in temporal arteritis. Scattered giant cells are the usual agents of elastolysis but tuberculoid (sarcoid) infiltrates often take over in the later stages. In acute polymyalgia, the phenomenon probably becomes diffuse and humoral. Elastolysis may be a direct pathogenetic link between polymyalgia and other vascular diseases such as idiopathic aneurysm and atherosclerosis.

  5. Effects of Thought Suppression on Provoked Men’s Alcohol-Related Physical Aggression in the Laboratory

    Science.gov (United States)

    Gallagher, Kathryn E.; Lisco, Claire G.; Parrott, Dominic J.; Giancola, Peter R.

    2013-01-01

    Objective This study utilized a comprehensive theoretical approach to provide the first data on the impact of thought suppression on provoked men’s alcohol-related aggression. Method A diverse community sample (58% African-American) of males between the ages of 21 and 35 (M = 25.25) were randomly assigned to one of two beverage conditions (i.e., alcohol, no-alcohol control). Following beverage consumption, participants were provoked via reception of electric shocks and a verbal insult from a fictitious male opponent. Participants’ physical aggression was measured using a shock-based aggression task. Results Results indicated that acute alcohol intoxication significantly increased physical aggression among lower, but not higher, thought suppressing men. Conclusions Results suggest that, under conditions of interpersonal provocation, alcohol intoxication produces a myopic focus on hostile thoughts and angry affect in lower, but not higher, suppression men. This pattern of results provides support for the durability of the alcohol myopia effect and highlights the need for continued examination of alcohol’s role in the disruption of protective factors for men’s aggression. It is important for research to continue to identify modifiable cognitive variables that influence self-regulation of behavior; however, it is imperative that researchers consider the extent to which these variables withstand alcohol’s effects. PMID:25337430

  6. Reductions in heel bone quality across gestation are attenuated in pregnant adolescents with higher prepregnancy weight and greater increases in PTH across gestation.

    Science.gov (United States)

    Whisner, Corrie M; Young, Bridget E; Witter, Frank R; Harris, Zena Leah; Queenan, Ruth A; Cooper, Elizabeth M; O'Brien, Kimberly O

    2014-09-01

    Few studies have examined the effect of maternal calcium intake and vitamin D status on bone health across gestation in pregnant adolescents. This study aimed to characterize maternal bone quality and determinants of bone-quality change across gestation in pregnant adolescents. Healthy pregnant adolescents (n = 156; aged 13 to 18 years) with singleton pregnancies and at 12 to 30 weeks gestation at enrollment were recruited from two urban maternity clinics in Baltimore, MD, and Rochester, NY, for this prospective longitudinal study. Maternal serum was collected at midgestation and at delivery for assessment of bone biomarkers and calcitropic hormones. Maternal bone quality (assessed by heel ultrasound) and sonographic fetal biometry were measured up to three times across pregnancy. Racially diverse teens (64.7% African American, 35.3% white) were followed from 21.0 (interquartile range [IQR] 17.3, 27.0) weeks of gestation until delivery at 40.0 (IQR 39.0, 40.7) weeks. Significant decreases in calcaneal speed of sound (SOS), broadband ultrasound attenuation (BUA), and quantitative ultrasound index (QUI) (-9.2 ± 16.1 m/s, -3.2 (-8.0, 2.1) dB/MHz and -5.3 ± 8.8, respectively) were evident across pregnancy. Multivariate analysis controlling for baseline measures and measurement intervals was used to identify independent predictors of normalized (per week) calcaneal bone loss. Weekly decreases in bone quality were not significantly associated with maternal calcium intake or 25(OH)D concentration. Greater weekly reductions in calcaneal bone quality were evident in teens with lower prepregnancy weight (BUA, p = 0.006 and QUI, p = 0.012) and among those with lower weekly increase in PTH (SOS, p = 0.046). Overall, significant decreases in calcaneal bone quality occurred across pregnancy in adolescents, but the magnitude of this loss was attenuated in those with greater prepregnancy weight and weekly increases in PTH. Further studies are needed to

  7. Leishmania major infection in humanized mice induces systemic infection and provokes a nonprotective human immune response.

    Directory of Open Access Journals (Sweden)

    Anja Kathrin Wege

    Full Text Available BACKGROUND: Leishmania (L. species are the causative agent of leishmaniasis. Due to the lack of efficient vaccine candidates, drug therapies are the only option to deal with cutaneous leishmaniasis. Unfortunately, chemotherapeutic interventions show high toxicity in addition to an increased risk of dissemination of drug-resistant parasites. An appropriate laboratory animal based model is still missing which allows testing of new drug strategies in the context of human immune cells in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Humanized mice were infected subcutaneously with stationary phase promastigote L. major into the footpad. The human immune response against the pathogen and the parasite host interactions were analyzed. In addition we proved the versatility of this new model to conduct drug research studies by the inclusion of orally given Miltefosine. We show that inflammatory human macrophages get infected with Leishmania parasites at the site of infection. Furthermore, a Leishmania-specific human-derived T cell response is initiated. However, the human immune system is not able to prevent systemic infection. Thus, we treated the mice with Miltefosine to reduce the parasitic load. Notably, this chemotherapy resulted in a reduction of the parasite load in distinct organs. Comparable to some Miltefosine treated patients, humanized mice developed severe side effects, which are not detectable in the classical murine model of experimental leishmaniasis. CONCLUSIONS/SIGNIFICANCE: This study describes for the first time L. major infection in humanized mice, characterizes the disease development, the induction of human adaptive and innate immune response including cytokine production and the efficiency of Miltefosine treatment in these animals. In summary, humanized mice might be beneficial for future preclinical chemotherapeutic studies in systemic (visceral leishmaniasis allowing the investigation of human immune response, side effects of the drug

  8. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups.

    Science.gov (United States)

    George, Jaya A; Micklesfield, L K; Norris, S A; Crowther, N J

    2014-06-01

    There are few data on the contribution of body composition to bone mineral density (BMD) in non-Caucasian populations. We therefore studied the contribution of body composition, and possible confounding of 25-hydroxyvitamin D and PTH, to BMD at various skeletal sites in black African (BA) and Asian Indian (AI) subjects. This was a cross-sectional study in Johannesburg, South Africa. BMD, body fat, and lean mass were measured using dual x-ray absorptiometry and abdominal fat distribution by ultrasound in 714 healthy subjects, aged 18-65 years. Whole-body (subtotal), hip, femoral neck, and lumbar spine (lumbar) BMD were significantly higher in BA than AI subjects (P < .001 for all). Whole-body lean mass positively associated with BMD at all sites in both ethnic groups (P < .001 for all) and partially explained the higher BMD in BA females compared with AI females. Whole-body fat mass correlated positively with lumbar BMD in BA (P = .001) and inversely with subtotal BMD in AI subjects (P < .0001). Visceral adiposity correlated inversely with subtotal BMD in the BA (P = .037) and with lumbar BMD in the AI group (P = .005). No association was found between serum 25-hydroxyvitamin D and BMD. PTH was inversely associated with hip BMD in the BA group (P = .01) and with subtotal (P = .002), hip (P = .001), and femoral BMD (P < .0001) in the AI group. Significant differences in whole-body and site-specific BMD between the BA and AI groups were observed, with lean mass the major contributor to BMD at all sites in both groups. The contribution of other components of body composition differed by site and ethnic group.

  9. Ictal brain SPET during seizures pharmacologically provoked with pentylenetetrazol: a new diagnostic procedure in drug-resistant epileptic patients

    Energy Technology Data Exchange (ETDEWEB)

    Calcagni, Maria Lucia; Giordano, Alessandro; Bruno, Isabella; Di Giuda, Daniela; De Rossi, Giuseppe; Troncone, Luigi [Department of Nuclear Medicine, Universita Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168 Roma (Italy); Parbonetti, Giovanni; Colicchio, Gabriella [Department of Neurosurgery, Universita Cattolica del Sacro Cuore, Roma (Italy)

    2002-10-01

    Functional brain imaging plays an important role in seizure focus localisation. However, truly ictal single-photon emission tomography (SPET) studies are not routinely performed owing to technical problems associated with the use of tracers and methodological and logistical difficulties. In this study we tried to resolve both of these issues by means of a new procedure: technetium-99m ethyl cysteinate dimer (ECD) brain SPET performed during seizures pharmacologically provoked with pentylenetetrazol, a well-known central and respiratory stimulant. We studied 33 drug-resistant epileptic patients. All patients underwent anamnestic evaluation, neuropsychological and psychodynamic assessment, magnetic resonance imaging, interictal and ictal video-EEG monitoring, and interictal and ictal SPET with {sup 99m}Tc-ECD. In order to obtain truly ictal SPET, 65 mg of pentylenetetrazol was injected every 2 minutes and, immediately the seizure began, 740 MBq of {sup 99m}Tc-ECD was injected. The scintigraphic findings were considered abnormal if a single area of hyperperfusion was present and corresponded to the site of a single area of hypoperfusion at interictal SPET: the ''hypo-hyperperfusion'' SPET pattern. In 27 of the 33 patients (82%), interictal-ictal SPET showed the hypo-hyperperfusion SPET pattern. Video-EEG showed a single epileptogenic zone in 21/33 patients (64%), and MRI showed anatomical lesions in 19/33 patients (57%). Twenty-two of the 27 patients with hypo-hyperperfusion SPET pattern underwent ablative or palliative surgery and were seizure-free at 3 years of follow-up. No adverse effects were noted during pharmacologically provoked seizure. It is concluded that ictal brain SPET performed during pharmacologically provoked seizure provides truly ictal images because {sup 99m}Tc-ECD is injected immediately upon seizure onset. Using this feasible procedure it is possible to localise the focus, to avoid the limitations due to the unpredictability

  10. [Type V phosphodiesterase inhibitor erection-provoking test with audio-visual sexual stimulation for the diagnosis of erectile dysfunction].

    Science.gov (United States)

    Zhu, Xuan-Wen; Guo, Jun-Ping; Zhang, Feng-Bin; Zhong, Da-Chuan; Fang, Jia-Jie; Li, Fang-Yin

    2008-05-01

    To evaluate the type V phosphodiesterase (PDE-5) inhibitor erection-provoking test with audio-visual sexual stimulation in the diagnosis of erectile dysfunction. A total of 853 out-patients diagnosed with erectile dysfunction were divided into an injury and a non-injury group. After scored on IIEF-5 questionnaires, all the patients received oral administration of PDE-5 inhibitors and, 30 minutes later, audio-visual sexual stimulation. The data on penile erection were recorded with Rigiscan Plus. The patients with mild, moderate and severe ED accounted for 18.8, 31.9 and 49.3% in the injury group, and 50.6, 39.8 and 9.6% in the non-injury group, with statistic differences between the two groups in the mild and severe parts (P erectile dysfunction.

  11. In vivo

    Science.gov (United States)

    Freudenblum, Julia; Iglesias, José A; Hermann, Martin; Walsen, Tanja; Wilfinger, Armin; Meyer, Dirk; Kimmel, Robin A

    2018-02-08

    The three-dimensional architecture of the pancreatic islet is integral to beta cell function, but the process of islet formation remains poorly understood due to the difficulties of imaging internal organs with cellular resolution. Within transparent zebrafish larvae, the developing pancreas is relatively superficial and thus amenable to live imaging approaches. We performed in vivo time-lapse and longitudinal imaging studies to follow islet development, visualizing both naturally occurring islet cells and cells arising with an accelerated timecourse following an induction approach. These studies revealed previously unappreciated fine dynamic protrusions projecting between neighboring and distant endocrine cells. Using pharmacological compound and toxin interference approaches, and single-cell analysis of morphology and cell dynamics, we determined that endocrine cell motility is regulated by phosphoinositide 3-kinase (PI3K) and G-protein-coupled receptor (GPCR) signaling. Linking cell dynamics to islet formation, perturbation of protrusion formation disrupted endocrine cell coalescence, and correlated with decreased islet cell differentiation. These studies identified novel cell behaviors contributing to islet morphogenesis, and suggest a model in which dynamic exploratory filopodia establish cell-cell contacts that subsequently promote cell clustering. © 2018. Published by The Company of Biologists Ltd.

  12. In Vivo

    Science.gov (United States)

    Lau, Melissa; Li, Jianli; Cline, Hollis T

    2017-01-01

    The neurovascular niche is a specialized microenvironment formed by the interactions between neural progenitor cells (NPCs) and the vasculature. While it is thought to regulate adult neurogenesis by signaling through vascular-derived soluble cues or contacted-mediated cues, less is known about the neurovascular niche during development. In Xenopus laevis tadpole brain, NPCs line the ventricle and extend radial processes tipped with endfeet to the vascularized pial surface. Using in vivo labeling and time-lapse imaging in tadpoles, we find that intracardial injection of fluorescent tracers rapidly labels Sox2/3-expressing NPCs and that vascular-circulating molecules are endocytosed by NPC endfeet. Confocal imaging indicates that about half of the endfeet appear to appose the vasculature, and time-lapse analysis of NPC proliferation and endfeet-vascular interactions suggest that proliferative activity does not correlate with stable vascular apposition. Together, these findings characterize the neurovascular niche in the developing brain and suggest that, while signaling to NPCs may occur through vascular-derived soluble cues, stable contact between NPC endfeet and the vasculature is not required for developmental neurogenesis.

  13. IN VIVO

    Science.gov (United States)

    Jamila, Nargis; Khan, Naeem; Khan, Amir Atlas; Khan, Imran; Khan, Sadiq Noor; Zakaria, Zainal Amiruddin; Khairuddean, Melati; Osman, Hasnah; Kim, Kyong Su

    2017-01-01

    Garcinia hombroniana , known as "manggis hutan" (jungle mangosteen) in Malaysia, is distributed in tropical Asia, Borneo, Thailand, Andaman, Nicobar Islands, Vietnam and India. In Malaysia, its ripened crimson sour fruit rind is used as a seasoning agent in curries and culinary dishes. Its roots and leaves decoction is used against skin infections and after child birth. This study aimed to evaluate in vivo hepatoprotective and in vitro cytotoxic activities of 20% methanolic ethyl acetate (MEA) G. hombroniana bark extract. In hepatoprotective activity, liver damage was induced by treating rats with 1.0 mL carbon tetrachloride (CCl 4 )/kg and MEA extract was administered at a dose of 50, 250 and 500 mg/kg 24 h before intoxication with CCl 4 . Cytotoxicity study was performed on MCF-7 (human breast cancer), DBTRG (human glioblastoma), PC-3 (human prostate cancer) and U2OS (human osteosarcoma) cell lines. 1 H, 13 C-NMR (nuclear magnetic resonance), and IR (infrared) spectral analyses were also conducted for MEA extract. In hepatoprotective activity evaluation, MEA extract at a higher dose level of 500 mg/kg showed significant (pIR spectra exhibited bands, signals and J (coupling constant) values representing aromatic/phenolic constituents. From the results, it could be concluded that MEA extract has potency to inhibit hepatotoxicity and MCF-7 and DBTRG cancer cell lines which might be due to the phenolic compounds depicted from NMR and IR spectra.

  14. Multigene expression in vivo: supremacy of large versus small terminators for T7 RNA polymerase.

    Science.gov (United States)

    Du, Liping; Villarreal, Seth; Forster, Anthony C

    2012-04-01

    Designing and building multigene constructs is commonplace in synthetic biology. Yet functional successes at first attempts are rare because the genetic parts are not fully modular. In order to improve the modularity of transcription, we previously showed that transcription termination in vitro by bacteriophage T7 RNA polymerase could be made more efficient by substituting the standard, single, TΦ large (class I) terminator with adjacent copies of the vesicular stomatitis virus (VSV) small (class II) terminator. However, in vitro termination at the downstream VSV terminator was less efficient than at the upstream VSV terminator, and multigene overexpression in vivo was complicated by unexpectedly inefficient VSV termination within Escherichia coli cells. Here, we address hypotheses raised in that study by showing that VSV or preproparathyroid hormone (PTH) small terminators spaced further apart can work independently (i.e., more efficiently) in vitro, and that VSV and PTH terminations are severely inhibited in vivo. Surprisingly, the difference between class II terminator function in vivo versus in vitro is not due to differences in plasmid supercoiling, as supercoiling had a minimal effect on termination in vitro. We therefore turned to TΦ terminators for "BioBrick" synthesis of a pentameric gene construct suitable for overexpression in vivo. This indeed enabled coordinated overexpression and copurification of five His-tagged proteins using the first construct attempted, indicating that this strategy is more modular than other strategies. An application of this multigene overexpression and protein copurification method is demonstrated by supplying five of the six E. coli translation factors required for reconstitution of translation from a single cell line via copurification, greatly simplifying the reconstitution. Copyright © 2011 Wiley Periodicals, Inc.

  15. It Takes Two: Sexual Communication Patterns and the Sexual and Relational Adjustment of Couples Coping With Provoked Vestibulodynia.

    Science.gov (United States)

    Rancourt, Kate M; Flynn, Michelle; Bergeron, Sophie; Rosen, Natalie O

    2017-03-01

    Provoked vestibulodynia (PVD) is a prevalent vulvovaginal pain condition that is associated with sexual and relational consequences for women and their partners. Greater perceived quality of sexual communication has been associated with women's lower pain during intercourse and with couples' better sexual and relational well-being. Whether couples' collaborative (eg, expressing feelings or problem solving) and negative (eg, withdrawing or criticizing) sexual communication patterns (SCPs) are differentially associated with couples' adjustment to PVD is unknown. To examine associations between collaborative and negative SCPs and women's pain and the sexual and relationship adjustment of women with PVD and their partners. Women diagnosed with PVD (N = 87) and their partners completed the Sexual Communication Patterns Questionnaire and measurements of pain (women only), sexual functioning, sexual satisfaction, sexual distress, and relationship satisfaction. (i) Numerical rating scale of pain during intercourse, (ii) Female Sexual Function Index and International Index of Erectile Function, (iii) Global Measure of Sexual Satisfaction, (iv) Female Sexual Distress Scale-Revised, and (v) Couple Satisfaction Index. When women reported greater collaborative SCP, they also reported higher sexual and relationship satisfaction. When women reported greater negative SCP, they reported less relationship satisfaction and had partners who reported greater sexual distress. When partners reported greater collaborative SCP, they also reported higher relationship satisfaction and had female partners who were less sexually distressed. When partners reported higher negative SCP, they also reported less relationship satisfaction. There were no associations between SCP and women's or partners' sexual functioning or women's pain. Collaborative SCP may benefit couples' sexual and relational well-being, whereas negative SCP may impede sexual and relational adjustment to PVD. Findings

  16. Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice.

    Science.gov (United States)

    Kawamura, Ai; Miyagawa, Shigeru; Fukushima, Satsuki; Kawamura, Takuji; Kashiyama, Noriyuki; Ito, Emiko; Watabe, Tadashi; Masuda, Shigeo; Toda, Koichi; Hatazawa, Jun; Morii, Eiichi; Sawa, Yoshiki

    2016-01-14

    Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection. Syngeneic mice and tacrolimus-injected immunosuppressed allogeneic mice formed teratocarcinomas with identical phenotypes, characteristic, and time courses, as assessed by imaging tools including (18)F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells, and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models.

  17. Responses to scenarios that may provoke acts of conflict and aggression among the general public: an exploratory study.

    Science.gov (United States)

    Lowe, Nathan C; May, David C

    2011-05-01

    The purpose of this article is to use empirical research and theory to investigate the context that may provoke individuals to engage in acts of conflict and aggression. A random sample of the general public from a midsouthern state was surveyed to explore this inquiry. Respondents were asked to indicate their level of reaction to a number of situations that often lead people to engage in conflict and/or aggression with other people. Several sociodemographic factors served as control variables in the study. The findings of the Pearson product-moment correlations suggest that respondents were more likely to report that they would respond more aggressively as the situations presented to them were perceived as being more physically threatening to them and/or their loved ones. Also, gender and age were the most significant predictors of engagement in acts of conflict and aggression in the multiple ordinal least squares regression analyses. Strengths and drawbacks of the study and direction of future research are also discussed.

  18. Randomized clinical trial of multimodal physiotherapy treatment compared to overnight lidocaine ointment in women with provoked vestibulodynia: Design and methods.

    Science.gov (United States)

    Morin, Mélanie; Dumoulin, Chantale; Bergeron, Sophie; Mayrand, Marie-Hélène; Khalifé, Samir; Waddell, Guy; Dubois, Marie-France

    2016-01-01

    Provoked vestibulodynia (PVD) is a highly prevalent and debilitating condition yet its management relies mainly on non-empirically validated interventions. Among the many causes of PVD, there is growing evidence that pelvic floor muscle (PFM) dysfunctions play an important role in its pathophysiology. Multimodal physiotherapy, which addresses these dysfunctions, is judged by experts to be highly effective and is recommended as a first-line treatment. However, the effectiveness of this promising intervention has been evaluated through only two small uncontrolled trials. The proposed bi-center, single-blind, parallel group, randomized controlled trial (RCT) aims to evaluate the efficacy of multimodal physiotherapy and compare it to a frequently used first-line treatment, topical overnight application of lidocaine, in women with PVD. A total of 212 women diagnosed with PVD according to a standardized protocol were eligible for the study and were randomly assigned to either multimodal physiotherapy or lidocaine treatment for 10weeks. The primary outcome measure is pain during intercourse (assessed with a numerical rating scale). Secondary measures include sexual function, pain quality, psychological factors (including pain catastrophizing, anxiety, depression and fear of pain), PFM morphology and function, and patients' global impression of change. Assessments are made at baseline, post-treatment and at the 6-month follow-up. This manuscript presents and discusses the rationale, design and methodology of the first RCT investigating physiotherapy in comparison to a commonly prescribed first-line treatment, overnight topical lidocaine, for women with PVD. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and related psychostimulants: mechanisms and mediators

    Science.gov (United States)

    Vanattou-Saïfoudine, N; McNamara, R; Harkin, A

    2012-01-01

    Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption. PMID:22671762

  20. Error-provoking conditions in the medication use process: the case of a government hospital in Ghana.

    Science.gov (United States)

    Koffuor, George Asumeng; Anto, Berko Panyin; Abaitey, Alfred K

    2012-03-01

    This study aimed to explore error-provoking factors prevalent in hospitals that have the potential to cause medication errors and to create awareness of the existence of medication errors. A total of 200 medical folders of in-patients in the health facility were randomly selected and assessed based on a checklist to record potential medication errors. The medication use process and working environment as well as drug packages and labels in the pharmacy were observed, and potential medication errors were documented. Of the 162 valid in-patient folders studied, 60.5% of the patients did not receive the actual quantity of drugs they were supposed to. Illegible handwriting on medication orders and prescription were common observations in the folders studied. Look-alike medicine packages and labeling were found. The working space in the dispensary was congested, and distractions (e.g., ringing personal telephones, being called from one task to attend to another, and unnecessary conversation between personnel) were common. This study has highlighted the vulnerability of the medication use process in the study site to medication errors. The findings may just be a tip of the iceberg; therefore, the researchers plan undertaking a multicenter study. In the absence of that, however, there is a need for a national policy on patient safety, and a national policy on incident reporting would help in determining the incidence, types, and potential causes of medication errors to improve patient safety.

  1. Reduced striatal activation during reward anticipation due to appetite-provoking cues in chronic schizophrenia: a fMRI study.

    Science.gov (United States)

    Grimm, O; Vollstädt-Klein, S; Krebs, L; Zink, M; Smolka, M N

    2012-02-01

    The occurrence of weight gain in schizophrenia (SZ) has profound clinical impact and interacts with antipsychotic medication, life style and disease severity. The functional neuroanatomy underlying altered nutritional behavior is unraveled, but dysregulated reward anticipation might be one of the involved neuronal mechanisms. The striatum, a core region of the reward network and salience attribution, was previously shown to regulate appetite perception and eating behavior. We studied patients suffering from chronic schizophrenia with a stable medication in comparison to age and gender matched healthy adults. Every subject had to undergo a 6h fasting period before a newly developed, appetite-provoking fMRI task was applied. Subjects saw visual stimuli of appetitive food items in a 3Tesla scanner. In healthy controls food images elicited stronger activation in the striatum compared to SZ patients. When adjusting a ROI-based striatal activation for medication and weight, the group difference remained still significant. This points an effect of illness independent of antipsychotic medication. These data underscore the involvement of the striatum into salience attribution, reward anticipation and the neuronal pathways leading to altered eating behavior and weight gain in schizophrenia. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Reproduction and mode of delivery in women with vaginismus or localised provoked vestibulodynia: a Swedish register-based study.

    Science.gov (United States)

    Möller, L; Josefsson, A; Bladh, M; Lilliecreutz, C; Sydsjö, G

    2015-02-01

    To compare sociodemographics, parity and mode of delivery between women diagnosed with vaginismus or localised provoked vestibulodynia (LPV) to women without a diagnosis before first pregnancy. Retrospective, population-based register study. Sweden. All women born in Sweden 1973-83 who gave birth for the first time or remained nulliparous during the years 2001-09. Nationally linked registries were used to identify the study population. Women diagnosed with vaginismus or LPV were compared to all other women. Odds ratios for parity and mode of delivery were calculated using multinominal regression analysis and logistic regression. Parity and mode of delivery. Women with vaginismus/LPV were more likely to be unmarried (P = 0.001), unemployed (P = 0.012), have a higher educational level (P vaginismus/LPV more often delivered by caesarean section (P vaginismus/LPV were more likely to suffer a perineal laceration (adjusted OR 1.87, 95% CI 1.56-2.25). Women with vaginismus/LPV are less likely to give birth and those that do are more likely to deliver by caesarean section and have a caesarean section based upon maternal request. Those women delivering vaginally are more likely to suffer perineal laceration. These findings point to the importance of not only addressing sexual function in women with vaginismus/LPV but reproductive function as well. © 2014 Royal College of Obstetricians and Gynaecologists.

  3. Exogenous interleukin-6, interleukin-13, and interferon-gamma provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice

    Directory of Open Access Journals (Sweden)

    Huang Szu-Wei

    2011-11-01

    Full Text Available Abstract Background Neonatal mice developed neurological disease and pulmonary dysfunction after an infection with a mouse-adapted human Enterovirus 71 (EV71 strain MP4. However, the hallmark of severe human EV71 infection, pulmonary edema (PE, was not evident. Methods To test whether EV71-induced PE required a proinflammatory cytokine response, exogenous pro-inflammatory cytokines were administered to EV71-infected mice during the late stage of infection. Results After intracranial infection of EV71/MP4, 7-day-old mice developed hind-limb paralysis, pulmonary dysfunction, and emphysema. A transient increase was observed in serum IL-6, IL-10, IL-13, and IFN-γ, but not noradrenaline. At day 3 post infection, treatment with IL-6, IL-13, and IFN-γ provoked mild PE and severe emphysema that were accompanied by pulmonary dysfunction in EV71-infected, but not herpes simplex virus-1 (HSV-1-infected control mice. Adult mice did not develop PE after an intracerebral microinjection of EV71 into the nucleus tractus solitarii (NTS. While viral antigen accumulated in the ventral medulla and the NTS of intracerebrally injected mice, neuronal loss was observed in the ventral medulla only. Conclusions Exogenous IL-6, IL-13, and IFN-γ treatment could induce mild PE and exacerbate pulmonary abnormality of EV71-infected mice. However, other factors such as over-activation of the sympathetic nervous system may also be required for the development of classic PE symptoms.

  4. Provoking, disturbing, hacking

    DEFF Research Database (Denmark)

    Groth, Sanne Krogh

    2013-01-01

    The article is a discussion of works by two Danish composers who both, with self-constructed instruments challenge computer music both as genre, the understanding and use of conventional technology and the relation to history. At first glance, the use of the homemade instruments appears as a comm...

  5. Provoking, disturbing, hacking

    DEFF Research Database (Denmark)

    Groth, Sanne Krogh

    Among the artists on the contemporary Danish scene of computer music and sound art the musician and composer Goodiepal (Gæoudjiparl van den Dobbelsteen or Parl Kristian Bjørn Vester) is by no comparison the most controversial and provocative. This statement is applicable whether we meet him as mu...

  6. Moderate Ingestion of Alcohol Is Associated With Acute Ethanol-Induced Suppression of Circulating CTX in a PTH-Independent Fashion*

    Science.gov (United States)

    Sripanyakorn, Supannee; Jugdaohsingh, Ravin; Mander, Adrian; Davidson, Sarah L.; Thompson, Richard P. H.; Powell, Jonathan J.

    2009-01-01

    The “J shape” curve linking the risk of poor bone health to alcohol intake is now well recognized from epidemiological studies. Ethanol and nonethanol components of alcoholic beverages could influence bone remodeling. However, in the absence of a solid underlying mechanism, the positive association between moderate alcoholic intake and BMD remains questionable because of confounding associated social factors. The objective of this work was to characterize the short-term effects of moderate alcohol consumption on circulating bone markers, especially those involved in bone resorption. Two sequential blood-sampling studies were undertaken in fasted healthy volunteers (age, 20–47 yr) over a 6-h period using beer of different alcohol levels (2% ethanol; p ≤ 0.01, RM-ANOVA), 0.6 liters of beer (6 h). The early effect on bone resorption is well described after the intake of energy, mediated by glucagon-like peptide-2, but the late effect of moderate alcohol ingestion is novel, seems to be ethanol specific, and is mediated in a non–calcitonin- and a non–PTH-dependent fashion, thus providing a mechanism for the positive association between moderate alcohol ingestion and BMD. PMID:19257829

  7. p21 loss blocks senescence following Apc loss and provokes tumourigenesis in the renal but not the intestinal epithelium

    NARCIS (Netherlands)

    Cole, A.M.; Ridgway, R.A.; Derkits, S.E.; Parry, L.; Barker, N.; Clevers, H.; Clarke, A.R.; Sansom, O.J.

    2010-01-01

    Senescence has been implicated as an important mechanism of tumour suppression in a number of human malignancies, including colorectal cancer (CRC). However, we still have a relatively poor understanding of how the underlying mutations that occur in cancer cause senescence and its relevance in vivo.

  8. Infusion of sodium bicarbonate in experimentally induced metabolic acidosis does not provoke cerebrospinal fluid (CSF) acidosis in calves.

    Science.gov (United States)

    Abeysekara, Saman; Zello, Gordon A; Lohmann, Katharina L; Alcorn, Jane; Hamilton, Don L; Naylor, Jonathan M

    2012-01-01

    In a crossover study, 5 calves were made acidotic by intermittent intravenous infusion of isotonic hydrochloric acid (HCl) over approximately 24 h. This was followed by rapid (4 h) or slow (24 h) correction of blood pH with isotonic sodium bicarbonate (NaHCO(3)) to determine if rapid correction of acidemia produced paradoxical cerebrospinal fluid (CSF) acidosis. Infusion of HCl produced a marked metabolic acidosis with respiratory compensation. Venous blood pH (mean ± S(x)) was 7.362 ± 0.021 and 7.116 ± 0.032, partial pressure of carbon dioxide (Pco(2), torr) 48.8 ± 1.3 and 34.8 ± 1.4, and bicarbonate (mmol/L), 27.2 ± 1.27 and 11 ± 0.96; CSF pH was 7.344 ± 0.031 and 7.240 ± 0.039, Pco(2) 42.8 ± 2.9 and 34.5 ± 1.4, and bicarbonate 23.5 ± 0.91 and 14.2 ± 1.09 for the period before the infusion of hydrochloric acid and immediately before the start of sodium bicarbonate correction, respectively. In calves treated with rapid infusion of sodium bicarbonate, correction of venous acidemia was significantly more rapid and increases in Pco(2) and bicarbonate in CSF were also more rapid. However, there was no significant difference in CSF pH. After 4 h of correction, CSF pH was 7.238 ± 0.040 and 7.256 ± 0.050, Pco(2) 44.4 ± 2.2 and 34.2 ± 2.1, and bicarbonate 17.8 ± 1.02 and 14.6 ± 1.4 for rapid and slow correction, respectively. Under the conditions of this experiment, rapid correction of acidemia did not provoke paradoxical CSF acidosis.

  9. Duodenal-jejunal bypass liner implantation provokes rapid weight loss and improved glycemic control, accompanied by elevated fasting ghrelin levels.

    Science.gov (United States)

    Koehestanie, Parweez; Dogan, Kemal; Berends, Frits; Janssen, Ignace; Wahab, Peter; Groenen, Marcel; Müller, Michael; de Wit, Nicole

    2014-03-01

    Endoscopic implantation of a duodenal-jejunal bypass liner (DJBL) is a novel bariatric technique to induce weight loss and remission of type 2 diabetes mellitus. Placement of the DJBL mimics the bypass component of the Roux-en-Y gastric bypass (RYGB) procedure. In this observational study, we evaluated improvement of glycemic control and weight loss in the course of the treatment (0 - 24 weeks after DJBL implantation) and analyzed accompanying gut hormone responses. 12 obese individuals with type 2 diabetes were selected for DJBL implantation. Body weight, fat mass, and fasting plasma levels of glucose, insulin, C-peptide, and glycated hemoglobin (HbA1c), were analyzed at 0, 1, 4 and 24 weeks post-implant. Fasting ghrelin, gastric inhibitory peptide (GIP), and glucagon-like peptide (GLP-1) were determined at 0, 1 and 4 weeks post-implant. Besides significant weight loss, fat mass, fasting insulin, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) index were also significantly decreased after DJBL implantation and a 42 % reduction was found in diabetes medication (P response in the first 4 weeks post-implant was significantly correlated with the fasting insulin and HOMA-IR response. Fasting ghrelin was found to be significantly elevated, in contrast to the decrease in ghrelin that is found after RYGB surgery. DJBL implantation provoked significant weight loss, a decrease in fat mass, and an early remission of type 2 diabetes, comparable to results seen after RYGB surgery. Gut hormone analyses revealed a potential role of fasting GLP-1 in early remission of type 2 diabetes. Interestingly, the DJBL-induced elevation of ghrelin contradicts the suggested role of reduced ghrelin levels after RYGB in improvement of glycemic control.

  10. Attenuation of microRNA-16 derepresses the cyclins D1, D2 and E1 to provoke cardiomyocyte hypertrophy

    Science.gov (United States)

    Huang, Shuai; Zou, Xiao; Zhu, Jie-Ning; Fu, Yong-Heng; Lin, Qiu-Xiong; Liang, Ye-You; Deng, Chun-Yu; Kuang, Su-Juan; Zhang, Meng-Zhen; Liao, Yu-Lin; Zheng, Xi-Long; Yu, Xi-Yong; Shan, Zhi-Xin

    2015-01-01

    Cyclins/retinoblastoma protein (pRb) pathway participates in cardiomyocyte hypertrophy. MicroRNAs (miRNAs), the endogenous small non-coding RNAs, were recognized to play significant roles in cardiac hypertrophy. But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy. This study investigates the potential role of microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy. An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC), and in a mouse with transverse aortic constriction (TAC) and in a mouse with subcutaneous injection of phenylephrine (PE) respectively. In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte and based on Ang-II-induced neonatal mouse ventricular cardiomyocyte respectively. We demonstrated that miR-16 expression was markedly decreased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats and mice. Overexpression of miR-16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes, and inhibition of miR-16 induced a hypertrophic phenotype in cardiomyocytes. Expressions of cyclins D1, D2 and E1, and the phosphorylated pRb were increased in hypertrophic myocardium and hypertrophic cardiomyocytes, but could be reversed by enforced expression of miR-16. Cyclins D1, D2 and E1, not pRb, were further validated to be modulated post-transcriptionally by miR-16. In addition, the signal transducer and activator of transcription-3 and c-Myc were activated during myocardial hypertrophy, and inhibitions of them prevented miR-16 attenuation. Therefore, attenuation of miR-16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2 and E1, and activating cyclin/Rb pathway, revealing that miR-16 might be a target to manage cardiac hypertrophy. PMID:25583328

  11. Memory-provoked rCBF-SPECT as a diagnostic tool in Alzheimer's disease?

    Energy Technology Data Exchange (ETDEWEB)

    Sundstroem, Torbjoern; Riklund, Katrine Aa. [Umeaa University, Umeaa University Hospital, Department of Radiation Sciences, Diagnostic Radiology, Umeaa (Sweden); Elgh, Eva; Naesman, Birgitta [Umeaa University, Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeaa (Sweden); Larsson, Anne [Umeaa University, Department of Radiation Sciences, Radiation Physics, Umeaa (Sweden); Nyberg, Lars [Umeaa University, Department of Psychology, Umeaa (Sweden)

    2006-01-01

    Alzheimer's disease (AD) is a primary degenerative disease that progressively affects all brain functions, with devastating consequences for the patient, the patient's family and society. Rest regional cerebral blood flow (rCBF) could have a strategic role in differentiating between AD patients and normal controls, but its use for this purpose has a low discriminatory capacity. The purpose of this study was to evaluate whether the diagnostic sensitivity of rCBF single-photon emission computed tomography (SPECT) could be increased by using an episodic memory task provocation, i.e. memory-provoked rCBF-SPECT (MP-SPECT). Eighteen persons (73.2{+-}4.8 years) with mild AD and 18 healthy elderly (69.4{+-}3.9 years) were included in the study. The subjects were injected with{sup 99m}Tc-hexamethylpropylene amine oxime (HMPAO) during memory provocation with faces and names, followed by an rCBF-SPECT study. The rCBF{sup 99m}Tc-HMPAO SPECT images were analysed using statistical parametric mapping (SPM2). Peaks with a false discovery rate corrected value of 0.05 were considered significant. On MP-SPECT, the AD group showed a significant rCBF reduction in the left parietal cortex in comparison with healthy elderly. At rest, no significant group differences were seen. Memory provocation increased the sensitivity of rCBF-SPECT for the detection of AD-related blood flow changes in the brain at the group level. Further studies are needed to evaluate MP-SPECT as a diagnostic tool at the individual level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might be sufficient in the clinical setting. (orig.)

  12. Pristanic acid provokes lipid, protein, and DNA oxidative damage and reduces the antioxidant defenses in cerebellum of young rats.

    Science.gov (United States)

    Busanello, Estela Natacha Brandt; Lobato, Vannessa Gonçalves Araujo; Zanatta, Ângela; Borges, Clarissa Günther; Tonin, Anelise Miotti; Viegas, Carolina Maso; Manfredini, Vanusa; Ribeiro, César Augusto João; Vargas, Carmen Regla; de Souza, Diogo Onofre Gomes; Wajner, Moacir

    2014-12-01

    Zellweger syndrome (ZS) and some peroxisomal diseases are severe inherited disorders mainly characterized by neurological symptoms and cerebellum abnormalities, whose pathogenesis is poorly understood. Biochemically, these diseases are mainly characterized by accumulation of pristanic acid (Prist) and other fatty acids in the brain and other tissues. In this work, we evaluated the in vitro influence of Prist on redox homeostasis by measuring lipid, protein, and DNA damage, as well as the antioxidant defenses and the activities of aconitase and α-ketoglutarate dehydrogenase in cerebellum of 30-day-old rats. The effect of Prist on DNA damage was also evaluated in blood of these animals. Some parameters were also evaluated in cerebellum from neonatal rats and in cerebellum neuronal cultures. Prist significantly increased malondialdehyde (MDA) levels and carbonyl formation and reduced sulfhydryl content and glutathione (GSH) concentrations in cerebellum of young rats. It also caused DNA strand damage in cerebellum and induced a high micronuclei frequency in blood. On the other hand, this fatty acid significantly reduced α-ketoglutarate dehydrogenase and aconitase activities in rat cerebellum. We also verified that Prist-induced increase of MDA levels was totally prevented by melatonin and attenuated by α-tocopherol but not by the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester, indicating the involvement of reactive oxygen species in this effect. Cerebellum from neonate rats also showed marked alterations of redox homeostasis, including an increase of MDA levels and a decrease of sulfhydryl content and GSH concentrations elicited by Prist. Finally, Prist provoked an increase of dichlorofluorescein (DCFH) oxidation in cerebellum-cultivated neurons. Our present data indicate that Prist compromises redox homeostasis in rat cerebellum and blood and inhibits critical enzymes of the citric acid cycle that are susceptible to free radical attack. The

  13. The secretory response of parathyroid hormone to acute hypocalcemia in vivo is independent of parathyroid glandular sodium/potassium-ATPase activity

    DEFF Research Database (Denmark)

    Martuseviciene, Giedre; Hofman-Bang, Jacob; Clausen, Torben

    2011-01-01

    The involvement of sodium/potassium-ATPase in regulating parathyroid hormone (PTH) secretion is inferred from in vitro studies. Recently, the α-klotho-dependent rapid recruitment of this ATPase to the parathyroid cell plasma membrane in response to low extracellular calcium ion was suggested......-treated parathyroid glands, indicating inhibition of the ATPase. As ouabain induced systemic hyperkalemia, the effect of high potassium on hormone secretion was also examined but was found to have no effect. Thus, inhibition of the parathyroid gland sodium/potassium-ATPase activity in vivo had no effect...

  14. TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice

    Science.gov (United States)

    Zhang, D.; Gaussin, V.; Taffet, G. E.; Belaguli, N. S.; Yamada, M.; Schwartz, R. J.; Michael, L. H.; Overbeek, P. A.; Schneider, M. D.

    2000-01-01

    The transforming-growth-factor-beta-activated kinase TAK1 is a member of the mitogen-activated protein kinase kinase kinase family, which couples extracellular stimuli to gene transcription. The in vivo function of TAK1 is not understood. Here, we investigated the potential involvement of TAK1 in cardiac hypertrophy. In adult mouse myocardium, TAK1 kinase activity was upregulated 7 days after aortic banding, a mechanical load that induces hypertrophy and expression of transforming growth factor beta. An activating mutation of TAK1 expressed in myocardium of transgenic mice was sufficient to produce p38 mitogen-activated protein kinase phosphorylation in vivo, cardiac hypertrophy, interstitial fibrosis, severe myocardial dysfunction, 'fetal' gene induction, apoptosis and early lethality. Thus, TAK1 activity is induced as a delayed response to mechanical stress, and can suffice to elicit myocardial hypertrophy and fulminant heart failure.

  15. Fecal sacs attract insects to the nest and provoke an activation of the immune system of nestlings.

    Science.gov (United States)

    Ibáñez-Álamo, Juan Diego; Ruiz-Raya, Francisco; Rodríguez, Laura; Soler, Manuel

    2016-01-01

    Nest sanitation is a widespread but rarely studied behavior in birds. The most common form of nest sanitation behavior, the removal of nestling feces, has focused the discussion about which selective pressures determine this behavior. The parasitism hypothesis, which states that nestling fecal sacs attract parasites that negatively affect breeding birds, was proposed 40 years ago and is frequently cited as a demonstrated fact. But, to our knowledge, there is no previous experimental test of this hypothesis. We carried out three different experiments to investigate the parasitism hypothesis. First, we used commercial McPhail traps to test for the potential attraction effect of nestling feces alone on flying insects. We found that traps with fecal sacs attracted significantly more flies (Order Diptera), but not ectoparasites, than the two control situations. Second, we used artificial blackbird (Turdus merula) nests to investigate the combined attraction effect of feces and nest materials on arthropods (not only flying insects). Flies, again, were the only group of arthropods significantly attracted by fecal sacs. We did not detect an effect on ectoparasites. Third, we used active blackbird nests to investigate the potential effect of nestling feces in ecto- and endoparasite loads in real nestlings. The presence of fecal sacs near blackbird nestlings did not increase the number of louse flies or chewing lice, and unexpectedly reduced the number of nests infested with mites. The endoparasite prevalence was also not affected. In contrast, feces provoked an activation of the immune system as the H/L ratio of nestlings living near excrements was significantly higher than those kept under the two control treatments. Surprisingly, our findings do not support the parasitism hypothesis, which suggests that parasites are not the main reason for fecal sac removal. In contrast, the attraction of flies to nestling feces, the elevation of the immune response of chicks, and the

  16. Visceral hypersensitivity is provoked by 2,4,6-trinitrobenzene sulfonic acid-induced ileitis in rats

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Shah

    2016-07-01

    Full Text Available Background and Aims: Crohn’s Disease (CD, a chronic Inflammatory Bowel Disease, can occur in any part of the gastrointestinal tract, but most frequently in the ileum. Visceral hypersensitivity contributes for development of chronic abdominal pain in this disease. Currently, the understanding of the mechanism underlying hypersensitivity of Crohn’s ileitis has been hindered by a lack of specific animal model. The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS-induced ileitis rats.Methods: Male Sprague-Dawley rats were anaesthetized and laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in 30% ethanol, n = 48, an equal volume of 30% Ethanol (n = 24 and Saline (n = 24, respectively. Visceral hypersensitivity was assessed by visceromotor responses (VMR to 20, 40, 60, 80 and 100 mmHg colorectal distension pressure (CRD at day 1, 3, 7, 14, 21 and 28. Immediately after CRD test, the rats were euthanized for collecting the terminal ileal segment for histopathological examinations and ELISA of myleoperoxidase and cytokines (TNF-α, IL-1β, IL-6, and dorsal root ganglia (T11 for determination of calcitonin gene-related peptide by immunohistochemistry, respectively. Results: Among all groups, TNBS-treatment showed transmural inflammation initially at 3 days, reached maximum at 7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05 VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive positive cells increased (P < 0.05 in dorsal root ganglia at day 7 to 21, which was persistently consistent with visceral hypersensitivity in TNBS-treated rats.Conclusions: TNBS injection into the ileum induced transmural ileitis including granuloma and visceral hypersensitivity. As this model mimics clinical manifestations of CD, it may provide a road map to probe the pathogenesis of gut inflammation and visceral

  17. Fucoidan effectively provokes the innate immunity of white shrimp Litopenaeus vannamei and its resistance against experimental Vibrio alginolyticus infection.

    Science.gov (United States)

    Kitikiew, Suwaree; Chen, Jiann-Chu; Putra, Dedi Fazriansyah; Lin, Yong-Chin; Yeh, Su-Tuen; Liou, Chyng-Hwa

    2013-01-01

    In this study, we examined the effect of fucoidan on the immune response of white shrimp Litopenaeus vannamei and its resistance against Vibrio alginolyticus infection. Fucoidan induced degranulation, caused changes in the cell morphology, and increased activation of prophenoloxidase (proPO) and the production of superoxide anions in vitro. Shrimp that received fucoidan via immersion at 100, 200, and 400 mg l(-1) after 3 h showed haemocyte proliferation and a higher mitotic index of haematopoietic tissue. In another experiment, the haemocyte count, phenoloxidase (PO) activity, and respiratory bursts (RBs) were examined after the shrimp had been fed diets containing fucoidan at 0 (control), 0.5, 1.0, and 2.0 g kg(-1) for 7-21 days. Results indicated that these parameters directly increased with time. The immune parameters of shrimp fed the 1.0 g kg(-1) diet were significantly higher than those of shrimp fed the 2.0 g kg(-1) diet after 14 and 21 days. Phagocytic activity and the clearance efficiency against V. alginolyticus were significantly higher in shrimp fed the 1.0 g kg(-1) diet compared to those of shrimp fed the 0, 0.5 and 2.0 g kg(-1) diets. In a separate experiment, shrimp that had been fed diets containing fucoidan for 21 days were challenged with V. alginolyticus at 10(6) colony-forming units shrimp(-1). Survival rates of shrimp fed the 1.0 and 2.0 g kg(-1) diets were significantly higher than those of shrimp fed the 0 and 0.5 g kg(-1) diets for 96-120 h. We concluded that fucoidan provokes innate immunity of shrimp as evidenced by haemocyte degranulation, proPO activation, and the mitotic index of haematopoietic tissue, and that dietary administration of fucoidan at 1.0 g kg(-1) enhanced the immune response of shrimp and their resistance against V. alginolyticus infection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Poliovirus infection and expression of the poliovirus protein 2B provoke the disassembly of the Golgi complex, the organelle target for the antipoliovirus drug Ro-090179.

    Science.gov (United States)

    Sandoval, I V; Carrasco, L

    1997-06-01

    Infection of Vero cells with poliovirus results in complete disassembly of the Golgi complex. Milestones of the process of disassembly are the release to the cytosol of the beta-COP bound to Golgi membranes, the disruption of the cis-Golgi network into fragments scattered throughout the cytoplasm, and the disassembly of the stacked cisternae by a process mediated by long tubular structures. Transient expression of the viral protein 2B in COS-7 cells also causes the disassembly of the Golgi complex by a process preceded by the accumulation of the protein in the Golgi area. Vero cells infected for 3 h show no recognizable Golgi complexes at the ultrastructural level and display an enormously swollen endoplasmic reticulum (ER) with extensive areas of its surface heavily coated. Ro-090179 (Ro), a flavonoid isolated from the herb Agastache rugosa, provokes the specific swelling and disruption of the Golgi complex and strongly inhibits poliovirus infection. Ro provokes the swelling and the disruption of the stacked cisternae and trans-Golgi elements without affecting the cis-most Golgi cisternae much. Moreover, Ro inhibits the fusion of the Golgi complex with the ER in cells treated with brefeldin A and provokes the accumulation of the intermediate compartment membrane protein p58 into ERD2-positive Golgi elements but has no effect on the anterograde transport involved in protein secretion. Our results indicate that the secretory pathway and specifically the Golgi complex are preferential targets of poliovirus.

  19. Maximizing PTH Anabolic Osteoporosis Therapy

    Science.gov (United States)

    2015-09-01

    Medical and Molecular Genetics, IUSM11 5. Center for Computational Biology and Bioinformatics, IUSM12 6. Department of Pediatrics , IUSM13 7. Herman B...Wells Center for Pediatric Research14 8. Cellular & Integrative Physiology15 9. Center for Translational Musculoskeletal Research, School of Health...in our colony at Indiana University Bioresearch Facility, Indiana University School of 156 Dentistry . Our local Institutional Animal Care and Use

  20. Lumbar internal disc derangement in patients with chronic low back pain: diagnostic value of the MR imaging findings as compared with provoked discography as the standard

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyeon Seon; Park, Jee Young; Lee, Sang Ho; Ahn, Yong [Wooridul spine Hospital, Seoul (Korea, Republic of); Lee, Sang Yeun [Puchon Daesung Hospital, Puchon (Korea, Republic of)

    2006-04-15

    The aim of this study was to evaluate the diagnostic value of the MR imaging findings with provoked discography used as the standard for painful lumbar disc derangement. Two hundred patients (412 discs), (age rang: 21-77 year), with chronic low back pain underwent MRI and provoked discography. We evaluated the MRI T2-WI findings such as disc degeneration, high-Intensity zones and endplate abnormalities. Subsequently, provocative discography was independently performed with using MR imaging, and a painful disc was defined when moderate to severe and concordant pain was provoked. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the MRI findings with using provoked discography as the standard. 400 discs showed abnormal findings such as disc degeneration, HIZ and endplate abnormalities on the T2-WI images. 12 discs showed normal finding. HIZ or endplate abnormalities were always combined with disc degeneration. The prevalence of each findings were disc degeneration (400 discs: 97.1%), HIZ (111 discs: 26.9%), type I endplate abnormalities (34 discs: 8.3%), type II endplate abnormalities (75 discs: 18.2%), the combined findings of HIZ and type I endplate abnormalities (2 discs: 0.5%) and the combined findings of HIZ and type II endplate abnormalities (7 discs: 1.7%). The disc degeneration showed high sensitivity (99.5%) and low specificity (5.0%), so only the NPV (91.7%) was significant, and not the PPV (47.8%). Each findings of HIZ (sensitivity, 36.5%, specificity, 81.4%; PPV, 63.18%; NPV, 59.5%), type I endplate abnormalities (11.0%, 94.1%, 61.8% and 54.8%, respectively), type II endplate abnormalities (19.8%, 83.2%, 50.7% and 54.3%, respectively), the combined findings of HIZ and type I endplate abnormalities (0.5%, 99.6%, 50.0% and 53.4%, respectively) and the combined findings of HIZ and type II endplate abnormalities (26.0%, 99.1%, 71.4% and 53.8%, respectively) show high specificity, but low

  1. Moderate ingestion of alcohol is associated with acute ethanol-induced suppression of circulating CTX in a PTH-independent fashion.

    Science.gov (United States)

    Sripanyakorn, Supannee; Jugdaohsingh, Ravin; Mander, Adrian; Davidson, Sarah L; Thompson, Richard Ph; Powell, Jonathan J

    2009-08-01

    intake of energy, mediated by glucagon-like peptide-2, but the late effect of moderate alcohol ingestion is novel, seems to be ethanol specific, and is mediated in a non-calcitonin- and a non-PTH-dependent fashion, thus providing a mechanism for the positive association between moderate alcohol ingestion and BMD.

  2. Definição de valores de corte para medida de PTH intraoperatório no tratamento cirúrgico do hiperparatiroidismo secundário e terciário

    Directory of Open Access Journals (Sweden)

    Monique Nakayama Ohe

    2013-08-01

    Full Text Available Avaliamos medida de PTH intraoperatório (IO-PTH no intuito de melhorar índices de sucesso no tratamento cirúrgico do hiperparatiroidismo associado à doença renal. MÉTODO: Oitenta e seis pacientes realizaram paratiroidectomia total com autoimplante em musculatura pré-esternal entre abril de 2000 e outubro de 2009 com 26,5 meses de seguimento em média, prospectivo. Foram divididos em dois grupos: hiperparatiroidismo secundário (HPS - pacientes em diálise e hiperparatiroidismo terciário (HPT - transplantados renais. Medido IO-PTH (Elecsys-PTH-Immunoassay/Roche na indução anestésica (IOPTH-0' e 20 minutos (IOPTH-20' após a retirada das paratireoides. RESULTADOS: 80,2% (69/86 do total de pacientes apresentaram queda de 80% ou mais do IOPTH-20' e todos se curaram. Em 11/86 (12,7% pacientes, foi observada queda entre 70-79%, sendo que dois (18,1% deles evoluíram com falha cirúrgica. 6/86 (6,9% pacientes apresentaram redução de IOPTH-20' menor do que 70%: dois foram curados; três apresentaram paratireoide supranumerária/ectópica que foi localizada e removida; um paciente evoluiu com persistência da doença após término da cirurgia com a retirada de quatro paratireoides. CONCLUSÃO: Queda do IOPTH-20' de 80% ou mais foi preditor de cura em todos os pacientes renais durante o período avaliado. Redução menor que 70% sugere paratireoide hiperfuncionante não reconhecida/supranumerária, sendo preditor de falha cirúrgica em 66.6%. A queda marginal de 70%-79% delega ao cirurgião experiente a decisão de continuar ou não o procedimento cirúrgico.

  3. The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver

    Directory of Open Access Journals (Sweden)

    Markus Heine

    2014-09-01

    Full Text Available Semiconductor quantum dots (QD and superparamagnetic iron oxide nanocrystals (SPIO have exceptional physical properties that are well suited for biomedical applications in vitro and in vivo. For future applications, the direct injection of nanocrystals for imaging and therapy represents an important entry route into the human body. Therefore, it is crucial to investigate biological responses of the body to nanocrystals to avoid harmful side effects. In recent years, we established a system to embed nanocrystals with a hydrophobic oleic acid shell either by lipid micelles or by the amphiphilic polymer poly(maleic anhydride-alt-1-octadecene (PMAOD. The goal of the current study is to investigate the uptake processes as well as pro-inflammatory responses in the liver after the injection of these encapsulated nanocrystals. By immunofluorescence and electron microscopy studies using wild type mice, we show that 30 min after injection polymer-coated nanocrystals are primarily taken up by liver sinusoidal endothelial cells. In contrast, by using wild type, Ldlr-/- as well as Apoe-/- mice we show that nanocrystals embedded within lipid micelles are internalized by Kupffer cells and, in a process that is dependent on the LDL receptor and apolipoprotein E, by hepatocytes. Gene expression analysis of pro-inflammatory markers such as tumor necrosis factor alpha (TNFα or chemokine (C-X-C motif ligand 10 (Cxcl10 indicated that 48 h after injection internalized nanocrystals did not provoke pro-inflammatory pathways. In conclusion, internalized nanocrystals at least in mouse liver cells, namely endothelial cells, Kupffer cells and hepatocytes are at least not acutely associated with potential adverse side effects, underlining their potential for biomedical applications.

  4. HRCT and bronchial asthma: visualization of the pathophysiologic changes of the pulmonary parenchyma after inhalation provocation; HRCT und Asthma bronchiale: Visualisierung pathophysiologischer Veraenderungen des Lungenparenchyms nach inhalativer Provokation

    Energy Technology Data Exchange (ETDEWEB)

    Schueller, G.; Neumann, K.; Helbich, T.; Herold, C.J. [Univ. Klinik fuer Radiodiagnostik, Abt. fuer konservative Faecher, Vienna (Austria); Riemer, H. [Univ. Klinik fuer Innere Medizin IV, Abt. fuer Pulmologie, Vienna (Austria); Backfrieder, W. [Allgemeines Krankenhaus, Vienna (Austria). Inst. fuer Biomedizinische Technik und Physik; Sertl, K. [Krankenhaus der Stadt Wien-Floridsdorf (Austria). Abt. fuer Innere Medizin; Pittner, B. [Vienna Univ. (Austria). Inst. fuer Medizinische Statistik

    2004-03-01

    alterations of the lung parenchyma subsequent to inhalation provocation. In healthy individuals, these parenchymal alterations were not documented by pulmonary function tests. (orig.) [German] Ziel: Bei Patienten mit leichtem intermittierenden Asthma bronchiale, aber mit Hyperreaktivitaet auch im freien Intervall, und bei gesunden Probanden sollen mithilfe der hoch aufloesenden Computertomographie (HRCT) roentgenmorphologische Veraenderungen des Lungenparenchyms vor sowie nach inhalativer Histaminprovokation und darauf folgender Lyse durch Salbutamol charakterisiert und mit Ergebnissen von Lungenfunktionstests (FEV{sub 1}, Blutgase) verglichen werden. Methoden: Fuenfzehn Asthmatiker mit bronchialer Hyperreaktivitaet mit FEV{sub 1}-Abfall>20% und PaO{sub 2}-Abfall>10 mmHg nach Provokation (PC20%+), zwoelf Asthmatiker mit FEV{sub 1}-Abfall<20% und PaO{sub 2}-Abfall>10 mmHg nach Provokation (PC20%-) sowie acht Probanden ohne bronchiale Hyperreaktivitaet wurden mit der spirometrisch kontrollierten HRCT bei hohen Fuellungsvolumina vor und nach inhalativer Bronchoprovokation sowie nach Broncholyse untersucht. Es wurden die gesamte und periphere Lungendichte sowie der strukturelle Anteil solider pulmonaler Strukturen bestimmt. Ergebnisse: In allen Gruppen fand sich nach Provokation eine signifikante Abnahme (p<0,0005), nach Broncholyse eine signifikante Zunahme (p<0,0002) der Lungendichte. Die Aenderungen solider Lungenanteile waren nach Provokation und Lyse nicht signifikant unterschiedlich (p>0,05). Bei den hyperreaktiven Patienten fanden sich signifikante PaO{sub 2}-Abnahmen nach Provokation sowie signifikante PaO{sub 2}-Steigerungen nach Lyse (p<0,05). In der Gruppe PC20%+ wurde nach Provokatio ein mittlerer FEV{sub 1}-Abfall von 27,8% beobachtet, in den anderen Gruppen war dieser <20%. Es wurden keine signifikanten Korrelationen zwischen radiologischen und funktionellen Lungentestergebnissen asthmatischer Patienten und Probanden beobachtet. Die bei gesunden Probanden mit der

  5. Interferon-gamma deficiency modifies the motor and co-morbid behavioral pathology and neurochemical changes provoked by the pesticide paraquat.

    Science.gov (United States)

    Litteljohn, D; Mangano, E; Shukla, N; Hayley, S

    2009-12-29

    In addition to nigrostriatal pathology and corresponding motor disturbances, Parkinson's disease (PD) is often characterized by co-morbid neuropsychiatric symptoms, most notably anxiety and depression. Separate lines of evidence indicate that inflammatory processes associated with microglial activation and cytokine release may be fundamental to the progression of both PD and its co-morbid psychiatric pathology. Accordingly, we assessed the contribution of the pro-inflammatory cytokine, interferon-gamma (IFN-gamma), to a range of PD-like pathology provoked by the ecologically relevant herbicide and dopamine (DA) toxin, paraquat. To this end, paraquat provoked overt motor impairment (reduced home-cage activity and impaired vertical climbing) and signs of anxiety-like behavior (reduced open field exploration) in wild-type but not IFN-gamma-deficient mice. Correspondingly, paraquat promoted somewhat divergent variations in neurochemical activity among wild-type and IFN-gamma null mice at brain sites important for both motor (striatum) and co-morbid affective pathologies (dorsal hippocampus, medial prefrontal cortex, and locus coeruleus). Specifically, the herbicide provoked a dosing regimen-dependent reduction in striatal DA levels that was prevented by IFN-gamma deficiency. In addition, the herbicide influenced serotonergic and noradrenergic activity within the dorsal hippocampus and medial prefrontal cortex; and elevated noradrenergic activity within the locus coeruleus. Although genetic ablation of IFN-gamma had relatively few effects on monoamine variations within the locus coeruleus and prefrontal cortex, loss of the pro-inflammatory cytokine did normalize the paraquat-induced noradrenergic alterations within the hippocampus. These findings further elucidate the functional implications of paraquat intoxication and suggest an important role for IFN-gamma in the striatal and motor pathology, as well as the co-morbid behavioral and hippocampal changes induced by

  6. Relationship between nongenital tender point tenderness and intravaginal muscle pain intensity: ratings in women with provoked vestibulodynia and implications for treatment.

    Science.gov (United States)

    Phillips, Nancy; Brown, Candace; Bachmann, Gloria; Wan, Jim; Wood, Ronald; Ulrich, Dagny; Bachour, Candi; Foster, David

    2016-12-01

    Vulvodynia is a chronic vulvar pain disorder and fibromyalgia is a chronic widespread musculoskeletal pain disorder, both of unknown etiology. Association of these conditions is well documented. Intravaginal algometer measurement of tenderness to pressure applied to the pelvic floor muscles helps define vulvodynia associated with musculoskeletal factors. Women with both vulvodynia and fibromyalgia might have increased pelvic muscle pain compared to women with vulvodynia alone, defining the possible link of these 2 conditions. We sought to: (1) correlate pain intensity during the nongenital tender point tenderness examination to pain intensity with the vaginal algometer in women with provoked vestibulodynia, and (2) determine whether subjects with provoked vestibulodynia and fibromyalgia had higher pain intensity scores with the vaginal algometer than those without fibromyalgia. In all, 92 subjects referred for vulvar pain were confirmed to have provoked vestibulodynia using the cotton swab test. A diagnosis of fibromyalgia was made if pain was present (numeric rating scale >1) in at least 11 sites of the 18-point nongenital tender point tenderness exam. Vaginal pain sensitivity was measured using an intravaginal pressure algometer, where 0.1, 0.3, and 0.5 kg/cm(2) forces were applied digitally in random assignment by force and location to the right and left iliococcygeus muscle regions and the posterior vaginal wall. Both tender point tenderness and algometer pain intensity were reported on a 0 (no pain) to 10 (worse pain) numeric rating scale. Correlations were computed between the composite pain intensity (total of rating scale from each pressure threshold at specified site) of nongenital and those of iliococcygeus regions and the posterior vaginal wall. Independent t tests were used to determine differences in iliococcygeus regions and the posterior vaginal algometer pain ratings and presence or absence of fibromyalgia. The significance level was at P palpation

  7. Does the solid-liquid crystal phase transition provoke the spin-state change in spin-crossover metallomesogens?

    Science.gov (United States)

    Seredyuk, M; Gaspar, A B; Ksenofontov, V; Galyametdinov, Y; Kusz, J; Gütlich, P

    2008-01-30

    crossover behavior at T(1/2) centered around 140 K. The thermal spin transition is accompanied by a pronounced change of color from dark red (LS) to orange (HS). The light-induced excited spin state trapping (LIESST) effect has been investigated in compounds C(6)-2, C(12)-2 and C(18)-2. The T(1/2)LIESST is 56 K (C(6)-2), 48 K (C(16)-2), and 56 K (C(18)-2). On the basis of differential scanning calorimetry, optical polarizing microscopy, and X-ray diffraction findings for C(18)-1, C(12)-2, and C(18)-2 at high temperature a smectic mesophase SX has been identified with layered structures similar to C(6)-1 and C(6)-2. The compounds [Fe(C(n)-trenH)](Cl)2 x sH2O (n = 16 (C(16)-3, s = 3.5, C(16)-4, s = 0.5, C(16)-5, s = 0), 18 (C(18)-3, s = 3.5, C(18)-4, s = 0.5, C(18)-5, s = 0), 20 (C(20)-3, s = 3.5, C(20)-4, s = 0.5, C(20)-5, s = 0)) and [Fe(C18-tren)](F)2 x sH2O (C(18)-6, s = 3.5, C(18)-7, s = 0) show a very particular spin-state change, while [Fe(C18-tren)](Br)2 x 3H2O (C(18)-8) together with [Fe(C18-tren)](I)2 (C(18)-9) are in the LS state (10-400 K) and present mesomorphic behavior like that observed for the complexes C(18)-1, C(12)-2, and C(18)-2. In compounds C(n)-3 50% of the Fe(II) ions undergo spin-state change at T(1/2) = 375 K induced by releasing water, and in partially dehydrated compounds (s = 0.5) the Cr-->SA phase transition occurs at 287 K (C(16)-4), 301 K (C(18)-4) and 330 K (C(20)-4). For the fully dehydrated materials C(n)-5 50% of the Fe(II) ions are in the HS state and show paramagnetic behavior between 10 and 400 K. In the partially dehydrated C(n)-4 the spin transition is induced by the change of the aggregate state of matter (solidliquid crystal). For compound C(18)-6 the full dehydration to C(18)-7 provokes the spin-state change of nearly 50% of the Fe(II) ions. The compounds C(n)-3 and C(18)-6 are dark purple in the LS state and become light purple-brown when 50% of the Fe(II) atoms are in the HS state.

  8. In vivo differentiation of human periodontal ligament cells leads to formation of dental hard tissue.

    Science.gov (United States)

    Wolf, M; Lossdörfer, S; Abuduwali, N; Meyer, R; Kebir, S; Götz, W; Jäger, A

    2013-11-01

    Following trauma, periodontal disease, or orthodontic tooth movement, residual periodontal ligament (PDL) cells at the defect site are considered mandatory for successful regeneration of the injured structures. Recent developments in tissue engineering focus, as one pillar, on the transplantation of PDL cells to support periodontal regeneration processes. Here, we examined the ability of osteogenically predifferentiated PDL cells to undergo further osteoblastic or cementoblastic differentiation and to mineralize their extracellular matrix when transplanted in an in vivo microenvironment. Using collagen sponges as carriers, osteogenically predifferentiated human PDL cells were transplanted subcutaneously into six immunocompromised CD-1® nude mice. Following explantation after 28 days, osteogenic and cementogenic marker protein expression was visualized immunohistochemically. After 28 days, transplanted PDL cells revealed both cellular, cytoplasmatic and extracellular immunoreactivity for the chosen markers alkaline phosphatase, osteopontin, PTH-receptor 1, and osteocalcin. Specific osteogenic and cementoblastic differentiation was demonstrated by RUNX2 and CEMP1 immunoreactivity. Early stages of mineralization were demonstrated by calcium and phosphate staining. Our results reinforce the previously published reports of PDL cell mineralization in vivo and further demonstrate the successful induction of specific osteogenic and cementogenic differentiation of transplanted human PDL cells in vivo. These findings reveal promising possibilities for supporting periodontal remodeling and regeneration processes with PDL cells being potential target cells with which to influence the process of orthodontically induced root resorption.

  9. Are P.T.H. plasma levels useful for the selection of patients with secondary hyperparathyroidism for preoperative MIBI ({sup 99m}Tc)/{sup 123}I dual-isotope scintigraphy?;La concentration plasmatique de PTH permet-elle de selectionner les patients atteints d'hyperparathyroidie secondaire pour beneficier de la scintigraphie double isotope MIBI ({sup 99m}Tc)/{sup 123}I preoperatoire?

    Energy Technology Data Exchange (ETDEWEB)

    Balogova, S.; Sauer, A.M.; Dudczak, J.; Pascal, O.; Kerrou, K.; Huchet, V.; Montravers, F.; Talbot, J.N. [Universite Pierre-et-Marie-Curie, Service de medecine nucleaire, hopital Tenon, 75 - Paris (France); Perie, S.; Lacau St-Guily, J. [Universite Pierre-et-Marie-Curie, ORL, hopital Tenon, 75 - Paris (France); Nataf, V. [Universite Pierre-et-Marie-Curie, hopital Tenon, Service de radiopharmacie, 75 - Paris (France); Balogova, S. [Faculte de medecine, universite Comenius, Bratislava (Slovakia)

    2010-07-15

    The utility of preoperative scintigraphy in case of secondary hyperparathyroidism is questioned by some authors. Obviously, an imaging modality that will detect all hyperplastic glands, including the ectopic ones, would be of interest in those patients at high risk for surgery. However, scintigraphy has a limited detection rate in some patients. We investigated whether one of the following parameters would identify a subgroup of patients in whom the detection rate would be optimal: age, gender, hemodialysis and duration since its onset, and plasma levels of parathyrin (P.T.H.). Methods: Retrospective series of 38 patients referred for preoperative parathyroid scintigraphy due to secondary hyperparathyroidism who then underwent para thyroidectomy. Scintigraphy was performed 20 min and then 3 h after injection of 8 MBq/kg of sestamibi ({sup 99m}Tc) with a previous ingestion of 0.1 MBq/kg iodine-123, 3 h before. Result: No significant correlation was observed between the number of glands detected on scintigraphy (and confirmed by postoperative histology) and plasma P.T.H. levels (r = -0.17). A weak positive correlation (r = +0.34) was noted in the group of six non-hemo dialysed patients. No significant relationship between this number of detected glands and a clinical parameter was observed. Conclusion: In our experience, these parameters do not permit to select, among patients with secondary hyperparathyroidism and scheduled for para thyroidectomy, those who will better benefit from parathyroid scintigraphy. (authors)

  10. Overexpression of Human and Fly Frataxins in Drosophila Provokes Deleterious Effects at Biochemical, Physiological and Developmental Levels

    Science.gov (United States)

    Soriano, Sirena; Botella, José A.; Schneuwly, Stephan; Martínez-Sebastián, María J.; Moltó, María D.

    2011-01-01

    Background Friedreich's ataxia (FA), the most frequent form of inherited ataxias in the Caucasian population, is caused by a reduced expression of frataxin, a highly conserved protein. Model organisms have contributed greatly in the efforts to decipher the function of frataxin; however, the precise function of this protein remains elusive. Overexpression studies are a useful approach to investigate the mechanistic actions of frataxin; however, the existing literature reports contradictory results. To further investigate the effect of frataxin overexpression, we analyzed the consequences of overexpressing human (FXN) and fly (FH) frataxins in Drosophila. Methodology/Principal Findings We obtained transgenic flies that overexpressed human or fly frataxins in a general pattern and in different tissues using the UAS-GAL4 system. For both frataxins, we observed deleterious effects at the biochemical, histological and behavioral levels. Oxidative stress is a relevant factor in the frataxin overexpression phenotypes. Systemic frataxin overexpression reduces Drosophila viability and impairs the normal embryonic development of muscle and the peripheral nervous system. A reduction in the level of aconitase activity and a decrease in the level of NDUF3 were also observed in the transgenic flies that overexpressed frataxin. Frataxin overexpression in the nervous system reduces life span, impairs locomotor ability and causes brain degeneration. Frataxin aggregation and a misfolding of this protein have been shown not to be the mechanism that is responsible for the phenotypes that have been observed. Nevertheless, the expression of human frataxin rescues the aconitase activity in the fh knockdown mutant. Conclusion/Significance Our results provide in vivo evidence of a functional equivalence for human and fly frataxins and indicate that the control of frataxin expression is important for treatments that aim to increase frataxin levels. PMID:21779322

  11. Theacrine, a purine alkaloid obtained from Camellia assamica var. kucha, attenuates restraint stress-provoked liver damage in mice.

    Science.gov (United States)

    Li, Wei-Xi; Li, Yi-Fang; Zhai, Yu-Jia; Chen, Wei-Min; Kurihara, Hiroshi; He, Rong-Rong

    2013-07-03

    Theacrine (1,3,7,9-tetramethyluric acid), a purine alkaloid, has proven to be beneficial in maintaining several brain functions and is being studied for potential medicinal uses in recent years. In this study, we isolated theacrine from Camellia assamica var. kucha and investigated its protective effects on liver damage induced by restraint stress in mice. Results showed that 18 h of restraint stress could induce liver damage, with an obvious increase in levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST). This finding was further confirmed by hepatic pathological examination, which showed inflammatory cell infiltration and focal necrosis of hepatocytes. However, oral administration of theacrine (10, 20, 30 mg/kg for 7 consecutive days) was found to decrease plasma ALT and AST levels, reduce hepatic mRNA levels of inflammatory mediators (IL-1β, TNF-α, IL-6, and IFN-γ), and reverse the histologic damages in stressed mice. Simultaneously, theacrine also significantly decreased the content of malondialdehyde and increased oxygen radical absorbance capacity (ORAC) level in the plasma and liver of stressed mice. These results suggested that the protective effects of theacrine on stress-induced liver damage might be correlated with its antioxidative activity. The antioxidative capacity of theacrine was further evaluated by in vitro ORAC and cellular antioxidant activity assay. The results suggested that the antioxidative capacity of theacrine was not due to the direct action on free radical clearance. Moreover, the elevated activities and gene expressions of superoxide dismutase, catalase, and glutathione peroxidase, as well as the reduced activity of xanthine oxidase by theacrine treatment in stressed mice suggested that the antioxidative activity might be due to the strengthening of the antioxidant system in vivo. On the basis of the above results, theacrine is possibly a good candidate for protecting against or treating lifestyle

  12. The in vivo biofilm

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Alhede, Maria; Alhede, Morten

    2013-01-01

    Bacteria can grow and proliferate either as single, independent cells or organized in aggregates commonly referred to as biofilms. When bacteria succeed in forming a biofilm within the human host, the infection often becomes very resistant to treatment and can develop into a chronic state. Biofilms...... have been studied for decades using various in vitro models, but it remains debatable whether such in vitro biofilms actually resemble in vivo biofilms in chronic infections. In vivo biofilms share several structural characteristics that differ from most in vitro biofilms. Additionally, the in vivo...... experimental time span and presence of host defenses differ from chronic infections and the chemical microenvironment of both in vivo and in vitro biofilms is seldom taken into account. In this review, we discuss why the current in vitro models of biofilms might be limited for describing infectious biofilms...

  13. Intranasal oxytocin reduces provoked symptoms in female patients with posttraumatic stress disorder despite exerting sympathomimetic and positive chronotropic effects in a randomized controlled trial.

    Science.gov (United States)

    Sack, M; Spieler, D; Wizelman, L; Epple, G; Stich, J; Zaba, M; Schmidt, U

    2017-02-17

    Posttraumatic stress disorder (PTSD) is a severe psychiatric disease accompanied by neuroendocrine changes such as adrenergic overdrive and hence an elevated cardiovascular morbidity. Current pharmacotherapeutic options for PTSD are less than suboptimal, necessitating the development of PTSD-specific drugs. Although the neuropeptide oxytocin has been repeatedly suggested to be effective in PTSD treatment, there are, to our knowledge, only three studies that have assessed its efficacy on the intensity of PTSD symptoms in PTSD patients - among them one symptom provocation study in male veterans. To evaluate for the first time how oxytocin influences the intensity of provoked PTSD symptoms and, furthermore, cardiac control in female PTSD patients, we assessed their psychic and cardiac response to trauma-script exposure with and without oxytocin pretreatment in a double-blind randomized placebo-controlled study. We used a within-subject design to study 35 female PTSD patients who received oxytocin and placebo in a 2-week interval. Furthermore, we performed a small pilot study to get an idea of the relation of the stress-modulated endogenous oxytocin levels and heart rate - we correlated oxytocin serum levels with the heart rate of 10 healthy individuals before and after exposure to the Trier Social Stress Test (TSST). Intranasal oxytocin treatment was followed by a reduction of provoked total PTSD symptoms, in particular of avoidance, and by an elevation in baseline and maximum heart rate together with a drop in the pre-ejection period, a marker for sympathetic cardiac control. Furthermore, we found a positive correlation between endogenous oxytocin levels and heart rate both before and after TSST challenge in healthy control subjects. This study provides the first evidence that oxytocin treatment reduces the intensity of provoked PTSD symptoms in female PTSD patients. The small size of both samples and the heterogeneity of the patient sample restrict the

  14. Massage treatment and medial tibial stress syndrome; A commentary to provoke thought about the way massage therapy is used in the treatment of MTSS.

    Science.gov (United States)

    Fogarty, Sarah

    2015-07-01

    As students and practitioners we are taught about the treatment and causative factors of medial shin pain, in particular' shin splints' or the more recent term; medial tibial stress syndrome (MTSS). During the years there have been many theories, conjecture and misunderstandings about the mechanisms of 'shin splints/medial tibial stress syndrome' however the ramifications of these mechanisms on how massage treatment is delivered have not being discussed. The evidence for the treatment of MTSS is largely clinical with little evidence of any treatment being proven to be effective in treating MTSS. The aim of this article is to present a summary of the mechanisms of MTSS and a commentary to provoke thought about the way massage therapy is used in the treatment of MTSS based on these mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Effect of variations in dietary Pi intake on intestinal Pi transporters (NaPi-IIb, PiT-1, and PiT-2) and phosphate-regulating factors (PTH, FGF-23, and MEPE).

    Science.gov (United States)

    Aniteli, Tatiana Martins; de Siqueira, Flávia Ramos; Dos Reis, Luciene Machado; Dominguez, Wagner Vasques; de Oliveira, Elizabeth Maria Costa; Castelucci, Patrícia; Moysés, Rosa Maria Affonso; Jorgetti, Vanda

    2018-01-25

    Hyperphosphatemia is a common condition in patients with chronic kidney disease (CKD) and can lead to bone disease, vascular calcification, and increased risks of cardiovascular disease and mortality. Inorganic phosphate (Pi) is absorbed in the intestine, an important step in the maintenance of homeostasis. In CKD, it is not clear to what extent Pi absorption is modulated by dietary Pi. Thus, we investigated 5/6 nephrectomized (Nx) Wistar rats to test whether acute variations in dietary Pi concentration over 2 days would alter hormones involved in Pi metabolism, expression of sodium-phosphate cotransporters, apoptosis, and the expression of matrix extracellular phosphoglycoprotein (MEPE) in different segments of the small intestine. The animals were divided into groups receiving different levels of dietary phosphate: low (Nx/LPi), normal (Nx/NPi), and high (Nx/HPi). Serum phosphate, fractional excretion of phosphate, intact serum fibroblast growth factor 23 (FGF-23), and parathyroid hormone (PTH) were significantly higher and ionized calcium was significantly lower in the Nx/HPi group than in the Nx/LPi group. The expression levels of NaPi-IIb and PiT-1/2 were increased in the total jejunum mucosa of the Nx/LPi group compared with the Nx/HPi group. Modification of Pi concentration in the diet affected the apoptosis of enterocytes, particularly with Pi overload. MEPE expression was higher in the Nx/HPi group than in the Nx/NPi. These data reveal the importance of early control of Pi in uremia to prevent an increase in serum PTH and FGF-23. Uremia may be a determining factor that explains the expressional modulation of the cotransporters in the small intestine segments.

  16. ex vivo DNA assembly

    Directory of Open Access Journals (Sweden)

    Adam B Fisher

    2013-10-01

    Full Text Available Even with decreasing DNA synthesis costs there remains a need for inexpensive, rapid and reliable methods for assembling synthetic DNA into larger constructs or combinatorial libraries. Advances in cloning techniques have resulted in powerful in vitro and in vivo assembly of DNA. However, monetary and time costs have limited these approaches. Here, we report an ex vivo DNA assembly method that uses cellular lysates derived from a commonly used laboratory strain of Escherichia coli for joining double-stranded DNA with short end homologies embedded within inexpensive primers. This method concurrently shortens the time and decreases costs associated with current DNA assembly methods.

  17. El nivel de la hormona paratiroidea (PTH y no el de fósforo sérico es predictor de la progresión de la enfermedad renal en pacientes mayores con enfermedad renal crónica avanzada

    Directory of Open Access Journals (Sweden)

    Néstor Gabriel Toapanta Gaibor

    2017-03-01

    Conclusiones: En nuestro grupo de pacientes de edad avanzada el deterioro de la función renal es muy lento, especialmente en los pacientes en estadio 5. La albuminuria y la PTH al inicio del seguimiento son factores pronósticos en la evolución de su función renal.

  18. Scaphoid kinematics in vivo

    NARCIS (Netherlands)

    Moojen, Thybout M.; Snel, Jeroen G.; Ritt, Marco J. P. F.; Venema, Henk W.; Kauer, John M. G.; Bos, Kurt E.

    2002-01-01

    The purpose of this study was to quantify 3-dimensional (3-D) in vivo scaphoid kinematics during flexion-extension motion (FEM) and radial-ulnar deviation (RUD) of the hand. The right wrists of 11 healthy volunteers were imaged by spiral computed tomography during RUD and 5 of those wrists also

  19. Can an exercise bicycle be safely used in the epilepsy monitoring unit?: An exercise method to provoke epileptic seizures and the related safety issues.

    Science.gov (United States)

    Kim, Jiyoung; Jung, Dae Soo; Hwang, Kyoung Jin; Seo, Ji-Hye; Na, Geon-Youb; Hong, Seung Bong; Joo, Eun Yeon; Seo, Dae-Won

    2015-05-01

    Long-term videoelectroencephalogram (video-EEG) monitoring is performed to diagnose an epileptic seizure and to investigate the differential diagnosis of paroxysmal events. To provoke an epileptic seizure, an exercise method is performed in some cases during long-term video-EEG recording in the epilepsy monitoring unit (EMU). The purpose of this study was two-fold: to assess the frequency and severity of adverse events associated with the use of an exercise bicycle and to find a way to safely use it in the EMU. A retrospective survey was performed on all epileptic seizure videos recorded in the EMU from January 2012 to December 2013. Three hundred and fifty patients were included in this study. Eleven patients experienced an epileptic seizure while riding the exercise bicycle in the EMU. One patient's foot got stuck between the cycling pedal and its strap, and one patient fell off the exercise bicycle during the epileptic seizure. However, there were no serious adverse events over two years. Epileptic seizures were not frequent while riding the exercise bicycle, and serious injuries did not occur. But, there is a need to improve the safety in the EMU to control the potentially dangerous factors associated with the use of the exercise bicycle and to continuously monitor the patients with help from the staff. Copyright © 2015. Published by Elsevier Inc.

  20. Talking About Sex When Sex Is Painful: Dyadic Sexual Communication Is Associated With Women's Pain, and Couples' Sexual and Psychological Outcomes in Provoked Vestibulodynia.

    Science.gov (United States)

    Rancourt, Kate M; Rosen, Natalie O; Bergeron, Sophie; Nealis, Logan J

    2016-11-01

    Provoked vestibulodynia (PVD) is a recurrent vulvovaginal pain condition associated with psychological and sexual consequences for affected women and their partners, including lower quality of dyadic sexual communication compared to pain-free couples. Although greater sexual communication is associated with positive sexual and relational outcomes for both pain-free couples and couples experiencing painful sex, little is known about its role in women's pain and psychological outcomes, especially in a relational context. The present study examined associations between dyadic sexual communication and pain, sexual satisfaction, sexual functioning, and depressive symptoms in a sample of 107 couples in which the woman was diagnosed with PVD via a standardized gynecological assessment. Women completed a measure of pain intensity, and both members of the couple completed measures of their dyadic sexual communication, sexual satisfaction, sexual functioning, and depressive symptoms. Analyses were guided by the actor-partner interdependence model. Women and partners' own perceptions of greater dyadic sexual communication were associated with their own greater sexual satisfaction and sexual functioning, and lower depressive symptoms. Partners' perceptions of greater dyadic sexual communication were also associated with women's lower pain and greater sexual satisfaction. Results point to the importance of dyadic coping conceptualizations for both individual and interpersonal outcomes in PVD. Dyadic sexual communication may be a key treatment target for interventions aimed at improving the pain and psychological and sexual impairments of women with PVD and their partners.

  1. To say or not to say: Dyadic ambivalence over emotional expression and its associations with pain, sexuality, and distress in couples coping with provoked vestibulodynia.

    Science.gov (United States)

    Awada, Nayla; Bergeron, Sophie; Steben, Marc; Hainault, Victoria-Ann; McDuff, Pierre

    2014-05-01

    Provoked vestibulodynia (PVD) is a highly prevalent and taxing female genital pain condition. Despite the intimate nature of this pain and the fact that affective factors such as anxiety have been shown to modulate its manifestations, no study has yet explored the emotional regulation of couples in which the woman suffers from PVD. Ambivalence over emotional expression (AEE) is an emotional regulation variable that quantifies the extent to which a person is comfortable with the way she or he expresses emotions. We examined whether the dyadic AEE of couples in which the woman suffers from PVD was differentially associated with women's pain and couples' psychological, sexual, and relational functioning. Couples (N = 254), in which the woman suffered from PVD, completed the AEE questionnaire. A couple typology of dyadic AEE was created. Dependent measures for both members of the couple were the global measure of sexual satisfaction scale, the Beck depression inventory II, and the revised dyadic adjustment scale. The female sexual function index and the sexual history form were used to assess the sexual function of women and men, respectively. Women also completed the pain rating index of the McGill pain questionnaire. Couples, in which both partners were considered low on AEE, had the highest scores on sexual satisfaction (P = 0.02) and function (P sexual, and relational outcomes. Results indicate that emotional regulation may be important to consider in the assessment and treatment of couples coping with PVD. © 2014 International Society for Sexual Medicine.

  2. Perceiving the target's state or state provoked by the target? An analysis of the descriptive and evaluative knowledge in person perception.

    Science.gov (United States)

    Mignon, Astrid; Mollaret, Patrick

    2012-12-01

    In line with the theory of traits as generalized affordances, the present article argues that target's states (TSs) and states provoked by a target (other's states (OSs) towards target) are two components of the meaning of traits referring, respectively, to a descriptive and to an evaluative knowledge of people. A preliminary study confirmed that TS and OS were equally representative of a trait. Two studies were designed to study the effects of practising the use of traits as either TS or OS categories (an induction procedure) on a subsequent person perception task, requiring participants to rate photographed targets on a series of traits. Results show that both the differentiation between targets and evaluative consistency of ratings were enhanced under the OS condition compared to TS and control (with no practice of traits) conditions. Importantly, Study 2 tends to show that the effects of the induction procedure are not limited to the practised traits but also generalize to unpractised traits. Implications of these findings for social perception research are discussed. ©2011 The British Psychological Society.

  3. Rhizobacterial salicylate production provokes headaches

    NARCIS (Netherlands)

    Bakker, Peter|info:eu-repo/dai/nl/074744623; Ran, L.X.; Mercado-Blanco, J.

    2014-01-01

    Background Salicylic acid (SA) is produced in significant amounts by certain plant growth promoting rhizosphere bacteria, and some of these rhizobacteria have the ability to induce systemic resistance against diseases in plants. Exogenous application of SA to plants has long been known to lead to

  4. In-vivo

    Science.gov (United States)

    Zhu, Timothy C; Kim, Michele M; Liang, Xing; Finlay, Jarod C; Busch, Theresa M

    2015-02-01

    Dosimetry of singlet oxygen ( 1 O 2 ) is of particular interest because it is the major cytotoxic agent causing biological effects for type-II photosensitizers during photodynamic therapy (PDT). An in-vivo model to determine the singlet oxygen threshold dose, [ 1 O 2 ] rx,sh , for PDT was developed. An in-vivo radiation-induced fibrosarcoma (RIF) tumor mouse model was used to correlate the radius of necrosis to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include five photosensitizer-specific photochemical parameters along with [ 1 O 2 ] rx,sh . Photosensitizer-specific model parameters were determined for benzoporphyrin derivative monoacid ring A (BPD) and compared with two other type-II photosensitizers, Photofrin ® and m-tetrahydroxyphenylchlorin (mTHPC) from the literature. The mean values (standard deviation) of the in-vivo [ 1 O 2 ] rx,sh are approximately 0.56 (0.26) and 0.72 (0.21) mM (or 3.6×10 7 and 4.6×10 7 singlet oxygen per cell to reduce the cell survival to 1/e) for Photofrin ® and BPD, respectively, assuming that the fraction of generated singlet oxygen that interacts with the cell is 1. While the values for the photochemical parameters (ξ, σ, g , β) used for BPD were preliminary and may need further refinement, there is reasonable confidence for the values of the singlet oxygen threshold doses. In comparison, the [ 1 O 2 ] rx,sh value derived from in-vivo mouse study was reported to be 0.4 mM for mTHPC-PDT. However, the singlet oxygen required per cell is reported to be 9×10 8 per cell per 1/ e fractional kill in an in-vitro mTHPC-PDT study on a rat prostate cancer cell line (MLL cells) and is reported to be 7.9 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC-PDT. A theoretical analysis is provided to relate the number of in-vitro singlet oxygen required per cell to reach cell killing of 1/ e to in-vivo singlet

  5. Human interleukin 1. beta. (IL-1. beta. ), a more powerful inducer of bone demineralization than interleukin 1. cap alpha. IL-1. cap alpha. ), parathyroid hormone (PTH) or prostaglandin E/sub 2/ (PGE/sub 2/) in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Chin, R.C.; Hodges, Y.C.; Allison, A.C.

    1986-03-01

    Effects of human IL-1..cap alpha.. and IL-1..beta.., prepared by recombinant DNA technology on cultures of rat fetal long bones, prelabelled with /sup 45/Ca were studied. IL-1..beta.. was found to be the most powerful inducer of bone calcium loss so far known. Maximal activity (2.5 times the control rate of calcium loss) was induced by IL-1..beta.. at concentrations between 1 x 10/sup -10/ M to 6 x 10/sup -12/ M. With IL-1..cap alpha.. maximal activity (1.5 times the control rate of calcium loss) was obtained at 6 x 10/sup -10/ M. With bovine PTH (1-34) maximal activity (1.8 times the control rate of calcium loss) was obtained at 1 x 10/sup -8/ M. With PGE/sub 2/ maximal activity (1.6 times the control rate of calcium loss) was obtained at 1 x 10/sup -7/ M. The calcium loss induced by IL-1..beta.. was inhibited in the presence of 1 x 10/sup -7/ M indomethacin, 5 x 10/sup -5/ M naproxen or ketorolac, or 5 x 10/sup -6/ M cyclohexamide. These findings suggest that protein synthesis and prostaglandin formation are required to mediate bone demineralization induced by IL-1..beta...

  6. Active and Passive Components of Pelvic Floor Muscle Tone in Women with Provoked Vestibulodynia: A Perspective Based on a Review of the Literature.

    Science.gov (United States)

    Thibault-Gagnon, Stéphanie; Morin, Mélanie

    2015-11-01

    Pelvic floor muscle (PFM) dysfunctions, especially elevated tone or tension, are suggested to play an important role in the pathophysiology of provoked vestibulodynia (PVD). However, the involvement of the PFMs remains misunderstood as the assessment of muscle tone is complex and requires a thorough understanding of muscle physiology in relation to the characteristics and limitations of current PFM assessment tools. The aim of this review was to describe the structures and mechanisms involved in muscle tone in normally innervated muscle, and to discuss and relate these concepts to the PFM findings in women with PVD. A narrative overview of the literature retrieved from searches of electronic databases and hand searches. Muscle tone in a normally innervated muscle comprises both active (contractile) and passive (viscoelastic) components. Current methods for evaluating PFM tone such as digital palpation, ultrasound imaging, pressure perineometry, dynamometry, and electromyography may evaluate different components. Research findings suggestive of PFM hypertonicity in women with PVD include elevated general PFM tone, changes in viscoelastic properties, and at least in some women, abnormal increases in electrogenic activity. There is a growing body of evidence to support the involvement of PFM hypertonicity in the pathophysiology of PVD. Limitations of the instruments as well as their properties should be considered when evaluating PFM tone in order to obtain better insight into which component of PFM tone is assessed. Future research is required for further investigating the underlying mechanisms of PFM hypertonicity, and studying the specific effects of physiotherapeutic interventions on PFM tone in women with PVD. © 2015 International Society for Sexual Medicine.

  7. Can Fear, Pain, and Muscle Tension Discriminate Vaginismus from Dyspareunia/Provoked Vestibulodynia? Implications for the New DSM-5 Diagnosis of Genito-Pelvic Pain/Penetration Disorder.

    Science.gov (United States)

    Lahaie, Marie-Andrée; Amsel, Rhonda; Khalifé, Samir; Boyer, Stephanie; Faaborg-Andersen, Marie; Binik, Yitzchak M

    2015-08-01

    Fear has been suggested as the crucial diagnostic variable that may distinguish vaginismus from dyspareunia. Unfortunately, this has not been systematically investigated. The primary purpose of this study, therefore, was to investigate whether fear as evaluated by subjective, behavioral, and psychophysiological measures could differentiate women with vaginismus from those with dyspareunia/provoked vestibulodynia (PVD) and controls. A second aim was to re-examine whether genital pain and pelvic floor muscle tension differed between vaginismus and dyspareunia/PVD sufferers. Fifty women with vaginismus, 50 women with dyspareunia/PVD, and 43 controls participated in an experimental session comprising a structured interview, pain sensitivity testing, a filmed gynecological examination, and several self-report measures. Results demonstrated that fear and vaginal muscle tension were significantly greater in the vaginismus group as compared to the dyspareunia/PVD and no-pain control groups. Moreover, behavioral measures of fear and vaginal muscle tension were found to discriminate the vaginismus group from the dyspareunia/PVD and no-pain control groups. Genital pain did not differ significantly between the vaginismus and dyspareunia/PVD groups; however, genital pain was found to discriminate both clinical groups from controls. Despite significant statistical differences on fear and vaginal muscle tension variables between women suffering from vaginismus and dyspareunia/PVD, a large overlap was observed between these conditions. These findings may explain the great difficulty health professionals experience in attempting to reliably differentiate vaginismus from dyspareunia/PVD. The implications of these data for the new DSM-5 diagnosis of Genito-Pelvic Pain/Penetration Disorder are discussed.

  8. Dysregulation of the Bmi-1/p16Ink4a pathway provokes an aging-associated decline of submandibular gland function

    Science.gov (United States)

    Yamakoshi, Kimi; Katano, Satoshi; Iida, Mayu; Kimura, Hiromi; Okuma, Atsushi; Ikemoto-Uezumi, Madoka; Ohtani, Naoko; Hara, Eiji; Maruyama, Mitsuo

    2015-01-01

    Bmi-1 prevents stem cell aging, at least partly, by blocking expression of the cyclin-dependent kinase inhibitor p16Ink4a. Therefore, dysregulation of the Bmi-1/p16Ink4a pathway is considered key to the loss of tissue homeostasis and development of associated degenerative diseases during aging. However, because Bmi-1 knockout (KO) mice die within 20 weeks after birth, it is difficult to determine exactly where and when dysregulation of the Bmi-1/p16Ink4a pathway occurs during aging in vivo. Using real-time in vivo imaging of p16Ink4a expression in Bmi-1-KO mice, we uncovered a novel function of the Bmi-1/p16Ink4a pathway in controlling homeostasis of the submandibular glands (SMGs), which secrete saliva into the oral cavity. This pathway is dysregulated during aging in vivo, leading to induction of p16Ink4a expression and subsequent declined SMG function. These findings will advance our understanding of the molecular mechanisms underlying the aging-related decline of SMG function and associated salivary gland hypofunction, which is particularly problematic among the elderly. PMID:25832744

  9. Sexual and relationship intimacy among women with provoked vestibulodynia and their partners: associations with sexual satisfaction, sexual function, and pain self-efficacy.

    Science.gov (United States)

    Bois, Katy; Bergeron, Sophie; Rosen, Natalie O; McDuff, Pierre; Grégoire, Catherine

    2013-08-01

    Provoked vestibulodynia (PVD) is the most frequent subtype of vulvodynia. Women report negative consequences of PVD on their sexual and romantic relationships. Researchers have recently highlighted the importance of examining interpersonal factors such as intimacy, and of including both women and their partners in study designs. The aim of this study was to investigate sexual and relationship intimacy as defined by the Interpersonal Process Model of Intimacy and their associations with sexual satisfaction, sexual function, pain self-efficacy, and pain intensity among women with PVD and their partners. Ninety-one heterosexual women (M age = 27.38, SD = 6.04) diagnosed with PVD and their partners (M age = 29.37, SD = 7.79) completed measures of sexual and relationship intimacy, sexual satisfaction, sexual function, pain self-efficacy, and pain intensity. Dependent measures were the (i) Global Measure of Sexual Satisfaction Scale; (ii) Female Sexual Function Index; (iii) Painful Intercourse Self-Efficacy Scale; and (iv) visual analog scale of pain intensity during intercourse. After controlling for women's age, women's greater sexual intimacy (β = 0.49, P satisfaction and higher pain self-efficacy (β = 0.39, P = 0.001), beyond the effects of partners' sexual intimacy. Also, women's greater sexual intimacy (β = 0.24, P = 0.05) and women's greater relationship intimacy (β = 0.54, P = 0.003) were associated with greater women's sexual function, beyond the effects of partners' sexual and relationship intimacy. Women's self-reported sexual and relationship intimacy in the couple relationship may promote higher sexual satisfaction, sexual function, and pain self-efficacy, as well as possibly foster greater sexual well-being among women with PVD. The authors discuss implications for the inclusion of emotional and interpersonal aspects of the couple's dynamic in clinical interventions and future research in PVD. © 2013

  10. A comparison of cognitive-behavioral couple therapy and lidocaine in the treatment of provoked vestibulodynia: study protocol for a randomized clinical trial.

    Science.gov (United States)

    Corsini-Munt, Serena; Bergeron, Sophie; Rosen, Natalie O; Steben, Marc; Mayrand, Marie-Hélène; Delisle, Isabelle; McDuff, Pierre; Aerts, Leen; Santerre-Baillargeon, Marie

    2014-12-23

    Provoked vestibulodynia (PVD), a frequent form of chronic genital pain, is associated with decreased sexual function for afflicted women, as well as impoverished sexual satisfaction for women and their partners. Pain and sexuality outcomes for couples with PVD are influenced by interpersonal factors, such as pain catastrophizing, partner responses to pain, ambivalence over emotional expression, attachment style and perceived relationship and sexual intimacy. Despite recommendations in the literature to include the partner in cognitive-behavioral therapy targeted at improving pain and sexuality outcomes, no randomized clinical trial has tested the efficacy of this type of intervention and compared it to a first-line medical intervention. This bi-center, randomized clinical trial is designed to examine the efficacy of cognitive-behavioral couple therapy compared to topical lidocaine. It is conducted across two Canadian university-hospital centers. Eligible women diagnosed with PVD and their partners are randomized to one of the two interventions. Evaluations are conducted using structured interviews and validated self-report measures at three time points: Pre-treatment (T1: prior to randomization), post-treatment (T2), and 6-month follow-up (T3). The primary outcome is the change in reported pain during intercourse between T1 and T2. Secondary outcomes focus on whether there are significant differences between the two treatments at T2 and T3 on (a) the multidimensional aspects of women's pain and (b) women and partners' sexuality (sexual function and satisfaction), psychological adjustment (anxiety, depression, catastrophizing, self-efficacy, and quality of life), relationship factors (partner responses and dyadic adjustment) and self-reported improvement and treatment satisfaction. In order to detect an effect size as small as 0.32 for secondary outcomes, a sample of 170 couples is being recruited (27% dropout expected). A clinically significant decrease in pain is

  11. A low protein diet during pregnancy provokes a lasting shift of hepatic expression of genes related to cell cycle throughout ontogenesis in a porcine model

    Directory of Open Access Journals (Sweden)

    Oster Michael

    2012-03-01

    Full Text Available Abstract Background In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. Adverse environmental conditions during fetal development provoke an intrauterine adaptive response termed 'fetal programming', which may lead to both persistently biased responsiveness to extrinsic factors and permanent consequences for the organismal phenotype. This leads to the hypothesis that the offspring's transcriptome exhibits short-term and long-term changes, depending on the maternal diet. In order to contribute to a comprehensive inventory of genes and functional networks that are targets of nutritional programming initiated during fetal life, we applied whole-genome microarrays for expression profiling in a longitudinal experimental design covering prenatal, perinatal, juvenile, and adult ontogenetic stages in a porcine model. Pregnant sows were fed either a gestational low protein diet (LP, 6% CP or an adequate protein diet (AP, 12% CP. All offspring was nursed by foster sows receiving standard diets. After weaning, all offspring was fed standard diets ad libitum. Results Analyses of the hepatic gene expression of the offspring at prenatal (94 dies post conceptionem, dpc and postnatal stages (1, 28, 188 dies post natum, dpn included comparisons between dietary groups within stages as well as comparisons between ontogenetic stages within diets to separate diet-specific transcriptional changes and maturation processes. We observed differential expression of genes related to lipid metabolism (e.g. Fatty acid metabolism, Biosynthesis of steroids, Synthesis and degradation of ketone bodies, FA elongation in mitochondria, Bile acid synthesis and cell cycle regulation (e.g. Mitotic roles of PLK, G1/S checkpoint regulation, G2/M DNA damage checkpoint regulation. Notably, at stage 1 dpn no regulation of a distinct pathway was found in LP offspring. Conclusions The transcriptomic

  12. Effect Modifying Role of Serum Calcium on Mortality-Predictability of PTH and Alkaline Phosphatase in Hemodialysis Patients: An Investigation Using Data from the Taiwan Renal Registry Data System from 2005 to 2012.

    Directory of Open Access Journals (Sweden)

    Yen-Chung Lin

    Full Text Available Predicting mortality in dialysis patients based on low intact parathyroid hormone levels is difficult, because aluminum intoxication, malnutrition, older age, race, diabetes, or peritoneal dialysis may influence these levels. We investigated the clinical implications of low parathyroid hormone levels in relation to the mortality of dialysis patients using sensitive, stratified, and adjusted models and a nationwide dialysis database. We analyzed data from 2005 to 2012 that were held on the Taiwan Renal Registry Data System, and 94,983 hemodialysis patients with valid data regarding their intact parathyroid levels were included in this study. The patient cohort was subdivided based on the intact parathyroid hormone and alkaline phosphatase levels. The mean hemodialysis duration within this cohort was 3.5 years. The mean (standard deviation age was 62 (14 years. After adjusting for age, sex, diabetes, the hemodialysis duration, serum albumin levels, hematocrit levels, calcium levels, phosphate levels, and the hemodialysis treatment adequacy score, the single-pool Kt/V, the crude and adjusted all-cause mortality rates increased when alkaline phosphatase levels were higher or intact parathyroid hormone levels were lower. In general, at any given level of serum calcium or phosphate, patients with low intact parathyroid hormone levels had higher mortality rates than those with normal or high iPTH levels. At a given alkaline phosphatase level, the hazard ratio for all-cause mortality was 1.33 (p 9.5 mg/dL, but in the group with intact parathyroid hormone levels > 300 pg/mL and serum calcium levels > 9.5 mg/dL, the hazard ratio was 0.92 (95% confidence interval 0.85-1.01. Hence, maintaining albumin-corrected high serum calcium levels at > 9.5 mg/dL may correlate with poor prognoses for patients with low intact parathyroid hormone levels.

  13. Umsetzung des KDSF-Datenmodells in VIVO

    OpenAIRE

    Walther, Tatiana; Hauschke, Christian

    2017-01-01

    Im Rahmen des Projekts „Umsetzung Kerndatensatz Forschung in VIVO“ wird am Open Science Lab der Technischen Informationsbibliothek Hannover (TIB) der Versuch unternommen, den Kerndatensatz Forschung in das Forschungsinformationssystem VIVO zu integrieren. Entwurf KDSF-VIVO-Alignment und KDSF-VIVO-Extension: https://github.com/VIVO-DE/VIVO-KDSF-Integration

  14. Maximizing PTH Anabolic Osteoporosis Therapy. Revision

    Science.gov (United States)

    2016-09-01

    Mouse Core yielded chimeric mice that underwent partial recombination of the targeting construct. Specifically, the 3’ loxP site was successfully...and correctly incorporated into intron 7, but the 5’ loxP site was excluded from the recombination event within intron 3 despite being included in the...Molecular Genetics , Indiana University School of Medicine, Indianapolis, Indiana 46202-5126 The unfolded protein response (UPR) maintains protein homeostasis

  15. In vivo histamine optical nanosensors.

    Science.gov (United States)

    Cash, Kevin J; Clark, Heather A

    2012-01-01

    In this communication we discuss the development of ionophore based nanosensors for the detection and monitoring of histamine levels in vivo. This approach is based on the use of an amine-reactive, broad spectrum ionophore which is capable of recognizing and binding to histamine. We pair this ionophore with our already established nanosensor platform, and demonstrate in vitro and in vivo monitoring of histamine levels. This approach enables capturing rapid kinetics of histamine after injection, which are more difficult to measure with standard approaches such as blood sampling, especially on small research models. The coupling together of in vivo nanosensors with ionophores such as nonactin provide a way to generate nanosensors for novel targets without the difficult process of designing and synthesizing novel ionophores.

  16. Voltammetric and Mathematical Evidence for Dual Transport Mediation of Serotonin Clearance In Vivo

    Science.gov (United States)

    Wood, Kevin M.; Zeqja, Anisa; Nijhout, H. Frederik; Reed, Michael C.; Best, Janet; Hashemi, Parastoo

    2014-01-01

    The neurotransmitter serotonin underlies many of the brain’s functions. Understanding serotonin neurochemistry is important for improving treatments for neuropsychiatric disorders such as depression. Antidepressants commonly target serotonin clearance via serotonin transporters (SERTs) and have variable clinical effects. Adjunctive therapies, targeting other systems including serotonin autoreceptors, also vary clinically and carry adverse consequences. Fast scan cyclic voltammetry (FSCV) is particularly well suited for studying antidepressant effects on serotonin clearance and autoreceptors by providing real-time chemical information on serotonin kinetics in vivo. However, the complex nature of in vivo serotonin responses makes it difficult to interpret experimental data with established kinetic models. Here, we electrically stimulated the mouse medial forebrain bundle (MFB) to provoke and detect terminal serotonin in the substantia nigra reticulata (SNr). In response to MFB stimulation we found three dynamically distinct serotonin signals. To interpret these signals we developed a computational model that supports two independent serotonin reuptake mechanisms (high affinity, low efficiency reuptake mechanism and low affinity, high efficiency reuptake system) and bolsters an important inhibitory role for the serotonin autoreceptors. Our data and analysis, afforded by the powerful combination of voltammetric and theoretical methods, gives new understanding of the chemical heterogeneity of serotonin dynamics in the brain. This diverse serotonergic matrix likely contributes to clinical variability of antidepressants. PMID:24702305

  17. In vivo magnetic resonance spectroscopy; In vivo magnetisk resonansspektroskopi

    Energy Technology Data Exchange (ETDEWEB)

    Bakken, Inger Johanne; Skjetne, Tore; Gribbestad, Ingrid S.; Kvistad, Kjell Arne

    2002-07-01

    Magnetic resonance tomography (MR) has become a highly useful tool for diagnostic imaging. The technology is in a process of rapid development with new and better methods emerging for the imaging of anatomic and pathologic aspects. With some additional equipment, the MR instrument may also be used for in vivo magnetic resonance spectroscopy (MRS). In vivo MRS provides biochemical information about metabolites in a given tissue volume. This type of biochemical information can be extracted from volumes the size of a sugar lump within a recording period of about five minutes. New technologies also allow extracting such information from several volumes during one recording in which the information is processed as metabolic pictures. The method has found clinical applications in several fields, including the evaluation of brain tumours and epilepsy. The use of in vivo MRS will probably increase in the years ahead, especially, perhaps, for the follow-up of various therapeutic regimens. All suppliers of MR equipment now provide in vivo MRS sets and routines for recording and data analysis have become very user-friendly. (author)

  18. Nanoparticle formulation enhanced protective immunity provoked by PYGPI8p-transamidase related protein (PyTAM) DNA vaccine in Plasmodium yoelii malaria model.

    Science.gov (United States)

    Cherif, Mahamoud Sama; Shuaibu, Mohammed Nasir; Kodama, Yukinobu; Kurosaki, Tomoaki; Helegbe, Gideon Kofi; Kikuchi, Mihoko; Ichinose, Akitoyo; Yanagi, Tetsuo; Sasaki, Hitoshi; Yui, Katsuyuki; Tien, Nguyen Huy; Karbwang, Juntra; Hirayama, Kenji

    2014-04-07

    We have previously reported the new formulation of polyethylimine (PEI) with gamma polyglutamic acid (γ-PGA) nanoparticle (NP) to have provided Plasmodium yoelii merozoite surface protein-1 (PyMSP-1) plasmid DNA vaccine with enhanced protective cellular and humoral immunity in the lethal mouse malaria model. PyGPI8p-transamidase-related protein (PyTAM) was selected as a possible candidate vaccine antigen by using DNA vaccination screening from 29 GPI anchor and signal sequence motif positive genes picked up using web-based bioinformatics tools; though the observed protection was not complete. Here, we observed augmented protective effect of PyTAM DNA vaccine by using PEI and γ-PGA complex as delivery system. NP-coated PyTAM plasmid DNA immunized mice showed a significant survival rate from lethal P. yoelii challenge infection compared with naked PyTAM plasmid or with NP-coated empty plasmid DNA group. Antigen-specific IgG1 and IgG2b subclass antibody levels, proportion of CD4 and CD8T cells producing IFN-γ in the splenocytes and IL-4, IFN-γ, IL-12 and TNF-α levels in the sera and in the supernatants from ex vivo splenocytes culture were all enhanced by the NP-coated PyTAM DNA vaccine. These data indicates that NP augments PyTAM protective immune response, and this enhancement was associated with increased DC activation and concomitant IL-12 production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Comparison of in vivo and ex vivo imaging of the microvasculature with 2-photon fluorescence microscopy

    Science.gov (United States)

    Steinman, Joe; Koletar, Margaret; Stefanovic, Bojana; Sled, John G.

    2016-03-01

    This study evaluates 2-Photon fluorescence microscopy of in vivo and ex vivo cleared samples for visualizing cortical vasculature. Four mice brains were imaged with in vivo 2PFM. Mice were then perfused with a FITC gel and cleared in fructose. The same regions imaged in vivo were imaged ex vivo. Vessels were segmented automatically in both images using an in-house developed algorithm that accounts for the anisotropic and spatially varying PSF ex vivo. Through non-linear warping, the ex vivo image and tracing were aligned to the in vivo image. The corresponding vessels were identified through a local search algorithm. This enabled comparison of identical vessels in vivo/ex vivo. A similar process was conducted on the in vivo tracing to determine the percentage of vessels perfused. Of all the vessels identified over the four brains in vivo, 98% were present ex vivo. There was a trend towards reduced vessel diameter ex vivo by 12.7%, and the shrinkage varied between specimens (0% to 26%). Large diameter surface vessels, through a process termed 'shadowing', attenuated in vivo signal from deeper cortical vessels by 40% at 300 μm below the cortical surface, which does not occur ex vivo. In summary, though there is a mean diameter shrinkage ex vivo, ex vivo imaging has a reduced shadowing artifact. Additionally, since imaging depths are only limited by the working distance of the microscope objective, ex vivo imaging is more suitable for imaging large portions of the brain.

  20. In aqua vivo EPID dosimetry

    NARCIS (Netherlands)

    Wendling, Markus; McDermott, Leah N.; Mans, Anton; Olaciregui-Ruiz, Ígor; Pecharromán-Gallego, Raul; Sonke, Jan-Jakob; Stroom, Joep; van Herk, Marcel; Mijnheer, Ben J.

    2012-01-01

    At the Netherlands Cancer Institute--Antoni van Leeuwenhoek Hospital in vivo dosimetry using an electronic portal imaging device (EPID) has been implemented for almost all high-energy photon treatments of cancer with curative intent. Lung cancer treatments were initially excluded, because the

  1. In aqua vivo EPID dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Wendling, Markus; McDermott, Leah N.; Mans, Anton; Olaciregui-Ruiz, Igor; Pecharroman-Gallego, Raul; Sonke, Jan-Jakob; Stroom, Joep; Herk, Marcel J.; Mijnheer, Ben van [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands)

    2012-01-15

    Purpose: At the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital in vivo dosimetry using an electronic portal imaging device (EPID) has been implemented for almost all high-energy photon treatments of cancer with curative intent. Lung cancer treatments were initially excluded, because the original back-projection dose-reconstruction algorithm uses water-based scatter-correction kernels and therefore does not account for tissue inhomogeneities accurately. The aim of this study was to test a new method, in aqua vivo EPID dosimetry, for fast dose verification of lung cancer irradiations during actual patient treatment. Methods: The key feature of our method is the dose reconstruction in the patient from EPID images, obtained during the actual treatment, whereby the images have been converted to a situation as if the patient consisted entirely of water; hence, the method is termed in aqua vivo. This is done by multiplying the measured in vivo EPID image with the ratio of two digitally reconstructed transmission images for the unit-density and inhomogeneous tissue situation. For dose verification, a comparison is made with the calculated dose distribution with the inhomogeneity correction switched off. IMRT treatment verification is performed for each beam in 2D using a 2D {gamma} evaluation, while for the verification of volumetric-modulated arc therapy (VMAT) treatments in 3D a 3D {gamma} evaluation is applied using the same parameters (3%, 3 mm). The method was tested using two inhomogeneous phantoms simulating a tumor in lung and measuring its sensitivity for patient positioning errors. Subsequently five IMRT and five VMAT clinical lung cancer treatments were investigated, using both the conventional back-projection algorithm and the in aqua vivo method. The verification results of the in aqua vivo method were statistically analyzed for 751 lung cancer patients treated with IMRT and 50 lung cancer patients treated with VMAT. Results: The improvements by

  2. Modest dietary K+ restriction provokes insulin resistance of cellular K+ uptake and phosphorylation of renal outer medulla K+ channel without fall in plasma K+ concentration.

    Science.gov (United States)

    Chen, Pei; Guzman, John P; Leong, Patrick K K; Yang, Li E; Perianayagam, Anjana; Babilonia, Elisa; Ho, Jennifer S; Youn, Jang H; Wang, Wen Hui; McDonough, Alicia A

    2006-05-01

    Extracellular K(+) concentration ([K(+)]) is closely regulated by the concerted regulatory responses of kidney and muscle. In this study, we aimed to define the responses activated when dietary K(+) was moderately reduced from a control diet (1.0% K(+)) to a 0.33% K(+) diet for 15 days. Although body weight and baseline plasma [K(+)] (4.0 mM) were not reduced in the 0.33% K(+) group, regulatory responses to conserve plasma [K(+)] were evident in both muscle and kidney. Insulin-stimulated clearance of K(+) from the plasma was estimated in vivo in conscious rats with the use of tail venous and arterial cannulas. During infusion of insulin.(50 mU.kg(-1).min(-1)), plasma [K(+)] level fell to 3.2 +/- 0.1 mM in the 1.0% K(+) diet group and to only 3.47 +/- 0.07 mM in the 0.33% K(+) diet group (P < 0.01) with no reduction in urinary K(+) excretion, which is evidence of insulin resistance to cellular K(+) uptake. Insulin-stimulated cellular K(+) uptake was quantitated by measuring the K(+) infusion rate necessary to clamp plasma K(+) at baseline (in micromol.kg(-1).min(-1)) during 5 mU of insulin.kg(-1).min(-1) infusion: 9.7 +/- 1.5 in 1% K(+) diet was blunted to 5.2 +/- 1.7 in the 0.33% K(+) diet group (P < 0.001). Muscle [K(+)] and Na(+)-K(+)-ATPase activity and abundance were unchanged during the 0.33% K(+) diet. Renal excretion, which was measured overnight in metabolic cages, was reduced by 80%, from 117.6 +/- 10.5 micromol/h/animal (1% K(+) diet) to 24.2 +/- 1.7 micromol/h/animal (0.33% K(+) diet) (P < 0.001). There was no significant change in total abundance of key renal K(+) transporters, but 50% increases in both renal PTK cSrc abundance and ROMK phosphorylation in the 0.33% K(+) vs. 1% K(+) diet group, previously established to be associated with internalization of ROMK. These results indicate that plasma [K(+)] can be maintained during modest K(+) restriction due to a decrease in insulin-stimulated cellular K(+) uptake as well as renal K(+) conservation

  3. Photoactivated In Vivo Proximity Labeling.

    Science.gov (United States)

    Beck, David B; Bonasio, Roberto

    2017-06-19

    Identification of molecular interactions is paramount to understanding how cells function. Most available technologies rely on co-purification of a protein of interest and its binding partners. Therefore, they are limited in their ability to detect low-affinity interactions and cannot be applied to proteins that localize to difficult-to-solubilize cellular compartments. In vivo proximity labeling (IPL) overcomes these obstacles by covalently tagging proteins and RNAs based on their proximity in vivo to a protein of interest. In IPL, a heterobifunctional probe comprising a photoactivatable moiety and biotin is recruited by a monomeric streptavidin tag fused to a protein of interest. Following UV irradiation, candidate interacting proteins and RNAs are covalently biotinylated with tight spatial and temporal control and subsequently recovered using biotin as an affinity handle. Here, we describe experimental protocols to discover novel protein-protein and protein-RNA interactions using IPL. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  4. In vivo imaging of sulfotransferases

    Science.gov (United States)

    Barrio, Jorge R; Kepe, Vladimir; Small, Gary W; Satyamurthy, Nagichettiar

    2013-02-12

    Radiolabeled tracers for sulfotransferases (SULTs), their synthesis, and their use are provided. Included are substituted phenols, naphthols, coumarins, and flavones radiolabeled with .sup.18F, .sup.123I, .sup.124I, .sup.125I, or .sup.11C. Also provided are in vivo techniques for using these and other tracers as analytical and diagnostic tools to study sulfotransferase distribution and activity, in health and disease, and to evaluate therapeutic interventions.

  5. Fibroblast Growth Factor (FGF) 23 Regulates the Plasma Levels of Parathyroid Hormone In Vivo Through the FGF Receptor in Normocalcemia, But Not in Hypocalcemia

    DEFF Research Database (Denmark)

    Mace, Maria L; Gravesen, Eva; Nordholm, Anders

    2018-01-01

    of this regulation is however not well understood. Surprisingly, in uremia, concomitantly elevated FGF23 and PTH levels are observed. The parathyroid gland rapidly loses its responsiveness to extracellular calcium in vitro and a functional parathyroid cell line has currently not been established. Therefore, the aim......The calcium and phosphate homeostasis is regulated by a complex interplay between parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and calcitriol. Experimental studies have demonstrated an inhibitory effect of FG23 on PTH production and secretion; the physiological role...... hypocalcemia. We demonstrated that FGF23 rapidly inhibited PTH secretion and that this effect was completely blocked by inhibition of the FGF receptor. Furthermore, inhibition of the FGF receptor by itself significantly increased PTH levels, indicating that FGF23 has a suppressive tonus on the parathyroid...

  6. Nanomaterials for In Vivo Imaging.

    Science.gov (United States)

    Smith, Bryan Ronain; Gambhir, Sanjiv Sam

    2017-02-08

    In vivo imaging, which enables us to peer deeply within living subjects, is producing tremendous opportunities both for clinical diagnostics and as a research tool. Contrast material is often required to clearly visualize the functional architecture of physiological structures. Recent advances in nanomaterials are becoming pivotal to generate the high-resolution, high-contrast images needed for accurate, precision diagnostics. Nanomaterials are playing major roles in imaging by delivering large imaging payloads, yielding improved sensitivity, multiplexing capacity, and modularity of design. Indeed, for several imaging modalities, nanomaterials are now not simply ancillary contrast entities, but are instead the original and sole source of image signal that make possible the modality's existence. We address the physicochemical makeup/design of nanomaterials through the lens of the physical properties that produce contrast signal for the cognate imaging modality-we stratify nanomaterials on the basis of their (i) magnetic, (ii) optical, (iii) acoustic, and/or (iv) nuclear properties. We evaluate them for their ability to provide relevant information under preclinical and clinical circumstances, their in vivo safety profiles (which are being incorporated into their chemical design), their modularity in being fused to create multimodal nanomaterials (spanning multiple different physical imaging modalities and therapeutic/theranostic capabilities), their key properties, and critically their likelihood to be clinically translated.

  7. Reproducibility and Variation of Diffusion Measures in the Squirrel Monkey Brain, In Vivo and Ex Vivo

    Science.gov (United States)

    Schilling, Kurt; Gao, Yurui; Stepniewska, Iwona; Choe, Ann S; Landman, Bennett A; Anderson, Adam W

    2016-01-01

    Purpose Animal models are needed to better understand the relationship between diffusion MRI (dMRI) and the underlying tissue microstructure. One promising model for validation studies is the common squirrel monkey, Saimiri sciureus. This study aims to determine (1) the reproducibility of in vivo diffusion measures both within and between subjects; (2) the agreement between in vivo and ex vivo data acquired from the same specimen and (3) normal diffusion values and their variation across brain regions. Methods Data were acquired from three healthy squirrel monkeys, each imaged twice in vivo and once ex vivo. Reproducibility of fractional anisotropy (FA), mean diffusivity (MD), and principal eigenvector (PEV) was assessed, and normal values were determined both in vivo and ex vivo. Results The calculated coefficients of variation (CVs) for both intra-subject and inter-subject MD were below 10% (low variability) while FA had a wider range of CVs, 2–14% intra-subject (moderate variability), and 3–31% inter-subject (high variability). MD in ex vivo tissue was lower than in vivo (30%–50% decrease), while FA values increased in all regions (30–39% increase). The mode of angular differences between in vivo and ex vivo PEVs was 12 degrees. Conclusion This study characterizes the diffusion properties of the squirrel monkey brain and serves as the groundwork for using the squirrel monkey, both in vivo and ex vivo, as a model for diffusion MRI studies. PMID:27587226

  8. In vivo dosimetry in brachytherapy.

    Science.gov (United States)

    Tanderup, Kari; Beddar, Sam; Andersen, Claus E; Kertzscher, Gustavo; Cygler, Joanna E

    2013-07-01

    In vivo dosimetry (IVD) has been used in brachytherapy (BT) for decades with a number of different detectors and measurement technologies. However, IVD in BT has been subject to certain difficulties and complexities, in particular due to challenges of the high-gradient BT dose distribution and the large range of dose and dose rate. Due to these challenges, the sensitivity and specificity toward error detection has been limited, and IVD has mainly been restricted to detection of gross errors. Given these factors, routine use of IVD is currently limited in many departments. Although the impact of potential errors may be detrimental since treatments are typically administered in large fractions and with high-gradient-dose-distributions, BT is usually delivered without independent verification of the treatment delivery. This Vision 20/20 paper encourages improvements within BT safety by developments of IVD into an effective method of independent treatment verification.

  9. In vivo dosimetry in brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Tanderup, Kari [Department of Oncology, Aarhus University Hospital, Aarhus 8000 (Denmark); Department of Clinical Medicine, Aarhus University, Aarhus 8000 (Denmark); Beddar, Sam [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Andersen, Claus E.; Kertzscher, Gustavo [Center of Nuclear Technologies, Technical University of Denmark, Roskilde 4000 (Denmark); Cygler, Joanna E. [Department of Physics, Ottawa Hospital Cancer Centre, Ottawa, Ontario K1H 8L6 (Canada)

    2013-07-15

    In vivo dosimetry (IVD) has been used in brachytherapy (BT) for decades with a number of different detectors and measurement technologies. However, IVD in BT has been subject to certain difficulties and complexities, in particular due to challenges of the high-gradient BT dose distribution and the large range of dose and dose rate. Due to these challenges, the sensitivity and specificity toward error detection has been limited, and IVD has mainly been restricted to detection of gross errors. Given these factors, routine use of IVD is currently limited in many departments. Although the impact of potential errors may be detrimental since treatments are typically administered in large fractions and with high-gradient-dose-distributions, BT is usually delivered without independent verification of the treatment delivery. This Vision 20/20 paper encourages improvements within BT safety by developments of IVD into an effective method of independent treatment verification.

  10. The phenomenon of “QT stunning”: The abnormal QT prolongation provoked by standing persists even as the heart rate returns to normal in patients with long QT syndrome

    Science.gov (United States)

    Adler, Arnon; van der Werf, Christian; Postema, Pieter G.; Rosso, Raphael; Bhuiyan, Zahir A.; Kalman, Jonathan M.; Vohra, Jitendra K.; Guevara-Valdivia, Milton E.; Marquez, Manlio F.; Halkin, Amir; Benhorin, Jesaia; Antzelevitch, Charles; Wilde, Arthur A.M.; Viskin, Sami

    2012-01-01

    BACKGROUND Patients with long QT syndrome (LQTS) have inadequate shortening of the QT interval in response to the sudden heart rate accelerations provoked by standing—a phenomenon of diagnostic value. We now validate our original observations in a cohort twice as large. We also describe that this abnormal QT-interval response persists as the heart rate acceleration returns to baseline. OBJECTIVES To describe a novel observation, termed “QT stunning” and to validate previous observations regarding the “QT-stretching” phenomenon in patients with LQTS by using our recently described “standing test.” METHODS The electrocardiograms of 108 patients with LQTS and 112 healthy subjects were recorded in the supine position. Subjects were then instructed to stand up quickly and remain standing for 5 minutes during continuous electrocardiographic recording. The corrected QT interval was measured at baseline (QTcbase), when heart rate acceleration without appropriate QT-interval shortening leads to maximal QT stretching (QTcstretch) and upon return of heart rate to baseline (QTcreturn). RESULTS QTcstretch lengthened significantly more in patients with LQTS (103 ± 80 ms vs 66 ± 40 ms in controls; P QT interval in response to standing in patients with LQTS. Our study also shows that this abnormal response persists even after the heart rate slows back to baseline. PMID:22300664

  11. A comprehensive review of mercury provoked autism.

    Science.gov (United States)

    Geier, D A; King, P G; Sykes, L K; Geier, M R

    2008-10-01

    Emerging evidence supports the theory that some autism spectrum disorders (ASDs) may result from a combination of genetic/biochemical susceptibility, specifically a reduced ability to excrete mercury (Hg), and exposure to Hg at critical developmental periods. Elemental/inorganic Hg is released into the air/water where it becomes methylated and accumulates in animal tissues. The US population is primarily exposed to methyl-Hg by fish consumption. In addition, many pharmaceuticals have been, and some continue to be, a ubiquitous source of danger because they contain mercurials. Mercurials may be found in drugs for the eye, ear, nose, throat, and skin; in bleaching creams; as preservatives in cosmetics, tooth pastes, lens solutions, vaccines, allergy test and immunotherapy solutions; in antiseptics, disinfectants, and contraceptives; in fungicides and herbicides; in dental fillings and thermometers; and many other products. Hg has been found to cause immune, sensory, neurological, motor, and behavioural dysfunctions similar to traits defining/associated with ASDs, and that these similarities extend to neuroanatomy, neurotransmitters, and biochemistry. Furthermore, a review of molecular mechanisms indicates that Hg exposure can induce death, disorganization and/or damage to selected neurons in the brain similar to that seen in recent ASD brain pathology studies, and this alteration may likely produce the symptoms by which ASDs are diagnosed. Finally, a review of treatments suggests that ASD patients who undergo protocols to reduce Hg and/or its effects show significant clinical improvements in some cases. In conclusion, the overwhelming preponderance of the evidence favours acceptance that Hg exposure is capable of causing some ASDs.

  12. Drugs that may provoke Kounis syndrome.

    Science.gov (United States)

    Rodrigues, Maria Catarina Luís; Coelho, Daniela; Granja, Cristina

    2013-01-01

    Kounis Syndrome (KS) is the contemporary occurrence of Acute Coronary Syndromes (ACS) with an allergic or hypersensitivity reaction. This syndrome has been reported in association with a variety of drugs, food, insect stings, environmental exposures and medical conditions. Cases of KS seem to be more often encountered in everyday clinical practice than anticipated. It is believed that the lack of awareness of this association may lead to underreporting. We report a case of KS secondary to diclofenac intake.

  13. A Comparison of General Case In Vivo and General Case Simulation Plus In Vivo Training.

    Science.gov (United States)

    McDonnell, John J.; Ferguson, Brad

    1988-01-01

    The study examined the relative effectiveness and efficiency of general case in vivo and general case simulation plus in vivo training in teaching six students with moderate and severe disabilities to purchase items in fast-food restaurants. Although both strategies led to reliable performance in nontrained settings, the in vivo instruction…

  14. The effect of radiofrequency ablation on different organs: Ex vivo and in vivo comparative studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Na [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Rhim, Hyunchul, E-mail: rhimhc@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Choi, Dongil; Kim, Young-sun; Lee, Min Woo; Chang, Ilsoo; Lee, Won Jae; Lim, Hyo K. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of)

    2011-11-15

    Objective: The purposes of this study are to evaluate the ex vivo and in vivo efficacy of radiofrequency ablation (RFA) on different porcine tissues by the ablation of three different sites simultaneously. Materials and methods: A multichannel RFA system, enables three separate tumors to be ablated simultaneously, was used. RFA procedures were applied to normal porcine liver, kidney, and muscle together ex vivo (n = 12) and in vivo (n = 17). Pre-impedances, defined as baseline systemic impedances of tissues before beginning RFA, and the areas of ablation zones were measured and compared. Results: The areas of ablation zones among three organs had a significant difference in decreasing order as follows: liver, muscle, and kidney in the ex vivo study (p = 0.001); muscle, liver, and kidney in the in vivo study (p < 0.0001). The areas of ablation zones between ex vivo and in vivo had a significant difference in the liver and muscle (each p < 0.05). There was no significant correlation between the areas of ablation zones and pre-impedances in both studies. Conclusions: Renal RFA produced the smallest ablation zone in both in vivo and ex vivo studies. Muscular RFA demonstrated the largest ablation zone in the in vivo study, and hepatic RFA showed the largest ablation zone in the ex vivo study. This variability in the tissues should be considered for performing an optimized RFA for each organ site.

  15. Ex Vivo ERG analysis of photoreceptors using an In Vivo ERG system

    Science.gov (United States)

    Vinberg, Frans; Kolesnikov, Alexander V.; Kefalov, Vladimir J.

    2014-01-01

    The Function of the retina and effects of drugs on it can be assessed by recording transretinal voltage across isolated retina that is perfused with physiological medium. However, building ex vivo ERG apparatus requires substantial amount of time, resources and expertise. Here we adapted a commercial in vivo ERG system for transretinal ERG recordings from rod and cone photoreceptors and compared rod and cone signalling between ex vivo and in vivo environments. We found that the rod and cone a- and b-waves recorded with the transretinal ERG adapter and a standard in vivo ERG system are comparable to those obtained from live anesthetized animals. However, ex vivo responses are somewhat slower and their oscillatory potentials are suppressed as compared to those recorded in vivo. We found that rod amplification constant (A) was comparable between ex vivo and in vivo conditions, ∼10 - 30 s-2 depending on the choice of response normalization. We estimate that the A in cones is between 3 and 6 s-2 in ex vivo conditions and by assuming equal A in vivo we arrive to light funnelling factor of 3 for cones in the mouse retina. The ex vivo ERG adapter provides a simple and affordable alternative to designing a custom-built transretinal recordings setup for the study of photoreceptors. Our results provide a roadmap to the rigorous quantitative analysis of rod and cone responses made possible with such a system. PMID:24959652

  16. In vivo facilitated diffusion model.

    Directory of Open Access Journals (Sweden)

    Maximilian Bauer

    Full Text Available Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and one-dimensional sliding along the DNA contour is still beneficial in the crowded interior of cells is highly disputed. Here we use a simple model for the bacterial genome inside the cell and present a semi-analytical model for the in vivo target search of transcription factors within the facilitated diffusion framework. Without having to resort to extensive simulations we determine the mean search time of a lac repressor in a living E. coli cell by including parameters deduced from experimental measurements. The results agree very well with experimental findings, and thus the facilitated diffusion picture emerges as a quantitative approach to gene regulation in living bacteria cells. Furthermore we see that the search time is not very sensitive to the parameters characterizing the DNA configuration and that the cell seems to operate very close to optimal conditions for target localization. Local searches as implied by the colocalization mechanism are only found to mildly accelerate the mean search time within our model.

  17. Deletion of Rac in Mature Osteoclasts Causes Osteopetrosis, an Age-Dependent Change in Osteoclast Number, and a Reduced Number of Osteoblasts In Vivo

    Science.gov (United States)

    Zhu, Meiling; Sun, Ben-hua; Saar, Katarzyna; Simpson, Christine; Troiano, Nancy; Dallas, Sarah L; Tiede-Lewis, LeAnn M; Nevius, Erin; Pereira, João P; Weinstein, Robert S; Tommasini, Steven M; Insogna, Karl L

    2016-01-01

    Rac1 and Rac2 are thought to have important roles in osteoclasts. Therefore, mice with deletion of both Rac1 and Rac2 in mature osteoclasts (DKO) were generated by crossing Rac1flox/flox mice with mice expressing Cre in the cathepsin K locus and then mating these animals with Rac2−/− mice. DKO mice had markedly impaired tooth eruption. Bone mineral density (BMD) was increased 21% to 33% in 4- to 6-week-old DKO mice at all sites when measured by dual-energy X-ray absorptiometry (DXA) and serum cross-linked C-telopeptide (CTx) was reduced by 52%. The amount of metaphyseal trabecular bone was markedly increased in DKO mice, but the cortices were very thin. Spinal trabecular bone mass was increased. Histomorphometry revealed significant reductions in both osteoclast and osteoblast number and function in 4- to 6-week-old DKO animals. In 14- to 16-week-old animals, osteoclast number was increased, although bone density was further increased. DKO osteoclasts had severely impaired actin ring formation, an impaired ability to generate acid, and reduced resorptive activity in vitro. In addition, their life span ex vivo was reduced. DKO osteoblasts expressed normal differentiation markers except for the expression of osterix, which was reduced. The DKO osteoblasts mineralized normally in vitro, indicating that the in vivo defect in osteoblast function was not cell autonomous. Confocal imaging demonstrated focal disruption of the osteocytic dendritic network in DKO cortical bone. Despite these changes, DKO animals had a normal response to treatment with once-daily parathyroid hormone (PTH). We conclude that Rac1 and Rac2 have critical roles in skeletal metabolism. PMID:26496249

  18. In vivo and ex vivo confocal endomicroscopy of pancreatic cystic lesions: A prospective study.

    Science.gov (United States)

    Krishna, Somashekar G; Modi, Rohan M; Kamboj, Amrit K; Swanson, Benjamin J; Hart, Phil A; Dillhoff, Mary E; Manilchuk, Andrei; Schmidt, Carl R; Conwell, Darwin L

    2017-05-14

    To investigate the reproducibility of the in vivo endoscopic ultrasound (EUS) - guided needle based confocal endomicroscopy (nCLE) image patterns in an ex vivo setting and compare these to surgical histopathology for characterizing pancreatic cystic lesions (PCLs). In a prospective study evaluating EUS-nCLE for evaluation of PCLs, 10 subjects underwent an in vivo nCLE (AQ-Flex nCLE miniprobe; Cellvizio, MaunaKea, Paris, France) during EUS and ex vivo probe based CLE (pCLE) of the PCL (Gastroflex ultrahigh definition probe, Cellvizio) after surgical resection. Biopsies were obtained from ex vivo CLE-imaged areas for comparative histopathology. All subjects received intravenous fluorescein prior to EUS and pancreatic surgery for in vivo and ex vivo CLE imaging respectively. A total of 10 subjects (mean age 53 ± 12 years; 5 female) with a mean PCL size of 34.8 ± 14.3 mm were enrolled. Surgical histopathology confirmed 2 intraductal papillary mucinous neoplasms (IPMNs), 3 mucinous cystic neoplasms (MCNs), 2 cystic neuroendocrine tumors (cystic-NETs), 1 serous cystadenoma (SCA), and 2 squamous lined PCLs. Characteristic in vivo nCLE image patterns included papillary projections for IPMNs, horizon-type epithelial bands for MCNs, nests and trabeculae of cells for cystic-NETs, and a "fern pattern" of vascularity for SCA. Identical image patterns were observed during ex vivo pCLE imaging of the surgically resected PCLs. Both in vivo and ex vivo CLE imaging findings correlated with surgical histopathology. In vivo nCLE patterns are reproducible in ex vivo pCLE for all major neoplastic PCLs. These findings add further support the application of EUS-nCLE as an imaging biomarker in the diagnosis of PCLs.

  19. Experimental cystic echinococcosis therapy: In vitro and in vivo combined 5-fluorouracil/albendazole treatment.

    Science.gov (United States)

    Pensel, Patricia E; Elissondo, Natalia; Gambino, Guillermo; Gamboa, Gabriela Ullio; Benoit, J P; Elissondo, María C

    2017-10-15

    Human cystic echinococcosis is a zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato (s. l.). Although benzimidazole compounds such as albendazole (ABZ) and mebendazole have been the cornerstone of chemotherapy for the disease, there is often no complete recovery after treatment. Hence, new strategies are required to improve treatment of human cystic echinococcosis. The goals of the current study were as follows: (i) to evaluate the in vitro efficacy of the 5-fluorouracil (5-FU) and ABZ combination against E. granulosus s. l. protoscoleces and cysts, (ii) to compare the clinical efficacy of 5-FU alone or in combination with ABZ in infected mice. The combination of 5-FU+ABZ had a stronger in vitro effect against larval stage than that did both drugs alone. Even at the lowest concentration of 5-FU+ABZ combination (1μg/ml), the reduction of the viability of protoscoleces and cysts was greater than that observed with drugs alone at 10μg/ml. The results were confirmed at the ultrastructural level by scanning electron microscopy. These data helped to justify the in vivo investigations assessing the therapeutic potential of the combination of 5-FU and ABZ suspension in CF-1 mice infected with E. granulosus sensu stricto (s. s.) metacestodes. Treatment with 5-FU (10mg/kg) or 5-FU (10mg/kg) + ABZ suspension (5mg/kg) reduced the weight of cysts recovered from mice compared with control groups. Interestingly, the effect of 5-FU given weekly for 5 consecutive weeks was comparable to that observed with ABZ suspension under a daily schedule during 30days. Co-administration of 5-FU with ABZ did not enhance the in vivo efficacy of drugs alone calculated in relation to cysts weights. However, the combination provoked greater ultrastructural alterations compared to the monotherapy. In conclusion, we demonstrated the efficacy of 5-FU either alone or co-administrated with ABZ against murine experimental cystic echinococcosis. Since 5-FU treatments

  20. Mobile in vivo biopsy and camera robot.

    Science.gov (United States)

    Rentschler, Mark E; Dumpert, Jason; Platt, Stephen R; Farritor, Shane M; Oleynikov, Dmitry

    2006-01-01

    A mobile in vivo biopsy robot has been developed to perform a biopsy from within the abdominal cavity while being remotely controlled. This robot provides a platform for effectively sampling tissue. The robot has been used in vivo in a porcine model to biopsy portions of the liver and mucosa layer of the bowel. After reaching the specified location, the grasper was actuated to biopsy the tissue of interest. The biopsy specimens were gathered from the grasper after robot retraction from the abdominal cavity. This paper outlines the steps towards the successful design of an in vivo biopsy robot. The clamping forces required for successful biopsy are presented and in vivo performance of this robot is addressed.

  1. Towards In Vivo Imaging of Cancer Sialylation

    Directory of Open Access Journals (Sweden)

    Ivan Martinez-Duncker

    2011-01-01

    Full Text Available In vivo assessment of tumor glucose catabolism by positron emission tomography (PET has become a highly valued study in the medical management of cancer. Emerging technologies offer the potential to evaluate in vivo another aspect of cancer carbohydrate metabolism related to the increased anabolic use of monosaccharides like sialic acid (Sia. Sia is used for the synthesis of sialylated oligosaccharides in the cell surface that in cancer cells are overexpressed and positively associated to malignancy and worse prognosis because of their role in invasion and metastasis. This paper addresses the key points of the different strategies that have been developed to image Sia expression in vivo and the perspectives to translate it from the bench to the bedside where it would offer the clinician highly valued complementary information on cancer carbohydrate metabolism that is currently unavailable in vivo.

  2. Comparison of In-Vivo and Ex-Vivo Viscoelastic Behavior of the Spinal Cord.

    Science.gov (United States)

    Ramo, Nicole L; Shetye, Snehal S; Streijger, Femke; Lee, Jae H T; Troyer, Kevin L; Kwon, Brian K; Cripton, Peter; Puttlitz, Christian M

    2017-12-26

    Despite efforts to simulate the in-vivo environment, post-mortem degradation and lack of blood perfusion complicate the use of ex-vivo derived material models in computational studies of spinal cord injury. In order to quantify the mechanical changes that manifest ex-vivo, the viscoelastic behavior of in-vivo and ex-vivo porcine spinal cord samples were compared. Stress-relaxation data from each condition were fit to a non-linear viscoelastic model using a novel characterization technique called the direct fit method. To validate the presented material models, the parameters obtained for each condition were used to predict the respective dynamic cyclic response. Both ex-vivo and in-vivo samples displayed non-linear viscoelastic behavior with a significant increase in relaxation with applied strain. However, at all three strain magnitudes compared, ex-vivo samples experienced a higher stress and greater relaxation than in-vivo samples. Significant differences between model parameters also showed distinct relaxation behaviors, especially in non-linear relaxation modulus components associated with the short-term response (0.1 to 1 second). The results of this study underscore the necessity of utilizing material models developed from in-vivo experimental data for studies of spinal cord injury, where the time-dependent properties are critical. The ability of each material model to accurately predict the dynamic cyclic response validates the presented methodology and supports the use of the in-vivo model in future high-resolution finite element modeling efforts. Neural tissues (such as the brain and spinal cord) display time-dependent, or viscoelastic, mechanical behavior making it difficult to model how they respond to various loading conditions, including injury. Methods that aim to characterize the behavior of the spinal cord almost exclusively use ex-vivo cadaveric or animal samples, despite evidence that time after death affects the behavior compared to that in a

  3. Muscle-Driven In Vivo Nanogenerator

    KAUST Repository

    Li, Zhou

    2010-05-05

    (Figure Presented) A nanogenerator based on a single piezoelectric fine wire producing an alternating current (AC) is successfully used for the harvesting of biomechanical energy under in vivo conditions. We demonstrate the implanting and working of such a nanogenerator in a live rat where it harvests energy generated by its breathing or heart beating. This study shows the potential of applying these nanogenerators for driving in vivo nanodevices. © 2010 WILEY-VCH Verlag GmbH & Co. KCaA, Weinheim.

  4. Streptococcal and Staphylococcal L Forms in vivo

    Science.gov (United States)

    1975-05-13

    4. Overturf, C-ary D.., and Mortimer, Edward A., Jr. Studies of the Relationship Between the Production of Bacteriocines bv Group A Streptococci and...unfavorable milieu because of some stabilizing substance in exudate, prob.ably a polyamine. Third, penicillin did not induce L form production in vivo. Fourth...substance in exudate, probably a polyamine. Third, penicillin did not induce L form production in vivo. Fourth, no evidence that L foim. behave as

  5. In-vivo optical investigation of psoriasis

    Science.gov (United States)

    Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

    2011-03-01

    Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. The average size of dot vessels in Psoriasis was measured to be 974 μm2 which is much higher compared to healthy skin. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

  6. In vivo studies of opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

  7. In vivo and ex vivo methods of growing a liver bud through tissue connection.

    Science.gov (United States)

    Yanagi, Yusuke; Nakayama, Koichi; Taguchi, Tomoaki; Enosawa, Shin; Tamura, Tadashi; Yoshimaru, Koichiro; Matsuura, Toshiharu; Hayashida, Makoto; Kohashi, Kenichi; Oda, Yoshinao; Yamaza, Takayoshi; Kobayashi, Eiji

    2017-10-26

    Cell-based therapy has been proposed as an alternative to orthotopic liver transplantation. The novel transplantation of an in vitro-generated liver bud might have therapeutic potential. In vivo and ex vivo methods for growing a liver bud are essential for paving the way for the clinical translation of liver bud transplantation. We herein report a novel transplantation method for liver buds that are grown in vivo involving orthotopic transplantation on the transected parenchyma of the liver, which showed long engraftment and marked growth in comparison to heterotopic transplantation. Furthermore, this study demonstrates a method for rapidly fabricating scalable liver-like tissue by fusing hundreds of liver bud-like spheroids using a 3D bioprinter. Its system to fix the shape of the 3D tissue with the needle-array system enabled the fabrication of elaborate geometry and the immediate execution of culture circulation after 3D printing-thereby avoiding an ischemic environment ex vivo. The ex vivo-fabricated human liver-like tissue exhibited self-tissue organization ex vivo and engraftment on the liver of nude rats. These achievements conclusively show both in vivo and ex vivo methods for growing in vitro-generated liver buds. These methods provide a new approach for in vitro-generated liver organoids transplantation.

  8. Osteoprotegerin Levels in Primary Hyperparathyroidism

    DEFF Research Database (Denmark)

    Stilgren, L S; Hegedüs, L M; Beck-Nielsen, H

    2003-01-01

    The effect of parathyroid hormone (PTH) on the production of osteoprotegerin (OPG) remains controversial. Most in vitro studies indicate that PTH decreases OPG secretion by the osteoblast, but in vivo observations are conflicting. In primary hyperparathyroidism (PHPT), hypersecretion of PTH leads...

  9. Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo

    Science.gov (United States)

    Chiaretti, M.; Mazzanti, G.; Bosco, S.; Bellucci, S.; Cucina, A.; LeFoche, F.; Carru, G. A.; Mastrangelo, S.; Di Sotto, A.; Masciangelo, R.; Chiaretti, A. M.; Balasubramanian, C.; DeBellis, G.; Micciulla, F.; Porta, N.; Deriu, G.; Tiberia, A.

    2008-11-01

    The aim of this research is focused on the biological effects of multi wall carbon nanotubes (MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We studied the serum immunological modifications after intraperitoneal administration of the MWCNTs. We did not observe any antigenic reaction; the screening of ANA, anti-ENA, anti-cardiolipin, C-ANCA and P-ANCA was negative. No quantitative modification of immunoglobulins was observed, hence no modification of humoral immunity was documented. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic

  10. In vivo and ex vivo inflammatory markers of common metabolic phenotypes in humans

    DEFF Research Database (Denmark)

    Mærkedahl, Rasmus Baadsgaard; Frøkiær, Hanne; Stenbæk, Marie Grøntved

    2018-01-01

    BACKGROUND: Low-grade systemic inflammation (LGSI) is often characterized by elevated levels of interleukin (IL)6, tumor necrosis factor (TNF)α, and C-reactive protein (CRP). Other serum proteins, ex vivo-stimulated cytokine production, and leukocyte count have, however, also been suggested LGSI-markers...... also correlated with leukocyte count. Ex vivo-produced cytokines were intercorrelated and correlated with leukocyte count, but did not correlate with the serum immune markers. MS score, body mass index, and glycated hemoglobin (HbA1c) were associated with 8%-16% higher inflammatory score per standard...... fasting serum markers of LGSI and leukocyte counts associated best with measures of MS-associated LGSI, whereas ex vivo cytokine production was only associated with prevailing glycemia and dyslipidemia. Taken together, this indicates that the relationship between in vivo and ex vivo inflammatory markers...

  11. Resveratrol Induces Apoptosis-Like Death and Prevents In Vitro and In Vivo Virulence of Entamoeba histolytica.

    Science.gov (United States)

    Pais-Morales, Jonnatan; Betanzos, Abigail; García-Rivera, Guillermina; Chávez-Munguía, Bibiana; Shibayama, Mineko; Orozco, Esther

    2016-01-01

    Entamoeba histolytica causes amoebiasis, an infection that kills 100,000 individuals each year. Metronidazole and its derivatives are currently used against this protozoan, but these drugs present adverse effects on human health. Here, we investigated the effect of resveratrol (a natural compound) on E. histolytica trophozoites viability, as well as its influence on the parasite virulence. Trophozoites growth was arrested by 72 μM resveratrol and the IC50 was determined as 220 μM at 48 h. Cells appeared smaller, rounded and in clusters, with debris-containing vacuoles and with abnormally condensed chromatin. Resveratrol triggered reactive oxygen species production. It caused lipid peroxidation and produced phosphatidylserine externalization and DNA fragmentation this latter evidenced by TUNEL assays. It also provoked an increase of intracellular Ca2+ concentration, activated calpain and decreased superoxide dismutase activity, indicating that an apoptosis-like event occurred; however, autophagy was not detected. Cytopathic activity, phagocytosis, encystment and in vivo virulence were diminished dramatically by pre-incubation of trophozoites with resveratrol, evidencing that resveratrol attenuated the trophozoite virulence in vitro. Interestingly, after the inoculation of virulent trophozoites, animals treated with the drug did not develop or developed very small abscesses. Our findings propose that resveratrol could be an alternative to contend amoebiasis.

  12. Resveratrol Induces Apoptosis-Like Death and Prevents In Vitro and In Vivo Virulence of Entamoeba histolytica

    Science.gov (United States)

    Pais-Morales, Jonnatan; Betanzos, Abigail; García-Rivera, Guillermina; Chávez-Munguía, Bibiana; Shibayama, Mineko; Orozco, Esther

    2016-01-01

    Entamoeba histolytica causes amoebiasis, an infection that kills 100,000 individuals each year. Metronidazole and its derivatives are currently used against this protozoan, but these drugs present adverse effects on human health. Here, we investigated the effect of resveratrol (a natural compound) on E. histolytica trophozoites viability, as well as its influence on the parasite virulence. Trophozoites growth was arrested by 72 μM resveratrol and the IC50 was determined as 220 μM at 48 h. Cells appeared smaller, rounded and in clusters, with debris-containing vacuoles and with abnormally condensed chromatin. Resveratrol triggered reactive oxygen species production. It caused lipid peroxidation and produced phosphatidylserine externalization and DNA fragmentation this latter evidenced by TUNEL assays. It also provoked an increase of intracellular Ca2+ concentration, activated calpain and decreased superoxide dismutase activity, indicating that an apoptosis-like event occurred; however, autophagy was not detected. Cytopathic activity, phagocytosis, encystment and in vivo virulence were diminished dramatically by pre-incubation of trophozoites with resveratrol, evidencing that resveratrol attenuated the trophozoite virulence in vitro. Interestingly, after the inoculation of virulent trophozoites, animals treated with the drug did not develop or developed very small abscesses. Our findings propose that resveratrol could be an alternative to contend amoebiasis. PMID:26731663

  13. In vivo skin irritation potential of a Castanea sativa (Chestnut) leaf extract, a putative natural antioxidant for topical application.

    Science.gov (United States)

    Almeida, Isabel F; Valentão, Patrícia; Andrade, Paula B; Seabra, Rosa M; Pereira, Teresa M; Amaral, M Helena; Costa, Paulo C; Bahia, M Fernanda

    2008-11-01

    Topical application of natural antioxidants has proven to be effective in protecting the skin against ultraviolet-mediated oxidative damage and provides a straightforward way to strengthen the endogenous protection system. However, natural products can provoke skin adverse effects, such as allergic and irritant contact dermatitis. Skin irritation potential of Castanea sativa leaf ethanol:water (7:3) extract was investigated by performing an in vivo patch test in 20 volunteers. Before performing the irritation test, the selection of the solvent and extraction method was guided by the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging test and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron-chelating activity and the phenolic composition (high performance liquid chromatography/diode array detection) were evaluated for the extract obtained under optimized conditions. The extraction method adopted consisted in 5 short extractions (10 min.) with ethanol:water (7:3), performed at 40 degrees. The IC(50) found for the iron chelation and DPPH scavenging assays were 132.94 +/- 9.72 and 12.58 +/- 0.54 microg/ml (mean +/- S.E.M.), respectively. The total phenolic content was found to be 283.8 +/- 8.74 mg GAE/g extract (mean +/- S.E.M.). Five phenolic compounds were identified in the extract, namely, chlorogenic acid, ellagic acid, rutin, isoquercitrin and hyperoside. The patch test carried out showed that, with respect to irritant effects, this extract can be regarded as safe for topical application.

  14. Resveratrol Induces Apoptosis-Like Death and Prevents In Vitro and In Vivo Virulence of Entamoeba histolytica.

    Directory of Open Access Journals (Sweden)

    Jonnatan Pais-Morales

    Full Text Available Entamoeba histolytica causes amoebiasis, an infection that kills 100,000 individuals each year. Metronidazole and its derivatives are currently used against this protozoan, but these drugs present adverse effects on human health. Here, we investigated the effect of resveratrol (a natural compound on E. histolytica trophozoites viability, as well as its influence on the parasite virulence. Trophozoites growth was arrested by 72 μM resveratrol and the IC50 was determined as 220 μM at 48 h. Cells appeared smaller, rounded and in clusters, with debris-containing vacuoles and with abnormally condensed chromatin. Resveratrol triggered reactive oxygen species production. It caused lipid peroxidation and produced phosphatidylserine externalization and DNA fragmentation this latter evidenced by TUNEL assays. It also provoked an increase of intracellular Ca2+ concentration, activated calpain and decreased superoxide dismutase activity, indicating that an apoptosis-like event occurred; however, autophagy was not detected. Cytopathic activity, phagocytosis, encystment and in vivo virulence were diminished dramatically by pre-incubation of trophozoites with resveratrol, evidencing that resveratrol attenuated the trophozoite virulence in vitro. Interestingly, after the inoculation of virulent trophozoites, animals treated with the drug did not develop or developed very small abscesses. Our findings propose that resveratrol could be an alternative to contend amoebiasis.

  15. Ischemic small intestine-in vivo versus ex vivo bioimpedance measurements.

    Science.gov (United States)

    Strand-Amundsen, Runar J; Reims, Henrik M; Tronstad, Christian; Kalvøy, Håvard; Martinsen, Ørjan G; Høgetveit, Jan O; Ruud, Tom E; Tønnessen, Tor I

    2017-05-01

    Bioimpedance has been used to investigate changes in electrical parameters during ischemia in various tissues. The small intestine is a multi-layered structure, with several distinct tissue types, and ischemia related changes occur at different times in the different intestinal layers. When investigating how the electrical properties in the small intestine is affected by ischemia, some researchers have used ex vivo models while others have used in vivo models. In this study, we compare ischemic time development of electrical parameters in ischemic in vivo versus ex vivo small intestine. Measurements were performed using a two-electrode setup, with a Solartron 1260/1294 impedance gain-phase analyser. Electrodes were placed on the surface of ischemic pig jejunum, applying a voltage and measuring the resulting electrical admittance. In each pig, 4 segments of the jejunum were made ischemic by clamping the mesenteric arteries and veins, resulting in a 30 cm central zone of warm ischemia and edema. The in vivo part of the experiment lasted 10 h, after which 3 pieces of perfused small intestine were resected, stored in Ringer-acetat at 38 °C, and measured during a 10 h ex vivo experiment. Main results and significance: We found significant differences (p  vivo and ex vivo measurements as a function of ischemic time development. We also observed some similarities in the trends. In vivo, we measured an overall decrease in impedance during the duration of the experiment, probably as a result from the formation of edema. Ex vivo, the low frequency impedance increased initially for approximately 3 h before starting to decrease.

  16. In vivo cell tracking with bioluminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Eun; Kalimuthu, Senthilkumar; Ahn, Byeong Cheol [Dept. of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu (Korea, Republic of)

    2015-03-15

    Molecular imaging is a fast growing biomedical research that allows the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In vivo tracking of cells is an indispensable technology for development and optimization of cell therapy for replacement or renewal of damaged or diseased tissue using transplanted cells, often autologous cells. With outstanding advantages of bioluminescence imaging, the imaging approach is most commonly applied for in vivo monitoring of transplanted stem cells or immune cells in order to assess viability of administered cells with therapeutic efficacy in preclinical small animal models. In this review, a general overview of bioluminescence is provided and recent updates of in vivo cell tracking using the bioluminescence signal are discussed.

  17. In Vivo Immunogenic Response to Allogeneic Mesenchymal Stem Cells and the Role of Preactivated Mesenchymal Stem Cells Cotransplanted with Allogeneic Islets

    Directory of Open Access Journals (Sweden)

    Régis Linhares Oliveira

    2017-01-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent cells capable of differentiating into cells from the mesenchymal lineage. The hypoimmunogenic characteristic of MSCs has encouraged studies using allogeneic MSCs for the treatment of autoimmune diseases and inflammatory conditions. Promising preclinical results and the safety of allogeneic MSC transplantation have created the possibility of “off-the-shelf” clinical application of allogeneic cells. This study has aimed to evaluate the survival of untreated and IFN-γ- and TNF-α-treated (preactivated allogeneic MSCs transplanted under the kidney capsule of immunocompetent mice together with the role of preactivated MSCs after cotransplantation with allogeneic islets. The preactivation of MSCs upregulated the gene expression of anti-inflammatory molecules and also enhanced their immunomodulatory capacity in vitro. In vivo, allogeneic MSCs provoked an immunogenic response, with the infiltration of inflammatory cells at the transplant site and full graft rejection in both the untreated and preactivated groups. Allogeneic islets cotransplanted with preactivated MSCs prolonged graft survival for about 6 days, compared with islet alone. The present results corroborate the hypothesis that allogeneic MSCs are not immune-privileged and that after playing their therapeutic role they are rejected. Strategies that reduce allogeneic MSC immunogenicity can potentially prolong their in vivo persistence and improve the therapeutic effects.

  18. The small-molecule IAP antagonist AT406 inhibits pancreatic cancer cells in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Yongsheng; Meng, Qinghua [Department of General Surgery, Jinan Central Hospital of Shandong University, Jinan (China); Chen, Bo [Department of Biliary and Pancreatic Surgery, East Hospital Affiliated to Tongji University in Shanghai, Shanghai (China); Shen, Haiyu; Yan, Bing [Department of General Surgery, Jinan Central Hospital of Shandong University, Jinan (China); Sun, Baoyou, E-mail: sunbaoyou_sdu@yeah.net [Department of General Surgery, Shandong Provincial Hospital Affiliated to Shandong University, No.9677 Jing-Shi Road, Jinan 250014 (China)

    2016-09-09

    In the present study, we tested the anti-pancreatic cancer activity by AT406, a small-molecule antagonist of IAP (inhibitor of apoptosis proteins). In established (Panc-1 and Mia-PaCa-2 lines) and primary human pancreatic cancer cells, treatment of AT406 significantly inhibited cell survival and proliferation. Yet, same AT406 treatment was non-cytotoxic to pancreatic epithelial HPDE6c7 cells. AT406 increased caspase-3/-9 activity and provoked apoptosis in the pancreatic cancer cells. Reversely, AT406′ cytotoxicity in these cells was largely attenuated with pre-treatment of caspase inhibitors. AT406 treatment caused degradation of IAP family proteins (cIAP1 and XIAP) and release of cytochrome C, leaving Bcl-2 unaffected in pancreatic cancer cells. Bcl-2 inhibition (by ABT-737) or shRNA knockdown dramatically sensitized Panc-1 cells to AT406. In vivo, oral administration of AT406 at well-tolerated doses downregulated IAPs (cIAP1/XIAP) and inhibited Panc-1 xenograft tumor growth in severe combined immunodeficient (SCID) nude mice. Together, our preclinical results suggest that AT406 could be further evaluated as a promising anti-pancreatic cancer agent. - Highlights: • AT406 is cytotoxic to established/primary human pancreatic cancer cells. • AT406 provokes caspase-dependent apoptosis in pancreatic cancer cells. • AT406 causes degradation of key IAPs and promotes cytochrome C release. • Bcl-2 inhibition or knockdown dramatically sensitizes Panc-1 cells to AT406. • Oral administration of AT406 inhibits Panc-1 tumor growth in SCID nude mice.

  19. In vivo virtual intraoperative surgical photoacoustic microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seunghoon, E-mail: hsh860504@gmail.com; Kim, Sehui, E-mail: sehui0916@nate.com; Kim, Jeehyun, E-mail: jeehk@knu.ac.kr, E-mail: chulhong@postech.edu [School of Electrical Engineering and Computer Science, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Lee, Changho, E-mail: ch31037@postech.edu; Jeon, Mansik, E-mail: msjeon@postech.edu [Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784 (Korea, Republic of); Kim, Chulhong, E-mail: jeehk@knu.ac.kr, E-mail: chulhong@postech.edu [Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784 (Korea, Republic of); Department of Biomedical Engineering, The State University of New York at Buffalo, Buffalo, New York 14221 (United States)

    2013-11-11

    We developed a virtual intraoperative surgical photoacoustic microscopy system by combining with a commercial surgical microscope and photoacoustic microscope (PAM). By sharing the common optical path in the microscope and PAM system, we could acquire the PAM and microscope images simultaneously. Moreover, by employing a beam projector to back-project 2D PAM images onto the microscope view plane as augmented reality, the conventional microscopic and 2D cross-sectional PAM images are concurrently mapped on the plane via an ocular lens of the microscope in real-time. Further, we guided needle insertion into phantom ex vivo and mice skins in vivo.

  20. Crosswalking Research Vocabularies in VIVO.pptx

    OpenAIRE

    Elsborg, Don; Gross, Benjamin; Ilik, Violeta; Porter, Simon; gov, pfrank loc; Javed, Muhammad; edu, jaf cornell

    2017-01-01

    Many VIVO sites use different vocabularies to indicate the research areas they are affiliated with. For example the biological sciences uses PubMed MeSH subject headings but the Physical sciences might use a controlled vocabulary from a commercial vendor like Clarivate’s Web of Science Keywords or FAST terms from the Library of Congress. This can lead to redundancy and confusion on a VIVO site that allows the end user to filter based on a vocabulary term. The same or similar terms might displ...

  1. Natural-source d-α-tocopheryl acetate inhibits oxidant stress and modulates atopic asthma in humans in vivo.

    Science.gov (United States)

    Hoskins, Aimee; Roberts, Jackson L; Milne, Ginger; Choi, Leena; Dworski, Ryszard

    2012-05-01

    Asthma is associated with oxidant stress and diminished antioxidant defenses. Yet, the mechanistic role of oxidant stress and antioxidant supplementation in human asthmatics remains uncertain. We determined the effect of high doses of the antioxidant natural-source d-α-tocopheryl acetate for 16 weeks on allergen-induced airway oxidant stress, inflammation, and bronchial responsiveness to methacholine and allergen in atopic asthmatics in vivo. Thirty-three mild atopic asthmatics underwent bronchoscopy with baseline bronchoalveolar lavage and segmental allergen challenge. The allergen-challenged airway was lavaged 24 h later. At least 3 weeks later, patients underwent inhaled challenges with methacholine and specific allergen. Volunteers took 1500 IU of natural-source d-α-tocopheryl acetate daily for at least 16 weeks. At the end of the treatment, the two bronchoscopies and inhaled methacholine and allergen challenges were repeated. F(2)-isoprostanes, specific markers of oxidant stress, and selected Th1 and Th2 cytokines were analyzed in the lavage fluid. Following supplementation of natural-source d-α-tocopheryl acetate, plasma concentrations of α-tocopherol increased and γ-tocopherol decreased. Both baseline and allergen-induced F(2)-isoprostanes significantly decreased, providing biochemical evidence for an antioxidant effect. Natural-source d-α-tocopheryl acetate reduced allergen-provoked concentrations of interleukin 3 and interleukin 4 and augmented levels of interleukin 12 in bronchoalveolar lavage fluid. Natural-source d-α-tocopheryl acetate improved airway responsiveness to methacholine but did not alter airway reactivity to specific allergen. Inhibition of oxidant stress by natural-source d-α-tocopheryl acetate modulates allergic inflammation and airway hyperresponsiveness in human atopic asthmatics in vivo. These results need to be confirmed by a randomized placebo-controlled trial. © 2012 John Wiley & Sons A/S.

  2. Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin conjugate 4I: In vitro and in vivo studies.

    Directory of Open Access Journals (Sweden)

    Yao Yuan

    Full Text Available Photodynamic antimicrobial chemotherapy (PACT, as a novel and effective therapeutic modality to eradicate drug resistant bacteria without provoking multidrug resistance, has attracted increasing attention. This study examined the antimicrobial efficacy of the novel cationic amino acid-porphyrin conjugate 4I with four lysine groups against two different clinical isolated strains (drug sensitive and multidrug resistant of the Acinetobacter baumannii species and its toxicity on murine dermal fibroblasts in vitro, as well as the therapeutic effect of PACT on acute, potentially lethal multidrug resistant strain excisional wound infections in vivo. The PACT protocol exposed 4I to illumination, exhibiting high antimicrobial efficacy on two different strains due to a high yield of reactive oxygen species (ROS and non-selectivity to microorganisms. The photoinactivation effects of 4I against two different strains were dose-dependent. At 3.9 μM and 7.8 μM, PACT induced 6 log units of inactivation of sensitive and multidrug resistant strains. In contrast, 4I alone and illumination alone treatments had no visibly antimicrobial effect. Moreover, cytotoxicity tests revealed the great safety of the photosensitizer 4I in mice. In the in vivo study, we found 4I-mediated PACT was not only able to kill bacteria but also accelerated wound recovery. Compared with non-treated mice, over 2.89 log reduction of multidrug resistant Acinetobacter baumannii strain was reached in PACT treat mice at 24 h post-treatment. These results imply that 4I-mediated PACT therapy is an effective and safe alternative to conventional antibiotic therapy and has clinical potential for superficial drug-resistant bacterial infections.

  3. Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin conjugate 4I: In vitro and in vivo studies.

    Science.gov (United States)

    Yuan, Yao; Liu, Zi-Quan; Jin, Heng; Sun, Shi; Liu, Tian-Jun; Wang, Xue; Fan, Hao-Jun; Hou, Shi-Ke; Ding, Hui

    2017-01-01

    Photodynamic antimicrobial chemotherapy (PACT), as a novel and effective therapeutic modality to eradicate drug resistant bacteria without provoking multidrug resistance, has attracted increasing attention. This study examined the antimicrobial efficacy of the novel cationic amino acid-porphyrin conjugate 4I with four lysine groups against two different clinical isolated strains (drug sensitive and multidrug resistant) of the Acinetobacter baumannii species and its toxicity on murine dermal fibroblasts in vitro, as well as the therapeutic effect of PACT on acute, potentially lethal multidrug resistant strain excisional wound infections in vivo. The PACT protocol exposed 4I to illumination, exhibiting high antimicrobial efficacy on two different strains due to a high yield of reactive oxygen species (ROS) and non-selectivity to microorganisms. The photoinactivation effects of 4I against two different strains were dose-dependent. At 3.9 μM and 7.8 μM, PACT induced 6 log units of inactivation of sensitive and multidrug resistant strains. In contrast, 4I alone and illumination alone treatments had no visibly antimicrobial effect. Moreover, cytotoxicity tests revealed the great safety of the photosensitizer 4I in mice. In the in vivo study, we found 4I-mediated PACT was not only able to kill bacteria but also accelerated wound recovery. Compared with non-treated mice, over 2.89 log reduction of multidrug resistant Acinetobacter baumannii strain was reached in PACT treat mice at 24 h post-treatment. These results imply that 4I-mediated PACT therapy is an effective and safe alternative to conventional antibiotic therapy and has clinical potential for superficial drug-resistant bacterial infections.

  4. In vivo and ex vivo proton MR spectroscopy of primary and secondary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Bourne, Roger M.; Stanwell, Peter; Stretch, Jonathan R.; Scolyer, Richard A.; Thompson, John F.; Mountford, Carolyn E.; Lean, Cynthia L

    2005-03-01

    In vivo magnetic resonance (MR) spectroscopy at 1.5T was performed on a large polypoid cutaneous melanoma, and two enlarged lymph nodes containing metastatic melanoma, from three patients. Spectra were acquired in vivo from voxels wholly within the primary tumour or secondary lymph node and were thus uncontaminated by signals from adjacent tissue. Tissue biopsies taken after resection of primary tumours and secondary lymph nodes were examined by 8.5T magnetic resonance spectroscopy (MRS) and the results compared with the in vivo spectra, and with spectra from normal skin and a benign skin lesion. There was good agreement between the dominant features of 1.5T spectra acquired in vivo and 8.5T spectra acquired from resected tissue. However, less intense resonances observed at 8.5T in malignant biopsy tissue were not consistently observed at 1.5T in vivo. In vivo spectra from primary and metastatic melanoma showed high levels of choline metabolites. An intense lactate resonance was also present in the in vivo spectrum of primary melanoma. All 8.5T spectra of biopsies from primary and secondary melanoma showed high levels of choline metabolites and lactate, and additional resonances consistent with elevated levels of taurine, alanine, lysine, and glutamate/glutamine relative to normal and benign tissue. Elevated levels of choline, lactate, taurine, and amino acids appear to be clinically useful markers for identifying the pathology of primary and metastatic melanoma.

  5. Ex-vivo MR Volumetry of Human Brain Hemispheres

    Science.gov (United States)

    Kotrotsou, Aikaterini; Bennett, David A.; Schneider, Julie A.; Dawe, Robert J.; Golak, Tom; Leurgans, Sue E.; Yu, Lei; Arfanakis, Konstantinos

    2013-01-01

    Purpose The aims of this work were to: a) develop an approach for ex-vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, b) longitudinally assess regional brain volumes postmortem, and c) investigate the relationship between MR volumetric measurements performed in-vivo and ex-vivo. Methods An approach for ex-vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex-vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex-vivo was assessed. The relationship between in-vivo and ex-vivo volumetric measurements was investigated in seven elderly subjects imaged both ante-mortem and postmortem. Results The presented approach for ex-vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than inter-subject volume variation. A close linear correspondence was detected between in-vivo and ex-vivo volumetric measurements. Conclusion Regional brain volumes measured with the presented approach for ex-vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in-vivo and ex-vivo MR volumetric measurements suggests that the presented approach captures information linked to ante-mortem macrostructural brain characteristics. PMID:23440751

  6. In vivo dosimetry in external beam radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mijnheer, Ben [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam 1066 CX (Netherlands); Beddar, Sam [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Izewska, Joanna [Division of Human Health, International Atomic Energy Agency, Vienna 1400 (Austria); Reft, Chester [Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, Illinois 60637 (United States)

    2013-07-15

    In vivo dosimetry (IVD) is in use in external beam radiotherapy (EBRT) to detect major errors, to assess clinically relevant differences between planned and delivered dose, to record dose received by individual patients, and to fulfill legal requirements. After discussing briefly the main characteristics of the most commonly applied IVD systems, the clinical experience of IVD during EBRT will be summarized. Advancement of the traditional aspects of in vivo dosimetry as well as the development of currently available and newly emerging noninterventional technologies are required for large-scale implementation of IVD in EBRT. These new technologies include the development of electronic portal imaging devices for 2D and 3D patient dosimetry during advanced treatment techniques, such as IMRT and VMAT, and the use of IVD in proton and ion radiotherapy by measuring the decay of radiation-induced radionuclides. In the final analysis, we will show in this Vision 20/20 paper that in addition to regulatory compliance and reimbursement issues, the rationale for in vivo measurements is to provide an accurate and independent verification of the overall treatment procedure. It will enable the identification of potential errors in dose calculation, data transfer, dose delivery, patient setup, and changes in patient anatomy. It is the authors' opinion that all treatments with curative intent should be verified through in vivo dose measurements in combination with pretreatment checks.

  7. Ebola Virus Persistence in Semen Ex Vivo.

    Science.gov (United States)

    Fischer, Robert J; Judson, Seth; Miazgowicz, Kerri; Bushmaker, Trent; Munster, Vincent J

    2016-02-01

    On March 20, 2015, a case of Ebola virus disease was identified in Liberia that most likely was transmitted through sexual contact. We assessed the efficiency of detecting Ebola virus in semen samples by molecular diagnostics and the stability of Ebola virus in ex vivo semen under simulated tropical conditions.

  8. In vivo conservation of animal genetic resources

    NARCIS (Netherlands)

    Boettcher, P.; Martin, J.F.; Gandini, G.; Joshi, B.K.; Oldenbroek, J.K.

    2013-01-01

    These guidelines present the basic concepts involved in the development and implementation of in vivo conservation plans for animal genetic resources for food and agriculture. The guidelines are intended for use by policy-makers in the management of animal genetic resources, managers of animal

  9. Three-dimensional carpal kinematics in vivo

    NARCIS (Netherlands)

    Moojen, T. M.; Snel, J. G.; Ritt, M. J. P. F.; Kauer, J. M. G.; Venema, H. W.; Bos, K. E.

    2002-01-01

    Objective. The purpose of this study was to accurately quantify three-dimensional in vivo kinematics of all carpal bones in flexion and extension and radial and ulnar deviation. Design and methods. The right wrists of 11 healthy volunteers were imaged by spiral CT with rotational increments of

  10. In vivo biomechanics of cruciate ligament injuries

    NARCIS (Netherlands)

    Van de Velde, S.K.

    2016-01-01

    Measuring biomechanics of the knee with an acceptable degree of accuracy is difficult. When the in vivo knee joint motion is analyzed in all its six degrees-of-freedom without compromising on physiological loading conditions, the task becomes even more challenging. This thesis offers a brief

  11. Ex vivo MRI in extracorporeal liver surgery

    NARCIS (Netherlands)

    Wolf, RFE; Slooff, MJH; Peeters, PMJG; deJong, KP; Kamman, RL; Mooyaart, EL

    1995-01-01

    Extracorporeal resection of hepatic tumors that were considered inoperable in the past is now possible in selected cases, Such procedures require high-quality preoperative images for the exact delineation of the tumor extent and for an optimal planning of the line of parenchymal division, In-vivo CT

  12. Fiberoptic imaging of cavernous nerves in vivo.

    Science.gov (United States)

    Boyette, Lisa B; Reardon, Michael A; Mirelman, Andrew J; Kirkley, Terry D; Lysiak, Jeffrey J; Tuttle, Jeremy B; Steers, William D

    2007-12-01

    A critical intraoperative variable for the return of tumescence following radical prostatectomy is preservation of the cavernous nerves. We developed a nontoxic technique that would allow high resolution, in vivo real-time imaging specifically of the cavernous nerves. The cavernous nerves were labeled by injecting a fluorescent retrograde nerve tracer into the corpus cavernosum of male rats. Nerves were subsequently imaged in vivo using fiberoptic confocal fluorescent microscopy. Initial screening trials were performed to decide on a nerve tracer capable of axonal labeling, optimize injection concentration and characterize retrograde transport time. Toxicity studies included intracavernous pressure monitoring following electrical nerve stimulation, apoptotic staining of injected cavernous tissue and measurement of lipid peroxidation in nerves exposed to laser emissions during imaging. In vivo real-time video sequences of fluorescently labeled cavernous nerves were recorded. The screening trial indicated that the B subunit of cholera toxin conjugated to AlexaFluor 488 (Invitrogen) provided optimal imaging after 9 days of retrograde transport. Toxicity studies showed that maximal intracavernous pressure responses did not differ between labeled and unlabeled nerves (p = 0.9671). Tracer injection did not increase apoptosis in cavernous tissue and laser exposure did not increase lipid peroxidation in nerves. In vivo real-time imaging of the cavernous nerves is possible with no measurable toxicity, allowing the maintenance of erection. This novel imaging modality may allow urologists to identify cavernous nerves during pelvic surgery.

  13. In vivo gluten challenge in coeliac disease

    Directory of Open Access Journals (Sweden)

    HJ Ellis

    2001-01-01

    Full Text Available In vivo gluten challenge has been used since the early 1950s to study the role of cereal fractions in celiac disease. While early studies relied on crude indicators of celiac toxicity, the advent of jejunal biopsy and sophisticated immunohistochemical techniques has allowed accurate studies to be performed. Studies to determine the nature of the cereal component that is toxic to patients with celiac disease have concentrated on wheat because of its nutritional importance. A number of in vitro studies indicated the presence of one or more celiac-activating epitopes with the N-terminus of the A-gliadin molecule. In vivo challenge with three synthetic peptides subsequently indicated the toxicity of a peptide corresponding to amino acids 31 to 49 of A-gliadin. In vivo gluten challenge is the gold standard for the assessment of celiac toxicity; however, jejunal biopsy is a relatively invasive procedure, thus, other methods have been investigated. Direct infusion of the rectum with gluten has been shown to result in an increase in mucosal intraepithelial lymphocytes, occurring only in celiac patients. This method has been used to study the celiac toxicity of gliadin subfractions. The in vitro technique of small intestinal biopsy organ culture is also a useful tool and appears to give the same results as in vivo challenge. The importance of tiny amounts of gliadin in the diet, such as that which occurs in wheat starch, has been studied by in vivo challenge; this technique has clarified the position of oats in the gluten-free diet. Several studies suggest that this cereal may be included in the diet of most adult celiac patients. Studies of the transport of gliadin across the enterocyte following ingestion or challenge suggest that gliadin may be metabolized by a different pathway in celiac disease. This could result in an abnormal presentation to the immune system, triggering a pathogenic rather than a tolerogenic response.

  14. Antimicrobial Blue Light Therapy for Infectious Keratitis: Ex Vivo and In Vivo Studies.

    Science.gov (United States)

    Zhu, Hong; Kochevar, Irene E; Behlau, Irmgard; Zhao, Jie; Wang, Fenghua; Wang, Yucheng; Sun, Xiaodong; Hamblin, Michael R; Dai, Tianhong

    2017-01-01

    To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis. We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colony-forming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety. Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log10) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea. Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted.

  15. Evaluation of a novel electrosurgical sealing mode in an ex vivo and in vivo porcine model.

    Science.gov (United States)

    Thiel, Karolin; Linzenbold, Walter; Enderle, Markus D; Nold, B; Königsrainer, Alfred; Schenk, Martin; Thiel, Christian

    2017-09-18

    Bipolar vessel sealing has been successfully introduced in a variety of procedures like prostatectomy, hysterectomy, and nephrectomy. In this study, we evaluated a new sealing mode-the thermoSEAL® mode (TSM)-operated with the VIO3 generator in an ex vivo and in vivo animal study and compared the results with the commercially available BiClamp mode (BCM), operated with the VIO300D generator. Two different instruments were used in combination with both modes, BiCision® and BiClamp® 201T (Erbe Elektromedizin GmbH). In the ex vivo experiment, the sealing of renal arteries was evaluated using both instruments and modes. For the in vivo study, different types of arteries and veins were sealed using both modes and instruments in a side-by-side comparison for acute complications in a total of four animals. Mean burst pressure was in all cases significantly above 360 mmHg (p vivo setting was significantly shorter for TSM compared to BCM: BiCision® (3.7 ± 0.4 vs. 7.1 ± 0.3 s; p vivo study was significantly shorter for TSM in combination with BiCision® for arteries [TSM 3.0 ± 0.7 s vs. BCM 6.5 ± 1.3 s, (p 90%) were noted for both instruments and modes. While both modes used with two different instruments reveal high safety characterized by a high burst pressure, low thermal damage (ex vivo) zones, and high sealing rates (in vivo), the thermoSEAL® mode convinces by its fast sealing speed probably helping to reduce operation time.

  16. Microwave ablation of primary and secondary liver tumours: ex vivo, in vivo, and clinical characterisation.

    Science.gov (United States)

    Amabile, Claudio; Ahmed, Muneeb; Solbiati, Luigi; Meloni, Maria Franca; Solbiati, Marco; Cassarino, Simone; Tosoratti, Nevio; Nissenbaum, Yitzhak; Ierace, Tiziana; Goldberg, S Nahum

    2017-02-01

    The aim of this study was to compare the performance of a microwave ablation (MWA) apparatus in preclinical and clinical settings. The same commercial 2.45 GHz MWA apparatus was used throughout this study. In total 108 ablations at powers ranging from 20 to 130 W and lasting from 3 to 30 min were obtained on ex vivo bovine liver; 28 ablations at 60 W, 80 W and 100 W lasting 5 and 10 min were then obtained in an in vivo swine model. Finally, 32 hepatocellular carcinomas (HCCs) and 19 liver metastases in 46 patients were treated percutaneously by administering 60 W for either 5 or 10 min. The treatment outcome was characterised in terms of maximum longitudinal and transversal axis of the induced ablation zone. Ex vivo ablation volumes increased linearly with deposited energy (r2 = 0.97), with higher sphericity obtained at lower power for longer ablation times. Larger ablations were obtained on liver metastases compared to HCCs treated with 60 W for 10 min (p vivo swine model at 60 W were substantially smaller than the ex vivo and clinical results (either populations). No statistically significant difference was observed between ex vivo results at 60 W and HCC results (p > 0.08). For the selected MW ablation device, ex vivo data on bovine liver was more predictive of the actual clinical performance on liver malignancies than an in vivo porcine model. Equivalent MW treatments yielded a significantly different response for HCC and metastases at higher deposited energy, suggesting that outcomes are not only device-specific but must also be characterised on a tissue-by-tissue basis.

  17. In vivo percutaneous microwave ablation in kidneys: Correlation with ex vivo data and ablation work.

    Science.gov (United States)

    Marcelin, C; Leiner, J; Nasri, S; Petitpierre, F; Le Bras, Y; Yacoub, M; Grenier, N; Bernhard, J C; Cornelis, F

    2017-10-21

    To compare diameters of in vivo microwave ablation (MWA) performed in swine kidneys with ex vivo diameters, and to correlate with ablation work (AW), a new metric reflecting total energy delivered. Eighteen in vivo MWA were performed in 6 swine kidneys successively using one or two antennas (MicroThermX®). Ablation consisted in delivering power (45-120W) for 5-15minutes. Ex vivo diameters were provided by the vendors and obtained on bovine liver tissue. AW was defined as the sum of (power)*(time)*(number of antennas) for all phases of an ablation (in kJoules). Kidneys were removed laparoscopically immediately after ablation. After sacrifice, ablations zones were evaluated macroscopically, and maximum diameters of the zones were recorded. Wilcoxon sum rank test and Pearson's correlation were used for comparisons. For a single antenna (n=12), the in vivo diameters ranged from 12 to 35mm, and 15-49mm for 2 antennas (n=6). The in vivo diameters remained shorter than ex vivo diameters by 8.6%±30.1 on 1 antenna and 11.7%±26.5 on 2 antennas (P=0.31 and 0.44, respectively). AW ranged from 13.5 to 108kJ. Diameters increased linearly with AW both with 1 and 2 antennas, but only moderate correlations were observed (r=0.43 [95% confidence interval: -0.19; 0.81], P=0.16; and 0.57 [-0.44; 0.95], P=0.24, respectively). Although diameters after in vivo renal MWA increased linearly with AW, the moderate correlation and wide standard deviations observed may justify a careful imaging monitoring during treatment delivery and settings adaptation, if needed, for optimal ablation. Copyright © 2017 Editions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  18. In vivo and ex vivo effects of propofol on myocardial performance in rats with obstructive jaundice

    Directory of Open Access Journals (Sweden)

    Ren Hong-Mei

    2011-12-01

    Full Text Available Abstract Background Responsiveness of the "jaundiced heart" to propofol is not completely understood. The purpose of this study was to evaluate the effect of propofol on myocardial performance in rats with obstructive jaundice. Methods Male Sprague-Dawley rats (n = 40 were randomly allocated into two groups, twenty underwent bile duct ligation (BDL, and 20 underwent a sham operation. Seven days after the surgery, propofol was administered in vivo and ex vivo (Langendorff preparations. Heart rate, left ventricular end-systolic pressure (LVESP left ventricular end-diastolic pressure (LVEDP, and maximal rate for left ventricular pressure rise and decline (± dP/dtmax were measured to determine the influence of propofol on the cardiac function of rats. Results Impaired basal cardiac function was observed in the isolated BDL hearts, whereas in vivo indices of basal cardiac function (LVESP and ± dP/dt in vivo were significantly higher in rats that underwent BDL compared with controls. With low or intermediate concentrations of propofol, these indices of cardiac function were within the normal physiologic range in both groups, and responsiveness to propofol was unaffected by BDL. When the highest concentration of propofol was administrated, a significant decline in cardiac function was observed in the BDL group. Conclusions In rats that underwent BDL, basal cardiac performance was better in vivo and worse ex vivo compared with controls. Low and intermediate concentrations of propofol did not appear to impair cardiac function in rats with obstructive jaundice.

  19. Digital Radiography for Determination of Primary Tooth Length: In Vivo and Ex Vivo Studies

    Directory of Open Access Journals (Sweden)

    Maria D. Basso

    2015-01-01

    Full Text Available Background. Methods for determining the root canal length of the primary tooth should yield accurate and reproducible results. In vitro studies show some limitations, which do not allow their findings to be directly transferred to a clinical situation. Aim. To compare the accuracy of radiographic tooth length obtained from in vivo digital radiograph with that obtained from ex vivo digital radiograph. Method. Direct digital radiographs of 20 upper primary incisors were performed in teeth (2/3 radicular resorption that were radiographed by an intraoral sensor, according to the long-cone technique. Teeth were extracted, measured, and mounted in a resin block, and then radiographic template was used to standardise the sensor-target distance (30 cm. The apparent tooth length (APTL was obtained from the computer screen by means of an electronic ruler accompanying the digital radiography software (CDR 2.0, whereas the actual tooth length (ACTL was obtained by means of a digital calliper following extraction. Data were compared to the ACTL by variance analysis and Pearson’s correlation test. Results. The values for APTL obtained from in vivo radiography were slightly underestimated, whereas those values obtained from ex vivo were slightly overestimated. No significance was observed (P≤0.48 between APTL and ACTL. Conclusion. The length of primary teeth estimated by in vivo and ex vivo comparisons using digital radiography was found to be similar to the actual tooth length.

  20. Development of a multilayered palate substitute in rabbits: a histochemical ex vivo and in vivo analysis.

    Science.gov (United States)

    Martín-Piedra, M A; Alaminos, M; Fernández-Valadés-Gámez, R; España-López, A; Liceras-Liceras, E; Sánchez-Montesinos, I; Martínez-Plaza, A; Sánchez-Quevedo, M C; Fernández-Valadés, R; Garzón, I

    2017-03-01

    Current tissue engineering technology focuses on developing simple tissues, whereas multilayered structures comprising several tissue types have rarely been described. We developed a highly biomimetic multilayered palate substitute with bone and oral mucosa tissues using rabbit cells and biomaterials subjected to nanotechnological techniques based on plastic compression. This novel palate substitute was autologously grafted in vivo, and histological and histochemical analyses were used to evaluate biointegration, cell function, and cell differentiation in the multilayered palate substitute. The three-dimensional structure of the multilayered palate substitute was histologically similar to control tissues, but the ex vivo level of cell and tissue differentiation were low as determined by the absence of epithelial differentiation although cytokeratins 4 and 13 were expressed. In vivo grafting was associated with greater cell differentiation, epithelial stratification, and maturation, but the expression of cytokeratins 4, 13, 5, and 19 at did not reach control tissue levels. Histochemical analysis of the oral mucosa stroma and bone detected weak signals for proteoglycans, elastic and collagen fibers, mineralization deposits and osteocalcin in the multilayered palate substitute cultured ex vivo. However, in vivo grafting was able to induce cell and tissue differentiation, although the expression levels of these components were always significantly lower than those found in controls, except for collagen in the bone layer. These results suggest that generation of a full-thickness multilayered palate substitute is achievable and that tissues become partially differentiated upon in vivo grafting.

  1. Ex Vivo and in Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac Fibrosis

    Directory of Open Access Journals (Sweden)

    Sanne de Jong

    2014-12-01

    Full Text Available Cardiac fibrosis is a major hallmark of cardiac diseases. For evaluation of cardiac fibrosis, the development of highly specific and preferably noninvasive methods is desired. Our aim was to evaluate CNA35, a protein known to specifically bind to collagen, as a specific marker of cardiac fibrosis. Fluorescently labeled CNA35 was applied ex vivo on tissue sections of fibrotic rat, mouse, and canine myocardium. After quantification of CNA35, sections were examined with picrosirius red (PSR and compared to CNA35. Furthermore, fluorescently labeled CNA35 was administered in vivo in mice. Hearts were isolated, and CNA35 labeling was examined in tissue sections. Serial sections were histologically examined with PSR. Ex vivo application of CNA35 showed specific binding to collagen and a high correlation with PSR (Pearson r = .86 for mice/rats and r = .98 for canine; both p < .001. After in vivo administration, CNA35 labeling was observed around individual cardiomyocytes, indicating its ability to penetrate cardiac endothelium. High correlation was observed between CNA35 and PSR (r = .91, p < .001. CNA35 specifically binds to cardiac collagen and can cross the endothelial barrier. Therefore, labeled CNA35 is useful to specifically detect collagen both ex vivo and in vivo and potentially can be converted to a noninvasive method to detect cardiac fibrosis.

  2. Quantification of carbon nanomaterials in vivo.

    Science.gov (United States)

    Wang, Haifang; Yang, Sheng-Tao; Cao, Aoneng; Liu, Yuanfang

    2013-03-19

    A diverse array of carbon nanomaterials (NMs), including fullerene, carbon nanotubes (CNTs), graphene, nanodiamonds, and carbon nanoparticles, have been discovered and widely applied in a variety of industries. Carbon NMs have been detected in the environment and have a strong possibility of entering the human body. The safety of carbon NMs has thus become a serious concern in academia and society. To achieve strict biosafety assessments, researchers need to fully understand the effects and fates of NMs in the human body, including information about absorption, distribution, metabolism, excretion, and toxicity (ADME/T). To acquire the ADME data, researchers must quantify NMs, but carbon NMs are very difficult to quantify in vivo. The carbon background in a typical biological system is high, particularly compared with the much lower concentration of carbon NMs. Moreover, carbon NMs lack a specific detection signal. Therefore, isotopic labeling, with its high sensitivity and specificity, is the first choice to quantify carbon NMs in vivo. Previously, researchers have used many isotopes, including ¹³C, ¹⁴C, ¹²⁵I, ¹³¹I, ³H, ⁶⁴Cu, ¹¹¹In, ⁸⁶Y, 99mTc, and ⁶⁷Ga, to label carbon NMs. We used these isotopic labeling methods to study the ADME of carbon NMs via different exposure pathways in animal models. Except for the metabolism of carbon NMs, which has seldom been investigated, significant amounts of data have been reported on the in vivo absorption, distribution, excretion, and toxicity of carbon NMs, which have revealed characteristic behaviors of carbon NMs, such as reticuloendothelial system (RES) capture. However, the complexity of the biological systems and diverse preparation and functionalization of the same carbon NMs have led to inconsistent results across different studies. Therefore, the data obtained so far have not provided a compatible and systematic profile of biosafety. Further efforts are needed to address these problems. In

  3. Cytogenotoxicity screening of source water, wastewater and treated water of drinking water treatment plants using two in vivo test systems: Allium cepa root based and Nile tilapia erythrocyte based tests.

    Science.gov (United States)

    Hemachandra, Chamini K; Pathiratne, Asoka

    2017-01-01

    Biological effect directed in vivo tests with model organisms are useful in assessing potential health risks associated with chemical contaminations in surface waters. This study examined the applicability of two in vivo test systems viz. plant, Allium cepa root based tests and fish, Oreochromis niloticus erythrocyte based tests for screening cytogenotoxic potential of raw source water, water treatment waste (effluents) and treated water of drinking water treatment plants (DWTPs) using two DWTPs associated with a major river in Sri Lanka. Measured physico-chemical parameters of the raw water, effluents and treated water samples complied with the respective Sri Lankan standards. In the in vivo tests, raw water induced statistically significant root growth retardation, mitodepression and chromosomal abnormalities in the root meristem of the plant and micronuclei/nuclear buds evolution and genetic damage (as reflected by comet scores) in the erythrocytes of the fish compared to the aged tap water controls signifying greater genotoxicity of the source water especially in the dry period. The effluents provoked relatively high cytogenotoxic effects on both test systems but the toxicity in most cases was considerably reduced to the raw water level with the effluent dilution (1:8). In vivo tests indicated reduction of cytogenotoxic potential in the tested drinking water samples. The results support the potential applications of practically feasible in vivo biological test systems such as A. cepa root based tests and the fish erythrocyte based tests as complementary tools for screening cytogenotoxicity potential of the source water and water treatment waste reaching downstream of aquatic ecosystems and for evaluating cytogenotoxicity eliminating efficacy of the DWTPs in different seasons in view of human and ecological safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. 3D morphological analysis of the mouse cerebral vasculature: Comparison of in vivo and ex vivo methods.

    Science.gov (United States)

    Steinman, Joe; Koletar, Margaret M; Stefanovic, Bojana; Sled, John G

    2017-01-01

    Ex vivo 2-photon fluorescence microscopy (2PFM) with optical clearing enables vascular imaging deep into tissue. However, optical clearing may also produce spherical aberrations if the objective lens is not index-matched to the clearing material, while the perfusion, clearing, and fixation procedure may alter vascular morphology. We compared in vivo and ex vivo 2PFM in mice, focusing on apparent differences in microvascular signal and morphology. Following in vivo imaging, the mice (four total) were perfused with a fluorescent gel and their brains fructose-cleared. The brain regions imaged in vivo were imaged ex vivo. Vessels were segmented in both images using an automated tracing algorithm that accounts for the spatially varying PSF in the ex vivo images. This spatial variance is induced by spherical aberrations caused by imaging fructose-cleared tissue with a water-immersion objective. Alignment of the ex vivo image to the in vivo image through a non-linear warping algorithm enabled comparison of apparent vessel diameter, as well as differences in signal. Shrinkage varied as a function of diameter, with capillaries rendered smaller ex vivo by 13%, while penetrating vessels shrunk by 34%. The pial vasculature attenuated in vivo microvascular signal by 40% 300 μm below the tissue surface, but this effect was absent ex vivo. On the whole, ex vivo imaging was found to be valuable for studying deep cortical vasculature.

  5. Correlation of In Vivo and Ex Vivo ADC and T2 of In Situ and Invasive Murine Mammary Cancers

    Science.gov (United States)

    Fan, Xiaobing; Macleod, Kay; Mustafi, Devkumar; Conzen, Suzanne D.; Markiewicz, Erica; Zamora, Marta; Vosicky, James; Mueller, Jeffrey; Karczmar, Gregory S.

    2015-01-01

    Ex vivo MRI may aid in the evaluation of surgical specimens, and provide valuable information regarding the micro-anatomy of mammary/breast cancer. The use of ex vivo MRI to study mouse mammary cancer would be enhanced if there is a strong correlation between parameters derived from in vivo and ex vivo scans. Here, we report the correlation between apparent diffusion coefficient (ADC) and T2 values measured in vivo and ex vivo in mouse mammary glands with in situ cancers (mammary intraepithelial neoplasia (MIN)) and invasive cancers (those which spread outside the ducts into surrounding tissue). MRI experiments were performed on the Polyoma middle T oncoprotein breast cancer mouse model (n = 15) in a 9.4T scanner. For in vivo experiments, T2-weighted (T2W) images were acquired to identify abnormal regions, then ADC and T2 values were measured for nine selected slices. For ex vivo experiments, a midline incision was made along the spine, and then skin, glands, and tumors were gently peeled from the body. Tissue was fixed in formalin, placed around a mouse-sized sponge, and sutured together mimicking the geometry of the gland when attached to the mouse. The same pulse sequences used for in vivo experiments were repeated for ex vivo scans at room temperature. Regions of interest were manually traced on T2W images defining features that could be identified on in vivo and ex vivo images. The results demonstrate a strong positive correlations between in vivo and ex vivo invasive cancers for ADC (r = 0.89, p vivo and ex vivo in situ cancers for ADC (r = 0.61, p vivo ADC value was about 54% of the in vivo value; and the average ex vivo T2 was similar to the in vivo value for cancers. Although motion, fixation, and temperature differences affect ADC and T2, these results show a reliable relationship between ADC and T2 in vivo and ex vivo. As a result ex vivo images can provide valuable information with clinical and research applications. PMID:26208092

  6. In vivo immuno-reactivity analysis of the porous three-dimensional chitosan/SiO2 and chitosan/SiO2 /hydroxyapatite hybrids.

    Science.gov (United States)

    Guo, Mengxia; Dong, Yifan; Xiao, Jiangwei; Gu, Ruicai; Ding, Maochao; Huang, Tao; Li, Junhua; Zhao, Naru; Liao, Hua

    2018-01-03

    Inorganic/organic hybrid silica-chitosan (CS) scaffolds have promising potential for bone defect repair, due to the controllable mechanical properties, degradation behavior, and scaffold morphology. However, the precise in vivo immuno-reactivity of silica-CS hybrids with various compositions is still poorly defined. In this study, we fabricated the three-dimensional (3D) interconnected porous chitosan-silica (CS/SiO2 ) and chitosan-silica-hydroxyapatite (CS/SiO2 /HA) hybrids, through sol-gel process and 3D plotting skill, followed by the naturally or freeze drying separately. Scanning electron microscopy demonstrated the hybrids possessed the uniform geometric structure, while, transmission electron microscopy displayed nanoscale silica, or HA nanoparticles dispersed homogeneously in the CS matrix, or CS/silica hybrids. After intramuscular implantation, CS/SiO2 and CS/SiO2 /HA hybrids triggered a local and limited monocyte/macrophage infiltration and myofiber degeneration. Naturally dried CS/SiO2 hybrid provoked a more severe inflammation than the freeze-dried ones. Dendritic cells were attracted to invade into the implants embedded-muscle, but not be activated to prime the adaptive immunity, because the absence of cytotoxic T cells and B cells in muscle received the implants. Fluorescence-activated cell sorting (FACS) analysis indicated the implanted hybrids were incapable to initiate splenocytes activation. Plasma complement C3 enzyme linked immunosorbent assay (ELISA) assay showed the hybrids induced C3 levels increase in early implanting phase, and the subsequent striking decrease. Thus, the present results suggest that, in vivo, 3D plotted porous CS/SiO2 and CS/SiO2 /HA hybrids are relatively biocompatible in vivo, which initiate a localized inflammatory procedure, instead of a systematic immune response. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2018 Wiley Periodicals, Inc.

  7. In vivo toxicity study of Lantana camara

    OpenAIRE

    Badakhshan Mahdi Pour; Sreenivasan Sasidharan

    2011-01-01

    Objective: To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara (L. Camara) in Artemia salina. Methods: The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. Results: All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Conclusions: Methanolic...

  8. Gut proteases target Yersinia invasin in vivo

    Directory of Open Access Journals (Sweden)

    Freund Sandra

    2011-04-01

    Full Text Available Abstract Background Yersinia enterocolitica is a common cause of food borne gastrointestinal disease. After oral uptake, yersiniae invade Peyer's patches of the distal ileum. This is accomplished by the binding of the Yersinia invasin to β1 integrins on the apical surface of M cells which overlie follicle associated lymphoid tissue. The gut represents a barrier that severely limits yersiniae from reaching deeper tissues such as Peyer's patches. We wondered if gut protease attack on invasion factors could contribute to the low number of yersiniae invading Peyer's patches. Findings Here we show that invasin is rapidly degraded in vivo by gut proteases in the mouse infection model. In vivo proteolytic degradation is due to proteolysis by several gut proteases such as trypsin, α-chymotrypsin, pancreatic elastase, and pepsin. Protease treated yersiniae are shown to be less invasive in a cell culture model. YadA, another surface adhesin is cleaved by similar concentrations of gut proteases but Myf was not cleaved, showing that not all surface proteins are equally susceptible to degradation by gut proteases. Conclusions We demonstrate that gut proteases target important Yersinia virulence factors such as invasin and YadA in vivo. Since invasin is completely degraded within 2-3 h after reaching the small intestine of mice, it is no longer available to mediate invasion of Peyer's patches.

  9. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo.

    Science.gov (United States)

    Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Felder, Paul; Cusumano, Andrew; Moley, Kelle H

    2017-08-24

    Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an ex vivo testicular explant model and in vivo exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration in vivo Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar in vivo and ex vivo. Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo. © FASEB.

  10. In vivo and ex vivo sentinel node mapping does not identify the same lymph nodes in colon cancer

    DEFF Research Database (Denmark)

    Andersen, Helene Schou; Bennedsen, Astrid Louise Bjørn; Burgdorf, Stefan Kobbelgaard

    2017-01-01

    sentinel node mapping in vivo with indocyanine green and ex vivo with methylene blue in order to evaluate if the sentinel lymph nodes can be identified by both techniques. METHODS: Patients with colon cancer UICC stage I-III were included from two institutions in Denmark from February 2015 to January 2016....... In vivo sentinel node mapping with indocyanine green during laparoscopy and ex vivo sentinel node mapping with methylene blue were performed in all patients. RESULTS: Twenty-nine patients were included. The in vivo sentinel node mapping was successful in 19 cases, and ex vivo sentinel node mapping...... mapping. Lymph node metastases were found in 10 patients, and only two had metastases in a sentinel node. CONCLUSION: Placing a deposit in relation to the tumor by indocyanine green in vivo or of methylene blue ex vivo could only identify sentinel lymph nodes in a small group of patients....

  11. Correlations between in vivo (1)H MRS and ex vivo (1)H HRMAS metabolite measurements in adult human gliomas.

    NARCIS (Netherlands)

    Opstad, K.S.; Wright, A.J.; Bell, B.A.; Griffiths, J.R.; Howe, F.A.

    2010-01-01

    PURPOSE: To assess how accurately ex vivo high-resolution magic angle spinning (HRMAS) proton magnetic resonance spectroscopy ((1)H MRS) from small biopsy tissues relate to in vivo (1)H MRS (from larger tumor volumes) in human astrocytomas. MATERIALS AND METHODS: In vivo (PRESS, TE = 30 msec) and ex

  12. Comparison of in vivo cardiac function with ex vivo cardiac performance of the rat heart after thoracic irradiation

    NARCIS (Netherlands)

    Franken, N. A.; Camps, J. A.; van Ravels, F. J.; van der Laarse, A.; Pauwels, E. K.; Wondergem, J.

    1997-01-01

    The aim of the study was to compare in vivo cardiac function with ex vivo cardiac performance after local heart irradiation in the same rat. Left ventricular ejection fraction (LVEF) was measured in vivo by radionuclide ventriculography in Sprague-Dawley rats up to 16 months after a single dose of

  13. Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies.

    Science.gov (United States)

    Abdelbary, Ghada A; Amin, Maha M; Zakaria, Mohamed Y

    2017-11-01

    Vesicular drug carriers for ocular delivery have gained a real potential. Proniosomal gels as ocular drug carriers have been proven to be an effective way to improve bioavailability and patient compliance. Formulation and in vitro/ex vivo/in vivo characterization of ketoconazole (KET)-loaded proniosomal gels for the treatment of ocular keratitis. The effect of formulation variables; HLB value, type and concentration of non-ionic surfactants (Tweens, Spans, Brijs and Pluronics) with or without lecithin on the entrapment efficiency (EE%), vesicle size and in vitro KET release was evaluated. An ex vivo corneal permeation study to determine the level of KET in the external eye tissue of albino rabbits and an in vivo assessment of the level of KET in the aqueous humors were performed. In vivo evaluation showed an increase in bioavailability up to 20-folds from the optimum KET proniosomal gel formula in the aqueous humor compared to drug suspension (KET-SP). The selected formulae were composed of spans being hydrophobic suggesting the potential use of a more hydrophobic surfactant as Span during the formulation of formulae. Factors that stabilize the vesicle membrane and increase the entrapment efficiency of KET (namely low HLB, long alkyl chain, high phase transition temperature) slowed down the release profile. Proniosomal gels as drug delivery carriers were proven to be a promising approach to increase corneal contact and permeation as well as retention time in the eye resulting in a sustained action and enhanced bioavailability.

  14. Sleep deprivation decreases neuronal excitability and responsiveness in rats both in vivo and ex vivo.

    Science.gov (United States)

    Borbély, Sándor; Világi, Ildikó; Haraszti, Zsófia; Szalontai, Örs; Hajnik, Tünde; Tóth, Attila; Détári, László

    2017-12-11

    Sleep deprivation has severe consequences for higher nervous functions. Its effects on neuronal excitability may be one of the most important factors underlying functional deterioration caused by sleep loss. In the present work, excitability changes were studied using two complementary in vivo and ex vivo models. Auditory evoked potentials were recorded from freely-moving animals in vivo. Amplitude of evoked responses showed a near-continuous decrease during deprivation. Prevention of sleep also reduced synaptic efficacy ex vivo, measured from brain slices derived from rats that underwent sleep deprivation. While seizure susceptibility was not affected significantly by sleep deprivation in these preparations, the pattern of spontaneous seizure activity was altered. If seizures developed, they lasted longer and tended to contain more spikes in slices obtained from sleep-deprived than from control rats. Current-source density analysis revealed that location and sequence of activation of local cortical networks recruited by seizures did not change by sleep deprivation. Moderate differences seen in the amplitude of individual sinks and sources might be explained by smaller net transmembrane currents as a consequence of decreased excitability. These findings contradict the widely accepted conception of synaptic homeostasis suggesting gradual increase of excitability during wakefulness. Our results also indicate that decreased neuronal excitability caused by sleep deprivation is preserved in slices prepared from rats immediately after deprivation. This observation might mean new opportunities to explore the effects of sleep deprivation in ex vivo preparations that allow a wider range of experimental manipulations and more sophisticated methods of analysis than in vivo preparations. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Role of the metabolism of parathyroid hormone. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Teitelbaum, Anne P. [Univ. of Rochester, NY (United States)

    1978-01-01

    The heterogeneity of parathyroid hormone (PTH) in plasma has prompted investigations of the metabolism of PTH and its relationship to hormone action. The time course of tissue distribution and metabolism of electrolytically iodinated PTH (E-PTH) previously shown to retain biological activity was compared with that of inactive PTH iodinated with Chloramine-T (CT-PTH). Labeled PTH (0.4 μg) was injected in the saphenous veins of anesthetized rats which were sacrificed at 1, 3, 5, 10, and 20 min. Tissue extracts from kidney, liver, and serum were chromatographed to separate intact PTH from its metabolites. In the kidney, the initial rate of degradation of E-PTH was greater than that of CT-PTH. The difference in initial rates of metabolism may be due, in part, to receptor-specific hydrolysis on peritubular cell membranes which selectively act on biologically active PTH molecules. PTH-responsive adenyl cyclase activity in isolated kidney cortex plasma membranes was measured and PTH metabolism was monitored simultaneously. When degradation was completely blocked by histone f3 (1 mg/ml), adenyl cyclase activity was significantly increased over control. In addition, when adenyl cyclase activity was negligible, the rate of PTH degradation by the membranes was not significantly diminished. Consistent with the in vivo data was the observation that E-PTH is metabolized by these membranes at a greater rate than CT-PTH. The data demonstrate the existence of a receptor-specific metabolism at sites which are independent of PTH receptor mediated adenyl cyclase activity.

  16. In vivo Raman spectroscopy of cervix cancers

    Science.gov (United States)

    Rubina, S.; Sathe, Priyanka; Dora, Tapas Kumar; Chopra, Supriya; Maheshwari, Amita; Krishna, C. Murali

    2014-03-01

    Cervix-cancer is the third most common female cancer worldwide. It is the leading cancer among Indian females with more than million new diagnosed cases and 50% mortality, annually. The high mortality rates can be attributed to late diagnosis. Efficacy of Raman spectroscopy in classification of normal and pathological conditions in cervix cancers on diverse populations has already been demonstrated. Our earlier ex vivo studies have shown the feasibility of classifying normal and cancer cervix tissues as well as responders/non-responders to Concurrent chemoradiotherapy (CCRT). The present study was carried out to explore feasibility of in vivo Raman spectroscopic methods in classifying normal and cancerous conditions in Indian population. A total of 182 normal and 132 tumor in vivo Raman spectra, from 63 subjects, were recorded using a fiberoptic probe coupled HE-785 spectrometer, under clinical supervision. Spectra were acquired for 5 s and averaged over 3 times at 80 mW laser power. Spectra of normal conditions suggest strong collagenous features and abundance of non-collagenous proteins and DNA in case of tumors. Preprocessed spectra were subjected to Principal Component-Linear Discrimination Analysis (PCLDA) followed by leave-one-out-cross-validation. Classification efficiency of ~96.7% and 100% for normal and cancerous conditions respectively, were observed. Findings of the study corroborates earlier studies and suggest applicability of Raman spectroscopic methods in combination with appropriate multivariate tool for objective, noninvasive and rapid diagnosis of cervical cancers in Indian population. In view of encouraging results, extensive validation studies will be undertaken to confirm the findings.

  17. In vivo dosimetry during tangential breast treatment.

    Science.gov (United States)

    Heukelom, S; Lanson, J H; van Tienhoven, G; Mijnheer, B J

    1991-12-01

    The 3-dimensional (3-D) dose distribution as calculated in clinical practice for tangential breast treatment was verified by means of in vivo dosimetry. Clinical practice in our institution implies the use of 8 MV X-ray beams, a 2-D treatment planning system, collimator rotation and a limited set of patient data for dose calculations. By positioning diodes at the central beam axes as well as in the periphery of the breast the magnitude of the dose values at the isocentre and in points situated in the high-dose regions behind the lung could be assessed. The position of the diodes was verified by means of an on-line portal imaging device. The reproducibility of these in vivo dose measurements was better than 2% (1 SD). Our study showed that on the average the dose delivery at the isocentre is 2% less and at the points behind the lung, 5.7% higher with respect to the calculated dose values. Detailed analysis of these in vivo dosimetry results, based on dose measurements performed with a breast shaped phantom, yielded the magnitudes of the errors in the predicted dose due to several limitations in the dose calculation algorithms and dose calculation procedure. These limitations are each introducing an error of several percent but are compensating each other for the dose calculation at the isocentre. We concluded that the dose distribution in a patient for our treatment technique and dose calculation procedure can be predicted with a 2-D treatment planning system in an acceptable way. A more accurate prediction of the dose distribution can be performed but requires an estimation of the lack of scatter due to missing tissue, the change in the dose distribution due to oblique incident beams and the incorporation of the actual output of the treatment machine in the assessment of the number of monitor units.

  18. Sampling system for in vivo ultrasound images

    DEFF Research Database (Denmark)

    Jensen, Jorgen Arendt; Mathorne, Jan

    1991-01-01

    Newly developed algorithms for processing medical ultrasound images use the high frequency sampled transducer signal. This paper describes demands imposed on a sampling system suitable for acquiring such data and gives details about a prototype constructed. It acquires full clinical images at a s...... at a sampling frequency of 20 MHz with a resolution of 12 bits. The prototype can be used for real time image processing. An example of a clinical in vivo image is shown and various aspects of the data acquisition process are discussed....

  19. In vivo toxicity study of Lantana camara.

    Science.gov (United States)

    Pour, Badakhshan Mahdi; Sasidharan, Sreenivasan

    2011-06-01

    To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara (L. Camara) in Artemia salina. The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Methanolic extract of L. camara is relatively safe on short-term exposure.

  20. In vivo dosimetry during pelvic treatment.

    Science.gov (United States)

    Heukelom, S; Lanson, J H; Mijnheer, B J

    1992-10-01

    High precision in vivo entrance and exit dose measurements have been performed with p-type diodes on patients during 8 MV X-ray irradiation of the pelvis, to investigate the accuracy of dose calculations in this region. Based on phantom measurements the accuracy of the p-type diode measuring system itself, i.e. the agreement with ionisation chamber dose measurements, was shown to be better than 0.7% while the reproducibility in the dose determination was 1.1%, 1.5% and 1.6% (1 S.D.) at the entrance point, isocentre and exit point, respectively, for the wedged lateral fields. Patient movement and the uncertainty in the diode position increased these values to 1.7%, 1.5% and 3.1% (1 S.D.) for dose determinations on patients. From the entrance and exit in vivo dose values the dose actually delivered to the isocentre was determined. For the anterior-posterior beams a good correspondence for most patients was observed at the entrance and exit point and at the isocentre between the in vivo and calculated dose values. For the wedged lateral beams a systematic deviation of about 3% was observed. In addition to the in vivo dose measurements phantom dose measurements have been performed to quantify the accuracy of the dose calculation algorithms including the computation of the number of monitor units. These measurements also served to quantify the effects of the actual patient on the dose delivery. The measurements showed that accurate calculation of the dose requires a separation of the head and phantom scatter contribution of the output of the treatment machine. The dependence of the wedge factor on field size, depth and source-skin-distance has also to be considered for accurate dose calculations. The effect of the patient on the dose calculation is mainly related to the actual electron densities of fat and bone structures compared to water: neglecting these densities in the dose computation could yield deviations up to 8.5% for the exit point in wedged beams. Based on

  1. Comparison of In Vivo and Ex Vivo MRI of the Human Hippocampal Formation in the Same Subjects.

    Science.gov (United States)

    Wisse, L E M; Adler, D H; Ittyerah, R; Pluta, J B; Robinson, J L; Schuck, T; Trojanowski, J Q; Grossman, M; Detre, J A; Elliott, M A; Toledo, J B; Liu, W; Pickup, S; Das, S R; Wolk, D A; Yushkevich, P A

    2017-11-01

    Multiple techniques for quantification of hippocampal subfields from in vivo MRI have been proposed. Linking in vivo MRI to the underlying histology can help validate and improve these techniques. High-resolution ex vivo MRI can provide an intermediate modality to map information between these very different imaging modalities. This article evaluates the ability to match information between in vivo and ex vivo MRI in the same subjects. We perform rigid and deformable registration on 10 pairs of in vivo (3 T, 0.4 × 0.4 × 2.6 mm3) and ex vivo (9.4 T, 0.2 × 0.2 × 0.2 mm3) scans, and describe differences in MRI appearance between these modalities qualitatively and quantitatively. The feasibility of using this dataset to validate in vivo segmentation is evaluated by applying an automatic hippocampal subfield segmentation technique (ASHS) to in vivo scans and comparing SRLM (stratum/radiatum/lacunosum/moleculare) surface to manual tracing on corresponding ex vivo scans (and in 2 cases, histology). Regional increases in thickness are detected in ex vivo scans adjacent to the ventricles and were not related to scanner, resolution differences, or susceptibility artefacts. Satisfactory in vivo/ex vivo registration and subvoxel accuracy of ASHS segmentation of hippocampal SRLM demonstrate the feasibility of using this dataset for validation, and potentially, improvement of in vivo segmentation methods. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Comparison of two in vivo and two ex vivo tests to assess the antibacterial activity of several antiseptics.

    Science.gov (United States)

    Messager, S; Goddard, P A; Dettmar, P W; Maillard, J-Y

    2004-10-01

    An ex vivo test was adapted to mimic the in vivo conditions of testing antiseptic activity on human forearms and in the European Standard Hygienic Handwash Test (BSEN 1499). The study was to validate the ex vivo protocols using 4.8% (w/v) para-chloro-meta-xylenol (PCMX, neat Dettol), 0.5% (w/v) triclosan in 70% (v/v) isopropanol, and 2% (v/v) povidone-iodine against a high bacterial inoculum (>10(8) cfu/mL) of Escherichia coli NCTC 10538. Two ex vivo tests using human skin samples, including one introducing a mechanical rubbing effect, were compared with two corresponding in vivo tests (the forearm test and the BSEN handwashing test). All antiseptics assessed in vivo (forearm and handwash tests) produced reductions in bacterial counts that were significantly greater than those for the non-medicated soft soap control. When assessed ex vivo without rubbing, only PCMX and povidone-iodine achieved reductions significantly greater than soft soap. When assessed ex vivo with mechanical rubbing, only PCMX and triclosan achieved reductions significantly greater than soft soap. Overall, the antiseptics at the concentrations tested were more active when tested in vivo than ex vivo. The addition of a mechanical effect, either in vivo by the volunteers washing their hands or ex vivo by a drill rubbing two skin samples against each other, produced a significantly greater reduction in bacterial concentrations. The ex vivo tests were easily adapted to mimic in vivo protocols. The value of such tests, particularly the one that includes a rubbing effect, may be significant as they avoid the need for human volunteers.

  3. Experimental in Vivo Models of Candidiasis

    Directory of Open Access Journals (Sweden)

    Esther Segal

    2018-02-01

    Full Text Available Candidiasis is a multifaceted fungal disease including mucosal-cutaneous, visceral, and disseminated infections caused by yeast species of the genus Candida. Candida infections are among the most common human mycoses. Candida species are the third to fourth most common isolates from bloodstream infections in neutropenic or immunocompromised hospitalized patients. The mucosal-cutaneous forms—particularly vaginal infections—have a high prevalence. Vaginitis caused by Candida species is the second most common vaginal infection. Hence, candidiasis is a major subject for research, including experimental in vivo models to study pathogenesis, prevention, or therapy of the disease. The following review article will focus on various experimental in vivo models in different laboratory animals, such as mammals (mice, rats, rabbits, the fruit fly–Drosophila melanogaster, the larvae of the moth Galleria mellonella, or the free-living nematode Caenorhabditis elegans. The review will describe the induction of the different clinical forms of candidiasis in the various models and the validity of such models in mimicking the human clinical situations. The use of such models for the assessment of antifungal drugs, evaluation of potential vaccines to protect before candidiasis, exploration of Candida virulence factors, and comparison of pathogenicity of different Candida species will be included in the review. All of the above will be reported as based on published studies of numerous investigators as well as on the research of the author and his group.

  4. Responsive corneosurfametry following in vivo skin preconditioning.

    Science.gov (United States)

    Uhoda, E; Goffin, V; Pierard, G E

    2003-12-01

    Skin is subjected to many environmental threats, some of which altering the structure and function of the stratum corneum. Among them, surfactants are recognized factors that may influence irritant contact dermatitis. The present study was conducted to compare the variations in skin capacitance and corneosurfametry (CSM) reactivity before and after skin exposure to repeated subclinical injuries by 2 hand dishwashing liquids. A forearm immersion test was performed on 30 healthy volunteers. 2 daily soak sessions were performed for 5 days. At inclusion and the day following the last soak session, skin capacitance was measured and cyanoacrylate skin-surface strippings were harvested. The latter specimens were used for the ex vivo microwave CSM. Both types of assessments clearly differentiated the 2 hand dishwashing liquids. The forearm immersion test allowed the discriminant sensitivity of CSM to increase. Intact skin capacitance did not predict CSM data. By contrast, a significant correlation was found between the post-test conductance and the corresponding CSM data. In conclusion, a forearm immersion test under realistic conditions can discriminate the irritation potential between surfactant-based products by measuring skin conductance and performing CSM. In vivo skin preconditioning by surfactants increases CSM sensitivity to the same surfactants.

  5. In vivo measurement of surgical gestures.

    Science.gov (United States)

    Dubois, Patrick; Thommen, Quentin; Jambon, Anne Claire

    2002-01-01

    Virtual reality techniques are now more and more widely used in the field of surgical training. However, the realism of the simulation devices requires a good knowledge of the mechanical behavior of the living organs. To provide perioperative measurement of laparoscopic surgical operations, we equipped a conventional operating grasper with a force sensor and a position sensor. The entire apparatus was connected to a PC that controlled the real-time data acquisition. After calibrating the sensors, we conducted three series of in vivo measurements on animals under video control. A standardized protocol was set up to perform various surgical gestures in a reproducible manner. Under these conditions, we can assess an original tool for a quantitative approach of surgical gestures' mechanics. The preliminary results will be extended by measurements during other operations and with other surgical instruments. The in vivo quantification of the mechanical interactions between operating instruments and anatomical structures is of great interest for the introduction of the force feedback in virtual surgery, for the modeling of the mechanical behavior of living organs, and for the design of new surgical instruments. This quantification of manipulations opens new prospects in the evaluation of surgical practices.

  6. In Vivo Pharmacodynamic Imaging of Proteasome Inhibition

    Directory of Open Access Journals (Sweden)

    Erin A. Kimbrel

    2009-05-01

    Full Text Available Inhibiting the proteolytic activity of the 26S proteasome has been shown to have selective apoptotic effects on cancer cells and to be clinically efficacious in certain malignancies. There is an unmet medical need for additional proteasome inhibitors, and their development will be facilitated by surrogate markers of proteasome function. Toward this end, ectopic fusion of the destruction domain from ornithine decarboxylase (ODC to reporter proteins is often used for assessing proteasome function. For luciferase-based reporters, we hypothesized that the oxygen-dependent destruction domain (ODD from hypoxia-inducible factor 1α (HIF-1α may provide improved sensitivity over luciferase-ODC, owing to its extremely rapid turnover by the proteasome (HIF-1α has a half-life of less than 5 minutes. In the current study, we show that ODD-luciferase affords a greater dynamic range and faster kinetics than luciferase-ODC in sensing proteasome inhibition in vitro. Importantly, ODD-luciferase also serves as an effective in vivo marker of proteasome function in xenograft tumor models, with inhibition being detected by noninvasive imaging within 3 hours of bortezomib administration. These data establish ODD-luciferase as a surrogate marker of proteasome function that can be used both in vitro and in vivo for the development of novel proteasome inhibitors.

  7. In Vivo Bioreactors for Mandibular Reconstruction

    Science.gov (United States)

    Tatara, A.M.; Wong, M.E.; Mikos, A.G.

    2014-01-01

    Large mandibular defects are difficult to reconstruct with good functional and aesthetic outcomes because of the complex geometry of craniofacial bone. While the current gold standard is free tissue flap transfer, this treatment is limited in fidelity by the shape of the harvested tissue and can result in significant donor site morbidity. To address these problems, in vivo bioreactors have been explored as an approach to generate autologous prefabricated tissue flaps. These bioreactors are implanted in an ectopic site in the body, where ossified tissue grows into the bioreactor in predefined geometries and local vessels are recruited to vascularize the developing construct. The prefabricated flap can then be harvested with vessels and transferred to a mandibular defect for optimal reconstruction. The objective of this review article is to introduce the concept of the in vivo bioreactor, describe important preclinical models in the field, summarize the human cases that have been reported through this strategy, and offer future directions for this exciting approach. PMID:25139360

  8. Can in vivo surface dental enamelmicrobiopsies be used to measure remote lead exposure?

    Science.gov (United States)

    Olympio, Kelly Polido Kaneshiro; Huila, Manuel Fernando Gonzalez; de Almeida Baldini Cardoso, Cristiane; da Silva Ferreira, Ana Paula Sacone; Ortiz, Adrielly Garcia; Toma, Henrique Eisi; da Silva, Ricardo Henrique Alves; Luz, Maciel Santos; Cardoso, Maria Regina Alves; Kelmer, Gislayne Aparecida Rodrigues; de Oliveira, Pedro Vitoriano; Bechara, Etelvino José Henriques; Günhter, Wanda Maria Risso; Buzalaf, Marília Afonso Rabelo

    2017-12-20

    Measuring lead in the surface dental enamel (SDE) using biopsies is a rapid, safe, and painless procedure. The dental enamel lead levels (DELLs) decrease from the outermost superficial layer to the inner layer of dental enamel, which becomes crucial for the biopsy depth (BD) measurement. However, whether the origin of lead found in SDE is fully endogenous is not yet established. There is also controversy about the biopsy protocol. The aims of this study were to investigate if DELLs are altered by extrinsic contamination (A) and to evaluate the real geometric figure formed by the erosion provoked by biopsy procedure and the respective BD in SDE (B). To accomplish the aim A, lead from 90 bovine incisor crowns lead was determined by graphite furnace atomic absorption spectrometer as a function of exposure time and lead concentration. Two biopsies were performed in each tooth, before and after lead exposure. Six 15-tooth groups differed by exposure time (1 or 30 min) and lead concentrations (A. 0 mg/L-placebo, B. 0.01 mg/L-standard for drinking water, or C. 0.06 mg/L-concentration found in contaminated groundwater). Phosphorus was determined by an inductively coupled plasm optical emission spectrometer to quantify the enamel removed. To compare intakes/losses of lead in SDE among the groups, values of DELL differences between before and after lead exposure were compared by ANOVA (p bottom surface area, analyzed by microscopy, showed an irregular area, with regions of peaks and valleys, where areas with depth ranging from 0.2 (peaks) to 1.8 μm (valleys) (± 0.1 μm) could be found. BD carried out in vivo is commonly calculated using the cylinder height formula. The real BD was shown to be very similar to already published data. In conclusion, the SDE of erupted teeth does not seem to be susceptible to environmental lead intake, being thus reliable to measure remote exposures to lead.

  9. Design and In Vivo Characterization of Immunoconjugates Targeting HIV gp160

    Science.gov (United States)

    Song, Kejing; Maresh, Grace A.; Frank, Anderson; Worthylake, David; Chung, Hye-Kyung; Polacino, Patricia; Hamer, Dean H.; Coyne, Cody P.; Rosenblum, Michael G.; Marks, John W.; Chen, Gang; Weiss, Deborah; Ghetie, Victor; Vitetta, Ellen S.; Robinson, James E.; Hu, Shiu-Lok

    2016-01-01

    ABSTRACT The envelope (Env) glycoprotein of HIV is expressed on the surface of productively infected cells and can be used as a target for cytotoxic immunoconjugates (ICs), in which cell-killing moieties, including toxins, drugs, or radionuclides, are chemically or genetically linked to monoclonal antibodies (MAbs) or other targeting ligands. Such ICs could be used to eliminate persistent reservoirs of HIV infection. We have found that MAbs which bind to the external loop of gp41, e.g., MAb 7B2, make highly effective ICs, particularly when used in combination with soluble CD4. We evaluated the toxicity, immunogenicity, and efficacy of the ICs targeted with 7B2 in mice and in simian-human immunodeficiency virus-infected macaques. In the macaques, we tested immunotoxins (ITs), consisting of protein toxins bound to the targeting agent. ITs were well tolerated and initially efficacious but were ultimately limited by their immunogenicity. In an effort to decrease immunogenicity, we tested different toxic moieties, including recombinant toxins, cytotoxic drugs, and tubulin inhibitors. ICs containing deglycosylated ricin A chain prepared from ricin toxin extracted from castor beans were the most effective in killing HIV-infected cells. Having identified immunogenicity as a major concern, we show that conjugation of IT to polyethylene glycol limits immunogenicity. These studies demonstrate that cytotoxic ICs can target virus-infected cells in vivo but also highlight potential problems to be addressed. IMPORTANCE It is not yet possible to cure HIV infection. Even after years of fully effective antiviral therapy, a persistent reservoir of virus-infected cells remains. Here we propose that a targeted conjugate consisting of an anti-HIV antibody bound to a toxic moiety could function to kill the HIV-infected cells that constitute this reservoir. We tested this approach in HIV-infected cells grown in the lab and in animal infections. Our studies demonstrated that these

  10. Comparative In vivo, Ex vivo, and In vitro Toxicity Studies of Engineered Nanomaterials

    Science.gov (United States)

    Efforts to reduce the number of animals in engineered nanomaterials (ENM) toxicity testing have resulted in the development of numerous alternative toxicity testing methods, but in vivo and in vitro results are still evolving and variable. This inconsistency could be due to the f...

  11. In-vivo multispectral video endoscopy towards in-vivo hyperspectral video endoscopy.

    Science.gov (United States)

    Hohmann, Martin; Kanawade, R; Klämpfl, F; Douplik, A; Mudter, J; Neurath, M F; Albrecht, H

    2017-04-01

    For in-vivo diagnostics of cancer and pre-cancer in the stomach, there is no endoscopic procedure offering both high sensitivity and high specificity. Our data suggest that multispectral or hyperspectral imaging may be helpful to solve this problem. It is successfully applied to the detection and analysis of easily reachable carcinomas, ex-vivo samples of hollow organ mucosal carcinomas and also histological samples. An endoscopy system which allows flexible multispectral videoendoscopy for in-vivo diagnostics has so far been unavailable. To overcome this problem, we modified a standard Olympus endoscopy system to conduct in-vivo multispectral imaging of the upper GI tract. The pilot study is performed on 14 patients with adeno carcinomas in the stomach. For analysis, Support Vector Machine with linear and Gaussian Kernel, AdaBoost, RobustBoost and Random-Forest-walk are used and compared for the data classification with a leave-one-out strategy. The margin of the carcinoma for the training of the classifier is drawn by expert-labeling. The cancer findings are cross-checked by biopsies. We expect that the present study will help to improve the further development of hyperspectral endoscopy and to overcome some of the problems to be faced in this process. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. In vivo and ex vivo vessel wall MRI of the circle of Willis

    NARCIS (Netherlands)

    Harteveld, A.A.|info:eu-repo/dai/nl/413650286

    2017-01-01

    In recent years, several MRI sequences have been developed for direct evaluation of the intracranial vessel wall and its pathology in vivo. These MRI sequences enable detection of intracranial vessel wall abnormalities, including those that have not yet caused luminal narrowing. The research field

  13. Automated Segmentation of in Vivo and Ex Vivo Mouse Brain Magnetic Resonance Images

    Directory of Open Access Journals (Sweden)

    Alize E.H. Scheenstra

    2009-01-01

    Full Text Available Segmentation of magnetic resonance imaging (MRI data is required for many applications, such as the comparison of different structures or time points, and for annotation purposes. Currently, the gold standard for automated image segmentation is nonlinear atlas-based segmentation. However, these methods are either not sufficient or highly time consuming for mouse brains, owing to the low signal to noise ratio and low contrast between structures compared with other applications. We present a novel generic approach to reduce processing time for segmentation of various structures of mouse brains, in vivo and ex vivo. The segmentation consists of a rough affine registration to a template followed by a clustering approach to refine the rough segmentation near the edges. Compared with manual segmentations, the presented segmentation method has an average kappa index of 0.7 for 7 of 12 structures in in vivo MRI and 11 of 12 structures in ex vivo MRI. Furthermore, we found that these results were equal to the performance of a nonlinear segmentation method, but with the advantage of being 8 times faster. The presented automatic segmentation method is quick and intuitive and can be used for image registration, volume quantification of structures, and annotation.

  14. Combined in vivo and ex vivo analysis of mesh mechanics in a porcine hernia model.

    Science.gov (United States)

    Kahan, Lindsey G; Lake, Spencer P; McAllister, Jared M; Tan, Wen Hui; Yu, Jennifer; Thompson, Dominic; Brunt, L Michael; Blatnik, Jeffrey A

    2017-07-21

    Hernia meshes exhibit variability in mechanical properties, and their mechanical match to tissue has not been comprehensively studied. We used an innovative imaging model of in vivo strain tracking and ex vivo mechanical analysis to assess effects of mesh properties on repaired abdominal walls in a porcine model. We hypothesized that meshes with dissimilar mechanical properties compared to native tissue would alter abdominal wall mechanics more than better-matched meshes. Seven mini-pigs underwent ventral hernia creation and subsequent open repair with one of two heavyweight polypropylene meshes. Following mesh implantation with attached radio-opaque beads, fluoroscopic images were taken at insufflation pressures from 5 to 30 mmHg on postoperative days 0, 7, and 28. At 28 days, animals were euthanized and ex vivo mechanical testing performed on full-thickness samples across repaired abdominal walls. Testing was conducted on 13 mini-pig controls, and on meshes separately. Stiffness and anisotropy (the ratio of stiffness in the transverse versus craniocaudal directions) were assessed. 3D reconstructions of repaired abdominal walls showed stretch patterns. As pressure increased, both meshes expanded, with no differences between groups. Over time, meshes contracted 17.65% (Mesh A) and 0.12% (Mesh B; p = 0.06). Mesh mechanics showed that Mesh A deviated from anisotropic native tissue more than Mesh B. Compared to native tissue, Mesh A was stiffer both transversely and craniocaudally. Explanted repaired abdominal walls of both treatment groups were stiffer than native tissue. Repaired tissue became less anisotropic over time, as mesh properties prevailed over native abdominal wall properties. This technique assessed 3D stretch at the mesh level in vivo in a porcine model. While the abdominal wall expanded, mesh-ingrown areas contracted, potentially indicating stresses at mesh edges. Ex vivo mechanics demonstrate that repaired tissue adopts mesh properties, suggesting

  15. Evaluation of the In Vivo and Ex Vivo Binding of Novel BC1 Cannabinoid Receptor Radiotracers

    Energy Technology Data Exchange (ETDEWEB)

    Miller, A.; Gatley, J.; Gifford, A.

    2002-01-01

    The primary active ingredient of marijuana, 9-tetrahydrocannabinol, exerts its psychoactive effects by binding to cannabinoid CB1 receptors. These receptors are found throughout the brain with high concentrations in the hippocampus and cerebellum. The current study was conducted to evaluate the binding of a newly developed putative cannabinoid antagonist, AM630, and a classical cannabinoid 8-tetrahydrocannabinol as potential PET and/or SPECT imaging agents for brain CB1 receptors. For both of these ligands in vivo and ex vivo studies in mice were conducted. AM630 showed good overall brain uptake (as measure by %IA/g) and a moderately rapid clearance from the brain with a half-clearance time of approximately 30 minutes. However, AM630 did not show selective binding to CB1 cannabinoid receptors. Ex vivo autoradiography supported the lack of selective binding seen in the in vivo study. Similar to AM630, 8-tetrahydrocanibol also failed to show selective binding to CB1 receptor rich brain areas. The 8-tetrahydrocanibol showed moderate overall brain uptake and relatively slow brain clearance as compared to AM630. Further studies were done with AM2233, a cannabinoid ligand with a similar structure as AM630. These studies were done to develop an ex vivo binding assay to quantify the displacement of [131I]AM2233 binding by other ligands in Swiss-Webster and CB1 receptor knockout mice. By developing this assay we hoped to determine the identity of an unknown binding site for AM2233 present in the hippocampus of CB1 knockout mice. Using an approach based on incubation of brain slices prepared from mice given intravenous [131I]AM2233 in either the presence or absence of AM2233 (unlabelled) it was possible to demonstrate a significant AM2233-displacable binding in the Swiss-Webster mice. Future studies will determine if this assay is appropriate for identifying the unknown binding site for AM2233 in the CB1 knockout mice.

  16. In vivo treatment with diphenyl ditelluride induces neurodegeneration in striatum of young rats: Implications of MAPK and Akt pathways

    Energy Technology Data Exchange (ETDEWEB)

    Heimfarth, Luana; Loureiro, Samanta Oliveira; Dutra, Márcio Ferreira; Andrade, Cláudia; Pettenuzzo, Letícia; Guma, Fátima T. Costa Rodrigues; Gonçalves, Carlos Alberto Saraiva [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil); Batista Teixeira da Rocha, João [Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS Brazil (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil)

    2012-10-15

    In the present report 15 day-old Wistar rats were injected with 0.3 μmol of diphenyl ditelluride (PhTe){sub 2}/kg body weight and parameters of neurodegeneration were analyzed in slices from striatum 6 days afterwards. We found hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein—GFAP and vimentin) and from neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H, respectively) and increased MAPK (Erk, JNK and p38MAPK) as well as PKA activities. The treatment induced reactive astrogliosis in the striatum, evidenced by increased GFAP and vimentin immunocontent as well as their mRNA overexpression. Also, (PhTe){sub 2} significantly increased the propidium iodide (PI) positive cells in NeuN positive population without altering PI incorporation into GFAP positive cells, indicating that in vivo exposure to (PhTe){sub 2} provoked neuronal damage. Immunohistochemistry showed a dramatic increase of GFAP staining characteristic of reactive astrogliosis. Moreover, increased caspase 3 in (PhTe){sub 2} treated striatal slices suggested apoptotic cell death. (PhTe){sub 2} exposure decreased Akt immunoreactivity, however phospho-GSK-3-β (Ser9) was unaltered, suggesting that this kinase is not directly implicated in the neurotoxicity of this compound. Therefore, the present results shed light into the mechanisms of (PhTe){sub 2}-induced neurodegeneration in rat striatum, evidencing a critical role for the MAPK and Akt signaling pathways and disruption of cytoskeletal homeostasis, which could be related with apoptotic neuronal death and astrogliosis. -- Highlights: ► Diphenyl ditelluride causes apoptotic neuronal death in the striatum of young rats. ► Diphenyl ditelluride causes reactive astrogliosis in the striatum of rats. ► Diphenyl ditelluride disrupts the homeostasis of the cytoskeleton of the striatum. ► The actions of diphenyl ditelluride are mediated by MAPK and Akt

  17. In vivo and ex vivo sentinel node mapping does not identify the same lymph nodes in colon cancer.

    Science.gov (United States)

    Andersen, Helene Schou; Bennedsen, Astrid Louise Bjørn; Burgdorf, Stefan Kobbelgaard; Eriksen, Jens Ravn; Eiholm, Susanne; Toxværd, Anders; Riis, Lene Buhl; Rosenberg, Jacob; Gögenur, Ismail

    2017-07-01

    Identification of lymph nodes and pathological analysis is crucial for the correct staging of colon cancer. Lymph nodes that drain directly from the tumor area are called "sentinel nodes" and are believed to be the first place for metastasis. The purpose of this study was to perform sentinel node mapping in vivo with indocyanine green and ex vivo with methylene blue in order to evaluate if the sentinel lymph nodes can be identified by both techniques. Patients with colon cancer UICC stage I-III were included from two institutions in Denmark from February 2015 to January 2016. In vivo sentinel node mapping with indocyanine green during laparoscopy and ex vivo sentinel node mapping with methylene blue were performed in all patients. Twenty-nine patients were included. The in vivo sentinel node mapping was successful in 19 cases, and ex vivo sentinel node mapping was successful in 13 cases. In seven cases, no sentinel nodes were identified. A total of 51 sentinel nodes were identified, only one of these where identified by both techniques (2.0%). In vivo sentinel node mapping identified 32 sentinel nodes, while 20 sentinel nodes were identified by ex vivo sentinel node mapping. Lymph node metastases were found in 10 patients, and only two had metastases in a sentinel node. Placing a deposit in relation to the tumor by indocyanine green in vivo or of methylene blue ex vivo could only identify sentinel lymph nodes in a small group of patients.

  18. Comparison of ex vivo and in vivo micro-computed tomography of rat tibia at different scanning settings.

    Science.gov (United States)

    Longo, Amanda B; Salmon, Phil L; Ward, Wendy E

    2017-08-01

    The parameters of a micro-computed tomography (μCT) scan, including whether a bone is imaged in vivo or ex vivo, determine the quality of the resulting image. In turn, this impacts the accuracy of the trabecular and cortical outcomes. The absolute impact of μCT scanning at different voxel sizes and whether the sample is imaged in vivo or ex vivo on the morphological outcomes of the proximal tibia in the rat is unknown. The right proximal tibia of 6-month-old Sham-control and ovariectomized (OVX) rats (n = 8/group) was scanned using μCT (SkyScan 1176, Bruker, Kontich, Belgium) using three sets of parameters (9 μm ex vivo, 18 μm ex vivo, 18 μm in vivo) to compare the trabecular and cortical outcomes. Regardless of scan protocols, differences between Sham and OVX groups were observed as expected. At a voxel size of 18 μm, scanning in vivo or ex vivo had no effect on any of the outcomes measured. However, compared to a 9 μm voxel size scan, imaging at 18 μm resulted in significant underestimation of the connectivity density (p vivo scanning. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1690-1698, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  19. In vivo effect of the lipido-sterolic extract of Serenoa repens (Permixon) on mast cell accumulation and glandular epithelium trophism in the rat prostate.

    Science.gov (United States)

    Mitropoulos, Dionisios; Kyroudi, Aspasia; Zervas, Anastasios; Papadoukakis, Stefanos; Giannopoulos, Aris; Kittas, Christos; Karayannacos, Panagiotis

    2002-04-01

    The Serenoa repens lipido-sterolic extract (SRLSE, Permixon, Pierre Fabre Medicament, Castres, France) is used to treat benign prostate hyperplasia. We studied the in vivo effect of SRLSE on mast cell accumulation and the histological characteristics of the rat ventral prostate. Adult Wistar rats received either tocopherol or SRLSE (50 and 100 mg/kg body weight, respectively) every second day for 90 days. Histological features were studied in hematoxylin-eosin stained tissue sections while mean mast cell numbers were determined in Giemsa-stained sections. The central region of the ventral prostate in treated animals showed significant changes with acinar epithelium becoming flat or low cuboidal. In the same region, mean mast cell number per optical field in the control, low-dose and high-dose groups were, respectively, 4.7+/-0.7, 3.4+/-1.0 and 2.4+/-0.6, showing a dose-dependent, statistically significant decrease. Administering SRLSE significantly reduces mast cell accumulation and provokes epithelium atrophy within the central area of the rat ventral prostate. These phenomena may participate in the clinical activity of the drug.

  20. In Vivo Monitoring of Parathyroid Hormone Treatment after Myocardial Infarction in Mice with [68Ga]Annexin A5 and [18F]Fluorodeoxyglucose Positron Emission Tomography

    OpenAIRE

    Sebastian Lehner; Andrei Todica; Yordan Vanchev; Christopher Uebleis; Hao Wang; Tanja Herrler; Carmen Wängler; Paul Cumming; Guido Böning; Wolfgang M Franz; Peter Bartenstein; Marcus Hacker; Stefan Brunner

    2014-01-01

    [68Ga]Annexin A5 positron emission tomography (PET) reveals the externalization of phosphatidylserine as a surrogate marker for apoptosis. We tested this technique for therapy monitoring in a murine model of myocardial infarction (MI) including parathyroid hormone (PTH) treatment. MI was induced in mice, and they were assigned to the saline or the PTH group. On day 2, they received [68Ga]annexin A5 PET or histofluorescence TUNEL staining. Mice had 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-PET exa...

  1. [Advances of in vivo confocal scanning laser microscopy].

    Science.gov (United States)

    Tian, Ke-bin; Zhou, Guo-yu

    2006-02-01

    In vivo confocal scanning laser microscopy is being widely established as a time-saving, non-invasive, investigative methods in the study of body surfaces. Skin can be observed in its native state in vivo without the fixing, sectioning and staining that is necessary for routine histology. It is a new technology that can provide detailed images of tissue architecture and cellular morphology of living tissue. This paper reviews the fundamentals of in vivo confocal imaging and its clinical applications.

  2. In Vivo Monitoring Program Manual, PNL-MA-574

    Energy Technology Data Exchange (ETDEWEB)

    Lynch, Timothy P.

    2010-07-01

    An overview of the administration for the In Vivo Monitoring Program (IVMP) for Hanford. This includes organizational structure and program responsibilities; coordination of in vivo measurements; scheduling measurements; performing measurements; reporting results; and quality assurance. Overall responsibility for the management of the IVMP rests with the Program Manager (PM). The PM is responsible for providing the required in vivo counting services for Hanford Site contractor employees in accordance with Department of Energy (DOE) requirements and the specific statements of work.

  3. Ex vivo lung perfusion review of a revolutionary technology.

    Science.gov (United States)

    Makdisi, George; Makdisi, Tony; Jarmi, Tambi; Caldeira, Christiano C

    2017-09-01

    Donor lung shortage has been the main reason to the increasing number of patients waiting for lung transplant. Ex vivo lung perfusion (EVLP) is widely expanding technology to assess and prepare the lungs who are considered marginal for transplantation. the outcomes are encouraging and comparable to the lungs transplanted according to the standard criteria. in this article, we will discuss the history of development, the techniques and protocols of ex vivo, and the logics and rationales for ex vivo use.

  4. In vivo endoscopic multi-beam optical coherence tomography

    Science.gov (United States)

    Standish, Beau A.; Lee, Kenneth K. C.; Mariampillai, Adrian; Munce, Nigel R.; Leung, Michael K. K.; Yang, Victor X. D.; Vitkin, I. Alex

    2010-02-01

    A multichannel optical coherence tomography (multi-beam OCT) system and an in vivo endoscopic imaging probe were developed using a swept-source OCT system. The distal optics were micro-machined to produce a high numerical aperture, multi-focus fibre optic array. This combination resulted in a transverse design resolution of rabbit study to acquire in vivo structural images of the colon and ex vivo images of the oesophagus and trachea. A good correlation between the structural multi-beam OCT images and H&E histology was achieved, demonstrating the feasibility of this high-resolution system and its potential for in vivo human endoscopic imaging.

  5. In vivo efficacy of oral and intraperitoneal administration of extracts ...

    African Journals Online (AJOL)

    In vivo efficacy of oral and intraperitoneal administration of extracts of Warburgia ugandensis (Canellaceae) in experimental treatment of old world cutaneous leishmaniasis caused by Leishmania major .

  6. Quantifying drug-protein binding in vivo.

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, B; Bench, G; Keating III, G; Palmblad, M; Vogel, J; Grant, P G; Hillegonds, D

    2004-02-17

    Accelerator mass spectrometry (AMS) provides precise quantitation of isotope labeled compounds that are bound to biological macromolecules such as DNA or proteins. The sensitivity is high enough to allow for sub-pharmacological (''micro-'') dosing to determine macromolecular targets without inducing toxicities or altering the system under study, whether it is healthy or diseased. We demonstrated an application of AMS in quantifying the physiologic effects of one dosed chemical compound upon the binding level of another compound in vivo at sub-toxic doses [4].We are using tissues left from this study to develop protocols for quantifying specific binding to isolated and identified proteins. We also developed a new technique to quantify nanogram to milligram amounts of isolated protein at precisions that are comparable to those for quantifying the bound compound by AMS.

  7. Implantable optoelectronic probes for in vivo optogenetics

    Science.gov (United States)

    Iseri, Ege; Kuzum, Duygu

    2017-06-01

    More than a decade has passed since optics and genetics came together and lead to the emerging technologies of optogenetics. The advent of light-sensitive opsins made it possible to optically trigger the neurons into activation or inhibition by using visible light. The importance of spatiotemporally isolating a segment of a neural network and controlling nervous signaling in a precise manner has driven neuroscience researchers and engineers to invest great efforts in designing high precision in vivo implantable devices. These efforts have focused on delivery of sufficient power to deep brain regions, while monitoring neural activity with high resolution and fidelity. In this review, we report the progress made in the field of hybrid optoelectronic neural interfaces that combine optical stimulation with electrophysiological recordings. Different approaches that incorporate optical or electrical components on implantable devices are discussed in detail. Advantages of various different designs as well as practical and fundamental limitations are summarized to illuminate the future of neurotechnology development.

  8. In Vivo Cytogenetic Studies on Aspartame

    Directory of Open Access Journals (Sweden)

    Entissar S. AlSuhaibani

    2010-01-01

    Full Text Available Aspartame (a-Laspartyl-L-phenylalanine 1-methylester is a dipeptide low-calorie artificial sweetener that is widely used as a nonnutritive sweetener in foods and drinks. The safety of aspartame and its metabolic breakdown products (phenylalanine, aspartic acid and methanol was investigated in vivo using chromosomal aberration (CA test and sister chromatid exchange (SCE test in the bone marrow cells of mice. Swiss Albino male mice were exposed to aspartame (3.5, 35, 350 mg/kg body weight. Bone marrow cells isolated from femora were analyzed for chromosome aberrations and sister chromatid exchanges. Treatment with aspartame induced dose dependently chromosome aberrations at all concentrations while it did not induce sister chromatid exchanges. On the other hand, aspartame did not decrease the mitotic index (MI. However, statistical analysis of the results show that aspartame is not significantly genotoxic at low concentration.

  9. Human skeletal muscle releases leptin in vivo

    DEFF Research Database (Denmark)

    Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund

    2012-01-01

    Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle...... and adipose tissue leptin release in vivo. We recruited 16 healthy male human participants. Catheters were inserted into the femoral artery and vein draining skeletal muscle, as well as an epigastric vein draining the abdominal subcutaneous adipose tissue. By combining the veno-arterial differences in plasma...... leptin with measurements of blood flow, leptin release from both tissues was quantified. To induce changes in leptin, the participants were infused with either saline or adrenaline in normo-physiological concentrations. The presence of leptin in skeletal muscle was confirmed by western blotting. Leptin...

  10. Towards clinically translatable in vivo nanodiagnostics

    Science.gov (United States)

    Park, Seung-Min; Aalipour, Amin; Vermesh, Ophir; Yu, Jung Ho; Gambhir, Sanjiv S.

    2017-05-01

    Nanodiagnostics as a field makes use of fundamental advances in nanobiotechnology to diagnose, characterize and manage disease at the molecular scale. As these strategies move closer to routine clinical use, a proper understanding of different imaging modalities, relevant biological systems and physical properties governing nanoscale interactions is necessary to rationally engineer next-generation bionanomaterials. In this Review, we analyse the background physics of several clinically relevant imaging modalities and their associated sensitivity and specificity, provide an overview of the materials currently used for in vivo nanodiagnostics, and assess the progress made towards clinical translation. This work provides a framework for understanding both the impressive progress made thus far in the nanodiagnostics field as well as presenting challenges that must be overcome to obtain widespread clinical adoption.

  11. High-wavenumber FT-Raman spectroscopy for in vivo and ex vivo measurements of breast cancer

    DEFF Research Database (Denmark)

    Garcia-Flores, A. F.; Raniero, L.; Canevari, R. A.

    2011-01-01

    The identification of normal and cancer breast tissue of rats was investigated using high-frequency (HF) FT-Raman spectroscopy with a near-infrared excitation source on in vivo and ex vivo measurements. Significant differences in the Raman intensities of prominent Raman bands of lipids and proteins...... structures (2,800-3,100 cm(-1)) as well as in the broad band of water (3,100-3,550 cm(-1)) were observed in mean normal and cancer tissue spectra. The multivariate statistical analysis methods of principal components analysis (PCA) and linear discriminant analysis (LDA) were performed on all high......-frequency Raman spectra of normal and cancer tissues. LDA results with the leave-one-out cross-validation option yielded a discrimination accuracy of 77.2, 83.3, and 100% for in vivo transcutaneous, in vivo skin-removed, and ex vivo biopsy HF Raman spectra. Despite the lower discrimination value for the in vivo...

  12. In vivo nanotoxicity assays in plant models.

    Science.gov (United States)

    Kumari, Mamta; Ernest, Vinita; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2012-01-01

    Increasing application of silver nanoparticles (SNPs) and zinc oxide nanoparticles (nZnO) in consumer products like textiles, cosmetics, washing machines and other household products increases their chance to reach the environment. Intensive research is required to assess the nanoparticles' toxicity to the environmental system. The toxicological effect of nanoparticles has been studied at the miniscule scale and requires intensive research to be conducted to assess its unknown effects. Plants are the primary target species which need to be included to develop a comprehensive toxicity profile for nanoparticles. So far, the mechanisms of toxicity of nanoparticles to the plant system remains largely unknown and little information on the potential uptake of nanoparticles by plants and their subsequent fate within the food chain is available. The phytoxicological behaviour of silver and zinc oxide nanoparticles on Allium cepa and seeds of Zea mays (maize), Cucumis sativus (cucumber) and Lycopersicum esculentum (tomato) was done. The in vitro studies on A. cepa have been done to check the cytotoxicological effects including mitotic index, chromosomal aberrations, vagrant chromosomes, sticky chromosomes, disturbed metaphase, breaks and formation of micronucleus. In vitro and in vivo studies on seed systems exposed to different concentration of nanoparticles dispersion to check phytotoxicity end point as root length, germination effect, adsorption and accumulation of nanoparticles (uptake studies) into the plant systems. In vivo studies in a seed system was done using phytagel medium. Biochemical studies were done to check effect on protein, DNA and thiobarbituric acid reactive species concentration. FT-IR studies were done to analyze the functional and conformational changes in the treated and untreated samples. The toxicological effects of nanoparticles had to be studied at the miniscule scale to address existing environment problems or prevent future problems. The

  13. In vivo dedifferentiation of adult adipose cells.

    Directory of Open Access Journals (Sweden)

    Yunjun Liao

    Full Text Available Adipocytes can dedifferentiate into fibroblast-like cells in vitro and thereby acquire proliferation and multipotent capacities to participate in the repair of various organs and tissues. Whether dedifferentiation occurs under physiological or pathological conditions in vivo is unknown.A tissue expander was placed under the inguinal fat pads of rats and gradually expanded by injection of water. Samples were collected at various time points, and morphological, histological, cytological, ultrastructural, and gene expression analyses were conducted. In a separate experiment, purified green fluorescent protein+ adipocytes were transplanted into C57 mice and collected at various time points. The transplanted adipocytes were assessed by bioluminescence imaging and whole-mount staining.The expanded fat pad was obviously thinner than the untreated fat pad on the opposite side. It was also tougher in texture and with more blood vessels attached. Hematoxylin and eosin staining and transmission electron microscopy indicated there were fewer monolocular adipocytes in the expanded fat pad and the morphology of these cells was altered, most notably their lipid content was discarded. Immunohistochemistry showed that the expanded fat pad contained an increased number of proliferative cells, which may have been derived from adipocytes. Following removal of the tissue expander, many small adipocytes were observed. Bioluminescence imaging suggested that some adipocytes survived when transplanted into an ischemic-hypoxic environment. Whole-mount staining revealed that surviving adipocytes underwent a process similar to adipocyte dedifferentiation in vitro. Monolocular adipocytes became multilocular adipocytes and then fibroblast-like cells.Mature adipocytes may be able to dedifferentiate in vivo, and this may be an adipose tissue self-repair mechanism. The capacity of adipocytes to dedifferentiate into stem cell-like cells may also have a more general role in the

  14. "Gold nanoparticles composite-folic acid conjugated graphene oxide nanohybrids" for targeted chemo-thermal cancer ablation: In vitro screening and in vivo studies.

    Science.gov (United States)

    Chauhan, Gaurav; Chopra, Vianni; Tyagi, Amit; Rath, Goutam; Sharma, Rakesh K; Goyal, Amit K

    2017-01-01

    Nano-graphene oxide (GO) nanometal composite (specifically nanogold and nanosilver) have shown to be a promising material for anticancer therapeutics. Owing to their high drug loading capacity, photothermal and synergizing effects, it is very important to exploit them for targeted chemo-thermal cancer therapeutics. In this work, gold nanoparticles (AuNPs) were selected as the composite metal, folic acid (FA) was taken as GO surface functionalization moiety for active tumor targeting of model anticancer drug Doxorubicin (Dox). AuNPs composite-folate conjugated graphene oxide (FA-GO@Au) nano-platforms were synthesized and characterized in detail. Near-infrared (NIR) sensitivity resulted in an aggravated release of both Dox and ionic gold from the nanohybrid surface. Simultaneous delivery of Dox and AuNPs in the cellular vicinity was further enhanced after localized NIR exposure which resulted in significantly improved cancer cell toxicity. Mechanistic evaluation revealed G0/G1 phase arrest due to increased DNA intercalation and provoked early apoptosis under NIR influence. Pharmacokinetics and organ distribution studies were carried out in healthy mice and rabbits to estimate the actual bio fate of these nanohybrids. In vivo studies showed substantial tumor regression in solid tumor model in Balb/c mice and NIR exposure induced photo-thermal effects further resulted in better tumor management. Study provides substantial evidences both at in vitro and in vivo level to support the fact that NIR induced local photo-thermal effects can solely be used as a tumor targeting tool. This NIR dependent nanohybrid approach presents a precise and flexible strategy for targeted chemotherapy and photo-thermal tumor ablation. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. In vitro and in vivo Development of Cloned Ovine Embryos using in vitro and in vivo Matured Oocytes

    DEFF Research Database (Denmark)

    Holm, P; Nagashima, H; Sun, F-J

    1995-01-01

    Cloning of sheep embryos by nucleus transplantation can be achieved by using in vivo matured (oviductal) oocytes and in vivo culture. However, these steps involve cumbersome procedures. Therefore, the effects of in vivo vs. the equivalent in vitro procedures on the pre-implantation development...... matured oocytes were enucleated and fused with inserted blastomeres from donor embryos. In vitro matured oocytes were enucleated and allowed to age prior to blastomere insertion and electrofusion. Fused embryos were cultured for approximately 132 h either in vivo in ligated sheep oviducts or in vitro...

  16. Avaliação e recondicionamento pulmonar ex vivo Ex vivo lung evaluation and reconditioning

    Directory of Open Access Journals (Sweden)

    Paulo Manuel Pêgo-Fernandes

    2010-12-01

    Full Text Available OBJETIVO: Apenas 15% dos pulmões doados são aproveitados para transplante. Um novo método de Perfusão Pulmonar Ex Vivo (PPEV foi desenvolvido e pode ser usado para avaliação e recondicionamento de pulmões "marginais" e rejeitados para o transplante. Esse trabalho relata nossa experiência com a avaliação funcional da PPEV. MÉTODOS: Foram estudados pulmões de 12 doadores considerados inapropriados para transplante pulmonar. Após a captação, os pulmões são perfundidos ex vivo com Steen Solution, uma solução de composição eletrolítica extracelular com alta pressão coloidosmótica. Um oxigenador de membrana ligado ao circuito recebe uma mistura gasosa (nitrogênio e dióxido de carbono e "desoxigena" o perfusato, mantendo uma concentração de gases semelhante a do sangue venoso. Os pulmões são gradualmente aquecidos, perfundidos e ventilados. A avaliação dos órgãos é feita por gasometrias e medidas como a resistência vascular pulmonar (RVP e complacência pulmonar (CP. RESULTADOS: A PaO2 (FiO2 100% passou de um valor médio de 193,3 mmHg no doador para 495,3 mmHg durante a PPEV. Após uma hora de PPEV, a RVP média era de 737,3 dinas/seg/ cm5 e a CP era de 42,2 ml/cmH2O. CONCLUSÕES: O modelo de avaliação pulmonar ex vivo pode melhorar a capacidade de oxigenação de pulmões "marginais" inicialmente rejeitados para transplante. Isso denota um grande potencial do método para aumentar a disponibilidade de pulmões para transplante e, possivelmente, reduzir o tempo de espera nas filas.OBJECTIVE: Only about 15% of the potential candidates for lung donation are considered suitable for transplantation. A new method for ex vivo lung perfusion (EVLP has been developed and can be used for evaluation and reconditioning of "marginal" and unacceptable lungs. This is a report of functional evaluation experience with ex vivo perfusion of twelve donor lungs deemed unacceptable in São Paulo, Brazil. METHODS: After harvesting, the

  17. Ex vivo and in vivo coherent Raman imaging of the peripheral and central nervous system

    Science.gov (United States)

    Huff, Terry Brandon

    A hallmark of nervous system disorders is damage or degradation of the myelin sheath. Unraveling the mechanisms underlying myelin degeneration and repair represent one of the great challenges in medicine. This thesis work details the development and utilization of advanced optical imaging methods to gain insight into the structure and function of myelin in both healthy and diseased states in the in vivo environment. This first part of this thesis discusses ex vivo studies of the effects of high-frequency stimulation of spinal tissues on the structure of the node of Ranvier as investigated by coherent anti-Stokes Raman scattering (CARS) imaging (manuscript submitted to Journal of Neurosciece). Reversible paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation, beginning minutes after the onset and continuing for up to 10 min after stimulation was ceased. A mechanistic study revealed a Ca2+ dependent pathway: high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down. Also, the construction of dual-scanning CARS microscope for large area mapping of CNS tissues is detailed (Optics Express, 2008, 16:19396-193409). A confocal scanning head equipped with a rotating polygon mirror provides high speed, high resolution imaging and is coupled with a motorized sample stage to generate high-resolution large-area images of mouse brain coronal section and guinea pig spinal cord cross section. The polygon mirror decreases the mosaic acquisition time significantly without reducing the resolution of individual images. The ex vivo studies are then extended to in vivo imaging of mouse sciatic nerve tissue by CARS and second harmonic generation (SHG) imaging (Journal of Microscopy, 2007, 225: 175-182). Following a minimally invasive surgery to open the skin, CARS imaging of myelinated axons and SHG imaging of the

  18. Physiologic assessment of the ex vivo donor lung for transplantation.

    Science.gov (United States)

    Yeung, Jonathan C; Cypel, Marcelo; Machuca, Tiago N; Koike, Terumoto; Cook, Douglas J; Bonato, Riccardo; Chen, Manyin; Sato, Masaaki; Waddell, Thomas K; Liu, Mingyao; Slutsky, Arthur S; Keshavjee, Shaf

    2012-10-01

    The evaluation of donor lungs by normothermic ex vivo acellular perfusion has improved the safety of organ utilization. However, this strategy requires a critical re-evaluation of the parameters used to assess lungs during ex vivo perfusion compared with those traditionally used to evaluate the donor lung in vivo. Using a porcine model, we studied the physiology of acellular lung perfusion with the aim of improving the accuracy of clinical ex vivo evaluation. Porcine lungs after 10 hours of brain death and 24 hours of cold ischemia and uninjured control lungs were perfused for 12 hours and then transplanted. PaO2, compliance, airway pressure and pulmonary vascular resistance were measured. Ventilation with 100% nitrogen and addition of red blood cells to the perfusate were used to clarify the physiologic disparities between in vivo blood perfusion and ex vivo acellular perfusion. During 12 hours of ex vivo perfusion, injured lungs developed edema with decreased compliance and increased airway pressure, but ex vivo PO2 remained stable. After transplantation, injured lungs demonstrated high vascular resistance and poor PaO2. A reduced effect of shunt on ex vivo lung perfusion PO2 was found to be attributable to the linearization of the relationship between oxygen content and PO2, which occurs with acellular perfusate. Ex vivo PO2 may not be the first indication of lung injury and, taken alone, may be misleading in assessing the ex vivo lung. Thus, evaluation of other physiologic parameters takes on greater importance. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  19. Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

    Energy Technology Data Exchange (ETDEWEB)

    Galanzha, Ekaterina I. [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Zharov, Vladimir P., E-mail: zharovvladimirp@uams.edu [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

    2013-12-10

    Despite progress in detecting circulating tumor cells (CTCs), existing assays still have low sensitivity (1–10 CTC/mL) due to the small volume of blood samples (5–10 mL). Consequently, they can miss up to 10{sup 3}–10{sup 4} CTCs, resulting in the development of barely treatable metastasis. Here we analyze a new concept of in vivo CTC detection with enhanced sensitivity (up to 10{sup 2}–10{sup 3} times) by the examination of the entire blood volume in vivo (5 L in adults). We focus on in vivo photoacoustic (PA) flow cytometry (PAFC) of CTCs using label-free or targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances, magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time spectral identification, nonlinear signal amplification, and the integration with PAFC in vitro. We demonstrate PAFC’s capability to detect rare leukemia, squamous carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well as the release of CTCs from primary tumors triggered by palpation, biopsy or surgery, increasing the risk of metastasis. CTC lifetime as a balance between intravasation and extravasation rates was in the range of 0.5–4 h depending on a CTC metastatic potential. We introduced theranostics of CTCs as an integration of nanobubble-enhanced PA diagnosis, photothermal therapy, and feedback through CTC counting. In vivo data were verified with in vitro PAFC demonstrating a higher sensitivity (1 CTC/40 mL) and throughput (up to 10 mL/min) than conventional assays. Further developments include detection of circulating cancer-associated microparticles, and super-resolution PAFC beyond the diffraction and spectral limits.

  20. Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

    Directory of Open Access Journals (Sweden)

    Ekaterina I. Galanzha

    2013-12-01

    Full Text Available Despite progress in detecting circulating tumor cells (CTCs, existing assays still have low sensitivity (1–10 CTC/mL due to the small volume of blood samples (5–10 mL. Consequently, they can miss up to 103–104 CTCs, resulting in the development of barely treatable metastasis. Here we analyze a new concept of in vivo CTC detection with enhanced sensitivity (up to 102–103 times by the examination of the entire blood volume in vivo (5 L in adults. We focus on in vivo photoacoustic (PA flow cytometry (PAFC of CTCs using label-free or targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances, magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time spectral identification, nonlinear signal amplification, and the integration with PAFC in vitro. We demonstrate PAFC’s capability to detect rare leukemia, squamous carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well as the release of CTCs from primary tumors triggered by palpation, biopsy or surgery, increasing the risk of metastasis. CTC lifetime as a balance between intravasation and extravasation rates was in the range of 0.5–4 h depending on a CTC metastatic potential. We introduced theranostics of CTCs as an integration of nanobubble-enhanced PA diagnosis, photothermal therapy, and feedback through CTC counting. In vivo data were verified with in vitro PAFC demonstrating a higher sensitivity (1 CTC/40 mL and throughput (up to 10 mL/min than conventional assays. Further developments include detection of circulating cancer-associated microparticles, and super-rsesolution PAFC beyond the diffraction and spectral limits.

  1. Analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine.

    Directory of Open Access Journals (Sweden)

    Christine L Clouser

    2011-01-01

    Full Text Available Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity. In this study, we examined the ribonucleotide reductase inhibitor, gemcitabine, both in cell culture and in C57Bl/6 mice infected with LP-BM5 murine leukemia virus (LP-BM5 MuLV, a murine AIDS model. Gemcitabine decreased infectivity of MuLV in cell culture with an EC50 in the low nanomolar range with no detectable cytotoxicity. Similarly, gemcitabine significantly decreased disease progression in mice infected with LP-BM5. Specifically, gemcitabine treatment decreased spleen size, plasma IgM, and provirus levels compared to LP-BM5 MuLV infected, untreated mice. Gemcitabine efficacy was observed at doses as low as 1 mg/kg/day in the absence of toxicity. Higher doses of gemcitabine (3 mg/kg/day and higher were associated with toxicity as determined by a loss in body mass. In summary, our findings demonstrate that gemcitabine has antiretroviral activity ex vivo and in vivo in the LP-BM5 MuLV model. These observations together with a recent ex vivo study with HIV-1, suggest that gemcitabine has broad antiretroviral activity and could be particularly useful in vivo when used in combination drug therapy.

  2. In vivo and ex vivo applications of gold nanoparticles for biomedical SERS imagingi

    Science.gov (United States)

    Yigit, Mehmet V; Medarova, Zdravka

    2012-01-01

    Surface enhanced Raman scattering (SERS) is a signal-increasing phenomenon that occurs whenever Raman scattering on a metal surface is enhanced many orders of magnitude. Recently SERS has received considerable attention due to its ultrasensitive multiplex imaging capability with strong photostability. It provides rich molecular information on any Raman molecule adsorbed to rough metal surfaces. The signal enhancement is so remarkable that identification of a single molecule is possible. SERS has become a genuine molecular imaging technique. Gold nanoparticles, encoded with Raman reporters, provide a SERS signal and have been used as imaging probes, often referred to as SERS nanoparticles. They have been used for molecular imaging in vivo, ex vivo and in vitro. Detection of picomolar concentrations of target molecules has been achieved by functionalizing the nanoparticles with target recognition ligands. This review focuses on recent achievements in utilizing SERS nanoparticles for in vivo molecular imaging. In the near future, SERS technology may allow detection of disease markers at the single cell level. PMID:23133814

  3. In vivo prevention of transplant arteriosclerosis by ex vivo-expanded human regulatory T cells.

    Science.gov (United States)

    Nadig, Satish N; Wieckiewicz, Joanna; Wu, Douglas C; Warnecke, Gregor; Zhang, Wei; Luo, Shiqiao; Schiopu, Alexandru; Taggart, David P; Wood, Kathryn J

    2010-07-01

    Transplant arteriosclerosis is the hallmark of chronic allograft dysfunction (CAD) affecting transplanted organs in the long term. These fibroproliferative lesions lead to neointimal thickening of arteries in all transplanted allografts. Luminal narrowing then leads to graft ischemia and organ demise. To date, there are no known tolerance induction strategies that prevent transplant arteriosclerosis. Therefore, we designed this study to test the hypothesis that human regulatory T cells (T(reg) cells) expanded ex vivo can prevent transplant arteriosclerosis. Here we show the comparative capacity of T(reg) cells, sorted via two separate strategies, to prevent transplant arteriosclerosis in a clinically relevant chimeric humanized mouse system. We found that the in vivo development of transplant arteriosclerosis in human arteries was prevented by treatment of ex vivo-expanded human T(reg) cells. Additionally, we show that T(reg) cells sorted on the basis of low expression of CD127 provide a more potent therapy to conventional T(reg) cells. Our results demonstrate that human T(reg) cells can inhibit transplant arteriosclerosis by impairing effector function and graft infiltration. We anticipate our findings to serve as a foundation for the clinical development of therapeutics targeting transplant arteriosclerosis in both allograft transplantation and other immune-mediated causes of vasculopathy.

  4. In vivo Prevention of Transplant Arteriosclerosis by ex vivo Expanded Human Regulatory T Cells

    Science.gov (United States)

    Nadig, Satish N.; Więckiewicz, Joanna; Wu, Douglas C.; Warnecke, Gregor; Zhang, Wei; Luo, Shiqiao; Schiopu, Alexandru; Taggart, David P.; Wood, Kathryn J.

    2010-01-01

    Transplant arteriosclerosis (TA) is the hallmark of chronic allograft dysfunction (CAD) affecting transplanted organs in the long term [1,2]. These fibroproliferative lesions lead to neointimal thickening of arteries in all transplanted allografts [2]. Luminal narrowing then leads to graft ischemia and organ demise. To date, there are no known tolerance induction strategies that prevent TA [3,4]. Therefore, this study was designed to test the hypothesis that human regulatory T cells (Treg cells) expanded ex vivo could prevent TA. Here we show the comparative capacity of Treg cells, sorted via two separate strategies, to prevent TA in a clinically relevant chimeric humanized mouse system. We found that the in vivo development of TA in human arteries was prevented with the treatment of ex vivo expanded human Treg cells. Additionally, we show that Treg cells sorted based on the low expression of CD127 (IL-7Rα) provide a more potent therapy to conventional Treg cells. Our results demonstrate, for the first time, that human Treg cells can inhibit TA by impairing effector function and graft infiltration. We anticipate our findings to serve as a foundation for the clinical development of therapeutics targeting TA in both allograft transplantation and other immune-mediated causes of vasculopathy [5]. PMID:20473306

  5. A Convenient In Vivo Model Using Small Interfering RNA Silencing to Rapidly Assess Skeletal Gene Function.

    Directory of Open Access Journals (Sweden)

    Wen Zhang

    Full Text Available It is difficult to study bone in vitro because it contains various cell types that engage in cross-talk. Bone biologically links various organs, and it has thus become increasingly evident that skeletal physiology must be studied in an integrative manner in an intact animal. We developed a model using local intraosseous small interfering RNA (siRNA injection to rapidly assess the effects of a target gene on the local skeletal environment. In this model, 160-g male Sprague-Dawley rats were treated for 1-2 weeks. The left tibia received intraosseous injection of a parathyroid hormone 1 receptor (Pth1r or insulin-like growth factor 1 receptor (Igf-1r siRNA transfection complex loaded in poloxamer 407 hydrogel, and the right tibia received the same volume of control siRNA. All the tibias received an intraosseous injection of recombinant human parathyroid hormone (1-34 (rhPTH (1-34 or insulin-like growth factor-1 (IGF-1. Calcein green and alizarin red were injected 6 and 2 days before euthanasia, respectively. IGF-1R and PTH1R expression levels were detected via RT-PCR assays and immunohistochemistry. Bone mineral density (BMD, microstructure, mineral apposition rates (MARs, and strength were determined by dual-energy X-ray absorptiometry, micro-CT, histology and biomechanical tests. The RT-PCR and immunohistochemistry results revealed that IGF-1R and PTH1R expression levels were dramatically diminished in the siRNA-treated left tibias compared to the right tibias (both p<0.05. Using poloxamer 407 hydrogel as a controlled-release system prolonged the silencing effect of a single dose of siRNA; the mRNA expression levels of IGF-1R were lower at two weeks than at one week (p<0.01. The BMD, bone microstructure parameters, MAR and bone strength were significantly decreased in the left tibias compared to the right tibias (all p<0.05. This simple and convenient local intraosseous siRNA injection model achieved gene silencing with very small quantities of

  6. In vivo antimalarial and cytotoxic properties of Annona senegalensis ...

    African Journals Online (AJOL)

    The in vivo animal antimalarial and in vitro cytotoxic activities of the methanol extract of Annona senegalensis Pers. (Annonaceae) was investigated in this study. The in vivo antimalarial activity of the methanol extract against Plasmodium berghei was assessed using the 4-day suppressive test procedure. The extract of A.

  7. In vivo anti-inflammatory activity of Liquidambar formosana Hance ...

    African Journals Online (AJOL)

    Purpose: To evaluate the anti-inflammatory activity of Liquidambar formosana Hance infructescence (Liquidambaris fructus, ELF) in vivo, and clarify its underlying mechanisms. Methods: The in vivo anti-inflammatory activity of ELF was examined by xylene-induced ear swelling test in mice as well as carrageenan-induced ...

  8. Cancer ameliorating potential of Phyllanthus amarus: In vivo and in ...

    African Journals Online (AJOL)

    It also significantly reduced the number of aberrant cells and frequency of aberrations per cell in vivo. Conclusion: Ameliorating potential of P. amarus was dose and duration dependant. These extracts significantly reduced the mutagenicity and genotoxicity that were produced due to AFB1 treatment both in vitro and in vivo.

  9. Comparison of ex vivo stability of copeptin and vasopressin

    NARCIS (Netherlands)

    Heida, Judith E; Boesten, Lianne S M; Ettema, Esmée M; Muller Kobold, Anneke C.; Franssen, Casper F M; Gansevoort, Ron T; Zittema, Debbie

    BACKGROUND: Copeptin, part of the vasopressin precursor, is increasingly used as marker for vasopressin and is claimed to have better ex vivo stability. However, no study has directly compared the ex vivo stability of copeptin and vasopressin. METHODS: Blood of ten healthy volunteers was collected

  10. In vivo monitoring of angiogenesis within Matrigel chambers using MRI

    DEFF Research Database (Denmark)

    Holm, David; Ley, Carsten Dan; Søgaard, Lise Vejby

    2006-01-01

    Angiogenesis is a critical process in tumour development and presents an important target for the development of a range of anti-cancer agents . To assess the in vivo efficacy of these ‘angiotherapeutics', a simple and reproducible in vivo model would be of significant value. Here we show...

  11. In vivo monitoring of angiogenesis within Matrigel chambers using MRI

    DEFF Research Database (Denmark)

    Peters, David Alberg; Ley, Carsten Dan; Simonsen, Helle Juhl

    Angiogenesis is a critical process in tumour de- velopment and presents an important target for the development of a range of anti-cancer agents1,2. To assess the in vivo efficacy of these ‘angiotherapeutics’, a sim ple and reproducible in vivo model would be of significant value. Here we show.......of angiogenesis and arteriogene- sis....

  12. Nevomelanocytic atypia detection by in vivo reflectance confocal microscopy

    Directory of Open Access Journals (Sweden)

    Ingrida Vaišnorienė

    2014-01-01

    Conclusions: Nevus with histopathologically confirmed nevomelanocytic atypia (dysplastic nevus could not be distinguished from nevus without atypia using analyzed in vivo RCM features of melanocytic atypia. More accurate diagnostics by means of in vivo RCM needs further investigation on reflectance of single and nested cutaneous melanocytes in benign and malignant skin lesions.

  13. Effect of benzylaminopurine on in vivo multiplication of French ...

    African Journals Online (AJOL)

    SARAH

    2014-02-28

    Feb 28, 2014 ... Objective: In vivo macropropagation is an alternative simple and cheap technique for banana multiplication. However, the response of cv. “Itoke Sege” to in vivo macropropagation combined with different benzylaminopurine (BAP) concentrations is not known. This study was conducted to determine the.

  14. Mechanical properties of the human Achilles tendon, in vivo

    DEFF Research Database (Denmark)

    Kongsgaard, M; Nielsen, C H; Hegnsvad, S

    2011-01-01

    Ultrasonography has been widely applied for in vivo measurements of tendon mechanical properties. Assessments of human Achilles tendon mechanical properties have received great interest. Achilles tendon injuries predominantly occur in the tendon region between the Achilles-soleus myotendinous...... Achilles tendon in vivo by the use of ultrasonography and 2) assess the between-day reproducibility of these measurements....

  15. Synovial tissue hypoxia and inflammation in vivo.

    LENUS (Irish Health Repository)

    Ng, C T

    2012-02-01

    INTRODUCTION: Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO(2)) in patients with inflammatory arthritis with macroscopic\\/microscopic inflammation and local levels of proinflammatory mediators. METHODS: Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO(2) under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), interferon gamma (IFNgamma), IL6, macrophage inflammatory protein 3alpha (MIP3alpha) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. RESULTS: The tPO(2) was 22.5 (range 3.2-54.1) mm Hg and correlated inversely with macroscopic synovitis (r=-0.421, p=0.02), sublining CD3 cells (-0.611, p<0.01) and sublining CD68 cells (r=-0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO(2) in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor alpha (TNFalpha), IL1beta, IFNgamma and MIP3alpha in patients with tPO(2) <20 mm Hg (all p values <0.05). CONCLUSIONS: This is the first study to show a direct in vivo correlation between synovial tPO(2), inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.

  16. Viral Vectors for in Vivo Gene Transfer

    Science.gov (United States)

    Thévenot, E.; Dufour, N.; Déglon, N.

    The transfer of DNA into the nucleus of a eukaryotic cell (gene transfer) is a central theme of modern biology. The transfer is said to be somatic when it refers to non-germline organs of a developed individual, and germline when it concerns gametes or the fertilised egg of an animal, with the aim of transmitting the relevant genetic modification to its descendents [1]. The efficient introduction of genetic material into a somatic or germline cell and the control of its expression over time have led to major advances in understanding how genes work in vivo, i.e., in living organisms (functional genomics), but also to the development of innovative therapeutic methods (gene therapy). The efficiency of gene transfer is conditioned by the vehicle used, called the vector. Desirable features for a vector are as follows: Easy to produce high titer stocks of the vector in a reproducible way. Absence of toxicity related to transduction (transfer of genetic material into the target cell, and its expression there) and no immune reaction of the organism against the vector and/or therapeutic protein. Stability in the expression of the relevant gene over time, and the possibility of regulation, e.g., to control expression of the therapeutic protein on the physiological level, or to end expression at the end of treatment. Transduction of quiescent cells should be as efficient as transduction of dividing cells. Vectors currently used fall into two categories: non-viral and viral vectors. In non-viral vectors, the DNA is complexed with polymers, lipids, or cationic detergents (described in Chap. 3). These vectors have a low risk of toxicity and immune reaction. However, they are less efficient in vivo than viral vectors when it comes to the number of cells transduced and long-term transgene expression. (Naked DNA transfer or electroporation is rather inefficient in the organism. This type of gene transfer will not be discussed here, and the interested reader is referred to the

  17. Persistence of DNA studied in different ex vivo and in vivo rat models simulating the human gut situation

    NARCIS (Netherlands)

    Wilcks, A.; Hoek, van A.H.A.M.; Joosten, R.G.; Jacobsen, B.B.L.; Aarts, H.J.M.

    2004-01-01

    This study aimed to evaluate the possibility of DNA sequences from genetically modified plants to persist in the gastrointestinal (GI) tract. PCR analysis and transformation assays were used to study DNA persistence and integrity in various ex vivo and in vivo systems using gnotobiotic rats. DNA

  18. Humanized In Vivo Model for Streptococcal Impetigo

    Science.gov (United States)

    Scaramuzzino, Dominick A.; McNiff, Jennifer M.; Bessen, Debra E.

    2000-01-01

    An in vivo model for group A streptococcal (GAS) impetigo was developed, whereby human neonatal foreskin engrafted onto SCID mice was superficially damaged and bacteria were topically applied. Severe infection, indicated by a purulent exudate, could be induced with as few as 1,000 CFU of a virulent strain. Early findings (48 h) showed a loss of stratum corneum and adherence of short chains of gram-positive cocci to the external surface of granular keratinocytes. This was followed by an increasing infiltration of polymorphonuclear leukocytes (neutrophils) of mouse origin, until a thick layer of pus covered an intact epidermis, with massive clumps of cocci accumulated at the outer rim of the pus layer. By 7 days postinoculation, the epidermis was heavily eroded; in some instances, the dermis contained pockets (ulcers) filled with cocci, similar to that observed for ecthyma. Importantly, virulent GAS underwent reproduction, resulting in a net increase in CFU of 20- to 14,000-fold. The majority of emm pattern D strains had a higher gross pathology score than emm pattern A, B, or C (A–C) strains, consistent with epidemiological findings that pattern D strains have a strong tendency to cause impetigo, whereas pattern A–C strains are more likely to cause pharyngitis. PMID:10768985

  19. In vivo characterization of corneal biomechanics.

    Science.gov (United States)

    Piñero, David P; Alcón, Natividad

    2014-06-01

    Interest in corneal biomechanics has increased with the development of new refractive surgery techniques aimed at modifying corneal properties and a variety of surgical options for corneal ectasia management. The human cornea behaves as soft biological material. It is a viscoelastic tissue and its response to a force applied to it depends not only on the magnitude of the force, but also on the velocity of the application. There are concerns about the limitations to measuring corneal biomechanical properties in vivo. To date, 2 systems are available for clinical use: the Ocular Response Analyzer, a dynamic bidirectional applanation device, and the Corvis ST, a dynamic Scheimpflug analyzer device. These devices are useful in clinical practice, especially for planning some surgical procedures and earlier detection of ectatic conditions, but further research is needed to connect the clinical measurements obtained with these devices to the standard mechanical properties. Neither author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  20. In vivo human buccal permeability of nicotine

    DEFF Research Database (Denmark)

    Adrian, Charlotte L; Olin, Helle B D; Dalhoff, Kim

    2006-01-01

    -smokers using a buccal perfusion cell. The disappearance of nicotine from perfusion solutions with pH 6.0, 7.4, and 8.1 was studied for 3h. The apparent permeability of nicotine (P(app)) was determined at each pH value. Parotid saliva was collected in an attempt to assess systemic levels of nicotine......(app) values and non-ionised nicotine, which indicates that the nicotine transfer occurred by means of passive diffusion. P(app) values of 0.60 x 10(-4) and 6.18 x 10(-4)cms(-1) were obtained for the mono-protonated and non-ionised species of nicotine, respectively. The analysis of the parotid saliva samples...... indicated that these samples might be useful in the assessment of systemic absorption of nicotine. Previous buccal in vitro models underestimated the in vivo human permeability of nicotine. However, the in vitro models were capable of predicting the effect of pH on the nicotine permeability....

  1. Experimental glomerular endothelial injury in vivo.

    Directory of Open Access Journals (Sweden)

    George Haddad

    Full Text Available The microvascular endothelium of the kidney glomerulus is injured in Shiga-like toxigenic bacterial infection, genetic or acquired loss of complement regulatory protein function, and allo-immune responses of solid-organ or bone marrow transplantation. Existing models of diseases with glomerular endothelial cell (EC injury, collectively grouped as thrombotic microangiopathies, are problematic, impeding investigation of the mechanisms of microvascular defense and repair. To develop a model of glomerular endothelial injury in the mouse, we conjugated the M. oreades lectin to the cytotoxin, saporin, (LS to selectively injure the glomerular endothelium. Injury of the microvasculature was evaluated by light, immunofluorescence, and electron microscopy, and by quantitative RT-PCR of cell-type specific transcripts. Renal function was evaluated by quantitation of serum creatinine. The toxin conjugate induced apoptosis of microvascular ECs in vitro, and subtle histologic features of thrombotic microangiopathy in vivo that were enhanced by co-injection of 50 μg/kg LPS. Among LS/LPS-treated animals, loss of glomerular EC staining correlated with decreased expression of EC-specific transcripts, and impaired kidney function. Selective injury of the glomerular microvasculature with LS toxin conjugate and LPS elicits histologic features of thrombotic microangiopathy and acute kidney failure.

  2. In vitro, ex vivo and in vivo anti-hypertensive activity of Chrysophyllum cainito L. extract.

    Science.gov (United States)

    Mao, Li-Mei; Qi, Xue-Wen; Hao, Ji-Heng; Liu, Hai-Feng; Xu, Qing-Hua; Bu, Pei-Li

    2015-01-01

    Chrysophyllum cainito L., a traditional herbal medicine, could have the potential for management of hypertension due to presence of polyphenolic compounds. The extracts and fractions of the pulp of plant were evaluated for in vitro (inhibition of angiotensin I converting enzyme/ACE assay), ex vivo (isolated aorta relaxation assay) and in vivo (salt induced hypertensive rat assay). The alcoholic and aqueous extract (ALE and AQE respectively) of fruit of plant C. cainito was having 14.8 and 9.2% yield respectively. The fractionation with ethyl alcohol (EAF) and butanol (BTF) yielded 2.52 & 2.17% respectively from ALE and 0.46 & 0.31% respectively from AQE with respect to fruit pulp dry weight. More phenolic content was found in ALE (3.75±0.15 mg gallic acid equivalent or GAE g(-1) of dry power of fruit pulp) compared to AQE and maximum in ethyl acetate fraction of ALE (ALE-EAF) (2.32±0.21 mg GAE g(-1) of dry power of fruit pulp) among all fractions. ACE inhibition activity was found to be maximum in ALE-EAF 62.5±7.34%. While ex vivo study using isolated tissue of aorta showed again showed maximum activity (62.82±6.19 and 46.47±8.32% relaxation with 50 µg mL(-1) and 10 µg mL(-1) GAE concentration respectively). ALE-EAF reduced the elevated arterial pressure of salt induced hypertensive rat significantly to the level of normotensive animal group. Results of ALE-EAF have shown its potential as a source for novel constituent for the treatment hypertension and should further be studied for isolation of specific constituent for more effectiveness.

  3. In vitro-in vivo correlation in skin permeation.

    Science.gov (United States)

    Mohammed, D; Matts, P J; Hadgraft, J; Lane, M E

    2014-02-01

    In vitro skin permeation studies have been used extensively in the development and optimisation of delivery of actives in vivo. However, there are few reported correlations of such in vitro studies with in vivo data. The aim of this study was to investigate the skin permeation of a model active, niacinamide, both in vitro and in vivo. Conventional diffusion cell studies were conducted in human skin to determine niacinamide permeation from a range of vehicles which included dimethyl isosorbide (DMI), propylene glycol (PG), propylene glycol monolaurate (PGML), N-methyl 2-pyrrolidone (NMP), Miglyol 812N® (MG), and mineral oil (MO). Single, binary or ternary systems were examined. The same vehicles were subsequently examined to investigate niacinamide delivery in vivo. For this proof-of-concept study one donor was used for the in vitro studies and one volunteer for the in vivo investigations to minimise biovariability. Analysis of in vitro samples was conducted using HPLC and in vivo uptake of niacinamide was evaluated using Confocal Raman spectroscopy (CRS). The amount of niacinamide permeated through skin in vitro was linearly proportional to the intensity of the niacinamide signal determined in the stratum corneum in vivo. A good correlation was observed between the signal intensities of selected vehicles and niacinamide signal intensity. The findings provide further support for the use of CRS to monitor drug delivery into and across the skin. In addition, the results highlight the critical role of the vehicle and its disposition in skin for effective dermal delivery.

  4. Phosphorescent nanosensors for in vivo tracking of histamine levels

    Science.gov (United States)

    Cash, Kevin J.; Clark, Heather A.

    2013-01-01

    Continuously tracking bio-analytes in vivo will enable clinicians and researchers to profile normal physiology and monitor diseased states. Current in vivo monitoring system designs are limited by invasive implantation procedures and bio-fouling, limiting the utility of these tools for obtaining physiologic data. In this work, we demonstrate the first success in optically tracking histamine levels in vivo using a modular, injectable sensing platform based on a diamine oxidase and a phosphorescent oxygen nanosensor. Our new approach increases the range of measureable analytes by combining an enzymatic recognition element with a reversible nanosensor capable of measuring the effects of enzymatic activity. We use these enzyme nanosensors (EnzNS) to monitor the in vivo histamine dynamics as the concentration rapidly increases and decreases due to administration and clearance. The EnzNS system measured kinetics that match those reported from ex vivo measurements. This work establishes a modular approach to in vivo nanosensor design for measuring a broad range of potential target analytes. Simply replacing the recognition enzyme, or both the enzyme and nanosensor, can produce a new sensor system capable of measuring a wide range of specific analytical targets in vivo. PMID:23767828

  5. Nevomelanocytic atypia detection by in vivo reflectance confocal microscopy.

    Science.gov (United States)

    Vaišnorienė, Ingrida; Rotomskis, Ričardas; Kulvietis, Vytautas; Eidukevičius, Rimantas; Zalgevičienė, Violeta; Laurinavičienė, Aida; Venius, Jonas; Didžiapetrienė, Janina

    2014-01-01

    In vivo reflectance confocal microscopy (RCM) is a promising novel technology for non-invasive early diagnostics of cutaneous melanoma. However, the possibility to detect melanocytic atypia in nevi by means of in vivo RCM remains unknown. The aim of the study was to evaluate the significance of in vivo RCM features of melanocytic atypia for the diagnosis of melanocytic nevi, dysplastic nevi and cutaneous melanoma. A total of 138 melanocytic skin lesions comprising 25 melanocytic nevi, 69 dysplastic nevi and 44 melanomas were analyzed by means of dermoscopy, in vivo RCM and routine histopathology. In vivo RCM images were analyzed for the arrangement of keratinocytes in epidermis, pagetoid cells and junctional melanocytic nests and correlated refractivity aspects of nests with histopathology. Separately and all together taken the in vivo RCM features of melanocytic atypia were significant in differential diagnosis of benign and malignant melanocytic skin lesions, though none of the features was significant in discriminating nevi without cytologic atypia of dysplastic nevi. In vivo RCM feature of dense cell clusters corresponded with melanin containing nevomelanocytes on histopathology though exact correspondence of non-homogeneous and atypical sparse cell clusters remained questionable. Nevus with histopathologically confirmed nevomelanocytic atypia (dysplastic nevus) could not be distinguished from nevus without atypia using analyzed in vivo RCM features of melanocytic atypia. More accurate diagnostics by means of in vivo RCM needs further investigation on reflectance of single and nested cutaneous melanocytes in benign and malignant skin lesions. Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  6. Anterior Cruciate Ligament Strain In Vivo

    Science.gov (United States)

    Luque-Seron, Juan Antonio; Medina-Porqueres, Ivan

    2016-01-01

    Context: Distinct exercises have been proposed for knee rehabilitation after anterior cruciate ligament (ACL) reconstruction. There is a need to understand ACL strain behavior during different rehabilitation exercises to protect the graft from excessive strain that could interfere with its healing process. Objective: To critically review studies that directly measured normal ACL strain in vivo during different movements, conditions, or exercises to gain insight into which of them may produce more strain on the ligament or the ligament graft in the case of reconstructed knees. Data Sources: A literature search of PubMed, CINAHL, SPORTDiscus, and PEDro databases was conducted. Keywords included anterior cruciate ligament, strain, stress, deformation, transducer, rehabilitation, rehabilitation exercise, physical therapy, and physiotherapy. Study Selection: Inclusion criteria were (1) peer-reviewed studies published in English or Spanish, (2) research conducted on adult human subjects with normal ACLs and healthy knees, and (3) ACL strain directly measured during different movements, conditions, or exercises by using a transducer. Study Design: Systematic review. Level of Evidence: Level 4. Data Extraction: Specific data were abstracted from the selected studies, including isometric quadriceps and hamstrings activity, active and passive flexion-extension of the knee, closed kinetic chain exercises, and application of joint compressive load. Results: A total of 10 studies met all criteria and were included in the final analysis. The strain values produced by closed kinetic chain and open kinetic chain exercises were similar. However, closed kinetic chain exercises appear to attenuate the strain increase that occurs in open kinetic chain exercises when increasing resistance. Conclusion: These data may be relevant to develop rehabilitation exercises or programs that do not endanger the healing ACL graft and to provide a basis for future clinical trials. PMID:27418161

  7. Electron microscopy methods for studying in vivo DNA replication intermediates.

    Science.gov (United States)

    Lopes, Massimo

    2009-01-01

    The detailed understanding of the DNA replication process requires structural insight. The combination of psoralen crosslinking and electron microscopy has been extensively exploited to reveal the fine architecture of in vivo DNA replication intermediates. This approach proved instrumental to uncover the basic mechanisms of DNA duplication, as well as the perturbation of this process by genotoxic treatments. The replication structures need to the stabilized in vivo (by psoralen crosslinking) prior to extraction and enrichment procedures, finally leading to the visualization at the transmission electron microscope. This chapter outlines the procedures required to visualize in vivo replication intermediates of genomic DNA, extracted from budding yeast or cultured mammalian cells.

  8. In vivo and In vitro Evaluations of Intestinal Gabapentin Absorption

    DEFF Research Database (Denmark)

    Larsen, Malte Selch; Frølund, Sidsel; Nøhr, Martha Kampp

    2015-01-01

    cells. The effect of co-application of the LAT-inhibitor, BCH, and the b(0,+)-substrate, L-lysine, on intestinal transport of gabapentin was evaluated in vivo and in vitro. RESULTS: Gabapentin showed dose-dependent oral absorption kinetics and dose-independent disposition kinetics. Co-application of BCH...... inhibited intestinal absorption in vivo and apical uptake in vitro, whereas no effect was observed following co-application of L-lysine. CONCLUSIONS: The present study shows for the first time that BCH was capable of inhibiting intestinal absorption of gabapentin in vivo. Furthermore, in Caco-2 cell...

  9. AAV serotype influences gene transfer in corneal stroma in vivo

    OpenAIRE

    Sharma, Ajay; Jonathan C K Tovey; Ghosh, Arkasubhra; Mohan, Rajiv R.

    2010-01-01

    This study evaluated the cellular tropism and relative transduction efficiency of three AAV serotypes, AAV6, AAV8 and AAV9, for corneal gene delivery using mouse cornea in vivo and donor human cornea ex vivo. The AAV6, AAV8 and AAV9 serotypes having AAV2 plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Viral vectors (109 vg/μl) were topically applied onto mouse cornea in vivo and human cornea ex viv...

  10. VIVO Lab at the German National Library of Science and Technology: Review and Outlook

    OpenAIRE

    Walther, Tatiana; Blümel, Ina; Heller, Lambert

    2016-01-01

    This poster gives an overview about past, current and future activities of the VIVO Lab – a sub-group of the Open Science Lab at the German National Library of Science and Technology (TIB). In the past there have been several corporate projects and implementations around VIVO, including the past corporate VIVO project – VIVO for the TIB, which was complemented with the additional features (VIVOPath and VIVO Deutsches Handbuch). The current subject area of the VIVO Lab covers, among other thi...

  11. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    Science.gov (United States)

    Williams, Jonathan M.

    2017-01-01

    ABSTRACT Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. PMID:28151409

  12. Ex Vivo and In Vivo Characterization of Interpolymeric Blend/Nanoenabled Gastroretentive Levodopa Delivery Systems

    Directory of Open Access Journals (Sweden)

    Ndidi C. Ngwuluka

    2017-01-01

    Full Text Available One approach for delivery of narrow absorption window drugs is to formulate gastroretentive drug delivery systems. This study was undertaken to provide insight into in vivo performances of two gastroretentive systems (PXLNET and IPB matrices in comparison to Madopar® HBS capsules. The pig model was used to assess gastric residence time and pharmacokinetic parameters using blood, cerebrospinal fluid (CSF, and urine samples. Histopathology and cytotoxicity testing were also undertaken. The pharmacokinetic parameters indicated that levodopa was liberated from the drug delivery systems, absorbed, widely distributed, metabolized, and excreted. Cmax were 372.37, 257.02, and 461.28 ng/mL and MRT were 15.36, 14.98, and 13.30 for Madopar HBS capsules, PXLNET, and IPB, respectively. In addition, X-ray imaging indicated that the gastroretentive systems have the potential to reside in the stomach for 7 hours. There was strong in vitro-in vivo correlation for all formulations with r2 values of 0.906, 0.935, and 0.945 for Madopar HBS capsules, PXLNET, and IPB, respectively. Consequently, PXLNET and IPB matrices have pertinent potential as gastroretentive systems for narrow absorption window drugs (e.g., L-dopa and, in this application specifically, enhanced the central nervous system and/or systemic bioavailability of such drugs.

  13. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    Directory of Open Access Journals (Sweden)

    Michael D. Burkitt

    2017-02-01

    Full Text Available Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems.

  14. Assembly and characterization of a nonlinear optical microscopy for in vivo and ex vivo tissue imaging

    Science.gov (United States)

    Pratavieira, S.; Buzzá, H. H.; Jorge, A. E.; Grecco, C.; Pires, L.; Cosci, A.; Bagnato, V. S.; Kurachi, C.

    2014-02-01

    The purpose of this study is the assembly and characterization of a custom-made non-linear microscope. The microscope allows the adjustment for in vitro, in vivo and ex vivo imaging of biological samples. Two galvanometer mirrors conjugated by two spherical mirrors are used for the lateral scan and for the axial scan a piezoeletric stage is utilized. The excitation is done using a tunable femtosecond Ti: Sapphire laser. The light is focused in tissue by an objective lens 20X, water immersion, numerical aperture of 1.0, and working distance of 2.0 mm. The detection system is composed by a cut off filter that eliminates laser light back reflections and diverse dichroic filters can be chosen to split the emitted signal for the two photomultiplier detector. The calibration and resolution of the microscope was done using a stage micrometer with 10 μm divisions and fluorescent particle slide, respectively. Fluorescence and second harmonic generation images were performed using epithelial and hepatic tissue, the images have a sub-cellular spatial resolution. Further characterization and differentiation of tissue layers can be obtained by performing axial scanning. By means of the microscope it is possible to have a three dimensional reconstruction of tissues with sub-cellular resolution.

  15. Population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space.

    Science.gov (United States)

    Feng, Lei; Jeon, Tina; Yu, Qiaowen; Ouyang, Minhui; Peng, Qinmu; Mishra, Virendra; Pletikos, Mihovil; Sestan, Nenad; Miller, Michael I; Mori, Susumu; Hsiao, Steven; Liu, Shuwei; Huang, Hao

    2017-12-01

    Animal models of the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate, have been irreplaceable in neurobiological studies. However, a population-averaged macaque brain diffusion tensor imaging (DTI) atlas, including comprehensive gray and white matter labeling as well as bony and facial landmarks guiding invasive experimental procedures, is not available. The macaque white matter tract pathways and microstructures have been rarely recorded. Here, we established a population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space incorporating bony and facial landmarks, and delineated microstructures and three-dimensional pathways of major white matter tracts in vivo MRI/DTI and ex vivo (postmortem) DTI of ten rhesus macaque brains were acquired. Single-subject macaque brain DTI template was obtained by transforming the postmortem high-resolution DTI data into in vivo space. Ex vivo DTI of ten macaque brains was then averaged in the in vivo single-subject template space to generate population-averaged macaque brain DTI atlas. The white matter tracts were traced with DTI-based tractography. One hundred and eighteen neural structures including all cortical gyri, white matter tracts and subcortical nuclei, were labeled manually on population-averaged DTI-derived maps. The in vivo microstructural metrics of fractional anisotropy, axial, radial and mean diffusivity of the traced white matter tracts were measured. Population-averaged digital atlas integrated into in vivo space can be used to label the experimental macaque brain automatically. Bony and facial landmarks will be available for guiding invasive procedures. The DTI metric measurements offer unique insights into heterogeneous microstructural profiles of different white matter tracts.

  16. Persistence of DNA studied in different ex vivo and in vivo rat models simulating the human gut situation

    DEFF Research Database (Denmark)

    Wilcks, Andrea; van Hoek, A.H.A.M.; Joosten, R.G.

    2004-01-01

    This study aimed to evaluate the possibility of DNA sequences from genetically modified plants to persist in the gastrointestinal (GI) tract. PCR analysis and transformation assays were used to study DNA persistence and integrity in various ex vivo and in vivo systems using gnotobiotic rats. DNA...... studied was either plasmid DNA, naked plant DNA or plant DNA embedded in maize flour. Ex vivo experiments performed by incubating plant DNA in intestinal samples, showed that DNA is rapidly degraded in the upper part of the GI tract whereas degradation is less severe in the lower part. In contrast...

  17. Selected recent in vivo studies on chemical measurements in invertebrates.

    Science.gov (United States)

    Majdi, S; Ren, L; Fathali, H; Li, X; Ewing, A G

    2015-06-07

    In vivo measurements of neurotransmitters and related compounds have provided a better understanding of the chemical interactions that are a major part in functioning of brains. In addition, a great deal of technology has been developed to measure chemical species in other areas of living organisms. A key part of this work has been sampling technologies as well as direct measurements in vivo. This is extremely important when sampling from the smallest animal systems. Yet, very small invertebrate systems are excellent models and often have better defined and more easily manipulated genetics. This review focuses on in vivo measurements, electrochemical methods, fluorescence techniques, and sampling and is further narrowed to work over approximately the last three years. Rapid developments of in vivo studies in these model systems should aid in finding solutions to biological and bioanalytical challenges related to human physiological functions and neurodegenerative diseases.

  18. In vivo endoscopic multi-beam optical coherence tomography

    Energy Technology Data Exchange (ETDEWEB)

    Standish, Beau A; Mariampillai, Adrian; Munce, Nigel R; Leung, Michael K K; Vitkin, I Alex [Deptartment of Medical Biophysics, University of Toronto, Toronto (Canada); Lee, Kenneth K C; Yang, Victor X D [Ontario Cancer Institute/University Health Network, Toronto (Canada)], E-mail: standish@ee.ryerson.ca

    2010-02-07

    A multichannel optical coherence tomography (multi-beam OCT) system and an in vivo endoscopic imaging probe were developed using a swept-source OCT system. The distal optics were micro-machined to produce a high numerical aperture, multi-focus fibre optic array. This combination resulted in a transverse design resolution of <10 {mu}m full width half maximum (FWHM) throughout the entire imaging range, while also increasing the signal intensity within the focus of the individual channels. The system was used in a pre-clinical rabbit study to acquire in vivo structural images of the colon and ex vivo images of the oesophagus and trachea. A good correlation between the structural multi-beam OCT images and H and E histology was achieved, demonstrating the feasibility of this high-resolution system and its potential for in vivo human endoscopic imaging.

  19. The Expanding Toolbox of In Vivo Bioluminescent Imaging.

    Science.gov (United States)

    Xu, Tingting; Close, Dan; Handagama, Winode; Marr, Enolia; Sayler, Gary; Ripp, Steven

    2016-01-01

    In vivo bioluminescent imaging (BLI) permits the visualization of engineered bioluminescence from living cells and tissues to provide a unique perspective toward the understanding of biological processes as they occur within the framework of an authentic in vivo environment. The toolbox of in vivo BLI includes an inventory of luciferase compounds capable of generating bioluminescent light signals along with sophisticated and powerful instrumentation designed to detect and quantify these light signals non-invasively as they emit from the living subject. The information acquired reveals the dynamics of a wide range of biological functions that play key roles in the physiological and pathological control of disease and its therapeutic management. This mini review provides an overview of the tools and applications central to the evolution of in vivo BLI as a core technology in the preclinical imaging disciplines.

  20. A method to study in vivo stability of DNA nanostructures.

    Science.gov (United States)

    Surana, Sunaina; Bhatia, Dhiraj; Krishnan, Yamuna

    2013-11-01

    DNA nanostructures are rationally designed, synthetic, nanoscale assemblies obtained from one or more DNA sequences by their self-assembly. Due to the molecularly programmable as well as modular nature of DNA, such designer DNA architectures have great potential for in cellulo and in vivo applications. However, demonstrations of functionality in living systems necessitates a method to assess the in vivo stability of the relevant nanostructures. Here, we outline a method to quantitatively assay the stability and lifetime of various DNA nanostructures in vivo. This exploits the property of intact DNA nanostructures being uptaken by the coelomocytes of the multicellular model organism Caenorhabditis elegans. These studies reveal that the present fluorescence based assay in coelomocytes of C. elegans is an useful in vivo test bed for measuring DNA nanostructure stability. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  1. ANTIOXIDANTS AMELIORATION OF ARSENICAL-INDUCED EFFECTS IN VIVO

    Science.gov (United States)

    Antioxidant amelioration of arsenical-induced effects in vivo. ES Hunter and EH Rogers. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC. Antioxidants have been reported to ameliorate the effects of many developmental toxicants. We tested the hypothesis that oxi...

  2. Endocrine disrupting properties in vivo of widely used azole fungicides

    DEFF Research Database (Denmark)

    Taxvig, Camilla; Vinggaard, Anne; Hass, Ulla

    2008-01-01

    The endocrine-disrupting potential of four commonly used azole fungicides, propiconazole, tebuconazole, epoxiconazole and ketoconazole, were tested in two short-term in vivo studies. Initially, the antiandrogenic effects of propiconazole and tebuconazole (50, 100 and 150 mg/kg body weight/day eac...... as endocrine disruptors in vivo, although the profile of action in vivo varies. As ketoconazole is known to implicate numerous endocrine-disrupting effects in humans, the concern for the effects of the other tested azole fungicides in humans is growing.......The endocrine-disrupting potential of four commonly used azole fungicides, propiconazole, tebuconazole, epoxiconazole and ketoconazole, were tested in two short-term in vivo studies. Initially, the antiandrogenic effects of propiconazole and tebuconazole (50, 100 and 150 mg/kg body weight/day each...

  3. In vivo spectral micro-imaging of tissue

    Science.gov (United States)

    Demos, Stavros G; Urayama, Shiro; Lin, Bevin; Saroufeem, Ramez; Ghobrial, Moussa

    2012-11-27

    In vivo endoscopic methods an apparatuses for implementation of fluorescence and autofluorescence microscopy, with and without the use of exogenous agents, effectively (with resolution sufficient to image nuclei) visualize and categorize various abnormal tissue forms.

  4. Modulating Hippocampal Plasticity with In Vivo Brain Stimulation

    National Research Council Canada - National Science Library

    Rohan, Joyce G; Carhuatanta, Kim A; McInturf, Shawn M; Miklasevich, Molly K; Jankord, Ryan

    2015-01-01

    .... However, the mechanisms by which tDCS effects brain function remain under scrutiny. We have demonstrated that in vivo tDCS in rats produced a lasting effect on hippocampal synaptic plasticity, as measured using extracellular recordings...

  5. In silico vs. in vivo human intestinal permeability.

    Science.gov (United States)

    Idkaidek, N M; Najib, N

    2014-12-01

    The aim of this research is to calculate human intestinal permeability in silico and correlate results with those measured in vivo. Optimized human intestinal permeability values were calculated for 16 drugs by de-convolution of human plasma profiles using Parameter Estimation module of SimCYP program V13. Results showed high in silico-in vivo correlation coefficient of 0.89 for drugs with high/low permeability values. In silico permeability, if properly optimized, can be used as surrogate for in vivo permeability for BCS class I drugs and hence is suggested that such methodology could be employed as a support for waiver of in vivo studies. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Endothelial cells present antigens in vivo

    Directory of Open Access Journals (Sweden)

    Tellides George

    2004-03-01

    Full Text Available Abstract Background Immune recognition of vascular endothelial cells (EC has been implicated in allograft rejection, protection against pathogens, and lymphocyte recruitment. However, EC pervade nearly all tissues and predominate in none, complicating any direct test of immune recognition. Here, we examined antigen presentation by EC in vivo by testing immune responses against E. coli β-galactosidase (β-gal in two lines of transgenic mice that express β-gal exclusively in their EC. TIE2-lacZ mice express β-gal in all EC and VWF-lacZ mice express β-gal in heart and brain microvascular EC. Results Transgenic and congenic wild type FVB mice immunized with β-gal expression vector DNA or β-gal protein generated high titer, high affinity antisera containing comparable levels of antigen-specific IgG1 and IgG2a isotypes, suggesting equivalent activation of T helper cell subsets. The immunized transgenic mice remained healthy, their EC continued to express β-gal, and their blood vessels showed no histological abnormalities. In response to β-gal in vitro, CD4+ and CD8+ T cells from immunized transgenic and FVB mice proliferated, expressed CD25, and secreted IFN-γ. Infection with recombinant vaccinia virus encoding β-gal raised equivalent responses in transgenic and FVB mice. Hearts transplanted from transgenic mice into FVB mice continued to beat and the graft EC continued to express β-gal. These results suggested immunological ignorance of the transgene encoded EC protein. However, skin transplanted from TIE2-lacZ onto FVB mice lost β-gal+ EC and the hosts developed β-gal-specific antisera, demonstrating activation of host immune effector mechanisms. In contrast, skin grafted from TIE2-lacZ onto VWF-lacZ mice retained β-gal+ EC and no antisera developed, suggesting a tolerant host immune system. Conclusion Resting, β-gal+ EC in transgenic mice tolerize specific lymphocytes that would otherwise respond against β-gal expressed by EC within

  7. Semiconductor quantum dot toxicity in a mouse in vivo model

    Science.gov (United States)

    Bozrova, Svetlana V.; Baryshnikova, Maria A.; Nabiev, Igor; Sukhanova, Alyona

    2017-01-01

    Quantum dots (QDs) are increasingly widely used in clinical medicine. Their most promising potential applications are cancer diagnosis, including in vivo tumour imaging and targeted drug delivery. In this connection, the main questions are whether or not QDs are toxic for humans and, if they are, what concentration is relatively harmless. We have carried out in vivo experiments with CdSe/ZnS fluorescent semiconductor core/shell QDs, which are currently the most widely used in research.

  8. Development and in vivo evaluation of mucoadhesive tablets of Rebapimide

    OpenAIRE

    Gudas, Ganesh Kumar; Jaswanth, A; Bhikshapathi, V.R.N.

    2016-01-01

    The aim of the present work was in vitro and in vivo evaluation of mucoadhesive tablets of rebapimide to prolong the gastric residence time after oral administration. The solubility of rebapimide was enhanced by kneading technique with that mixture formulations were prepared by using 33 full factorial designs to explore the effects of  gum Kondagogu, gum Olibanum and Guar  gum (as independent variables) on mucoadhesive strength, drug release and Ex vivo residence time (as dependent variables)...

  9. In vitro and in vivo production of pectic enzymes, polygalacturonase ...

    African Journals Online (AJOL)

    Possible in vitro and in vivo production of pectic enzyme polygalacturonase and pH on the activity of the enzyme were investigated. The results of the assay for the production of polygalacturonase (PG) by the pathogen showed that the activity was 142.9 RVU in vitro and 166.7 RVU, in vivo at temperature 25°C. The optimum ...

  10. Dissecting Neuronal Participation to Focal Epileptic Events in Vivo

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0631 TITLE: Dissecting Neuronal Participation to Focal Epileptic Events in Vivo PRINCIPAL INVESTIGATOR: Stelios M...SUBTITLE 5a. CONTRACT NUMBER Dissecting Neuronal Participation to Focal Epileptic Events in Vivo 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...rational approaches to therapy we need to understand the role that individual neurons of different types play in epileptic events. The two-photon

  11. Draft guidelines on in vivo conservation of animal genetic resources

    OpenAIRE

    Boettcher, P.; Martin, J.F.; Gandini, G.; Joshi, B.K.; Oldenbroek, J.K.; Sponenberg, P.

    2012-01-01

    These guidelines present the basic concepts involved in the establishment and implementation of in vivo conservation plans for animal genetic resources for food and agriculture. The guidelines are intended for use by policy makers in the management of animal genetic resources, managers of animal breeding organizations, persons responsible for training in animal genetic resource management and any stakeholders with a leading role in designing and implementing in vivo conservation of animal gen...

  12. Defining human mesenchymal stem cell efficacy in vivo

    Directory of Open Access Journals (Sweden)

    Lennon Donald P

    2010-10-01

    Full Text Available Abstract Allogeneic human mesenchymal stem cells (hMSCs can suppress graft versus host disease (GvHD and have profound anti-inflammatory and regenerative capacity in stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of disease. There is significant clinical hMSC variability in efficacy and the ultimate response in vivo. The challenge in hMSC based therapy is defining the efficacy of hMSC in vivo. Models which may provide insight into hMSC bioactivity in vivo would provide a means to distinguish hMSCs for clinical utility. hMSC function has been described as both regenerative and trophic through the production of bioactive factors. The regenerative component involves the multi-potentiality of hMSC progenitor differentiation. The secreted factors generated by the hMSCs are milieu and injury specific providing unique niches for responses in vivo. These bioactive factors are anti-scarring, angiogenic, anti-apoptotic as well as regenerative. Further, from an immunological standpoint, hMSC's can avoid host immune response, providing xenographic applications. To study the in vivo immuno-regulatory effectiveness of hMSCs, we used the ovalbumin challenge model of acute asthma. This is a quick 3 week in vivo pulmonary inflammation model with readily accessible ways of measuring effectiveness of hMSCs. Our data show that there is a direct correlation between the traditional ceramic cube score to hMSCs attenuation of cellular recruitment due to ovalbumin challenge. The results from these studies verify the in vivo immuno-modulator effectiveness of hMSCs and support the potential use of the ovalbumin model as an in vivo model of hMSC potency and efficacy. Our data also support future directions toward exploring hMSCs as an alternative therapeutic for the treatment of airway inflammation associated with asthma.

  13. The recent in vivo ESR imaging in Yamagata

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Hidekatsu; Ohya, Hiroaki [Inst. for Life Support Technology, Matsuei, Yamagata (Japan)

    2002-04-01

    In vivo ESR imaging systems operating at ca. 700 MHz were developed in our institute. ESR imaging of living small animals that had received some nitroxide radicals and their reduced form have been conducted. These imaging techniques can be applied to some disease models. We think that the ESR imaging of nitroxide radicals in the biological systems is useful to estimate in vivo reduction or oxidation, i.e., redox status in the target area (such as the brain). (author)

  14. Would the Discovery of ETI Provoke a Religious Crisis?

    Science.gov (United States)

    Peters, Ted

    Noting how some prophets of crisis forecast that traditional religious traditions are vulnerable to challenge if not collapse upon confirmation of the existence of extraterrestrial intelligent beings, this chapter subjects this claim to examination. Citing findings from the Peters ETI Religious Crisis Survey, we find evidence that those who affirm religious belief have no difficulty affirming the existence of ETI and incorporating ETI into their respective worldviews. This applies to Orthodox Christians, Roman Catholics, mainline Protestants, Evangelical Protestants, Jews, Mormons, Buddhists, and to those who self-identify as non-religious. Surprisingly, the self-identified non-religious respondents are the only ones who fear a religious crisis precipitated by contact with extraterrestrials, a crisis expected to happen to others but not to themselves. Turning to the new field of Astrotheology, the question of de-centering both geocentrism and anthropocentrism is raised in light of the prospect of discovering intelligent celestial neighbors.