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2.4 Prevention and treatment of osteoporosis
Bisphosphonate potency in bone resorption and in the induction of apoptosis: zoledronic acid was the most effective compound. The proapoptotic efficacy of zoledronic acid on breast cancer cells was confirmed in two subsequent studies [70, 71]. In the first, Jadgev et al. [70] showed that acute exposure to zoledronic acid 2, 6 and 12 h ; , more accurately reflecting the in vivo condition than longterm exposure 72 h ; , was sufficient to determine an antitumor effect in breast cancer cells. A synergic action with paclitaxel was also observed. Moreover, zoledronic acid-induced apoptosis was inhibited by the addition of intermediates of the mevalonate pathway completely inhibited by geranylgeraniol and partially by farnesol ; , suggesting that amino-bisphosphonate activity on breast cancer cells is strictly related to the inhibition of enzymes of the same pathway [70]. The second study aimed to identify the signaling pathways involved in zoledronic acid-induced apoptosis [71]. Zoledronate treatment was shown to induce the failure of Ras protein membrane localization, the release of mitochondrial cytochrome c into the cytosol and the subsequent activation of caspase-3 proteases [71]. Such events were inhibited by the addition of farnesol, and by forced expression of bcl-2. The authors suggested that the reduced Ras protein prenylation, with impaired membrane localization and functioning, represents the initial event inducing apoptosis [71]. This apoptosis is associated with the release of cythocrome c into the cytosol and the subsequent activation of the caspase cascade. Fromigue et al. [72] demonstrated that the apoptosis of breast cancer cells induced by clodronate, pamidronate, ibandronate and zoledronic acid was almost completely reversed by the z-VAD-fmk caspase inhibitor. This suggests a role of caspase activation in bisphosphonate-induced apoptosis. When analyzing non-amino-bisphosphonate-induced apoptosis, mechanisms other than the lack of Ras-protein prenylation need to be considered. In fact, caspase activation should be induced by toxic ATP analogs accumulating intracellularly. Bisphosphonate activity was also observed in other cancer cell lines. Shipman et al. [73] demonstrated that the amino-bisphosphonate incadronate may induce apoptosis of human multiple myeloma cells in vitro. This effect is mediated by the inhibition of the mevalonate pathway [74], and is completely abrogated by forced expression of bcl-2 [75]. Moreover, pamidronate and clodronate were shown to inhibit cell proliferation and to induce apoptosis in the UMR 106-01 clonal rat osteosarcoma cell line in a dose- and time-dependent fashion [76]. Recently, Riebeling et al. [77] reported that pamidronate can induce apoptosis and inhibit.
Derived from and inscribed within a colonial legacy. Drawing from critical anti-racist feminist frameworks, I discuss intersecting and interlocking hierarchies of power that maintain inequalities structured on the basis of race and gender. The invisibility of these structures of power and the attendant discursive economy of violence are communicated through institutions of legitimation, including the mass media, a topic I explore in the following chapter. However, this discursive economy of violence is also rendered legitimate through the very definitions employed to define and describe violence. I trace these definitions, highlighting the role of common sense, as grounded in structures of White dominance, and the resulting explanatory frameworks that are deployed to explain violence as experienced by racialized women of colour. My point of departure necessarily begins with a contextualization of race and its relationship to White structures of dominance. Contextualizing Race within the Power of Whiteness Scholars have repeatedly pointed to the history of Canada both as a colonizing and colonized country see Bannerji 2000; Thobani 2002a; Razack 1998a, 1998b, 2002 ; . This dual and somewhat contradictory historical formation has undoubtedly shaped the way in which the state continues to stratify groups in the interests of maintaining a hierarchical structure of power and privilege. Violence is one effective way by which particular groups are kept in their place. But rather than espouse a limited definition of violence that tends to be ingrained in our common-sense stock of knowledge, the definition of violence I adhere to in this chapter encompasses the spectrum of coercive, physical, and institutional power in other words, it subsumes the very character, instruments, and goals of domination. A crucial way in which power is naturalized and communicated is through structures of dominance. These structures are grounded in predominant "ways of seeing, " to borrow a phrase from John Berger 1972 ; . The latter derive from and reinforce the dominant common-sense stock of knowledge that which is taken for granted, assumed, and reproduced over time. Stuart Hall 1990a ; argues that a society's common-sense stock of knowledge is never homogeneous or monolithic. Rather, it is filled with contradictory bits and pieces of knowledge that are acquired, transformed, and reproduced over time. Drawing from Gramsci, Hall 1979, 325-26 ; reasons, "It is precisely its `spontaneous' quality, its transparency, its `naturalness, ' its refusal to be made to examine the premises on which it is founded, its resistance to change or to correction, its effect of instant recognition, and the closed circle in which one moves which makes common sense, at one and the same time, `spontaneous, ' ideological and unconscious. You cannot learn, through common sense, how things are: you can only discover where they fit into the existing scheme of things." It is the commonalities inherent in the shared language of power, through which consent is obtained, that become.
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| Intravenous ibandronateThis section combines data from other reviews where a TCA was used as a comparator treatment. It is, therefore, not a systematic review since a systematic search for all trials of TCAs was not conducted. It specifically does not include comparisons of TCAs with other TCAs and ibritumomab.
To release bone-bound bisphosphonate, a direct effect on mature osteoclasts appears to be the most important route of action. As a result of recent discoveries concerning their molecular mechanism of action, bisphosphonates can be grouped into two classes. The simple bisphosphonates that closely resemble PPi such as clodronate, etidronate and tiludronate ; can be metabolically incorporated into non-hydrolysable analogues of ATP that accumulate intracellularly in osteoclasts, resulting in induction of osteoclast apoptosis. By contrast, the more potent, nitrogen-containing bisphosphonates such as pamidronate, alendronate, risedronate, ibandronate and zoledronate ; appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids FPP and GGPP ; that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. Loss of bone-resorptive activity and osteoclast apoptosis is due primarily to loss of geranylgeranylated small GTPases. Identification of FPP synthase as the target of nitrogen-containing bisphosphonates has also helped explain the molecular basis for the adverse effects of these agents in the GI tract and on the immune system. 684. Calcitonin for osteoporosis and bone pain - Mehta N.M., Malootian A. and Gilligan J.P. [N.M. Mehta, Unigene Laboratories Inc., 110 Little Falls Road, Fairfield, NJ 07004, United States] CURR. PHARM. DES. 2003 9 32 ; - summ in ENGL Calcitonin has been approved for the treatment of osteoporosis and other diseases involving accelerated bone turnover for approximately 25 years. The most commonly studied and prescribed form is salmon calcitonin, which has a greater efficacy in clinical use. A wealth of well-controlled clinical studies have demonstrated that calcitonin preserves or increases bone mineral density BMD ; and reduces the risk of vertebral fractures in osteoporosis. Recent studies have indicated that while a low BMD is correlated with an increase in fracture risk, increases in BMD alone do not explain the antifracture efficacy of antiresorptive therapies such as calcitonin. Therapies that moderately increase BMD may reduce fracture risk by reducing the rate of bone turnover and maintaining the integrity of the trabecular architecture, resulting in the preservation of bone strength and quality in osteoporotic patients. An advantage of calcitonin that is not shared by other antiresorptive therapies is its direct analgesic effect on bone pain. Calcitonin has been demonstrated to be clinically useful in improving pain, not only from the acute vertebral fractures of osteoporosis, but also in Paget's disease, bone malignancies, and other sources or musculoskelctal pain. Drugs containing calcitonin may be approved for additional indications in the near future, and as more convenient routes of administration such as the oral route become available, the demand for the calcitonin peptide is expected to increase. 685. Mechanism of organophosphates nerve gases and pesticides ; and antidotes: Electron transfer and oxidative stress Kovacic P. [P. Kovacic, Department of Chemistry, San Diego State University, San Diego, CA 92182-0130, United States] - CURR. MED. CHEM. 2003 10 24 ; - summ in ENGL Evidence indicates that nerve gas toxins operate in ways in addition to inhibition of acetylcholine esterase. Alternative bioactivities are discussed with focus on electron transfer. The main class, including pralidoxime 2-PAM ; , incorporates conjugated iminium and oxime moieties that are electron affinic. Various physiological properties of iminium and oxime species are reviewed. The organophosphates encompass both nerve gases and insecticides, possessing similar properties, but different activities. Toxic manifestations are apparently due, in part, to oxidative stress. Alkylation of DNA takes place which may lead to generation of reactive oxygen species. Structure-activity relationships are examined, including reduction potentials and the captodative effect. 686. Mechanism of drug and toxic actions of Gossypol: Focus on reactive oxygen species and electron transfer - Kovaci P. [P. Kovacic, Department of Chemistry, San Diego State University, San Diego, CA 92182-1030, United States] - CURR. MED. CHEM. 2003 10 24 ; - summ in ENGL Gossypol, a constituent of cottonseeds, displays various drug properties, including antifertility and anticancer. Toxicity is shown 95.
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Significant bone loss occurs subsequent to organ transplantation 2, 9, 15 ; . Osteopenia is severe in some and tolerable in other patients. Bone loss occurs in cases with normal or low initial bone mineral density. The risk of the individual patient seems to be unpredictable 16 ; . In patients who have received bone marrow, heart, and liver transplants, prophylactic treatment with calcium supplementation 1719 ; , vitamin D 18 20 ; , calcitonin 17 ; , estrogen, or testosterone 21 ; has been considered but does not prevent bone loss. Conflicting results were achieved with various bisphosphonates as prophylaxis of posttransplantation osteoporosis. The first-generation compound etidronate could prevent postmenopausal or corticosteroid-induced osteoporosis 10, 11 ; but did not prevent posttransplantation osteoporosis 18, 20 ; , probably because of its relative weak potency. Only in the stable phase more than 1 yr after transplantation did patients with already manifest posttransplantation osteoporosis seem to benefit from first-generation bisphosphonates 22, 23 ; . The third-generation aminobisphosphonate pamidronate is more potent and seems to be able to prevent the occurrence of posttransplantation osteoporosis 19, 24, 25 ; . However, all studies done so far were performed without controls or lack power because of the small number of patients. Therefore, we performed a large, prospective, randomized study for prevention of osteopenia after kidney transplantation. Bisphosphonates are favorable compounds because of the few side effects and efficacy in both genders. They are incorporated into the bone and exert a variety of molecular mechanisms to inhibit osteoclast activity and bone resorption 26 ; . There are various bisphosphonates that demonstrate great differences in their potency, route of administration, and effect on lymphocytes 27 ; . Ibandronate was selected for its high po and idarubicin
| Treatment: All patients will receive a treatment with Ibandronate 50 mg p.o. daily for 2 years or Ibandronate 6 mg i.v. every 4 weeks for 2 years The decision of oral or intravenous application will be up to the patient. Patients will be randomised to receive either No cytotoxic treatment or 6 cycles of chemotherapy with Capecitabine 2000 mg m divided to two daily doses on days 1 14 q day 22 Dose adjustment will be possible in case of NCI-CTC grade 2 toxicity see dose modification ; . Patients with hormonsensitive disease 10% stained cells for estrogen and or progesterone receptor ; will receive Anastrozol 1 mg p.o. per day for 5 years.
The variability in response of the pulmonary arterial mean pressure following the intravenous injection of 4 ganglion blocking agents is summarized in table 4. There is no report on the effects of 4 other drugs, including chlorisoiidamine, mecamylamine, pentamethonium and azamethonium. There are 3 explanations for the variability in response of pulmonary arterial pressure, namely and ifex.
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Ibandronate is approved for the prevention and treatment of postmenopausal osteoporosis.
Several benzodiazepines have been shown to possess antischistosomal properties, among them the anticonvulsant clonazepam and its methyl derivative designated Ro 11-3128.12 The latter compound was very effective in animals as well as in a preliminary human study, but activity was confined to S. mansoni and S. haematobium, while S. japonicum was not affected. Immature schistosomes are also sensitive to Ro 11-3128. The problem is that, not surprisingly for a benzodiazepine, the drug causes severe and long-lasting sedation, accompanied by ataxia and muscle relaxation. This could be prevented by administering the benzodiazepine antagonist Ro 15-1788, which does not block the antischistosomal activity, but unfortunately the effect of the and ifosfamide.
Necessary to prescribe them for overall fracture prevention. The MOBILE study employed a randomized, double-blind method referred to as a "noninferior" trial. A total of 1, 609 women with osteoporosis were assigned to once-monthly or daily oral ibandronate. All monthly regimens proved "noninferior" to daily dosing, and the highest monthly dose 150 mg ; proved superior to the daily regimen, in terms of lumbar spine BMD increase at 1 year. All regimens were similarly tolerated. Those who would criticize this methodology will be interested to recall that noninferiority trials were exactly the mechanism that led the way from daily to weekly dosing for alendronate and risedronate. Which patients are best suited to ibandronate? Until nonvertebral fracture data become available, however, many clinicians may feel that ibandronate is best suited for these patients: women who feel that even once weekly dosing is too inconvenient, and younger postmenopausal women who are not at high or immediate risk for hip or other nonvertebral fractures.
Network, announced that it has changed its name to Time For Lyme, Inc. The move is designed to address the expansion of the not-for-profit group's efforts toward eradicating Lyme disease beyond its Greenwich roots. The board of directors selected Time for Lyme the trademarked name of the organization's popular annual gala fundraiser because of its established brand identity. They have also used the Time for Lyme name in conjunction with educational seminars, a video and the first walk-athon to raise funds for Lyme disease research. Time for Lyme, Inc. remains an affiliate of the Lyme Disease Association, Inc., a national organization. Since it began in 1998 as a grassroots effort to support local families struggling with undiagnosed or late diagnosed Lyme disease, Time for Lyme has become involved in numerous activities beyond its original mission. It has produced and disseminated educational materials including a video based on a local seminar it presented that are now being used around the nation. In addition, it is partnering with the LDA to raise funds for and to endow the Lyme Disease Research Center at Columbia University in New York City. It has also worked at both the state and federal levels to advocate for legislation related to Lyme disease issues, including insurance coverage, reporting of cases and government funding for research. "A `task force' exists for a limited time and purpose, " said Time for Lyme co-president Diane Blanchard. "Although we wish our work to find a cure was already completed, the reality is that it will continue into the foreseeable future. So we need a name that reflects our long-term goals. Until we have a cure it is indeed Time for Lyme." In announcing the name change, Blanchard and the organization's copresident Deborah Siciliano thanked the local Greenwich community for its ongoing support, which, they said, Page 31 and iloprost.
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2700 Nucleic Acids Research, 1996, Vol. 24, No. 14 observed even when using the 3 kb -gal cDNA insert, suggesting that this IRES may have a general application in the construction of high titer retroviruses. As -gal expressing vectors are widely used, not only in gene therapy applications but also in developmental studies, LNFZ offers a distinct improvement over current viruses. Two gene retroviral vectors containing picornavirus internal ribosome entry sites possess the distinct advantage that selection for expression of one of the genes ensures expression of the other, which is not the situation when other strategies are used 8, 12, 13 ; . Finally, the low sequence homology between the FMDV IRES and the EMCV or Po IRES together with its smaller size should make this IRES segment an ideal candidate in the construction of useful tricistronic retroviral vectors. ACKNOWLEDGEMENTS We thank Dr E. Martinez-Salas for the plasmid pBIR encoding foot-and-mouth disease virus IRES. We thank Stella Lau for expert technical assistance. This work was supported by grants DK 43727 and DK 38531 from the NIH.
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Transplant as a candidate variable p 0.04 and 0.006, respectively ; . Taken together, our results demonstrated that CARV infections, especially those involving the lower respiratory tract, were associated with a significant risk for the subsequent development of BOS stage 1 and death and that this viral risk was distinct from the risk attributable to acute rejection and infliximab.
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Early clinical trials demonstrated efficacy and tolerability of intravenous ibandronate in the prevention or treatment of postmenopausal and corticosteroid-associated osteoporosis when administered once every 3 months and intal
22, no 3, 1999 - short review · kurze ü bersicht the new bisphosphonate ibandronate in the treatment of tumor-induced hypercalcemia herrmann, k and ibritumomab.
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