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Sample records for renal peripheral benzodiazepine

  1. Selective pharmacological modulation of renal peripheral-type benzodiazepine binding by treatment with diuretic drugs

    International Nuclear Information System (INIS)

    Lukeman, D.S.; Vaughn, D.A.; Fanestil, D.D.

    1988-01-01

    The authors have assessed the effects of in vivo administration of different classes of diuretic drugs on the expression of the peripheral-type benzodiazepine binding site (PBBS) in crude membranes derived from the cortex and outer medulla of rat kidney by saturation analysis with the PBBS-selective ligands [ 3 H]RO5-4864 and [ 3 H]PH 11195 in cortex and [ 3 H]RO5-4864 in outer medulla. Administration for 14-15 days of furosemide, a drug that blocks NaCl-KCl coupled transport in the thick ascending limb of the loop of Henle, produced a significant doubling in the PBBS density (B/sub max/) in outer medulla, a region of the kidney rich in thick ascending limbs, and produced a lesser but significant increase in PBBS density in the cortex. Conversely, administration for 14-15 days of the carbonic anhydrase inhibitor acetazolamide, which acts predominantly in the proximal tubule, and hydrochlorothiazide, which acts predominantly in the early distal tubule, elicited statistically significant increases in PBBS density in renal cortex but not in renal outer medulla. Furthermore, all drug treatments were without effect on the equilibrium dissociation constants (K/sub d/s) of [ 3 H]RO5-4864 and [ 3 H]PK 11195 binding to cortical and outer medullary membrane preparations. These findings demonstrate that the PBBS can be selectively up-regulated in different regions of the kidney by diuretic drugs with different modes/sites of action. 50 references, 1 table

  2. Imaging of a glioma using peripheral benzodiazepine receptor ligands

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    Starosta-Rubinstein, S.; Ciliax, B.J.; Penney, J.B.; McKeever, P.; Young, A.B.

    1987-02-01

    Two types of benzodiazepine receptors have been demonstrated in mammalian tissues, one which is localized on neuronal elements in brain and the other, on glial cells and in peripheral tissues such as kidney. In vivo administration of /sup 3/H-labeled PK 11195 (1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide) or (/sup 3/H)flunitrazepam with 5 mg of clonazepam per kg to rats with intracranial C6 gliomas resulted in high levels of tritiated-drug binding to the tumor as shown by quantitative autoradiography. Pharmacological studies indicated that the bound drugs labeled the peripheral benzodiazepine binding site. Binding to the peripheral benzodiazepine site was confirmed primarily to malignant cells with little binding to adjacent normal brain tissue or to necrotic tissue. Tumor cell binding was completely inhibited by preadministration of the peripheral benzodiazepine blocking agent PK 11195 at 5 mg/kg. The centrally selective benzodiazepine ligand clonazepam had no effect on PK 11195 binding to the tumor cells. When binding to other tumor cell lines grown in nude mice and nude athymic rats was evaluated, little or no peripheral benzodiazepine binding was detected on human pheochromocytoma (RN1) and neuroblastoma (SK-N-MC, SK-N-SH) tumor cells, respectively. However, high densities of peripheral benzodiazepine binding sites were observed on tumors derived from a human glioma cell line (ATCC HTB 14, U-87 MG). The presence of high concentrations of specific peripheral benzodiazepine receptors on glial tumors suggests that human primary central nervous system tumors could be imaged and diagnosed using peripheral benzodiazepine ligands labeled with positron- or gamma-emitting isotopes.

  3. Preservation of peripheral benzodiazepine receptors: differential effects of freezing on [3H]Ro 5-4864 and [3H]PK 11195 binding

    International Nuclear Information System (INIS)

    Basile, A.S.; Ostrowski, N.L.; Skolnick, P.

    1987-01-01

    A statistically significant decrease in the density of peripheral benzodiazepine receptors was observed in renal membranes of rats beginning 2 weeks after adrenalectomy when compared with sham-operated controls. This decrease in peripheral benzodiazepine receptor density was manifest as a decrease in the Bmax of two ligands [ 3 H]Ro 5-4864 and [ 3 H]PK 11195, without accompanying changes in their apparent affinity (Kd) for this site. Similar changes were not seen in another aldosterone-sensitive organ, the submandibular salivary gland. The decrease in peripheral benzodiazepine receptor density in observed in adrenalectomized rat renal membranes was restored to control levels after 1 week of aldosterone administration using a dose (12.5 micrograms/kg/day) that had no effect on peripheral benzodiazepine receptor density in sham-operated animals. In contrast, dexamethasone administration (50 micrograms/kg/day, 1 week) had no effect on renal peripheral benzodiazepine receptor density when administered to either adrenalectomized or sham-operated rats. Further, adrenal demedullation had no effect on renal peripheral benzodiazepine receptor density or affinity. The decrease in peripheral benzodiazepine receptor density was localized to the renal cortex and the outer stripe of the medulla by gross dissection of renal slices and renal tissue section autoradiography. The specific effect of adrenalectomy on renal peripheral benzodiazepine receptor density, the lack of direct effect of aldosterone on [ 3 H]Ro 5-4864 binding, and the localization of the change in peripheral benzodiazepine receptor density to the renal cortex and outer stripe suggests that these changes may reflect an adaptation of the renal nephron (possibly the distal convoluted tubule, intermediate tubule and/or the collecting duct) to the loss of mineralocorticoid hormones

  4. Radioligands for PET studies of central benzodiazepine receptors and PK (peripheral benzodiazepine) binding sites -current status

    International Nuclear Information System (INIS)

    Pike, V.W.; Osman, S.; Shah, F.; Turton, D.R.; Waters, S.L.; Crouzel, C.; Nutt, D.J.

    1993-01-01

    The status of the radiochemical development and biological evaluation of radioligands for PET studies of central benzodiazepine (BZ) receptors and the so-called peripheral benzodiazepine binding sites, here discriminated and referred to as PK binding sites, is reviewed against current pharmacological knowledge, indicating those agents with present value and those with future potential. Practical recommendations are given for the preparation of two useful radioligands for PET studies, [N-methyl- 11 C]flumazenil for central BZ receptors, and [N-methyl- 11 C]PK 11195 for PK binding sites. Quality assurance and plasma metabolite analysis are also reviewed for these radioligands and practical recommendations are given on methodology for their performance. (Author)

  5. Peripheral benzodiazepine receptors are decreased during cocaine withdrawal in humans.

    Science.gov (United States)

    Javaid, J I; Notorangelo, M P; Pandey, S C; Reddy, P L; Pandey, G N; Davis, J M

    1994-07-01

    In the present study, homovanillic acid in plasma (pHVA) and benzodiazepine receptors (3H-PK11195 binding) in neutrophil membranes were determined in blood obtained from cocaine-dependent (DSM-III-R) adult male inpatients at baseline-(within 72 hr of last cocaine use) and after 3 weeks of cocaine abstinence, and normal controls. The mean (+/- SEM) pHVA at baseline (10.3 ng/ml +/- 1.1) was similar to normals and did not change after 3 weeks of cocaine abstinence. Similarly, the binding indices of benzodiazepine receptors in cocaine-dependent subjects as a group were not significantly different than in normal controls. In 10 cocaine-dependent subjects, however, where both blood samples were available, the number of 3H-PK11195 binding sites was significantly (p < 0.05) decreased after 3 weeks of cocaine abstinence (mean +/- sem: Bmax = 6371 +/- 657 fmol/mg protein) compared with baseline (Bmax = 7553 +/- 925 fmol/mg protein), although there were no differences in the binding affinity (mean +/- sem: KD = 8.6 +/- 1.2 nmol/L after 3 weeks of abstinence compared with 8.1 +/- 1.0 nmol/L at baseline). These preliminary results suggest that peripheral benzodiazepine receptors may play an important role in the pathophysiology of cocaine withdrawal in cocaine-dependent human subjects.

  6. Pet imaging of peripheral benzodiazepine binding sites in brain tumors

    International Nuclear Information System (INIS)

    Junck, L.; Jewett, D.M.; Olsen, J.M.; Kilbourn, M.R.; Koeppe, R.A.; Young, A.B.; Greenberg, H.S.; Kuhl, D.E.

    1991-01-01

    Studies in vitro have shown that the peripheral-type benzodiazepine binding site (PBBS) is present in moderate to high density on malignant gliomas as well as in areas of reactive gliosis, but in low density in normal brain. PK 11195 is an isoquinoline derivative that binds selectively to the PBBS but not to the central benzodiazepine receptor. We have used [ 11 C]PK 11195 with positron emission tomography (PET) to study brain tumors and cerebral infarcts. Preliminary results showed that, in 13 of 18 patients with astrocytomas, [ 11 C]PK 11195 radioactivity was increased in tumor compared to remote brain and that the concentration ratios of tumor-to-remote brain were higher for high grade astrocytomas than for low grade astrocytomas. Pharmacokinetic analysis suggests that the increased activity in tumor probably does not result from alterations in blood flow or vascular permeability. Patients with lymphoma, meningioma, medulloblastoma, brain metastasis, and neurosarcoidosis have also shown increased radioactivity in tumor. Among eight patients with acute and subacute cerebral infarcts, activity in the infarct was increased in seven and was often greatest at the periphery. We conclude that [ 11 C]PK 11195 is a promising radiopharmaceutical for further investigation of brain tumors as well as diseases characterized by reactive gliosis

  7. Benzodiazepines

    Science.gov (United States)

    ... injectable preparation and as a syrup (primarily for pediatric patients). Benzodiazepines with a longer duration of ... and clorazepate are also used as anticonvulsants. Methods of abuse Abuse is frequently associated with ...

  8. Peripheral-type benzodiazepine receptors in the central nervous system: localization to olfactory nerves.

    Science.gov (United States)

    Anholt, R R; Murphy, K M; Mack, G E; Snyder, S H

    1984-02-01

    Binding levels of [3H]Ro5-4864, a ligand selective for peripheral-type benzodiazepine receptors, are substantially higher in homogenates of the olfactory bulb than in the rest of the brain. Among peripheral tissues evaluated, high levels of [3H]Ro5-4864 binding are found in the nasal epithelium. Drug displacement studies show that these binding sites are pharmacologically of the peripheral type. Their presence in the nasal epithelium and in the olfactory bulb can be demonstrated in several different mammalian species. Autoradiographic studies of murine nose reveal a bipolar staining pattern around the cell bodies of the olfactory receptor cells, suggesting the presence of peripheral-type benzodiazepine receptors on both processes of these bipolar neurons. In the brain a high density of [3H]Ro5-4864 binding sites occurs in the nerve fiber and glomerular layers of the olfactory bulb. Throughout the rest of the brain [3H]Ro5-4864-associated silver grains are diffusely distributed with intense staining over the choroid plexus and along the ependymal linings of the ventricles. Both the distribution and the ontogenic development of the peripheral-type benzodiazepine receptors differ from the central-type receptors. Intranasal irrigation with 5% ZnSO4 results in a 50% reduction of peripheral-type benzodiazepine receptors in the olfactory bulb without affecting the density of central-type benzodiazepine receptors. Thus, [3H]Ro5-4864 binding sites in the olfactory bulb appear in large part to be localized to olfactory nerves which originate in the nasal epithelium.

  9. Peripheral-type benzodiazepine receptor: a protein of mitochondrial outer membranes utilizing porphyrins as endogenous ligands

    International Nuclear Information System (INIS)

    Snyder, S.H.; Verma, A.; Trifiletti, R.R.

    1987-01-01

    The peripheral-type benzodiazepine receptor is a site identified by its nanomolar affinity for [ 3 H]diazepam, similar to the affinity of diazepam for the central-type benzodiazepine receptor in the brain. The peripheral type benzodiazepine receptor occurs in many peripheral tissues but has discrete localizations as indicated by autoradiographic studies showing uniquely high densities of the receptors in the adrenal cortex and in Leydig cells of the testes. Subcellular localization studies reveal a selective association of the receptors with the outer membrane of mitochondria. Photoaffinity labeling of the mitochondrial receptor with [ 3 H]flunitrazepam reveals two discrete labeled protein bands of 30 and 35 kDa, respectively. The 35-kDa band appears to be identical with the voltage-dependent anion channel protein porin. Fractionation of numerous peripheral tissues reveals a single principal endogenous ligand for the receptor, consisting of porphyrins, which display nanomolar affinity. Interactions of porphyrins with the mitochondrial receptor may clarify its physiological role and account for many pharmacological actions of benzodiazepines

  10. Food deprivation modulates gamma-aminobutyric acid receptors and peripheral benzodiazepine binding sites in rats.

    Science.gov (United States)

    Weizman, A; Bidder, M; Fares, F; Gavish, M

    1990-12-03

    The effect of 5 days of food deprivation followed by 5 days of refeeding on gamma-aminobutyric acid (GABA) receptors, central benzodiazepine receptors (CBR), and peripheral benzodiazepine binding sites (PBzS) was studied in female Sprague-Dawley rats. Starvation induced a decrease in the density of PBzS in peripheral organs: adrenal (35%; P less than 0.001), kidney (33%; P less than 0.01), and heart (34%; P less than 0.001). Restoration of [3H]PK 11195 binding to normal values was observed in all three organs after 5 days of refeeding. The density of PBzS in the ovary, pituitary, and hypothalamus was not affected by starvation. Food deprivation resulted in a 35% decrease in cerebellar GABA receptors (P less than 0.01), while CBR in the hypothalamus and cerebral cortex remained unaltered. The changes in PBzS observed in the heart and kidney may be related to the long-term metabolic stress associated with starvation and to the functional changes occurring in these organs. The down-regulation of the adrenal PBzS is attributable to the suppressive effect of hypercortisolemia on pituitary ACTH release. The reduction in cerebellar GABA receptors may be an adaptive response to food deprivation stress and may be relevant to the proaggressive effect of hunger.

  11. RENAL INVOLVEMENT IN SUBJECTS WITH PERIPHERAL ATHEROSCLEROSIS

    International Nuclear Information System (INIS)

    FAWZY, A.; IBRAHIM, S.

    2008-01-01

    Ischemic nephropathy is an important cause of renal failure.Sub-clinical renal function abnormalities may exist in patients with extra renal atherosclerosis and may precede the onset of overt ischemic nephropathy. To assess the impact of extrarenal atherosclerosis on the kidney, the study evaluated renal function in 50 subjects with differing degrees of peripheral atherosclerosis without manifest clinical or laboratory signs of ischemic nephropathy and renovascular hypertension.All laboratory testing including total LDL and HDL-cholesterol, triglycerides, ultrasonography with Doppler analysis for the localization of peripheral vascular disease (carotid and lower limb arteries), and non-invasive evaluation of renal function by radionuclide studies of renal plasma flow (MAG3 clearance) and glomerular filtration (DTPA clearance) were determined as well as smoking habit was recorded. By combining sonographic data on arterial tree stenosis (ATS), the subjects were grouped according to the atherosclerotic vascular damage (ATS involvement). The results showed no change in plasma creatinine while DTPA clearance was increased from 91.58±26.53 to 93.47±24.82 ml/min/1.73 m. MAG3 clearance was progressively declined with the severity of vascular damage from 244.86 ± 60.60 to 173.59±58.74 ml/min/1.73 m.Stepwise, multiple regression analysis indicated that MAG3 clearance was best explained by ATS involvement (standardized B coefficient -0.40; P< 0.001), smoking habit (-0.34;P=0.004) and serum LDL-cholesterol (-0.24; P<0.035).It could be concluded that the renal hemodynamic profile in atherosclerotic patients might constitute functional evidence of the silent phase of ischemic renal disease. The findings suggest that renal function should be carefully assessed in patients with extrarenal atherosclerosis, particularly in those with classic cardiovascular risk factors

  12. Midazolam inhibits chondrogenesis via peripheral benzodiazepine receptor in human mesenchymal stem cells.

    Science.gov (United States)

    Chen, Yung-Ching; Wu, King-Chuen; Huang, Bu-Miin; So, Edmund Cheung; Wang, Yang-Kao

    2018-05-01

    Midazolam, a benzodiazepine derivative, is widely used for sedation and surgery. However, previous studies have demonstrated that Midazolam is associated with increased risks of congenital malformations, such as dwarfism, when used during early pregnancy. Recent studies have also demonstrated that Midazolam suppresses osteogenesis of mesenchymal stem cells (MSCs). Given that hypertrophic chondrocytes can differentiate into osteoblast and osteocytes and contribute to endochondral bone formation, the effect of Midazolam on chondrogenesis remains unclear. In this study, we applied a human MSC line, the KP cell, to serve as an in vitro model to study the effect of Midazolam on chondrogenesis. We first successfully established an in vitro chondrogenic model in a micromass culture or a 2D high-density culture performed with TGF-β-driven chondrogenic induction medium. Treatment of the Midazolam dose-dependently inhibited chondrogenesis, examined using Alcian blue-stained glycosaminoglycans and the expression of chondrogenic markers, such as SOX9 and type II collagen. Inhibition of Midazolam by peripheral benzodiazepine receptor (PBR) antagonist PK11195 or small interfering RNA rescued the inhibitory effects of Midazolam on chondrogenesis. In addition, Midazolam suppressed transforming growth factor-β-induced Smad3 phosphorylation, and this inhibitory effect could be rescued using PBR antagonist PK11195. This study provides a possible explanation for Midazolam-induced congenital malformations of the musculoskeletal system through PBR. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. Identification, characterization and potent antitumor activity of ECO-4601, a novel peripheral benzodiazepine receptor ligand.

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    Gourdeau, Henriette; McAlpine, James B; Ranger, Maxime; Simard, Bryan; Berger, Francois; Beaudry, Francis; Farnet, Chris M; Falardeau, Pierre

    2008-05-01

    ECO-4601 is a structurally novel farnesylated dibenzodiazepinone discovered through DECIPHER technology, Thallion's proprietary drug discovery platform. The compound was shown to have a broad cytotoxic activity in the low micromolar range when tested in the NCI 60 cell line panel. In the work presented here, ECO-4601 was further evaluated against brain tumor cell lines. Preliminary mechanistic studies as well as in vivo antitumor evaluation were performed. Since ECO-4601 has a benzodiazepinone moiety, we first investigated if it binds the central and/or peripheral benzodiazepine receptors. ECO-4601 was tested in radioligand binding assays on benzodiazepine receptors obtained from rat hearts. The ability of ECO-4601 to inhibit the growth of CNS cancers was evaluated on a panel of mouse, rat and human glioma cell lines using a standard MTT assay. Antitumor efficacy studies were performed on gliomas (rat and human), human breast and human prostate mouse tumor xenografts. Antitumor activity and pharmacokinetic analysis of ECO-4601 was evaluated following intravenous (i.v.), subcutaneous (s.c.), and intraperitoneal (i.p.) bolus administrations. ECO-4601 was shown to bind the peripheral but not the central benzodiazepine receptor and inhibited the growth of CNS tumor cell lines. Bolus s.c. and i.p. administration gave rise to low but sustained drug exposure, and resulted in moderate to significant antitumor activity at doses that were well tolerated. In a rat glioma (C6) xenograft model, ECO-4601 produced up to 70% tumor growth inhibition (TGI) while in a human glioma (U-87MG) xenograft, TGI was 34%. Antitumor activity was highly significant in both human hormone-independent breast (MDA-MB-231) and prostate (PC-3) xenografts, resulting in TGI of 72 and 100%, respectively. On the other hand, i.v. dosing was followed by rapid elimination of the drug and was ineffective. Antitumor efficacy of ECO-4601 appears to be associated with the exposure parameter AUC and/or sustained

  14. Proposed protocols for peripheral and renal Doppler

    International Nuclear Information System (INIS)

    Fonseca Portuguez, Adriana

    2009-01-01

    A literature review was performed in order to prepare a summary of the important concepts of Doppler and applications in peripheral vascular evaluation and renal. The normal characteristics are summarized and explained in each vascular system and diagnostic criteria of the disorders frequently encountered in practice. Requested more studies have been identified and proposed protocols and report sheets have been developed to standardize the methodology of realization of several Doppler studies. The variability between operators has been treated to reduce as much as possible and follow-up studies have provided in patients who need. (author) [es

  15. Peripheral benzodiazepines receptor (PBR stimulates steroidogenesis: A potential neuroprotective pathway following brain damage

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    George E. Barreto

    2015-04-01

    Full Text Available The effects of neuroactive steroids have been highly assessed for their significance on inflammation resolution induced by cytotoxic agents. Steroids are derived from cholesterol, and this regulatory pathway may be a target for possible protective strategies. For example, the increased expression of peripheral benzodiazepine receptor (PBR stimulates steroids production, and the action of specific ligands on PBR favors the reduction of glial activity and act as a protective mechanism. The augmented expression of PBR and steroidogenic acute regulatory protein (StAR after injury is associated with local production of steroids by glial cells. For instance, cholesterol is captured by StAR in the outer mitochondrial membrane that transfers it to PBR, which uses it as substrate for the enzyme P450scc in the inner mitochondrial membrane. Some ligands, such as 4'-Chlorodiazepam (Ro5-4864 and isoquinoline carboxamide (PK 11195, act as agonists of the PBR receptor. Previous studies indicate that Ro5-4864 reduces neuronal loss, thus implying the regulation of mitochondrial transition after a traumatic brain injury. In this work, we assess the effects of PBR ligands directly involved in neuronal cell survival and proliferation after injury, thereby activating potential downstream targets as novel therapeutic approaches.

  16. Nootropic nefiracetam inhibits proconvulsant action of peripheral-type benzodiazepines in epileptic mutant EL mice.

    Science.gov (United States)

    Nakamoto, Yurie; Shiotani, Tadashi; Watabe, Shigeo; Nabeshima, Toshitaka; Yoshii, Mitsunobu

    2004-10-01

    Piracetam and structurally related nootropics are known to potentiate the anticonvulsant effects of antiepileptic drugs. It remains to be seen, however, whether these nootropics inhibit proconvulsant actions of many toxic agents including Ro 5-4864, a specific agonist for peripheral-type benzodiazepine receptors (PBR). The present study was designed to address this issue using EL mice, an animal model of epilepsy. In behavioral pharmacological experiments, EL mice were highly susceptible to convulsions induced by Ro 5-4864 (i.p.) in comparison with nonepileptic DDY mice. Nefiracetam administered orally to EL mice inhibited spontaneous seizures. In DDY mice, convulsions induced by Ro 5-4864 were prevented by nefiracetam when administered by i.v. injection. Aniracetam (i.v.) was partially effective, but piracetam and oxiracetam were ineffective as anticonvulsants. Binding assay for brain tissues revealed a higher density of mitochondrial PBR in EL mice compared with DDY mice. Binding of the PBR ligands Ro 5-4864 to either EL or DDY mouse brain was inhibited by micromolar concentrations of these nootropic agents in the sequence of nefiracetam > aniracetam > oxiracetam, piracetam. This rank order is identical to potency as anticonvulsants. These data suggest that nefiracetam may prevent toxic effects of PBR agonists through interacting with PBR.

  17. Interactions of pyrethroid insecticides with GABAA and peripheral-type benzodiazepine receptors

    International Nuclear Information System (INIS)

    Devaud, L.L.

    1988-01-01

    Pyrethroid insecticides are potent proconvulsants in the rat. All pyrethroids evincing proconvulsant activity elicited a similar 25-30% maximal reduction of seizure threshold. The Type II pyrethroids were the most potent proconvulsants with 1RαS, cis cypermethrin having an ED 50 value of 6.3 nmol/kg. The proconvulsant activity of both Type I and Type II pyrenthroids was blocked by pretreatment with PK 11195, the peripheral-type benzodiazepine receptor (PTBR) antagonist. In contrast, phenytoin did not antagonize the proconvulsant activity of either deltamethrin or permethrin. Pyrethroids displaced the specific binding of [ 3 H]Ro5-4864 to rat brain membranes with a significant correlation between the log EC 50 values for their activities as proconvulsants and the log IC 50 values for their inhibition of [ 3 H]Ro5-4864 binding. Both Ro5-4864 and pyrethroid insecticides were found to influence specific [ 35 S]TBPS binding in a GABA-dependent manner. PK 11195 and the Type II pyrethroid, deltamethrin antagonized the Ro5-4864-induced modulation of [ 35 S]TBPS binding. Pyrethroid insecticides, Ro5-4864 and veratridine influenced GABA-gated 36 Chloride influx. Moreover, the Type II pyrethroids elicited an increase in 36 chloride influx in the absence of GABA-stimulation. Both of these actions were antagonized by PK 11195 and tetrodotoxin

  18. Synthesis and evaluation of radioiodinated ligands for the study of peripheral benzodiazepine receptors using SPECT

    International Nuclear Information System (INIS)

    Katsifis, A.; Mattner, F.; Mardon, K.; Dikic, B.; Papazian, V.; Greguric, I.

    2002-01-01

    Full text: The peripheral benzodiazepine receptor (PBR) is a multimeric protein complex located in the outer mitochondrial membrane and predominantly found in steroid producing organs and glial cells in the brain. The PBR have been implicated in the control of cell proliferation and differentiation and shown to display increased levels in a variety of malignant tumours and neurodegenerative disorders. A series of potent imidazo[1,2-a]pyridines have been prepared for development as radiopharmaceuticals to study these disorders in patients using nuclear medicine imaging techniques. In vitro studies indicate that compounds substituted with an electronegative atom in the 6 position of the pyridine ring, a lipophilic group or halogen in the 4'-position of the 2-phenyl ring, and lower alkyl methyl or ethyl substituents on the amide nitrogens of the side chain, exhibit high affinity and selective binding. ' N'N'-dimethyl- and the N'N'-diethyl 6-chloro-(4'-iodophenyl)imidazo[1,2-a]pyridine-3-acetamide 1 and 2 displayed optimum in vitro properties and were thus selected for radiolabelling with the diagnostic radionuclide iodine-123. Radioiodination was achieved by iododestannylation of the corresponding tributyl stannane precursor in the presence of peracetic acid. Purification by C-18 reverse phase HPLC gave the desired products in 70-80% radiochemical yields and in greater than 98% radiochemical purity. Biodistribution studies in normal rodents indicated high uptake of radioactivity in tissues with known PBR sites. Preliminary imaging studies in rodents bearing mammary adenocarcinomas indicated high uptake in the tumour with retention of activity after 24 h. The synthesis, structure activity studies, radiolabelling and biological studies of these compounds will be presented

  19. Peripheral-type benzodiazepine receptors in bronchoalveolar lavage cells of patients with interstitial lung disease

    International Nuclear Information System (INIS)

    Branley, Howard M.; Bois, Roland M. du; Wells, Athol U.; Jones, Hazel A.

    2007-01-01

    Introduction: PK11195 is a ligand with high affinity for peripheral benzodiazepine receptors (PBRs), which are present in large numbers in macrophages. PBRs play a role in antioxidant pathways and apoptosis, key factors in control of lung health. Intrapulmonary PBRs, assessed in vivo by positron emission tomography (PET), are decreased in interstitial lung disease (ILD) despite increased macrophage numbers. We wished to ascertain whether the observed decrease in in vivo expression of PBRs in the PET scans could be accounted for by a reduction in PBRs per cell by saturation-binding assays of R-PK11195 in cells obtained by bronchoalveolar lavage (BAL). Methods: We performed receptor saturation-binding assays with [ 3 H]-R-PK11195 on a mixed population of cells recovered by BAL to quantify the number of R-PK11195 binding sites per macrophage in 10 subjects with ILD and 10 normal subjects. Results: Receptor affinity [dissociation constant (Kd)] was similar in ILD patients and controls. However, R-PK11195 binding sites per cell [(maximal binding sites available (B max )] were decreased in macrophages obtained by BAL from subjects with ILD compared to normal (P<.0005). Microautoradiography confirmed localization of R-PK11195 to macrophages in a mixed inflammatory cell population obtained by BAL. Conclusion: These results demonstrate that in vitro PBR expression per cell on macrophages obtained by BAL is reduced in patients with ILD indicating a potentially functionally different macrophage phenotype. As PBRs are involved in the orchestration of lung inflammatory responses, this finding offers further insight into the role of macrophages in the pathogenesis of ILDs and offers a potential avenue for pharmacological strategy

  20. Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Wilson, Alan A.; Garcia, Armando; Parkes, Jun; McCormick, Patrick; Stephenson, Karin A.; Houle, Sylvain; Vasdev, Neil

    2008-01-01

    Introduction: A novel [ 18 F]-radiolabelled phenoxyanilide, [ 18 F]-FEPPA, has been synthesized and evaluated, in vitro and ex vivo, as a potential positron emission tomography imaging agent for the peripheral benzodiazepine receptor (PBR). Methods: [ 18 F]-FEPPA and two other radiotracers for imaging PBR, namely [ 11 C]-PBR28 and [ 11 C]-PBR28-d3, were synthesised and evaluated in vitro and ex vivo as potential PBR imaging agents. Results: [ 18 F]-FEPPA is efficiently prepared in one step from its tosylate precursor and [ 18 F]-fluoride in high radiochemical yields and at high specific activity. FEPPA displayed a K i of 0.07 nM for PBR in rat mitochondrial membrane preparations and a suitable lipophilicity for brain penetration (log P of 2.99 at pH 7.4). Upon intravenous injection into rats, [ 18 F]-FEPPA showed moderate brain uptake [standard uptake value (SUV) of 0.6 at 5 min] and a slow washout (SUV of 0.35 after 60 min). Highest uptake of radioactivity was seen in the hypothalamus and olfactory bulb, regions previously reported to be enriched in PBR in rat brain. Analysis of plasma and brain extracts demonstrated that [ 18 F]-FEPPA was rapidly metabolized, but no lipophilic metabolites were observed in either preparation and only 5% radioactive metabolites were present in brain tissue extracts. Blocking studies to determine the extent of specific binding of [ 18 F]-FEPPA in rat brain were problematic due to large perturbations in circulating radiotracer and the lack of a reference region. Conclusions: Further evaluation of the potential of [ 18 F]-FEPPA will require the employment of rigorous kinetic models and/or appropriate animal models

  1. Peripheral benzodiazepine receptors in the brain of cirrhosis patients with manifest hepatic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Iversen, Peter; Bender, Dirk; Munk, Ole L.; Cumming, Paul [Aarhus University Hospital, PET Centre, Aarhus (Denmark); Aagaard Hansen, Dorthe; Keiding, Susanne [Aarhus University Hospital, PET Centre, Aarhus (Denmark); Aarhus University Hospital, Department of Medicine V (Hepatology), Aarhus (Denmark); Rodell, Anders [Aarhus University Hospital, Centre of Functionally Integrative Neuroscience (CFIN), Aarhus (Denmark)

    2006-07-15

    It has been suggested that ammonia-induced enhancement of peripheral benzodiazepine receptors (PBRs) in the brain is involved in the development of hepatic encephalopathy (HE). This hypothesis is based on animal experiments and studies of post-mortem human brains using radiolabelled PK11195, a specific ligand for PBR, but to our knowledge has not been tested in living patients. The aim of the present study was to test this hypothesis by measuring the number of cerebral PBRs in specific brain regions in cirrhotic patients with an acute episode of clinically manifest HE and healthy subjects using dynamic {sup 11}C-PK11195 brain PET. Eight cirrhotic patients with an acute episode of clinically manifest HE (mean arterial ammonia 81 {mu}mol/l) and five healthy subjects (22 {mu}mol/l) underwent dynamic {sup 11}C-PK11195 and {sup 15}O-H{sub 2}O PET, co-registered with MR images. Brain regions (putamen, cerebellum, cortex and thalamus) were delineated on co-registered {sup 15}O-H{sub 2} {sup 15}O and MR images and copied to the dynamic {sup 15}O-H{sub 2}O and {sup 11}C-PK11195 images. Regional cerebral blood flow (CBF) ({sup 15}O-H{sub 2}O scan) and the volume of distribution of PK11195 ({sup 11}C-PK11195 scan) were calculated by kinetic analysis. There were regional differences in the CBF, with lowest values in the cortex and highest values in the putamen in both groups of subjects (p<0.05), but no significant differences between the groups. There were no significant differences in the volume of distribution of PK11195 (V{sub d}) between regions or between the two groups of subjects. Mean values of V{sub d} ranged from 1.0 to 1.1 in both groups of subjects. The results do not confirm the hypothesis of an increased number of PBRs in patients with HE. (orig.)

  2. In vivo labelling in several rat tissues of 'peripheral type' benzodiazepine binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Benavides, J.; Guilloux, F.; Rufat, P.; Uzan, A.; Renault, C.; Dubroeucq, M.C.; Gueremy, C.; Le Fur, G. (Pharmuka Laboratoires, 92 - Gennevilliers (France))

    1984-03-16

    'Peripheral type' benzodiazepine binding sites in several rat tissues were labelled by intravenous injection of (/sup 3/H)PK 11195 and (/sup 3/H)RO5-4864. Binding was saturable in all tissues studied and regional distribution paralleled the in vitro binding. A similar potency order of displacing compounds was found in vivo and in vitro PK 11195 > PK 11211 > RO5-4864 > diazepam > dipyridamole > clonazepam. These results demonstrate the feasibility of using this technique to examine the effects of pharmacological manipulation on the binding sites in their native state. However, some properties (broader maximum during time course, higher percentage of particulate binding in the brain and independence of temperature) make (/sup 3/H)PK 11195 the most suitable ligand for this kind of studies.

  3. Radiosynthesis and in vivo evaluation of N-[11C]methylated imidazopyridineacetamides as PET tracers for peripheral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Sekimata, Katsuhiko; Hatano, Kentaro; Ogawa, Mikako; Abe, Junichiro; Magata, Yasuhiro; Biggio, Giovanni; Serra, Mariangela; Laquintana, Valentino; Denora, Nunzio; Latrofa, Andrea; Trapani, Giuseppe; Liso, Gaetano; Ito, Kengo

    2008-01-01

    Imidazopyridineacetoamide 5-8, a series of novel and potentially selective peripheral benzodiazepine receptor (PBR) ligands with affinities comparable to those of known PBR ligands, was investigated. Radiosyntheses of [ 11 C]5, 6, 7 or 8 was accomplished by N-methylation of the corresponding desmethyl precursors with [ 11 C]methyl iodide in the presence of NaH in dimethylformamide (DMF), resulting in 25% to 77% radiochemical yield and specific activitiy of 20 to 150 MBq/nmol. Each of the labeled compounds was injected in ddY mice, and the radioactivity and weight of dissected peripheral organs and brain regions were measured. Organ distribution of [ 11 C]7 was consistent with the known PBR distribution. Moreover, [ 11 C]7 showed the best combination of brain uptake and PBR binding, leading to its high retention in the olfactory bulb and cerebellum, areas where PBR density is high in mouse brain. Coinjection of PK11195 or unlabeled 7 significantly reduced the brain uptake of [ 11 C]7. These results suggest that [ 11 C]7 could be a useful radioligand for positron emission tomography imaging of PBRs

  4. Modulation of cholinephosphotransferase activity in breast cancer cell lines by Ro5-4864, a peripheral benzodiazepine receptor agonist

    International Nuclear Information System (INIS)

    Akech, Jacqueline; Roy, Somdutta Sinha; Das, Salil K.

    2005-01-01

    Changes in phospholipid and fatty acid profile are hallmarks of cancer progression. Increase in peripheral benzodiazepine receptor expression has been implicated in breast cancer. The benzodiazepine, Ro5-4864, increases cell proliferation in some breast cancer cell lines. Biosynthesis of phosphatidylcholine (PC) has been identified as a marker for cells proliferating at high rates. Cholinephosphotransferase (CPT) is the terminal enzyme for the de novo biosynthesis of PC. We have addressed here whether Ro5-4864 facilitates some cancer causing mechanisms in breast cancer. We report that cell proliferation increases exponentially in aggressive breast cancer cell lines 11-9-1-4 and BT-549 when treated with nanomolar concentrations of Ro5-4864. This increase is seen within 24 h of treatment, consistent with the cell doubling time in these cells. Ro5-4864 also upregulates c-fos expression in breast cancer cell lines 11-9-1-4 and BT-549, while expression in non-tumorigenic cell line MCF-12A was either basal or slightly downregulated. We further examined the expression of the CPT gene in breast cancer (11-9-1-4, BT-549) and non-tumorigenic cell lines (MCF-12A, MCF-12F). We found that the CPT gene is overexpressed in breast cancer cell lines compared to the non-tumorigenic cell lines. Furthermore, the activity of CPT in forming PC is increased in the breast cancer cell lines cultured for 24 h. Additionally, we examined the CPT activity in the presence of nanomolar concentrations of Ro5-4864. Biosynthesis of PC was increased in breast cancer cell lines upon treatment. We therefore propose that Ro5-4864 facilitates PC formation, a process important in membrane biogenesis for proliferating cells

  5. Radiosynthesis and initial evaluation of [{sup 18}F]-FEPPA for PET imaging of peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Alan A. [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8 (Canada)], E-mail: alan.wilson@camhpet.ca; Garcia, Armando; Parkes, Jun [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); McCormick, Patrick [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Stephenson, Karin A. [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Houle, Sylvain; Vasdev, Neil [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8 (Canada)

    2008-04-15

    Introduction: A novel [{sup 18}F]-radiolabelled phenoxyanilide, [{sup 18}F]-FEPPA, has been synthesized and evaluated, in vitro and ex vivo, as a potential positron emission tomography imaging agent for the peripheral benzodiazepine receptor (PBR). Methods: [{sup 18}F]-FEPPA and two other radiotracers for imaging PBR, namely [{sup 11}C]-PBR28 and [{sup 11}C]-PBR28-d3, were synthesised and evaluated in vitro and ex vivo as potential PBR imaging agents. Results: [{sup 18}F]-FEPPA is efficiently prepared in one step from its tosylate precursor and [{sup 18}F]-fluoride in high radiochemical yields and at high specific activity. FEPPA displayed a K{sub i} of 0.07 nM for PBR in rat mitochondrial membrane preparations and a suitable lipophilicity for brain penetration (log P of 2.99 at pH 7.4). Upon intravenous injection into rats, [{sup 18}F]-FEPPA showed moderate brain uptake [standard uptake value (SUV) of 0.6 at 5 min] and a slow washout (SUV of 0.35 after 60 min). Highest uptake of radioactivity was seen in the hypothalamus and olfactory bulb, regions previously reported to be enriched in PBR in rat brain. Analysis of plasma and brain extracts demonstrated that [{sup 18}F]-FEPPA was rapidly metabolized, but no lipophilic metabolites were observed in either preparation and only 5% radioactive metabolites were present in brain tissue extracts. Blocking studies to determine the extent of specific binding of [{sup 18}F]-FEPPA in rat brain were problematic due to large perturbations in circulating radiotracer and the lack of a reference region. Conclusions: Further evaluation of the potential of [{sup 18}F]-FEPPA will require the employment of rigorous kinetic models and/or appropriate animal models.

  6. Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis

    OpenAIRE

    Tokuda, Kazuhiro; O’Dell, Kazuko A.; Izumi, Yukitoshi; Zorumski, Charles F.

    2010-01-01

    Benzodiazepines (BDZs) enhance γ-aminobutyric acid-A (GABAA) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors (translocator protein 18kDa, TSPO) and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectivel...

  7. Mitochondrial benzodiazepine receptors regulate steroid biosynthesis.

    OpenAIRE

    Mukhin, A G; Papadopoulos, V; Costa, E; Krueger, K E

    1989-01-01

    Recent observations on the steroid synthetic capability within the brain open the possibility that benzodiazepines may influence steroid synthesis in nervous tissue through interactions with peripheral-type benzodiazepine recognition sites, which are highly expressed in steroidogenic cells and associated with the outer mitochondrial membrane. To examine this possibility nine molecules that exhibit a greater than 10,000-fold difference in their affinities for peripheral-type benzodiazepine bin...

  8. Synthesis of [123I]iodine labelled imidazo[1,2-b] pyridazines as potential probes for the study of peripheral benzodiazepine receptors using SPECT

    International Nuclear Information System (INIS)

    Katsifis, A.; Mattner, F.; Dikic, B.; Barlin, G.

    2004-01-01

    The pyridazines 3-acetamidomethyl-6-chloro-2-(4'-iodophenyl)imidazo[1,2-b]pyridazine 1 (IC 50 = 1.6 nM) and 3-benzamidomethyl-6-iodo-2-(4'-t-butylphenyl)imidazo[1,2-b] pyridazine 2 (IC 50 = 4.2 nM), are high affinity and selective ligands for the peripheral benzodiazepine receptors (PBR) compared to the central benzodiazepine counterparts. The [ 123 I]1 and [ 123 I]2 labelled analogues of these compounds were subsequently synthesised for the potential study of the PBR in vivo using SPECT. Radioiodination of [ 123 I]1 was achieved by iododestannylation of the corresponding tributyl tin precursor with Na[ 123 I] in the presence of peracetic acid or chloramine-T and the product isolated by C-18 RP HPLC. Radioiodination of [ 123 I]2 was achieved by copper assisted bromine [ 123 I]iodine exchange of the corresponding bromo precursor in the presence of acetic acid and sodium bisulfate as reducing agent at 200 C. Purification of the crude products were achieved by semi-preparative C-18 RP HPLC to give the products in radiochemical yields > 90%. The products were obtained in > 97% chemical and radiochemical purity and with specific activities > 180 GBq/μmol. (orig.)

  9. Synthesis of [{sup 123}I]iodine labelled imidazo[1,2-b] pyridazines as potential probes for the study of peripheral benzodiazepine receptors using SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Katsifis, A.; Mattner, F.; Dikic, B. [Radiopharmaceuticals Div. ANSTO, Menai, NSW (Australia); Barlin, G. [Div. of Neurosciences, John Curtin School of Medical Research, Australian National Univ., Canberra (Australia)

    2004-07-01

    The pyridazines 3-acetamidomethyl-6-chloro-2-(4'-iodophenyl)imidazo[1,2-b]pyridazine 1 (IC{sub 50} = 1.6 nM) and 3-benzamidomethyl-6-iodo-2-(4'-t-butylphenyl)imidazo[1,2-b] pyridazine 2 (IC{sub 50} = 4.2 nM), are high affinity and selective ligands for the peripheral benzodiazepine receptors (PBR) compared to the central benzodiazepine counterparts. The [{sup 123}I]1 and [{sup 123}I]2 labelled analogues of these compounds were subsequently synthesised for the potential study of the PBR in vivo using SPECT. Radioiodination of [{sup 123}I]1 was achieved by iododestannylation of the corresponding tributyl tin precursor with Na[{sup 123}I] in the presence of peracetic acid or chloramine-T and the product isolated by C-18 RP HPLC. Radioiodination of [{sup 123}I]2 was achieved by copper assisted bromine [{sup 123}I]iodine exchange of the corresponding bromo precursor in the presence of acetic acid and sodium bisulfate as reducing agent at 200 C. Purification of the crude products were achieved by semi-preparative C-18 RP HPLC to give the products in radiochemical yields > 90%. The products were obtained in > 97% chemical and radiochemical purity and with specific activities > 180 GBq/{mu}mol. (orig.)

  10. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Vowinckel, E; Reutens, D; Becher, B

    1997-01-01

    Activated glial cells are implicated in regulating and effecting the immune response that occurs within the CNS as part of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). The peripheral benzodiazepine receptor (PBR) is expressed in glial cells. We...... examined the utility of using in vitro and in vivo ligand binding to the PBR as a measure of lesion activity in autoimmune CNS demyelinating diseases. Applying a combined autoradiography and immunohistochemical approach to spinal cord and brain tissues from mice with EAE, we found a correlation at sites...... of inflammatory lesions between [3H]-PK11195 binding and immunoreactivity for the activated microglial/macrophage marker Mac-1/CD11b. In MS tissues, [3H]-PK11195 binding correlated with sites of immunoreactivity for the microglial/macrophage marker CD68, at the edges of chronic active plaques. Positron emission...

  11. Radiosynthesis and in vivo evaluation of N-[{sup 11}C]methylated imidazopyridineacetamides as PET tracers for peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Sekimata, Katsuhiko [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan); Hatano, Kentaro [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan)], E-mail: hatanok@nils.go.jp; Ogawa, Mikako [Photon Medical Research Center, Hamamatsu University School of Medicine, Shizuoka 431-3192 Japan (Japan); Abe, Junichiro [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan); Magata, Yasuhiro [Photon Medical Research Center, Hamamatsu University School of Medicine, Shizuoka 431-3192 Japan (Japan); Biggio, Giovanni; Serra, Mariangela [Department of Experimental Biology, University of Cagliari, Cagliari 09100 (Italy); Laquintana, Valentino; Denora, Nunzio; Latrofa, Andrea; Trapani, Giuseppe; Liso, Gaetano [Pharmaco-Chemistry Department, University of Bari, Bari 70125 (Italy); Ito, Kengo [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan)

    2008-04-15

    Imidazopyridineacetoamide 5-8, a series of novel and potentially selective peripheral benzodiazepine receptor (PBR) ligands with affinities comparable to those of known PBR ligands, was investigated. Radiosyntheses of [{sup 11}C]5, 6, 7 or 8 was accomplished by N-methylation of the corresponding desmethyl precursors with [{sup 11}C]methyl iodide in the presence of NaH in dimethylformamide (DMF), resulting in 25% to 77% radiochemical yield and specific activitiy of 20 to 150 MBq/nmol. Each of the labeled compounds was injected in ddY mice, and the radioactivity and weight of dissected peripheral organs and brain regions were measured. Organ distribution of [{sup 11}C]7 was consistent with the known PBR distribution. Moreover, [{sup 11}C]7 showed the best combination of brain uptake and PBR binding, leading to its high retention in the olfactory bulb and cerebellum, areas where PBR density is high in mouse brain. Coinjection of PK11195 or unlabeled 7 significantly reduced the brain uptake of [{sup 11}C]7. These results suggest that [{sup 11}C]7 could be a useful radioligand for positron emission tomography imaging of PBRs.

  12. Differential effect of detergents on [3H]Ro 5-4864 and [3H]PK 11195 binding to peripheral-type benzodiazepine-binding sites

    International Nuclear Information System (INIS)

    Awad, M.; Gavish, M.

    1988-01-01

    The present study demonstrates a differential effect of various detergent treatments on [ 3 H]Ro 5-4864 and [ 3 H]PK 11195 binding to peripheral benzodiazepine binding sites (PBS). Triton X-100 caused a decrease of about 70% in [ 3 H]Ro 5-4864 binding to membranes from various peripheral tissues of rat, but had only a negligible effect on [ 3 H]PK 11195 binding. A similar effect of Triton X-100 was observed on guinea pig and rabbit kidney membranes. The decrease in [ 3 H]Ro 5-4864 binding after treatment with Triton X-100 was apparently due to a decrease in the density of PBS, since the affinity remained unaltered. The detergents 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS), Tween 20, deoxycholic acid, or digitonin (0.0125%) caused only a minor change in [ 3 H]Ro 5-4864 and [ 3 H]PK 11195 binding to rat kidney membranes; but when concentrations were substantially increased (0.1%), all detergents caused a decrease of at least 50% in [ 3 H]Ro 5-4864 binding, while [ 3 H]PK 11195 binding to rat kidney membranes remained unaffected by the first three detergents, with only a minor decrease (15%) after treatment with digitonin

  13. Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis.

    Science.gov (United States)

    Tokuda, Kazuhiro; O'Dell, Kazuko A; Izumi, Yukitoshi; Zorumski, Charles F

    2010-12-15

    Benzodiazepines (BDZs) enhance GABA(A) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors [translocator protein (18 kDa) (TSPO)] and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ, with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition after stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA [17-phenyl-(3α,5α)-androst-16-en-3-ol], a blocker of neurosteroid effects on GABA(A) receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN (2-[2-(4-fluorophenyl)-1H-indol-3-yl]-N,N-dihexylacetamide), a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated 1 d before midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity.

  14. Rapid and efficient radiosynthesis of [{sup 123}I]I-PK11195, a single photon emission computed tomography tracer for peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Pimlott, Sally L. [Department of Clinical Physics, West of Scotland Radionuclide Dispensary, Western Infirmary, G11 6NT Glasgow (United Kingdom)], E-mail: s.pimlott@clinmed.gla.ac.uk; Stevenson, Louise [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom); Wyper, David J. [Institute of Neurological Sciences, Southern General Hospital, G51 4TF Glasgow (United Kingdom); Sutherland, Andrew [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom)

    2008-07-15

    Introduction: [{sup 123}I]I-PK11195 is a high-affinity single photon emission computed tomography radiotracer for peripheral benzodiazepine receptors that has previously been used to measure activated microglia and to assess neuroinflammation in the living human brain. This study investigates the radiosynthesis of [{sup 123}I]I-PK11195 in order to develop a rapid and efficient method that obtains [{sup 123}I]I-PK11195 with a high specific activity for in vivo animal and human imaging studies. Methods: The synthesis of [{sup 123}I]I-PK11195 was evaluated using a solid-state interhalogen exchange method and an electrophilic iododestannylation method, where bromine and trimethylstannyl derivatives were used as precursors, respectively. In the electrophilic iododestannylation method, the oxidants peracetic acid and chloramine-T were both investigated. Results: Electrophilic iododestannylation produced [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than achievable using the halogen exchange method investigated. Using chloramine-T as oxidant provided a rapid and efficient method of choice for the synthesis of [{sup 123}I]I-PK11195. Conclusions: [{sup 123}I]I-PK11195 has been successfully synthesized via a rapid and efficient electrophilic iododestannylation method, producing [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than previously achieved.

  15. Rapid and efficient radiosynthesis of [123I]I-PK11195, a single photon emission computed tomography tracer for peripheral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Pimlott, Sally L.; Stevenson, Louise; Wyper, David J.; Sutherland, Andrew

    2008-01-01

    Introduction: [ 123 I]I-PK11195 is a high-affinity single photon emission computed tomography radiotracer for peripheral benzodiazepine receptors that has previously been used to measure activated microglia and to assess neuroinflammation in the living human brain. This study investigates the radiosynthesis of [ 123 I]I-PK11195 in order to develop a rapid and efficient method that obtains [ 123 I]I-PK11195 with a high specific activity for in vivo animal and human imaging studies. Methods: The synthesis of [ 123 I]I-PK11195 was evaluated using a solid-state interhalogen exchange method and an electrophilic iododestannylation method, where bromine and trimethylstannyl derivatives were used as precursors, respectively. In the electrophilic iododestannylation method, the oxidants peracetic acid and chloramine-T were both investigated. Results: Electrophilic iododestannylation produced [ 123 I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than achievable using the halogen exchange method investigated. Using chloramine-T as oxidant provided a rapid and efficient method of choice for the synthesis of [ 123 I]I-PK11195. Conclusions: [ 123 I]I-PK11195 has been successfully synthesized via a rapid and efficient electrophilic iododestannylation method, producing [ 123 I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than previously achieved

  16. Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the central nervous system inflammation of experimental autoimmune encephalomyelitis: a possible probe for imaging multiple sclerosis

    International Nuclear Information System (INIS)

    Mattner, F.; Katsifis, A.; Ballantyne, P.; Staykova, M.; Willenborg, D.O.

    2005-01-01

    Peripheral benzodiazepine receptors (PBRs) are upregulated on macrophages and activated microglia, and radioligands for the PBRs can be used to detect in vivo neuroinflammatory changes in a variety of neurological insults, including multiple sclerosis. Substituted 2-phenyl imidazopyridine-3-acetamides with high affinity and selectivity for PBRs have been prepared that are suitable for radiolabelling with a number of positron emission tomography and single-photon emission computed tomography (SPECT) isotopes. In this investigation, the newly developed high-affinity PBR ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo [1,2-a]pyridine-3-acetamide, or CLINDE, was radiolabelled with 123 I and its biodistribution in the central nervous system (CNS) of rats with experimental autoimmune encephalomyelitis (EAE) evaluated. EAE was induced in male Lewis rats by injection of an emulsion of myelin basic protein and incomplete Freund's adjuvant containing Mycobacterium butyricum. Biodistribution studies with 123 I-CLINDE were undertaken on EAE rats exhibiting different clinical disease severity and compared with results in controls. Disease severity was confirmed by histopathology in the spinal cord of rats. The relationship between inflammatory lesions and PBR ligand binding was investigated using ex vivo autoradiography and immunohistochemistry on rats with various clinical scores. 123 I-CLINDE uptake was enhanced in the CNS of all rats exhibiting EAE when compared to controls. Binding reflected the ascending nature of EAE inflammation, with lumbar/sacral cord > thoracic cord > cervical cord > medulla. The amount of ligand binding also reflected the clinical severity of disease. Ex vivo autoradiography and immunohistochemistry revealed a good spatial correspondence between radioligand signal and foci of inflammation and in particular ED-1 + cells representing macrophages and microglia. These results demonstrate the ability of 123 I-CLINDE to measure in vivo

  17. Omega 3 (peripheral type benzodiazepine binding) site distribution in the rat immune system: an autoradiographic study with the photoaffinity ligand [3H]PK 14105

    International Nuclear Information System (INIS)

    Benavides, J.; Dubois, A.; Dennis, T.; Hamel, E.; Scatton, B.

    1989-01-01

    The anatomical distribution of omega 3 (peripheral type benzodiazepine binding) sites in the immune system organs of the rat has been studied autoradiographically at both macroscopic and microscopic levels of resolution using either reversible or irreversible (UV irradiation) labeling with [ 3 H]PK 14105. In thymus sections, [ 3 H]PK 14105 labeled with high affinity (Kd, derived from saturation experiments = 10.8 nM) a single population of sites which possessed the pharmacological characteristics of omega 3 sites. In the thymus gland, higher omega 3 site densities were detected in the cortex than in the medulla; in these subregions, silver grains were associated to small (10-18 microns diameter) cells. In the spleen, omega 3 sites were more abundant in the white than in the red pulp. In the white pulp, silver grains were denser in the marginal zone than in the vicinity of the central artery and labeling was, as in the thymus, associated to small cytoplasm-poor cells. In the red pulp, omega 3 site associated silver grains were observed mainly in the Bilroth cords. In the lymph nodes, the medullary region showed a higher labeling than the surrounding follicles and paracortex. A significant accumulation of silver grains was observed in the lymph node medullary cords. In the intestine, Peyer patches were particularly enriched in omega 3 sites (especially in the periphery of the follicles). The distribution of omega 3 sites in the immune system organs suggests a preferential labeling of cells of T and monocytic lineages. This is consistent with the proposed immunoregulatory properties of some omega 3 site ligands

  18. Pharmacological evaluation of [123I]-CLINDE: a radioiodinated imidazopyridine-3-acetamide for the study of peripheral benzodiazepine binding sites (PBBS).

    Science.gov (United States)

    Mattner, Filomena; Mardon, Karine; Katsifis, Andrew

    2008-04-01

    The study aims to evaluate the iodinated imidazopyridine, N',N'-diethyl-6-Chloro-(4'-[(123)I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide ([(123)I]-CLINDE) as a tracer for the study of peripheral benzodiazepine binding sites (PBBS). In vitro studies were performed using membrane homogenates and sections from kidney, adrenals, and brain cortex of Sprague-Dawley (SD) rats and incubated with [(123)I]-CLINDE. For in vivo studies, the rats were injected with [(123)I]-CLINDE. In competition studies, PBBS-specific drugs PK11195 and Ro 5-4864 and the CBR specific drug Flumazenil were injected before the radiotracer. In vitro binding studies in adrenal, kidney, and cortex mitochondrial membranes indicated that [(123)I]-CLINDE binds with high affinity to PBBS, K(d) = 12.6, 0.20, and 3.84 nM, respectively. The density of binding sites was 163, 5.3, and 0.34 pmol/mg protein, respectively. In vivo biodistribution indicated high uptake in adrenals (5.4), heart (1.5), lungs (1.5), kidney (1.5) %ID/g at 6 h p.i. In the central nervous system (CNS), the olfactory bulbs displayed the highest uptake; up to six times the activity in blood. Pre-administration of unlabeled CLINDE, PK11195 and Ro 5-4864 (1 mg/kg) reduced the uptake of [(123)I]-CLINDE by 70-55% in olfactory bulbs. In the kidney and heart, a reduction of 60-80% ID/g was observed, while an increase was observed in the adrenals requiring 10 mg/kg for significant displacement. Flumazenil had no effect on uptake in peripheral organs and brain. Metabolite analysis indicated >90% of the radioactivity in the above tissues was intact [(123)I]-CLINDE. [(123)I]-CLINDE displays high and selective uptake for the PBBS and warrants further development as a probe for imaging PBBS using single photon emission computed tomography (SPECT).

  19. Pharmacological evaluation of [{sup 123}I]-CLINDE: a radioiodinated imidazopyridine-3-acetamide for the study of peripheral benzodiazepine binding sites (PBBS)

    Energy Technology Data Exchange (ETDEWEB)

    Mattner, Filomena; Katsifis, Andrew [Australian Nuclear Science and Technology Organisation, Radiopharmaceuticals Research Institute, PMB 1 Menai, N.S.W., Sydney (Australia); Mardon, Karine [The University of Queensland, Centre for Studies in Drug Disposition, Brisbane (Australia)

    2008-04-15

    The study aims to evaluate the iodinated imidazopyridine, N',N'-diethyl-6-Chloro-(4'-[{sup 123}I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide ([{sup 123}I]-CLINDE) as a tracer for the study of peripheral benzodiazepine binding sites (PBBS). In vitro studies were performed using membrane homogenates and sections from kidney, adrenals, and brain cortex of Sprague-Dawley (SD) rats and incubated with [{sup 123}I]-CLINDE. For in vivo studies, the rats were injected with [{sup 123}I]-CLINDE. In competition studies, PBBS-specific drugs PK11195 and Ro 5-4864 and the CBR specific drug Flumazenil were injected before the radiotracer. In vitro binding studies in adrenal, kidney, and cortex mitochondrial membranes indicated that [{sup 123}I]-CLINDE binds with high affinity to PBBS, K{sub d} = 12.6, 0.20, and 3.84 nM, respectively. The density of binding sites was 163, 5.3, and 0.34 pmol/mg protein, respectively. In vivo biodistribution indicated high uptake in adrenals (5.4), heart (1.5), lungs (1.5), kidney (1.5) %ID/g at 6 h p.i. In the central nervous system (CNS), the olfactory bulbs displayed the highest uptake; up to six times the activity in blood. Pre-administration of unlabeled CLINDE, PK11195 and Ro 5-4864 (1 mg/kg) reduced the uptake of [{sup 123}I]-CLINDE by 70-55% in olfactory bulbs. In the kidney and heart, a reduction of 60-80% ID/g was observed, while an increase was observed in the adrenals requiring 10 mg/kg for significant displacement. Flumazenil had no effect on uptake in peripheral organs and brain. Metabolite analysis indicated >90% of the radioactivity in the above tissues was intact [{sup 123}I]-CLINDE. [{sup 123}I]-CLINDE displays high and selective uptake for the PBBS and warrants further development as a probe for imaging PBBS using single photon emission computed tomography (SPECT). (orig.)

  20. Pharmacological evaluation of [123I]-CLINDE: a radioiodinated imidazopyridine-3-acetamide for the study of peripheral benzodiazepine binding sites (PBBS)

    International Nuclear Information System (INIS)

    Mattner, Filomena; Katsifis, Andrew; Mardon, Karine

    2008-01-01

    The study aims to evaluate the iodinated imidazopyridine, N',N'-diethyl-6-Chloro-(4'-[ 123 I]iodophenyl)imidazo [1,2-a]pyridine-3-acetamid e ([ 123 I]-CLINDE) as a tracer for the study of peripheral benzodiazepine binding sites (PBBS). In vitro studies were performed using membrane homogenates and sections from kidney, adrenals, and brain cortex of Sprague-Dawley (SD) rats and incubated with [ 123 I]-CLINDE. For in vivo studies, the rats were injected with [ 123 I]-CLINDE. In competition studies, PBBS-specific drugs PK11195 and Ro 5-4864 and the CBR specific drug Flumazenil were injected before the radiotracer. In vitro binding studies in adrenal, kidney, and cortex mitochondrial membranes indicated that [ 123 I]-CLINDE binds with high affinity to PBBS, K d = 12.6, 0.20, and 3.84 nM, respectively. The density of binding sites was 163, 5.3, and 0.34 pmol/mg protein, respectively. In vivo biodistribution indicated high uptake in adrenals (5.4), heart (1.5), lungs (1.5), kidney (1.5) %ID/g at 6 h p.i. In the central nervous system (CNS), the olfactory bulbs displayed the highest uptake; up to six times the activity in blood. Pre-administration of unlabeled CLINDE, PK11195 and Ro 5-4864 (1 mg/kg) reduced the uptake of [ 123 I]-CLINDE by 70-55% in olfactory bulbs. In the kidney and heart, a reduction of 60-80% ID/g was observed, while an increase was observed in the adrenals requiring 10 mg/kg for significant displacement. Flumazenil had no effect on uptake in peripheral organs and brain. Metabolite analysis indicated >90% of the radioactivity in the above tissues was intact [ 123 I]-CLINDE. [ 123 I]-CLINDE displays high and selective uptake for the PBBS and warrants further development as a probe for imaging PBBS using single photon emission computed tomography (SPECT). (orig.)

  1. Effect of Smoking on Peripheral Blood Lymphocyte Subsets of Patients With Chronic Renal Failure.

    Science.gov (United States)

    Düvenci Birben, Özlem; Akçay, Şule; Sezer, Siren; Şirvan, Şale; Haberal, Mehmet

    2016-11-01

    Smoking is known to suppress the immune system. It is also known that chronic renal failure affects the immune system. However, the number of studies investigating the effects of chronic renal failure and smoking together is limited. In our study, we examined whether smoking affects the diminished response of the immune system in patients with chronic renal failure. We compared peripheral blood lymphocyte subsets in smoking and nonsmoking patients with chronic renal failure. We also used the Fagerström Test for Nicotine Dependence to evaluate its correlation with the lymphocyte subset count in patients who are current smokers. Our study included 126 patients with chronic renal failure. According to their smoking habits, patients were divided into 2 groups: smokers and nonsmokers. The average age of patients who were smokers was 53.2 ± 1.5 years, with average age of nonsmokers being 59.2 ± 2.2 years. The average duration of smoking in smokers was 30.7 ± 2.7 packyears. We found that the percentage of cluster of differentiation 16-56 cells (natural killer cells) and lymphocyte percentage were significantly lower among smokers in our study (P chronic renal failure, similar to that shown in healthy smokers. According to our findings, patients with chronic renal failure, where infection is the primary reason for mortality and morbidity, must be questioned for smoking and referred to smoking cessation clinics. Because of its immunosuppressive effects, smoking behaviors must be solved preoperatively in transplant candidates.

  2. Strategy for improved [11C]DAA1106 radiosynthesis and in vivo peripheral benzodiazepine receptor imaging using microPET, evaluation of [11C]DAA1106

    International Nuclear Information System (INIS)

    Probst, Katrin C.; Izquierdo, David; Bird, Joseph L.E.; Brichard, Laurent; Franck, Dominic; Davies, John R.; Fryer, Tim D.; Richards, Hugh K.; Clark, John C.; Davenport, Anthony P.; Weissberg, Peter L.; Warburton, Elizabeth A.

    2007-01-01

    Introduction: The peripheral benzodiazepine receptor (PBR) has shown considerable potential as a clinical marker of neuroinflammation and tumour progression. [ 11 C]DAA1106 ([ 11 C]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)-acetamide) is a promising positron emission tomography (PET) radioligand for imaging PBRs. Methods: A four-step synthetic route was devised to prepare DAA1123, the precursor for [ 11 C]DAA1106. Two robust, high yielding methods for radiosynthesis based on [ 11 C]-O-methylation of DAA1123 were developed and implemented on a nuclear interface methylation module, producing [ 11 C]DAA1106 with up to 25% radiochemical yields at end-of-synthesis based on [ 11 C]CH 3 I trapped. Evaluation of [ 11 C]DAA1106 for in vivo imaging was performed in a rabbit model with microPET, and the presence of PBR receptor in the target organ was further corroborated by immunohistochemistry. Results: The standard solution method produced 2.6-5.2 GBq (n=19) of [ 11 C]DAA1106, whilst the captive solvent method produced 1.6-6.3 GBq (n=10) of [ 11 C]DAA1106. Radiochemical purities obtained were 99% and specific radioactivity at end-of-synthesis was up to 200 GBq/μmol for both methods. Based on radiochemical product, shorter preparation times and simplicity of synthesis, the captive solvent method was chosen for routine productions of [ 11 C]DAA1106. In vivo microPET [ 11 C]DAA1106 scans of rabbit kidney demonstrated high levels of binding in the cortex. The subsequent introduction of nonradioactive DAA1106 (0.2 μmol) produced considerable displacement of the radioactive signal in this region. The presence of PBR in kidney cortex was further corroborated by immunohistochemistry. Conclusions: A robust, high yielding captive solvent method of [ 11 C]DAA1106 production was developed which enabled efficacious in vivo imaging of PBR expressing tissues in an animal model

  3. Evaluation of C.L.I.N.D.E. as potent peripheral-type benzodiazepine receptor tracer in a rat model of micro-glial activation

    Energy Technology Data Exchange (ETDEWEB)

    Arlicot, N.; Guilloteau, D.; Chalon, S. [Institut National de la Sante et de la Recherche Medicale (INSERM), U619, 37 - Tours (France); Universite Francois Rabelais de Tours, 37 (France); Katsifis, A.; Mattner, F. [ANSTO, Sydney (Australia)

    2008-02-15

    The peripheral-type benzodiazepine receptors (P.B.R.) are localized in mitochondria of glial cells and are very low expressed in normal brain. Their expression rises after micro-glial activation consecutive to brain injury. Accordingly, P.B.R. are potential targets to evaluate neuro inflammatory changes in a variety of C.N.S. disorders. To date no effective tool is available to explore P.B.R. by SPECT. We characterized here 6-chloro-2-(4 iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine- 3-acetamide, C.L.I.N.D.E., in a rat model of excitotoxic lesion. Excitotoxicity was induced in male Wistar rats by unilateral intra striatal injection of different amounts of quinolinic acid (Q.A.: 75, 150 or 300 nmol). One week later, 2 groups of rats (n = 5-6/group) were i.v. injected with [{sup 125}I]-C.L.I.N.D.E. (0.4 MBq), one group being pre-injected with P.K.11195 (5 mg/kg). Brains were removed 30 min after tracer injection and the radioactivity of cerebral areas measured. Complementary ex vivo autoradiography and immunohistochemical studies using O.X.-42 were performed on brain sections In the control group, [{sup 125}I]-C.L.I.N.D.E. binding was significantly higher ( p < 0.001) in lesioned than that in intact side (striatum: 0.552 {+-} 0.109 vs. 0.123 {+-} 0.012% I.D./g tissue; cortex: 0.385 {+-} 0.126 vs. 0.131 {+-} 0.007% with 300 nmol Q.A.). This binding disappeared in rats pretreated with P.K.11195 ( p < 0.001), showing specific binding of C.L.I.N.D.E. to P.B.R.. Ex vivo autoradiography and immunohistochemistry were consistent with this, revealing a spatial correspondence between radioactivity signal and activated micro-glia. Regression analysis yielded a significant correlation ( p < 0.001) between the ligand binding and the dose of Q.A.. These results demonstrate that C.L.I.N.D.E. is suitable for P.B.R. in vivo SPECT imaging to explore their involvement in neuro degenerative disorders associated with micro-glial activation. (authors)

  4. Mitochondrial benzodiazepine receptors regulate steroid biosynthesis

    International Nuclear Information System (INIS)

    Mukhin, A.G.; Papadopoulos, V.; Costa, E.; Krueger, K.E.

    1989-01-01

    Recent observations on the steroid synthetic capability within the brain open the possibility that benzodiazepines may influence steroid synthesis in nervous tissue through interactions with peripheral-type benzodiazepine recognition sites, which are highly expressed in steroidogenic cells and associated with the outer mitochondrial membrane. To examine this possibility nine molecules that exhibit a greater than 10,000-fold difference in their affinities for peripheral-type benzodiazepine binding sites were tested for their effects on a well-established steroidogenic model system, the Y-1 mouse adrenal tumor cell line. 4'-Chlorodiazepam, PK 11195, and PK 14067 stimulated steroid production by 2-fold in Y-1 cells, whereas diazepam, flunitrazepam, zolpidem, and PK 14068 displayed a lower (1.2- to 1.5-fold) maximal stimulation. In contrast, clonazepam and flumazenil did not stimulate steroid synthesis. The potencies of these compounds to inhibit 3 H-labeled PK 11195 binding to peripheral-type benzodiazepine recognition sites correlated with their potencies to stimulate steroid production. Similar findings were observed in bovine and rat adrenocortical cell preparations. These results suggest that ligands of the peripheral-type benzodiazepine recognition site acting on this mitochondrial receptor can enhance steroid production. This action may contribute specificity to the pharmacological profile of drugs preferentially acting on the benzodiazepine recognition site associated with the outer membrane of certain mitochondrial populations

  5. Mitochondrial benzodiazepine receptors regulate steroid biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Mukhin, A.G.; Papadopoulos, V.; Costa, E.; Krueger, K.E. (Georgetown Univ. School of Medicine, Washington, DC (USA))

    1989-12-01

    Recent observations on the steroid synthetic capability within the brain open the possibility that benzodiazepines may influence steroid synthesis in nervous tissue through interactions with peripheral-type benzodiazepine recognition sites, which are highly expressed in steroidogenic cells and associated with the outer mitochondrial membrane. To examine this possibility nine molecules that exhibit a greater than 10,000-fold difference in their affinities for peripheral-type benzodiazepine binding sites were tested for their effects on a well-established steroidogenic model system, the Y-1 mouse adrenal tumor cell line. 4{prime}-Chlorodiazepam, PK 11195, and PK 14067 stimulated steroid production by 2-fold in Y-1 cells, whereas diazepam, flunitrazepam, zolpidem, and PK 14068 displayed a lower (1.2- to 1.5-fold) maximal stimulation. In contrast, clonazepam and flumazenil did not stimulate steroid synthesis. The potencies of these compounds to inhibit {sup 3}H-labeled PK 11195 binding to peripheral-type benzodiazepine recognition sites correlated with their potencies to stimulate steroid production. Similar findings were observed in bovine and rat adrenocortical cell preparations. These results suggest that ligands of the peripheral-type benzodiazepine recognition site acting on this mitochondrial receptor can enhance steroid production. This action may contribute specificity to the pharmacological profile of drugs preferentially acting on the benzodiazepine recognition site associated with the outer membrane of certain mitochondrial populations.

  6. Pooled analysis of the CONFIRM Registries: outcomes in renal disease patients treated for peripheral arterial disease using orbital atherectomy.

    Science.gov (United States)

    Lee, Michael S; Yang, Tae; Adams, George L; Mustapha, Jihad; Das, Tony

    2014-08-01

    Patients with renal disease typically have severely calcified peripheral arterial disease. As a result, this population may have worse clinical outcomes following endovascular intervention compared to patients without renal insufficiency. Clinical trials typically exclude this patient population. Analysis of the CONFIRM I-III registries revealed 1105 patients with renal disease (1777 lesions) and 1969 patients without renal disease (2907 lesions) who underwent orbital atherectomy. This subanalysis compared the composite procedural complication rate including dissection, perforation, slow flow, vessel closure, spasm, embolism, and thrombus formation in patients with and without renal disease. Patients with renal disease had a higher prevalence of diabetes (Patherectomy resulted in similar low rates of procedural complications in the renal disease group compared with the non-renal disease group despite more unfavorable baseline clinical and lesion characteristics in the renal disease group.

  7. Characterization of astrocytic and neuronal benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Bender, A.S.

    1988-01-01

    Primary cultures of astrocytes and neurons express benzodiazepine receptors. Neuronal benzodiazepine receptors were of high-affinity, K{sub D} values were 7.5-43 nM and the densities of receptors (B{sub max}) were 924-4131 fmol/mg protein. Astrocytes posses a high-affinity benzodiazepine receptor, K{sub D} values were 6.6-13 nM. The B{sub max} values were 6,033-12,000 fmol/mg protein. The pharmacological profile of the neuronal benzodiazepine receptor was that of the central-type benzodiazepine receptor, where clonazepam has a high-affinity and Ro 5-4864 (4{prime}-chlorodiazepam) has a low-affinity. Whereas astrocytic benzoidazepine receptor was characteristic of the so called peripheral-type benzodiazepine receptors, which shows a high-affinity towards Ro 5-4863, and a low-affinity towards clonazepam. The astrocytic benzodiazepine receptors was functionally correlated with voltage dependent calcium channels, since dihydropyridines and benzodiazepines interacted with ({sup 3}H) diazepam and ({sup 3}H) nitrendipine receptors with the same rank order of potency, showing a statistically significant correlation. No such correlation was observed in neurons.

  8. A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure.

    Science.gov (United States)

    Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A; Vengamma, B; Sivakumar, V; Kolli, Satyarao

    2017-01-01

    To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure ( n = 100) and severe renal failure patients ( n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics.

  9. A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure

    Science.gov (United States)

    Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A.; Vengamma, B.; Sivakumar, V.; Kolli, Satyarao

    2017-01-01

    Objective: To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Materials and Methods: Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. Results: The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure (n = 100) and severe renal failure patients (n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Conclusion: Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics. PMID:29204008

  10. Benzodiazepine poisoning in elderly

    OpenAIRE

    Perković-Vukčević Nataša; Vuković-Ercegović Gordana; Šegrt Zoran; Đorđević Snežana; Jović-Stošić Jasmina

    2016-01-01

    Background/Aim. Benzodiazepines are among the most frequently ingested drugs in self-poisonings. Elderly may be at greater risk compared with younger individuals due to impaired metabolism and increased sensitivity to benzodiazepines. The aim of this study was to assess toxicity of benzodiazepines in elderly attempted suicide. Methods. A retrospective study of consecutive presentations to hospital after self-poisoning with benzodiazepines was done. Collecte...

  11. [Suicidal poisoning with benzodiazepines].

    Science.gov (United States)

    Chodorowski, Z; Sein Anand, J

    1997-01-01

    In the period from 1987 to 1996, 103 patients with suicidal benzodiazepines poisoning were treated, including 62 women and 41 men from 16 to 79 (mean 34) years old. 23 persons were poisoned only by benzodiazepines, in 80 remaining cases intoxications were mixed eg. including benzodiazepines and alcohol, tricyclic antidepressants, barbiturates, opioids, phenothiazines. The main causes of suicides were mainly depression, drug addiction and alcoholism. Nobody died in the benzodiazepines group, while mortality rate in the group of mixed poisoning was 4%. Prescribing benzodiazepines by physicians was quite often not justified and facilitated, among others, accumulation of the dose sufficient for suicide attempt. Flumazenil was efficient for leading out from coma in 86% of cases with poisoning only by benzodiazepines and 13% of cases with mixed intoxications mainly containing benzodiazepines and alcohol or carbamazepine.

  12. Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

    Science.gov (United States)

    Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

    2016-03-01

    Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels. © 2015 International Federation for Cell Biology.

  13. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis

    DEFF Research Database (Denmark)

    Schrier, R W; Arroyo, V; Bernardi, M

    1988-01-01

    Renal sodium and water retention and plasma volume expansion have been shown to precede ascites formation in experimental cirrhosis. The classical "underfilling" theory, in which ascites formation causes hypovolemia and initiates secondary renal sodium and water retention, thus seems unlikely...... with cirrhosis. Arterial vasodilators and arteriovenous fistula are other examples in which renal sodium and water retention occur secondary to a decreased filling of the arterial vascular tree. An increase in cardiac output and hormonal stimulation are common features of cirrhosis, arteriovenous fistula...... and drug-induced peripheral arterial vasodilation. However, a predilection for the retained sodium and water to transudate into the abdominal cavity occurs with cirrhosis because of the presence of portal hypertension. The Peripheral Arterial Vasodilation Hypothesis also explains the continuum from...

  14. Benzodiazepine poisoning in elderly.

    Science.gov (United States)

    Vukcević, Natasa Perković; Ercegović, Gordana Vuković; Segrt, Zoran; Djordjević, Snezana; Stosić, Jasmina Jović

    2016-03-01

    Benzodiazepines are among the most frequently ingested drugs in self-poisonings. Elderly may be at greater risk compared with younger individuals due to impaired metabolism and increased sensitivity to benzodiazepines. The aim of this study was to assess toxicity of benzodiazepines in elderly attempted suicide. A retrospective study of consecutive presentations to hospital after self-poisoning with benzodiazepines was done. Collected data consisted of patient's characteristics (age, gender), benzodiazepine ingested with its blood concentrations at admission, clinical findings including vital signs and Glasgow coma score, routine blood chemistry, complications of poisoning, details of management, length of hospital stay and outcome. According the age, patients are classified as young (15-40-year old), middle aged (41-65-year old) and elderly (older than 65). During a 2-year observational period 387 patients were admitted because of pure benzodiazepine poisoning. The most frequently ingested drug was bromazepam, the second was diazepam. The incidence of coma was significantly higher, and the length of hospital stay significantly longer in elderly. Respiratory failure and aspiration pneumonia occurred more frequently in old age. Also, flumazenil was more frequently required in the group of elderly patients. Massive benzodiazepines overdose in elderly may be associated with a significant morbidity, including deep coma with aspiration pneumonia, respiratory failure, and even death. Flumazenil is indicated more often to reduce CNS depression and prevent complications of prolonged unconsciousness, but supportive treatment and proper airway management of comatose patients is the mainstay of the treatment of acute benzodiazepine poisoning.

  15. Benzodiazepine absetzen im Alter

    DEFF Research Database (Denmark)

    Wolter, Dirk

    2017-01-01

    Although viewed critically in geriatrics, benzodiazepine use is still common among old people. Before reducing the dosage the following questions must be considered: 1. Are there indications for benzodiazepine treatment and will discontinuation cause relevant rebound symptoms of the initial disor...

  16. Benzodiazepine abuse among the elderly

    Directory of Open Access Journals (Sweden)

    Shalini Singh

    2016-01-01

    Full Text Available Benzodiazepines belong to the hypnotic-sedative class of drugs which have anxiolytic, sedative, and hypnotic properties. These drugs have been in clinical use for at least half a century. The propensity for development of dependence, especially on prescription benzodiazepines, coupled with the risk of falls and cognitive impairment due to benzodiazepines makes the elderly population susceptible to adverse outcomes with the use of benzodiazepines, and hence, cautious use is desired in this population. This review discusses the various aspects pertaining to benzodiazepine abuse in the elderly including pharmacology, prevalence of abuse, adverse consequences of benzodiazepine abuse, and subsequently assessment and management of elderly patients with benzodiazepine abuse.

  17. Analysis of infusion-site reactions in renal transplant recipients receiving peripherally administered rabbit antithymocyte globulin as compared with basiliximab.

    Science.gov (United States)

    Erickson, Abbie L; Roberts, Keri; Malek, Sayeed K; Chandraker, Anil K; Tullius, Stefan G; Gabardi, Steven

    2010-06-01

    Antithymocyte globulin rabbit (r-ATG) has been used for the treatment and prevention of acute rejection in renal transplant recipients (RTR). Current manufacturer recommendations for r-ATG dictate the need for administration through a high-flow vein (central line). Previous studies have shown peripheral administration of r-ATG to be safe; however, these studies suggest the co-administration of heparin and hydrocortisone and did not compare the infusion-site reaction rates to a control group. A retrospective analysis was conducted of adult RTR receiving r-ATG or basiliximab between January 2004 and October 2006. Each agent was administered through a dedicated peripheral line. The primary endpoint was the incidence of infusion-site reactions. Other endpoints included the need to replace the intravenous catheter and the incidence of systemic thrombosis within 1 month of transplantation. During the study period, 152 peripheral infusions of r-ATG and 92 peripheral infusions of basiliximab were administered. No difference in infusion-site reactions was noted between the groups. There was also no difference either in the need for peripheral line replacement or the rates of systemic thrombosis. Peripheral administration of r-ATG is safe and can be infused without concomitant heparin and hydrocortisone. This method of r-ATG infusion was shown to be as safe as peripherally administered basiliximab.

  18. Change of Peripheral Blood Treg/Thl7 in Cognitive Impairment with Chronic Renal Failure Patients.

    Science.gov (United States)

    Wang, Jie; Li, Xue-Bin; Huang, Peng; Huang, Mei-Ying; Gu, Xian-Jun

    2018-01-01

    To investigate the changes in peripheral blood Treg/Th17 cell balance and its significance in patients with chronic renal failure (CRF) and cognitive impairment. A total of 71 patients with CRF were enrolled as a study group. The patients were divided into a cognitive impairment group and a normal cognitive function group according to the Mini-Mental State Examination (MMSE). Peripheral blood Treg and Th17 cells were analyzed by flow cytometry and their relevant cytokines (IL-17, IL-10 and TGF-β) and other biochemical indicators, including C-reactive protein (CRP) and IL-6, were determined by ELISA. Thepatients with both CRF and cognitive impairment were older than the cognitive normal groups. Peripheral blood Treg cells by Flow cytometry (the CRF cognitive impairment group 5.57±1.3%, CRF group with normal cognitive function 7.5 ± 0.9% and normal control group 9.7 ± 1.7%,Pcognitive impairment than in the group without cognitive impairment ( IL-10, 7.4±4.2 pg/mL, 13.8±3.9 pg/mL, 18.3±3.2 pg/mL; TGF-β 335.6±175.3 pg/mL, 512.7 ± 114.6 pg/mL, 953.8±373.4 pg/mL P cognitive impairment group 3.3 ± 0.7%, CRF group with normal cognitive function2.2 ± 0.5% and normal control group 1.5 ± 0.3%),and cytokine levels (IL-17, IL-6 and CRP) were higher in the group with cognitive impairment IL-6 (21.3 ± 5.1 pg/mL), IL-17 (18.5 ± 4.2 pg/mL) and CRP (20.3 ± 5.9 mg/L) in the CRF group with cognitive impairment when compared with the CRF group and normal cognitive function (12.2 ± 4.5 pg/mL, 12.1 ± 3.7 pg/mL and 13.5 ± 4.6 mg/L, respectively) or the normal control group (9.2 ± 5.8 pg/mL, 7.4 ± 2.6 pg/mL and 3.2 ± 1.3 mg/L, respectively, Pcognitive impairment in patients with CRF. © 2018 The Author(s). Published by S. Karger AG, Basel.

  19. Benzodiazepine poisoning in elderly

    Directory of Open Access Journals (Sweden)

    Perković-Vukčević Nataša

    2016-01-01

    Full Text Available Background/Aim. Benzodiazepines are among the most frequently ingested drugs in self-poisonings. Elderly may be at greater risk compared with younger individuals due to impaired metabolism and increased sensitivity to benzodiazepines. The aim of this study was to assess toxicity of benzodiazepines in elderly attempted suicide. Methods. A retrospective study of consecutive presentations to hospital after self-poisoning with benzodiazepines was done. Collected data consisted of patient's characteristics (age, gender, benzodiazepine ingested with its blood concentrations at admission, clinical findings including vital signs and Glasgow coma score, routine blood chemistry, complications of poisoning, details of management, length of hospital stay and outcome. According the age, patients are classified as young (15-40-year old, middle aged (41-65-year old and elderly (older than 65. Results. During a 2-year observational period 387 patients were admitted because of pure benzodiazepine poisoning. The most frequently ingested drug was bromazepam, the second was diazepam. The incidence of coma was significantly higher, and the length of hospital stay significantly longer in elderly. Respiratory failure and aspiration pneumonia occurred more frequently in old age. Also, flumazenil was more frequently required in the group of elderly patients. Conclusion. Massive benzodiazepines overdose in elderly may be associated with a significant morbidity, including deep coma with aspiration pneumonia, respiratory failure, and even death. Flumazenil is indicated more often to reduce CNS depression and prevent complications of prolonged unconsciousness, but supportive treatment and proper airway management of comatose patients is the mainstay of the treatment of acute benzodiazepine poisoning.

  20. Attention Span, Anxiety and Benzodiazepine Receptors

    Science.gov (United States)

    1991-02-26

    increasse the central and peripheral effects of emotional stress ,-- FL combines 0nly the clinically favorable attributes of both classes of drugs, as...Pieri, P. PoIc. E.P. Bonetti, P. Cumin , R. Schaffner and W. Haefely, 1981, Selective antagonist of benzodiazepines, Nature 290, 514. Karobath, M. and G...34intimidaring" and/or stressful stimuli. In such a condition, flumazenil can be expected to have a stabilizing effect on emotional responses normally triggered

  1. Change of Peripheral Blood Treg/Thl7 in Cognitive Impairment with Chronic Renal Failure Patients

    Directory of Open Access Journals (Sweden)

    Jie Wang

    2018-01-01

    Full Text Available Background/Aims: To investigate the changes in peripheral blood Treg/Th17 cell balance and its significance in patients with chronic renal failure (CRF and cognitive impairment. Methods: A total of 71 patients with CRF were enrolled as a study group. The patients were divided into a cognitive impairment group and a normal cognitive function group according to the Mini-Mental State Examination (MMSE. Peripheral blood Treg and Th17 cells were analyzed by flow cytometry and their relevant cytokines (IL-17, IL-10 and TGF-β and other biochemical indicators, including C-reactive protein (CRP and IL-6, were determined by ELISA. Results: Thepatients with both CRF and cognitive impairment were older than the cognitive normal groups. Peripheral blood Treg cells by Flow cytometry (the CRF cognitive impairment group 5.57±1.3%, CRF group with normal cognitive function 7.5 ± 0.9% and normal control group 9.7 ± 1.7%,P<0.05 and its related cytokines (IL-10 and TGF-β by ELISA detection were lower in the group with cognitive impairment than in the group without cognitive impairment ( IL-10, 7.4±4.2 pg/mL, 13.8±3.9 pg/mL, 18.3±3.2 pg/mL; TGF-β 335.6±175.3 pg/mL, 512.7 ± 114.6 pg/mL, 953.8±373.4 pg/mL P < 0.05, respectively.However, Th17 cell numbers (the CRF cognitive impairment group 3.3 ± 0.7%, CRF group with normal cognitive function2.2 ± 0.5% and normal control group 1.5 ± 0.3%,and cytokine levels (IL-17, IL-6 and CRP were higher in the group with cognitive impairment IL-6 (21.3 ± 5.1 pg/mL, IL-17 (18.5 ± 4.2 pg/mL and CRP (20.3 ± 5.9 mg/L in the CRF group with cognitive impairment when compared with the CRF group and normal cognitive function (12.2 ± 4.5 pg/mL, 12.1 ± 3.7 pg/mL and 13.5 ± 4.6 mg/L, respectively or the normal control group (9.2 ± 5.8 pg/mL, 7.4 ± 2.6 pg/mL and 3.2 ± 1.3 mg/L, respectively, P<0.05. The frequencies of Treg in patients with CRF were positively correlated with the MMSE scores ((r = 0.518, P < 0.05, but the

  2. Gamma-aminobutyric acid-modulated benzodiazepine binding sites in bacteria

    International Nuclear Information System (INIS)

    Lummis, S.C.R.; Johnston, G.A.R.; Nicoletti, G.; Holan, G.

    1991-01-01

    Benzodiazepine binding sites, which were once considered to exist only in higher vertebrates, are here demonstrated in the bacteria E. coli. The bacterial [ 3 H]diazepam binding sites are modulated by GABA; the modulation is dose dependent and is reduced at high concentrations. The most potent competitors of E.Coli [ 3 H]diazepam binding are those that are active in displacing [ 3 H]benzodiazepines from vertebrate peripheral benzodiazepine binding sites. These vertebrate sites are not modulated by GABA, in contrast to vertebrate neuronal benzodiazepine binding sites. The E.coli benzodiazepine binding sites therefore differ from both classes of vertebrate benzodiazepine binding sites; however the ligand spectrum and GABA-modulatory properties of the E.coli sites are similar to those found in insects. This intermediate type of receptor in lower species suggests a precursor for at least one class of vertebrate benzodiazepine binding sites may have existed

  3. Synthesis of substituted [{sup 123}I]imidazo[1,2-a]pyridines as potential probes for the study of the peripheral benzodiazepine receptors using SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Katsifis, A.; Mattner, F.; Dikic, B.; Papazian, V. [Radiopharmaceuticals Div. R and D, ANSTO, Menai, NSW (Australia)

    2000-07-01

    The imidazo[1,2-a]pyridines N,N'-dimethyl-6-chloro-(4'-iodophenyl)imidazo[1,2-a]pyridine-3-acetamide 1. N,N'-diethyl-6-chloro-(4'-iodophenyl)imidazo[1,2-a]pyridine-3-acetamide 2, and N-methyl-6-chloro-(4'-iodophenyl)imidazo[1,2-a]pyridine-3-acetamide 3, are high affinity and selective ligands for the peripheral benzodiazepineodiazepine receptors (PBR). The [{sup 123}I]1-3 labelled analogues of these compounds were subsequently synthesised for the potential study of the PBR in vivo using SPECT. Radioiodination was achieved by iododestannylation reactions of the corresponding tributyl tin precursors with Na[{sup 123}I] in the presence of peracetic acid, chloramine-T or Iodogen. Purification of the crude product was achieved by semipreparative C-18 RP HPLC to give the products in radiochemical yields of 40-85%. The products were obtained in >97% chemical and radiochemical purity and with specific activities >80 GBq/{mu}mol. (orig.)

  4. Synthesis of substituted [123I]imidazo[1,2-a]pyridines as potential probes for the study of the peripheral benzodiazepine receptors using SPECT

    International Nuclear Information System (INIS)

    Katsifis, A.; Mattner, F.; Dikic, B.; Papazian, V.

    2000-01-01

    The imidazo[1,2-a]pyridines N,N'-dimethyl-6-chloro-(4'-iodophenyl)imidazo[1,2-a]pyridine-3-acetamide 1. N,N'-diethyl-6-chloro-(4'-iodophenyl)imidazo[1,2-a]pyridine-3-acetamide 2, and N-methyl-6-chloro-(4'-iodophenyl)imidazo[1,2-a]pyridine-3-acetamide 3, are high affinity and selective ligands for the peripheral benzodiazepineodiazepine receptors (PBR). The [ 123 I]1-3 labelled analogues of these compounds were subsequently synthesised for the potential study of the PBR in vivo using SPECT. Radioiodination was achieved by iododestannylation reactions of the corresponding tributyl tin precursors with Na[ 123 I] in the presence of peracetic acid, chloramine-T or Iodogen. Purification of the crude product was achieved by semipreparative C-18 RP HPLC to give the products in radiochemical yields of 40-85%. The products were obtained in >97% chemical and radiochemical purity and with specific activities >80 GBq/μmol. (orig.)

  5. Isotopically labelled benzodiazepines

    International Nuclear Information System (INIS)

    Liebman, A.A.

    1987-01-01

    This paper reports on the benzodiazepines which are a class of therapeutic agents. Improvements in the analytical methodology in the areas of biochemistry and pharmacology were significant, particularly in the application of chromatographic and spectroscopic techniques. In addition, the discovery and subsequent development of tritium and carbon-14 as an analytical tool in the biological sciences were essentially post-world war II phenomena. Thus, as these new chemical entities were found to be biologically active, they could be prepared in labeled form for metabolic study, biological half-life determination (pharmacokinetics), tissue distribution study, etc. This use of tracer methodology has been liberally applied to the benzodiazepines and also more recently to the study of receptor-ligand interactions, in which tritium, carbon-11 or fluorine-18 isotopes have been used. The history of benzodiazepines as medicinal agents is indeed an interesting one; an integral part of that history is their use in just about every conceivable labeled form

  6. Radiosynthesis of [11C]D.P.A.-713, [11C]D.P.A.-715 and [11C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

    International Nuclear Information System (INIS)

    Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B.; Kassiou, M.; James, M.; Creelman, A.; Fulton, R.; Kassiou, M.; Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C.; Selleri, S.

    2008-01-01

    11 C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon 11 (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[ 11 C]methyl iodide (in D.M.S.O./D.M.F (100/200 μL) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [ 11 C]methyl triflate (in acetone (300μL) containing aq. 3 M NaOH (4μL) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

  7. [{sup 18}F]D.P.A.-714: a novel fluorine-18-labelled pyrazolo[1,5-a]pyrimidine acetamide for imaging the peripheral benzodiazepine receptors with PET - radiosynthesis on a zymate-xp robotic system

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Damont, A.; Hinnen, F.; Kuhnast, B.; Chauveau, F.; Van camp, N.; Hantraye, P.; Tavitian, B. [Servvice Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); James, M.; Creelman, A.; Fulton, R.; Kassiou, M. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Vercouillie, J.; Guilloteau, D. [Universite Francois Rabelais de Tours, 37 (France); Vercouillie, J.; Guilloteau, D. [Centre Hospitalier Regional Universitaire, 37 - Tours (France); Selleri, S.; Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia)

    2008-02-15

    {sup 11}C D.P.A.-713 (N,N-diethyl-2-[2-(4-[{sup 11}C]methoxy-phenyl)-5,7-dimethyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) is a recently developed carbon-11-labelled (half life: 20.4 min)pyrazolo[1,5-a]pyrimidine acetamide for the in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.)). Preliminary results obtained in a rodent-model demonstrates that {sup 11}C D.P.A.-713 showed a high potential to in vivo image neuro-inflammation and additionally, this radioligand allowed a higher contrast between the lesioned area and the corresponding area in the intact contralateral hemisphere when compared to the radioligand of reference. D.P.A-714 (N,N-diethyl-2-[2-[4-(2-fluoro-ethoxy)phenyl] -5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]acetamide), a chemically closely related derivative of D.P.A.-713, had been designed with a fluorine atom in its structure, allowing ultimate labelling with fluorine-18, a longer-lived positron-emitter (half life:109.8 min) and today one of the most attractive PET isotopes for radiopharmaceutical chemistry. D.P.A.-714 as well as its corresponding tosylated derivative have been re-synthesized in 2 chemicals steps from D.P.A.-713. D.P.A.-714 has then been labelled at its aromatic fluoro-ethoxy group from the corresponding tosyl-derivative using the K{sup 18}FF-kryptofix{sub 222} (in CH{sub 3}CN (3 mL) at 85 degrees C for 5 min or D.M.S.O. (600 {mu}L) at 130 degrees C for 5 min). {sup 18}FD.P.A.-714 was then purified using semi preparative X terra reverse phase H.P.L.C., adequately formulated for i.v. injection and was found to be > 95% chemically and radiochemically pure. The total synthesis time was less than 90 min and the specific radioactivities at the end of the radiosynthesis ranged from 1 to 3 Ci/micro-mole. (N.C.)

  8. Radiosynthesis of [{sup 11}C]D.P.A.-713, [{sup 11}C]D.P.A.-715 and [{sup 11}C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B. [Service Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); Kassiou, M.; James, M.; Creelman, A.; Fulton, R. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia); Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C. [Radiopharmaceuticals Research Institute, ANSTO, NSW (Australia); Selleri, S. [Degli Studi di Firenze Univ., Dipt. di Scienze Farmaceutiche (Italy)

    2008-02-15

    {sup 11}C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon{sup 11} (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[{sup 11}C]methyl iodide (in D.M.S.O./D.M.F (100/200 {mu}L) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [{sup 11}C]methyl triflate (in acetone (300{mu}L) containing aq. 3 M NaOH (4{mu}L) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

  9. Synthesis and carbon-11-labeling of p-MeO-SSR180575, a novel indoleacetamide-based candidate for PET imaging of the peripheral benzodiazepine receptor (TSPO 18 kDa)

    International Nuclear Information System (INIS)

    Damont, A.L.; Le Helleix, St.; Kuhnast, B.; Boisgard, R.; Tavitian, B.; Dolle, F.; Marguet, F.; Puech, F.

    2011-01-01

    Complete text of publication follows: Objectives: The 3-iso-quinolinecarboxamide [ 11 C]PK11195, despite its low brain uptake and high level of nonspecific binding, is still the most widely used PET-radioligand for the in vivo imaging of the peripheral benzodiazepine receptor (PBR or TSPO 18 kDa). Several new PBR radioligands are currently developed to replace [ 11 C]PK11195 [1], e.g the pyrazolo[1, 5-a]pyrimidine-acetamides [ 11 C]DPA-713 and [ 18 F]DPA-714, the imidazo[1, 2-a]pyridine-acetamides [ 11 C]CLINME and [ 18 F]PBR111 and the N-benzyl-N-(2-phenoxy-aryl)- acetamides [ 11 C]PBR28 and [ 18 F]FEDAA1106. Another attractive newly identified chemical class of structures are the indole-acetamides and notably compounds derived from the lead compound SSR180575 [2]. Herein are reported the synthesis and the labelling with the positron-emitter carbon-11 (half-life: 20.38 min) of a novel derivative of SSR180575, bearing a para methoxy function on its phenyl ring. Methods: p-MeO-SSR180575 (1) was synthesized from commercially available 4-chloro-2-nitrotoluene in 10 steps. O-demethylation, performed with a boron tribromide solution in dichloromethane at low temperature, afforded the free phenol derivative 2. Carbon-11 labeling of p-MeO-SSR180575 (1) was performed using a TRACERLab FX-C Pro synthesizer (GEMS) and comprised (1) trapping of [ 11 C]MeOTf at -10 C in acetone (0.3 mL) containing the nor-derivative 2 (O-demethylated, 0.6-0.9 mg) and aq. 3N NaOH (8 μL); (2) heating at 110 C for 2 min; (3) concentration to dryness and taking up the residue in 1.0 mL of the HPLC mobile phase; (4) purification using semi-preparative reversed-phase HPLC (Waters Symmetry R C-18 - eluent: CH 3 CN / H 2 O / TFA: 50 / 50 / 0.1 (v:v:v) - flow rate: 5 mL/min - detection at 254 nm) and (5) SepPak Plus R C-18-based formulation for i.v. injection approach was the pyridazine ring formation reaction that proceeded partially: the maximum conversion of the intermediate diester-indole reacting

  10. Synthesis and carbon-11-labeling of p-MeO-SSR180575, a novel indoleacetamide-based candidate for PET imaging of the peripheral benzodiazepine receptor (TSPO 18 kDa)

    International Nuclear Information System (INIS)

    Damont, A.; Le Helleix, St.; Kuhnast, B.; Boisgard, R.; Tavitian, B.; Dolle, F.; Marguet, F.; Puech, F.

    2011-01-01

    Complete text of publication follows: Objectives: The 3-iso-quinolinecarboxamide [ 11 C]PK11195, despite its low brain uptake and high level of nonspecific binding, is still the most widely used PET-radioligand for the in vivo imaging of the peripheral benzodiazepine receptor (PBR or TSPO 18 kDa). Several new PBR radioligands are currently developed to replace [ 11 C]PK11195, e.g the pyrazolo[1, 5-a]pyrimidine-acetamides [ 11 C]DPA-713 and [ 18 F]DPA-714, the imidazo[1, 2-a]pyridine-acetamides [ 11 C]CLINME and [ 18 F]PBR111 and the N-benzyl-N-(2-phenoxy-aryl)- acetamides [ 11 C]PBR28 and [ 18 F]FEDAA1106. Another attractive newly identified chemical class of structures are the indole-acetamides and notably compounds derived from the lead compound SSR180575. Herein are reported the synthesis and the labelling with the positron-emitter carbon-11 (half-life: 20.38 min) of a novel derivative of SSR180575, bearing a para methoxy function on its phenyl ring. Methods: p-MeO-SSR180575 (1) was synthesized from commercially available 4-chloro-2-nitrotoluene in 10 steps. O-demethylation, performed with a boron tribromide solution in dichloromethane at low temperature, afforded the free phenol derivative 2. Carbon-11 labeling of p-MeO-SSR180575 (1) was performed using a TRACERLab FX-C Pro synthesizer (GEMS) and comprised (1) trapping of [ 11 C]MeOTf at -10 C in acetone (0.3 mL) containing the nor-derivative 2 (O-demethylated, 0.6-0.9 mg) and aq. 3N NaOH (8 μL); (2) heating at 110 C for 2 min; (3) concentration to dryness and taking up the residue in 1.0 mL of the HPLC mobile phase; (4) purification using semi-preparative reversed-phase HPLC (Waters Symmetry C-18 - eluent: CH 3 CN / H 2 O / TFA: 50 / 50 / 0.1 (v:v:v) - flow rate: 5 mL/min - detection at 254 nm) and (5) SepPak R Plus C-18-based formulation for i.v. injection. Results: p-MeO-SSR180575 (1) was obtained in 10% overall yield. The tricky and low-yielding step in our approach was the pyridazine ring formation

  11. Predictors of long-term benzodiazepine abstinence in participants of a randomized controlled benzodiazepine withdrawal program.

    NARCIS (Netherlands)

    Oude Voshaar, R.C.; Gorgels, W.J.M.J.; Mol, A.J.J.; Balkom, A.J.L.M. van; Mulder, J.; Lisdonk, E.H. van de; Breteler, M.H.M.; Zitman, F.G.

    2006-01-01

    OBJECTIVE: To identify predictors of resumed benzodiazepine use after participation in a benzodiazepine discontinuation trial. METHOD: We performed multiple Cox regression analyses to predict the long-term outcome of a 3-condition, randomized, controlled benzodiazepine discontinuation trial in

  12. Predictors of long-term benzodiazepine abstinence in participants of a randomized controlled benzodiazepine withdrawal program

    NARCIS (Netherlands)

    Oude Voshaar, R.C.; Gorgels, W.J.M.J.; Mol, A.J.J.; Balkom, A.J.L.M. van; Mulder, J.; Lisdonk, E.H. van de; Breteler, M.H.M.; Zitman, F.G.

    2006-01-01

    Objective: To identify predictors of resumed benzodiazepine use after participation in a benzodiazepine discontinuation trial. Method: We performed multiple Cox regression analyses to predict the long-term outcome of a 3-condition, randomized, controlled benzodiazepine discontinuation trial in

  13. Epstein-Barr virus-associated peripheral T-Cell lymphoma involving spleen in a renal transplant patient.

    Science.gov (United States)

    Lee, Hye Kyung; Kim, Hee Jung; Lee, Eun Hee; Kim, Suk Young; Park, Tae In; Kang, Chang Suk; Yang, Woo Ick

    2003-01-01

    The incidence of posttransplantation lymphoproliferative disorders (PTLDs) has increased in recent years. Although rare, various types of T-cell lymphoma have been reported and their association with Epstein-Barr virus (EBV) has been compared with B-cell PTLDs. We report a case of splenic peripheral T-cell lymphoma occurring in a 47-yr-old male patient 7 yr after renal allograft transplantation. The spleen showed sinusoidal proliferation of focal CD30 positive, large, atypical lymphoid cells. Positivity for CD3 and cytolytic granule-associated proteins was also demonstrated in the tumor cells, while anaplastic large cell lymphoma kinase (ALK) and CD8 were not expressed. Strong nuclear signals for EBV mRNA were noted by EBER1 in situ hybridization. A molecular genetic study demonstrated a rearrangement of the gamma T-cell receptor gene. To our knowledge, this case is unique in terms of a posttransplant T-cell lymphoma that shows focal CD30, cytolytic granule-associated proteins, and EBV positivity. PMID:12692428

  14. Stability of solubilized benzodiazepine receptors

    NARCIS (Netherlands)

    Janssen, M.J; Ensing, K; de Zeeuw, R.A

    1997-01-01

    According to the observations of other researchers, benzodiazepine receptors solubilized with sodium deoxycholate are unstable, but stability can be improved by exchanging deoxycholate for Triton X-100. In our experiments we conclude that the choice of detergent is not the restrictive factor for the

  15. Radiosynthesis of 7-chloro-N, N-dimethyl-5-[11C] methyl-4-oxo-3-phenyl-3, 5-dihydro-4H pyridazino [4, 5-b]indole-1-acetamide, [11C]SSR180575, a novel radioligand for imaging the TSPO (peripheral benzodiazepine receptor) with PET

    International Nuclear Information System (INIS)

    Thominiaux, C.; Damont, A.L.; Kuhnast, B.; Demphel, St.; Le Helleix, St.; Chauveau, F.; Boutin, H.; Van Camp, N.; Boisgard, R.; Tavitian, B.; Dolle, F.; Boisnard, S.; Rivron, L.; Roy, S.; Allen, J.; Chauveau, F.; Boutin, H.; Van Camp, N.; Boisgard, R.; Tavitian, B.; Rooney, T.; Benavides, J.; Hantraye, Ph.

    2010-01-01

    SSR180575 (7-chloro-N, N, 5-trimethyl-4-oxo-3-phenyl-3, 5-dihydro-4H-pyridazino [4, 5-b]indole-1-acetamide) is the lead compound of an original pyridazino-indole series of potent and highly selective TSPO (peripheral benzodiazepine receptor) ligands. Isotopic labeling of SSR180575 with the short-lived positron-emitter carbon-11 (T1/2: 20.38 min) at its 5-methyl-pyridazino[4, 5-b]indole moiety as well as at its N, N-dimethylacetamide function by methylation of the corresponding nor-analogues was investigated. Best results in terms of radiochemical yields and purities were obtained for the preparation of [indole-N-methyl- 11 C]SSR180575, where routine production batches of 4.5-5.0 GBq of radiochemically pure (499%) i.v. injectable solutions (specific radioactivities: 50-90 GBq/μmol) could be prepared within a total synthesis time of 25 min (HPLC purification included) starting from a 55 GBq [ 11 C]CO 2 cyclotron production batch (non decay-corrected overall radiochemical yields: 8-9%). The process comprises (1) trapping at -10 C of [ 11 C]methyl triflate in DMF (300 μl) containing 0.2-0.3 mg of the indole precursor for labeling and 4 mg of K 2 CO 3 (excess); (2) heating at 120 C for 3 min; (3) dilution of the residue with 0.5 ml of the HPLC mobile phase and (4) purification using semi-preparative reversed phase HPLC (Zorbax R SB-C-18). In vivo pharmacological properties of [indole-N-methyl- 11 C]SSR180575 as a candidate for imaging neuro-inflammation with positron emission tomography are currently evaluated. (authors)

  16. Type-I interferon receptor expression: its circadian rhythm and downregulation after interferon-alpha administration in peripheral blood cells from renal cancer patients.

    Science.gov (United States)

    Shiba, Masahiro; Nonomura, Norio; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Inoue, Hitoshi; Tsujimura, Akira; Nishimura, Kazuo; Okuyama, Akihiko

    2009-04-01

    To investigate the regulation of interferon-alpha (IFN-alpha) receptor expression in metastatic renal cell carcinoma (RCC) after IFN-alpha administration. Blood sampling was carried out in eight patients with metastatic RCC and six healthy volunteers. Flow-cytometric analysis using a monoclonal antibody against the active subunit of the type-I IFN-alpha receptor (IFNAR2) was carried out to examine the circadian rhythm of IFNAR2 expression in peripheral blood mononuclear cells (PBMC) as well as its downregulation after IFN-alpha administration. According to its circadian rhythm IFNAR2 in PBMC had a peak expression at night. Once IFN-alpha is administered, IFNAR2 levels in PBMC showed downregulation within 48 h and recovered within another 48 h. Our findings might support the establishment of an optimal schedule for IFN-alpha administration.

  17. Identification, characterization, and purification of a 65,000 dalton protein in rat brain is photolabeled by nitro-containing benzodiazepines

    Energy Technology Data Exchange (ETDEWEB)

    Bowling, A.C.

    1988-01-01

    Benzodiazepines bind to two well-characterized classes of nanomolar-affinity binding sites, the central and the peripheral types. Although these sites appear to mediate many of the effects of these compounds, they cannot account for all of the biochemical and physiologic effects of the benzodiazepines. In this investigation, a protein that is photolabeled by NO{sub 2}-containing benzodiazepines was identified and characterized in rat brain by performing photaffinity labeling experiments with ({sup 3}H)-clonazepam and ({sup 3}H)-flunitrazepam. These experiments demonstrate that this photolabeled protein has a molecular weight of 65,000 daltons. Photolabeling of the protein was saturable, inhibited in a stereoselective manner by benzodiazepine enantiomers, inhibited by therapeutically-relevant concentrations of many different NO{sub 2}-containing benzodiazepines, and was not inhibited by more than 70 non-benzodiazepine compounds. The photolabeled protein is distinct from the central and peripheral sites on the basis of molecular weight, benzodiazepine inhibitory potencies, subcellular localization, and tissue distribution.

  18. Benzodiazepine receptor antagonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy....

  19. Expression and clinical significance of NF-毷B, CTGF and OPN in mononuclear cells in peripheral blood as well as renal tissues in patients with IgA nephropathy

    Directory of Open Access Journals (Sweden)

    Cheng-Luo Hao

    2016-06-01

    Full Text Available Objective: To study the expression and clinical significance of NF-kB, CTGF and OPN in mononuclear cells in peripheral blood as well as renal tissues in patients with IgA nephropathy. Methods: A total of 25 nephropathy patients diagnosed with IgA nephropathy and 25 patients receiving nephrectomy due to trauma or tumor in our hospital were studied. Peripheral blood and kidney tissues were collected to test NF-kB, CTGF, OPN, T-bet, GATA-3, RORγT and Foxp3 expressions. Results: CTGF and OPN percentages in peripheral blood mononuclear cells and kidney tissues of nephropathy patients were higher than those of the control group. NF-kB, CTGF and OPN expressions were significantly higher in M1, E1, S1 group patients’ peripheral blood mononuclear cells and renal tissues than those in M0, E1 and S1 group. T-bet, GATA-3 and RORγT expressions in nephropathy patients’ peripheral blood were significantly higher than those in the control group, and were positively correlated with NF-kB, CTGF and OPN expressions. The expression of Foxp3 was significantly lower than that of control group, and was negatively correlated with NF-kB, CTGF and OPN expressions. Conclusions: The expression of NF-kB, CTGF and OPN in peripheral blood mononuclear cells and renal tissue in patients with IgA nephropathy is abnormally high and can evaluate the prognosis of the disease and the differentiation of CD4+T cells.

  20. Determination of the bone-mineral content of the peripheral skeleton (ulna and calcaneus) in chronic renal failure patients on maintenance dialysis using 125 I-photon absorptiometry

    International Nuclear Information System (INIS)

    Hieber, U.

    1982-01-01

    The bone-mineral content (BMC) of the peripheral skeleton was measured in 53 chronic renal-failure patients on maintenance dialysis using the 125 I photon absorptiometry according to Cameron. 39.6% of the patients were found to have a clearly pathological calcium content in calcaneus and ulna (33%). In total BMC assessments 43.4% of the patients examined showed strongly reduced BMC values at two measurement sites at least. Average bone-mineral content was below the value of the corresponding normal groups in all age groups of the dialysis patients. In addition, a significant correlation was verified to exist between the calcium contents of calcaneus and ulna. A significant correlation was found as well between reduced BMC values and dialysis duration. The correlation between the increased serum level of alkaline phosphatase and the reduced mineral content of the skeleton was significant as well. A minor but not significant correlation existed between the increase of the parathormone (PTH) level in the serum and the decrease of calcium content in calcaneus and ulna. A good correlation was found when contrasting the results of visual roentgenography and the BMC values established by photodensitometry: the median BMC value of patients with clear pathological X-ray findings was significantly below the one of patients without pathological X-ray findings. However, photon absorptiometry is superior to the subjective evaluation of X-ray pictures in the early diagnosis of bone diseases involving bone-mineral loss. (orig.) [de

  1. Chronic use of benzodiazepines among older adults

    Directory of Open Access Journals (Sweden)

    Jussara Mendonça Alvarenga

    2014-12-01

    Full Text Available OBJECTIVE To analyze the perception of and motivation for the chronic use of benzodiazepine among older adults. METHODS A qualitative study was conducted on 22 older adults living in Bambuí, MG, Southeastern Brazil, who were taking benzodiazepines and had the clinical and cognitive ability to respond to interview questions. The collected data were analyzed on the basis of the “signs, meanings, and actions” model. RESULTS The main reasons pointed out for the use of benzodiazepines were “nervousness”, “sleep problems”, and “worry” due to family and financial problems, everyday problems, and existential difficulties. None of the interviewees said that they used benzodiazepines in a dose higher than that recommended or had been warned by health professionals about any risks of their continuous use. Different strategies were used to obtain the prescription for the medication, and any physician would prescribe it, indicating that a bond was established with the drug and not with the health professional or healthcare service. Obtaining and consuming the medication turned into a crucial issue because benzodiazepine assumes the status of an essential food, which leads users to not think but sleep. It causes a feeling of relief from their problems such as awareness of human finitude and fragility, existential difficulties, and family problems. CONCLUSIONS Benzodiazepine assumes the characteristics of polyvalence among older adults, which extrapolate specific clinical indications, and of essentiality to deal with life’s problems in old age. Although it relieves the “nerves”, the chronic use of benzodiazepines buffers suffering and prevents older adults from going through the suffering. This shows important difficulties in the organization and planning of strategies that are necessary for minimizing the chronic use in this population.

  2. Electrocardiographic Manifestations of Benzodiazepine Toxicity

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    Nahid Kazemzadeh

    2014-11-01

    Full Text Available Background: The aim of this study was to evaluate and compare the clinical and electrocardiographic (ECG manifestations of benzodiazepines (BZs. Methods: In this retrospective study, all BZ-poisoned patients hospitalized at Loghman Hakim Hospital between September 2010 and March 2011 were evaluated. Patients’ information including age, sex, time elapsed between the ingestion and presentation, and type of the BZ used were extracted from the patients' charts and recorded. ECGs on presentation to the emergency department (ED were evaluated and parameters such as PR interval, QRS duration, corrected QT, amplitude of S wave in lead I, height of R wave and R/S ratio in the lead aVR were also measured and recorded. Results: Oxazepam, chlordiazepoxide, lorazepam, alprazolam, diazepam, and clonazepam were ingested by 9 (3%, 13 (4.4%, 29 (9.9%, 105 (35.8%, 65 (22.2%, and 72 (24.6% patients, respectively. Mean PR interval was reported to be 0.16 ± 0.03 sec and PR interval of greater than 200 msec was detected in 12 (4.5% patients. Mean QRS duration was 0.07 ± 0.01sec and QRS≥120 msec was observed in 7 (2.6% cases. Conclusion: Diazepam is the only BZ that does not cause QRS widening and oxazepam is the only one not causing PR prolongation. It can be concluded that if a patient refers with a decreased level of consciousness and accompanying signs of BZ toxicity, QRS widening in ECG rules out diazepam, whereas PR prolongation rules out oxazepam toxicity.

  3. Are the effects of benzodiazepines on discrimination and punishment dissociable?

    Science.gov (United States)

    Hodges, H; Green, S

    1987-01-01

    Studies have shown that benzodiazepines (BZs) both disrupt discrimination and increase resistance to punishment. Using a delayed response task, we provide evidence that effects of BZs on discrimination cannot be fully explained by deficits in either short or long term memory, or by intolerance for delay of reward. A schedule with rewarded, nonrewarded (Time out: TO) and conflict components was used to investigate effects in rats of compounds active at the BZ receptor on successive discrimination and punished responding in parallel. The GABA transaminase inhibitor ethanolamine-O-sulphate exerted additive effects with chlordiazepoxide (CDP) on punished but not TO responding. Both GABA and CDP injected into the amygdala selectively increased conflict rates, but with peripheral treatment CDP also increased TO rates. Two inverse BZ agonists, CGS 8216 and FG 7142 antagonzied the anti-conflict effects of GABA and CDP, given within the amygdala or peripherally, but the increase in TO rates induced by systemic CDP was counteracted only by peripheral treatments. These compounds also reduced rates of conflict responding below baseline, consistent with anxiogenic activity. Effects of the BZ antagonist Ro 15-1788 were broadly similar to those of the inverse agonists, except that it did not antagonise the anti-conflict action of intra-amygdaloid GABA, nor significantly reduce punished responding at the single dose used. We conclude from these results that the anti-conflict effects of BZs are mediated by a GABAergic amygdaloid mechanism, but that the same mechanism is not involved in BZ effects on discrimination.

  4. Peripheral neuropathy

    Science.gov (United States)

    ... peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy; Chronic pain - peripheral neuropathy ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  5. Effect of long-term high-fat diet intake on peripheral insulin sensibility, blood pressure, and renal function in female rats

    Directory of Open Access Journals (Sweden)

    Noemi A. V. Roza

    2016-02-01

    Full Text Available Background: This study determines whether -week high-fat diet (HFD consumption alters insulin sensitivity, kidney function, and blood pressure (BP in female rats when compared with standard rodent diet (ND intake in gender- and age-matched rats. Methods: The present study investigates, in female Wistar HanUnib rats, the effect of long-term high-fat fed group (HFD compared with standard chow on BP by an indirect tail-cuff method using an electrosphygmomanometer, insulin and glucose function, and kidney function by creatinine and lithium clearances. Results: The current study shows glucose tolerance impairment, as demonstrated by increased fasting blood glucose (ND: ±2.8 vs. HFD: 87±3.8 mg/dL associated with reduced insulin secretion (ND: 0.58±0.07 vs. HFD: 0.40±0.03 ng/mL in 8-week female HFD-treated rats. The incremental area under the curve (AUC, ND: 1,4558.0±536.0 vs. HFD: 1,6507.8±661.9, homeostasis model assessment of insulin resistance (HOMA-IR index, and the first-order rate constant for the disappearance of glucose (Kitt were significantly enhanced in 8-week HFD-treated rats compared with age-matched ND group (respectively, P=0.03, P=0.002, and P<0.0001. The current study also shows a significantly higher systolic BP measured in 5 and 8 weeks posttreatment in HFD (5-week HFD-treated: 155.25±10.54 mmHg and 8-week HFD-treated: 165±5.8 mmHg (P=0.0001, when compared to BP values in 5-week ND, 137±4.24 mmHg and 8-week ND, 131.75±5.8 mmHg age-matched group. Otherwise, the glomerular filtration rate and renal sodium handling evaluated by FENa, FEPNa and FEPPNa, were unchanged in both groups. Conclusion: We may conclude that 8-week female HFD-fed rats compared with ND group stimulate harmful effects, such as BP rise and peripheral glucose intolerance. The increased BP occurs through insulin resistance and supposedly decreased vasodilatation response without any change on renal function.

  6. Effect of long-term high-fat diet intake on peripheral insulin sensibility, blood pressure, and renal function in female rats.

    Science.gov (United States)

    Roza, Noemi A V; Possignolo, Luiz F; Palanch, Adrianne C; Gontijo, José A R

    2016-01-01

    This study determines whether 8-week high-fat diet (HFD) consumption alters insulin sensitivity, kidney function, and blood pressure (BP) in female rats when compared with standard rodent diet (ND) intake in gender- and age-matched rats. The present study investigates, in female Wistar HanUnib rats, the effect of long-term high-fat fed group (HFD) compared with standard chow on BP by an indirect tail-cuff method using an electrosphygmomanometer, insulin and glucose function, and kidney function by creatinine and lithium clearances. The current study shows glucose tolerance impairment, as demonstrated by increased fasting blood glucose (ND: 78±2.8 vs. HFD: 87±3.8 mg/dL) associated with reduced insulin secretion (ND: 0.58±0.07 vs. HFD: 0.40±0.03 ng/mL) in 8-week female HFD-treated rats. The incremental area under the curve (AUC, ND: 1,4558.0±536.0 vs. HFD: 1,6507.8±661.9), homeostasis model assessment of insulin resistance (HOMA-IR) index, and the first-order rate constant for the disappearance of glucose (Kitt) were significantly enhanced in 8-week HFD-treated rats compared with age-matched ND group (respectively, P=0.03, P=0.002, and P<0.0001). The current study also shows a significantly higher systolic BP measured in 5 and 8 weeks posttreatment in HFD (5-week HFD-treated: 155.25±10.54 mmHg and 8-week HFD-treated: 165±5.8 mmHg) (P=0.0001), when compared to BP values in 5-week ND, 137±4.24 mmHg and 8-week ND, 131.75±5.8 mmHg age-matched group. Otherwise, the glomerular filtration rate and renal sodium handling evaluated by FENa, FEPNa and FEPPNa, were unchanged in both groups. We may conclude that 8-week female HFD-fed rats compared with ND group stimulate harmful effects, such as BP rise and peripheral glucose intolerance. The increased BP occurs through insulin resistance and supposedly decreased vasodilatation response without any change on renal function.

  7. Pharmacological evaluation of an [(123)I] labelled imidazopyridine-3-acetamide for the study of benzodiazepine receptors.

    Science.gov (United States)

    Mattner, Filomena; Mardon, Karine; Loc'h, Christian; Katsifis, Andrew

    2006-06-13

    In vitro binding of the iodinated imidazopyridine, N',N'-dimethyl-6-methyl-(4'-[(123)I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide [(123)I]IZOL to benzodiazepine binding sites on brain cortex, adrenal and kidney membranes is reported. Saturation experiments showed that [(123)I]IZOL, bound to a single class of binding site (n(H)=0.99) on adrenal and kidney mitochondrial membranes with a moderate affinity (K(d)=30 nM). The density of binding sites was 22+/-6 and 1.2+/-0.4 pmol/mg protein on adrenal and kidney membranes, respectively. No specific binding was observed in mitochondrial-synaptosomal membranes of brain cortex. In biodistribution studies in rats, the highest uptake of [(123)I]IZOL was found 30 min post injection in adrenals (7.5% ID/g), followed by heart, kidney, lung (1% ID/g) and brain (0.12% ID/g), consistent with the distribution of peripheral benzodiazepine binding sites. Pre-administration of unlabelled IZOL and the specific PBBS drugs, PK 11195 and Ro 5-4864 significantly reduced the uptake of [(123)I]IZOL by 30% (p<0.05) in olfactory bulbs and by 51-86% (p<0.01) in kidney, lungs, heart and adrenals, while it increased by 30% to 50% (p<0.01) in the rest of the brain and the blood. Diazepam, a mixed CBR-PBBS drug, inhibited the uptake in kidney, lungs, heart, adrenals and olfactory bulbs by 32% to 44% (p<0.01) but with no effect on brain uptake and in blood concentration. Flumazenil, a central benzodiazepine drug and haloperidol (dopamine antagonist/sigma receptor drug) displayed no effect in [(123)I]IZOL in peripheral organs and in the brain. [(123)I]IZOL may deserve further development for imaging selectively peripheral benzodiazepine binding sites.

  8. Synthesis of 3-Substituted 1,4-Benzodiazepin-2-ones

    Directory of Open Access Journals (Sweden)

    Kyungjin Kim

    1998-01-01

    Full Text Available The preparation of 3-substituted 1,4-benzodiazepines by benzodiazepine enolate alkylation has been explored. Employing this approach, multigram quantities of benzodiazepine 1 have been prepared for animal studies to evaluate a new approach for the treatment of the autoimmune disease systemic lupus erythematosus (SLE.

  9. Acute myocardial infarction with multiple coronary thromboses in a young addict of amphetamines and benzodiazepines

    Directory of Open Access Journals (Sweden)

    Mohammed A. Al Shehri

    2016-07-01

    Full Text Available A 35-year-old man of average build and a smoker, with a background of a psychiatric disorder, was brought by his neighbor to the emergency department after an hour of severe chest pain. Upon arrival at the hospital he had cardiac arrest, was resuscitated, and moved to the catheterization laboratory with inferior, posterior, and lateral myocardial infarction. Coronary angiography showed an unusual thrombosis in multiple coronary branches. Toxicology report showed high levels of amphetamines and benzodiazepines in the patient’s original blood sample. The patient was kept under ventilation for 18 days, with difficult recovery due to severe withdrawal manifestations, ventilation acquired pneumonia, and rhabdomyolysis inducing acute renal failure. The patient regained near normal left ventricular function after baseline severe regional and global dysfunction. We postulate a relationship between the use of amphetamines, potentiated by benzodiazepines, and occurrence of acute thrombosis of multiple major coronary arteries.

  10. The benzodiazepine withdrawal syndrome and its management.

    OpenAIRE

    Onyett, S R

    1989-01-01

    The literature on benzodiazepine dependence and withdrawal is reviewed with an emphasis on social and psychological considerations. The problems of when to prescribe, identifying withdrawal symptoms, effective communication with the patient, the structure of withdrawal programmes, and the use of drugs, psychological approaches and other services are discussed.

  11. Benzodiazepine Synthesis and Rapid Toxicity Assay

    Science.gov (United States)

    Fletcher, James T.; Boriraj, Grit

    2010-01-01

    A second-year organic chemistry laboratory experiment to introduce students to general concepts of medicinal chemistry is described. Within a single three-hour time window, students experience the synthesis of a biologically active small molecule and the assaying of its biological toxicity. Benzodiazepine rings are commonly found in antidepressant…

  12. Benzodiazepines: minder gebruiken is beter gebruiken

    NARCIS (Netherlands)

    Oei, T.T.; Loonen, A.J.M.

    1981-01-01

    The benzodiazepines take an important place in the treatment of anxiety and sleep-disorders. The pharmacokinetic, pharmacodynamic and therapeutic properties of these drugs are shortly dealt with, whereafter the development of tolerance and dependence is considered in more detail. The clinical

  13. Benzodiazepine maintenance for alcohol dependence: A case series

    Directory of Open Access Journals (Sweden)

    Shivanand Kattimani

    2017-01-01

    Full Text Available Alcohol addiction is a chronic relapsing syndrome. Benzodiazepines remain as the mainstay for detoxification, taking care of the acute withdrawal syndrome. There is fear of dependence and abuse of benzodiazepines on prolonged use. Here, we selectively interviewed ten cases who were on longer duration of benzodiazepines to elicit their potential perceived benefits, attitudes, and any adverse effect. Three patients experienced adverse effects. None of them had features of benzodiazepine dependence. We opine that in select cases, benzodiazepine use should persist beyond detox period, and its benefits continue beyond the acute withdrawal phase while monitoring their safety/adverse effects.

  14. Benzodiazepines for psychosis-induced aggression or agitation

    DEFF Research Database (Denmark)

    Zaman, Hadar; Sampson, Stephanie J; Beck, Alison Ls

    2017-01-01

    of global state, clearly more people receiving placebo showed no improvement in the medium term (one to 48 hours) (n = 102, 1 RCT, RR 0.62, 95% CI 0.40 to 0.97, very low quality evidence). Benzodiazepines versus antipsychoticsWhen compared with haloperidol, there was no observed effect for benzodiazepines...... improved when receiving benzodiazepines compared with olanzapine (n = 150, 1 RCT, RR 1.84, 95% CI 1.06 to 3.18, very low quality evidence). People receiving benzodiazepines were less likely to experience extrapyramidal effects in the medium term compared to people receiving haloperidol (n = 233, 6 RCTs, RR...... 0.13, 95% CI 0.04 to 0.41, low quality evidence).Benzodiazepines versus combined antipsychotics/antihistaminesWhen benzodiazepine was compared with combined antipsychotics/antihistamines (haloperidol plus promethazine), there was a higher risk of no improvement in people receiving benzodiazepines...

  15. Autoradiographic localization of benzodiazepine receptors in the rat kidney

    Energy Technology Data Exchange (ETDEWEB)

    Beaumont, K.; Healy, D.P.; Fanestil, D.D.

    1984-11-01

    The localization of benzodiazepine (BZD) receptors in the rat kidney was studied by autoradiography after in vitro labeling of kidney slices with flunitrazepam. The affinity, density, and rank order of displacement of (/sup 3/H)-flunitrazepam by several BZDs (RO 5-4864 > diazepam > clonazepam) demonstrated that binding was to BZD receptors of the peripheral type. In autoradiograms obtained with tritium-sensitive film, a high density of silver grains was obtained in the outer medulla, with lower densities in the cortex. Binding was absent from the inner medulla (papilla). In higher resolution autoradiograms obtained with an emulsion-coated cover slip procedure, silver grains were seen to be concentrated over a tubular element in both outer medulla and cortex, identifiable by morphology and distribution as the thick ascending limb of the loop of Henle and the distal convoluted tubule. The identity of the labeled tubules was confirmed by immunofluorescent localization in adjacent slices of Tamm-Horsfall protein, a specific marker for these segments of tubules. Investigation of the effects of peripherally specific BZDs such as RO 5-4864 on distal tubule function is indicated.

  16. (/sup 3/H)Clonazepam, like (/sup 3/H)flunitrazepam, is a photoaffinity label for the central type of benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Sieghart, W. (Vienna Univ. (Austria)); Moehler, H. (Hoffmann-La Roche (F.) and Co., Basel (Switzerland))

    1982-06-16

    (/sup 3/H)Clonazepam, like (/sup 3/H)flunitrazepam, is irreversibly bound to membrane proteins of brain tissue when exposed to UV light. In polyacrylamide gel electrophoresis followed by fluorography, the same pattern of photolabelled proteins was obtained in cerebellum and in hippocampus when either (/sup 3/H)clonazepam or (/sup 3/H)flunitrazepam was used as photoaffinity label. Since (/sup 3/H)clonazepam does not interact with the peripheral type of benzodiazepine binding site present in the brain, these results confirm previous evidence that the proteins photolabelled with (/sup 3/H)flunitrazepam are associated with the central type of benzodiazepine receptor.

  17. Benzodiazepine receptor ligand influences on learning: an endogenous modulatory mechanism mediated by benzodiazepines possibly of alimentary origin

    Directory of Open Access Journals (Sweden)

    I. Izquierdo

    1991-01-01

    Full Text Available In rats pre-but not post-training ip administration of either flumazenil, a central benzodiazepine (BSD receptor antagonist, or of n-butyl-B-carboline-carboxylate (BCCB, an inverse agonist, enhanced retention of inhibitory avoidance learning. Flumazenil vlocked the enhancing effect of BCCB, and the inhibitory effect of the BZD agonists clonazepam and diazepam also given pre-training. Post-training administration of these drugs had no effects. The peripheral BZD receptor agonist/chloride channel blocker Ro5-4864 had no effect on the inhibitory avoidance task when given ip prior to training, buth it caused enhancement when given immediately post-training either ip or icv. This effect was blocked by PK11195, a competitive antagonist of Ro5-4864. These results suggest that ther is an endogenous mechanism mediated by BZD agonists, which is sensitive to inverse agonists and that normally down-regulates the formation of memories through a mechanism involving GABA-A receptors and the corresponding chloride channels. The most likely agonists for the endogenous mechanism suggested are the diazepam-like BZDs found in brain whose origin is possibly alimentary. Levels of these BZDs in the cortex were found to sharply decrease after inhibitory acoidance training or mere exposure to the training apparatus.

  18. Qualitative variation of photolabelled benzodiazepine receptors in different species.

    Science.gov (United States)

    Hebebrand, J; Friedl, W; Lentes, K U; Propping, P

    1986-01-01

    In order to examine whether species differences of benzodiazepine receptor subunits exist, we compared the fluorographic pattern of photoaffinity labelled subunits after SDS-PAGE in five species: fish, frog, chicken, mouse and calf. Each species showed a distinct pattern of specifically labelled proteins. We conclude that species variation of benzodiazepine receptor does indeed exist.

  19. Memory impairment in those who attempted suicide by benzodiazepine overdose

    NARCIS (Netherlands)

    Verwey, B.; Eling, P.A.T.M.; Wientjes, H.J.F.M.; Zitman, F.G.

    2000-01-01

    Backgroud: a prospective study was done to investigate the presence of anterograde amnesia in suicide attempters who took benzodiazepines (BZ) and to study the correlation with sedation. Method: in 43 patients, who attempted suicide by taking benzodiazepines, memory perfomrance was tested on a

  20. Flumazenil in treatment benzodiazepine withdrawal syndrome: Case report

    Directory of Open Access Journals (Sweden)

    Ramah Aleksandar J.

    2015-01-01

    Full Text Available Background: Today in the world and in Serbia is growing number of people who are addicted to benzodiazepine. A particular problem is the process of detoxification and treatment of benzodiazepine withdrawal syndrome due to a recurrence of symptoms of anxiety disorder, availability of benzodiazepines, falling motivation. Standard procedures have often proved unsuccessful and the last decade, and the search for new protocols, including the flumazenil, benzodiazepine receptor antagonist, is actualized. Case report: The patient aged 48 years was admitted to the specialist psychiatric clinic, for treatment of benzodiazepine addiction. Anxiety disorder was diagnosed since adolescence perennial addiction on benzodiazepines and the initial withdrawal syndrome. Former motivated topical treatments for detoxification were unsuccessful. The presence of dual diagnosis, persistence of both disorders in perennial cycle, treatment resistance and actual motivation contributed to the decision to opt rapid detoxification from benzodiazepines by flumazenil application protocol, for hospital treatment by adjuvant therapy with lamotrigine. After discharge from hospital in stable condition it was with no signs of withdrawal syndrome and a rebound of anxiety symptoms. Lamotrigine medication continued including CBT, held during the one-year abstinence monitoring, with sufficient social functionality. Discussion: The efficacy and safety of flumazenil in the treatment of benzodiazepine withdrawal syndrome was investigated in numerous clinical trials, and the mechanism of action is complex, from the benzodiazepine antagonist to inverse agonist in certain circumstances, as well as 'up-regulation' receptors, which together leads to a reduction in symptoms of abstinence syndrome and anxiety in the longer term after treatment, thereby acting favorably to the adherence and remission. Conclusions: Flumazenil protocol is an efficient method in the treatment of the benzodiazepine

  1. Fluorescent-labeled ligands for the benzodiazepine receptor - Part 1 : Synthesis and characterization of fluorescent-labeled benzodiazepines

    NARCIS (Netherlands)

    Janssen, M.J; Hulst, A.J R L; Kellogg, R.M; Hendriks, M.M W B; Ensing, K; de Zeeuw, R.A

    Because radioactive labeled ligands in receptor assays have several disadvantages, we synthesized a number of fluorescent-labeled benzodiazepines. Several fluorophores were attached at different positions of 1,4-benzodiazepine molecules in order to assess the impact of the fluorophores and their

  2. The impact of benzodiazepine use on methadone maintenance treatment outcomes.

    Science.gov (United States)

    Brands, Bruna; Blake, Joan; Marsh, David C; Sproule, Beth; Jeyapalan, Renuka; Li, Selina

    2008-01-01

    The purposes of this study were to examine predictors of benzodiazepine use among methadone maintenance treatment patients, to determine whether baseline benzodiazepine use influenced ongoing use during methadone maintenance treatment, and to assess the effect of ongoing benzodiazepine use on treatment outcomes (i.e., opioid and cocaine use and treatment retention). A retrospective chart review of 172 methadone maintenance treatment patients (mean age = 34.6 years; standard deviation = 8.5 years; 64% male) from January 1997 to December 1999 was conducted. At baseline, 29% were "non-users" (past year) of benzodiazepine, 36% were "occasional users," and 35% were "regular/problem users." Regular/problem users were more likely to have started opioid use with prescription opioids, experienced more overdoses, and reported psychiatric comorbidity. Being female, more years of opioid use, and a history of psychiatric treatment were significant predictors of baseline benzodiazepine use. Ongoing benzodiazepine users were more likely to have opioid-positive and cocaine-positive urine screens during methadone maintenance treatment. Only ongoing cocaine use was negatively related to retention. Benzodiazepine use by methadone maintenance treatment patients is associated with a more complex clinical picture and may negatively influence treatment outcomes.

  3. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    International Nuclear Information System (INIS)

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-01-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of [ 3 H]Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in [14C]iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress [an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures], although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results

  4. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  5. Disability pension as predictor of later use of benzodiazepines among benzodiazepine users

    OpenAIRE

    Hartz, Ingeborg; Tverdal, Aage; Skille, Eivind Å.; Skurtveit, Svetlana

    2010-01-01

    The original publication is available at: http://dx.doi.org/10.1016/j.socscimed.2009.11.015 The proportion of Norwegians on disability pensions has doubled since the 1980s. The Norwegian Government wants action to stimulate the working capacity in those disability pensioners who have the potential to work. Information on factors that may impair rehabilitation efforts, including the unfavourable use of benzodiazepines, may be useful in this context. A longitudinal design, including data on ...

  6. Analytical methodologies for the determination of benzodiazepines in biological samples.

    Science.gov (United States)

    Persona, Karolina; Madej, Katarzyna; Knihnicki, Paweł; Piekoszewski, Wojciech

    2015-09-10

    Benzodiazepine drugs belong to important and most widely used medicaments. They demonstrate such therapeutic properties as anxiolytic, sedative, somnifacient, anticonvulsant, diastolic and muscle relaxant effects. However, despite the fact that benzodiazepines possess high therapeutic index and are considered to be relatively safe, their use can be dangerous when: (1) co-administered with alcohol, (2) co-administered with other medicaments like sedatives, antidepressants, neuroleptics or morphine like substances, (3) driving under their influence, (4) using benzodiazepines non-therapeutically as drugs of abuse or in drug-facilitated crimes. For these reasons benzodiazepines are still studied and determined in a variety of biological materials. In this article, sample preparation techniques which have been applied in analysis of benzodiazepine drugs in biological samples have been reviewed and presented. The next part of the article is focused on a review of analytical methods which have been employed for pharmacological, toxicological or forensic study of this group of drugs in the biological matrices. The review was preceded by a description of the physicochemical properties of the selected benzodiazepines and two, very often coexisting in the same analyzed samples, sedative-hypnotic drugs. Copyright © 2015. Published by Elsevier B.V.

  7. Association of peripheral NK cell counts with Helios+ IFN-γ- Tregs in patients with good long-term renal allograft function.

    Science.gov (United States)

    Trojan, K; Zhu, L; Aly, M; Weimer, R; Bulut, N; Morath, C; Opelz, G; Daniel, V

    2017-06-01

    Little is known about a possible interaction of natural killer (NK) cells with regulatory T cells (T reg ) in long-term stable kidney transplant recipients. Absolute counts of lymphocyte and T reg subsets were studied in whole blood samples of 136 long-term stable renal transplant recipients and 52 healthy controls using eight-colour fluorescence flow cytometry. Patients were 1946 ± 2201 days (153-10 268 days) post-transplant and showed a serum creatinine of 1·7 ± 0·7 mg/dl. Renal transplant recipients investigated > 1·5 years post-transplant showed higher total NK cell counts than recipients studied express the phenotype Helios + interferon (IFN)-γ - and appear to have stable FoxP3 expression and originate from the thymus. Furthermore, high total NK cells were associated with T reg that co-express the phenotypes interleukin (IL)-10 - transforming growth factor (TGF)-β + (P = 0·013), CD183 + CD62L - (P = 0·003), CD183 + CD62 + (P = 0·001), CD183 - CD62L + (P = 0·002), CD252 - CD152 + (P term good allograft function and the statistical association of these two lymphocyte subsets with each other suggest a direct or indirect (via DC) interaction of these cell subpopulations that contributes to good long-term allograft acceptance. Moreover, we speculate that regulatory NK cells are formed late post-transplant that are able to inhibit graft-reactive effector cells. © 2017 British Society for Immunology.

  8. Benzodiazepines II: Waking Up on Sedatives: Providing Optimal Care When Inheriting Benzodiazepine Prescriptions in Transfer Patients

    Directory of Open Access Journals (Sweden)

    Jeffrey Guina

    2018-01-01

    Full Text Available This review discusses risks, benefits, and alternatives in patients already taking benzodiazepines when care transfers to a new clinician. Prescribers have the decision—sometimes mutually agreed-upon and sometimes unilateral—to continue, discontinue, or change treatment. This decision should be made based on evidence-based indications (conditions and timeframes, comorbidities, potential drug-drug interactions, and evidence of adverse effects, misuse, abuse, dependence, or diversion. We discuss management tools involved in continuation (e.g., monitoring symptoms, laboratory testing, prescribing contracts, state prescription databases, stages of change and discontinuation (e.g., tapering, psychotherapeutic interventions, education, handouts, reassurance, medications to assist with discontinuation, and alternative treatments.

  9. 1,4-Benzodiazepine N-Nitrosoamidines: Useful Intermediates in the Synthesis of Tricyclic Benzodiazepines

    Directory of Open Access Journals (Sweden)

    Carlos del Pozo

    2006-08-01

    Full Text Available 1,4-Benzodiazepine N-nitrosoamidines have been used as scaffolds for the preparation of different tricyclic derivatives. Replacement of the N-nitrosoamidine moiety through treatment with the nucleophiles acetylhydrazine, aminoacetaldehyde dimethylacetal and 1-amino-2-propanol, followed by an acid-catalyzed cyclization step, afforded triazolo and imidazobenzodiazepines 1, 6, and 7, respectively, in good yields. When acetylhydrazine is used as a nucleophile, the overall process provides an alternative route to alprazolam (1b and triazolam (1c, respectively.

  10. Benzodiazepines - Their role in aggression and why GPs should prescribe with caution.

    Science.gov (United States)

    Jones, Katy A; Nielsen, Suzanne; Bruno, Raimondo; Frei, Matthew; Lubman, Dan I

    2011-11-01

    Benzodiazepines are widely prescribed in Australia, despite concerns about their potential for abuse and dependence. Paradoxical reactions, disinhibition and amnesia are all associated with benzodiazepine use, misuse and intoxication. While violent and aggressive behaviour may be a consequence of such disinhibition, there is limited information available regarding the links between benzodiazepine use and violence. This article aims to examine the existing evidence on the relationship between benzodiazepines, violence and aggression. While current evidence suggests that benzodiazepines rarely induce violence, it is important to note that the available literature is limited in its scope and that benzodiazepine related violence is often severe and of potential concern to frontline workers. Mediating risk factors for benzodiazepine related violence include concurrent alcohol use, benzodiazepine dose, a history of aggression and underlying impulsivity. Comprehensive assessment and alternate nonpharmacological treatment options should be considered before prescribing benzodiazepines within primary care.

  11. Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

    DEFF Research Database (Denmark)

    Donskov, F; Bennedsgaard, K M; Von Der Maase, H

    2002-01-01

    The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty...... response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 (P=0.027), CD8 (P=0.028), CD57 (P=0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 (P=0.026), CD8 (P=0...... of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients....

  12. AHR-11797: a novel benzodiazepine antagonist

    International Nuclear Information System (INIS)

    Johnson, D.N.; Kilpatrick, B.F.; Hannaman, P.K.

    1986-01-01

    AHR-11797(5,6-dihydro-6-methyl-1-phenyl- 3 H-pyrrolo[3,2,1-ij]quinazolin-3-one) displaced 3 H-flunitrazepam (IC 50 = 82 nM) and 3 H-Ro 15-1877 (IC 50 = 104 nM) from rat brain synaptosomes. AHR-11797 did not protect mice from seizures induced by maximal electroshock or subcutaneous Metrazol (scMET), nor did it induce seizures in doses up to the lethal dose. However, at 31.6 mg/kg, IP, it significantly increased the anticonvulsant ED 50 of chlordiazepoxide (CDPX) from 1.9 to 31.6 mg/kg, IP. With 56.7 mg/kg, IP, of AHR-11797, CDPX was inactive in doses up to 100 mg/kg, IP. AHR-11797 did not significantly increase punished responding in the Geller and Seifter conflict procedure, but it did attenuate the effects of diazepam. Although the compound is without anticonvulsant or anxiolytic activity, it did have muscle relaxant properties. AHR-11797 blocked morphine-induced Straub tail in mice (ED 50 = 31 mg/kg, IP) and it selectively suppressed the polysnaptic linguomandibular reflex in barbiturate-anesthetized cats. The apparent muscle relaxant activity of AHR-11797 suggests that different receptor sites are involved for muscle relaxant vs. anxiolytic/anticonvulsant activities of the benzodiazepines

  13. Benzodiazepine use in general population, the municipality of Berane, Montenegro

    Directory of Open Access Journals (Sweden)

    Šoškić Miomir

    2016-01-01

    Full Text Available Background: Benzodiazepines can be classified as one of the most frequently prescribed categories of medication. This medication category is distinguished by a high risk of tolerance and dependence, in the case of long-term, excessive use. Aim: The aim of our study was to analyse the use of benzodiazepines in the general population, municipality of Berane, Montenegro, during the previous year. Methods: Research was based on the analysis of 1000 prescriptions of benzodiazepines, issued by physicians in Primary Health Care. The diagnostic manual utilised for the purpose of this research was International Classification of Diseases (ICD-10. The survey was conducted for a period of 40 days during January and February 2015. Results: The study was performed in the general population, age from 18 to 98 years (621 females and 379 males. The average age of all participants in the study was 64.1±13.1 years. Analysis of data confirmed that the most frequently prescribed from the group of benzodiazepines were: diazepam (42.2%, bromazepam (30.3%, lorazepam (16.4%, alprazolam (6.4%, nitrazepam (2.6% and clonazepam (2.1%. The significant statistical difference (x2=58.664; p<0.001 was found between female patients who used benzodiazepines in 62.1% of cases, compared to male patients who used benzodiazepines in 37.9% of cases. It was confirmed that benzodiazepines were usually prescribed for 17 different diagnoses, mostly for diagnoses from the group I, viz. cluster-diseases of the circulatory system (39.7%, group F-mental and behavioural disorders (31.1% and group E-endocrine, nutritional and metabolic diseases (7.7%. Conclusion: Studies about drug utilisation provide plenty of useful information which can be further used with the aim of achieving more rational prescribing and more effective patient treating.

  14. [Can one talk of benzodiazepine "drunkenness"? About acute benzodiazepine intoxication, without suicidal or mortiferous tendencies].

    Science.gov (United States)

    Menecier, P; Texier, M A; Las, R; Ploton, L

    2012-02-01

    When we refer to "drunkenness", more often than not, we think of alcohol or cannabis being the instigator rather than pharmacological drugs, even if outside the toxic origins, "drunkenness" may also occur without any substance intake: one can be drunk on love, poetry, music and even mania. Benzodiazepine "drunkenness" is not a classical notion in medicine. But the concept of addictology allows one to enlarge different approaches and to consider the relationship with psychoactive substances according to the same references. So, in a single fashion, between use and misuse, is it possible to resort to the same concepts for pharmacological drugs, including "drunkenness"? Any intake of a psychoactive substance, limited in time, which will take the consumer some time to recover from, can be called simple use, intoxication or drunkenness. Intoxication is rather a classical medical concept linked with poisoning, and hence the toxicological aspects prevail particularly through the concept of a toxidrome. However, little research has been done on "drunkenness" in other medical aspects, neither psychological aspects nor sociological aspects. If poisoning is defined as soon as a poison is introduced into the body, the intoxication arises after a threshold (that toxicology usually defines), but no means are available to measure the onset of the inebriation, neither any ingested amounts nor any toxic concentration in the body. It is hard to define "drunkenness" simply. At first, it is most often seen as a pathology in medicine, unlike in every day life. "Drunkenness" can be the result of physiological disturbances, notably through the effects of substances and can therefore be the manifestation of a cerebral dysfunction. Alternatively, it can arise from a variation of emotional or sensorial stimuli. If the feelings associated with drunkenness are positive and pleasant a repetition will occur in the search to reproduce enjoyable effects in reference to neurophysiological models

  15. CT findings of renal abscess

    International Nuclear Information System (INIS)

    Lee, Myung Jun; Kim, Mi Young; Woo, Jung Ju; Kim, Ho Kyun; Kim, Won Hong; Jeon, Jeong Dong; Jeon, Woo Ki; Han, Chang Yul

    1996-01-01

    The purpose of this study is to determine characteristic CT findings in renal abscess. Twenty cases of renal abscess were retrospectively analyzed for CT findings relating to the shape and extent of the abscess, change of nephrogram, peripheral rim enhancement, wedge-shaped enhancement on delayed scans, enlargement of the kidney involved and associated findings. Seven patients had a renal abscess at the right kidney, nine at the lift kidney and two bilaterally. The abscesses were round in 18 cases and finger-like in two. Rim enhancement around renal abscess was seen in four cases (20%). Changes in the nephrogram around the abscess were seen in 12 cases (60%). In all six patients who had undergone delayed postcontrast scans, wedge-shaped enhancement was shown around the abscess (100%). In the observation of the extent of renal abscesses, 14 cases were within the kidney, six cases extended the beyond renal capsule, and two were loculated in the renal fascia itself. Renal enlargement was seen in nine cases (45%). These results suggest that CT findings such as delayed wedge-shaped enhancement, change of nephrogram, peripheral rim enhancement, renal enlargement, and associated findings are valuable for diagnosis, and that CT also gives information concerning the extent, evolution and complication of a renal abscess

  16. Benzodiazepines, opioids and driving: an overview of the experimental research.

    Science.gov (United States)

    Leung, Stefanie Y

    2011-05-01

    Road crashes contribute significantly to the total burden of injury in Australia, with the risk of injury being associated with the presence of drugs and/or alcohol in the driver's blood. Increasingly, some of the most commonly detected drugs include prescription medicines, the most notable of these being benzodiazepines and opioids. However, there is a paucity of experimental research into the effects of prescribed psychoactive drugs on driving behaviours. This paper provides an overview of experimental studies investigating the effects of prescribed doses of benzodiazepines and opioids on driving ability, and points to future directions for research. There is growing epidemiological evidence linking the therapeutic use of benzodiazepines and opioids to an increased crash risk. However, the current experimental literature remains unclear. Limitations to study methodologies have resulted in inconsistent findings. Limited experimental evidence exists to inform policy and guidelines regarding fitness-to-drive for patients taking prescribed benzodiazepines and opioids. Further experimental research is required to elucidate the effects of these medications on driving, under varying conditions and in different medical contexts. This will ensure that doctors prescribing benzodiazepines and opioids are well informed, and can appropriately advise patients of the risks associated with driving whilst taking these medications. © 2011 Australasian Professional Society on Alcohol and other Drugs.

  17. Takotsubo Cardiomyopathy and Catatonia in the Setting of Benzodiazepine Withdrawal

    Directory of Open Access Journals (Sweden)

    Teng J. Peng

    2016-01-01

    Full Text Available We report two serious and unusual complications of benzodiazepine withdrawal in a single patient: takotsubo cardiomyopathy and catatonia. This 61-year-old female patient was brought to the emergency department with lethargy and within hours had declined into a state of catatonia. Although there was never a complaint of chest pain, ECG showed deep anterior T-wave inversions and cardiac enzymes were elevated. An echocardiogram was consistent with takotsubo cardiomyopathy. She later received 1 mg of midazolam and within minutes had resolution of catatonic symptoms. Careful history revealed that she had omitted her daily dose of lorazepam for 3 days prior to admission. To our knowledge, the case presented herein is the first report of simultaneous catatonia and takotsubo cardiomyopathy in the setting of benzodiazepine withdrawal. The pathogenesis of both conditions is poorly understood but may be indirectly related to the sudden decrease in γ-aminobutyric acid (GABA signaling during benzodiazepine withdrawal.

  18. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment

    DEFF Research Database (Denmark)

    Askgaard, Gro; Hallas, Jesper; Fink-Jensen, Anders

    2016-01-01

    BACKGROUND: Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option......, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. METHODS: The study was a register-based cohort study of patients admitted for alcohol...... withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. RESULTS: A total...

  19. Metabolism of anxiolytics and hypnotics: benzodiazepines, buspirone, zoplicone, and zolpidem.

    Science.gov (United States)

    Chouinard, G; Lefko-Singh, K; Teboul, E

    1999-08-01

    1. The benzodiazepines are among the most frequently prescribed of all drugs and have been used for their anxiolytic, anticonvulsant, and sedative/hypnotic properties. Since absorption rates, volumes of distribution, and elimination rates differ greatly among the benzodiazepine derivatives, each benzodiazepine has a unique plasma concentration curve. Although the time to peak plasma levels provides a rough guide, it is not equivalent to the time to clinical onset of effect. The importance of alpha and beta half-lives in the actions of benzodiazepines is discussed. 2. The role of cytochrome P450 isozymes in the metabolism of benzodiazepines and in potential pharmacokinetic interactions between the benzodiazepines and other coadministered drugs is discussed. 3. Buspirone, an anxiolytic with minimal sedative effects, undergoes extensive metabolism, with hydroxylation and dealkylation being the major pathways. Pharmacokinetic interactions of buspirone with other coadministered drugs seem to be minimal. 4. Zopiclone and zolpidem are used primarily as hypnotics. Both are extensively metabolized; N-demethylation, N-oxidation, and decarboxylation of zopiclone occur, and zolpidem undergoes oxidation of methyl groups and hydroxylation of a position on the imidazolepyridine ring system. Zopiclone has a chiral centre, and demonstrates stereoselective pharmacokinetics. Metabolic drug-drug interactions have been reported with zopiclone and erythromycin, trimipramine, and carbamazepine. Reports to date indicate minimal interactions of zolpidem with coadministered drugs; however, it has been reported to affect the Cmax and clearance of chlorpromazepine and to decrease metabolism of the antiviral agent ritonavin. Since CYP3A4 has been reported to play an important role in metabolism of zolpidem, possible interactions with drugs which are substrates and/or inhibitors of that CYP isozyme should be considered.

  20. Peripheral reactions

    International Nuclear Information System (INIS)

    Greiner, D.

    1978-01-01

    Peripheral collisions, that is, collisions involving a small amount of overlap of nuclear matter, are discussed including inclusive interactions, the magnitude of the peripheral cross section, fragmentation, a compilation of experiments and available data, limiting fragmentation, factorization, some models, fragment momentum distributions, and future research directions

  1. Prospective cohort study into post-disaster benzodiazepine use demonstrated only short-term increase.

    NARCIS (Netherlands)

    Dorn, T.; Yzermans, C.J.; Zee, J. van der

    2007-01-01

    OBJECTIVES: Benzodiazepines are typically prescribed for anxiety and insomnia, two complaints often reported after disasters. Benzodiazepines can cause mental or physical dependence, especially when taken for a long time. This study aims at evaluating benzodiazepine use in a disaster-stricken

  2. Bromine-75-labeled 1,4-benzodiazepines: potential agents for the mapping of benzodiazepine receptors in vivo: concise communication

    Energy Technology Data Exchange (ETDEWEB)

    Scholl, H.; Kloster, G.; Stoecklin, G.

    1983-05-01

    We have prepared four different 1,4-benzodiazepines, labeled at C-7 with the 1.6-hr positron emitter Br-75 or the 57-hr gamma emitter Br-77, as potential radio-pharmaceuticals for the mapping of cerebral benzodiazepine receptor areas. The triazene method was used and optimized. Yields at the no-carrier-added level were 20%. (7-/sup 75/Br)-5-(2-flophenyl)-1-methyl-1,3-dihydro-2H-1,4-benzodiazepine-2-one (Br-75 BFB) was isolated with a minimum specific activity of 20,000 Ci/mmole. Biodistribution in mice shows that BFB is taken up rapidly by the brain and is retained there at useful concentrations for significant periods of time. The maximum uptake is observed at 0.25 min. Brain-to-blood concentration ratios are larger than 2 during the interval (0.25 to 10 min) investigated.

  3. Oral Pre-anaesthetic Medication with a New Benzodiazepine Hypnotic

    African Journals Online (AJOL)

    A new benzodiazepine derivative (Ro 5-4200) was used as a hypnotic in a pilot study on 30 patients the night before an operation. The dosage used was 2 mg (1 tablet). Results proved very encouraging, and it was then decided to conduct a controlled double-blind trial comparing Ro 5-4200, phenobarbital 100 mg and a ...

  4. Oral Pre-anaesthetic Medication with a New Benzodiazepine Hypnotic

    African Journals Online (AJOL)

    1973-01-20

    Jan 20, 1973 ... A new benzodiazepine derivative (Ro 5-4200) was used as a hypnotic in a pilot study on 30 patients the night before an operation. The dosage used was 2 mg (1 tablet). Results proved very encouraging, and it was then decided to conduct a controlled double-blind trial com- paring Ro 5-4200, ...

  5. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Kjaergard, L L; Gluud, C

    2001-01-01

    The pathogenesis of hepatic encephalopathy is unknown. It has been suggested that liver failure leads to the accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition which may progress to coma. Several trials have assessed benzodiazepine receptor...

  6. Estimation of Cessation Rates among Danish Users of Benzodiazepines

    DEFF Research Database (Denmark)

    Støvring, Henrik; Gasse, Christiane

    Background: Widespread and longterm use of benzodiazepines constitute a public health problem. Health care authorities hence advice that use should not exceed three months, in particular for the elderly and patients with a past diagnosis of drug addiction. Objectives: Estimate the shape...

  7. Sex differences among recipients of benzodiazepines in Dutch general practice.

    NARCIS (Netherlands)

    Waals, F.W. van der; Mohrs, J.; Foets, M.

    1993-01-01

    Objective: To analyse sex differences among recipients of benzodiazepines in Dutch general practice. Design-Study of consultations and associated interventions as recorded in the Dutch national survey of general practice. Setting: Practices of 45 general practitioners monitored during 1 April to 30

  8. Phenylboronic acid catalysed synthesis of 1,5-benzodiazepines via ...

    Indian Academy of Sciences (India)

    Phenylboronic acid has been found to be an efficient catalyst for the synthesis of 1,5-benzodiazepine derivatives via cyclocondensation of -phenylenediamine and various ketones in good to excellent yields (82-91%) using acetonitrile as solvent at reflux condition. The remarkable advantages offered by this method are ...

  9. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Kjaergard, L L; Gluud, C

    2001-01-01

    The pathogenesis of hepatic encephalopathy is unknown. It has been suggested that liver failure leads to the accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition which may progress to coma. Several trials have assessed benzodiazepine receptor...... antagonists for hepatic encephalopathy, but the results are conflicting....

  10. Phenylboronic acid catalysed synthesis of 1,5-benzodiazepines via ...

    Indian Academy of Sciences (India)

    J. Chem. Sci. Vol. 125, No. 4, July 2013, pp. 745–749. c Indian Academy of Sciences. Phenylboronic acid catalysed synthesis of 1,5-benzodiazepines via cyclocondensation of ... active compounds and gaining great consideration in the field of .... thesis of this heterocycles was accomplished by con- densation reaction of ...

  11. [Benzodiazepin addiction: a silent addiction among older people].

    NARCIS (Netherlands)

    Oude Voshaar, R.C.

    2012-01-01

    Benzodiazepines are frequently prescribed for a longer period of time for anxiety disorders and insomnia in spite of the many guidelines to prescribe these drugs only short-term. These guidelines are based on the risk-benefit balance between long-term effectiveness and side effects like addiction,

  12. Treating acute seizures with benzodiazepines: does seizure duration matter?

    Science.gov (United States)

    Naylor, David E

    2014-10-01

    Several clinical trials have shown improved seizure control and outcome by early initiation of treatment with benzodiazepines, before arrival in the emergency department and before intravenous access can be established. Here, evidence is provided and reviewed for rapid treatment of acute seizures in order to avoid the development of benzodiazepine pharmacoresistance and the emergence of self-sustaining status epilepticus. Alterations in the physiology, pharmacology, and postsynaptic level of GABA-A receptors can develop within minutes to an hour and hinder the ability of synaptic inhibition to stop seizures while also impairing the efficacy of GABAergic agents, such as benzodiazepines, to boost impaired inhibition. In addition, heightened excitatory transmission further exacerbates the inhibitory/excitatory balance and makes seizure control even more resistant to treatment. The acute increase in the surface expression of NMDA receptors during prolonged seizures also may cause excitotoxic injury, cell death, and other pathological expressions and re-arrangements of receptor subunits that all contribute to long-term sequelae such as cognitive impairment and chronic epilepsy. In conclusion, a short window of opportunity exists when seizures are maximally controlled by first-line benzodiazepine treatment. After that, multiple pathological mechanisms quickly become engaged that make seizures increasingly more difficult to control with high risk for long-term harm.

  13. Psychological determinants of the intention to educate patients about benzodiazepines

    NARCIS (Netherlands)

    Ten Wolde, Geeske Brecht; Dijkstra, A.; Van Empelen, P.; Neven, A. Knuistingh; Zitman, F. G.

    Objective General practitioners and pharmacists do not properly educate their patients about the disadvantages of benzodiazepines. In order to increase and improve education, this study will investigate which psychological factors (i.e., beliefs, outcome expectation, social norm and self-efficacy)

  14. Micromolar-Affinity Benzodiazepine Receptors Regulate Voltage-Sensitive Calcium Channels in Nerve Terminal Preparations

    Science.gov (United States)

    Taft, William C.; Delorenzo, Robert J.

    1984-05-01

    Benzodiazepines in micromolar concentrations significantly inhibit depolarization-sensitive Ca2+ uptake in intact nerve-terminal preparations. Benzodiazepine inhibition of Ca2+ uptake is concentration dependent and stereospecific. Micromolar-affinity benzodiazepine receptors have been identified and characterized in brain membrane and shown to be distinct from nanomolar-affinity benzodiazepine receptors. Evidence is presented that micromolar, and not nanomolar, benzodiazepine binding sites mediate benzodiazepine inhibition of Ca2+ uptake. Irreversible binding to micromolar benzodiazepine binding sites also irreversibly blocked depolarization-dependent Ca2+ uptake in synaptosomes, indicating that these compounds may represent a useful marker for identifying the molecular components of Ca2+ channels in brain. Characterization of benzodiazepine inhibition of Ca2+ uptake demonstrates that these drugs function as Ca2+ channel antagonists, because benzodiazepines effectively blocked voltage-sensitive Ca2+ uptake inhibited by Mn2+, Co2+, verapamil, nitrendipine, and nimodipine. These results indicate that micromolar benzodiazepine binding sites regulate voltage-sensitive Ca2+ channels in brain membrane and suggest that some of the neuronal stabilizing effects of micromolar benzodiazepine receptors may be mediated by the regulation of Ca2+ conductance.

  15. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder

    DEFF Research Database (Denmark)

    Baandrup, Lone; Lindschou, Jane; Winkel, Per

    2016-01-01

    OBJECTIVES: We assessed if prolonged-release melatonin can facilitate withdrawal of long-term benzodiazepine usage in patients with schizophrenia or bipolar disorder. METHODS: Randomised, placebo-controlled, blinded, parallel superiority trial of 24 weeks duration. Participants were randomised...... to prolonged-release melatonin 2 mg daily versus matching placebo and were continuously guided to gradually reduce their usual benzodiazepine dosage. The primary outcome was mean benzodiazepine daily dosage at 24 weeks. Secondary outcomes included pattern of benzodiazepine dosage over time, benzodiazepine...... cessation proportion, and benzodiazepine withdrawal symptoms. RESULTS: In total, 86 patients (21-74 years) were enrolled: 42 were randomised to melatonin versus 44 to placebo. We found no significant effect of melatonin on mean benzodiazepine dosage at 24 weeks (melatonin group 8.01 mg versus placebo group...

  16. Phrenic neuropathy in chronic renal failure.

    OpenAIRE

    Zifko, U.; Auinger, M.; Albrecht, G.; Kästenbauer, T.; Lahrmann, H.; Grisold, W.; Wanke, T.

    1995-01-01

    BACKGROUND--Peripheral neuropathy and alterations in diaphragmatic muscle function are frequently caused by uraemia. Phrenic nerve function in patients with end stage renal failure, however, has not been examined to date. METHODS--An electrophysiological study of the phrenic nerve was performed to determine its possible involvement in 32 nondiabetic patients with end stage renal disease undergoing chronic haemodialysis. RESULTS--Seventeen patients had electrophysiological signs of peripheral ...

  17. Benzodiazepines: rat pinealocyte binding sites and augmentation of norepinephrine-stimulated N-acetyltransferase activity

    Energy Technology Data Exchange (ETDEWEB)

    Matthew, E.; Parfitt, A.G.; Sugden, D.; Engelhardt, D.L.; Zimmerman, E.A.; Klein, D.C.

    1984-02-01

    Studies of (/sup 3/H)diazepam binding to intact rat pineal cells were carried out in tissue culture preparations. The binding was saturable, reversible and proportional to the number of cells used. Scatchard analysis resulted in a linear plot (Kd . 23 nM, maximum binding sites (Bmax) . 1.56 pmol/mg of protein for cells in monolayer culture; Kd . 7 nM, Bmax . 1.3 pmol/mg of protein for cells in suspension culture). Inhibition constants (Ki) for clonazepam (500 nM), flunitrazepam (38 nM) and Ro-5-4864 (5 nM) indicated that the binding sites were probably of the ''peripheral'' type. In addition, the effects of diazepam on norepinephrine-stimulated N-acetyltransferase (NAT) activity were studied in organ culture and dissociated cell culture. Diazepam (10-50 microM) both prolonged and increased the magnitude of the norepinephrine-induced increase in NAT activity but did not affect the initial rate of rise of enzyme activity. The effect was dose-dependent and was also seen with clonazepam, flunitrazepam and Ro-5-4864, but not with Ro-15-1788. Diazepam, by itself, at these concentrations, had no effect on NAT, but enzyme activity was increased by higher concentrations (0.1-1 mM). Although a relationship between the (/sup 3/H)diazepam binding sites described here and the effect of benzodiazepines on NAT cannot be established from these studies, the data suggest that the benzodiazepines may alter melatonin levels through their action on NAT.

  18. Cross-validation, predictive validity, and time course of the Benzodiazepine Dependence Self-Report Questionnaire in a benzodiazepine discontinuation trial.

    NARCIS (Netherlands)

    Oude Voshaar, R.C.; Mol, A.J.J.; Gorgels, W.J.M.J.; Breteler, M.H.M.; Balkom, A.J.L.M. van; Lisdonk, E.H. van de; Kan, C.C.; Zitman, F.G.

    2003-01-01

    The Benzodiazepine Dependence Self-Report Questionnaire (Bendep-SRQ) measures the severity of benzodiazepine (BZ) dependence on four domains: awareness of problematic use, preoccupation with the availability of BZ, lack of compliance with the therapeutic regimen, and withdrawal. Although promising

  19. Cross-validation, predictive validity and time course of the Benzodiazepine Dependence Self-Report Questionnaire (Bendep-SRQ) in a benzodiazepine discontinuation trial

    NARCIS (Netherlands)

    Oude Voshaar, R.C.; Mol, A.J.J.; Gorgels, W.J.M.J.; Breteler, M.H.M.; Balkom, A.J.L.M. van; Lisdonk, E.H. van de; Zitman, F.G.

    2003-01-01

    The Benzodiazepine Dependence Self-Report Questionnaire (Bendep-SRQ) measures the severity of benzodiazepine (BZ) dependence on four domains: awareness of problematic use, preoccupation with the availability of BZ, lack of compliance with the therapeutic regimen, and withdrawal. Although promising

  20. Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: a comparison with the standard fixed dose benzodiazepine regimen.

    LENUS (Irish Health Repository)

    Cassidy, Eugene M

    2012-10-01

    The aim of the study was to compare symptom-triggered and standard benzodiazepine regimens for the treatment of alcohol withdrawal syndrome in an emergency department clinical decision unit. The authors found that the symptom-triggered approach reduced cumulative benzodiazepine dose and length of stay.

  1. [Embolization of a renal artery aneurysm. Effect of an ESWL?].

    Science.gov (United States)

    Bovenschulte, H

    2010-05-01

    The development of a peripheral aneurysm of the renal artery as a result of an ESWL is a rarely described complication. We discuss in the presented case the diagnosis and successful endovascular treatment of a complicated aneurysm of a renal segment artery with complete preservation of the renal parenchyma.

  2. Reducing Prescriptions of Long-acting Benzodiazepine Drugs in Denmark

    DEFF Research Database (Denmark)

    Eriksen, Sophie Isabel; Bjerrum, Lars

    2015-01-01

    Prolonged consumption of benzodiazepine drugs (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone; altogether Z drugs) is related to potential physiological and psychological dependence along with other adverse effects. This study aimed to analyse the prescribing of long...... to the prescription. The observed reduction in BZD use was correlated to the introduction of new national guidelines on prescription of addictive drugs, but this study was not designed to detect a causal relationship. The prescribing of long-acting BZD decreased considerably more than the prescribing of short......-acting BZD (half-life >10 hr), compared to short-acting BZD in Denmark during a 10-year period. Descriptive analysis of total sales data from the Danish Register of Medicinal Product Statistics, to individuals in the primary healthcare sector, of all BZD and Z-drugs in the period of 2003-2013. Prescription...

  3. Rectal benzodiazepines for premedication in children. Review and personal experience.

    Science.gov (United States)

    Govaerts, M J; Capouet, V

    1987-01-01

    Modern anesthetic techniques have modified the aims of premedication in pediatric practice. Anxiolysis, amnesia and easiness of induction are now the the main targets. This paper reviews both the literature and the personal experience of the authors on the subject. Many authors now prefer a benzodiazepine. Rectal instillation of benzodiazepine in solution avoids the trauma of the intramuscular route and produces a faster and more predictable effect, than suppositories. Diazepam (.1 to .2 mg/kg) and flunitrazepam (40 to 80 micrograms/kg) have been extensively used in this indication. Diazepam's duration of elimination being much longer than that of flunitrazepam, this last drug is preferred by many pediatric anesthetists. Midazolam (.4 to .5 mg/kg) has a much faster onset and shorter duration of action. It should thus be preferred if the environment enables the administration of premedication within 10 to 15 minutes of induction.

  4. Electronic and conformational properties of 2,3-benzodiazepine derivates

    International Nuclear Information System (INIS)

    Pelaggi, M.; Girlanda, R.; Chimirri, A.; Gitto, R.

    1996-01-01

    The molecular geometric and electronic structures of 2,3-benzodiazepine derivates have been studied by means of the MNDO-PM3 method. A number of electronic properties have been computed and examined in order to find indication of the role of the electronic characteristics of the different molecules and their pharmacological properties. Theoretical data indicate that both electronic and structural properties appear responsible for the varying degree of anticonvulsant activity exhibited by compounds 1-4

  5. Electronic and conformational properties of 2,3-benzodiazepine derivates

    Energy Technology Data Exchange (ETDEWEB)

    Pelaggi, M.; Girlanda, R. [Messina Univ. (Italy). Dip. di Fisica della Materia e Fisica dell`Ambiente; Chimirri, A.; Gitto, R. [Messina Univ. (Italy). Dip. Farmaco-Chimico

    1996-04-01

    The molecular geometric and electronic structures of 2,3-benzodiazepine derivates have been studied by means of the MNDO-PM3 method. A number of electronic properties have been computed and examined in order to find indication of the role of the electronic characteristics of the different molecules and their pharmacological properties. Theoretical data indicate that both electronic and structural properties appear responsible for the varying degree of anticonvulsant activity exhibited by compounds 1-4.

  6. Visualization of specific binding sites of benzodiazepine in human brain

    International Nuclear Information System (INIS)

    Shinotoh, H.; Yamasaki, T.; Inoue, O.; Itoh, T.; Suzuki, K.; Hashimoto, K.; Tateno, Y.; Ikehira, H.

    1986-01-01

    Using 11C-labeled Ro15-1788 and positron emission tomography, studies of benzodiazepine binding sites in the human brain were performed on four normal volunteers. Rapid and high accumulation of 11C activity was observed in the brain after i.v. injection of [11C]Ro15-1788, the maximum of which was within 12 min. Initial distribution of 11C activity in the brain was similar to the distribution of the normal cerebral blood flow. Ten minutes after injection, however, a high uptake of 11C activity was observed in the cerebral cortex and moderate uptake was seen in the cerebellar cortex, the basal ganglia, and the thalamus. The accumulation of 11C activity was low in the brain stem. This distribution of 11C activity was approximately parallel to the known distribution of benzodiazepine receptors. Saturation experiments were performed on four volunteers with oral administration of 0.3-1.8 mg/kg of cold Ro15-1788 prior to injection. Initial distribution of 11C activity following injection peaked within 2 min and then the accumulation of 11C activity decreased rapidly and remarkably throughout the brain. The results indicated that [11C] Ro15-1788 associates and dissociates to specific and nonspecific binding sites rapidly and has a high ratio of specific receptor binding to nonspecific binding in vivo. Carbon-11 Ro15-1788 is a suitable radioligand for the study of benzodiazepine receptors in vivo in humans

  7. Renal Osteodystrophy

    Directory of Open Access Journals (Sweden)

    Aynur Metin Terzibaşoğlu

    2004-12-01

    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  8. Is Peripheral Benzodiazepine Receptor (PBR) Gene Expression Involved in Breast Cancer Suppression by Dietary Soybean Protein?

    National Research Council Canada - National Science Library

    Das, Salil

    2006-01-01

    .... It has been established that women in Asian countries consume more soy protein than women in the United States and that the incidence of breast cancer in women in Asian countries is generally lower...

  9. Is Peripheral Benzodiazepine Receptor (PBR) Gene Expression Involved in Breast Cancer Suppression by Dietary Soybean Protein

    National Research Council Canada - National Science Library

    Das, Salil

    2004-01-01

    ...% casein and those of groups 3 and 4 received same diet containing 20% soybean protein. Animals of groups 2 and 4 received DMBA in sesame oil by gavage (15 mg per animal). Control animals (groups 1 and 3...

  10. Atuoradiographic detection of multiple sclerosis plaques with an ω3 (peripheral type benzodiazepine) binding site radiogland

    International Nuclear Information System (INIS)

    HAUW, J.J.; Sazdovitch, V.; Cornu, P.; Dubois, A.; Benavides, J.; Mac Kenzie, E.; Scatton, B.

    1989-01-01

    In Multiple Sclerosis (MS), the presence of monocyte-macrophages and microglial cells in active plaques is a constant feature. They are numerous at the border of active lesions where they constiture, with other cell types such as lymphocytes and oligodendrocytes the so-called flial wall. Monocyte-macrophages and microglial cells are thought to be directly involved in the process of demyelination. Some macrophages laden with meylin degradation products are also seen in the center of the plaqie, often located in the perivascular cuffs. In addition, astrocytic gliosis occurs in the center of the plaques. As all these cell types are richly endowed with ω3 sites, the feasibility of using ω3 site autoradiagraphy to detect the demyelination plaques in the brain of post-mortem cases of Multiple Sclerosis has been investigated. (Author). 8 refs

  11. Stories of Hell and Healing: Internet Users’ Construction of Benzodiazepine Distress and Withdrawal

    OpenAIRE

    Fixsen, Alison; Ridge, Damien T.

    2017-01-01

    Abstract Benzodiazepines are a group of drugs used mainly as sedatives, hypnotics, antiepileptics, and muscle relaxants. Consumption is recommended for 2 to 4 weeks only, due to fast onset of dependency and potentially distressing withdrawal symptoms. Few peer-review studies have drawn on the user experiences and language to appreciate firsthand experiences of benzodiazepine withdrawal or discontinuation syndrome. We looked extensively at patient stories of benzodiazepine withdrawal and recov...

  12. Renal venogram

    Science.gov (United States)

    ... be black. Other structures will be shades of gray. Veins are not normally seen in an x- ... Venogram - kidney; Renal vein thrombosis - venogram Images Kidney anatomy Kidney - blood and urine flow Renal veins References ...

  13. A captive solvent method for rapid N-[11C]methylation of secondary amides: application to the benzodiazepine, 4'-chlorodiazepam (RO5-4864)

    International Nuclear Information System (INIS)

    Watkins, G.L.; Jewett, D.M.; Mulholland, G.K.; Kilbourn, M.R.; Toorongian, S.A.

    1988-01-01

    [ 11 C]4'-Chlorodiazepam (RO5-4864), for PET studies of peripheral benzodiazepine receptors, was synthesized by alkylation of 1-desmethyl-4'-chlorodiazepam, in a small volume of acetone adsorbed on acrylic yarn, with [ 11 C]methyl iodide in the injection loop of a liquid chromatograph. The reaction mixture was introduced directly onto a small, disposable alumina chromatographic column. Elution with pentane: ethanol gave a product of high chemical and radiochemical purity. A simple heating and cooling device for the injection loop is described. (author)

  14. Balneotherapy Together with a Psychoeducation Program for Benzodiazepine Withdrawal: A Feasibility Study

    Science.gov (United States)

    De Maricourt, P.; Hergueta, Th.; Galinowski, A.; Salamon, R.; Diallo, A.; Vaugeois, C.; Lépine, J. P.; Olié, J. P.

    2016-01-01

    Benzodiazepines should be prescribed on a short-term basis, but a significant proportion of patients (%) use them for more than 6 months, constituting a serious public health issue. Indeed, few strategies are effective in helping patients to discontinue long-term benzodiazepine treatments. The aim of this study was to assess the feasibility and the impact of a program including cognitive behavioural therapy, psychoeducation, and balneotherapy in a spa resort to facilitate long-term discontinuation of benzodiazepines. We conducted a prospective multicentre cohort study. Patients with long-term benzodiazepine use were recruited with the aim of anxiolytic withdrawal by means of a psychoeducational program and daily balneotherapy during 3 weeks. The primary efficacy outcome measure was benzodiazepine use 6 months after the program, compared to use at baseline. A total of 70 subjects were enrolled. At 6 months, overall benzodiazepine intake had decreased by 75.3%, with 41.4% of patients completely stopping benzodiazepine use. The results also suggest a significantly greater improvement in anxiety and depression symptoms among patients who discontinued benzodiazepines compared to patients who only reduced their use. Our findings suggest that balneotherapy in association with a psychoeducative program is efficient in subjects with benzodiazepine addiction. PMID:27956923

  15. No role for benzodiazepines in posttraumatic stress disorder? A surplus of certainty despite scarce evidence.

    Science.gov (United States)

    Starcevic, Vladan

    2017-08-01

    This article addresses some of the controversies about the role of benzodiazepines in the treatment of posttraumatic stress disorder. Benzodiazepines have been admonished in treatment guidelines for posttraumatic stress disorder, but this is based on very little solid evidence. Although benzodiazepines do not seem to be effective in the treatment of the core posttraumatic stress disorder symptoms, their careful use as adjunctive agents for the symptoms such as anxiety and sleep disturbance may be useful. Future research needs to identify predictors of improved treatment outcomes in posttraumatic stress disorder with use of benzodiazepines.

  16. Balneotherapy Together with a Psychoeducation Program for Benzodiazepine Withdrawal: A Feasibility Study

    Directory of Open Access Journals (Sweden)

    P. De Maricourt

    2016-01-01

    Full Text Available Benzodiazepines should be prescribed on a short-term basis, but a significant proportion of patients (% use them for more than 6 months, constituting a serious public health issue. Indeed, few strategies are effective in helping patients to discontinue long-term benzodiazepine treatments. The aim of this study was to assess the feasibility and the impact of a program including cognitive behavioural therapy, psychoeducation, and balneotherapy in a spa resort to facilitate long-term discontinuation of benzodiazepines. We conducted a prospective multicentre cohort study. Patients with long-term benzodiazepine use were recruited with the aim of anxiolytic withdrawal by means of a psychoeducational program and daily balneotherapy during 3 weeks. The primary efficacy outcome measure was benzodiazepine use 6 months after the program, compared to use at baseline. A total of 70 subjects were enrolled. At 6 months, overall benzodiazepine intake had decreased by 75.3%, with 41.4% of patients completely stopping benzodiazepine use. The results also suggest a significantly greater improvement in anxiety and depression symptoms among patients who discontinued benzodiazepines compared to patients who only reduced their use. Our findings suggest that balneotherapy in association with a psychoeducative program is efficient in subjects with benzodiazepine addiction.

  17. Radioreceptor assay for benzodiazepines in biological fluids using a new dry and stable receptor preparation

    International Nuclear Information System (INIS)

    Lund, J.

    1981-01-01

    A method for determination of benzodiazepines in human blood, plasma, saliva and urine has been developed. The method is based upon the competition between 3 H-flunitrazepam and biologically active benzodiazepines in biological fluids for brain specific receptors, prepared in a stable, dry form and easy to handle. The pharmacological specificity for benzodiazepines of the dry stable receptor preparation is closely similar to that of fresh membrane-bound rat brain receptors. The method is specific for biologically active benzodiazepines; it is relatively rapid, sensitive and reproducible, and can be performed at room temperature. (author)

  18. Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

    Science.gov (United States)

    Yeung, Wing-Fai; Chung, Ka-Fai; Zhang, Zhang-Jin; Chan, Wai-Chi; Zhang, Shi-Ping; Ng, Roger Man-Kin; Chan, Connie Lai-Wah; Ho, Lai-Ming; Yu, Yee-Man; Lao, Li-Xing

    2017-03-31

    Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety. The purpose of the study is to evaluate the efficacy of using electroacupuncture as an adjunct treatment to gradual tapering of benzodiazepine doses in complete benzodiazepine cessation in long-term benzodiazepine users. The study protocol of a randomized, assessor- and subject-blinded, controlled trial is presented. One hundred and forty-four patients with histories of using benzodiazepines in ≥50% of days for more than 3 months will be randomly assigned in a 1:1 ratio to receive either electroacupuncture or placebo electroacupuncture combined with gradual benzodiazepine tapering schedule. Both experimental and placebo treatments will be delivered twice per week for 4 weeks. Major assessments will be conducted at baseline, week 6 and week 16 post-randomization. Primary outcome is the cessation rate of benzodiazepine use. Secondary outcomes include the percentage change in the doses of benzodiazepine usage and the severity of withdrawal symptoms experienced based on the Benzodiazepine Withdrawal Symptom Questionnaire, insomnia as measured by the Insomnia Severity Index, and anxiety and depressive symptoms as evaluated by the Hospital Anxiety and Depression Scale. Adverse events will also be measured at each study visit. Results of this study will provide high quality evidence of the efficacy and safety of electroacupuncture as an adjunct treatment for benzodiazepine tapering in long-term users. ClinicalTrials.gov NCT02475538 .

  19. Renal perfusion scintiscan

    Science.gov (United States)

    ... Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion Images Kidney anatomy Kidney - blood and urine flow Intravenous pyelogram References Rottenberg G, Andi AC. Renal ...

  20. Status epilepticus: Role for etiology in determining response to benzodiazepines.

    Science.gov (United States)

    Joshi, Suchitra; Rajasekaran, Karthik; Hawk, Kyle M; Chester, Stephen J; Goodkin, Howard P

    2018-04-01

    Clinical factors contributing to benzodiazepine failure in treating status epilepticus (SE) include suboptimal dosing and seizure duration. As many benzodiazepine-refractory episodes of SE arise from acute etiologies, we sought to determine whether etiology impacts SE treatment. The potency of diazepam to terminate SE induced by lithium-pilocarpine (LiPilo-SE) or kainic acid (KA-SE) in 3-week-old rats was studied by video-electroencephalography. Synaptic γ-aminobutyric acid type A receptor (GABAR)-mediated currents were recorded from dentate granule cells using voltage-clamp electrophysiology. Surface expression of γ2 subunit-containing GABARs and Kv4.2 potassium channels in hippocampal slices was determined using a biotinylation assay. Expression of phosphorylated forms of β2/3 and γ2 subunits was determined using phosphospecific antibodies and Western blotting. Diazepam failed to terminate late SE in LiPilo-SE animals but was successful in terminating KA-SE of 1- and 3-hour duration. One hour after SE onset, GABAR-mediated synaptic inhibition and γ2 subunit-containing GABAR surface expression were reduced in LiPilo-SE animals. These were unchanged in KA-SE animals at 1 and 3 hours. Phosphorylation of γ2 subunit residue S327 was unchanged in both models, although GABAR β3 subunit S408/409 residues were dephosphorylated in the LiPilo-SE animals. Kv4.2 potassium channel surface expression was increased in LiPilo-SE animals but reduced in KA-SE animals. SE-model-dependent differences support a novel hypothesis that the development of benzodiazepine pharmacoresistance may be etiologically predetermined. Further studies are required to investigate the mechanisms that underlie such etiological differences during SE and whether etiology-dependent protocols for the treatment of SE need to be developed. Ann Neurol 2018;83:830-841. © 2018 American Neurological Association.

  1. A control study on treatment for benzodiazepine dependence with trazodone

    Directory of Open Access Journals (Sweden)

    ZHANG Hong-ju

    2013-05-01

    Full Text Available Objective To determine the efficacy and safety of trazodone in the treatment of benzodiazepine dependence. Methods Forty insomnia patients who met the Classification and Diagnostic Criteria of Mental Disorders in China Third Edition (CCMD-3 of dependence syndrome due to benzodiazepine were involved in the study. Patients were randomly assigned to trazodone group and placebo group for 3 months. The efficacy were assessed by Withdrawal Symptoms Checklist, Hamilton Anxiety Rating Scale (HAMA and polysomnography (PSG. Adverse events were assessed by Treatment Emergent Symptom Scale (TESS. Results The Withdrawal Symptoms Checklist of trazodone group was significantly lower after 7 d treatment than that of placebo group (P = 0.000, and HAMA score of the trazodone group was also significantly lower after 15 d treatment than that of placebo group (P = 0.000. There were no difference in Withdrawal Symptoms Checklist and HAMA of placebo group before and after treatment. Withdrawal Symptoms Checklist and HAMA of the trazodone group were decreased after treatment (P = 0.000. In comparison with placebo group, sleep parameters of the trazodone, including total sleep time (TST, sleep efficiency (SE, sleep latency (SL and slow wave sleep (SWS time presented improvement after 7 d treatment (P = 0.000, for all. After trazodone treatment, total sleep time, slow wave sleep time, sleep efficiency and sleep latency were improved (P = 0.000, for all. No obvious adverse reaction occurred. There were no significant differences in TESS scores between pre? and post?treatment in both groups (P > 0.05. Conclusion Trazodone is markedly effective and safe in the treatment for benzodiazepine dependence.

  2. Benzodiazepine receptor and neurotransmitter studies in the brain of suicides

    Energy Technology Data Exchange (ETDEWEB)

    Manchon, M.; Kopp, N.; Rouzioux, J.J.; Lecestre, D.; Deluermoz, S.; Miachon, S.

    1987-12-14

    The characteristics of benzodiazepine binding sites were studied on frozen sections of hippocampus of 7 suicides and 5 controls subjects, using biochemical and autoradiographic techniques. /sup 3/H flunitrazepam was used as ligand, clonazepam and CL 218,872 as displacing agents. Some neurotransmitters or their derivatives were evaluated quantitatively in parallel in the hippocampal tissue by liquid chromatography. The authors observed mainly an increase in the Ki of CL 218,872 subtype I binding sites in suicides, and an increase in % of type I binding sites. Among neurotransmitters, only norepinephrine differed significantly between controls and suicides. 36 references, 3 figures, 1 table.

  3. Benzodiazepine receptor and neurotransmitter studies in the brain of suicides

    International Nuclear Information System (INIS)

    Manchon, M.; Kopp, N.; Rouzioux, J.J.; Lecestre, D.; Deluermoz, S.; Miachon, S.

    1987-01-01

    The characteristics of benzodiazepine binding sites were studied on frozen sections of hippocampus of 7 suicides and 5 controls subjects, using biochemical and autoradiographic techniques. 3 H flunitrazepam was used as ligand, clonazepam and CL 218,872 as displacing agents. Some neurotransmitters or their derivatives were evaluated quantitatively in parallel in the hippocampal tissue by liquid chromatography. The authors observed mainly an increase in the Ki of CL 218,872 subtype I binding sites in suicides, and an increase in % of type I binding sites. Among neurotransmitters, only norepinephrine differed significantly between controls and suicides. 36 references, 3 figures, 1 table

  4. Benzodiazepines still play a role in modern psychiatric therapy

    DEFF Research Database (Denmark)

    Jørgensen, Martin Balslev; Videbech, Poul; Osler, Merete

    2017-01-01

    Benzodiazepines (BZ) are widely used for anxiety across psychiatric diagnoses, but for the last decades regulation has been increasingly tight due to problems with tolerance, addiction, withdrawal symptoms and cognitive side effects. Some guidelines claim that BZ only work for a few weeks......, and that BZ cause traffic accidents, increased mortality and dementia. In Denmark, the use of BZ has been substantially reduced. In this article it is argued, that not all patients habituate, that most of the epidemiological findings are hampered by confounding, and that there still is a role for long...

  5. The relation between the blood benzodiazepine concentration and performance in suspected impaired drivers

    NARCIS (Netherlands)

    Smink, B.E.; Lusthof, K.J.; de Gier, J.J.; Uges, D.R.; Egberts, A.C.

    2008-01-01

    Several experimental studies have shown a negative influence of benzodiazepines on driving skills. The objective of this study is to study the relationship between the blood concentration of benzodiazepines and the influence on performance in field sobriety tests. A retrospective case file

  6. Benzodiazepines and risk for hepatic encephalopathy in patients with cirrhosis and ascites

    DEFF Research Database (Denmark)

    Grønbæk, Lisbet; Watson, Hugh; Vilstrup, Hendrik

    2018-01-01

    Background: There is limited evidence to support the belief that benzodiazepines increase cirrhosis patients’ risk of hepatic encephalopathy (HE). Objective: We aimed to examine the association between benzodiazepine use and HE development in cirrhosis patients. Methods: We used data on 865...

  7. Biochemical study of multiple drug recognition sites on central benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Trifiletti, R.R.

    1986-01-01

    The benzodiazepine receptor complex of mammalian brain possesses recognition sites which mediate (at least in part) the pharmacologic actions of the 1,4-benzodiazepines and barbiturates. Evidence is provided suggesting the existence of least seven distinct drug recognition sites on this complex. Interactions between the various recognition sites have been explored using radioligand binding techniques. This information is utilized to provide a comprehensive scheme for characterizing receptor-active drugs on an anxiolytic-anticonvulsant/proconvulsant continuum using radioligand binding techniques, as well as a comprehensive program for identifying potential endogenous receptor-active substances. Further evidence is provided here supporting the notion of benzodiazepine recognition site heterogeneity. Classical 1,4-benzodiazepines do not appear to differentiate two populations of benzodiazepine receptors in an equilibrium sense, but appear to do so in a kinetic sense. An apparent physical separation of the two receptor subtypes can be achieved by differential solubilization. The benzodiazepine binding subunit can be identified by photoaffinity labeling with the benzodiazepine agonist (/sup 3/H)flunitrazepan. Conditions for reproducible partial proteolytic mapping of (/sup 3/H)flunitrazepam photoaffinity labeled receptors are established. From these maps, it is concluded that there are probably no major differences in the primary sequence of the benzodiazepine binding subunit in various regions of the rat central nervous system.

  8. Differences in health status between long-term and short-term benzodiazepine users.

    NARCIS (Netherlands)

    Zandstra, S.M.; Furer, J.W.; Lisdonk, E.H. van de; Bor, J.H.J.; Zitman, F.G.; Weel, C. van

    2002-01-01

    BACKGROUND: Despite generally accepted advice to keep treatment short, benzodiazepines are often prescibed for more than six months. Prevention of long-term benzodiazepine use could be facilitated by the utilisation of risk indicators for long-term use. However, the characteristics of long-term

  9. Benzodiazepine antagonism by harmane and other beta-carbolines in vitro and in vivo.

    Science.gov (United States)

    Rommelspacher, H; Nanz, C; Borbe, H O; Fehske, K J; Müller, W E; Wollert, U

    1981-03-26

    Harmane and other related beta-carbolines are putative endogenous ligands of the benzodiazepine receptor. Since the compounds are potent convulsants they may have agonist activities at the benzodiazepine receptor while the benzodiazepines may be antagonists. This hypothesis was proved by comparing the in vivo and in vitro antagonism of benzodiazepines by harmane and other beta-carbolines. Harmane is clearly a competitive inhibitor of benzodiazepine receptor binding in vitro. Moreover, harmane-induced convulsions can be inhibited reversibly by diazepam in a manner which is consistent with the assumption of competitive antagonism in vivo. For some beta-carboline derivatives a correlation was found between the affinity for the benzodiazepine receptor in vitro and the convulsive potency in vivo. Thus, the data reported suggest that harmane or other related beta-carbolines are putative endogenous agonists of the benzodiazepine receptor. This suggestion is further supported by the observation that diazepam is equally potent in inhibiting harmane- or picrotoxin-induced convulsions, indicating a convulsive mechanism within the GABA receptor-benzodiazepine receptor system.

  10. Tapering off benzodiazepines in long-term users : an economic evaluation

    NARCIS (Netherlands)

    Oude Voshaar, Richard C; Krabbe, Paul F M; Gorgels, Wim J M J; Adang, Eddy M M; van Balkom, Anton J L M; van de Lisdonk, Eloy H; Zitman, Frans G

    2006-01-01

    BACKGROUND: Discontinuation of benzodiazepine usage has never been evaluated in economic terms. This study aimed to compare the relative costs and outcomes of tapering off long-term benzodiazepine use combined with group cognitive behavioural therapy (TO+CBT), tapering off alone (TOA) and usual

  11. An audit of prescribing practices for benzodiazepines and Z-drugs.

    LENUS (Irish Health Repository)

    Cadogan, C

    2015-03-01

    Concerns persist over the use of benzodiazepines and Z-drugs in Ireland. A prospective prescription audit was conducted in 81 community pharmacies across Ireland over a four week period. The study sought to assess the level of prescription compliance with key components of benzodiazepine and Z-drug prescribing guidelines. 28% of audit booklets issued were returned, yielding data on 4,418 prescriptions. The findings suggest that little progress has been made in improving the prescribing of benzodiazepines and Z-drugs in Ireland in the decade since publication of the Benzodiazepine Committee\\'s report. Fewer than one fifth of prescriptions (18.8%) were fully compliant with the assessment criteria and the majority (53.7%) had multiple discrepancies. This study highlights the importance of monitoring and auditing benzodiazepine and Z-drug prescribing practices. Interventions involving patients, prescribers and pharmacists are required to improve the prescribing and use of these medications in Ireland.

  12. Benzodiazepine prescription in relation to psychiatric diagnosis and patient characteristics: A pilot study

    Directory of Open Access Journals (Sweden)

    Marić Nađa P.

    2015-01-01

    Full Text Available Introduction: Benzodiazepines are widely used drugs which are often misused. Analysis of psychotropic drugs prescription in Serbia showed high prescription rate of benzodiazepines in the psychiatric patient population, with an increasing trend. Potential association between psychiatric diagnostic categories (organic brain syndrome, psychotic disorders, bipolar disorder, unipolar depression, anxiety disorder, personality disorder, or the sociodemographic characteristics of patients (gender, age, education, marital state and benzodiazepine prescribing practice was not thoroughly tested. Aim: By analyzing routine practice of the university clinic, the aim of this study was to examine whether there is an association between clinical or socio-demographic characteristics of the patients and benzodiazepine prescribing practice. Material and methods: This study was carried out by retrospective analysis of the patient's medical charts after hospital discharge (n=102. Data analysis included descriptive statistics, testing the difference between groups and correlation analysis. Results: At the discharge, 94.1% of patients had benzodiazepines prescribed, with an average dose of 4.6 ± 3.2mg lorazepam dose equivalents. It is shown that female patients were prescribed with higher doses of benzodiazepines than male patients (p=0.018, that the average dose was higher for patients treated with an overall larger number of psychiatric drugs (p = 0.013, as well as that hospital inpatients had higher doses compared to day hospital-treated patients (p = 0.011. Patients with a diagnosis of personality disorder had a slight upward trend of benzodiazepine dose (p=0.078. Conclusion: Current research provided a clear insight into the actual practice of benzodiazepine prescription at local university center. Similarly to our region, indications for prescribing benzodiazepines appear to be quite broad and not specific enough worldwide. This is why it is important to

  13. Benzodiazepine prescribing behaviour and attitudes: a survey among general practitioners practicing in northern Thailand

    Directory of Open Access Journals (Sweden)

    Critchley Julia

    2005-06-01

    Full Text Available Abstract Background Over-prescribing of benzodiazepines appears common in many countries, a better understanding of prescribing practices and attitudes may help develop strategies to reduce prescribing. This study aimed to evaluate benzodiazepine prescribing behaviour and attitudes in general practitioners practising in Chiang Mai and Lampoon, Thailand. Methods Questionnaire survey of general practitioners in community hospitals, to estimate: i use of benzodiazepines for anxiety/insomnia, panic disorder, depression, essential hypertension, and uncomplicated low back pain and ii views on the optimal duration of benzodiazepine use. Results Fifty-five of 100 general practitioners returned the completed questionnaires. They reported use of benzodiazepines for anxiety/insomnia (n = 51, 93%, panic disorder (n = 43, 78%, depression (n = 26, 43%, essential hypertension (n = 15, 27 % and uncomplicated low back pain (n = 10, 18%. Twenty-eight general practitioners would prescribe benzodiazepines for non-psychiatric conditions, 17 for use as muscle relaxants. Seventy-five per cent, 62% and 29% of the general practitioners agreed or totally agreed with the use of benzodiazepines for insomnia, anxiety and depression, respectively. Practitioners agreed that prescribing should be less than one week (80%; or from 1 week to 1 month (47%; or 1 to 4 months (16%; or 4 to 6 months (5% or more than 6 months (2%. Twenty-five general practitioners (45% accepted that they used benzodiazepines excessively in the past year. Conclusion A considerable proportion of general practitioners in Chiang Mai and Lampoon, Thailand inappropriately use benzodiazepines for physical illnesses, especially essential hypertension and uncomplicated low back pain. However, almost half of them thought that they overused benzodiazepines. General practitioner's lack of time, knowledge and skills should be taken into account in improving prescribing behaviour and attitudes.

  14. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  15. Use of benzodiazepines or benzodiazepine related drugs and the risk of cancer: a population-based case-control study

    DEFF Research Database (Denmark)

    Pottegård, Anton; Friis, Søren; Andersen, Morten

    2013-01-01

    AIM: Studies of the carcinogenic potential of benzodiazepines and related drugs (BZRD) have been equivocal. A recent study reported a 35% excess cancer risk among users of hypnotics, including benzodiazepines. METHOD: Using Danish nationwide registers, we conducted a matched case-control study...... of the association between BZRD and cancer risk. During 1 January 2002 and 31 December 2009, we identified 152 510 cases with a first time cancer who were matched (1:8) by age and gender to 1,220,317 cancer-free controls. A new-user design was applied by excluding all subjects who had used anxiolytics, hypnotics.......02), liver 1.81 (95% CI 1.18, 2.80), lung 1.38 (95% CI 1.23, 1.54), pancreas 1.35 (95% CI 1.02, 1.79) and kidney 1.39 (95% CI 1.01, 1.91). For tobacco-related cancers, the OR was 1.15 (95% CI 1.09, 1.22) and for the remaining cancer sites 1.01 (95% CI 0.94, 1.08). Sub-group analyses revealed only small...

  16. Imaging of Renal Leiomyomas

    Energy Technology Data Exchange (ETDEWEB)

    Derchi, L. E.; Grenier, N.; Heinz-Peer, G.; Dogra, V.; Franco, F.; Rollandi, G. A.; Deminiere, C. (Radiologia - DICMI, Univ. di Genova, Genova (Italy))

    2008-09-15

    Background: Renal leiomyomas are rare benign tumors of the kidney which can be found at autopsy as small capsular nodules in about 5% of cases. The clinical incidence of such lesions is much smaller, and only case reports or small series have been reported in the imaging literature. Purpose: To describe the imaging characteristics observed in a series of eight patients with pathology-proven asymptomatic leiomyomas of the kidney. Material and Methods: We reviewed the imaging findings observed in eight patients with pathologically proven asymptomatic renal leiomyomas discovered during studies performed for reasons unrelated to the kidney. All patients had undergone computed tomography (CT), two ultrasonography, and one magnetic resonance imaging (MRI). Results: Lesions ranged in size from 1.2 to 13 cm. Six were at the periphery of the kidney, compressed its outer surface, but did not cause disruption of the cortex; two involved the renal cortex. All had regular outer margins. A cleavage plane between the tumor and the kidney was revealed at CT and/or ultrasonography in three of the cases located at the periphery. At ultrasonography, leiomyomas appeared hypoechogenic. At CT, they were slightly hyperdense before contrast medium injection; all were hypodense to the renal cortex after contrast medium. Four were homogeneous, two were slightly heterogeneous, and the remaining two were frankly heterogeneous. The lesion studied by MRI, which was homogeneous at the postcontrast CT study, had a heterogeneous structure on both T1- and T2-weighted images, with internal areas of hypointensity on T1. Conclusion: There are some imaging findings that can help to suggest the diagnosis of renal leiomyomas. First, their density: all tumors examined before contrast were hyperdense to the kidney, with density similar to that of muscles, and all had lower enhancement than the adjacent renal parenchyma. Second, the location and margins of the tumors: most were peripheral, without

  17. Renal cancer.

    NARCIS (Netherlands)

    Corgna, E.; Betti, M.; Gatta, G.; Roila, F.; Mulder, P.H.M. de

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  18. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  19. High density of benzodiazepine binding sites in the substantia innominata of the rat

    International Nuclear Information System (INIS)

    Sarter, M.; Schneider, H.H.

    1988-01-01

    In order to study the neuronal basis of the pharmacological interactions between benzodiazepine receptor ligands and cortical cholinergic turnover, we examined the regional distribution of specific benzodiazepine binding sites using in vitro autoradiography. In the basal forebrain, the substantia innominata contained a high density of [ 3 H]lormetazepam (LMZ) binding sites (Bmax = 277 fmol/mg tissue; Kd = 0.55 nM). The label could be displaced by diazepam (IC50 = 100 nM), the benzodiazepine receptor antagonist beta-carboline ZK 93426 (45 nM) and the partial inverse agonist beta-carboline FG 7142 (540 nM). It is hypothesized that the amnesic effects of benzodiazepine receptor agonists are exerted through benzodiazepine receptors which are situated on cholinergic neurons in the substantia innominata and are involved in a tonic inhibition of cortical acetylcholine release. The benzodiazepine receptor antagonist ZK 93426 may exert its nootropic effects via benzodiazepine receptors in the substantia innominata and, consequently, by disinhibiting cortical acetylcholine release

  20. Preliminary finding: consumption of benzodiazepines in Brazil during the years 1988 and 1989.

    Science.gov (United States)

    Nappo, S; Carlini, E A

    1993-06-01

    This work investigates consumption of benzodiazepines in Brazil during the years 1988 and 1989, using the following sources of information provided to the Brazilian Ministry of Health by institutions that deal with benzodiazepines: (a) benzodiazepine stocks recorded at the beginning and end of each year; (b) Brazilian (internal) production of benzodiazepines; (c) imported and exported amounts of benzodiazepines; (d) amounts employed in the manufacture of brand-name products and in the making of prescription formulas. The records a, b and c furnished the 'calculated consumption', of benzodiazepines, in kilograms. The d records, on the other hand, directly furnished the 'informed consumption', also in kilograms. The data obtained were also expressed in terms of defined daily doses (DDDs)/1,000 inhabitants/day, considering the informed consumption and the Brazilian population. As for the DDDs/1000 inhabitants/day, they were found to be 23.03 and 18.48 for the years 1988 and 1989, respectively. A striking discrepancy was detected between the calculated and the informed consumption figures, the latter having exceeded the former by 2096 kg in 1988 and by 4909 kg in 1989. Diazepam was the primary drug responsible for this difference. Such results may suggest that an illicit, unrecorded trade of benzodiazepines is occurring in Brazil.

  1. Physiology and physiopathology of central type Benzodiazepine receptors: Study in the monkey and in human brain using positron emission tomography

    International Nuclear Information System (INIS)

    Hantraye, P.

    1987-01-01

    A new non-invasive technique that allows to study in a living subject central type benzodiazepine receptors is developed. A combined approach is applied using a specific positron-emitting radiotracer for the in vivo labelling of the receptors and positron emission tomography allowing, by external detection, a quantitative determination of tissue radioactivity. The radioligand used for the in vivo labelling of benzodiazepine receptors is the antagonist RO 15-1788 labelled with carbon 11. The various stages of the study are described: in vivo characterization in the monkey of central type benzodiazepine receptors; characterization of central type benzodiazepine receptors in human brain using selective molecules for the BZ1 benzodiazepine subclass; demonstration of the heterogeneity of central type benzodiazepine receptors in the brain; study of pathological alteration of benzodiazepine receptors in experimental epilepsy [fr

  2. [Impact of benzodiazepine dependence on the use of health services: study of the health of seniors].

    Science.gov (United States)

    Nkogho Mengue, Pamphile-Gervais; Abdous, Belkacem; Berbiche, Djamal; Préville, Michel; Voyer, Philippe

    2013-03-01

    The use of benzodiazepines is common among seniors. This consumption can cause an addiction whose criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition revised (DSM-IV-TR) do not always apply to the situation of the elderly. This research seeks to examine the link between the feeling of benzodiazepine dependence and the use of health services by seniors. A secondary objective is to describe the use of benzodiazepines among seniors living in the community. Data derive from a survey conducted in Quebec in 2005-2006 from a representative sample of 707 Francophones aged 65 and over living in the community. The feeling of benzodiazepine dependence was measured by a composite variable incorporating two questions inspired by the DSM-IV-TR. The use of health services was measured through the cumulative impact of consultation with health care professionals during a 12- month period. Older adults consumed a total of 745 benzodiazepines, including 117 (16.5%) which had a half-long life. The proportion of seniors who reported a feeling of dependence on benzodiazepines was estimated at 35.1 %. These seniors did not significantly make further use of health services for their addiction to benzodiazepines. The results of this study suggest that the use of benzodiazepines among seniors in Quebec is far from optimal. Moreover, the perceived need in addiction is not a significant factor in inducing seniors to use health services for the management of addiction. There is, therefore, a need for research to better understand the barriers associated with the use of health services by seniors addicted to benzodiazepines.

  3. Risk of pneumonia associated with incident benzodiazepine use among community-dwelling adults with Alzheimer disease.

    Science.gov (United States)

    Taipale, Heidi; Tolppanen, Anna-Maija; Koponen, Marjaana; Tanskanen, Antti; Lavikainen, Piia; Sund, Reijo; Tiihonen, Jari; Hartikainen, Sirpa

    2017-04-10

    Knowledge regarding whether benzodiazepines and similarly acting non-benzodiazepines (Z-drugs) are associated with an increased risk of pneumonia among older adults is lacking. We sought to investigate this association among community-dwelling adults with Alzheimer disease, a condition in which both sedative/hypnotic use and pneumonia are common. We obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland (2005-2011) from the Medication use and Alzheimer disease (MEDALZ) cohort, which incorporates national registry data on prescriptions, reimbursement, hospital discharges and causes of death. Incident users of benzodiazepines and Z-drugs were identified using a 1-year washout period and matched with nonusers using propensity scores. The association with hospital admission or death due to pneumonia was analyzed with the Cox proportional hazards model and adjusted for use of other psychotropic drugs in a time-dependent manner. Among 49 484 eligible participants with Alzheimer disease, 5232 taking benzodiazepines and 3269 taking Z-drugs were matched 1:1 with those not taking these drugs. Collectively, use of benzodiazepines and Z-drugs was associated with an increased risk of pneumonia (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.05-1.42). When analyzed separately, benzodiazepine use was significantly associated with an increased risk of pneumonia (adjusted HR 1.28, 95% CI 1.07-1.54), whereas Z-drug use was not (adjusted HR 1.10, 95% CI 0.84-1.44). The risk of pneumonia was greatest within the first 30 days of benzodiazepine use (HR 2.09, 95% CI 1.26-3.48). Benzodiazepine use was associated with an increased risk of pneumonia among patients with Alzheimer disease. Risk of pneumonia should be considered when weighing the benefits and risks of benzodiazepines in this population. © 2017 Canadian Medical Association or its licensors.

  4. Application of radioreceptor assay of benzodiazepines for toxicology

    International Nuclear Information System (INIS)

    Aaltonen, L.; Scheinin, M.

    1982-01-01

    A radioreceptor assay (RRA) for determining benzodiazepines (BZ) has been developed and applied to toxicological analysis of serum samples from 21 patients with acute BZ overdosage. The method was sensitive (e.g., lorazepam 17 nM, diazepam 41 nM), and specific for pharmacologically active BZ derivatives. The reproducibility of the results was good (intra-assay variation < 8%, inter-assay variation < 10%). Concentrations measured by the RRA showed a good correlation with those obtained by gas-liquid chromatographic analysis of the same samples. The quantitative results represent the sum of one or several parent substances and all biologically active metabolites, in proportion to their receptor binding affinities. (author)

  5. Simple synthesis, structure and ab initio study of 1,4-benzodiazepine-2,5-diones

    Science.gov (United States)

    Jadidi, Khosrow; Aryan, Reza; Mehrdad, Morteza; Lügger, Thomas; Ekkehardt Hahn, F.; Ng, Seik Weng

    2004-04-01

    A simple procedure for the synthesis of pyrido[2,1-c][1,4] benzodiazepine-6,12-dione ( 1) and 1,4-benzodiazepine-2,5-diones ( 2a- 2d), using microwave irradiation and/or conventional heating is reported. The configuration of 1 was determined by single-crystal X-ray diffraction. A detailed ab initio B3LYP/6-31G* calculation of structural parameters and substituent effects on ring inversion barriers (Δ G#) and also free energy differences (Δ G0) for benzodiazepines are reported.

  6. Synthesis, Anticonvulsant, Sedative and Anxiolytic Activities of Novel Annulated Pyrrolo[1,4]benzodiazepines

    Directory of Open Access Journals (Sweden)

    Kumaraswamy Sorra

    2014-09-01

    Full Text Available Four new pentacyclic benzodiazepine derivatives (PBDTs 13–16 were synthesized by conventional thermal heating and microwave-assisted intramolecular cyclocondensation. Their anticonvulsant, sedative and anxiolytic activities were evaluated by drug-induced convulsion models, a pentobarbital-induced hypnotic model and an elevated plus maze in mice. PBDT 13, a triazolopyrrolo[2,1-c][1,4]benzodiazepin-8-one fused with a thiadiazolone ring, exhibited the best anticonvulsant, sedative and anxiolytic effects in our tests. There was no significant difference in potency between PBDT 13 and diazepam, and we proposed that the action mechanism of PBDT 13 could be similar to that of diazepam via benzodiazepine receptors.

  7. Synthesis of a Benzodiazepine-derived Rhodium NHC Complex by C-H Bond Activation

    Energy Technology Data Exchange (ETDEWEB)

    Bergman, Roberg G.; Gribble, Jr., Michael W.; Ellman, Jonathan A.

    2008-01-30

    The synthesis and characterization of a Rh(I)-NHC complex generated by C-H activation of 1,4-benzodiazepine heterocycle are reported. This complex constitutes a rare example of a carbene tautomer of a 1,4-benzodiazepine aldimine stabilized by transition metal coordination and demonstrates the ability of the catalytically relevant RhCl(PCy{sub 3}){sub 2} fragment to induce NHC-forming tautomerization of heterocycles possessing a single carbene-stabilizing heteroatom. Implications for the synthesis of benzodiazepines and related pharmacophores via C-H functionalization are discussed.

  8. QuEChERS extraction of benzodiazepines in biological matrices

    Directory of Open Access Journals (Sweden)

    Jessica L. Westland

    2013-12-01

    Full Text Available Two common analytical chemical problems often encountered when using chromatographic techniques in drug analysis are matrix interferences and ion suppression. Common sample preparation often involves the dilution of the sample prior to injection onto an instrument, especially for liquid chromatography–mass spectrometry (LC–MS analyses. This practice frequently does not minimize or eliminate conditions that may cause ion-suppression and therefore, suffer more from reduced method robustness. In order to achieve higher quality results and minimize possible interferences, various sample preparation techniques may be considered. Through the use of QuEChERS (“catchers”, a novel sample preparation technique used for high aqueous content samples, benzodiazepines can be extracted from biological fluids, such as blood and urine. This approach has shown increased recoveries of target compounds when using quantification by both external and internal standard. This increase in the recoveries has been attributed to a matrix enhancement and was determined through the use of the method of standard addition. While improving the overall analytical method for gas chromatography–mass spectrometry (GC–MS analysis, it is not clear if this approach represents an overall benefit for laboratories that have both GC–MS and high performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS capability. Demonstrating evidence of variable ionization (enhancement, ion source inertness, etc., the method of quantification should be focused on in future studies. Keywords: Forensic science, QuEChERS, Drug analysis, Benzodiazepines, Gas Chromatography–Mass Spectrometry, Biological samples

  9. The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand

    Energy Technology Data Exchange (ETDEWEB)

    Basile, A.S.; Ostrowski, N.L.; Gammal, S.H.; Jones, E.A.; Skolnick, P. (National Institutes of Health, Bethesda, MD (USA))

    1990-02-01

    Autoradiographic analysis was used to examine radioligand binding to benzodiazepine (BZ) and GABAA receptors in the brains of rabbits with hepatic encephalopathy (HE). Thin sections of whole brain from normal rabbits and rabbits with HE were mounted on slides and subdivided into two groups. One group was washed before incubation with radioligand, while the second group was not prewashed. (3H)Flunitrazepam binding to BZ receptors was decreased by 22% to 42% (p less than 0.05) in the cerebral cortex, superior and inferior colliculi, and cerebellum of unwashed sections from rabbits with HE compared to all other groups. The binding of (3H)Ro 15-1788 to unwashed sections from rabbits with HE was reduced by a similar degree (18% to 37%, p less than 0.05) in the cerebral cortex, hippocampus, superior colliculus, and cerebellar cortex. Incubation of sections with the GABA-mimetic muscimol and NaCl produced an additional decrease in (3H)flunitrazepam binding to the cortex and hippocampus (25% to 31%, p less than 0.05) in unwashed HE rabbit brain, but increased radioligand binding (27% to 71%, p less than 0.05) to several regions in control rabbits. No changes in radioligand binding to either GABAA or peripheral benzodiazepine receptors was observed between HE and control rabbit sections. These findings are consistent with previous electrophysiologic and neurochemical observations indicating no significant changes in either the function or density of GABAA or BZ receptors in this model of HE. Further, they indicate that a reversible BZ receptor ligand with agonist properties is present in the brain in HE. This substance may contribute to the enhancement of GABAergic tone observed in this syndrome.

  10. Prevention of organophosphate-induced chronic epilepsy by early benzodiazepine treatment.

    Science.gov (United States)

    Shrot, Shai; Ramaty, Erez; Biala, Yoav; Bar-Klein, Guy; Daninos, Moshe; Kamintsky, Lyn; Makarovsky, Igor; Statlender, Liran; Rosman, Yossi; Krivoy, Amir; Lavon, Ophir; Kassirer, Michael; Friedman, Alon; Yaari, Yoel

    2014-09-02

    Poisoning with organophosphates (OPs) may induce status epilepticus (SE), leading to severe brain damage. Our objectives were to investigate whether OP-induced SE leads to the emergence of spontaneous recurrent seizures (SRSs), the hallmark of chronic epilepsy, and if so, to assess the efficacy of benzodiazepine therapy following SE onset in preventing the epileptogenesis. We also explored early changes in hippocampal pyramidal cells excitability in this model. Adult rats were poisoned with the paraoxon (450μg/kg) and immediately treated with atropine (3mg/kg) and obidoxime (20mg/kg) to reduce acute mortality due to peripheral acetylcholinesterase inhibition. Electrical brain activity was assessed for two weeks during weeks 4-6 after poisoning using telemetric electrocorticographic intracranial recordings. All OP-poisoned animals developed SE, which could be suppressed by midazolam. Most (88%) rats which were not treated with midazolam developed SRSs, indicating that they have become chronically epileptic. Application of midazolam 1min following SE onset had a significant antiepileptogenic effect (only 11% of the rats became epileptic; p=0.001 compared to non-midazolam-treated rats). Applying midazolam 30min after SE onset did not significantly prevent chronic epilepsy. The electrophysiological properties of CA1 pyramidal cells, assessed electrophysiologically in hippocampal slices, were not altered by OP-induced SE. Thus we show for the first time that a single episode of OP-induced SE in rats leads to the acquisition of chronic epilepsy, and that this epileptogenic outcome can be largely prevented by immediate, but not delayed, administration of midazolam. Extrapolating these results to humans would suggest that midazolam should be provided together with atropine and an oxime in the immediate pharmacological treatment of OP poisoning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Benzodiazepine effect of 125I-iomazenil-benzodiazepine receptor binding and serum corticosterone level in a rat model

    International Nuclear Information System (INIS)

    Fukumitsu, Nobuyoshi; Ogi, Shigeyuki; Uchiyama, Mayuki; Mori, Yutaka

    2005-01-01

    To test the change in free or unoccupied benzodiazepine receptor (BZR) density in response to diazepam, we investigated 125 I-iomazenil ( 125 I-IMZ) binding and serum corticosterone levels in a rat model. Wistar male rats, which received psychological stress using a communication box for 5 days, were divided into two groups according to the amount of administered diazepam: no diazepam [D (0)] group and 10 mg/kg per day [D (10)] group of 12 rats each. The standardized uptake value (SUV) of 125 I-IMZ of the D (10) group were significantly lower (P 125 I-IMZ, it is clear that diazepam competed with endogenous ligand for the free BZR sites, and the frontal, parietal and temporal cortices, globus pallidus, hippocampus, amygdala and hypothalamus are important areas in which 125 I-IMZ binding is strongly affected by administration of diazepam

  12. Renal scan

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003790.htm Renal scan To use the sharing features on this ... anaphylaxis . Alternative Names Renogram; Kidney scan Images Kidney anatomy Kidney - blood and urine flow References Chernecky CC, ...

  13. Neurological complications of renal dialysis and transplantation.

    Science.gov (United States)

    Karunaratne, Kushan; Taube, David; Khalil, Nofal; Perry, Richard; Malhotra, Paresh A

    2018-04-01

    Neurological complications from renal replacement therapy contribute significantly to morbidity and mortality in patients with renal failure. Such complications can affect either the central or peripheral nervous systems. Most neurological disturbances associated with the uraemic state do not respond fully to renal replacement therapy. There are also complications specifically associated with dialysis and transplantation. A multidisciplinary approach, involving both nephrologists and neurologists, is critical for the diagnosis and effective management of these disorders. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Intramolecular Azide to Alkene Cycloadditions for the Construction of Pyrrolobenzodiazepines and Azetidino-Benzodiazepines

    Czech Academy of Sciences Publication Activity Database

    Hemming, K.; Chambers, Christopher S.; Jamshaid, F.; O´Gorman, Paul A.

    2014-01-01

    Roč. 19, č. 10 (2014), s. 16737-16756 ISSN 1420-3049 Institutional support: RVO:61388971 Keywords : azide * cycloadditions * benzodiazepines Subject RIV: CC - Organic Chemistry Impact factor: 2.416, year: 2014

  15. [The efficacy of the native flumazenil for acute poisoning with benzodiazepines].

    Science.gov (United States)

    Zhu, X H; Li, J X; Wang, F

    2000-12-28

    To evaluate the efficacy of the native flumazenil for acute self-poisoning with benzodiazepines. One hundred and twenty-six patients with unconsciousness from benzodiazepines-induced self-poisoning were randomly divided into two groups: flumazenil group(Group II, 63 cases) were treated with flumazenil, and conventional-medicine group(Group I, 63 cases) with placebo(glucose, vitamin C, KCl). A modified Glasgow Coma Scale(MGCS) and Observer's Assessment of Alertness/Sedation Scale(OAA/S) were used in the assessment of consciousness. MGCS were increased by 5.3, 8.0, 9.4 and 7.3 at 15 min, 30 min, 60 min and 180 min after intravenous flumazenil(P treatment. Flumazenil might improve benzodiazepines-induced unconsciousness markedly and may be the most effective antagonist of benzodiazepines.

  16. Iodine-125 radioimmunoassay for the direct detection of benzodiazepines in blood and urine

    Energy Technology Data Exchange (ETDEWEB)

    Goddard, C.P.; Stead, A.H.; Mason, P.A.; Law, B.; Moffat, A.C.; McBrien, M.; Cosby, S.

    1986-05-01

    A radioimmunoassay (RIA) for the direct detection of benzodiazepines in blood and urine is described. It is based on a commercially available antiserum and an easily synthesised radio-iodinated derivative of clonazepam that allows the use of relatively simple gamma-counting procedures. The assay can detect low therapeutic levels of all of the benzodiazepines currently available in the UK in 50-..mu..l samples of blood and urine (1-50 ng ml/sup -1/, depending on the drug); no prior sample preparation is required. It is inexpensive, rapid, simple to perform and is broadly specific for the benzodiazepine class of drugs. The assay offers a most suitable means of screening large numbers of samples of forensic interest for the presence of the benzodiazepines.

  17. Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on

    DEFF Research Database (Denmark)

    Baandrup, Lone; Fasmer, Ole Bernt; Glenthøj, Birte Yding

    2016-01-01

    is associated with changes in circadian rhythm parameters. METHOD: Data were derived from a randomized, double-blinded clinical trial with 24 weeks follow-up. Participants were randomized to add-on treatment with prolonged-release melatonin (2 mg) or matching placebo, and usual benzodiazepine dosage...... significantly increased the interdaily stability and at a trend level decreased the intradaily variability compared with placebo. Benzodiazepine dose reduction was not associated with these circadian rhythm parameters. Activity counts were generally higher after benzodiazepine dose reduction compared with pre......BACKGROUND: Patients with severe mental illness often suffer from disruptions in circadian rest-activity cycles, which might partly be attributed to ongoing psychopharmacological medication. Benzodiazepines are frequently prescribed for prolonged periods despite recommendations of only short...

  18. An iodine-125 radioimmunoassay for the direct detection of benzodiazepines in blood and urine

    International Nuclear Information System (INIS)

    Goddard, C.P.; Stead, A.H.; Mason, P.A.; Law, B.; Moffat, A.C.; McBrien, M.; Cosby, S.

    1986-01-01

    A radioimmunoassay (RIA) for the direct detection of benzodiazepines in blood and urine is described. It is based on a commercially available antiserum and an easily synthesised radio-iodinated derivative of clonazepam that allows the use of relatively simple gamma-counting procedures. The assay can detect low therapeutic levels of all of the benzodiazepines currently available in the UK in 50-μl samples of blood and urine (1-50 ng ml -1 , depending on the drug); no prior sample preparation is required. It is inexpensive, rapid, simple to perform and is broadly specific for the benzodiazepine class of drugs. The assay offers a most suitable means of screening large numbers of samples of forensic interest for the presence of the benzodiazepines. (author)

  19. Renal Hemangiopericytoma

    Directory of Open Access Journals (Sweden)

    İbrahim Halil Bozkurt

    2015-03-01

    Full Text Available Hemangiopericytoma is an uncommon perivascular tumor originating from pericytes in the pelvis, head and tneck, and the meninges; extremely rarely in the urinary system. We report a case of incidentally detected renal mass in which radiologic evaluation was suggestive of renal cell carcinoma. First, we performed partial nephrectomy, and then, radical nephrectomy because of positive surgical margins and the pathological examination of the surgical specimen that revealed a hemangiopericytoma. No additional treatment was administered.

  20. Benzodiazepines and risk of all cause mortality in adults: cohort study.

    Science.gov (United States)

    Patorno, Elisabetta; Glynn, Robert J; Levin, Raisa; Lee, Moa P; Huybrechts, Krista F

    2017-07-06

    Objectives  To evaluate the risk of all cause mortality associated with initiating compared with not initiating benzodiazepines in adults, and to address potential treatment barriers and confounding related to the use of a non-active comparator group. Design  Retrospective cohort study. Setting  Large de-identified US commercial healthcare database (Optum Clinformatics Datamart). Participants  1:1 high dimensional propensity score matched cohort of benzodiazepine initiators, and randomly selected benzodiazepine non-initiators with a medical visit within 14 days of the start of benzodiazepine treatment (n=1 252 988), between July 2004 and December 2013. To address treatment barriers and confounding, patients were required to have filled one or more prescriptions for any medication in the 90 days and 91-180 days before the index date (ie, the date of starting benzodiazepine treatment for initiators and the date of the selected medical visit for benzodiazepine non-initiators) and the high dimensional propensity score was estimated on the basis of more than 300 covariates. Main outcome measure  All cause mortality, determined by linkage with the Social Security Administration Death Master File. Results  Over a six month follow-up period, 5061 and 4691 deaths occurred among high dimensional propensity score matched benzodiazepine initiators versus non-initiators (9.3 v 9.4 events per 1000 person years; hazard ratio 1.00, 95% confidence interval 0.96 to 1.04). A 4% (95% confidence interval 1% to 8%) to 9% (2% to 7%) increase in mortality risk was observed associated with the start of benzodiazepine treatment for follow-ups of 12 and 48 months and in subgroups of younger patients and patients initiating short acting agents. In secondary analyses comparing 1:1 high dimensional propensity score matched patients initiating benzodiazepines with an active comparator, ie, patients starting treatment with selective serotonin reuptake inhibitor antidepressants

  1. Synthesis of Riboflavines, Quinoxalinones and Benzodiazepines through Chemoselective Flow Based Hydrogenations

    Directory of Open Access Journals (Sweden)

    Marcus Baumann

    2014-07-01

    Full Text Available Robust chemical routes towards valuable bioactive entities such as riboflavines, quinoxalinones and benzodiazepines are described. These make use of modern flow hydrogenation protocols enabling the chemoselective reduction of nitro group containing building blocks in order to rapidly generate the desired amine intermediates in situ. In order to exploit the benefits of continuous processing the individual steps were transformed into a telescoped flow process delivering selected benzodiazepine products on scales of 50 mmol and 120 mmol respectively.

  2. Engagement in leisure activities and benzodiazepine use in a French community-dwelling elderly population.

    Science.gov (United States)

    Bazin, Fabienne; Noize, Pernelle; Dartigues, Jean-François; Ritchie, Karen Anne; Tavernier, Beatrice; Moore, Nicholas; Pariente, Antoine; Fourrier-Reglat, Annie

    2012-07-01

    The prevalence of benzodiazepine use among community-dwelling older persons varies between 10% and 30%. The aim of this study was to explore the association between leisure activities and the use of benzodiazepine among older persons living at home. The study population included 4848 persons aged 65 years and over living in either of two French cities. Information was collected from a questionnaire administered to the respondents by trained psychologists during face-to-face interviews at home and from a self-administered questionnaire. Baseline examination included socio-demographic characteristics, drug use and leisure activities. We classified as benzodiazepine users subjects who reported use of at least one benzodiazepine during the month preceding the interview. The association between the use of benzodiazepine and leisure activities was assessed by logistic regression adjusted on known potential confounders. More than 18% of participants reported use of at least one benzodiazepine. The adjusted odds ratio (OR) of benzodiazepine use associated with no or lower participation versus participation in the following activities were as follows: OR = 1.31 (95% confidence interval (CI): 1.09 to 1.58) for mental activity; OR = 1.50 (CI: 1.12 to 2.03) for physical activity; OR = 1.28 (CI: 1.05 to 1.55) for productive activity and OR = 0.82 (CI: 0.69 to 0.97) for recreational activity. Low engagement in stimulating activities and high engagement in sedentary activities were associated with recent benzodiazepine use. Copyright © 2011 John Wiley & Sons, Ltd.

  3. Benzodiazepine receptor binding in vivo with (/sup 3/)-Ro 15-1788

    Energy Technology Data Exchange (ETDEWEB)

    Goeders, N.E.; Kuhar, M.J.

    1985-07-29

    In vivo benzodiazepine receptor binding has generally been studied by ex vivo techniques. In this investigation, the authors identify the conditions where (/sup 3/H)-Ro 15-1788 labels benzodiazepine receptors by true in vivo binding, i.e. where workable specific to nonspecific ratios are obtained in intact tissues without homogenization or washing. (/sup 3/H)-Flunitrazepam and (/sup 3/H)-clonazepam did not exhibit useful in vivo receptor binding. 39 references, 5 figures, 1 table.

  4. Intramolecular Azide to Alkene Cycloadditions for the Construction of Pyrrolobenzodiazepines and Azetidino-Benzodiazepines

    Directory of Open Access Journals (Sweden)

    Karl Hemming

    2014-10-01

    Full Text Available The coupling of proline- and azetidinone-substituted alkenes to 2-azidobenzoic and 2-azidobenzenesulfonic acid gives precursors that undergo intramolecular azide to alkene 1,3-dipolar cycloadditions to give imine-, triazoline- or aziridine-containing pyrrolo[1,4]benzodiazepines (PBDs, pyrrolo[1,2,5]benzothiadiazepines (PBTDs, and azetidino[1,4]benzodiazepines. The imines and aziridines are formed after loss of nitrogen from a triazoline cycloadduct. The PBDs are a potent class of antitumour antibiotics.

  5. Addressing the Issue of Chronic, Inappropriate Benzodiazepine Use: How Can Pharmacists Play a Role?

    Directory of Open Access Journals (Sweden)

    Helen C. Gallagher

    2013-09-01

    Full Text Available Prescribing guidelines do not recommend the long-term use of benzodiazepines since their effectiveness with chronic use is out-weighed by risks including dependence, memory and cognitive impairment, hip fractures and traffic accidents. Despite these guidelines, historical data points to an increasing proportion of inappropriate, repeat prescribing of benzodiazepines in Ireland and elsewhere, with up to 33% of patients who use these drugs doing so long-term. The typical long-term benzodiazepine user is an older, socio-economically disadvantaged patient who has been prescribed these medicines by their general practitioner (GP and dispensed them by their community pharmacist. Misuse of benzodiazepines in nursing homes and psychiatric institutions is also of concern, with one Irish study indicating that almost half of all admissions to a psychiatric hospital were prescribed these drugs, usually despite a lack of clear clinical need. Discontinuation of benzodiazepines has proven to be of benefit, as it is followed by improvements in cognitive and psychomotor function, particularly in elderly patients. It is obvious that an inter-professional effort, focusing on the primary care setting, is required to address benzodiazepine misuse and to ensure appropriate pharmaceutical care. Pharmacists must be an integral part of this inter-professional effort, not least because they are uniquely positioned as the health professional with most frequent patient contact. There is already some supporting evidence that pharmacists’ involvement in interventions to reduce benzodiazepine use can have positive effects on patient outcomes. Here, this evidence is reviewed and the potential for pharmacists to play an expanded role in ensuring the appropriate use of benzodiazepines is discussed.

  6. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment: A register-based cohort study of subsequent benzodiazepine use, alcohol recidivism and mortality.

    Science.gov (United States)

    Askgaard, Gro; Hallas, Jesper; Fink-Jensen, Anders; Molander, Anna Camilla; Madsen, Kenneth Grønkjær; Pottegård, Anton

    2016-04-01

    Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. The study was a register-based cohort study of patients admitted for alcohol withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. A total of 1063 patients treated with chlordiazepoxide and 1365 patients treated with phenobarbital were included. After one year, the outcome rates per 100 person-years in the phenobarbital versus the chlordiazepoxide cohort were 9.20 vs. 5.13 for use of benzodiazepine, 37.9 vs. 37.9 for alcohol recidivism and 29 vs. 59 for mortality. Comparing phenobarbital to chlordiazepoxide treated, the HR of subsequent use of benzodiazepines was 1.56 (95%CI 1.05-2.30). Similarly, the HR for alcohol recidivism was 0.99 (95%CI 0.84-1.16). Lastly, the HR for 30-days and 1 year mortality was 0.25 (95%CI 0.08-0.78) and 0.51 (95%CI 0.31-0.86). There was no decreased risk of subsequent benzodiazepine use or alcohol recidivism in patients treated with phenobarbital compared to chlordiazepoxide. Phenobarbital treatment was associated with decreased mortality, which might be confounded by somatic comorbidity among patients receiving chlordiazepoxide. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Low-profile stent system for treatment of atherosclerotic renal artery stenosis : The GREAT trial

    NARCIS (Netherlands)

    Sapoval, Marc; Zahringer, Markus; Pattynama, Peter; Rabbia, Claudio; Vignali, Claudio; Maleux, Geert; Boyer, Louis; Szczerbo-Trojanowska, Malgorzata; Jaschke, Werner; Hafsahl, Geir; Downes, Mark; Beregi, Jean Paul; Veeger, Nic; Talen, Aly

    PURPOSE: The Palmaz Genesis Peripheral Stainless Steel Balloon Expandable Stent in Renal Artery Treatment (GREAT) Trial was designed to assess the safety and performance of a low-profile stent for the treatment of obstructive renal artery disease by looking at 6-month renal artery patency uniformly

  8. [Benzodiazepine dependence and the risk of depression and anxiety disorders: seniors' health study].

    Science.gov (United States)

    Nkogho Mengue, P-G; Abdous, B; Berbiche, D; Preville, M; Voyer, P

    2014-06-01

    The objective of this study is to examine the relationship between benzodiazepine dependence and anxiety disorders and depression in people aged 65 years and over. We referred to the data from the study on the health of seniors, a survey of a representative sample of 707 benzodiazepine users living in the community in Quebec, Canada. Benzodiazepine dependence, anxiety disorders and depression were measured using self-reported questionnaires based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth revised edition. Seniors have consumed an average daily dose of 6.1±7.6mg diazepam equivalent to an average of 205±130 days. The prevalence of benzodiazepine dependence has been estimated at 9.5%. This dependence increases the risk of minor depression for females (relative risk [RR]=4.36, confidence interval 95% [95% CI]=1.19 to 15.99). The results of this study suggest that the use of benzodiazepines is far from being optimal among seniors in Quebec. The proportion of seniors who develop an addiction is important. The results illustrate the need to develop and implement programs to improve the quality of benzodiazepine use among this population. Copyright © 2013 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  9. Nonmedical Abuse of Benzodiazepines in Opiate-Dependent Patients in Tehran, Iran

    Science.gov (United States)

    Babakhanian, Masuade; Sadeghi, Maliheh; Mansoori, Nader; Alam Mehrjerdi, Zahra; Tabatabai, Mahmood

    2012-01-01

    Objective: The purpose of the present preliminary study was to explore the prevalence of nonmedical abuse of benzodiazepines in a group of opiate-dependent patients who were on methadone maintenance treatment (MMT) program in outpatient clinics in the south-west of Tehran, Iran. Methods: 114 male and female opiate-dependent clients who met DSM.IV-TR criteria for opiate dependence with mean age 36.5 years participated in the study from 16 clinics and completed a self-report questionnaire on demographics and substance use details. Then the participants were interviewed on the details of nonmedical abuse of benzodiazepines. Results: The study findings indicated that the current nonmedical abuse of benzodiazepines was commonly prevalent among participants. The most common current benzodiazepines abused were alprazolam (100%) followed by chlordiazepoxide (96.5%), clonazepam (94.7%), diazepam (86.8%), lorazepam (79.8%) and oxazepam (73.7%) respectively. Depression (77%) and anxiety (72.8%) were frequently reported as the most important reasons associated with consuming benzodiazepines followed by problem in anger control (44.7%), suicide thought (12.3%), self-injury (7.9%), and suicide commitment (5.3%) respectively. Conclusion: Nonmedical abuse of benzodiazepines is an important problem among opiate addicts which should be considered in treatment interventions during MMT program. PMID:24644471

  10. An Update on the Synthesis of Pyrrolo[1,4]benzodiazepines

    Directory of Open Access Journals (Sweden)

    George Varvounis

    2016-01-01

    Full Text Available Pyrrolo[1,4]benzodiazepines are tricyclic compounds that are considered “privileged structures” since they possess a wide range of biological activities. The first encounter with these molecules was the isolation of anthramycin from cultures of Streptomyces, followed by determination of the X-ray crystal structure of the molecule and a study of its interaction with DNA. This opened up an intensive synthetic and biological study of the pyrrolo[2,1-c][1,4]benzodiazepines that has culminated in the development of the dimer SJG-136, at present in Phase II clinical trials. The synthetic efforts have brought to light some new synthetic methodology, while the contemporary work is focused on building trimeric pyrrolo[2,1-c][1,4]benzodiazepines linked together by various heterocyclic and aliphatic chains. It is the broad spectrum of biological activities of pyrrolo[1,2-a][1,4]benzodiazepines that has maintained the interest of researchers to date whereas several derivatives of the even less studied pyrrolo[1,2-d][1,4]benzodiazepines were found to be potent non-nucleoside HIV-1 reverse transcriptase inhibitors. The present review is an update on the synthesis of pyrrolo[2,1-c][1,4]benzodiazepines since the last major review of 2011, while the overview of the synthesis of the other two tricyclic isomers is comprehensive.

  11. Epidemic Use of Benzodiazepines among Older Adults in Israel: Epidemiology and Leverage Points for Improvement.

    Science.gov (United States)

    Steinman, Michael A; Low, Marcelo; Balicer, Ran D; Shadmi, Efrat

    2017-08-01

    Benzodiazepines and benzodiazepine-receptor agonists (BDZRAs, often known as "Z-drugs") are commonly used in older adults despite well-documented harms. To evaluate patterns of benzodiazepine and BDZRA use in Israel, focusing on potential leverage points where quality improvement initiatives might effectively curtail new use or the transition from intermittent to chronic use. We used national electronic medical data to assess a 10% random sample of adults receiving care in Clalit Health Services, which serves half of Israel's population. The sample included 267,221 adults, of whom 56,808 (21%) were age 65 and older. Medication use from 2013 to 2015 was ascertained using pharmacy dispensing data. In 2014, 7% of adults age 21-64 and 32% of adults age 65 and older received at least one benzodiazepine/BDZRA, including 49% of adults age 85 and older (P older users (59%) were long-term users of the drugs, and 21% of older adults who were short-term users in 2014 transitioned to medium- or long-term use in 2015. Older Arab Israelis were much less likely to receive benzodiazepine/BDZRAs than older Jewish Israelis (adjusted OR 0.28, 95% 0.25-0.31), but within each community there was no major variation in prescribing rates across clinics. Depression diagnosis was associated with particularly high rates of benzodiazepine/BDZRA use: 17% of older adults with depression received a benzodiazepine/BDZRA but no antidepressant, and 42% received both. Recent hospitalization increased the risk of new benzodiazepine/BDZRA use (adjusted OR 1.41, 95% CI 1.01-1.96), but the absolute risk increase was only 3%. Benzodiazepines/BDZRAs are used at exceptionally high rates by older Israeli adults, especially the oldest old. Important leverage points for quality improvement efforts include curtailing the transition from short-term to long-term use, reducing use in older adults with depression, and identifying reasons that explain large differences in benzodiazepine/BDZRA prescribing between

  12. Pattern of utilization of benzodiazepines in patients with hypertension: A pilot study

    Directory of Open Access Journals (Sweden)

    Divac Nevena

    2006-01-01

    Full Text Available Background/Aim. The analysis of drug prescribing in general practice in Serbia showed that the use of benzodiazepines is most frequently associated with hypertension. The aim of this study was to establish the correlation of the characteristics of patients with hypertension to antihypertensive drug therapy, and the intake of benzodiazepines. Methods. A special questionnaire was used for interviewing the patients (n = 171 chronically treated for hypertenson. Statistical tests used were χ2-test and Student's t-test. Results. No differences were noted in terms of age, gender, education, body weight, smoking habits and blood pressure (155±4.9/100±2.7 mmHg vs. 160±2.2/105±3.7 mmHg, between the group I (antihypertensive drugs+benzodiazepines: n = 79, and the group II (antihypertensives only: n = 92. The patients taking benzodiazepines received a lower number of different antihypertensive drugs (2.3±0.09 vs. 2.7±0.10; p < 0.01, but the total antihypertensive drug load was significantly greater than in the group II (2.6±0.10 vs. 1.9±0.15 defined daily doses (DDD/patient/day; p < 0.01. Benzodiazepines were taken for anxiety (62% and hypertension (21%, rarely for insomnia, mostly once a day, at bedtime. About half the patients took benzodiazepines regularly for months or years aware of the risk for addiction. Diazepam was used by 82% of the patients. The average daily exposure to benzodiazepines was 0.45±0.05 DDD/patient/day. The drug was bought without prescription in 25% of the patients, and without consulting a physician in 12% of them. Conclusion. The study confirmed a close association of hypertension with the use of benzodiazepines. The frequent use of benzodiazepines in the patients with hypertension might be caused by an inadequate response to antihypertensive drug therapy, besides anxiety and insomnia. The therapeutic efficacy of a long-term use of low doses of benzodiazepines in hypertension requires further investigation.

  13. The lesser evil? Initiating a benzodiazepine prescription in general practice

    Science.gov (United States)

    Anthierens, Sibyl; Habraken, Hilde; Petrovic, Mirko; Christiaens, Thierry

    2007-01-01

    Objective Chronic benzodiazepine (BZD) use is widespread and linked with adverse effects. There is consensus concerning the importance of initiating BZD as a crucial moment. Nevertheless specific research in this field is lacking. This paper addresses the views of GPs on why they start prescribing BZDs to first-time users. Design Qualitative study with five focus groups analysed using a systematic content analysis. Setting Regions of Ghent and Brussels in Belgium. Subjects A total of 35 general practitioners. Main outcome measure The GPs’ perspective on their initiating of BZD prescribing. Results GPs reported that they are cautious in initiating BZD usage. At the same time, GPs feel overwhelmed by the psychosocial problems of their patients. They show empathy by prescribing. They feel in certain situations there are no other solutions and they experience BZDs as the lesser evil. They admit to resorting to BZDs because of time restraint and lack of alternatives. GPs do not perceive the addictive nature of BZD consumption as a problem with first-time users. GPs do not specifically mention patients’ demand as an element for starting. Conclusion The main concern of GPs is to help the patient. GPs should be aware of the addictive nature of BZD even in low doses and a non-pharmacological approach should be seen as the best first approach. If GPs decide to prescribe a BZD they should make plain to the patient that the medication is only a “temporary” solution with clear agreements with regard to medication withdrawal. PMID:18041658

  14. Effect of chronic (-)-nicotine treatment on rat cerebral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Magata, Yasuhiro; Kitano, Haruhiro; Shiozaki, Toshiki; Iida, Yasuhiko; Nishizawa, Sadahiko; Saji, Hideo; Konishi, Junji

    2000-01-01

    The purpose of this study was to clarify the effect of (-)-nicotine on cerebral benzodiazepine receptors (BzR) with radiotracer methods. The effect of (-)-nicotine on BzR was examined in in vitro studies using chronic (-)-nicotine-treated rats using 3 H-diazepam. The in vitro radioreceptor assay showed a 14% increase in the maximum number of binding sites of BzR in chronic (-)-nicotine-treated rats in comparison with the control rats. Moreover, a convenient in vivo uptake index of 125 I-iomazenil was calculated and a higher uptake of the radioactivity was observed in the chronic (-)-nicotine-treated group than in the control group. Although further studies of the mechanism of (-)-nicotine on such BzR changes are required, an increase in the amount of BzR in the cerebral cortex was found in rats that underwent chronic (-)-nicotine treatment, and this result contributed to the understanding of the effects of (-)-nicotine and smoking on neural functions

  15. Sleep architecture in insomniacs with severe benzodiazepine abuse.

    Science.gov (United States)

    Manconi, Mauro; Ferri, Raffaele; Miano, Silvia; Maestri, Michelangelo; Bottasini, Valentina; Zucconi, Marco; Ferini-Strambi, Luigi

    2017-06-01

    Benzodiazepines (BZDs) are the most commonly prescribed compounds in insomnia. A long-term of BZDs use may cause dependence and abuse. The aim of this study was to evaluate sleep architecture and microstructure (in terms of cyclic alternating pattern - CAP - analysis and of sleep EEG power spectral analysis) in a group of long-term users of high doses of BZDs for their primary chronic insomnia. Twenty patients consecutively admitted at the Sleep Centre for drug discontinuation and 13 matched healthy controls underwent a full nocturnal video-polysomnographic recording, after one adaptation night. Significant differences were found in time in bed, REM sleep latency and sleep stage 1% which were increased in patients compared to controls, while CAP rate was dramatically decreased. During NREM sleep, patients showed a clear decrease in the relative power of delta band. Our data demonstrate that in adults with chronic insomnia, long-term use of high doses of BZDs induces a severe disruption of sleep microstructure, while sleep architecture seems to be much less affected. The long term use of high doses of BZDs for chronic insomnia induces a marked depression of slow wave activity and of its physiological instability. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  16. High enhancer, downer, withdrawal helper: Multifunctional nonmedical benzodiazepine use among young adult opioid users in New York City.

    Science.gov (United States)

    Mateu-Gelabert, Pedro; Jessell, Lauren; Goodbody, Elizabeth; Kim, Dongah; Gile, Krista; Teubl, Jennifer; Syckes, Cassandra; Ruggles, Kelly; Lazar, Jeffrey; Friedman, Sam; Guarino, Honoria

    2017-08-01

    Benzodiazepines are a widely prescribed psychoactive drug; in the U.S., both medical and nonmedical use of benzodiazepines has increased markedly in the past 15 years. Long-term use can lead to tolerance and dependence, and abrupt withdrawal can cause seizures or other life-threatening symptoms. Benzodiazepines are often used nonmedically in conjunction with other drugs, and with opioids in particular-a combination that can increase the risk for fatal and non-fatal overdose. This mixed-methods study examines nonmedical use of benzodiazepines among young adults in New York City and its relationship with opioid use. For qualitative analysis, 46 90-minute semi-structured interviews were conducted with young adult opioid users (ages 18-32). Interviews were transcribed and coded for key themes. For quantitative analysis, 464 young adult opioid users (ages 18-29) were recruited using Respondent-Driven Sampling and completed structured interviews. Benzodiazepine use was assessed via a self-report questionnaire that included measures related to nonmedical benzodiazepine and opioid use. Participants reported using benzodiazepines nonmedically for a wide variety of reasons, including: to increase the high of other drugs; to lessen withdrawal symptoms; and to come down from other drugs. Benzodiazepines were described as readily available and cheap. There was a high prevalence (93%) of nonmedical benzodiazepine use among nonmedical opioid users, with 57% reporting regular nonmedical use. In bivariate analyses, drug-related risk behaviours such as polysubstance use, drug binging, heroin injection and overdose were strongly associated with regular nonmedical benzodiazepine use. In multivariate analysis, growing up in a middle-income household (earning between $51,000 and $100,000 annually), lifetime overdose experience, having ever used cocaine regularly, having ever been prescribed benzodiazepines, recent drug binging, and encouraging fellow drug users to use benzodiazepines to

  17. An electronic intervention to improve safety for pain patients co-prescribed chronic opioids and benzodiazepines.

    Science.gov (United States)

    Zaman, Tauheed; Rife, Tessa L; Batki, Steven L; Pennington, David L

    2018-03-29

    Co-prescribing opioids and benzodiazepines increases overdose risk. A paucity of literature exists evaluating strategies to improve safety of co-prescribing. This study evaluated an electronic intervention to improve safety for patients co-prescribed chronic opioids for pain and benzodiazepines at 3 and 6 months. A prospective cohort study was conducted from December 2015 through May 2016 at San Francisco Veterans Affairs Health Care System. A clinical dashboard identified 145 eligible patients prescribed chronic opioids and benzodiazepines. Individualized taper and safety recommendations were communicated to prescribers via electronic medical record progress note and encrypted e-mail at baseline. Primary outcome was number of patients co-prescribed chronic opioids and benzodiazepines. Secondary outcomes included daily dose of opioids and benzodiazepines and number prescribed ≥100 mg morphine equivalent daily dose. Safety outcomes included number with opioid overdose education and naloxone distribution, annual urine drug screening, annual prescription drug monitoring program review, and signed opioid informed consent. Linear mixed models and generalized estimating equations were used to examine within-group change in outcomes between baseline and 3 and 6 months. Among the 145 patients, mean (standard deviation) age was 62 (11) years and 91.7% (133/145) were male. Number co-prescribed significantly decreased from 145/145 (100%) at baseline to 93/139 (67%) at 6-month follow-up (odds ratio [OR] = 0.53, 95% confidence interval [CI]: 0.34-0.81, P = .003). Mean opioid and benzodiazepine doses significantly decreased from 84.61 to 65.63 mg (95% CI: 8.32-27.86, P improve safety for patients co-prescribed chronic opioids for pain and benzodiazepines.

  18. MR angiography of in situ and transplanted renal arteries

    International Nuclear Information System (INIS)

    Smith, H.J.; Bakke, S.J.

    1993-01-01

    Three-dimensional (3D) time-of-flight (TOF) MR angiography (MRA) was performed in 34 patients with suspected renal artery disease. In situ (i.e., nontransplanted) renal arteries were studied with MRA in 14 patients. Of these, 12 had conventional angiography for comparison. Twenty-four MRAs of transplanted renal arteries were obtained in 20 patients; 8 of these had angiography as well. Significant stenoses of in situ renal arteries were diagnosed with a sensitivity of 100% and a specificity of 95%. The stenoses were all proximal; 3D TOF MRA proved inadequate for depiction of peripheral renal arteries. MRA and angiography showed good agreement between findings in 7 of 8 patients with renal transplants. In one patient with a renal transplant, MRA showed a significant stenosis of the arterial anastomosis which appeared completely normal at i.a. DSA, indicating that findings at MRA still need to be confirmed by more established alternative methods. (orig.)

  19. Benzodiazepine effect of {sup 125}I-iomazenil-benzodiazepine receptor binding and serum corticosterone level in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Fukumitsu, Nobuyoshi [Proton Medical Research Center, University of Tsukuba, Ibaragi, 305-8575 (Japan)]. E-mail: gzl13162@nifty.ne.jp; Ogi, Shigeyuki [Department of Radiology, Jikei University School of Medicine, Tokyo, 105-8461 (Japan); Uchiyama, Mayuki [Department of Radiology, Jikei University School of Medicine, Tokyo, 105-8461 (Japan); Mori, Yutaka [Department of Radiology, Jikei University School of Medicine, Tokyo, 105-8461 (Japan)

    2005-01-01

    To test the change in free or unoccupied benzodiazepine receptor (BZR) density in response to diazepam, we investigated {sup 125}I-iomazenil ({sup 125}I-IMZ) binding and serum corticosterone levels in a rat model. Wistar male rats, which received psychological stress using a communication box for 5 days, were divided into two groups according to the amount of administered diazepam: no diazepam [D (0)] group and 10 mg/kg per day [D (10)] group of 12 rats each. The standardized uptake value (SUV) of {sup 125}I-IMZ of the D (10) group were significantly lower (P<.05) than those of the D (0) group in the frontal, parietal and temporal cortices, globus pallidus, hippocampus, amygdala and hypothalamus. The serum corticosterone level ratio in the D (10) group was significantly lower than that in the D (0) group (P<.05). From the change in serum corticosterone levels, diazepam attenuated the psychological stress produced by the physical stress to animals in adjacent compartments. From the reduced binding of {sup 125}I-IMZ, it is clear that diazepam competed with endogenous ligand for the free BZR sites, and the frontal, parietal and temporal cortices, globus pallidus, hippocampus, amygdala and hypothalamus are important areas in which {sup 125}I-IMZ binding is strongly affected by administration of diazepam.

  20. Contrast-enhanced peripheral MRA

    DEFF Research Database (Denmark)

    Nielsen, Yousef W; Thomsen, Henrik S

    2012-01-01

    MRI contrast agent is injected intravenously and T1-weighted images are acquired in the subsequent arterial first-pass phase. In order to achieve high quality MR angiograms without interfering venous contamination or artifacts, a number of factors need to be taken into account. This includes magnetic......-state MRA. Gadolinium(Gd)-based contrast agents are used for CE-MRA of the peripheral arteries. Extracellular Gd agents have a pharmacokinetic profile similar to iodinated contrast media. Accordingly, these agents are employed for first-pass MRA. Blood-pool Gd-based agents are characterized by prolonged...... intravascular stay, due to macromolecular structure or protein binding. These agents can be used for first-pass, as well as steady-state MRA. Some Gd-based contrast agents with low thermodynamic stability have been linked to development of nephrogenic systemic fibrosis in patients with severe renal...

  1. Propylthiouracil and peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Valentina Van Boekel

    1992-06-01

    Full Text Available Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.

  2. Benzodiazepine use in medical out-patient clinics: a study from a developing country

    International Nuclear Information System (INIS)

    Patel, M.J.; Ahmer, S.; Khan, F.; Qureshi, A.W.A.; Shehzad, M.F.

    2013-01-01

    Objective: To estimate the prevalence of Benzodiazepine use in the outpatient setting of general medicine clinics at a single tertiary care centre. Methods: The prospective prevalence study was conducted in the outpatient setting of Internal Medicine Clinics at Aga Khan University Hospital, Karachi, from November to December 2009. All subjects were interviewed after informed consent and variables were recorded on a specially-designed proforma. Apart from basic demographics and comorbid conditions, duration, frequency and route of benzodiazepine use, as well as the reason and who initiated it was noted. Chi-square test and t test was applied to see the association of socio demographic or clinical factors with the use of benzodiazepine. Results: Of the 355 patients, 129 (36.33%) reported using the drug. The majority (n=86; 24.2%) were taking it on a daily basis. The highest numbers of patients using the drug were suffering from cardiovascular problems, 32 (25%) followed by 22 (17%) from endocrinology. Diazepam equivalent dose was around 7.04+-4, with a inter-quartile range of 3-96 weeks. Alprazolam (9%) was the most frequently prescribed Benzodiazepine. Conclusion: Benzodiazepine use is alarmingly high in the outpatient clinics of General Internal Medicine Department. There is no implementation of law to prevent its hazardous sale. In this regard all concerned should work collectively for awareness and irrational drug sale and use. (author)

  3. Degradation of benzodiazepines after 120 days of EMS deployment.

    Science.gov (United States)

    McMullan, Jason T; Jones, Elizabeth; Barnhart, Bruce; Denninghoff, Kurt; Spaite, Daniel; Zaleski, Erin; Silbergleit, Robert

    2014-01-01

    EMS treatment of status epilepticus improves outcomes, but the benzodiazepine best suited for EMS use is unclear, given potential high environmental temperature exposures. To describe the degradation of diazepam, lorazepam, and midazolam as a function of temperature exposure and time over 120 days of storage on active EMS units. Study boxes containing vials of diazepam, lorazepam, and midazolam were distributed to 4 active EMS units in each of 2 EMS systems in the southwestern United States during May-August 2011. The boxes logged temperature every minute and were stored in EMS units per local agency policy. Two vials of each drug were removed from each box at 30-day intervals and underwent high-performance liquid chromatography to determine drug concentration. Concentration was analyzed as mean (and 95%CI) percent of initial labeled concentration as a function of time and mean kinetic temperature (MKT). 192 samples were collected (2 samples of each drug from each of 4 units per city at 4 time-points). After 120 days, the mean relative concentration (95%CI) of diazepam was 97.0% (95.7-98.2%) and of midazolam was 99.0% (97.7-100.2%). Lorazepam experienced modest degradation by 60 days (95.6% [91.6-99.5%]) and substantial degradation at 90 days (90.3% [85.2-95.4%]) and 120 days (86.5% [80.7-92.3%]). Mean MKT was 31.6°C (95%CI 27.1-36.1). Increasing MKT was associated with greater degradation of lorazepam, but not midazolam or diazepam. Midazolam and diazepam experienced minimal degradation throughout 120 days of EMS deployment in high-heat environments. Lorazepam experienced significant degradation over 120 days and appeared especially sensitive to higher MKT exposure.

  4. Therapeutic response to benzodiazepine in panic disorder subtypes

    Directory of Open Access Journals (Sweden)

    Alexandre Martins Valença

    Full Text Available CONTEXT: This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam, a benzodiazepine. OBJECTIVES: To evaluate the clinical efficacy of clonazepam in a fixed dosage (2 mg/day, compared to placebo, in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes. TYPE OF STUDY: Randomized study with clonazepam and placebo. SETTING: Outpatient Anxiety and Depression Unit of the Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. PARTICIPANTS: 34 patients with a diagnosis of panic disorder with agoraphobia, between 18 and 55 years old. PROCEDURES: Administration of clonazepam or placebo for 6 weeks, in panic disorder patients, after they were classified within two subtypes of panic disorder: respiratory and non-respiratory. MAIN MEASUREMENTS: Changes in the number of panic attacks in comparison with the period before the beginning of the study; Hamilton Anxiety Scale; Global Clinical Impression Scale; and Patient's Global Impression scale. RESULTS: In the group that received clonazepam, by the end of the 6th week there was a statistically significant clinical improvement, shown by the remission of panic attacks (p < 0.001 and decrease in anxiety (p = 0.024. In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder, regarding the therapeutic response to clonazepam. CONCLUSION: Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder, suggesting there is no difference in the therapeutic response between the two subtypes.

  5. The association between benzodiazepine use and sleep quality in residential aged care facilities: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Lynna Chen

    2016-11-01

    Full Text Available Abstract Background Benzodiazepines are commonly prescribed in residential aged care facilities (RACFs for their sedative and anxiolytic effects. The objective of this study was to investigate the association between benzodiazepine use and sleep quality in residents of RACFs. Methods A cross-sectional study involving 383 participants was conducted in six Australian RACFs. Night-time sleep quality, day-time drowsiness and day-time napping behavior were assessed using a validated questionnaire. Logistic regression was used to compute adjusted odds ratios (AORs and 95% confidence intervals (CIs for the association between benzodiazepine use and sleep quality. Covariates included pain, dementia severity, depression, insomnia and other sedative use. Results Of the 383 residents (mean age 87.5 years, 77.5% female, 96(25.1% used a benzodiazepine on a regular basis. Residents who used long-acting benzodiazepines on a regular basis had higher night-time sleep quality than non-users (AOR = 4.00, 95%CI 1.06 – 15.15. Residents who used short-acting benzodiazepines on a PRN only basis had longer daytime napping times than non-users (AOR = 1.77, 95%CI 1.01 – 3.08. No benzodiazepine category was associated with day-time drowsiness. Conclusions The association between benzodiazepine use and sleep quality is dependent on the half-life and prescribing pattern of the benzodiazepine. Short-acting PRN benzodiazepines were associated with lower night time sleep quality and longer day-time napping compared to long-acting regular benzodiazepines. Longitudinal studies are needed to determine whether these findings reflect channeling of short-acting agents to residents at higher risk of sleep disorders.

  6. Suture Granuloma Mimicking Renal Cell Carcinoma: Magnetic Resonance Imaging (MRI and Pathologic Correlation

    Directory of Open Access Journals (Sweden)

    İbrahim İlker Öz

    2014-11-01

    Full Text Available Solid renal masses are generally distinguished with contrast enhancement and intratumoral fatty foci by radiological examinations. The present of enhancement is most important criteria for diagnosis of malignant lesions. Generally, a contrast enhanced solid mass in kidney is accepted as a neoplasm. Foreign body granuloma is an extraordinary cause of enhanced solid renal mass. This case of a renal suture granuloma demonstrated peripheral enhanced exophytic renal mass mimic renal cell carcinoma, and underwent surgery. At the solid renal mass with different radiological features, biopsy is an option to determining the necessity of surgery as well as the surgical approach.

  7. A case of William's syndrome associated peripheral pulmonary arterial stenosis

    International Nuclear Information System (INIS)

    Jung, Kyung Hwa; Hwang, Mi Soo; Kim, Sun Yong; Chang, Jae Chun; Park, Bok Hwan

    1988-01-01

    William's syndrome, in order to more completely delineate the total spectrum of the disorder, indicates that 'infantile hypercalcemia', 'peculiar facies' and 'supravalvular aortic stenosis.' In has other many vascular anomalies, such as peripheral pulmonary arterial stenosis, coronary arterial stenosis, celiac arterial stenosis, and renal aterial stenosis. Only 32% of the patients have evidence of supravalvular aortic stenosis. And it is very rare disease entity that has been reported rarely in Korea. Recently authors experienced a case that was questioned William's syndrome with peripheral pulmonary arterial stenosis, clinically and preliminary radiologically and this case was confirmed by operation. Here we report a case of William's syndrome with peripheral pulmonary arterial stenosis and reviewed literatures

  8. Genetic and psychosocial factors for benzodiazepine addiction. An analysis based on the results of the authors’ own research conducted in a group of benzodiazepine addicted and non-addicted individuals

    Directory of Open Access Journals (Sweden)

    Anna Konopka

    2017-03-01

    Full Text Available Purpose: In spite of the fact that the addictive potential of benzodiazepine (BDZ drugs has been known for a long time, benzodiazepine addiction remains a common problem for psychiatry to deal with. The etiology of benzodiazepine addiction is very complex. Among the risk factors, the course of the treatment, demographic status and psychological features of a patient seem to play an important role. The aim of this study was to investigate both psychological and genetic factors differentiating benzodiazepine addicts from non-addicted users.Methods: We analysed a cohort of 120 individuals treated with benzodiazepines divided into two groups: benzodiazepine addicts and non-addicted benzodiazepine users (the control group. In both groups we measured genetic polymorphisms of GABA A2 and MAOA. In both groups some psychometric measurements were performed – we investigated the level of depression, anxiety as a state and as a trait, personality features and the dominant coping style using the Beck Depression Scale, Hamilton Anxiety Scale, Five-Factor Personality Inventory NEO-FFI and the Coping Inventory for Stressful Situations [4,10,17,36,41,44].Results: There are some psychological and situational risk factors for benzodiazepine addiction such as high neuroticism, introversion and lack of the ability to release tension through interpersonal contacts, dominance of emotional coping style and high accumulation of critical life events during both childhood and adulthood. The genetic background still remains a field for further exploration.

  9. Peripheral Neuropathy and Agent Orange

    Science.gov (United States)

    ... Enter ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... 10 percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

  10. Stories of Hell and Healing: Internet Users' Construction of Benzodiazepine Distress and Withdrawal.

    Science.gov (United States)

    Fixsen, Alison M; Ridge, Damien

    2017-11-01

    Benzodiazepines are a group of drugs used mainly as sedatives, hypnotics, antiepileptics, and muscle relaxants. Consumption is recommended for 2 to 4 weeks only, due to fast onset of dependency and potentially distressing withdrawal symptoms. Few peer-review studies have drawn on the user experiences and language to appreciate firsthand experiences of benzodiazepine withdrawal or discontinuation syndrome. We looked extensively at patient stories of benzodiazepine withdrawal and recovery on Internet support sites and YouTube. Our analysis indicated that users employ rich metaphors to portray the psychologically disturbing and protracted nature of their suffering. We identified seven major themes: hell and isolation, anxiety and depression, alienation, physical distress, anger and remorse, waves and windows, and healing and renewal. By posting success stories, ex-users make known that "healing" can be a long, unpredictable process, but distress does lessen, and recovery can happen.

  11. Characterizing the Interrelationships of Prescription Opioid and Benzodiazepine Drugs With Worker Health and Workplace Hazards.

    Science.gov (United States)

    Kowalski-McGraw, Michele; Green-McKenzie, Judith; Pandalai, Sudha P; Schulte, Paul A

    2017-11-01

    Prescription opioid and benzodiazepine drug use, which has risen significantly, can affect worker health. Exploration of the scientific literature assessed (1) interrelationships of such drug use, occupational risk factors, and illness and injury, and (2) occupational and personal risk factor combinations that can affect their use. The scientific literature from 2000 to 2015 was searched to determine any interrelationships. Evidence for eight conceptual models emerged based on the search yield of 133 articles. These models summarize interrelationships among prescription opioid and benzodiazepine use with occupational injury and illness. Factors associated with the use of these drugs included fatigue, impaired cognition, falls, motor vehicle crashes, and the use of multiple providers. Prescription opioid and benzodiazepine drugs may be both a personal risk factor for work-related injury and a consequence of workplace exposures.

  12. Early ontogeny of the central benzodiazepine receptor in human embryos and fetuses

    Energy Technology Data Exchange (ETDEWEB)

    Hebebrand, J.; Hofmann, D.; Reichelt, R.; Schnarr, S.; Knapp, M.; Propping, P.; Foedisch, H.J.

    1988-01-01

    The early ontogeny of the central benzodiazepine receptor (BZR) was investigated in human embryos and fetuses between 7 and 26 weeks of gestation. Brain tissue was gained from terminated pregnancies or spontaneous abortions. Binding studies, which were performed with /sup 3/H-flunitrazepam (FNZ), revealed that specific benzodiazepine binding is already detectable at an embryonal age of 7 weeks post conception. Binding at this early stage can be displaced potently by clonazepam and the inverse agonist ..beta..-CCE. Additionally, /sup 3/H-FNZ binding is enhanced by GABA. Thus, benzodiazepine binding is of the central type. Receptor density increases steeply in whole brain between weeks 8 and 11 of gestation. In frontal cortex receptor density increases gradually between weeks 12 and 26 of gestation. No specific fetal disease entity (including trisomy 21) was consistently associated with exceptionally high or low B/sub max/-values.

  13. Daily rhythms of benzodiazepine receptor numbers in frontal lobe and cerebellum of the rat

    International Nuclear Information System (INIS)

    Brennan, M.J.W.; Volicer, L.; Moore-Ede, M.C.; Borsook, D.

    1985-01-01

    Behavioral, biochemical and neurophysiological evidence suggests that gamma-aminobutyric acid (GABA) may play an important role in the neural control of circadian rhythms. Central receptors for benzodiazepines are functionally coupled to GABA receptors and appear to mediate behavioral effects of exogenous benzodiazepines. The binding of 3 H-flunitrazepam to synaptic plasma membranes prepared from various regions of rat brain was examined at 6-hour intervals over a 36-hour period. Prominent daily rhythms in receptor number (Bmax) were observed in the frontal lobe and the cerebellum but not in the temporoparietal regions, hypothalamus or medulla/pons. Binding was highest during periods of sleep/low activity with a significant decrease occurring just prior to waking. These results suggest that daily fluctuations in benzodiazepine receptor numbers may be related to the temporal control of sleep/wake and muscle activity cycles. 23 references, 1 figure, 1 table

  14. 1-Methyl-beta-carboline (harmane), a potent endogenous inhibitor of benzodiazepine receptor binding.

    Science.gov (United States)

    Rommelspacher, H; Nanz, C; Borbe, H O; Fehske, K J; Müller, W E; Wollert, U

    1980-10-01

    The interaction of several beta-carbolines with specific [3H]-flunitrazepam binding to benzodiazepine receptors in rat brain membranes was investigated. Out of the investigated compounds, harmane and norharmane were the most potent inhibitors of specific [3H]-flunitrazepam binding, with IC50-values in the micromolar range. All other derivatives, including harmine, harmaline, and several tetrahydroderivatives were at least ten times less potent. Harmane has been previously found in rat brain and human urine, so it is the most potent endogenous inhibitor of specific [3H]-flunitrazepam binding known so far, with a several fold higher affinity for the benzodiazepine receptor than inosine and hypoxanthine. Thus, we suggest that harmane or other related beta-carbolines could be potential candidates as endogenous ligands of the benzodiazepine receptor.

  15. Dependence and withdrawal reactions to benzodiazepines and selective serotonin reuptake inhibitors. How did the health authorities react?

    DEFF Research Database (Denmark)

    Nielsen, Margrethe; Hansen, Ebba Holme; Gøtzsche, Peter C

    2013-01-01

    Our objective was to explore communications from drug agencies about benzodiazepine dependence and selective serotonin reuptake inhibitors (SSRIs) withdrawal reactions over time.......Our objective was to explore communications from drug agencies about benzodiazepine dependence and selective serotonin reuptake inhibitors (SSRIs) withdrawal reactions over time....

  16. Does tailoring really make a difference? : the development and evaluation of tailored interventions aimed at benzodiazepine cessation

    NARCIS (Netherlands)

    Wolde, Geeske Brecht ten

    2008-01-01

    Because of the problems associated with chronic benzodiazepine use, there is impetus to prevent and reduce chronic benzodiazepine use. The overall aim was to develop a 'tailor-made' intervention in order to reduce chronic use. Before developing tailored patient education, it is first of all

  17. The effects of benzodiazepine-receptor antagonists and partial inverse agonists on acute hepatic encephalopathy in the rat

    NARCIS (Netherlands)

    Bosman, D. K.; van den Buijs, C. A.; de Haan, J. G.; Maas, M. A.; Chamuleau, R. A.

    1991-01-01

    Two benzodiazepine-receptor partial inverse agonists (Ro 15-4513, Ro 15-3505) and one benzodiazepine-receptor antagonist (flumazenil) were administered to rats with hepatic encephalopathy due to acute liver ischemia. Significant improvement (P less than 0.002) of both the clinical grade of hepatic

  18. Renal candidiasis

    International Nuclear Information System (INIS)

    Khanna, S.; Malik, N.; Khandelwal, N.

    1990-01-01

    Most fungal infections of the urinary tract are caused by Candida albicans, a yeast-like saprophytic fungus which may become apathogen under various conditions which lower the host resistance. The use of computed tomography in the diagnosis of renal fungus balls is the subject of this communication with emphasis on the radiologists role in the recognition of this entity. (H.W.). 6 refs.; 2 figs

  19. Twenty-year trends in benzodiazepine dispensing in the Australian population.

    Science.gov (United States)

    Islam, M M; Conigrave, K M; Day, C A; Nguyen, Y; Haber, P S

    2014-01-01

    Considerable concern has been expressed about overprescribing of benzodiazepines and related harms. Past analyses have relied on World Health Organization-defined daily doses (DDD) which are sometimes out of keeping with clinical usage. This study examines 20-year (1992-2011) trends of benzodiazepine dispensing in Australia using both DDD and Ashton equivalent dose. Data from the Drug Utilisation Sub-Committee and the Pharmaceutical Benefits Scheme (PBS) website were analysed. Trends in number of prescriptions, DDD/1000 people/day and DDD/prescription were examined over time, and between states/territories. In the 20-year period, 174 080 904 scripts were recorded, with temazepam the most dispensed benzodiazepine (35% of scripts), followed by diazepam (23%). Overall recorded utilisation fell from 27.7 DDD/1000 people/day in 1992 to 20.8 in 2011 (24.9% decrease). There were striking changes in use of individual benzodiazepines over time, with reductions in oxazepam and flunitrazepam and dramatic increases in alprazolam. Since 1998, there has been a steady increase, albeit modest, in per script DDD. The DDD/1000 people/day for items dispensed through PBS/Repatriaton-PBS was highest in Tasmania and lowest in Northern Territory. Despite a modest overall decline in the amount of benzodiazepine dispensed, the level of use is still likely to reflect relative over-prescribing given the paucity of accepted indications for long-term use. Since 1998, there was a polynomial increase in quantity dispensed per script. The WHO-defined DDD for clonazepam seems inappropriate and could impede monitoring of its abuse. Other problems include lack of national data for medications not subsidised on PBS/Repatriation PBS. A broad policy approach is required, not one which targets only one particular benzodiazepine. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  20. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

    DEFF Research Database (Denmark)

    Baandrup, Lone; Fagerlund, Birgitte; Jennum, Poul

    2011-01-01

    Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged...... benzodiazepine administration in patients with schizophrenia. Furthermore, we aim to investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life....

  1. Renal hemangioma

    Directory of Open Access Journals (Sweden)

    Theodorico F. da Costa Neto

    2004-06-01

    Full Text Available INTRODUCTION: Renal hemangioma is a relatively rare benign tumor, seldom diagnosed as a cause of hematuria. CASE REPORT: A female 40-year old patient presented with continuous gross hematuria, anemia and episodic right lumbar pain, with onset about 3 months previously. The patient underwent multiple blood transfusions during her hospital stay and extensive imaging propedeutics was performed. Semi-rigid ureterorenoscopy evidenced a bleeding focus in the upper calix of the right kidney, with endoscopic treatment being unfeasible. The patient underwent right upper pole nephrectomy and presented a favorable outcome. Histopathological analysis of the surgical specimen showed that it was a renal hemangioma. COMMENTS: Imaging methods usually employed for diagnostic investigation of hematuria do not have good sensitivity for renal hemangioma. However, they are important to exclude the most frequent differential diagnoses. The ureterorenoscopy is the diagnostic method of choice and endoscopic treatment can be feasible when the lesion is accessible and electrocautery or laser are available. We emphasize the open surgical treatment as a therapeutic option upon failure of less invasive methods.

  2. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile

  3. Radiopharmaceuticals for renal studies

    International Nuclear Information System (INIS)

    Verdera, Silvia

    1994-01-01

    Between the diagnostic techniques using radiopharmaceuticals in nuclear medicine it find renal studies.A brief description about renal glomerular filtration(GFR) and reliability renal plasma flux (ERPF),renal blood flux measurement agents (RBF),renal scintillation agents and radiation dose estimates by organ physiology was given in this study.tabs

  4. Limited tryptic proteolysis of the benzodiazepine binding proteins in different species reveals structural homologies.

    Science.gov (United States)

    Friedl, W; Lentes, K U; Schmitz, E; Propping, P; Hebebrand, J

    1988-12-01

    Peptide mapping can be used to elucidate further the structural similarities of the benzodiazepine binding proteins in different vertebrate species. Crude synaptic membrane preparations were photoaffinity-labeled with [3H]flunitrazepam and subsequently degraded with various concentrations of trypsin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by fluorography allowed a comparison of the molecular weights of photolabeled peptides in different species. Tryptic degradation led to a common peptide of 40K in all species investigated, a finding indicating that the benzodiazepine binding proteins are structurally homologous in higher bony fishes and tetrapods.

  5. Neurocognitive performance, subjective well-being, and psychosocial functioning after benzodiazepine withdrawal in patients with schizophrenia or bipolar disorder

    DEFF Research Database (Denmark)

    Baandrup, Lone; Fagerlund, Birgitte; Glenthoj, Birte

    2017-01-01

    -tapering compared with normative data. Neither benzodiazepine withdrawal nor treatment group affected subjective well-being or psychosocial functioning. In conclusion, add-on melatonin does not seem to affect cognition, well-being, or psychosocial functioning in patients with severe mental illness. The observed......Chronic benzodiazepine use is common in patients with mental illness and is associated with cognitive impairment. It is unclear whether benzodiazepine-induced cognitive impairment is reversible. Amelioration of cognitive dysfunction may be facilitated during benzodiazepine tapering by add......-on melatonin due to its anti-inflammatory and neuroprotective properties. We examined how melatonin and benzodiazepine withdrawal affect cognition, subjective well-being, and psychosocial functioning. Eighty patients with schizophrenia or bipolar disorder were randomized to add-on treatment once daily...

  6. [Physical performance and sedation: comparative study of the effects of a benzodiazepine (temazepam) and of a non-benzodiazepine hypnotic (zolpidem)].

    Science.gov (United States)

    Gremion, G; Sutter-Weyrich, C; Rostan, A; Forster, A

    1992-09-01

    It is well-known that many athletes experience some form of precompetition stress that may result in insomnia during the night before their competition. Yet, sleep withdrawal even if only partial, has a negative influence on performance, particularly when the type of exercise requires good psychomotor performance The purpose of the present study was to investigate whether the intake of a hypnotic drug would have negative effects on physical performance capacity. The authors have compared the effects of oral temazepam, a medium half-life benzodiazepine vs oral zolpidem, a short half-life non-benzodiazepine drug, vs placebo. A randomized double-blind trial was used to assess endurance, resistance, strength and coordination in 26 athletes. The results did not show any differences between the three groups, neither in physical performance characteristic nor in coordination. It is concluded that as regards the performance capacity, there is no risk for stressed athletes to use sleep inducers the night before their competition.

  7. New benzodiazepine and Z-hypnotic users and disability pension: an eight-year nationwide observational follow-up study.

    Science.gov (United States)

    Tvete, Ingunn F; Bjørner, Trine; Skomedal, Tor

    2017-09-01

    To compare how newly initiated treatment with benzodiazepines, Z-hypnotics or both associates with the reception of disability pension among 40,661 individuals of a working age. Prescription register study. Norwegian nationwide prescriptions socio-economic and disability status data. Cox regression analyses. New benzodiazepine or Z-hypnotic users. Time to receive disability pension given benzodiazepine or Z-hypnotic use or both. Additional analyses focused on the benzodiazepine first redeemed. Among new users 8.65% of Z-hypnotic users, 12.29% of benzodiazepines users and 13.96% of combined Z-hypnotic and benzodiazepine users became disability pensioners. Z-hypnotic users were weaker associated with becoming disability pensioners (HR = 0.78, CI: 0.73-0.84) and combined users were stronger associated (HR = 1.09, CI: 1.01-1.17), than benzodiazepine users. Women had higher risk than men for becoming disability pensioners. Higher age, lower education, previous drug use and psychiatrist as first prescriber were risk factors. Comparing first benzodiazepine redeemed; clonazepam initiators were stronger associated with becoming disability pensioners than diazepam initiators were (HR = 2.22, CI: 1.81-2.71). No differences between other benzodiazepine users were found. Adjusting for known risk factors gave lower risk for Z-hypnotic users compared to benzodiazepine users for receiving disability pension. Combined use increased the risk further. Clonazepam initiators are especially at risk. These findings may be helpful in prescribing situations to identify and guide individuals at risk for becoming disability pensioners.

  8. Bilateral renal artery variation

    OpenAIRE

    Üçerler, Hülya; Üzüm, Yusuf; İkiz, Z. Aslı Aktan

    2014-01-01

    Each kidney is supplied by a single renal artery, although renal artery variations are common. Variations of the renal arteryhave become important with the increasing number of renal transplantations. Numerous studies describe variations in renalartery anatomy. Especially the left renal artery is among the most critical arterial variations, because it is the referred side forresecting the donor kidney. During routine dissection in a formalin fixed male cadaver, we have found a bilateral renal...

  9. Renal tuberculosis

    Directory of Open Access Journals (Sweden)

    Džamić Zoran

    2016-01-01

    Full Text Available Tuberculosis is still a significant health problem in the world, mostly in developing countries. The special significance lies in immunocompromised patients, particularly those suffering from the HIV. Urogenital tuberculosis is one of the most common forms of extrapulmonary tuberculosis, while the most commonly involved organ is the kidney. Renal tuberculosis occurs by hematogenous dissemination of mycobacterium tuberculosis from a primary tuberculosis foci in the body. Tuberculosis is characterized by the formation of pathognomonic lesions in the tissues - granulomata. These granulomata may heal spontaneously or remain stable for years. In certain circumstances in the body associated with immunosuppression, the disease may be activated. Central caseous necrosis occurs within tuberculoma, leading to formation of cavities that destroy renal parenchyma. The process may gain access to the collecting system, forming the caverns. In this way, infection can be spread distally to renal pelvis, ureter and bladder. Scaring of tissue by tuberculosis process may lead to development of strictures of the urinary tract. The clinical manifestations are presented by nonspecific symptoms and signs, so tuberculosis can often be overlooked. Sterile pyuria is characteristic for urinary tuberculosis. Dysuric complaints, flank pain or hematuria may be presented in patients. Constitutional symptoms of fever, weight loss and night sweats are presented in some severe cases. Diagnosis is made by isolation of mycobacterium tuberculosis in urine samples, by cultures carried out on standard solid media optimized for mycobacterial growth. Different imaging studies are used in diagnostics - IVU, CT and NMR are the most important. Medical therapy is the main modality of tuberculosis treatment. The first line anti-tuberculosis drugs include isoniazid, rifampicin, pyrazinamide and ethambutol. Surgical treatment is required in some cases, to remove severely damaged kidney, if

  10. Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure

    DEFF Research Database (Denmark)

    Gülberg, V; Møller, S; Henriksen, Jens Henrik Sahl

    2000-01-01

    homeostasis. Therefore, the aim of the present study was to investigate the possible role of CNP in renal function disturbances in patients with cirrhosis of the liver. METHODS: Peripheral venous and urinary concentrations of CNP were determined in samples from 11 healthy controls, 20 cirrhotic patients...... with normal renal function (creatinine clearance 117 (8) ml/min), and 20 cirrhotic patients with impaired renal function (creatinine clearance 35 (4) ml/min). In a second protocol, arterial and renal venous plasma concentrations of CNP were determined in 37 patients with cirrhosis of the liver to estimate...... renal extraction ratios of CNP. A sensitive and specific radioimmunoassay was applied after solid phase extraction of samples. RESULTS: Plasma CNP was lower in cirrhotic patients with normal and impaired renal function than in controls (3.0 (0.4) and 2.7 (0.2) v. 4.2 (0.4) pg/ml, respectively; p

  11. Renal denervation

    DEFF Research Database (Denmark)

    Olsen, Lene Kjær; Kamper, Anne-Lise; Svendsen, Jesper Hastrup

    2015-01-01

    PURPOSE OF REVIEW: Renal denervation (RDN) has, within recent years, been suggested as a novel treatment option for patients with resistant hypertension. This review summarizes the current knowledge on this procedure as well as limitations and questions that remain to be answered. RECENT FINDINGS...... selection, anatomical and physiological effects of RDN as well as possible beneficial effects on other diseases with increased sympathetic activity. The long awaited Symplicity HTN-3 (2014) results illustrated that the RDN group and the sham-group had similar reductions in BP. SUMMARY: Initial studies...

  12. Renal papillary necrosis

    Science.gov (United States)

    ... asking your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Bushinsky DA, Monk RD. Nephrolithiasis and nephrocalcinosis. ...

  13. CT differentiation of renal tumor invading parenchyma and pelvis: renal cell carcinoma vs transitional cell carcinoma

    International Nuclear Information System (INIS)

    Lee, Chang Hee; Cho, Seong Beum; Park, Cheol Min; Cha, In Ho; Chung, Kyoo Byung

    1994-01-01

    The differentiation between renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) is important due to the different methods of treatment and prognosis. But occasionally it is difficult to draw a distinction between the two diseases when renal parenchyma and renal collecting systems are invaded simultaneously. We reviewed CT scans of 37 cases of renal cell carcinoma and 12 cases of transitional cell carcinoma which showed involvement of renal parenchyma and renal sinus fat on CT. Retrospective analysis was performed by 3 abdominal radiologists. Check points were renal contour bulging or reinform shape, location of mass center, intact parenchyma overlying the tumor, cystic change, calcification, LN metastasis, vessel invasion, and perirenal extention. There were renal contour bulging due to the tumor mass in 33 out of 37 cases of renal cell carcinoma, where a and nine of 12 cases of transitional cell carcinoma maintained the reinform appearance. This is significant statiscal difference between the two(P<0.005). Center of all TCCs were located in the renal sinus, and 24 out of 35 cases of RCC were located in the cortex(P<0.005). Thirty-six out of 37 cases of RCC lost the overlying parenchyma, where as 4 out of 9 cases of well enhanced TCC had intact overlying parenchyma(P<0.005) RCC showed uptic change within the tumor mags in 31 cases which was significanity higher than the 4 cases in TCC(P<0.05). CT findings of renal cell carcinoma are contour bulging, peripheral location, obliteration of parenchyma, and cystic change. Findings of transitional cell carcinoma are reinform appearance, central location within the kidney, intact overlying parenchyma, and rare cystic change

  14. Benzodiazepine Use Among Low Back Pain Patients Concurrently Prescribed Opioids in the Military Health System

    Science.gov (United States)

    2017-08-27

    TYPE 08/27/2017 Poster 4. TITLE AND SUBTITLE Benzodiazepine Lise Among Lo\\v Back Pain Patients Concurrently Prescribed Opioids in the tvfilitary...PRO’-:iRAM ELEMENT NUMBER 5d. PROJECT NUMBER Se. TASK NUMBER Sf. WORK UNIT NUMBER 8. PERFORMING ORGANIZATION REPORT NUMBER 17356 10. SPONSOR

  15. Evaluation of benzodiazepines and zolpidem in nails and their stability after prolonged exposure to chlorinated water.

    Science.gov (United States)

    Moretti, Matteo; Andrello, Luisa; Visonà, Silvia; Vignali, Claudia; Groppi, Angelo; Freni, Francesca; Osculati, Antonio; Tajana, Luca; Morini, Luca

    2018-04-15

    The study aims the development and validation of a LC-MS/MS method for the identification and quantification of benzodiazepines and zolpidem in nails as alternative keratinized matrix to hair in long-term monitoring of anxiolytic and hypnotic drugs. Both fingernail and toenail samples (1-2 mm) were collected by clipping the excess overhang of the nail from volunteers and from postmortem cases. They were washed twice with organic solvents, dried under nitrogen stream, pulverized, immersed in a methanol solution (internal standard: diazepam-D5) and sonicated up to two hours. The solution was then direct injected in the LC-MS/MS system. Mass spectrometry was set in MRM mode, selecting two transitions for each substance. 32 analytes among benzodiazepines, metabolites and hypnotics were included in the list. The method fulfilled the internationally required criteria for validation. Limits of detection ranged from 0.03 pg/mg (zolpidem) to 13.1 pg/mg (bromazepam). 9 subjects under therapy were positive at 7 different benzodiazepines and/or metabolites (lorazepam, desalkylflurazepam, bromazepam, diazepam, alprazolam, lormetazepam and prazepam), while 5 molecules were measured in 4 postmortem cases (diazepam, desmethyldiazepam, delorazepam, 7-aminoclonazepam and zolpidem). In vitro experiments on eight authentic samples suggested that benzodiazepines in nails are influenced by the prolonged exposure to chlorinated water. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. SEX-DIFFERENCES AMONG RECIPIENTS OF BENZODIAZEPINES IN DUTCH GENERAL-PRACTICE

    NARCIS (Netherlands)

    van der Waals, F. W.; Mohrs, J.; Foets, M.

    1993-01-01

    Objective-To analyse sex differences among recipients of benzodiazepines in Dutch general practice. Design-Study of consultations and associated interventions as recorded in the Dutch national survey of general practice. Setting-Practices of 45 general practitioners monitored during 1 April to 30

  17. Quantitative autoradiography of muscarinic and benzodiazepine receptors in the forebrain of the turtle, Pseudemys scripta

    International Nuclear Information System (INIS)

    Schlegel, J.R.; Kriegstein, A.R.

    1987-01-01

    The distribution of muscarinic and benzodiazepine receptors was investigated in the turtle forebrain by the technique of in vitro receptor autoradiography. Muscarinic binding sites were labeled with 1 nM 3 H-quinuclidinyl benzilate ( 3 H-QNB), and benzodiazepine sites were demonstrated with the aid of 1 nM 3 H-flunitrazepam ( 3 H-FLU). Autoradiograms generated on 3 H-Ultrofilm apposed to tissue slices revealed regionally specific distributions of muscarinic and benzodiazepine binding sites that are comparable with those for mammalian brain. Dense benzodiazepine binding was found in the anterior olfactory nucleus, the lateral and dorsal cortices, and the dorsal ventricular ridge (DVR), a structure with no clear mammalian homologue. Muscarinic binding sites were most dense in the striatum, accumbens, DVR, lateral geniculate, and the anterior olfactory nucleus. Cortical binding sites were studied in greater detail by quantitative analysis of autoradiograms generated by using emulsion-coated coverslips. Laminar gradients of binding were observed that were specific for each radioligand; 3 H-QNB sites were most dense in the inner molecular layer in all cortical regions, whereas 3 H-FLU binding was generally most concentrated in the outer molecular layer and was least dense through all layers in the dorsomedial cortex. Because pyramidal cells are arranged in register in turtle cortex, the laminar patterns of receptor binding may reflect different receptor density gradients along pyramidal cell dendrites

  18. Consequences of early postnatal benzodiazepines exposure in rats. I. Cognitive-like behavior

    Czech Academy of Sciences Publication Activity Database

    Mikulecká, Anna; Šubrt, Martin; Stuchlík, Aleš; Kubová, Hana

    2014-01-01

    Roč. 8, Mar 28 (2014), s. 101 ISSN 1662-5153 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA305/09/0846 Institutional support: RVO:67985823 Keywords : benzodiazepines * clonazepam * cognitive functions * development * rats Subject RIV: FH - Neurology Impact factor: 3.270, year: 2014

  19. Quantitative analysis of benzodiazepines in vitreous humor by high-performance liquid chromatography

    Science.gov (United States)

    Bazmi, Elham; Behnoush, Behnam; Akhgari, Maryam; Bahmanabadi, Leila

    2016-01-01

    Objective: Benzodiazepines are frequently screened drugs in emergency toxicology, drugs of abuse testing, and in forensic cases. As the variations of benzodiazepines concentrations in biological samples during bleeding, postmortem changes, and redistribution could be biasing forensic medicine examinations, hence selecting a suitable sample and a validated accurate method is essential for the quantitative analysis of these main drug categories. The aim of this study was to develop a valid method for the determination of four benzodiazepines (flurazepam, lorazepam, alprazolam, and diazepam) in vitreous humor using liquid–liquid extraction and high-performance liquid chromatography. Methods: Sample preparation was carried out using liquid–liquid extraction with n-hexane: ethyl acetate and subsequent detection by high-performance liquid chromatography method coupled to diode array detector. This method was applied to quantify benzodiazepines in 21 authentic vitreous humor samples. Linear curve for each drug was obtained within the range of 30–3000 ng/mL with coefficient of correlation higher than 0.99. Results: The limit of detection and quantitation were 30 and 100 ng/mL respectively for four drugs. The method showed an appropriate intra- and inter-day precision (coefficient of variation forensic toxicology laboratory. PMID:27635251

  20. ACUTE POISONING WITH BENZODIAZEPINES AND OTHER HYPNOTICS: ETIOLOGIC CAUSE, SEX/AGE DISTRIBUTION AND CLINICAL OUTCOME

    Directory of Open Access Journals (Sweden)

    Petko Marinov

    2016-11-01

    Full Text Available Purpose: Poisoning with drugs occupies a leading position among the causes of acute intoxications. Etiological distribution of medicated poisoning in different countries, even if they are adjacent, is different. In the most studies it was reported that the highest incidence of poisoning is with benzodiazepines or other psychoactive drugs. A retrospective analysis of acute poisoning with benzodiazepines and other hypnotic drugs in the Varna region for 25 years period – from 1991 to 2015 was carried out. Material and Methods: The number of patients who received hospital treatment after poisoning with benzodiazepines is 1741, and those with other hypnotics is 293, representing respectively 26.37% and 4.44% of all drug intoxications. Results: The share of poisoning with benzodiazepines and hypnotics compared to all acute intoxications is 11.66%. They are more common in women – 1566 (77%. Men are 468 (23%, the ratio of men to women was 3.34:1. The largest number of intoxications is in the age group up to 24 years - 1123 (55.2%, and only 4.1% of patients over 60 years. Intentional suicide attempts are 1896 (93.2%. Death is registered in 8 (0.4% patients.

  1. Imaging benzodiazepine receptors in man with C-11-suriclone and positron emission tomography

    International Nuclear Information System (INIS)

    Frost, J.J.; Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Links, J.M.; Trifiletti, R.; Snyder, S.H.; Wagner, H.N. Jr.

    1985-01-01

    Suriclone is a potent cyclopyrrolone, anti-anxiety drug which binds to the benzodiazepine receptor complex (BZR) with high affinity. Suriclone binds to a site on the BZR distinct from the site where benzodiazepines bind. The K/sub D/ of suriclone at 37oC is 0.03 nM. C-11-suriclone (SUR) was synthesized by reacting C-CH3I with the appropriate amine precursor. SUR (1 μg/kg) was injected IV into a baboon alone or with 1 mg/kg of Ro-151788, a benzodiazepine antagonist, and serial PET scans of the brain were obtained. High radioactivity concentrations were observed in the cerebral cortex and cerebellum which contain high densities of BZR, intermediate concentrations in thalamus and low concentrations in the striatum. When Ro-151788 was given a uniform distribution of radioactivity was observed; the radioactivity was reduced to ca. 25% of control values in the brain which was contained within the PET slice. SUR (0.2 μg/kg) was next administered to a human subject. From 30-60 minutes after injection high radioactivity concentrations were observed in the cerebral cortex and cerebellum, intermediate concentrations in the thalamus and a low concentration in the caudate. Radioactivity in the cerebral cortex and cerebellum decreased slowly with time, implying that binding of SUR to a high affinity site had occurred. These results demonstrate utility of SUR for measuring binding to the benzodiazepine receptor complex non-invasively in man

  2. Consequences of early postnatal benzodiazepines exposure in rats. II. Social behavior

    Czech Academy of Sciences Publication Activity Database

    Mikulecká, Anna; Šubrt, Martin; Pařízková, Martina; Mareš, Pavel; Kubová, Hana

    2014-01-01

    Roč. 8, May 8 (2014), s. 169 ISSN 1662-5153 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA305/09/0846 Institutional support: RVO:67985823 Keywords : benzodiazepines * clonazepam * social behavior * development * rats Subject RIV: FH - Neurology Impact factor: 3.270, year: 2014

  3. Correlates of benzodiazepine dependence in the Netherlands Study of Depression and Anxiety

    NARCIS (Netherlands)

    Manthey, L.; Lohbeck, M.; Giltay, E.J.; van Veena, T.; Zitman, F.G.; Penninx, B.W.J.H.

    2012-01-01

    Aims: Benzodiazepines (BZDs) are effective in the short term against anxiety and insomnia. However, some BZD users develop BZD dependence after a relatively short period of time. Therefore, we aimed to identify the risk factors of BZD dependence. Design: An observational cohort study. Setting: The

  4. Latent trait standardization of the benzodiazepine dependence self-report questionnaire using the Rasch scaling model.

    NARCIS (Netherlands)

    Kan, C.C.; Ven, A.H.G.S. van der; Breteler, M.H.M.; Zitman, F.G.

    2001-01-01

    The aim of the present study was to obtain standardized scores that correspond with the raw scores on the four Rasch scales of the Benzodiazepine Dependence-Self Report Questionnaire (Bendep-SRQ). The eligible normative group for standardization of the Bendep-SRQ scales consisted of 217 general

  5. Latent Trait Standardization of the Benzodiazepine Dependence Self-Report Questionnaire using the Rasch Scaling Model

    NARCIS (Netherlands)

    Kan, C.C.; Ven, A.H.G.S. van der; Breteler, M.H.M.; Zitman, F.G.

    2001-01-01

    The aim of the present study was to obtain standardized scores that correspond with the raw scores on the four Rasch scales of the Benzodiazepine Dependence-Self Report Questionnaire (Bendep-SRQ). The eligible normative group for standardization of the Bendep-SRQ scales consisted of 217 general

  6. INTERACTION BETWEEN DELTA OPIOID RECEPTORS AND BENZODIAZEPINES IN CO2- INDUCED RESPIRATORY RESPONSES IN MICE

    Science.gov (United States)

    Borkowski, Anne H.; Barnes, Dylan C.; Blanchette, Derek R.; Castellanos, F. Xavier; Klein, Donald F.; Wilson, Donald A.

    2011-01-01

    The false-suffocation hypothesis of panic disorder (Klein, 1993) suggested δ-opioid receptors as a possible source of the respiratory dysfunction manifested in panic attacks occurring in panic disorder (Preter and Klein, 2008). This study sought to determine if a lack of δ-opioid receptors in a mouse model affects respiratory response to elevated CO2, and whether the response is modulated by benzodiazepines, which are widely used to treat panic disorder. In a whole-body plethysmograph, respiratory responses to 5% CO2 were compared between δ-opioid receptor knockout mice and wild-type mice after saline, diazepam (1 mg/kg), and alprazolam (0.3 mg/kg) injection. The results show that lack of δ-opioid receptors does not affect normal response to elevated CO2, but does prevent benzodiazepines from modulating that response. Thus, in the presence of benzodiazepine agonists, respiratory responses to elevated CO2 were enhanced in δ-opioid receptor knockout mice compared to wild-type mice. This suggests an interplay between benzodiazepine receptors and δ-opioid receptors in regulating the respiratory effects of elevated CO2, which might be related to CO2 induced panic. PMID:21561601

  7. Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A.; Alvarado, M.; Budinger, T.F.; Grossman, R.; Hensley, K.; West, M.S.; Kotake, Y.; Ono, M.; Floyd, R.A.

    2001-12-10

    Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hours after endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (2-3 fold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (>50 percent) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition ({approx}25 percent decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.

  8. Endovascular Management of Iatrogenic Native Renal Arterial Pseudoaneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Sildiroglu, Onur; Saad, Wael E.; Hagspiel, Klaus D.; Matsumoto, Alan H.; Turba, Ulku Cenk, E-mail: Turba@me.com [University of Virginia Health System, Department of Radiology (United States)

    2012-12-15

    Purpose: Our purpose was to evaluate iatrogenic renal pseudoaneurysms, endovascular treatment, and outcomes. Methods: This retrospective study (2003-2011) reported the technical and clinical outcomes of endovascular therapy for renal pseudoaneurysms in eight patients (mean age, 46 (range 24-68) years). Renal parenchymal loss evaluation was based on digital subtraction angiography and computed tomography. Results: We identified eight iatrogenic renal pseudoaneurysm patients with symptoms of hematuria, pain, and hematoma after renal biopsy (n = 3), surgery (n = 3), percutaneous nephrolithotomy (n = 1), and endoscopic shock-wave lithotripsy (n = 1). In six patients, the pseudoaneurysms were small-sized (<20 mm) and peripherally located and were treated solely with coil embolization (n = 5). In one patient, coil embolization was preceded by embolization with 500-700 micron embospheres to control active bleeding. The remaining two patients had large-sized ({>=}50 mm), centrally located renal pseudoaneurysms treated with thrombin {+-} coils. Technical success with immediate bleeding cessation was achieved in all patients. There were no procedure-related deaths or complications (mean follow-up, 23.5 (range, 1-67) months). Conclusions: Treatment of renal pseudoaneurysms using endovascular approach is a relatively safe and viable option regardless of location (central or peripheral) and size of the lesions with minimal renal parenchymal sacrifice.

  9. Renal calculus

    CERN Document Server

    Pyrah, Leslie N

    1979-01-01

    Stone in the urinary tract has fascinated the medical profession from the earliest times and has played an important part in the development of surgery. The earliest major planned operations were for the removal of vesical calculus; renal and ureteric calculi provided the first stimulus for the radiological investigation of the viscera, and the biochemical investigation of the causes of calculus formation has been the training ground for surgeons interested in metabolic disorders. It is therefore no surprise that stone has been the subject of a number of monographs by eminent urologists, but the rapid development of knowledge has made it possible for each one of these authors to produce something new. There is still a technical challenge to the surgeon in the removal of renal calculi, and on this topic we are always glad to have the advice of a master craftsman; but inevitably much of the interest centres on the elucidation of the causes of stone formation and its prevention. Professor Pyrah has had a long an...

  10. Assessment of dependence and anxiety among benzodiazepine users in a provincial municipality in Rio Grande do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Janaína Barden Schallemberger

    Full Text Available Abstract Introduction: Benzodiazepines are among the most prescribed drugs for anxiety and one of the most used drug classes in the world and have a high potential for addiction. The objective of this study was to assess levels of dependence and anxiety among users of these drugs in the public health system. Methods: This was a cross-sectional, descriptive and quantitative study. Benzodiazepine users treated on the public health system were selected. Anxiety levels were assessed with the Hamilton Anxiety Scale and dependency with the Benzodiazepine Dependence Self-Report Questionnaire. Results: Benzodiazepine use was higher among women and in older age groups. Duration of benzodiazepine use was greater than 1 year for all respondents. The dependence assessment indicated that more than half of users were dependent on taking benzodiazepines and most had a severe degree of anxiety. Conclusion: This study found evidence of prolonged and inappropriate use of benzodiazepines. It is necessary to educate users about the risks of these drugs and to develop strategies to rationalize use of these drugs by working with prescribers and dispensers.

  11. A Pharmacist-Physician Collaboration to Optimize Benzodiazepine Use for Anxiety and Sleep Symptom Control in Primary Care.

    Science.gov (United States)

    Furbish, Shannon M L; Kroehl, Miranda E; Loeb, Danielle F; Lam, Huong Mindy; Lewis, Carmen L; Nelson, Jennifer; Chow, Zeta; Trinkley, Katy E

    2017-08-01

    Benzodiazepines are prescribed inappropriately in up to 40% of outpatients. The purpose of this study is to describe a collaborative team-based care model in which clinical pharmacists work with primary care providers (PCPs) to improve the safe use of benzodiazepines for anxiety and sleep disorders and to assess the preliminary results of the impact of the clinical service on patient outcomes. Adult patients were eligible if they received care from the academic primary care clinic, were prescribed a benzodiazepine chronically, and were not pregnant or managed by psychiatry. Outcomes included baseline PCP confidence and knowledge of appropriate benzodiazepine use, patient symptom severity, and medication changes. Twenty-five of 57 PCPs responded to the survey. PCPs reported greater confidence in diagnosing and treating generalized anxiety and panic disorders than sleep disorder and had variable knowledge of appropriate benzodiazepine prescribing. Twenty-nine patients had at least 1 visit. Over 44 total patient visits, 59% resulted in the addition or optimization of a nonbenzodiazepine medication and 46% resulted in the discontinuation or optimization of a benzodiazepine. Generalized anxiety symptom severity scores significantly improved (-2.0; 95% confidence interval (CI): -3.57 to -0.43). Collaborative team-based models that include clinical pharmacists in primary care can assist in optimizing high-risk benzodiazepine use. Although these findings suggest improvements in safe medication use and symptoms, additional studies are needed to confirm these preliminary results.

  12. Le benzodiazepine nel trattamento dell’ansia: profilo clinico e farmacoeconomico

    Directory of Open Access Journals (Sweden)

    Barbara Cascio

    2005-12-01

    Full Text Available Anxiety disorders impose a significant economic burden on healthcare system, patients and society as a whole. A patient with anxiety disorders, especially with panic disorder, shows some difficulties to work or to maintain an acceptable social functioning, and, frequently, needs more medical care than a normal subject, often due to unnecessary or inappropriate diagnostic tests. Adequate psychiatric treatment of anxiety disorders can lead to higher direct specialists costs (psychiatric drugs and visits but this may be offset by a decrease in non-specialist care costs and in indirect costs. Benzodiazepines have been extensively used for the treatment of anxiety and related disorders since the 1960s. Although new pharmacological and psychological treatments for anxiety are available, a lot of psychiatrists continue to endorse benzodiazepines as primary or adjunctive treatment for these disturbs, especially in the early or acute phases of the illness. In Italy, benzodiazepines have been available also as generic drugs for some years. In order to be accepted for marketing, a generic drug has to demonstrate bioequivalence, considered a reliable proxy of therapeutic equivalence, with the standard formulation and its price has to be at least 20% cheaper than the originator drug. The use of generic drugs can contain drug expenditures and facilitate a competitive market. Despite that their prices are considerably higher than those of generics, branded benzodiazepines are still widely prescribed, because of prejudices and lack of information in the community of physicians and patients. In conclusion, benzodiazepines may treat anxiety disorders, mainly in early and acute phases, increasing quality of life and saving medical resources. The availability of generics allows for marginal reduction in initial investment in drug costs.

  13. Analysis of benzodiazepines and their metabolites using DBS cards and LC-MS/MS.

    Science.gov (United States)

    Lee, Heesang; Park, Yujin; Jo, Jiyeong; In, Sangwhan; Park, Yonghoon; Kim, Eunmi; Pyo, Jaesung; Choe, Sanggil

    2015-10-01

    Dried Blood Spot (DBS) has been used a blood extraction method for inherited metabolic disorder screening since 1960s. With introduction of LC-MS/MS, not only DBS could be used to analysis drugs in small blood volume, but in various fields, such as toxicology, drug therapeutic monitoring, drug diagnostic screening, and illicit drugs. In toxicology field, many drugs (e.g. benzodiazepines, acetaminophen, small molecule drugs) have been tested with DBS. Compared with earlier blood extraction methods (SPE and LLE), DBS has lots of advantages; lower blood volume (less than 50μL), shorter analysis time caused by a more concise analysis procedure and lower cost. We optimized the DBS procedure and LC-MS/MS conditions for 18 benzodiazepines, seven benzodiazepine metabolites, and one z-drug (zolpidem) analysis in blood. 30μL of whole blood was spotted on FTA DMPK card C and dried for 2h in a desiccator. A 6-mm disk was punched and vortexed for 1min in a centrifuge tube with 300μL methanol/acetonitrile mixture (1:1, v/v). After evaporation, redissolved in 100μL mobile phase of LC-MS/MS and 5μL was injected. In the analysis for 26 target compounds in blood, all of the method validation parameters - LLOD, LLOQ, accuracy (intra- and inter-assay), and precision (intra- and inter-assay) - were satisfied with method validation criteria, within 15%. The results of matrix effect, recovery, and process efficiency were good. We developed a fast and reliable sample preparation method using DBS for 26 benzodiazepines, benzodiazepine metabolites, and z-drug (zolpidem). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Benzodiazepine Consumption Is Associated With Lower Blood Pressure in Ambulatory Blood Pressure Monitoring (ABPM): Retrospective Analysis of 4938 ABPMs.

    Science.gov (United States)

    Mendelson, Nitsan; Gontmacher, Bella; Vodonos, Allina; Novack, Victor; Abu-AjAj, Muhammad; Wolak, Arik; Shalev, Haddar; Wolak, Talya

    2018-03-10

    The effect of chronic benzodiazepine use on blood pressure has not been documented. We aimed to evaluate whether regular benzodiazepine use can be associated to the results of ambulatory blood pressure monitoring (ABPM). A retrospective analysis of the ABPM database between 2009 and 2015 was performed. The study groups were divided according to benzodiazepine treatment at least 3 months before ABPM. Generalized estimating equation (GEE) model analysis was conducted to estimate the association between benzodiazepine treatment and ABPM test measurements. Multivariable COX regression survival analysis model for mortality and cardiovascular (CV) events was performed. A total of 4,938 ABPM studies were included in final analysis, 670 ABPMs of benzodiazepine-treated patients, and 4,268 of untreated patients. The benzodiazepine-treated group was significantly older, with a predominance of female patients, comprised more diabetic patients and consumed more antihypertensive medications. Adjustment for age, gender, diabetes mellitus, and number of antihypertensive medications, showed an association between benzodiazepine treatment and significantly lower ABPM measurements. When the analysis was split into those ≥60 years old and the other ABPM measurements only among ≥60 years old. Multivariable Cox regression survival analysis showed that regular benzodiazepine consumption was not associated with increased mortality or CV events (mean follow-up period of 42.4 ± 19.8 and 42.1 ± 20.0 months, respectively). Long-term use of benzodiazepines by ≥60 years old was independently associated with lower diastolic and systolic blood pressure in all parameters of ABPM, but not among younger patients.

  15. Vasculitic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Mona Amini

    2014-02-01

    Full Text Available Primary systemic vasculitis in pre-capillary arteries is associated with peripheral neuropathy. In some types of systematic vasculitis about 60 % of patients have peripheral nervous system (PNS involvement. In vasculitic peripheral neuropathies (VPN a necrotizing and inflammatory process leads to narrowing of vasa nervorum lumen and eventually the appearance of ischemic lesions in peripheral nerves. Some features might be suggestive of VPN, like: axonal nerve degeneration, wallerian-like degeneration, and diameter irregularity of nerve. Peripheral nervous system (PNS destruction during systemic vasculitides should be considered, due to its frequency and early occurrence in vasculitis progression. The first line treatment of non systematic VPNs is corticosteroid agents, but these drugs might worsen the VPNs or systemic vasculitis.

  16. Benzodiazepine Use During Hospitalization: Automated Identification of Potential Medication Errors and Systematic Assessment of Preventable Adverse Events.

    Directory of Open Access Journals (Sweden)

    David Franklin Niedrig

    Full Text Available Benzodiazepines and "Z-drug" GABA-receptor modulators (BDZ are among the most frequently used drugs in hospitals. Adverse drug events (ADE associated with BDZ can be the result of preventable medication errors (ME related to dosing, drug interactions and comorbidities. The present study evaluated inpatient use of BDZ and related ME and ADE.We conducted an observational study within a pharmacoepidemiological database derived from the clinical information system of a tertiary care hospital. We developed algorithms that identified dosing errors and interacting comedication for all administered BDZ. Associated ADE and risk factors were validated in medical records.Among 53,081 patients contributing 495,813 patient-days BDZ were administered to 25,626 patients (48.3% on 115,150 patient-days (23.2%. We identified 3,372 patient-days (2.9% with comedication that inhibits BDZ metabolism, and 1,197 (1.0% with lorazepam administration in severe renal impairment. After validation we classified 134, 56, 12, and 3 cases involving lorazepam, zolpidem, midazolam and triazolam, respectively, as clinically relevant ME. Among those there were 23 cases with associated adverse drug events, including severe CNS-depression, falls with subsequent injuries and severe dyspnea. Causality for BDZ was formally assessed as 'possible' or 'probable' in 20 of those cases. Four cases with ME and associated severe ADE required administration of the BDZ antagonist flumazenil.BDZ use was remarkably high in the studied setting, frequently involved potential ME related to dosing, co-medication and comorbidities, and rarely cases with associated ADE. We propose the implementation of automated ME screening and validation for the prevention of BDZ-related ADE.

  17. A simple method for the quantification of benzodiazepine receptors using iodine-123 iomazenil and single-photon emission tomography

    International Nuclear Information System (INIS)

    Ito, Hiroshi; Goto, Ryoui; Koyama, Masamichi; Kawashima, Ryuta; Ono, Shuichi; Sato, Kazunori; Fukuda, Hiroshi

    1996-01-01

    Iodine-123 iomazenil (Iomazenil) is a ligand for central type benzodiazepine receptors that is suitable for single-photon emission tomography (SPET). The purpose of this study was to develop a simple method for the quantification of its binding potential (BP). The method is based on a two-compartment model (K 1 , influx rate constant; k 2 ', efflux rate constant; V T '(=K 1 /k 2 '), the total distribution volumes relative to the total arterial tracer concentration), and requires two SPET scans and one blood sampling. For a given input function, the radioactivity ratio of the early to delayed scans can be considered to tabulate as a function of k 2 ', and a table lookup procedure provides the corresponding k 2 ' value, from which K 1 and V t ' values are then calculated. The arterial input function is obtained by calibration of the standard input function by the single blood sampling. SPET studies were performed on 14 patients with cerebrovascular diseases, dementia or brain tumours (mean age ±SD, 56.0±12.2). None of the patients had any heart, renal or liver disease. A dynamic SPET scan was performed following intravenous bolus injection of Iomazenil. A static SPET scan was performed at 180 min after injection. Frequent blood sampling from the brachial artery was performed on all subjects for determination of the arterial input function. Two-compartment model analysis was validated for calculation of the V T ' value of Iomazenil. Good correlations were observed between V T ' values calculated by three-compartment model analysis and those calculated by the present method, in which the scan time combinations (early scan/delayed scan) used were 15/180 min, 30/180 min or 45/180 min (all combinations: r=0.92), supporting the validity of this method. The present method is simple and applicable for clinical use. (orig.)

  18. Effect of 3-substituted 1,4-benzodiazepin-2-ones on maximal normalized rate of bradykinin-induced smooth muscle contraction in the presence of calcium channel blockers

    Directory of Open Access Journals (Sweden)

    P. A. Virych

    2017-05-01

    Full Text Available The development of modern organic chemistry and molecular modeling technologies simplify the search for potential inhibitors of various receptor systems and biological processes. The one of the directions is the development of analgesics of broad spectrum and low toxicity. It is important to search for inhibitors of the kinin-kallikrein system that regulates many functions: inflammation, pain, carcinogenesis, vascular tone, smooth muscle contraction and other. Derivatives of 3-substituted 1,4-benzodiazepine-2-ones have a unique spatial conformation that allows one to simulate β-structures of bioactive peptides. The functional activity of compounds is determined by properties of their peripheral chemical radicals. We analyzed the effect of 3-substituted 1,4-benzodiazepin-2-ones derivatives on the normalized maximal rate of bradykinin-induced smooth muscle contraction and relaxation of the stomach in the presence of calcium channel blockers: verapamil (1 μM, gadolinium (300 μM and 2-aminoethyl diphenylborinate (0.1 μM. The levels of bradykinin and 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones in incubation solution were 10–6 M. Data processing on dynamics of contraction was performed according to the method of Burdyha and Kosterin. Compounds MX-1775 and MX-1925 reduced maximal normalized rate (Vn of bradykinin-induced smooth muscle contraction in the presence of Gd3+ by 21.2% and 31.0% respectively. Compound MX-1925 increased Vn of relaxation by 11.6%. A similar effect is typical for MX-2011, where there is an increase by 34.6%. In the presence of verapamil this compound additionally decreased Vn contraction by 20.5%. Substances MX-1775, MX-2004 and MX-1925 restored maximal normalized rate of relaxation to original values of bradykinin-induced contraction. In the presence of 2-aminoethyldiphenylborinate MX-1775 additionally reduced Vn of contractions by 7.5%. 3-substituted 1,4-benzo­diazepine-2-ones did not change the maximal

  19. TRANSPLANTE RENAL

    Directory of Open Access Journals (Sweden)

    Soraia Geraldo Rozza Lopes

    2014-01-01

    Full Text Available El objetivo del estudio fue comprender el significado de espera del trasplante renal para las mujeres en hemodiálisis. Se trata de un estudio cualitativo-interpretativo, realizado con 12 mujeres en hemodiálisis en Florianópolis. Los datos fueron recolectados a través de entrevistas en profundidad en el domicilio. Fue utilizado el software Etnografh 6.0 para la pre-codificación y posterior al análisis interpretativo emergieron dos categorías: “las sombras del momento actual”, que mostró que las dificultades iniciales de la enfermedad están presentes, pero las mujeres pueden hacer frente mejor a la enfermedad y el tratamiento. La segunda categoría, “la luz del trasplante renal”, muestra la esperanza impulsada por la entrada en la lista de espera para un trasplante.

  20. Renal artery origins and variations: angiographic evaluation of 855 consecutive patients.

    Science.gov (United States)

    Ozkan, Uğur; Oğuzkurt, Levent; Tercan, Fahri; Kizilkiliç, Osman; Koç, Zafer; Koca, Nihal

    2006-12-01

    To determine angiographically the origins and variations of renal arteries. The study included 855 consecutive patients (163 females, 692 males; mean age, 61 years) living in the Cukurova region of Turkey, who underwent either aortofemoropopliteal (AFP) angiography for the investigation of peripheral arterial disease, or renal angiography for renovascular hypertension, and were prospectively evaluated. Renal arteries were visualized by non-selective catheterization during AFP angiography and by selective or non-selective catheterization during renal angiography. Locations of renal artery origins and renal artery variations, including the presence of extra renal arteries and division patterns were analyzed on angiograms. The origin of main renal arteries off the aorta was between the upper margin of L1 and lower margin of L2 vertebra in 98% of the patients, and in 74%, this was the origin of extra renal arteries. The most common location for renal artery origin was the L1-L2 intervertebral disc level. A single renal artery was present in both kidneys in 76% of patients. Renal artery variations included multiple arteries in 24%, bilateral multiple arteries in 5%, and early division in 8% of the cases. Additional renal arteries on the right side were found in 16% and on the left side in 13% of cases. Of all the extra renal arteries, the percentage of accessory and aberrant renal arteries were 49% and 51%, respectively. Renal arteries originated between the first and the second lumbar vertebral levels in most patients. Extra renal arteries were quite frequent. These results should be kept in mind when a non-invasive diagnostic search is performed for renal artery stenosis, or when renal surgery related to renal arteries is performed.

  1. Donating Peripheral Blood Stem Cells

    Science.gov (United States)

    ... Print this page My Cart Donating peripheral blood stem cells Peripheral blood stem cell (PBSC) donation is a nonsurgical procedure to collect ... Donating bone marrow Donor experiences videos Peripheral blood stem cell (PBSC) donation is one of two methods of ...

  2. Peripheral Neuropathy: Symptoms and Signs

    Science.gov (United States)

    ... Utah Research News Make a Difference Symptoms of Peripheral Neuropathy Print This Page Peripheral Neuropathy symptoms usually start ... more slowly over many years. The symptoms of peripheral neuropathy often include: A sensation of wearing an invisible “ ...

  3. Renal hemodynamic effects of activation of specific renal sympathetic nerve fiber groups.

    Science.gov (United States)

    DiBona, G F; Sawin, L L

    1999-02-01

    To examine the effect of activation of a unique population of renal sympathetic nerve fibers on renal blood flow (RBF) dynamics, anesthetized rats were instrumented with a renal sympathetic nerve activity (RSNA) recording electrode and an electromagnetic flow probe on the ipsilateral renal artery. Peripheral thermal receptor stimulation (external heat) was used to activate a unique population of renal sympathetic nerve fibers and to increase total RSNA. Total RSNA was reflexly increased to the same degree with somatic receptor stimulation (tail compression). Arterial pressure and heart rate were increased by both stimuli. Total RSNA was increased to the same degree by both stimuli but external heat produced a greater renal vasoconstrictor response than tail compression. Whereas both stimuli increased spectral density power of RSNA at both cardiac and respiratory frequencies, modulation of RBF variability by fluctuations of RSNA was small at these frequencies, with values for the normalized transfer gain being approximately 0.1 at >0.5 Hz. During tail compression coherent oscillations of RSNA and RBF were found at 0.3-0.4 Hz with normalized transfer gain of 0.33 +/- 0.02. During external heat coherent oscillations of RSNA and RBF were found at both 0.2 and 0.3-0.4 Hz with normalized transfer gains of 0. 63 +/- 0.05 at 0.2 Hz and 0.53 +/- 0.04 to 0.36 +/- 0.02 at 0.3-0.4 Hz. Renal denervation eliminated the oscillations in RBF at both 0.2 and 0.3-0.4 Hz. These findings indicate that despite similar increases in total RSNA, external heat results in a greater renal vasoconstrictor response than tail compression due to the activation of a unique population of renal sympathetic nerve fibers with different frequency-response characteristics of the renal vasculature.

  4. BILATERAL DUPLICATION OF RENAL ARTERIES

    OpenAIRE

    Prajkta A Thete; Mehera Bhoir; M.V.Ambiye

    2014-01-01

    Routine dissection of a male cadaver revealed the presence of bilateral double renal arteries. On the right side the accessory renal artery originated from the abdominal aorta just above the main renal artery. On the left side the accessory renal artery originated from the abdominal aorta about 1 cm above the main renal artery. Knowledge of the variations of renal vascular anatomy has importance in exploration and treatment of renal trauma, renal transplantation, renal artery embolization, su...

  5. High-dose benzodiazepine dependence: a qualitative study of patients' perception on cessation and withdrawal.

    Science.gov (United States)

    Liebrenz, Michael; Gehring, Marie-Therese; Buadze, Anna; Caflisch, Carlo

    2015-05-13

    Benzodiazepine withdrawal syndrome has been reported following attempts to withdraw even from low or therapeutic doses and has been compared to barbiturate and alcohol withdrawal. This experience is known to deter patients from future cessation attempts. Research on other psychotropic substances shows that the reasons and motivations for withdrawal attempts - as well as the experiences surrounding those attempts - at least partially predict future efforts at discontinuation as well as relapse. We therefore aimed to qualitatively explore what motivates patients to discontinue this medication as well as to examine their experiences surrounding previous and current withdrawal attempts and treatment interventions in order to positively influence future help-seeking behavior and compliance. To understand these patients better, we conducted a series of 41 unstructured, narrative, in-depth interviews among adult Swiss patients with a long-term dependent use of benzodiazepines in doses equivalent to more than 40 mg diazepam per day and/or otherwise problematic use (mixing benzodiazepines, escalating dosage, recreational use or illegal purchase). Mayring's qualitative content analysis was used to evaluate findings. These high-dose benzodiazepine-dependent patients decision to change consumption patterns were affected by health concerns, the feeling of being addicted and social factors. Discontinuation attempts were frequent and not very successful with fast relapse. Withdrawal was perceived to be a difficult, complicated, and highly unpredictable process. The first attempt at withdrawal occurred at home and typically felt better than at the clinic. Inpatient treatment was believed to be more effective with long term treatment (approaches) than short term. Patients preferred gradual reduction of usage to abrupt cessation (and had experienced both). While no clear preferences for withdrawal were found for benzodiazepines with specific pharmacokinetic properties, participants

  6. Peripheral Ulcerative Keratitis

    Science.gov (United States)

    ... oval in shape. Diagnosis A doctor's evaluation Sometimes culture The diagnosis of peripheral ulcerative keratitis is suspected when the doctor sees the affected cornea in a person who also has a severe and/or long- ...

  7. Tumors of peripheral nerves

    International Nuclear Information System (INIS)

    Ho, Michael; Lutz, Amelie M.

    2017-01-01

    Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [de

  8. Synthesis of substituted 1,4-diazepines and 1,5-benzodiazepines using an efficient heteropolyacid-catalyzed procedure.

    Science.gov (United States)

    Kaoua, Rachedine; Bennamane, Norah; Bakhta, Saliha; Benadji, Sihame; Rabia, Cherifa; Nedjar-Kolli, Bellara

    2010-12-28

    An efficient and improved procedure for the synthesis of 1,4-diazepine and 1,5-benzodiazepine derivatives via the reaction of ketimine intermediates with aldehydes in the presence of Keggin-type heteropolyacids (HPAs) was developed. High yields and short reaction times were obtained for both electron-releasing and electron-withdrawing substituted 1,4-diazepine  and 1,5-benzodiazepines derivatives.

  9. Synthesis of Substituted 1,4-Diazepines and 1,5-Benzodiazepines Using an Efficient Heteropolyacid-Catalyzed Procedure

    Directory of Open Access Journals (Sweden)

    Sihame Benadji

    2010-12-01

    Full Text Available An efficient and improved procedure for the synthesis of 1,4-diazepine and 1,5-benzodiazepine derivatives via the reaction of ketimine intermediates with aldehydes in the presence of Keggin-type heteropolyacids (HPAs was developed. High yields and short reaction times were obtained for both electron-releasing and electron-withdrawing substituted 1,4-diazepine  and 1,5-benzodiazepines derivatives.

  10. An Organocatalyzed and Ultrasound Accelerated Expeditious Synthetic Route to 1,5-Benzodiazepines under Solvent-Free Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Shinde, Pravin V.; Shingate, Bapurao B.; Shingare, Murlidhar S. [Babasaheb Ambedkar Marathwada University, Aurngabad (India)

    2011-04-15

    In the present work, successful implementation of ultrasound irradiations for the rapid synthesis of 1,5- benzodiazepine derivatives under solvent-free conditions is demonstrated. Use of a novel catalyst i.e. camphor sulphonic acid in combination with ultrasound technique is reported for the first time. Comparative study for the synthesis of 1,5-benzodiazepines using conventional as well as ultrasonication method is discussed.

  11. Promoting peripheral myelin repair

    OpenAIRE

    Zhou, Ye; Notterpek, Lucia

    2016-01-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the ...

  12. Role of bone marrow-derived stem cells, renal progenitor cells and ...

    African Journals Online (AJOL)

    Hayam Abdel Meguid El Aggan

    2013-04-06

    Apr 6, 2013 ... renal blood flow; MoAbs, monoclonal antibodies; PE, phycoerythrin;. FITC, fluorescein isothiocyanate. ... Detection of HSCs and MSCs in the peripheral blood using flow cytometry via detection of CD34, CD45, CD117 and ..... the peripheral capillary loops in 25–50% (cg2). Six biopsies showed an increase ...

  13. The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines.

    Science.gov (United States)

    Stanley, Joanna L; Lincoln, Rachael J; Brown, Terry A; McDonald, Louise M; Dawson, Gerard R; Reynolds, David S

    2005-05-01

    The mouse rotarod test of motor coordination/sedation is commonly used to predict clinical sedation caused by novel drugs. However, past experience suggests that it lacks the desired degree of sensitivity to be predictive of effects in humans. For example, the benzodiazepine, bretazenil, showed little impairment of mouse rotarod performance, but marked sedation in humans. The aim of the present study was to assess whether the mouse beam walking assay demonstrates: (i) an increased sensitivity over the rotarod and (ii) an increased ability to predict clinically sedative doses of benzodiazepines. The study compared the effects of the full benzodiazepine agonists, diazepam and lorazepam, and the partial agonist, bretazenil, on the mouse rotarod and beam walking assays. Diazepam and lorazepam significantly impaired rotarod performance, although relatively high GABA-A receptor occupancy was required (72% and 93%, respectively), whereas beam walking performance was significantly affected at approximately 30% receptor occupancy. Bretazenil produced significant deficits at 90% and 53% receptor occupancy on the rotarod and beam walking assays, respectively. The results suggest that the mouse beam walking assay is a more sensitive tool for determining benzodiazepine-induced motor coordination deficits than the rotarod. Furthermore, the GABA-A receptor occupancy values at which significant deficits were determined in the beam walking assay are comparable with those observed in clinical positron emission tomography studies using sedative doses of benzodiazepines. These data suggest that the beam walking assay may be able to more accurately predict the clinically sedative doses of novel benzodiazepine-like drugs.

  14. The benzodiazepine/GABA receptor complex during severe ethanol intoxication and withdrawal in the rat

    International Nuclear Information System (INIS)

    Hemmingsen, R.; Braestrup, C.; Nielsen, M.; Barry, D.I.

    1982-01-01

    The benzodiazepine/GABA (gammaaminobutyric acid) receptor complex was investigated during severe ethanol intoxication and withdrawal in the rat. The intragastric intubation technique was used to establish physical ethanol dependence in the animals. Cerebral cortex from male Wistar rats was studied 1) after 31/2 days of severe ethanol intoxication, 2) during the ethanol withdrawal reaction and 3) in a control group. The effect of GABA-ergic activation by muscimol and THIP (4,5,6,7-tetrahydroisoxazole(5,4-c)pyridin-3-01) on 3 H-diazepam binding was unchanged during ethanol intoxication and withdrawal, as was the affinity constant (Ksub(D)) and the maximal number of binding sites (Bsub(max)) for 3 H-flunitrazepam. In conclusion, the benzodiazepine/GABA receptor complex is unlikely to play any causual part in physical ethanol dependence. (author)

  15. Characteristics of benzodiazepine receptors in rats differing in predisposition to experimental alcoholism

    International Nuclear Information System (INIS)

    Burov, Yu.V.; Maiskii, A.I.; Yukhananov, R.Yu.

    1986-01-01

    This paper studies the number and affinity of benzodiazepine receptors for diazepam in the cerebral cortex and hippocampus of rats differently predisposed to the development of experimental alcoholism. Ethanol was injected once intraperitoneally, in a dose of 2.5 g/kg. Control animals received the same volume of physiological saline. Bound and free N-methyl-tritium-diazepam were separated by means of GF/B filters. The characteristics of benzodiazepine receptors are shown in rats differing in predisposition to the development of experimental alcoholism and in rats during voluntary chronic alcoholization. It is shown that weakening of functional acitivity of the GABA-benzodiazepam complex in animals predisposed to the development of experimental alcoholism is one of the neurochemical mechanisms of development of the abstinence syndrome

  16. [Appropriate use of benzodiazepines zolpidem and zopiclone in diseases attended in primary care].

    Science.gov (United States)

    Granados Menéndez, M Isabel; Salinero Fort, Miguel Angel; Palomo Ancillo, Marta; Aliaga Gutiérrez, Laura; García Escalonilla, Carmen; Ortega Orcos, Rebeca

    2006-01-01

    To estimate the proportion of benzodiazepine prescriptions that comply with the guidelines for appropriate prescription. To identify the variables associated with appropriate prescription. Observational, cross-sectional study. Monóvar Health Centre in Area IV, Madrid, Spain. Random sample of 270 active benzodiazepine prescriptions in adult patients from the prescriptions record of the OMI-AP V. 5.0 computer system. The chosen dimensions for appropriate prescription were: a) correct diagnostic indication; b) absence of benzodiazepines with long half-life in the elderly; c) existence of support or monitoring visits; d) overall appropriateness or coexistence of correct diagnostic indications and monitoring visits. Independent variables were recorded in relation to patient, person prescribing and prescription. Diagnostic indication, 75.6%; absence of benzodiazepines with long half-life in the elderly, 79.8%; existence of support visits, 63.3%; overall appropriateness, 53%. Main diagnoses: pure anxiety, 29%; anxiety related to other illness, 18.6%; insomnia, 14.8%; cardiovascular illness, 14.8%; alcohol and drug abuse, 4.5%; osteo-muscular illness, 4.4%; schizophrenia, 4.4%. Most prescribed substances: lorazepam, 27.8%; bromazepam, 23.7%. Average life of prescriptions: 18.58 months. Origins: health centre, 68.5%; out-patient psychiatry, 10%; hospital, 10%. The variable that is most closely associated with overall appropriateness, fitted with the rest of the variables, is out-patient psychiatry prescription (OR, 6.67; 95% CI, 1.92-23.18). The mean duration of the prescriptions infringes all standards. The overall appropriateness or correct coexistence of adequate diagnostic indication with follow-up visits is associated with out-patient Psychiatry prescription.

  17. A 5-year follow-up study of users of benzodiazepine: starting with diazepam versus oxazepam.

    Science.gov (United States)

    Tvete, Ingunn Fride; Bjørner, Trine; Skomedal, Tor

    2016-04-01

    Drug dependency may develop during long-term benzodiazepine use, indicated, for example, by dose escalation. The first benzodiazepine chosen may affect the risk of dose escalation. To detect possible differences in benzodiazepine use between new users of diazepam and oxazepam over time. This 5-year prescription database study included 19 747 new benzodiazepine users, inhabitants of Norway, aged 30-60 years, with first redemption for diazepam or oxazepam. Individuals starting on diazepam versus oxazepam were analysed by logistic regression with sex, age, other drug redemptions, prescriber's specialty, household income, education level, type of work, and vocational rehabilitation support as background variables. Time to reach a daily average intake of ≥1 defined daily doses (DDD) over a 3-month period was analysed using a Cox proportional hazard regression model. New users of oxazepam had a higher risk for dose escalation compared with new users of diazepam. This was true even when accounting for differences in sociodemographic status and previous drug use (hazard ratio [HR] 1.33, 95% confidence interval = 1.17 to 1.51). Most doctors prescribed, according to recommendations, oxazepam to individuals they may have regarded as prone to and at risk of dependency. However, these individuals were at higher risk for dose escalation even when accounting for differences in sociodemographic status and previous drug use. Differences between the two user groups could be explained by different preferences for starting drug, DDD for oxazepam being possibly too low, and some unaccounted differences in illness. © British Journal of General Practice 2016.

  18. A New Terminal Cyano Group-containing Benzodiazepine Alkaloid from the Mangrove Endophytic Fungus Penicillium sp. .

    Science.gov (United States)

    Li, Jing; Zhong, Yi-sheng; Yuan, Jie; Zhu, Xun; Lu, Yong-jun; Lin, Yong-cheng; Liu, Lan

    2015-09-01

    A new benzodiazepine alkaloid containing terminal cyano group has been isolated from a mangrove endophytic fungus, Penicillium 299#. Structure elucidation was determined by 1D and 2D NMR spectroscopy and the absolute configuration was determined by electronic circular dichroism (ECD). The new compound showed no cytotoxic activities in vitro against human cancer lines MDA-MB-435, HepG2, HCT-116, and Calu-3.

  19. Structure-Aided Design of Novel Inhibitors of HIV Protease Based on a Benzodiazepine Scaffold

    Czech Academy of Sciences Publication Activity Database

    Schimer, Jiří; Cígler, Petr; Veselý, J.; Grantz Šašková, Klára; Lepšík, Martin; Brynda, Jiří; Řezáčová, Pavlína; Kožíšek, Milan; Císařová, I.; Oberwinkler, H.; Kraeusslich, H. G.; Konvalinka, Jan

    2012-01-01

    Roč. 55, č. 22 (2012), s. 10130-10135 ISSN 0022-2623 R&D Projects: GA ČR GBP208/12/G016; GA ČR GAP207/11/1798 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514 Keywords : HIV protease inhibitor * rational drug design * 1,4-benzodiazepines Subject RIV: CE - Biochemistry Impact factor: 5.614, year: 2012

  20. Synthesis of spiro[indolo-1,5-benzodiazepines] from 3-acetyl ...

    Indian Academy of Sciences (India)

    Unknown

    also as potent virucides and non-nucleoside inhibi- tors of HIV-1 reverse transcriptase.2 Beside this,. 1,5-benzodiazepines ... printed circuits.8 Here we report the synthesis of spiro ... 3d. 5,6-Benzo 1727. 1701. 1672. 3218 3382. 4⋅22 (d, 2H, J = 17⋅91 Hz), 3⋅81 (d, 2H,. J = 17⋅8 .... R1 = R2 = CH3 show 88⋅88% inhibition.

  1. Maternal Characteristics of Women Exposed to Hypnotic Benzodiazepine Receptor Agonist during Pregnancy

    OpenAIRE

    Askaa, Bjarke; Jimenez-Solem, Espen; Enghusen Poulsen, Henrik; Traerup Andersen, Jon

    2014-01-01

    Background. There is little knowledge regarding the characteristics of women treated with hypnotic benzodiazepine receptor agonists (HBRAs) during pregnancy. In this large Danish cohort study, we characterize women exposed to HBRA during pregnancy. We determined changes in prevalence of HBRA use from 1997 to 2010 and exposure to HBRAs in relation to pregnancy. Methods. We performed a retrospective cohort study including 911,017 pregnant women in the period from 1997 to 2010. Information was r...

  2. Prescriptions for schedule II opioids and benzodiazepines increase after the introduction of computer-generated prescriptions.

    Science.gov (United States)

    McGerald, Genevieve; Dvorkin, Ronald; Levy, David; Lovell-Rose, Stephanie; Sharma, Adhi

    2009-06-01

    Prescriptions for controlled substances decrease when regulatory barriers are put in place. The converse has not been studied. The objective was to determine whether a less complicated prescription writing process is associated with a change in the prescribing patterns of controlled substances in the emergency department (ED). The authors conducted a retrospective nonconcurrent cohort study of all patients seen in an adult ED between April 19, 2005, and April 18, 2007, who were discharged with a prescription. Prior to April 19, 2006, a specialized prescription form stored in a locked cabinet was obtained from the nursing staff to write a prescription for benzodiazepines or Schedule II opioids. After April 19, 2006, New York State mandated that all prescriptions, regardless of schedule classification, be generated on a specialized bar-coded prescription form. The main outcome of the study was to compare the proportion of Schedule III-V opioids to Schedule II opioids and benzodiazepines prescribed in the ED before and after the introduction of a less cumbersome prescription writing process. Of the 26,638 charts reviewed, 2.1% of the total number of prescriptions generated were for a Schedule II controlled opioid before the new system was implemented compared to 13.6% after (odds ratio [OR] = 7.3, 95% confidence interval [CI] = 6.4 to 8.4). The corresponding percentages for Schedule III-V opioids were 29.9% to 18.1% (OR = 0.52, 95% CI = 0.49 to 0.55) and for benzodiazepines 1.4% to 3.9% (OR = 2.8, 95% CI = 2.4 to 3.4). Patients were more likely to receive a prescription for a Schedule II opioid or a benzodiazepine after a more streamlined computer-generated prescription writing process was introduced in this ED. (c) 2009 by the Society for Academic Emergency Medicine.

  3. CYP2C9 Genotypes Modify Benzodiazepine-Related Fall Risk: Original Results From Three Studies With Meta-Analysis.

    Science.gov (United States)

    Ham, Annelies C; Ziere, Gijsbertus; Broer, Linda; Swart, Karin M A; Enneman, Anke W; van Dijk, Suzanne C; van Wijngaarden, Janneke P; van der Zwaluw, Nikita L; Brouwer-Brolsma, Elske M; Dhonukshe-Rutten, Rosalie A M; van Schoor, Natasja M; Zillikens, M Carola; van Gelder, Teun; de Vries, Oscar J; Lips, Paul; Deeg, Dorly J H; de Groot, Lisette C P G M; Hofman, Albert; Witkamp, Renger F; Uitterlinden, André G; Stricker, Bruno H; van der Velde, Nathalie

    2017-01-01

    To investigate whether the CYP2C9*2 and *3 variants modify benzodiazepine-related fall risk. Three prospective studies; the Rotterdam Study, B-PROOF, and LASA. Community-dwelling individuals living in or near five Dutch cities. There were 11,485 participants aged ≥55 years. Fall incidents were recorded prospectively. Benzodiazepine use was determined using pharmacy dispensing records or interviews. Cox proportional hazard models adjusted for age and sex were applied to determine the association between benzodiazepine use and fall risk stratified for CYP2C9 genotype and comparing benzodiazepine users to nonusers. The results of the three studies were combined applying meta-analysis. Within benzodiazepine users, the association between genotypes and fall risk was also assessed. Three thousand seven hundred five participants (32%) encountered a fall during 91,996 follow-up years, and 4% to 15% (depending on the study population) used benzodiazepines. CYP2C9 variants had frequencies of 13% for the *2 allele and 6% for the *3 allele. Compared to nonusers, current benzodiazepine use was associated with an 18% to 36% increased fall risk across studies with a combined hazard ratio (HR) = 1.26 (95% confidence interval [CI], 1.13; 1.40). CYP2C9*2 or *3 allele variants modified benzodiazepine-related fall risk. Compared to nonusers, those carrying a CYP2C9*2 or *3 allele and using benzodiazepines had a 45% increased fall risk (HR, 1.45 95% CI, 1.21; 1.73), whereas CYP2C9*1 homozygotes using benzodiazepines had no increased fall risk (HR, 1.14; 95% CI, 0.90; 1.45). Within benzodiazepine users, having a CYP2C9*2 or *3 allele was associated with an increased fall risk (HR, 1.35; 95% CI, 1.06; 1.72). Additionally, we observed an allele dose effect; heterozygous allele carriers had a fall risk of (HR = 1.30; 95% CI, 1.05; 1.61), and homozygous allele carriers of (HR = 1.91 95% CI, 1.23; 2.96). CYP2C9*2 and *3 allele variants modify benzodiazepine-related fall risk. Those

  4. GABA/benzodiazepine receptor complex in long-sleep and short-sleep mice

    International Nuclear Information System (INIS)

    Marley, R.J.

    1987-01-01

    LS mice are more sensitive to benzodiazepine-induced anesthesia; however, the two lines do not differ in their hypothermic response to flurazepam. SS mice are more resistant to 3-mercaptopropionic acid-induced seizures and more sensitive to the anticonvulsant effects of benzodiazepines. The various correlates of GABA and benzodiazepine actions probably are the results of different mechanisms of action and/or differential regional control. Bicuculline competition for 3 H-GABA binding sites is greater in SS cerebellar tissue and 3 H-flunitrazepam binding is greater in the mid-brain region of LS mice. GABA enhancement of 3 H-flunitrazepma binding is greater in SS mice. Ethanol also enhances 3 H-flunitrazepam binding and increases the levels of 3 H-flunitrazepam binding above those observed for GABA. Using correlational techniques on data from LS and SS mice and several inbred mouse strains, it was demonstrated that a positive relationship exists between the degree of receptor coupling within the GABA receptor complex and the degree of resistance to seizures

  5. Enhancement of GABAergic transmission by zolpidem, an imidazopyridine with preferential affinity for type I benzodiazepine receptors.

    Science.gov (United States)

    Biggio, G; Concas, A; Corda, M G; Serra, M

    1989-02-28

    The effect of zolpidem, an imidazopyridine derivative with high affinity at the type I benzodiazepine recognition site, on the function of the GABAA/ionophore receptor complex was studied in vitro. Zolpidem, mimicking the action of diazepam, increased [3H]GABA binding, enhanced muscimol-stimulated 36Cl- uptake and reduced [35S]TBPS binding in rat cortical membrane preparations. Zolpidem was less effective than diazepam on the above parameters. Zolpidem induced a lower increase of [3H]GABA binding (23 vs. 35%) and muscimol-stimulated 36Cl- uptake (22 vs. 40%) and a smaller decrease of [35S]TBPS binding (47 vs. 77%) than diazepam. The finding that zolpidem enhanced the function of GABAergic synapses with an efficacy qualitatively and quantitatively different from that of diazepam suggests that this compound is a partial agonist at the benzodiazepine recognition site. Thus, our results are consistent with the view that the biochemical and pharmacological profile of a benzodiazepine recognition site ligand reflects its efficacy to enhance GABAergic transmission. Whether the preferential affinity of zolpidem at the type I site is involved in its atypical biochemical and pharmacological profile remains to be clarified.

  6. Impulsivity in men with prescription of benzodiazepines and methadone in prison.

    Science.gov (United States)

    Moreno-Ramos, Luis; Fernández-Serrano, María José; Pérez-García, Miguel; Verdejo-García, Antonio

    2016-06-14

    Benzodiazepines and methadone use has been associated with various neuropsychological impairments. However, to the best of our knowledge, no studies have been carried out on the effect of these substances (either separately or combined) on impulsive personality, including studies in prisoners. The aim of this study is to examine the impulsive personality of a sample of 134 male prisoners using the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (Torrubia, Avila, Molto, & Caseras, 2001) and the UPPS-P Scale (Cyders et al., 2007). Some of these were methadone users, methadone and benzodiazepines users, polydrug users in abstinence and non-dependent drug users. The results showed that drug users have greater sensitivity to reward, positive urgency, negative urgency and sensation seeking than non-dependent users. Methadone users showed more sensitivity to punishment and lack of perseverance with respect to other users. No differences were found between methadone+benzodiazepines users and other groups. The secondary aim is to examine which impulsive personality dimensions are related to the two motivational systems proposed by Gray (BIS-BAS) using exploratory factor analysis. Results showed two different components. One component was defined by the subscales sensitivity to reinforcement, positive urgency, negative urgency and sensation seeking. The second component was defined by the subscales sensitivity to punishment, lack of perseverance and lack of premeditation.

  7. Micellar Liquid Chromatography for the Determination of Some Less Prescribed Benzodiazepines

    Directory of Open Access Journals (Sweden)

    Hoonka Subhra

    2012-01-01

    Full Text Available A simple chromatographic procedure is reported for the determination of some less prescribed but equally important benzodiazepines (Clotiazepam, clozapine and pinazepam in serum. The optimization studies have been made in CN, C18 and C8 columns, using mobile phase containing sodium dodecyl sulphate (SDS modified with either propanol, butanol or pentanol. The method proposed for the determination of the three benzodiazepines using a mobile phase of 0.13 M SDS, 2.4% pentanol-0.01 M phosphate buffer- 0.1% triethylamine (pH 7 at 25°C and UV detection (240 nm in a C8 column. The serum samples was injected directly, without any pretreatment, eluted in less than 8 min, in accordance to their relative polarities, as indicated by their octanol-water partition coefficients. The limits of detection (ng/mL was in the 1.6 to 5.6 and 7 to 87 range, for aqueous and serum samples, respectively. Repeatability and intermediate precision was tested for three different concentrations of the drugs, resulting in the 0.1 to 2 range. The results obtained here for the separation of the three benzodiazepines in serum were also counter checked at Department of Bio-analytical Chemistry, Universitat Jaume I, Castelló, Spain.

  8. GABA and benzodiazepine receptors in the gerbil brain after transient ischemia: demonstration by quantitative receptor autoradiography

    International Nuclear Information System (INIS)

    Onodera, H.; Sato, G.; Kogure, K.

    1987-01-01

    Quantitative receptor autoradiography was used to measure the binding of gamma-aminobutyric acid (GABA) and benzodiazepine receptors after ischemia by means of transient occlusion of bilateral common carotid arteries in the gerbil. [ 3 H]Muscimol was used to label the GABAA receptors and [ 3 H]flunitrazepam to label central type benzodiazepine receptors. In the superolateral convexities of the frontal cortices, [ 3 H]muscimol binding was increased in 60% of the animals killed 3 days after ischemia, and decreased in 67% of the animals killed 27 days after ischemia. Twenty-seven days after ischemia, [ 3 H]flunitrazepam binding in the substantia nigra pars reticulata increased to 252% of the control, though the increase in [ 3 H]muscimol binding was not significant. In the dorsolateral region of the caudate putamen, marked neuronal necrosis and depletion of both [ 3 H]muscimol and [ 3 H]flunitrazepam binding sites were observed 27 days after ischemia, the ventromedial region being left intact. In spite of the depletion of pyramidal cells in the CA1 region of the hippocampus, both [ 3 H]muscimol and [ 3 H]flunitrazepam binding sites were preserved 27 days after ischemia. Since our previous study revealed that adenosine A1 binding sites were depleted in the CA1 subfield of the hippocampus after ischemia correlating with neuronal damage, GABAA and benzodiazepine receptors may not be distributed predominantly on the pyramidal cells in the CA1 region

  9. High daily doses of benzodiazepines among Quebec seniors: prevalence and correlates

    Directory of Open Access Journals (Sweden)

    Moride Yola

    2001-11-01

    Full Text Available Abstract Background Use of high daily doses of benzodiazepines is generally contraindicated for seniors. While both patient and physician factors may influence the use of high daily doses, previous research on the effect of patient factors has been extremely limited. The objectives of this study were to determine the one year prevalence of use of high daily doses of benzodiazepines, and examine physician and patient correlates of such use among Quebec community-dwelling seniors. Methods Patient information for 1423 community-dwelling Quebec seniors who participated in the Canadian Study of Health and Aging was linked to provincial health insurance administrative data bases containing detailed information on prescriptions received and prescribers. Results The standardized one year period prevalence of use of high daily doses of benzodiazepines was 7.9%. Use of high daily doses was more frequent among younger seniors and those who had reported anxiety during the previous year. Patients without cognitive impairment were more likely to receive high dose prescriptions from general practitioners, while those with cognitive impairment were more likely to receive high dose prescriptions from specialists. Conclusion High dose prescribing appears to be related to both patient and physician factors.

  10. [Driving under the influence of benzodiazepines and antidepressants: prescription and abuse].

    Science.gov (United States)

    Coutinho, Daniel; Vieira, Duarte Nuno; Teixeira, Helena M

    2011-01-01

    Benzodiazepines are drugs usually used in anxiety disorders, dyssomnias, convulsions, muscle disorders, alcohol and other drugs detoxification, as well as in preoperative sedation/amnesia. Moreover, antidepressants are mainly indicated in depression and as co-therapeutic drugs in other psychiatric disorders. The use of benzodiazepines and antidepressants is associated with some health and public safety problems. Decreased of attention, concentration, reflexes, visual capacity, motor coordination and reasoning, associated with increased reaction time and lack of awareness of driving impairment among these drug users, contributes to the increased risk on traffic safety linked with these drugs. This risk may further increase with non-compliance of medical prescription, drug abuse or concomitant use of alcohol. The relationship between the use of psychoactive drugs and road traffic safety is, however, an extremely complex subject and has a primordial importance in the clarification of the role of benzodiazepine and antidepressant effects on driving skills. The prevention of driving under the influence of these drugs depends on the awareness, among doctors, of the risks associated with their use. Thus, the consciousness of medical prescription, as well as providing clear information to patients is extremely important.

  11. Specialty training and the personal use of benzodiazepines by physicians affect their proneness to prescribe tranquilizers.

    Science.gov (United States)

    Linden, M; Gothe, H

    1998-03-01

    The decision on how to treat a patient does not depend on clinical matters or illness characteristics alone, but also on patient, physician and setting variables such as personality, training, or reimbursement. No research has yet been carried out to answer the question whether personal experience with medications also influences prescribing behavior. In this study, 124 physicians stratified according to specialty (neuropsychiatrists vs. general practitioners), type of institution (private practice vs. hospital), years of professional experience (young vs. old), and region (rural vs. urban) participated in a structured interview to evaluate their proneness to prescribe benzodiazepines for sleep disorders as well as their personal experience in taking benzodiazepines for their own sleep problems. Both specialty and personal experience were significantly related to proneness to prescribe. Other variables tested (region, institution, age, gender) did not help to explain the variance in benzodiazepine prescribing practice. Thus physician variables and, importantly, their own personal experience in taking the medication significantly influence treatment choice. Rational medical decision making and treatment guidelines must therefore take into account medical knowledge as well as knowledge of personal treatment preferences and professional biases.

  12. Brain concentrations of benzodiazepines are elevated in an animal model of hepatic encephalopathy

    International Nuclear Information System (INIS)

    Basile, A.S.; Pannell, L.; Jaouni, T.; Gammal, S.H.; Fales, H.M.; Jones, E.A.; Skolnick, P.

    1990-01-01

    Brain extracts from rats with hepatic encephalopathy due to thioacetamide-induced fulminant hepatic failure contained 4- to 6-fold higher concentrations of substances that inhibit radioligand binding to benzodiazepine receptors than corresponding control rat extracts. Both isocratic and gradient-elution HPLC indicated that this inhibitory activity was localized in 3-8 peaks with retention times corresponding to deschlorodiazepam, deschlorolorazepam, lorazepam, oxazepam, diazepam, and N-desmethyldiazepam. The presence of diazepam and N-desmethyldiazepam was confirmed by mass spectroscopy. Both mass spectroscopic and radiometric techniques indicated that the concentrations of N-desmethyldiazepam and diazepam in brain extracts from encephalopathic rats were 2-9 and 5-7 times higher, respectively, than in control brain extracts. While benzodiazepines have been identified previously in mammalian and plant tissues, this report demonstrates that concentrations of these substances are increased in a pathophysiological condition. These findings provide a rational basis for the use of benzodiazepine receptor antagonists in the management of hepatic encephalopathy in humans

  13. Memory Effects of Benzodiazepines: Memory Stages and Types Versus Binding-Site Subtypes

    Directory of Open Access Journals (Sweden)

    Miroslav M. Savic

    2005-01-01

    Full Text Available Benzodiazepines are well established as inhibitory modulators of memory processing. This effect is especially prominent when applied before the acquisition phase of a memory task. This minireview concentrates on the putative subtype selectivity of the acquisition-impairing action of benzodiazepines. Namely, recent genetic studies and standard behavioral tests employing subtype-selective ligands pointed to the predominant involvement of two subtypes of benzodiazepine binding sites in memory modulation. Explicit memory learning seems to be affected through the GABAA receptors containing the α1 and α5 subunits, whereas the effects on procedural memory can be mainly mediated by the α1 subunit. The pervading involvement of the α1 subunit in memory modulation is not at all unexpected because this subunit is the major subtype, present in 60% of all GABAA receptors. On the other hand, the role of α5 subunits, mainly expressed in the hippocampus, in modulating distinct forms of memory gives promise of selective pharmacological coping with certain memory deficit states.

  14. Radionuclide evaluation of renal transplants

    International Nuclear Information System (INIS)

    Yang Hong; Zhao Deshan

    2000-01-01

    Radionuclide renal imaging and plasma clearance methods can quickly quantitate renal blood flow and function in renal transplants. They can diagnose acute tubular necrosis and rejection, renal scar, surgical complications such as urine leaks, obstruction and renal artery stenosis after renal transplants. At the same time they can assess the therapy effect of renal transplant complications and can also predict renal transplant survival from early post-operative function studies

  15. Distal renal tubular acidosis

    Science.gov (United States)

    ... this disorder. Alternative Names Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA Images Kidney anatomy Kidney - blood and urine flow References Bose A, Monk RD, Bushinsky DA. Kidney ...

  16. Renal Failure in Dementia with Lewy Bodies Presenting as Catatonia

    Science.gov (United States)

    Fekete, Robert

    2013-01-01

    Catatonia, originally described by Karl Kahlbaum in 1874, may be regarded as a set of clinical features found in a subtype of schizophrenia, but the syndrome may also stem from organic causes including vascular parkinsonism, brain masses, globus pallidus lesions, metabolic derangements, and pharmacologic agents, especially first generation antipsychotics. Catatonia may include paratonia, waxy flexibility (cerea flexibilitas), stupor, mutism, echolalia, and catalepsy (abnormal posturing). A case of catatonia as a result of acute renal failure in a patient with dementia with Lewy bodies is described. This patient recovered after intravenous fluid administration and reinstitution of the atypical dopamine receptor blocking agent quetiapine, but benzodiazepines and amantadine are additional possible treatments. Recognition of organic causes of catatonia leads to timely treatment and resolution of the syndrome. PMID:23466522

  17. Renal Failure in Dementia with Lewy Bodies Presenting as Catatonia

    Directory of Open Access Journals (Sweden)

    Robert Fekete

    2013-01-01

    Full Text Available Catatonia, originally described by Karl Kahlbaum in 1874, may be regarded as a set of clinical features found in a subtype of schizophrenia, but the syndrome may also stem from organic causes including vascular parkinsonism, brain masses, globus pallidus lesions, metabolic derangements, and pharmacologic agents, especially first generation antipsychotics. Catatonia may include paratonia, waxy flexibility (cerea flexibilitas, stupor, mutism, echolalia, and catalepsy (abnormal posturing. A case of catatonia as a result of acute renal failure in a patient with dementia with Lewy bodies is described. This patient recovered after intravenous fluid administration and reinstitution of the atypical dopamine receptor blocking agent quetiapine, but benzodiazepines and amantadine are additional possible treatments. Recognition of organic causes of catatonia leads to timely treatment and resolution of the syndrome.

  18. Cardio-renal syndrome

    OpenAIRE

    Gnanaraj, Joseph; Radhakrishnan, Jai

    2016-01-01

    Cardio-renal syndrome is a commonly encountered problem in clinical practice. Its pathogenesis is not fully understood. The purpose of this article is to highlight the interaction between the cardiovascular system and the renal system and how their interaction results in the complex syndrome of cardio-renal dysfunction. Additionally, we outline the available therapeutic strategies to manage this complex syndrome.

  19. Renal inflammatory myofibroblastic tumor

    DEFF Research Database (Denmark)

    Heerwagen, S T; Jensen, C; Bagi, P

    2007-01-01

    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  20. Peripheral epithelial odontogenic tumor

    International Nuclear Information System (INIS)

    Carzoglio, J.; Tancredi, N.; Capurro, S.; Ravecca, T.; Scarrone, P.

    2006-01-01

    A new case of peripheral epithelial odontogenic tumor (Pindborg tumor) is reported. It is localized in the superior right gingival region, a less frequent site, and has the histopathological features previously reported. Immunochemical studies were performed, revealing a differential positive stain to cytokeratins in tumor cells deeply seated in the tumor mass, probably related to tumoral cell heterogeneity.Interestingly, in this particular case S-100 protein positive reactivity was also detected in arborescent cells intermingled with tumoral cells, resembling Langerhans cells. Even though referred in the literature in central Pindborg tumors, no references were found about their presence in peripheral tumors, like the one that is presented here

  1. Renal angioplasty for atherosclerotic renal artery stenosis: Cardiologist′s perspective

    Directory of Open Access Journals (Sweden)

    A S Gulati

    2013-01-01

    Full Text Available Atherosclerotic renal artery stenosis (ARAS is frequently associated with concomitant coronary and peripheral arterial disease with a significant impact on cardiovascular morbidity and mortality. Renal angioplasty of ARAS is more challenging because of increased incidence of technical failures, complications, and restenosis; while there is barely perceptible control of hypertension and only marginal improvement in renal function. This is because most of the patient population in recent randomized trials had unmanifested or clinically silent renovascular disease. Manifestations of RAS should be looked for and incorporated in the management plan particularly before deciding for revascularization. In the absence of clinical manifestation like renovascular hypertension, ischemic nephropathy, left ventricular failure, or unstable coronary syndromes; mere presence of RAS is analogous to presence of concomitant peripheral arterial disease which increases risk of adverse coronary events. Dormant-RAS in the absence of any manifestations can be managed with masterly inactivity. Chronological sequence of events and clinical condition of the patient help in decision making by identifying progressive renovascular disease. Selecting patients for renal artery stenting who actually will benefit from revascularization shall also decrease the unnecessary complications inherent with any interventional procedure. The present review is an attempt to analyze the current view on the diagnostic and management issues more specifically about the need and rationale behind angioplasty.

  2. Malaria induced acute renal failure: A single center experience

    International Nuclear Information System (INIS)

    KV Kanodia; AV Vanikar

    2010-01-01

    Malaria has protean clinical manifestations and renal complications, particularly acute renal failure that could be life threatening. To evaluate the incidence, clinical profile, ou come and predictors of mortality in patients with malarial acute renal failure, we retrospectively studied the last two years records of malaria induced acute renal failure in patients with peripheral smear positive for malarial parasites. One hundred (10.4%) (63 males, 37 females) malaria induced acute renal failure amongst 958 cases of acute renal failure were evaluated. Plasmodium (P). falciparum was reported in 85%, P. vivax in 2%, and both in 13% patients. The mean serum creatinine was 9.2 ± 4.2 mg%, and oligo/anuria was present in 82%; 78% of the patients required hemodialysis. Sixty four percent of the patients recovered completely, 10% incompletely, and 5% developed chronic kidney failure; mortality occurred in 21% of the patients. Low hemoglobin, oligo/anuria on admission, hyperbilirubinemia, cerebral malaria, disseminated intravascular coagulation, and high serum creatinine were the main predictors of mortality. We conclude that malaria is associated with acute renal failure, which occurs most commonly in plasmodium falciparum infected patients. Early diagnosis and prompt dialysis with supportive management can reduce morality and enhance recovery of renal function (Author).

  3. Cigarette smoking and cardio-renal events in patients with atherosclerotic renal artery stenosis.

    Directory of Open Access Journals (Sweden)

    Christopher A Drummond

    Full Text Available Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731 clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931 were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p<0.001. In addition, patients who smoke were also more likely to have bilateral renal artery stenoses and peripheral vascular disease (PVD. Longitudinal analysis showed that smokers experienced composite endpoint events (defined as first occurrence of: stroke; cardiovascular or renal death; myocardial infarction; hospitalization for congestive heart failure; permanent renal replacement; and progressive renal insufficiency defined as 30% reduction of GFR from baseline sustained for ≥ 60 days at a substantially younger age compared to non-smokers (67.1±9.0 versus 76.1±7.9, p<0.001. Using linear regression and generalized linear modeling analysis controlled by age, sex, and ethnicity, smokers had significantly higher cystatin C levels (1.3±0.7 vs 1.2±0.9, p<0.01 whereas creatinine and estimated glomerular filtration rate (eGFR were not different from non-smokers. From these data we conclude that smoking has a significant association with deleterious cardio-renal outcomes in patients with renovascular hypertension.

  4. Traumatic renal infarction

    International Nuclear Information System (INIS)

    Yashiro, Naobumi; Ohtomo, Kuni; Kokubo, Takashi; Itai, Yuji; Iio, Masahiro

    1986-01-01

    Four cases of traumatic renal artery occlusion were described and illustrated. In two cases, direct blows to the abdomen compressed the renal artery against the vertebral column. Clinically, they were severely injured with macroscopic hematuria. Aortograms showed abrupt truncation of renal arteries. In the other two, rapid deceleration caused sudden displacement of the kidney producing an intimal tear with resultant thrombosis. Although they showed little injury without macrohematuria, aortograms revealed tapered occlusion of renal arteries. One of them developed hypertension. ''Rim sign'' of post-contrast CT and hypertension resulted from traumatic renal artery occlusion were reviewed. (author)

  5. Peripheral Artery Disease

    Science.gov (United States)

    ... pressure High blood cholesterol Coronary heart disease Stroke Metabolic syndrome Screening and Prevention Taking action to control your risk factors can help prevent or delay peripheral artery disease (P.A.D.) and its complications. Know your family history of health problems related to P.A. ...

  6. Promoting peripheral myelin repair.

    Science.gov (United States)

    Zhou, Ye; Notterpek, Lucia

    2016-09-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and Z-drugs consumption in nine European countries.

    Science.gov (United States)

    Clay, Emilie; Falissard, Bruno; Moore, Nicholas; Toumi, Mondher

    2013-04-01

    Benzodiazepines (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone, altogether Z-drugs) are most commonly prescribed for the treatment of insomnia. However, long-term use of BZD/Z-drugs is associated with major adverse events including, but not limited to, falls and fractures, domestic and traffic accidents, confusion, cognitive impairment, Alzheimer's disease and cancer. The prolonged use of these drugs is thought to be related to severe withdrawal symptoms and potential dependency. The chronic and extensive use of BZD/Z drugs has become a public health issue and has led to multiple campaigns to reduce both prescription and consumption of BZD/Z-drugs. Prolonged-release (PR) melatonin is the first of a new class of melatonin receptor agonist drugs that has demonstrated clinically relevant efficacy on improving quality of sleep and morning alertness, with a good safety profile. This study aimed to analyze and evaluate the impact of anti-BZD/Z-drugs campaigns and the availability of alternative pharmacotherapy (PR-melatonin) on the consumption of BZD and Z-drugs in several European countries. Annual sales data from nine European countries were extracted from the IMS sales database and analyzed to determine whether trends in use of these treatment options were attributed to campaigns and/or availability and affordability of safer alternatives on the market. Campaigns aiming to reduce the use of BZD/Z-drugs failed when they were not associated with the availability and market uptake of PR-melatonin. The reimbursement of PR-melatonin supports better penetration rates and a higher reduction in sales for BZD/Z-drugs.

  8. The angiographic incidence of renal artery stenosis in the arterioscleritic population

    International Nuclear Information System (INIS)

    Wils, G.; Marchal, G.; Peene, P.; Baert, A.L.

    1990-01-01

    The incidence of renal artery stenosis was evaluated with intra-arterial digital subtraction anghiography in 100 consecutive patients referred for peripheral arteriopathy. Fifty-seven patients were normotensive, 43 were hypertensive. In the normotensive group, renal artery stenosis was found in ten patients (17.5%). In the hypertensive group renal artery stenosis was found in twelve patients (28%). It is concluded that the incidence of renal aretery stenosis is high in an arterioslcerotic population both in normotensive and hypertensive patients. (author). 16 refs.; 1 tab

  9. [18F]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors

    International Nuclear Information System (INIS)

    Gruender, G.; Lange-Asschenfeldt, C.; Vernaleken, I.; Lueddens, H.; Siessmeier, T.; Buchholz, H.-G.; Bartenstein, P.; Stoeter, P.; Drzezga, A.; Roesch, F.

    2001-01-01

    5-(2'-[ 18 F]Fluoroethyl)flumazenil ([ 18 F]FEF) is a fluorine-18 labelled positron emission tomography (PET) tracer for central benzodiazepine receptors. Compared with the established [ 11 C]flumazenil, it has the advantage of the longer half-life of the fluorine-18 label. After optimisation of its synthesis and determination of its in vitro receptor affinities, we performed first PET studies in humans. PET studies in seven healthy human volunteers were performed on a Siemens ECAT EXACT whole-body scanner after injection of 100-280 MBq [ 18 F]FEF. In two subjects, a second PET scan was conducted after pretreatment with unlabelled flumazenil (1 mg or 2.5 mg i.v., 3 min before tracer injection). A third subject was studied both with [ 18 F]FEF and with [ 11 C]flumazenil. Brain radioactivity was measured for 60-90 min p.i. and analysed with a region of interest-oriented approach and on a voxelwise basis with spectral analysis. Plasma radioactivity was determined from arterial blood samples and metabolites were determined by high-performance liquid chromatography. In human brain, maximum radioactivity accumulation was observed 4±2 min p.i., with a fast clearance kinetics resulting in 50% and 20% of maximal activities at about 10 and 30 min, respectively. [ 18 F]FEF uptake followed the known central benzodiazepine receptor distribution in the human brain (occipital cortex >temporal cortex >cerebellum >thalamus >pons). Pretreatment with unlabelled flumazenil resulted in reduced tracer uptake in all brain areas except for receptor-free reference regions like the pons. Parametric images of distribution volume and binding potential generated on a voxelwise basis revealed two- to three-fold lower in vivo receptor binding of [ 18 F]FEF compared with [ 11 C]flumazenil, while relative uptake of [ 18 F]FEF was higher in the cerebellum, most likely owing to its relatively higher affinity for benzodiazepine receptors containing the α6 subunit. Metabolism of [ 18 F]FEF was very

  10. The interaction of substituted benzamides with brain benzodiazepine binding sites in vitro.

    OpenAIRE

    Horton, R. W.; Lowther, S.; Chivers, J.; Jenner, P.; Marsden, C. D.; Testa, B.

    1988-01-01

    1. The interaction of substituted benzamides with brain benzodiazepine (BDZ) binding sites was examined by their ability to displace [3H]-flunitrazepam ([3H]-FNM) from specific binding sites in bovine cortical membranes in vitro. 2. Clebopride, Delagrange 2674, Delagrange 2335 and BRL 20627 displayed concentration-dependent displacement of [3H]-FNM with IC50 values of 73 nM, 132 nM, 7.7 microM and 5.9 microM, respectively. Other substituted benzamides including metoclopramide, sulpiride, tiap...

  11. The GABA-A benzodiazepine receptor complex: Role of pet and spect in neurology and psychiatry

    International Nuclear Information System (INIS)

    Juengling, F.D.; Schaefer, M.; Heinz, A.

    2002-01-01

    Nuclear medicine imaging techniques such as positron emission tomography (PET) and single photon emission tomography (SPECT) for selective depiction of GABA-A-benzodiazepine receptor (GBZR) binding are complementary investigations in the diagnostic process of neurological and psychiatric disorders. This review summarizes the current knowledge about options and limitations of PET and SPECT for in vivo diagnostics in neurology and psychiatry. The growing importance of GBZR-imaging for the understanding of pathophysiology and pharmacological treatment in different psychiatric syndromes is discussed. (orig.) [de

  12. Renal transplantation in high cardiovascular risk patients.

    Science.gov (United States)

    Bittar, Julio; Arenas, Paula; Chiurchiu, Carlos; de la Fuente, Jorge; de Arteaga, Javier; Douthat, Walter; Massari, Pablo U

    2009-10-01

    Current transplant success allows recipients with previous contraindications to transplant to have access to this procedure with more frequency and safety. The concept of high-risk patient has changed since the first stages of transplantation. In the first studies, the high-risk concept was based on probability of early graft failure or on a patient's clinical condition to cope with high perioperatory morbimortality. Later on, this concept implied immunological factors that were crucial to ensure transplant success because hypersensitized or polytransfused patients experienced a higher risk of acute rejection and subsequent graft loss. Afterward, the presence of various comorbidities would redefine the high-risk concept for renal transplant mainly considering recipient's clinical aspects. Currently, the change in epidemiological characteristics of patients starting dialysis causes that we now deal with a greater increase of elderly patients, diabetic patients, and patients with history of cardiovascular disease. Today, high-risk patients are those with clinical features that predict an increase in the risk of perioperative morbimortality or death with functioning graft. In this review, we will attempted to analyze currents results of renal transplant outcomes in terms of patients and graft survival in elderly patients, diabetic patients, and patients with previous cardiovascular disease from the most recent experiences in the literature and from experiences in our center. In any of the groups previously analyzed, survival offered by renal transplant is significantly higher compared to dialysis. Besides, these patients are the recipient group that benefit the most with the transplant because their mortality while remaining on dialysis is extremely high. Hence, renal transplantation should be offered more frequently to older patients, diabetic patients, and patients with pretransplant cardiac and peripheral vascular disease. A positive attitude toward renal

  13. sup(99m)Tc-DMSA renal scintigraphy in renal failure due to various renal diseases

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, S; Daijo, K; Okabe, T; Kawamura, J; Hara, A [Kyoto Univ. (Japan). Hospital

    1979-08-01

    Renal contours in renal failure were studied by means of sup(99m)Tc-dimercaptosuccinic acid (DMSA) renoscintigraphy. Renal cortical images were obtained even in renal failure cases. Causes of renal failure were chronic glomerulonephritis in 7, bilateral renal tuberculosis in 2, chronic pyelonephritis in 3, bilateral renal calculi in 3, diabetic nephropathy in 2, polycystic kidney disease in 2 and stomach cancer in 1.

  14. sup(99m)Tc-DMSA renal scintigraphy in renal failure due to various renal diseases

    International Nuclear Information System (INIS)

    Hosokawa, Shin-ichi; Daijo, Kazuyuki; Okabe, Tatsushiro; Kawamura, Juichi; Hara, Akira

    1979-01-01

    Renal contours in renal failure were studied by means of sup(99m)Tc-dimercaptosuccinic acid (DMSA) renoscintigraphy. Renal cortical images were obtained even in renal failure cases. Causes of renal failure were chronic glomerulonephritis in 7, bilateral renal tuberculosis in 2, chronic pyelonephritis in 3, bilateral renal calculi in 3, diabetic nephropathy in 2, polycystic kidney disease in 2 and stomach cancer in 1. (author)

  15. Increased thermolability of benzodiazepine receptors in cerebral cortex of a baboon with spontaneous seizures: a case report.

    Science.gov (United States)

    Squires, R; Naquet, R; Riche, D; Braestrup, C

    1979-06-01

    The benzodiazepine receptor in the cortex of 1 spontaneously epileptic baboon exhibited an increased rate of thermal inactivation at 65 degrees C when compared with those from 3 other baboons. In other respects (receptor concentration, affinities for flunitrazepam and diazepam, and response to changing pH), the benzodiazepine receptor from this animal was very similar to the receptors in the cortex of 3 other baboons. The 3H-QNB (muscarinic) and 3H-naloxone (opiate) binding sites in the brain of all 4 baboons appeared very similar with respect to all parameters studied (thermal stability, concentration, regional distribution, and affinities for respective ligands). An endogenous factor stabilizing the benzodiazepine receptor could be lacking in the spontaneously epileptic baboon.

  16. Development of chronic heart failure in a young woman with hypertension associated with renal artery stenosis with preserved renal function

    DEFF Research Database (Denmark)

    Byrne, Christina; Abdulla, Jawdat

    2014-01-01

    A 33-year-old woman with presumed essential hypertension and symptoms equivalent to New York Heart Association class II was suspected of heart failure and referred to echocardiography. The patient's ECG showed a left bundle branch block. Electrolytes, serum creatinine and estimated-glomerular fil......A 33-year-old woman with presumed essential hypertension and symptoms equivalent to New York Heart Association class II was suspected of heart failure and referred to echocardiography. The patient's ECG showed a left bundle branch block. Electrolytes, serum creatinine and estimated......-glomerular filtration rate as well as urine test for protein were all normal. The patient had no peripheral oedema. The transthoracic echocardiography confirmed systolic and diastolic dysfunction and an ejection fraction of 25% and left ventricular hypertrophy. Ultrasound of renal arteries and renal CT angiography...... (renal CTA) revealed a significant stenosis and an aneurysm corresponding to the right renal artery with challenges to traditional interventions....

  17. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

    DEFF Research Database (Denmark)

    Baandrup, Lone; Fagerlund, Birgitte; Jennum, Poul

    2011-01-01

    Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged...

  18. SYNTHESIS OF 1,2 FUSED SYSTEMS BASED ON THE 3-ARYLIDENE-5-PHENYL-1,2-DIHYDRO-3H-1,4- BENZODIAZEPINE-2-ONES

    Directory of Open Access Journals (Sweden)

    V. I. Pavlovsky

    2014-12-01

    Full Text Available By the reaction of 7-bromo-5-aryl-1,2-dihydro-3H-1,4-benzodiazepine-2-ones with Lawesson reagent, 7-bromo-5-aryl-1,2-dihydro-3H-1,4-benzodiazepine-2-tiones were synthesized from which 3-arylidene-7-bromo-2-hydrazino-5-phenyl-3H-1,4-benzodiazepines were obtained by the reaction with hydrazine hydrate. The condensation of 3-arylidene-7-bromo-2-hydrazino-5-phenyl-3H-1,4-benzodiazepines with triethylorthoformate (triethylorthoacetate or formic acid (acetic acid gave 4-arylidene-8-bromo-6-phenyl-4H-[1,2,4]triazolo[4,3-а][1,4]-benzodiazepines. Latter were also synthesized by the reaction of 7-bromo-5-aryl-1,2-dihydro-3H-1,4-benzodiazepine-2-tiones with acetylhydrazine. 4-Arylidene-8-bromo-6-phenyl-4H-[1,2,3,4] tetrazolo[1,5-а][1,4]-benzodiazepines were obtained by the reaction of 3-arylidene-7-bromo-2-hydrazino-5-phenyl-3H-1,4-benzodiazepines with sodium nitrite.

  19. Peripheral orbit model

    CERN Document Server

    Hara, Yasuo

    1975-01-01

    Peripheral orbit model, in which an incoming hadron is assumed to revolve in a peripheral orbit around a target hadron, is discussed. The non-diffractive parts of two-body reaction amplitudes of hadrons are expressed in terms of the radius, width an absorptivity of the orbit. The radius of the orbit is about 1 fm and the width of the orbit is determined by the range of the interaction between the hadrons. The model reproduces all available experimental data on differential cross-sections and polarizations of $K^{-}p\\to K^{-}p$ and $\\bar K^{\\circ}n$ reactions for all angles successfully. This contribution is not included in the proceedings since it will appear in Progress of Theoretical Physics Vol. 51 (1974) No 2. Any person interested in the subject may apply for reprints to the author.

  20. Frequency and clinical predictors of coronary artery disease in chronic renal failure renal transplant candidates.

    Science.gov (United States)

    de Albuquerque Seixas, Emerson; Carmello, Beatriz Leone; Kojima, Christiane Akemi; Contti, Mariana Moraes; Modeli de Andrade, Luiz Gustavo; Maiello, José Roberto; Almeida, Fernando Antonio; Martin, Luis Cuadrado

    2015-05-01

    Cardiovascular diseases are major causes of mortality in chronic renal failure patients before and after renal transplantation. Among them, coronary disease presents a particular risk; however, risk predictors have been used to diagnose coronary heart disease. This study evaluated the frequency and importance of clinical predictors of coronary artery disease in chronic renal failure patients undergoing dialysis who were renal transplant candidates, and assessed a previously developed scoring system. Coronary angiographies conducted between March 2008 and April 2013 from 99 candidates for renal transplantation from two transplant centers in São Paulo state were analyzed for associations between significant coronary artery diseases (≥70% stenosis in one or more epicardial coronary arteries or ≥50% in the left main coronary artery) and clinical parameters. Univariate logistic regression analysis identified diabetes, angina, and/or previous infarction, clinical peripheral arterial disease and dyslipidemia as predictors of coronary artery disease. Multiple logistic regression analysis identified only diabetes and angina and/or previous infarction as independent predictors. The results corroborate previous studies demonstrating the importance of these factors when selecting patients for coronary angiography in clinical pretransplant evaluation.

  1. Renal blood flow and oxygenation drive nephron progenitor differentiation.

    Science.gov (United States)

    Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K; Bates, Carlton M; Sims-Lucas, Sunder

    2014-08-01

    During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation. Copyright © 2014 the American Physiological Society.

  2. Application of gamma-aminobutyric acid type A-benzodiazepine receptor imaging for study of neuropsychiatric disorders

    International Nuclear Information System (INIS)

    Bao Weiqi; Qiu Chun; Guan Yihui

    2012-01-01

    Gamma-aminobutyric acid type A-benzodiazepine receptors are heterogeneous polypeptide pentamers widely spread in the central nervous system on the neuron membrane. Different subunit combinations educe various neuro-inhibitory pharmacological effects such as sedative, hypnosis, anticonvulsion and anxiolysis. PET can be utilized to study the binding of the receptors in vivo. PET radioligands of gamma-aminobutyric acid type A-benzodiazepine receptors can be classified into 3 types: antagonists,agonists and reverse agonists, of which antagonist radiotracer 11 C-flumazenil is the most commonly applied in epilepsy, anxiety disorders, depression, vegetative state,addiction and other neuro-psychiatric disorders. (authors)

  3. Temporal characteristics of stress-induced decrease in benzodiazepine reception in C57BL/6 and BALB/c mice.

    Science.gov (United States)

    Yarkova, M A; Seredenin, S B

    2014-10-01

    We studied the duration of the drop of specific (3)H-flunitrazepam binding by synaptosomal membranes from the brain of C57Bl/6 and BALB/c mice after open-field and "contact with predator" tests. It was found that reduced benzodiazepine reception in BALB/c mice after open-field test persisted for 1.5 h, but no changes of this parameter were found in C57Bl/6 mice. After contact with predator, the binding capacity of the benzodiazepine site of GABAA receptor was reduced for 8 h in BALB/c mice and for 24 h in C57Bl/6 mice.

  4. Imaging of renal osteodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Jevtic, V. E-mail: vladimir.jevtic@mf.uni-lj.si

    2003-05-01

    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination.

  5. Imaging of renal osteodystrophy

    International Nuclear Information System (INIS)

    Jevtic, V.

    2003-01-01

    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination

  6. Renal mucormycosis in a patient with AIDS

    International Nuclear Information System (INIS)

    Macias, M.; Leiva, M.C.; Acebal, M.; Algarra, J.; Luis, M.C. de.

    1996-01-01

    We report a case of renal mucormycosis in al HIV-positive patient presenting evidence of AIDS, with involvement of no other organs. Intravenous showed left kidney to be enlarged and nonfunctioning: US disclosed and enlarged organ, with no hydronephrosis and showing loss of corticomedullary differentiation: CT revealed the presence of a large mass of the density of water surrounded by peripheral enhancement. After surgical treatment, the necrotic tissue was found to contain hyphae corresponding to a mucor fungus. The patient improved significantly with amphotericin B. the radiological findings are discussed. (Author) 10 refs

  7. Hypothyroidism presenting as reversible renal impairment: an interesting case report.

    Science.gov (United States)

    Vikrant, Sanjay; Chander, Subhash; Kumar, Satish; Gupta, Dalip

    2013-10-01

    We describe an interesting case of reversible renal impairment secondary to hypothyroidism. A 57-years-old man was referred from peripheral institution for evaluation of elevated serum creatinine. He had vague complaints of weakness, lethargy and muscle ache but no urinary symptoms. He was found to have hypothyroidism, and thyroid hormone replacement therapy (THRT) was started which resulted in reversal of the renal dysfunction. There was marked improvement in estimated glomerular filtration rate. 99mTc DTPA renal scans done before and after THRT suggested hypothyroidism responsible for this reversible renal impairment. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown total amelioration of renal impairment as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. We suggest that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation.

  8. Inhibition of benzodiazepine binding in vitro by amentoflavone, a constituent of various species of Hypericum.

    Science.gov (United States)

    Baureithel, K H; Büter, K B; Engesser, A; Burkard, W; Schaffner, W

    1997-06-01

    Flower extracts of Hypericum perforatum, Hypericum hirsutum, Hypericum patulum and Hypericum olympicum efficiently inhibited binding of [3H]flumazenil to rat brain benzodiazepine binding sites of the GABAA-receptor in vitro with IC50 values of 6.83, 6.97, 13.2 and 6.14 micrograms/ml, respectively. Single constituents of the extracts like hypericin, the flavones quercetin and luteolin, the glycosylated flavonoides rutin, hyperoside and quercitrin and the biflavone 13, II8-biapigenin did not inhibit binding up to concentrations of 1 microM. In contrast, amentoflavone revealed an IC50 = 14.9 +/- 1.9 nM on benzodiazepine binding in vitro. Comparative HPLC analyses of hypericin and amentoflavone in extracts of different Hypericum species revealed a possible correlation between the amentoflavone concentration and the inhibition of flumazenil binding. For hypericin no such correlation was observed. Our experimental data demonstrate that amentoflavone, in contrast to hypericin, presents a very active compound with regard to the inhibition of [3H]-flumazenil binding in vitro and thus might be involved in the antidepressant effects of Hypericum perforatum extracts.

  9. Modulation of benzodiazepine by lysine and pipecolic acid on pentylenetetrazol-induced seizures

    International Nuclear Information System (INIS)

    Chang, Y.F.; Hargest, V.; Chen, J.S.

    1988-01-01

    L-lysine and its metabolite pipecolic acid (PA) have been studied for their effects on pentylenetetrazol (PTZ)-induced seizures in mice. L-Lysine of L-Pa i.p. significantly increased clonic and tonic latencies in a dose-dependent manner against 90 mg/kg PTZ-induced seizures. L-Lysine but not L-Pa enhanced the anticonvulsant effect of diazepam (DZ). L-Pa i.c.v. showed a slight decrease in clonic latency; it did not enhance the antiseizure activity of DZ; it caused seizures at 0.6 mmol/kg. D-PA i.c.v. displayed an opposite effect compared to its L-isomer. The anticonvulsant effect of L-lysine in terms of increase in seizure latency and survival was even more amplified when tested with a submaximal PTZ concentration. L-Lysine showed an enhancement of specific 3 H-flunitrazepam(FZ) binding to mouse brain membranes both in vitro an din vivo. The possibility of L-lysine acting as a modulator for the GABA/benzodiazepine receptors was demonstrated. Since L-PA showed enhancement of 3 H-FZ binding only in vitro but not in vivo, the anticonvulsant effect of L-PA may not be linked to the GABA/benzodiazepine receptor

  10. Soman- or kainic acid-induced convulsions decrease muscarinic receptors but not benzodiazepine receptors

    International Nuclear Information System (INIS)

    Churchill, L.; Pazdernik, T.L.; Cross, R.S.; Nelson, S.R.; Samson, F.E.

    1990-01-01

    [3H]Quinuclidinyl benzilate (QNB) binding to muscarinic receptors decreased in the rat forebrain after convulsions induced by a single dose of either soman, a potent inhibitor of acetylcholinesterase, or kainic acid, an excitotoxin. A Rosenthal plot revealed that the receptors decreased in number rather than affinity. When the soman-induced convulsions were blocked, the decrease in muscarinic receptors at 3 days was less extensive than when convulsions occurred and at 10 days they approached control levels in most of the brain areas. The most prominent decrements in QNB binding were in the piriform cortex where the decline in QNB binding is probably related to the extensive convulsion-associated neuropathology. The decrements in QNB binding after convulsions suggest that the convulsive state leads to a down-regulation of muscarinic receptors in some brain areas. In contrast to the decrease in QNB binding after convulsions, [3H]flunitrazepam binding to benzodiazepine receptors did not change even in the piriform cortex where the loss in muscarinic receptors was most prominent. Thus, it appears that those neuronal processes that bear muscarinic receptors are more vulnerable to convulsion-induced change than those with benzodiazepine receptors

  11. Modulation of acetylcholine release from rat striatal slices by the GABA/benzodiazepine receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Supavilai, P.; Karobath, M.

    1985-02-04

    GABA, THIP and muscimol enhance spontaneous and inhibit electrically induced release of tritium labelled compounds from rat striatal slices which have been pre-labelled with /sup 3/H-choline. Baclofen is inactive in this model. Muscimol can inhibit electrically induced release of tritiated material by approximately 75% with half maximal effects at 2 ..mu..M. The response to muscimol can be blocked by the GABA antagonists bicuculline methobromide, picrotoxin, anisatin, R 5135 and CPTBO (cyclopentylbicyclophosphate). Drugs which act on the benzodiazepine receptor (BR) require the presence of muscimol to be effective and they modulate the effects of muscimol in a bidirectional manner. Thus BR agonists enhance and inverse BR agonists attenuate the inhibitory effects of muscimol on electrically induced release. Ro15-1788, a BR antagonist, does not modulate the inhibitory effects of muscimol but antagonizes the actions of clonazepam, a BR agonist, and of DMCM, an inverse BR agonist. These results demonstrate that a GABA/benzodiazepine receptor complex can modulate acetylcholine release from rat striatal slices in vitro. 24 references, 3 figures, 5 table.

  12. Renal artery stenosis

    International Nuclear Information System (INIS)

    Desberg, A.; Paushter, D.M.; Lammert, G.K.; Hale, J.; Troy, R.; Novic, A.; Nally, J. Jr.

    1989-01-01

    Renal artery disease is a potentially correctable cause of hypertension. Previous studies have suggested the utility of duplex sonography in accurately detecting and grading the severity of renal artery stenosis. The purpose of this paper is to evaluate color flow Doppler for this use. Forty-three kidneys were examined by color-flow Doppler and conventional duplex sampling in patients with suspected renovascular hypertension or those undergoing aortography for unrelated reasons. Doppler tracings were obtained from the renal arteries and aorta with calculation of the renal aortic ratio (RAR) and resistive index (RI). Results of Doppler sampling with color flow guidance were compared with aortograms in a blinded fashion

  13. Incidental renal neoplasms

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Mikkelsen, Minne Nedergaard; Walter, Steen

    2014-01-01

    On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive...... series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients...

  14. Renal cell carcinoma in patient with crossed fused renal ectopia

    Directory of Open Access Journals (Sweden)

    Ozgur Cakmak

    2016-01-01

    Full Text Available Primary renal cell carcinomas have rarely been reported in patients with crossed fused renal ectopia. We presented a patient with right to left crossed fused kidney harbouring renal tumor. The most frequent tumor encountered in crossed fused renal ectopia is renal cell carcinoma. In this case, partial nephrectomy was performed which pave way to preservation of the uninvolved both renal units. Due to unpredictable anatomy, careful preoperative planning and meticulous delineation of renal vasculature is essential for preservation of the uninvolved renal units.

  15. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  16. Bilateral papillary renal cell carcinoma

    International Nuclear Information System (INIS)

    Gossios, K.; Vazakas, P.; Argyropoulou, M.; Stefanaki, S.; Stavropoulos, N.E.

    2001-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific. (orig.)

  17. Daspsone Induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    P A Sarojini

    1988-01-01

    Full Text Available A 24 year old lady being treated with 300 mg of dapsone daily for dermatitits herpetiformis, developed weakness and wasting of muscles of feet with claw hand deformity and t drop, 2 months tater. Neurological examination and nerve conduction studies conformed the presence of a peripheral motor neuropathy. Dapsone was discontinued and the patient was treated with cotrimatoxazole, gluten-free diet and supportive therapy. This satisfactorily controlled the dermatological lesion without adversely affecting the resolution of her neuropthy. Symptomatic improvement reported by the patient was confirmed by EMG and nerve conduction studies.

  18. Peripheral ossifying fibroma

    Directory of Open Access Journals (Sweden)

    Ameet Mani

    2010-01-01

    Full Text Available The peripheral ossifying fibroma (POF is an exophytic gingival mass of fibrous connective tissue covered with a surface epithelium associated with the formation of randomly dispersed foci of a mineralized product consisting of bone, cementum-like tissue, or dystrophic calcifications having a recurrent rate of nearly 20%. It is one of the most common reactive gingival lesions, which have often been called by the generic term "epulis." This case report describes the clinical and histopathological findings of POF, its differential diagnosis, and treatment.

  19. Contrast-enhanced peripheral MRA. Technique and contrast agents

    International Nuclear Information System (INIS)

    Nielsen, Yousef W.; Thomsen, Henrik S.

    2012-01-01

    In the last decade contrast-enhanced magnetic resonance angiography (CE-MRA) has gained wide acceptance as a valuable tool in the diagnostic work-up of patients with peripheral arterial disease. This review presents current concepts in peripheral CE-MRA with emphasis on MRI technique and contrast agents. Peripheral CE-MRA is defined as an MR angiogram of the arteries from the aortic bifurcation to the feet. Advantages of CE-MRA include minimal invasiveness and lack of ionizing radiation. The basic technique employed for peripheral CE-MRA is the bolus-chase method. With this method a paramagnetic MRI contrast agent is injected intravenously and T1-weighted images are acquired in the subsequent arterial first-pass phase. In order to achieve high quality MR angiograms without interfering venous contamination or artifacts, a number of factors need to be taken into account. This includes magnetic field strength of the MRI system, receiver coil configuration, use of parallel imaging, contrast bolus timing technique, and k-space filling strategies. Furthermore, it is possible to optimize peripheral CE-MRA using venous compression techniques, hybrid scan protocols, time-resolved imaging, and steady-state MRA. Gadolinium(Gd)-based contrast agents are used for CE-MRA of the peripheral arteries. Extracellular Gd agents have a pharmacokinetic profile similar to iodinated contrast media. Accordingly, these agents are employed for first-pass MRA. Blood-pool Gd-based agents are characterized by prolonged intravascular stay, due to macromolecular structure or protein binding. These agents can be used for first-pass, as well as steady-state MRA. Some Gd-based contrast agents with low thermodynamic stability have been linked to development of nephrogenic systemic fibrosis in patients with severe renal insufficiency. Using optimized technique and a stable MRI contrast agent, peripheral CE-MRA is a safe procedure with diagnostic accuracy close to that of conventional catheter X

  20. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    Khalid, S.; Khalid, M; Elfaki, M.; Hassan, N.; Suliman, S.M.

    2007-01-01

    Background Hypothyroidism induces significant changes in the function of organ systems such as the heart, muscles and brain. Renal function is also influenced by thyroid status. Physiological effects include changes in water and electrolyte metabolism, notably hyponatremia, and reliable alterations of renal hemodynamics, including decrements in renal blood flow, renal plasma flow, glomerular filtration rate (GFR). Objective Renal function is profoundly influenced by thyroid status; the purpose of the present study was to determine the relationship between renal function and thyroid status of patients with hypothyroidism. Design and Patients In 5 patients with primary hypothyroidism and control group renal functions are measured by serum creatinine and glomerular filtration rate (GFR) using modified in diet renal disease (MDRD) formula. Result In hypothyroidism, mean serum creatinine increased and mean estimated GFR decreased, compared to the control group mean serum creatinine decreased and mean estimated GFR Increased. The hypothyroid patients showed elevated serum creatinine levels (> 1.1mg/dl) compared to control group (p value .000). In patients mean estimated GFR decreased, compared to mean estimated GFR increased in the control group (p value= .002).

  1. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    Khalid, A. S; Ahmed, M.I; Elfaki, H.M; Hassan, N.; Suliman, S. M.

    2006-12-01

    Background hypothyroidism induces significant changes in the function of organ systems such as the heart, muscles and brain. Renal function is also influenced by thyroid status. Physiological effects include changes in water and electrolyte metabolism, notably hyponatraemia, and reliable alterations of renal hemodynamics, including decrements in renal blood flow, renal plasma flow, glomerular filtration rate (GFR). Objective renal function is profoundly influenced by thyroid status, the purpose of the present study was to determine the relationship between renal function and thyroid status of patients with hypothyroidism. Design and patients in 5 patients with primary hypothyroidism and control group renal functions are measured by serum creatinine and glomerular filtration rate(GFR) using modified in diet renal disease (MDRD) formula. Result in hypothyroidism, mean serum creatinine increased and mean estimated GFR decreased, compared to the control group mean serum creatinine decreased and mean estimated GFR increased. The hypothyroid patients showed elevated serum creatinine levels(>1.1 mg/d1) compared to control group (p value= 000). In patients mean estimated GFR increased in the control group (p value=.002).Conclusion thus the kidney, in addition to the brain, heart and muscle, is an important target of the action of thyroid hormones.(Author)

  2. Disappearing renal calculus.

    Science.gov (United States)

    Cui, Helen; Thomas, Johanna; Kumar, Sunil

    2013-04-10

    We present a case of a renal calculus treated solely with antibiotics which has not been previously reported in the literature. A man with a 17 mm lower pole renal calculus and concurrent Escherichia coli urine infection was being worked up to undergo percutaneous nephrolithotomy. However, after a course of preoperative antibiotics the stone was no longer seen on retrograde pyelography or CT imaging.

  3. Analysis of subcomponents of the gamma-aminobutyric acid/benzodiazepine receptor macromolecular complex in mammalian central nervous system

    International Nuclear Information System (INIS)

    McCabe, R.T.

    1987-01-01

    Since the presence of endogenous gamma-aminobutyric acid (GABA) may affect benzodiazepine binding to tissue sections in autoradiographic studies, a protocol designed to check for this influence has been investigated. [ 3 H]Flunitrazepam (1 nM) was used to label benzodiazepine receptors for autoradiographic localization. Bicuculline was added to the incubation medium of an additional set of tissue sections to antagonize any potential effect of endogenous GABA. Binding in these sections was compared to that occurring in another set in which excess GABA was added to create further GABA enhancement. Binding was also compared to adjacent sections which were treated similarly but also preincubated in distilled-deionized water to burst the cells by osmotic shock and eliminate endogenous GABA, thereby preventing any effect on benzodiazepine binding. The results indicated that endogenous GABA is indeed present in the slide-mounted tissue sections and is affecting benzodiazepine receptor binding differentially in various regions of the brain depending on the density of GABAergic innervation. Scatchard analysis of saturation data demonstrated that the alteration in BZ binding due to GABA was a result of a change in the affinity rather than number of receptors present

  4. Size-exclusion chromatographic reconstitution of the bovine brain benzodiazepine receptor : Effects of lipid environment on the binding characteristics

    NARCIS (Netherlands)

    Viel, G.T; Yang, Q; Lundahl, P; Ensing, K; de Zeeuw, R.A

    1997-01-01

    The benzodiazepine receptor from calf brain was solubilized with sodium deoxycholate (2 mg/ml) in the presence of 0.5 M KCl and protease inhibitors, and bound flunitrazepam with an equilibrium dissociation constant (K-d) of 2.7+/-1.2 nM and with 0.40+/-0.04 pmol binding sites per mg protein (B-max).

  5. CYP2C9 Genotypes Modify Benzodiazepine-Related Fall Risk: Original Results From Three Studies With Meta-Analysis

    NARCIS (Netherlands)

    Ham, Annelies C.; Ziere, Gijsbertus; Broer, Linda; Swart, Karin M. A.; Enneman, Anke W.; van Dijk, Suzanne C.; van Wijngaarden, Janneke P.; van der Zwaluw, Nikita L.; Brouwer-Brolsma, Elske M.; Dhonukshe-Rutten, Rosalie A. M.; van Schoor, Natasja M.; Zillikens, M. Carola; van Gelder, Teun; de Vries, Oscar J.; Lips, Paul; Deeg, Dorly J. H.; de Groot, Lisette C. P. G. M.; Hofman, Albert; Witkamp, Renger F.; Uitterlinden, André G.; Stricker, Bruno H.; van der Velde, Nathalie

    2017-01-01

    To investigate whether the CYP2C9*2 and *3 variants modify benzodiazepine-related fall risk. Three prospective studies; the Rotterdam Study, B-PROOF, and LASA. Community-dwelling individuals living in or near five Dutch cities. There were 11,485 participants aged ≥55 years. Fall incidents were

  6. Dependence and withdrawal reactions to benzodiazepines and selective serotonin reuptake inhibitors. How did the health authorities react?

    Science.gov (United States)

    Nielsen, Margrethe; Hansen, Ebba Holme; Gøtzsche, Peter C

    2013-01-01

    Our objective was to explore communications from drug agencies about benzodiazepine dependence and selective serotonin reuptake inhibitors (SSRIs) withdrawal reactions over time. Documentary study. We searched the web-sites of the European Medicines Agency and the drug agencies in USA, UK, and Denmark for documents mentioning benzodiazepines or SSRIs. We supplemented with other relevant literature that could contribute to our study. The searches were performed in 2009 in PubMed, Google, BMJ and JAMA. It took many years before the drug regulators acknowledged benzodiazepine dependence and SSRI withdrawal reactions and before the prescribers and the public were informed. Drug regulators relied mainly on the definitions of dependence and withdrawal reactions from the diagnostic psychiatric manuals, which contributed to the idea that SSRIs do not cause dependence, although it is difficult for many patients to stop treatment. In the perspective of a precautionary principle, drug agencies have failed to acknowledge that SSRIs can cause dependence and have minimised the problem with regard to its frequency and severity. In the perspective of a risk management principle, the drug agencies have reacted in concordance with the slowly growing knowledge of adverse drug reactions and have sharpened the information to the prescribers and the public over time. However, solely relying on spontaneous reporting of adverse effects leads to underestimation and delayed information about the problems. Given the experience with the benzodiazepines, we believe the regulatory bodies should have required studies from the manufacturers that could have elucidated the dependence potential of the SSRIs before marketing authorization was granted.

  7. Bioassay-guided isolation of apigenin with GABA-benzodiazepine activity from Tanacetum parthenium

    DEFF Research Database (Denmark)

    Jäger, Anna Katharina; Krydsfeldt, Katrine; Rasmussen, Hasse Bonde

    2009-01-01

    Extracts of Tanacetum parthenium are used in the prophylactic treatment of migraine and have also been used in Danish folk medicine for the treatment of epilepsy. An ethanol extract of T. parthenium showed high affinity for the GABA(A)-benzodiazepine site. An ethanol extract of T. parthenium was ...

  8. AC-3933, a benzodiazepine partial inverse agonist, improves memory performance in MK-801-induced amnesia mouse model.

    Science.gov (United States)

    Hashimoto, Takashi; Iwamura, Yoshihiro

    2016-05-01

    AC-3933, a novel benzodiazepine receptor partial inverse agonist, is a drug candidate for cognitive disorders including Alzheimer's disease. We have previously reported that AC-3933 enhances acetylcholine release in the rat hippocampus and ameliorates scopolamine-induced memory impairment and age-related cognitive decline in both rats and mice. In this study, we further evaluated the procognitive effect of AC-3933 on memory impairment induced by MK-801, an N-methyl-d-aspartate receptor antagonist, in mice. Unlike the acetylcholinesterase inhibitor donepezil and the benzodiazepine receptor inverse agonist FG-7142, oral administration of AC-3933 significantly ameliorated MK-801-induced memory impairment in the Y-maze test and in the object location test. Interestingly, the procognitive effects of AC-3933 on MK-801-induced memory impairment were not affected by the benzodiazepine receptor antagonist flumazenil, although this was not the case for the beneficial effects of AC-3933 on scopolamine-induced memory deficit. Moreover, the onset of AC-3933 ameliorating effect on scopolamine- or MK-801-induced memory impairment was different in the Y-maze test. Taken together, these results indicate that AC-3933 improves memory deficits caused by both cholinergic and glutamatergic hypofunction and suggest that the ameliorating effect of AC-3933 on MK-801-induced memory impairment is mediated by a mechanism other than inverse activation of the benzodiazepine receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. GABA(A)-benzodiazepine receptor complex sensitivity in 5-HT(1A) receptor knockout mice on a 129/Sv background.

    NARCIS (Netherlands)

    Pattij, T.; Groenink, L.; Oosting, R.S.; Gugten, J. van der; Maes, R.A.A.; Olivier, B.

    2002-01-01

    Previous studies in 5-HT(1A) receptor knockout (1AKO) mice on a mixed Swiss Websterx129/Sv (SWx129/Sv) and a pure 129/Sv genetic background suggest a differential gamma-aminobutyric acid (GABA(A))-benzodiazepine receptor complex sensitivity in both strains, independent from the anxious phenotype. To

  10. Bilateral triple renal arteries

    International Nuclear Information System (INIS)

    Pestemalci, Turan; Yildiz, Yusuf Zeki; Yildirim, Mehmet; Mavi, Ayfer; Gumusburun, Erdem

    2009-01-01

    Knowledge of the variations of the renal artery has grown in importance with increasing numbers of renal transplants, vascular reconstructions and various surgical and radio logic techniques being performed in recent years. We report the presence of bilateral triple renal arteries, discovered on routine dissection of a male cadaver. On the right side, one additional renal artery originated from the abdominal aorta (distributed to superior pole of the kidney) and one other originated from the right common iliac artery (distributed to lower pole of the kidney). On the left side, both additional renal arteries originated from the abdominal aorta. Our observation has been compared with variations described in the literature and their clinical importance has been emphasized. (author)

  11. Radiology of renal failure

    International Nuclear Information System (INIS)

    Griffiths, H.J.

    1990-01-01

    This book covers most aspects of imaging studies in patients with renal failure. The initial chapter provides basic information on contrast agents, intravenous urography, and imaging findings in the urinary tract disorders responsible for renal failure and in patients who have undergone transplantation. It illustrates common gastro-intestinal abnormalities seen on barium studies in patients with renal failure. It illustrates the cardiopulmonary complications of renal failure and offers advice for radiologic differentiation. It details different aspects of skeletal changes in renal failure, including a basic description of the pathophysiology of the changes; many excellent illustrations of classic bone changes, arthritis, avascular necrosis, and soft-tissue calcifications; and details of bone mineral analysis

  12. [Hypertension and renal disease

    DEFF Research Database (Denmark)

    Kamper, A.L.; Pedersen, E.B.; Strandgaard, S.

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...... nephropathy, effective blood pressure lowering is of paramount importance, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are agents of choice Udgivelsesdato: 2009/6/15...

  13. Multidisciplinary Prerounding Meeting as a Continuous Quality Improvement Tool: Leveraging to Reduce Continuous Benzodiazepine Use at an Academic Medical Center.

    Science.gov (United States)

    Flannery, Alexander H; Thompson Bastin, Melissa L; Montgomery-Yates, Ashley; Hook, Corrine; Cassity, Evan; Eaton, Phillip M; Morris, Peter E

    2018-01-01

    Evidence-based medicine often has many barriers to overcome prior to implementation in practice, hence the importance of continuous quality improvement. We report on a brief (≤10 minutes) multidisciplinary meeting prior to rounds to establish a dashboard for continuous quality improvement and studied the success of this meeting on a particular area of focus: continuous infusion benzodiazepine minimization. This was a prospective observational study of patients admitted to the medical intensive care unit (MICU) of a large academic medical center over a 4-month period. A morning multidisciplinary prerounding meeting was implemented to report on metrics required to establish a dashboard for MICU care for the previous 24 hours. Fellows and nurse practitioners on respective teams reported on key quality metrics and other important data related to patient census. Continuous benzodiazepines were tracked daily as the number of patients per team who had orders for a continuous benzodiazepine infusion. The aim of this report is to describe the development of the morning multidisciplinary prerounding meeting and its impact on continuous benzodiazepine use, along with associated clinical outcomes. The median number of patients prescribed a continuous benzodiazepine daily decreased over this time period and demonstrated a sustained reduction at 1 year. Furthermore, sedation scores improved, corresponding to a reduction in median duration of mechanical ventilation. The effectiveness of this intervention was mapped post hoc to conceptual models used in implementation science. A brief multidisciplinary meeting to review select data points prior to morning rounds establishes mechanisms for continuous quality improvement and may serve as a mediating factor for successful implementation when initiating and monitoring practice change in the ICU.

  14. An Update on Renal Artery Denervation and Its Clinical Impact on Hypertensive Disease

    OpenAIRE

    Bhat, Aditya; Kuang, Ye Min; Gan, Gary C. H.; Burgess, David; Denniss, Alan Robert

    2015-01-01

    Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal a...

  15. A Rare Renal Epithelial Tumor: Mucinous Cystadenocarcinoma Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Abdulkadir Tepeler

    2011-01-01

    Full Text Available Primary renal mucinous cystadenocarcinoma is a very rare lesion of kidney which originates from the metaplasia of the renal pelvic uroepithelium. Only one case with primary mucinous cystadenocarcinoma has been reported in the English literature. We report second case of mucinous cystadenocarcinoma which was radiologically classified as type-IIF Bosniak cyst in peripheral localization. We aimed to present this extreme and unusual entity with its radiological, surgical, and pathologic aspects under the light of literature.

  16. Drug-induced peripheral neuropathy

    DEFF Research Database (Denmark)

    Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed

    2014-01-01

    Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

  17. Synthesis and antimicrobial, antifungal and anthelmintic activities of 3H-1,5-benzodiazepine derivatives

    Directory of Open Access Journals (Sweden)

    RAJESH KUMAR

    2008-10-01

    Full Text Available The diazonium salt of 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide in the presence of sodium hydroxide was condensed with different β-diketones/β-ketoesters, 3a–e, to obtain new β-diketones/β-ketoesters, 4a–e. The β-diketones/β-ketoesters 4a–e were condensed with o-phenylenediamine (o-PDA in presence of p-toluenesulfonic acid/SiO2 to give biologically active 3H-1,5-benzodiazepines, 5a–e. All the newly synthesized compounds were characterized by elemental analysis and spectral studies. The compounds 5a–e was screened for their antimicrobial, antifungal and anthelmintic activities.

  18. Polysubstance Abuse: Alcohol, Opioids and Benzodiazepines Require Coordinated Engagement by Society, Patients, and Physicians

    Directory of Open Access Journals (Sweden)

    Ogbu, Uzor C

    2015-03-01

    Full Text Available The Centers for Disease Control and Prevention (CDC has published significant data trends related to substance abuse involving opioid pain relievers (OPR, benzodiazepines and alcohol in the United States. The CDC describes opioid misuse and abuse as an epidemic, with the use of OPR surpassing that of illicit drugs. Alcohol has also been a persistent problem and is associated with a number of emergency department visits and deaths independent of other substances. The use of these drugs in combination creates an additive effect with increased central nervous system suppression and a heightened risk of an overdose. We present a summary of the findings from the Morbidity and Mortality Weekly Report (MMWR with commentary on strategies to combat prescription drug and alcohol abuse. [West J Emerg Med. 2015;16(1:76–79.

  19. Benzodiazepine receptor distribution and cerebral blood flow in early blindness. A PET study

    International Nuclear Information System (INIS)

    Mishina, Masahiro; Senda, Michio; Kiyosawa, Motohiro

    2000-01-01

    We studied benzodiazepine receptor (BZR) distribution, which is thought to be affected by neuronal density in the cerebral cortex, and CBF using [ 11 C]flumazenil and [ 15 O]water PET in early blind (EB) and in blindfold sighted control (SC) subjects. PET images were co-registered to the subject's MRI. Using SPM96, MRI images were normalized in the Talairach and Tournoux coordinate system, and accordingly MRI-registered PET images were spatially normalized. Statistical parametric maps were computed on a voxel-by-voxel basis, using the general linear model. CBF for EB was significantly larger in the Brodmann area 17 and 18, especially anterior area, than that for SC, while there was no significant difference in BZR distribution. Our BZR data suggest that the amount of neurons do not change due to early visual deprivation in the visual cortex, in spite of high CBF in visual cortex of EB subjects. (author)

  20. Methodology for benzodiazepine receptor binding assays at physiological temperature. Rapid change in equilibrium with falling temperature

    International Nuclear Information System (INIS)

    Dawson, R.M.

    1986-01-01

    Benzodiazepine receptors of rat cerebellum were assayed with [ 3 H]-labeled flunitrazepam at 37 0 C, and assays were terminated by filtration in a cold room according to one of three protocols: keeping each sample at 37 degrees C until ready for filtration, taking the batch of samples (30) into the cold room and filtering sequentially in the order 1-30, and taking the batch of 30 samples into the cold room and filtering sequentially in the order 30-1. the results for each protocol were substantially different from each other, indicating that rapid disruption of equilibrium occurred as the samples cooled in the cold room while waiting to be filtered. Positive or negative cooperativity of binding was apparent, and misleading effects of gamma-aminobutyric acid on the affinity of diazepam were observed, unless each sample was kept at 37 0 C until just prior to filtration

  1. [Ion-dependency of the GABA-potentiating effects of benzodiazepine tranquilizers and harmane].

    Science.gov (United States)

    Abramets, I I; Komissarov, I V

    1984-06-01

    Experiments on an isolated spinal cord of 8-15-day-old rats have shown that one of the possible mechanisms of the GABA-potentiating action of the benzodiazepine tranquilizer, chlorodiazepoxide, may be a decrease in the intraneuronal concentration of Ca2+. This is evidenced by the enhancement of the GABA-potentiating action of chlorodiazepoxide under Ca2+ deficiency in the medium and in the presence of the blockers of the voltage-dependent Ca2+ ionic channels--Mn2+ and Co2+, and by the reduction of the effect in question under Ca2+ excess in the medium and in the presence of the K+ channels blockers--tetraethylammonium and 4-aminopyridine. The GABA-potentiating action of harmane is likely to be related to the blockade of the voltage-dependent K+ channels and elevation of the intracellular concentration of Ca2+.

  2. Benzodiazepine temazepam suppresses the transient auditory 40-Hz response amplitude in humans.

    Science.gov (United States)

    Jääskeläinen, I P; Hirvonen, J; Saher, M; Pekkonen, E; Sillanaukee, P; Näätänen, R; Tiitinen, H

    1999-06-18

    To discern the role of the GABA(A) receptors in the generation and attentive modulation of the transient auditory 40-Hz response, the effects of the benzodiazepine temazepam (10 mg) were studied in 10 healthy social drinkers, using a double-blind placebo-controlled design. Three hundred Hertz standard and 330 Hz rare deviant tones were presented to the left, and 1000 Hz standards and 1100 Hz deviants to the right ear of the subjects. Subjects attended to a designated ear and were to detect deviants therein while ignoring tones to the other. Temazepam significantly suppressed the amplitude of the 40-Hz response, the effect being equal for attended and non-attended tone responses. This suggests involvement of GABA(A) receptors in transient auditory 40-Hz response generation, however, not in the attentive modulation of the 40-Hz response.

  3. Clonazepam as Agonist Substitution Treatment for Benzodiazepine Dependence: A Case Report

    Directory of Open Access Journals (Sweden)

    Angelo Giovanni Icro Maremmani

    2013-01-01

    Full Text Available Nowadays, the misuse of benzodiazepines (BZDs is a cause for a serious concern among pharmacologically inexperienced patients, whether treated or untreated, that could lead to significant complications, including tolerance, dependence, and addiction. We present a case report in which an Italian patient affected by anxiety disorder and treated with BZDs presented a severe case of dependence on BZDs. We treated him according to an agonist substitution approach, switching from the abused BZD to a slow-onset, long-acting, high potency agonist (clonazepam, and looking at the methadone treatment model as paradigm. We decided to use clonazepam for its pharmacokinetic properties. The advantage of choosing a slow-onset, long-lasting BZD for the treatment of our patient was that it led us to a remarkable improvement in the clinical situation, including the cessation of craving, absence of withdrawal symptoms, reduced anxiety, improvements in social functioning, and a better cognition level.

  4. Zolpidem displays heterogeneity in its binding to the nonhuman primate benzodiazepine receptor in vivo.

    Science.gov (United States)

    Schmid, L; Bottlaender, M; Fuseau, C; Fournier, D; Brouillet, E; Mazière, M

    1995-10-01

    The distinctive pharmacological activity of zolpidem in rats compared with classical benzodiazepines has been related to its differential affinity for benzodiazepine receptor (BZR) subtypes. By contrast, in nonhuman primates the pharmacological activity of zolpidem was found to be quite similar to that of classical BZR agonists. In an attempt to explain this discrepancy, we examined the ability of zolpidem to differentiate BZR subtypes in vivo in primate brain using positron emission tomography. The BZRs were specifically labeled with [11C]flumazenil. Radiotracer displacement by zolpidem was monophasic in cerebellum and neocortex, with in vivo Hill coefficients close to 1. Conversely, displacement of [11C]flumazenil was biphasic in hippocampus, amygdala, septum, insula, striatum, and pons, with Hill coefficients significantly smaller than 1, suggesting two different binding sites for zolpidem. In these cerebral regions, the half-maximal inhibitory doses for the high-affinity binding site were similar to those found in cerebellum and neocortex and approximately 100-fold higher for the low-affinity binding site. The low-affinity binding site accounted for zolpidem binding characteristics contrast with those reported for rodents, where three different binding sites were found. Species differences in binding characteristics may explain why zolpidem has a distinctive pharmacological activity in rodents, whereas its pharmacological activity in primates is quite similar to that of classical BZR agonists, except for the absence of severe effects on memory functions, which may be due to the lack of substantial zolpidem affinity for a distinct BZR subtype in cerebral structures belonging to the limbic system.

  5. The elimination half-life of benzodiazepines and fall risk: two prospective observational studies.

    Science.gov (United States)

    de Vries, Oscar J; Peeters, Geeske; Elders, Petra; Sonnenberg, Caroline; Muller, Majon; Deeg, Dorly J H; Lips, Paul

    2013-11-01

    the STOPP criteria advise against the use of long-acting benzodiazepines (LBs). to study whether LBs are associated with a higher fall risk than short-acting benzodiazepines (SBs) (elimination half-life ≤ 10 h). we used base-line data and prospective fall follow-up from the Longitudinal Aging Study Amsterdam, a longitudinal cohort study including 1,509 community-dwelling older persons (Study 1) and from a separate fall prevention study with 564 older persons after a fall (Study 2). Time to the first fall after inclusion and number of falls in the first year after inclusion were the primary endpoints. both in Study 1 and Study 2 the use of SBs was associated with time to the first fall, hazard ratio (HR) 1.62 (95% CI: 1.03-2.56) and HR 1.64 (95% CI: 1.19-2.26),respectively. LBs were not significantly associated with time to first fall, HR 1.40 (0.85-2.31) and HR 1.08 (0.72-1.62). In both studies, the use of SBs was also associated with number of falls, odds ratio (OR) 1.28 (95% CI: 1.01-1.61) and OR 1.37 (95% CI: 1.10-1.70). LBs were not significantly associated with number of falls, OR 1.23 (0.96-1.57) and 1.10 (0.82-1.48). the use of SBs is not associated with a lower fall risk compared with LBs. The use of both SBs and LBs by old persons should be strongly discouraged.

  6. Premedication with benzodiazepines for upper gastrointestinal endoscopy: Comparison between oral midazolam and sublingual alprazolam

    Directory of Open Access Journals (Sweden)

    Vahid Sebghatollahi

    2017-01-01

    Full Text Available Background: Premedication with orally administered benzodiazepines is effective in reducing anxiety and discomfort related to endoscopic procedures. We evaluated the efficacy and safety of oral midazolam in comparison to sublingual alprazolam as premedication for esophagogastroduodenoscopy (EGD. Materials and Methods: Adult candidates for diagnostic EGD received either oral midazolam (7.5 mg in 15 cc apple juice or sublingual alprazolam (0.5 mg 30 min before EGD. Procedural anxiety and pain/discomfort were assessed using 11-point numerical rating scales. Patients' overall tolerance (using a four-point Likert scale and willingness to repeat the EGD, if necessary, were also assessed. Blood pressure, heart rate, and arterial oxygen saturation were monitored from medication to 30 min after the procedure. Results: Patients experienced a similar reduction in procedural anxiety after medication with oral midazolam and sublingual alprazolam; mean (standard deviation [SD] of 1.86 [1.63] and 2.02 [1.99] points, respectively, P = 0.91. Compared to oral midazolam, pain/discomfort scores were lower with sublingual alprazolam; mean (SD of 4.80 (3.01 versus 3.68 (3.28, P = 0.024. There was no significant difference between the two groups in patients' tolerance, willingness to repeat the procedure, or hemodynamic events. Conclusion: Oral midazolam and sublingual alprazolam are equally effective in reducing EGD-related anxiety; however, EGD-related pain/discomfort is lower with alprazolam. Both benzodiazepines are equally safe and can be used as premedication for patients undergoing diagnostic EGD.

  7. Determination of benzodiazepines in beverages using green extraction methods and capillary HPLC-UV detection.

    Science.gov (United States)

    Piergiovanni, Maurizio; Cappiello, Achille; Famiglini, Giorgio; Termopoli, Veronica; Palma, Pierangela

    2018-05-30

    Dispersive liquid-liquid microextraction with and without ultrasound assistance (DLLME, UA-DLLME) and microextraction with packed sorbent (MEPS) methods for the extraction and determination of eight different benzodiazepines (BDZ) (chlordiazepoxide, flurazepam, bromazepam, oxazepam, lorazepam, clobazam, clonazepam, and flunitrazepam) in three commercial non-alcoholic and light alcoholic beverages were optimized and compared. Benzodiazepines are frequently used for their extensive diffusion and strong numbing effect in drug-facilitated crimes (DFC). The tiny small amount of sample required for DLLME and MEPS extraction makes them very suitable for specimens collected at the crime scene of DFCs. Microextraction techniques are of increasing interest thanks to their accordance to green analytical chemistry (GAC) guidelines providing good recovery values. Ultrasound assistance (UA-DLLME) was used to investigate whether this type of energy can improve the recoveries of the analytes. Analyses of the extracts were performed with reverse-phase capillary high-performance liquid chromatography with UV detection (HPLC - UV), thanks to low environmental impact, robustness, diffusion, and affordability. Recovery percentages at three different concentrations in the three beverages were between 14.30% and 103.28% with intraday and interday RSD lower than ±2.78%. The same samples were extracted using a MEPS protocol, and the results were compared with those obtained with DLLME. MEPS gave recoveries between 20.90% and 101.88% for all matrices showing a better performance than DLLME at higher concentrations, though lower recoveries were observed with diluted samples. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Renal imaging in paediatrics

    International Nuclear Information System (INIS)

    Porn, U.; Hahn, K.; Fischer, S.

    2003-01-01

    The most frequent renal diseases in paediatrics include urinary tract infections, hydronephrosis, kidney anomalies and reflux. The main reason for performing DMSA scintigraphy in paediatrics is the detection of cortical abnormalities related to urinary tract infection. Because the amount of tracer retained in the tubular cells is associated with the distribution of functioning renal parenchyma in the kidney, it is possible, to evaluate the split renal function. In comparison to ultrasound and intravenous urography the sensitivity in the detection of acute as well as chronic inflammatory changes is very high, however less specific. An indication for a renography in neonates and children is beside an estimation of the total renal function and the calculation of the split renal function, the assessment of renal drainage in patients with unclear dilatation of the collecting system in ultrasound. The analysis of the time activity curve provides, especially for follow-up studies, a reproducible method to assess the urinary outflow. The diuretic scintigraphy allows the detection of urinary obstruction. Subsequently it is possible to image the micturition phase to detect vesico-ureteric reflux (indirect MCU) after drainage of tracer from the renal pelvis. An reflux in the ureters or the pelvicalyceal system is visible on the scintigraphic images and can be confirmed by time activity curves. A more invasive technique is the direct isotope cystography with bladder catheterization. The present paper should give an overview about the role of nuclear medicine in paediatric urology. (orig.) [de

  9. Perioperative acute renal failure.

    LENUS (Irish Health Repository)

    Mahon, Padraig

    2012-02-03

    PURPOSE OF REVIEW: Recent biochemical evidence increasingly implicates inflammatory mechanisms as precipitants of acute renal failure. In this review, we detail some of these pathways together with potential new therapeutic targets. RECENT FINDINGS: Neutrophil gelatinase-associated lipocalin appears to be a sensitive, specific and reliable biomarker of renal injury, which may be predictive of renal outcome in the perioperative setting. For estimation of glomerular filtration rate, cystatin C is superior to creatinine. No drug is definitively effective at preventing postoperative renal failure. Clinical trials of fenoldopam and atrial natriuretic peptide are, at best, equivocal. As with pharmacological preconditioning of the heart, volatile anaesthetic agents appear to offer a protective effect to the subsequently ischaemic kidney. SUMMARY: Although a greatly improved understanding of the pathophysiology of acute renal failure has offered even more therapeutic targets, the maintenance of intravascular euvolaemia and perfusion pressure is most effective at preventing new postoperative acute renal failure. In the future, strategies targeting renal regeneration after injury will use bone marrow-derived stem cells and growth factors such as insulin-like growth factor-1.

  10. Peripheral degenerative joint diseases

    Directory of Open Access Journals (Sweden)

    Nilzio Antonio da Silva

    2008-03-01

    Full Text Available Osteoarthritis, a degenerative joint disease, is the most commonrheumatic disorder mainly in a geriatric population. Manifestationsare pain, stiffness and functional loss in the affected joint.According to etiology it is classifi ed as primary (or idiopathicand secondary. Some risk factors for disease development aregenetics, race, age, sex, obesity, occupational activities andarticular biomechanics. Pathogenesis is the same for any cause orlocalization, being catabolic alterations, with synthesis, inhibitionand reparing intent of the cartilage matrix. Metalloproteinases andcytokines (IL-1,IL-6,TNF-α actions promote infl ammatory reactionand cartilage degradation. Pain, the most important symptom,does not correlate with radiologic fi ndings. Peripheral osteoarthritisoccurs predominantly in the knee, hip and hand. Diagnosis is basedon clinical features, laboratorial tests and radiological changes.Rheumatological associations’ guidelines for treatment includenon-pharmacologic (education, physiotherapy, assistive devices,and pharmacologic (analgesics, anti-infl ammatory drugs therapyand surgery. Arthroplasty seems to work better than medicines, butshould be used if other treatments have failed.

  11. Cadmium and renal cancer

    International Nuclear Information System (INIS)

    Il'yasova, Dora; Schwartz, Gary G.

    2005-01-01

    Background: Rates of renal cancer have increased steadily during the past two decades, and these increases are not explicable solely by advances in imaging modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that accumulates in the kidney cortex and is a cause of end-stage renal disease. Several observations suggest that cadmium may be a cause of renal cancer. Methods: We performed a systematic review of the literature on cadmium and renal cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological and eleven clinical studies. Results: Despite different methodologies, three large epidemiologic studies indicate that occupational exposure to cadmium is associated with increased risk renal cancer, with odds ratios varying from 1.2 to 5.0. Six of seven studies that compared the cadmium content of kidneys from patients with kidney cancer to that of patients without kidney cancer found lower concentrations of cadmium in renal cancer tissues. Conclusions: Exposure to cadmium appears to be associated with renal cancer, although this conclusion is tempered by the inability of studies to assess cumulative cadmium exposure from all sources including smoking and diet. The paradoxical findings of lower cadmium content in kidney tissues from patients with renal cancer may be caused by dilution of cadmium in rapidly dividing cells. This and other methodological problems limit the interpretation of studies of cadmium in clinical samples. Whether cadmium is a cause of renal cancer may be answered more definitively by future studies that employ biomarkers of cadmium exposure, such as cadmium levels in blood and urine

  12. Renal Branch Artery Stenosis

    DEFF Research Database (Denmark)

    Andersson, Zarah; Thisted, Ebbe; Andersen, Ulrik Bjørn

    2017-01-01

    Renovascular hypertension is a common cause of pediatric hypertension. In the fraction of cases that are unrelated to syndromes such as neurofibromatosis, patients with a solitary stenosis on a branch of the renal artery are common and can be diagnostically challenging. Imaging techniques...... that perform well in the diagnosis of main renal artery stenosis may fall short when it comes to branch artery stenosis. We report 2 cases that illustrate these difficulties and show that a branch artery stenosis may be overlooked even by the gold standard method, renal angiography....

  13. Renal artery stenosis.

    Science.gov (United States)

    Tafur-Soto, Jose David; White, Christopher J

    2015-02-01

    Atherosclerotic renal artery stenosis (RAS) is the single largest cause of secondary hypertension; it is associated with progressive renal insufficiency and causes cardiovascular complications such as refractory heart failure and flash pulmonary edema. Medical therapy, including risk factor modification, renin-angiotensin-aldosterone system antagonists, lipid-lowering agents, and antiplatelet therapy, is advised in all patients. Patients with uncontrolled renovascular hypertension despite optimal medical therapy, ischemic nephropathy, and cardiac destabilization syndromes who have severe RAS are likely to benefit from renal artery revascularization. Screening for RAS can be done with Doppler ultrasonography, CT angiography, and magnetic resonance angiography. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Cryoablation of Renal Angiomyolipoma

    DEFF Research Database (Denmark)

    Makki, Ahmad; Graumann, Ole; Hoyer, Soren

    2017-01-01

    BACKGROUND: Small series have reported that cryoablation (CA) is a safe and feasible minimally invasive nephron-sparing alternative for the treatment of renal angiomyolipomas (renal AMLs). The aim of the present study was to investigate the safety and efficacy of CA in patients with renal AML......-guided CA. The mean patient age was 46 years [interquartile range (IQR) 30] and the mean tumor volume was 50.1 cm(3) (IQR 53.3). In all cases, the procedure was effectively conducted with no conversion to open surgery, and no major complications were experienced. The mean follow-up time was 25 months (IQR...

  15. Acute renal failure in children

    International Nuclear Information System (INIS)

    Vergesslich, K.A.; Balzar, E.; Weninger, M.; Ponhold, W.; Sommer, G.; Wittich, G.R.; Vienna Univ.

    1987-01-01

    Acute renal failure (ARF) may be due to obstructive uropathy or renal parenchymal disease. Twenty-five children with acute renal failure secondary to renal parenchymal disease underwent ultrasonographic examination of the kidneys. Changes of renal size and cortical echogenicity were correlated with renal function. All patients presented with bilaterally enlarged kidneys with the exception in renal function resulted in normalization of renal size. With regard to cortical echogenicity two groups were formed. Group A comprised 11 patients whose kidneys had the same echogenicity as the liver, while in group B the kidneys were more echogenic (14 patients). Cortical echogenicity was always increased. Determination of creatinine levels showed a statistically significant difference between group A (3.32 mg% ± 1.40 S.D.) and group B (5.95 mg% ± 1.96 S.D.), p < 0.001. Changes in renal function were paralleled by rapid changes in renal size and cortical echogenicity. (orig.)

  16. Odontogenic keratocyst: a peripheral variant.

    Science.gov (United States)

    Vij, H; Vij, R; Gupta, V; Sengupta, S

    2011-01-01

    Odontogenic keratocyst, which is developmental in nature, is an intraosseous lesion though on rare occasions it may occur in an extraosseous location. The extraosseous variant is referred to as peripheral odontogenic keratocyst. Though, clinically, peripheral odontogenic keratocyst resembles the gingival cyst of adults, it has histologic features that are pathognomonic of odontogenic keratocyst. This article presents a case of this uncommon entity.

  17. Peripheral dentinogenic ghost cell tumor

    Directory of Open Access Journals (Sweden)

    Sushant S Kamat

    2013-01-01

    Full Text Available Dentinogenic ghost cell tumors (DGCT are uncommon lesions mainly with rare peripheral types. This report presents a case of peripheral DGCT on the left side of the mandibular alveolar ridge of a heavy smoker, a 68-year-old man, with main presenting feature as a mild pain. Submandibular lymphadenopathy and radiological "saucerization" were evident. Differential diagnosis included fibroma, neurofibroma, peripheral ameloblastoma, peripheral odontogenic fibroma, and peripheral giant cell granuloma. Histologically, ameloblastoma-like epithelial elements were seen in association with grouped ghost cells. Proliferating polyhedral cells and stellate reticulum-like cells with various densities were spread over a wide range of the field. The lesion was curetted and after 2 years of follow up, it did not recur.

  18. Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Todenhöfer Tilman

    2012-03-01

    Full Text Available Abstract Background Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma. Case presentation A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable. Conclusions Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.

  19. Renal tumors in infancy

    International Nuclear Information System (INIS)

    Lucaya, J.; Garcia, P.

    1997-01-01

    The classification of childhood renal masses in updated, including the clinical signs and imaging techniques currently employed to confirm their presence and type them. Several bening and malignant childhood tumors are described in substantial detail. (Author) 24 refs

  20. Renal cell carcinoma

    Science.gov (United States)

    ... kidney Patient Instructions Kidney removal - discharge Images Kidney anatomy Kidney tumor - CT scan Kidney metastases, CT scan Kidney - blood and urine flow References Campbell SC, Lane BR. Malignant renal tumors. In: Wein AJ, Kavoussi LR, Partin AW, ...

  1. Primary renal synovial sarcoma

    Directory of Open Access Journals (Sweden)

    Girish D. Bakhshi

    2012-03-01

    Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

  2. [Small renal mass].

    Science.gov (United States)

    Prokofiev, D; Kreutzer, N; Kress, A; Wissing, F; Pfeifer, H; Stolzenburg, J-U; Dietel, A; Schwalenberg, T; Do, M; Truß, M C

    2012-10-01

    The frequent application of ultrasound and radiological imaging for non-urological indications in recent years has resulted in an increase in the diagnosis of small renal masses. The treatment options for patients with a small renal mass include active surveillance, surgery (both open and minimally invasive) as well as ablative techniques. As there is a risk for metastatic spread even in small renal masses surgical extirpation remains the treatment of choice in most patients. Ablative procedures, such as cryoablation and radiofrequency ablation are appropriate for old and multi-morbid patients who require active treatment of a small renal mass. Active surveillance is an alternative for high-risk patients. Meticulous patient selection by the urologist and patient preference will determine the choice of treatment option in the future.

  3. Common paediatric renal conditions

    African Journals Online (AJOL)

    Few children in South Africa have access to dialysis or renal transplantation, so it is important to .... the chronic administration of antibiotics increases the risk of a UTI with a resistant .... factors for recurrent urinary tract infection in young women.

  4. Renal and perirenal abscesses

    International Nuclear Information System (INIS)

    Patterson, J.E.; Andriole, V.T.

    1987-01-01

    Our knowledge of the spectrum of renal abscesses has increased as a result of more sensitive radiologic techniques. The classification of intrarenal abscess now includes acute focal bacterial nephritis and acute multifocal bacterial nephritis, as well as the previously recognized renal cortical abscess, renal corticomedullary abscess, and xanthogranulomatous pyelonephritis. In general, the clinical presentation of these entities does not differentiate them; various radiographic studies can distinguish them, however. The intrarenal abscess is usually treated successfully with antibiotic therapy alone. Antistaphylococcal therapy is indicated for the renal cortical abscess, whereas therapy directed against the common gram-negative uropathogens is indicated for most of the other entities. The perinephric abscess is often an elusive diagnosis, has a more serious prognosis, and is more difficult to treat. Drainage of the abscess and sometimes partial or complete nephrectomy are required for resolution. 73 references

  5. Lithium and Renal Impairment

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Kessing, Lars Vedel; Nolen, Willem A

    2018-01-01

    INTRODUCTION: Lithium is established as an effective treatment of mania, of depression in bipolar and unipolar disorder, and in maintenance treatment of these disorders. However, due to the necessity of monitoring and concerns about irreversible adverse effects, in particular renal impairment......, after long-term use, lithium might be underutilized. METHODS: This study reviewed 6 large observational studies addressing the risk of impaired renal function associated with lithium treatment and methodological issues impacting interpretation of results. RESULTS: An increased risk of renal impairment...... associated with lithium treatment is suggested. This increased risk may, at least partly, be a result of surveillance bias. Additionally, the earliest studies pointed toward an increased risk of end-stage renal disease associated with lithium treatment, whereas the later and methodologically most sound...

  6. Renal dynamic scintigraphy in renal graft evaluation; Cintilografia renal dinamica na avaliacao do transplante renal

    Energy Technology Data Exchange (ETDEWEB)

    Cervo, Marco Antonio Cadorna; Amarante Junior, Jose Luiz de Medeiros; Souza, Ricardo Alberto Manhaes de; Evangelista, Maria Gardenia; Cavalcante, Carlos Alberto Provasi; Neder, Jacqueline de Roure e; Espinola, Ircania Jorge [Hospital Naval Marcilio Dias, Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear

    1996-12-31

    The goal of this was to describe the use of the dynamic renal scintigraphy in patients grafted. The authors described the scintigraphy method utilised and results were discussed 8 refs., 9 figs., 1 tab.

  7. VITAL COMPUTER MORPHOMETRY OF LIMPHOCYTES IN DIAGNOSIS OF ACUTE RENAL ALLOGRAFT REJECTION

    Directory of Open Access Journals (Sweden)

    A. V. Vatazin

    2009-01-01

    Full Text Available The article focuses on the results of the investigation of peripheral blood lymphocyte morphofunctional status in healthy volunteers and renal allograft recipients for early postoperative period. Working out noninvasive tests for diagnosis of acute renal allograft rejection based on the measuring of cell morphometric parameters by method of coherent phase microscopy (CPM. It was found out that the lymphocyte phase height was proportional cell image density and its geometrical thickness. Our results showed that the variations of immunocompetent cell morphometric indicants can be in advance the dynamics of blood creatine increasing and answer for early criteria of acute renal allograft rejection. 

  8. OBSTETRIC RENAL FAILURE

    Directory of Open Access Journals (Sweden)

    Rajeshwari

    2015-11-01

    Full Text Available Renal failure in obstetrics is rare but important complication, associated with significant mortality and long term morbidity.1,2 It includes acute renal failure due to obstetrical complications or due to deterioration of existing renal disease. AIMS AND OBJECTIVES: To evaluate the etiology and outcome of renal failure in obstetric patients. METHODS: We prospectively analyzed 30 pregnant and puerperal women with acute renal failure or pre-existing renal disease developing renal failure during pregnancy between November 2007 to sep-2009. Patients who presented/developed ARF during the hospital stay were included in this study. RESULTS: Among 30 patients, mean age was 23 years and 33 years age group. 12 cases (40% patients were primigravidae and 9(30% patients were multigravidae and 9 cases (30% presented in post-partum period. Eighteen cases (60% with ARF were seen in third trimester, followed by in postpartum period 9 cases (30%. Most common contributing factors to ARF were Pre-eclampsia, eclampsia and HELLP syndrome 60%, sepsis 56.6%, post abortal ARF 10%. DIC 40%. Haemorrhage as the aetiology for ARF was present 46%, APH in 20% and PPH in 26.6%. The type of ARF was renal in (63% and prerenal (36%; Oliguric seen in 10 patients (33% and high mortality (30%. Among the 20 pregnant patients with ARF, The average period of gestation was 33±2 weeks (30 -36 weeks, 5 cases (25% presented with intrauterine fetal demise and 18 cases (66% had preterm vaginal delivery and 2 cases (10% had induced abortion. And the average birth weight was 2±0.5 kg (1.5 kg. Eight cases (26% required dialysis. 80% of patients recovered completely of renal functions. 63% patients recovered without renal replacement therapy whereas 17% required dialysis. the maternal mortality was 20%, the main reason for mortality was septic shock and multi organ dysfunction (66%. CONCLUSION: ARF related pregnancy was seen commonly in the primigravidae and in the third trimester, the most

  9. Renal artery pseudoaneurysm

    Directory of Open Access Journals (Sweden)

    Luiz Inácio Roman

    Full Text Available Abstract The renal artery pseudoaneurysm embody a rare vascular complication coming of percutaneous procedures, renal biopsy, nephrectomy, penetrating traumas and more rarely blunt traumas. The clinical can be vary according the patient, the haematuria is the symptom more commom. Is necessary a high level of clinical suspicion for your diagnosis, this can be elucidated by through complementary exams as the eco-color Doppler and the computed tomography scan (CT. This report is a case of a patient submitted a right percutaneous renal biopsy and that, after the procedure started with macroscopic haematuria, urinary tenesmus and hypogastric pain. The diagnosis of pseudoaneurysm was given after one week of evolution when the patient was hospitalized because gross haematuria, tachycardia, hypotension and hypochondrium pain. In the angiotomography revealed a focal dilation of the accessory right renal inferior polar artery, dilation of renal pelvis and all the ureteral course with presence hyperdenso material (clots inside the middle third of the ureter. The treatment for the majority of this cases are conservative, through arterial embolization, indicated for thouse of smaller dimensions in patients who are hemodynamically stable. However, it was decided by clinical treatment with aminocaproic acid 1 g, according to previous studies for therapy of haematuria. The patient received discharge without evidence of macroscopic haematuria and with normal renal ultrasound, following ambulatory care.

  10. Risk of hip fractures associated with benzodiazepines: Applying common protocol to a multi-database nested case-control study. The protect project

    NARCIS (Netherlands)

    Requena, Gema; Logie, John; González-González, Rocío; Gardarsdottir, Helga|info:eu-repo/dai/nl/321858131; Afonso, Ana; Souverein, Patrick C.|info:eu-repo/dai/nl/243074948; Merino, Elisa Martin; Boudiaf, Nada; Huerta, Consuelo; Bate, Andrew; Alvarez, Yolanda; García-Rodríguez, Luis A.; Reynolds, Robert; Schlienger, Raymond G.; De Groot, Mark C.H.|info:eu-repo/dai/nl/313936455; Klungel, Olaf H.|info:eu-repo/dai/nl/181447649; De Abajo, Francisco J.

    2014-01-01

    Background: The association between benzodiazepines (BZD) and hip fractures has been estimated in several observational studies although diverse methodologies and definitions have hampered comparability. Objectives: To evaluate the discrepancies in the risk estimates of hip/femur fractures

  11. RENAL MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Elisangela Giachini

    2017-06-01

    Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

  12. Peripheral Auditory Mechanisms

    CERN Document Server

    Hall, J; Hubbard, A; Neely, S; Tubis, A

    1986-01-01

    How weIl can we model experimental observations of the peripheral auditory system'? What theoretical predictions can we make that might be tested'? It was with these questions in mind that we organized the 1985 Mechanics of Hearing Workshop, to bring together auditory researchers to compare models with experimental observations. Tbe workshop forum was inspired by the very successful 1983 Mechanics of Hearing Workshop in Delft [1]. Boston University was chosen as the site of our meeting because of the Boston area's role as a center for hearing research in this country. We made a special effort at this meeting to attract students from around the world, because without students this field will not progress. Financial support for the workshop was provided in part by grant BNS- 8412878 from the National Science Foundation. Modeling is a traditional strategy in science and plays an important role in the scientific method. Models are the bridge between theory and experiment. Tbey test the assumptions made in experim...

  13. (4Z-1-Dodecyl-4-(2-oxopropylidene-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-one

    Directory of Open Access Journals (Sweden)

    Jihad Sebhaoui

    2016-11-01

    Full Text Available In the title compound, C24H36N2O2, the orientation of the 2-oxopropylidene substituent is determined by the formation of an intramolecular N—H...O hydrogen bond. The benzodiazepine seven-membered ring adopts a slightly twisted boat conformation. The molecules pack in a bilayer fashion with the dodecyl chains intercalated to form the inner portion, and the benzodiazepine moieties on the outer surfaces.

  14. Renal damage after extracorporeal shock-wave lithotripsy detected by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Torii, Shinichiro; Machida, Toyohei; Ooishi, Yukihiko; Tashiro, Kazuya; Mochizuki, Atsushi; Yoshigoe, Fukuo

    1988-08-01

    The acute effects of extracorporeal Shock-wave lithotripsy (ESWL) on morphology of the renal parenchyma were evaluated by Magnetic Resonance Imaging (MRI) in 15 kidneys, before and immediately after (within 24 hours) ESWL in 11 cases. The renal parenchymal damages were observed by MRI as the changes of signal itensity of renal cortex and medulla, perirenal fluid, loss of corticomedullar differentiation, and other renal traumas. Loss of corticomedullar differentiation was seen in 9/11 cases and peripheral fluid of the kidney was seen in 4/11 cases. Irregular and edematous changes of renal capsula were seen in 5/11 cases. Obvious abnormal findings indicated renal trauma were not observed in this study. Several MRI findings may transient and reversible changes and the morpholigic changes detected by MRI may attributed to renal parenchymal obstruction and edema and decreasing of renal capillary flow, such as in renal contusion. It is concluded that MRI is very sensitive and the best technique to detect the effects and clinical trouble of ESWL.

  15. Renal damage after extracorporeal shock-wave lithotripsy detected by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Torii, Shinichiro; Machida, Toyohei; Ooishi, Yukihiko; Tashiro, Kazuya; Mochizuki, Atsushi; Yoshigoe, Fukuo

    1988-01-01

    The acute effects of extracorporeal Shock-wave lithotripsy (ESWL) on morphology of the renal parenchyma were evaluated by Magnetic Resonance Imaging (MRI) in 15 kidneys, before and immediately after (within 24 hours) ESWL in 11 cases. The renal parenchymal damages were observed by MRI as the changes of signal itensity of renal cortex and medulla, perirenal fluid, loss of corticomedullar differentiation, and other renal traumas. Loss of corticomedullar differentiation was seen in 9/11 cases and peripheral fluid of the kidney was seen in 4/11 cases. Irregular and edematous changes of renal capsula were seen in 5/11 cases. Obvious abnormal findings indicated renal trauma were not observed in this study. Several MRI findings may transient and reversible changes and the morpholigic changes detected by MRI may attributed to renal parenchymal obstruction and edema and decreasing of renal capillary flow, such as in renal contusion. It is concluded that MRI is very sensitive and the best technique to detect the effects and clinical trouble of ESWL. (author)

  16. Benzodiazepines and antipsychotic medications for treatment of acute cocaine toxicity in animal models--a systematic review and meta-analysis.

    Science.gov (United States)

    Heard, Kennon; Cleveland, Nathan R; Krier, Shay

    2011-11-01

    There are no controlled human studies to determine the efficacy of benzodiazepines or antipsychotic medications for prevention or treatment of acute cocaine toxicity. The only available controlled data are from animal models and these studies have reported inconsistent benefits. The objective of this study was to quantify the reported efficacy of benzodiazepines and antipsychotic medication for the prevention of mortality due to cocaine poisoning. We conducted a systematic review to identify English language articles describing experiments that compared a benzodiazepine or antipsychotic medication to placebo for the prevention of acute cocaine toxicity in an animal model. We then used these articles in a meta-analysis with a random-effects model to quantify the absolute risk reduction observed in these experiments. We found 10 articles evaluating antipsychotic medications and 15 articles evaluating benzodiazepines. Antipsychotic medications reduced the risk of death by 27% (95% CI, 15.2%-38.7%) compared to placebo and benzodiazepines reduced the risk of death by 52% (42.8%-60.7%) compared to placebo. Both treatments showed evidence of a dose-response effect, and no experiment found a statistically significant increase in risk of death. We conclude that both benzodiazepines and antipsychotic medications are effective for the prevention of lethality from cocaine toxicity in animal models.

  17. Evidence for involvement of the astrocytic benzodiazepine receptor in the mechanism of action of convulsant and anticonvulsant drugs

    International Nuclear Information System (INIS)

    Bender, A.S.; Hertz, L.

    1988-01-01

    The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit [ 3 H]diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel

  18. 125I-iomazenil - benzodiazepine receptor binding and serum corticosterone level during psychological stress in a rat model

    International Nuclear Information System (INIS)

    Fukumitsu, Nobuyoshi; Ogi, Shigeyuki; Uchiyama, Mayuki; Mori, Yutaka

    2004-01-01

    To test the hypothesis that benzodiazepine receptor density decreases in response to stress, we correlated 125 I-iomazenil ( 125 I-IMZ) binding with serum corticosterone levels in a rat model. Wistar male rats were divided into four groups; control group (CON, 10 rats), no physical or psychological stress; and one-, three-, and five-day stress groups of 12 rats each (1-DAY, 3-DAY, and 5-DAY, respectively), receiving psychological stress for the given number of days. Psychological stress were given to rats with a communication box. The standardized uptake value (SUV) of 125 I-iomazenil of the 3-DAY and 5-DAY showed that 125 I-iomazenil - benzodiazepine receptor binding was significantly reduced in the cortices, accumbens nuclei, amygdala and caudate putamen (p 125 I-IMZ is a useful radioligand to reflect received stress and its binding in the cortices, accumbens nuclei, amygdala and caudate putamen is strongly affected by psychological stress

  19. Synthesis of iodine-123 labelled analogues of imidazenil and ethyl-imidazenil for studying benzodiazepine receptors using SPECT

    International Nuclear Information System (INIS)

    Katsifis, A.; Mattner, F.; Dikic, B.; Najdovski, L.; Kassiou, M.

    1996-01-01

    The [ 123 I]iodinated analogues of the benzodiazepine receptor partial agonist imidazenil and N-ethyl imidazenil have been synthesised for the study of the central benzodiazepine receptor using SPECT. [ 123 I]Iodomidazenil and [ 123 I]N-ethyliodoimidazenil were prepared by nucleophilic bromine-iodine exchange in acetic acid at 150 o . The products were purified by semi-preparative reverse-phase HPLC with average radiochemical yields of 80% in a total synthesis time of 80 minutes. The specific activity was determined to be greater than 2500 Ci/mmol. The radiochemical and chemical purity assessed by radio-TLC and HPLC were found to be 98%. Alternatively, iododestannylation reactions via the trimethyltin precursors with Na[ 123 I] in the presence of Chloramine-T or peracetic acid resulted in yields of only 20-25% with the bulk of activity being lost as volatile methyl [ 123 I]iodide. (author)

  20. Synthesis, biological evaluation, and structure-activity relationship of clonazepam, meclonazepam, and 1,4-benzodiazepine compounds with schistosomicidal activity.

    Science.gov (United States)

    Menezes, Carla M S; Rivera, Gildardo; Alves, Marina A; do Amaral, Daniel N; Thibaut, Jean Pierre B; Noël, François; Barreiro, Eliezer J; Lima, Lídia M

    2012-06-01

    The inherent morbidity and mortality caused by schistosomiasis is a serious public health problem in developing countries. Praziquantel is the only drug in therapeutic use, leading to a permanent risk of parasite resistance. In search for new schistosomicidal drugs, meclonazepam, the 3-methyl-derivative of clonazepam, is still considered an interesting lead-candidate because it has a proven schistosomicidal effect in humans but adverse effects on the central nervous system did not allow its clinical use. Herein, the synthesis, in vitro biological evaluation, and molecular modeling of clonazepam, meclonazepam, and analogues are reported to establish the first structure-activity relationship for schistosomicidal benzodiazepines. Our findings indicate that the amide moiety [N(1) H-C(2) (=O)] is the principal pharmacophoric unit of 1,4-benzodiazepine schistosomicidal compounds and that substitution on the amide nitrogen atom (N(1) position) is not tolerated. © 2012 John Wiley & Sons A/S.

  1. Novel one-pot one-step synthesis of 2'-[(18)F]fluoroflumazenil (FFMZ) for benzodiazepine receptor imaging.

    Science.gov (United States)

    Yoon, Young Hyun; Jeong, Jae Min; Kim, Hyung Woo; Hong, Sung Hyun; Lee, Yun-Sang; Kil, Hee Sup; Chi, Dae Yoon; Lee, Dong Soo; Chung, June-Key; Lee, Myung Chul

    2003-07-01

    We describe the synthesis of 2'-[(18)F]fluoroflumazenil (FFMZ), which differs from the typically used [(18)F]fluoroethylflumazenil (FEFMZ) for benzodiazepine receptor imaging. For one-pot one-step labeling, the precursors, 2'-tosyloxyflumazenil (TFMZ) and 2'-mesyloxyflumazenil (MFMZ), were synthesized in three steps. The precursors were successfully labeled with no-carrier-added (18)F-fluoride which was activated by repeated azeotropic distillation with Kryptofix 2.2.2./potassium carbonate in MeCN. An automated system for labeling and purification of [(18)F]FFMZ was developed. Labeling efficiency and radiochemical purity of [(18)F]FFMZ after synthesis by the automated system were 68% and 98%, respectively. Specific binding of [(18)F]FFMZ to central benzodiazepine receptor of rats was demonstrated by phosphoimaging.

  2. Novel one-pot one-step synthesis of 2'-[18F]fluoroflumazenil (FFMZ) for benzodiazepine receptor imaging

    International Nuclear Information System (INIS)

    Young, Hyun Yoon; Jae, Min Jeong; Hyung, Woo Kim; Sung, Hyun Hong; Lee, Yun-Sang; Hee, Sup Kil; Dae, Yoon Chi; Dong, Soo Lee; Chung, June-Key; Myung, Chul Lee

    2003-01-01

    We describe the synthesis of 2'-[ 18 F]fluoroflumazenil (FFMZ), which differs from the typically used [ 18 F]fluoroethylflumazenil (FEFMZ) for benzodiazepine receptor imaging. For one-pot one-step labeling, the precursors, 2'-tosyloxyflumazenil (TFMZ) and 2'-mesyloxyflumazenil (MFMZ), were synthesized in three steps. The precursors were successfully labeled with no-carrier-added 18 F-fluoride which was activated by repeated azeotropic distillation with Kryptofix 2.2.2./potassium carbonate in MeCN. An automated system for labeling and purification of [ 18 F]FFMZ was developed. Labeling efficiency and radiochemical purity of [ 18 F]FFMZ after synthesis by the automated system were 68% and 98%, respectively. Specific binding of [ 18 F]FFMZ to central benzodiazepine receptor of rats was demonstrated by phosphoimaging

  3. Renal PTA stenting

    International Nuclear Information System (INIS)

    Tsetis, D.

    2012-01-01

    Full text: Renal artery stenosis (RAS) is a common condition that may lead to hypertension, progressive renal dysfunction and cardiovascular morbidity. Catheter-based therapy for symptomatic, haemodynamically significant, RAS has become the preferred method of revascularization. Balloon angioplasty has been the traditional treatment of choice for fibromuscular dysplasia, however stents are increasingly used for the treatment of atheromatous lesions; in many cases-such as in ostial lesions-, direct stenting is strongly indicated. Despite the increased use of endovascular therapy for renal artery stenosis, there is still controversy regarding the optimal management and the net benefit of this treatment. Several randomized trials of balloon angioplasty or stenting for renal artery stenosis compared with medical therapy alone have been conducted, however these could not show definite advantage of endovascular therapy. Problems encountered with those trials include enrollment of small number of patients, frequent crossover from medical to interventional therapy compromising the intention-to-treat results, or selection of patients that are not expected to show clear benefit. The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) is the most important of these trials; however, it,s study design was faulty and therefore did not provide conclusive evidence to answer the question of whether angioplasty and stenting or medical therapy is the best treatment for haemodynamically significant RAS. All expectations are now focused on the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial which was designed to answer the same question, and its methodologies took into consideration the weaknesses of the ASTRAL trial. Regarding stent device itself, it seems that the optimal design is probably a stainless steel, laser cut, open-cells stent mounted on a rapid exchange delivery balloon catheter compatible with 0.014-in and 0.018-in guidewire. As a future

  4. "Diazepam loading": ¿Can a strategy for preventing alcohol withdrawal be used to treat benzodiazepine use disorder?

    Science.gov (United States)

    Oliveras, Clara; Fortea, Adriana; Espinosa, Laura; Barrio, Pablo; Lligoña, Anna; Balcells-Olivero, Mercè

    2018-04-15

    Benzodiazepines (BZDs) are central nervous system (CNS) depressants which are widely used to treat insomnia and anxiety, despite having long-term adverse side effects. (Fortea González, Oriolo, Balcells Oliveró, Sánchez Del Valle & Castellvi, 2017). As with alcohol, continued use can lead to tolerance and dependence phenomena. Discontinuation in such cases can produce abstinence symptoms such as tremors, anxiety, seizures and, occasionally, death (Brett y Murnion, 2015).

  5. Novel modulatory effects of neurosteroids and benzodiazepines on excitatory and inhibitory neurons excitability: a multi-electrode array recording study

    OpenAIRE

    Puia, Giulia; Gullo, Francesca; Dossi, Elena; Lecchi, Marzia; Wanke, Enzo

    2012-01-01

    The balance between glutamate- and GABA-mediated neurotransmission in the brain is fundamental in the nervous system, but it is regulated by the “tonic” release of a variety of endogenous factors. One such important group of molecules are the neurosteroids (NSs) which, similarly to benzodiazepines (BDZs), enhance GABAergic neurotransmission. The purpose of our work was to investigate, at in vivo physiologically relevant concentrations, the effects of NSs and BDZs as GABA modulators on dissoci...

  6. Benzodiazepines have high-affinity binding sites and induce melanogenesis in B16/C3 melanoma cells.

    OpenAIRE

    Matthew, E; Laskin, J D; Zimmerman, E A; Weinstein, I B; Hsu, K C; Engelhardt, D L

    1981-01-01

    We found that two markers of differentiation, tyrosinase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) activity and melanin synthesis, are induced by diazepam in B16/C3 mouse melanoma cells. We also demonstrated high-affinity binding sites for [3H]diazepam in these cells by radioreceptor assay, and we visualized binding to the cell surface by fluorescence microscopy with a benzodiazepine analog conjugated to a fluorescein-labeled protein. Our studies also showed tha...

  7. Unsaturated free fatty acids increase benzodiazepine receptor agonist binding depending on the subunit composition of the GABAA receptor complex.

    Science.gov (United States)

    Witt, M R; Westh-Hansen, S E; Rasmussen, P B; Hastrup, S; Nielsen, M

    1996-11-01

    It has been shown previously that unsaturated free fatty acids (FFAs) strongly enhance the binding of agonist benzodiazepine receptor ligands and GABAA receptor ligands in the CNS in vitro. To investigate the selectivity of this effect, recombinant human GABAA/benzodiazepine receptor complexes formed by different subunit compositions (alpha x beta y gamma 2, x = 1, 2, 3, and 5; y = 1, 2, and 3) were expressed using the baculovirus-transfected Sf9 insect cell system. At 10(-4) M, unsaturated FFAs, particularly arachidonic (20:4) and docosahexaenoic (22:6) acids, strongly stimulated (> 200% of control values) the binding of [3H]flunitrazepam ([3H]FNM) to the alpha 3 beta 2 gamma 2 receptor combination in whole cell preparations. No effect or small increases in levels of unsaturated FFAs on [3H]FNM binding to alpha 1 beta x gamma 2 and alpha 2 beta x gamma 2 receptor combinations were observed, and weak effects (130% of control values) were detected using the alpha 5 beta 2 gamma 2 receptor combination. The saturated FFAs, stearic and palmitic acids, were without effect on [3H]FNM binding to any combination of receptor complexes. The hydroxylated unsaturated FFAs, ricinoleic and ricinelaidic acids, were shown to decrease the binding of [3H]FNM only if an alpha 1 beta 2 gamma 2 receptor combination was used. Given the heterogeneity of the GABAA/ benzodiazepine receptor subunit distribution in the CNS, the effects of FFAs on the benzodiazepine receptor can be assumed to vary at both cellular and regional levels.

  8. Impact of benzodiazepines on brain FDG-PET quantification after single-dose and chronic administration in rats

    International Nuclear Information System (INIS)

    Silva-Rodríguez, Jesús; García-Varela, Lara; López-Arias, Esteban; Domínguez-Prado, Inés; Cortés, Julia; Pardo-Montero, Juan; Fernández-Ferreiro, Anxo

    2016-01-01

    Introduction: Current guidelines for brain PET imaging advice against the injection of diazepam prior to brain FDG-PET examination in order to avoid possible interactions of benzodiazepines with the radiotracer uptake. Nevertheless, many patients undergoing PET studies are likely to be under chronic treatment with benzodiazepines, for example due to the use of different medications such as sleeping pills. Animal studies may provide an extensive and accurate estimation of the effect of benzodiazepines on brain metabolism in a well-defined and controlled framework. Aim: This study aims at evaluating the impact of benzodiazepines on brain FDG uptake after single-dose administration and chronic treatment in rats. Methods: Twelve Sprague–Dawley healthy rats were randomly divided into two groups, one treated with diazepam and the other used as control group. Both groups underwent PET/CT examinations after single-dose and chronic administration of diazepam (treated) or saline (controls) during twenty-eight days. Different atlas-based quantification methods were used to explore differences on the total uptake and uptake patterns of FDG between both groups. Results: Our analysis revealed a significant reduction of global FDG uptake after acute (−16.2%) and chronic (−23.2%) administration of diazepam. Moreover, a strong trend pointing to differences between acute and chronic administrations (p < 0.08) was also observed. Uptake levels returned to normal after interrupting the administration of diazepam. On the other hand, patterns of FDG uptake were not affected by the administration of diazepam. Conclusions: The administration of diazepam causes a progressive decrease of the FDG global uptake in the rat brain, but it does not change local patterns within the brain. Under these conditions, visual assessment and quantification methods based on regional differences such as asymmetry indexes or SPM statistical analysis would still be valid when administrating this

  9. Risk factors associated with iatrogenic opioid and benzodiazepine withdrawal in critically ill pediatric patients: a systematic review and conceptual model.

    Science.gov (United States)

    Best, Kaitlin M; Boullata, Joseph I; Curley, Martha A Q

    2015-02-01

    Analgesia and sedation are common therapies in pediatric critical care, and rapid titration of these medications is associated with iatrogenic withdrawal syndrome. We performed a systematic review of the literature to identify all common and salient risk factors associated with iatrogenic withdrawal syndrome and build a conceptual model of iatrogenic withdrawal syndrome risk in critically ill pediatric patients. Multiple databases, including PubMed/Medline, EMBASE, CINAHL, and the Cochrane Central Registry of Clinical Trials, were searched using relevant terms from January 1, 1980, to August 1, 2014. Articles were included if they were published in English and discussed iatrogenic withdrawal syndrome following either opioid or benzodiazepine therapy in children in acute or intensive care settings. Articles were excluded if subjects were neonates born to opioid- or benzodiazepine-dependent mothers, children diagnosed as substance abusers, or subjects with cancer-related pain; if data about opioid or benzodiazepine treatment were not specified; or if primary data were not reported. In total, 1,395 articles were evaluated, 33 of which met the inclusion criteria. To facilitate analysis, all opioid and/or benzodiazepine doses were converted to morphine or midazolam equivalents, respectively. A table of evidence was developed for qualitative analysis of common themes, providing a framework for the construction of a conceptual model. The strongest risk factors associated with iatrogenic withdrawal syndrome include duration of therapy and cumulative dose. Additionally, evidence exists linking patient, process, and system factors in the development of iatrogenic withdrawal syndrome. Most articles were prospective observational or interventional studies. Given the state of existing evidence, well-designed prospective studies are required to better characterize iatrogenic withdrawal syndrome in critically ill pediatric patients. This review provides data to support the

  10. A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein.

    Science.gov (United States)

    Guo, Fang; Wu, Shuo; Julander, Justin; Ma, Julia; Zhang, Xuexiang; Kulp, John; Cuconati, Andrea; Block, Timothy M; Du, Yanming; Guo, Ju-Tao; Chang, Jinhong

    2016-09-21

    Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past two decades, which highlights the pressing need for antiviral therapeutics. In a high throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound, which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV infected cultures with 2 μM of BDAA reduced the virion production by greater than 2 logs, the compound is not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug resistant viruses revealed that substitution of proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine or alanine confers YFV resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, substitution of P219 with glycine confers BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 localizes at the endoplasmic reticulum lumen side of the fifth putative trans-membrane domain of NS4B and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed important role and structural basis for NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs and attenuated viral infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever. Yellow fever is an acute viral hemorrhagic disease which threatens approximately one billion people living in tropical areas of Africa and Latin America. Although a highly effective yellow fever vaccine has been available for more than seven decades, the low vaccination rate fails to prevent outbreaks in at

  11. The prevalence and clinical predictors of incidental atherosclerotic renal artery stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Ozkan, Ugur [Baskent University Faculty of Medicine, Department of Radiology, Adana/Turkey (Turkey)], E-mail: radugur@yahoo.com; Oguzkurt, Levent; Tercan, Fahri [Baskent University Faculty of Medicine, Department of Radiology, Adana/Turkey (Turkey); Nursal, Tarik Z. [Baskent University Faculty of Medicine, Department of General Surgery, Ankara/Turkey (Turkey)

    2009-03-15

    Objective: To evaluate the prevalence of incidental renal artery stenosis due to atherosclerosis and associated risk factors in patients with peripheral arterial disease (PAD). Materials and methods: To determine renal artery stenosis, aortofemoropopliteal digital substraction angiographies (DSA) of 629 consecutive patients with PAD were prospectively reviewed. Angiographies were performed as catheter angiography with automated pump injection. Of the patients, 540 were male (86%) and 89 female (14%) (mean age {+-} S.D.: 61.5 {+-} 11.1 years). Statistical analysis was performed to determine the association of significant renal artery stenosis ({>=}60% diameter stenosis) with patient demographics (age, sex, reason for angiography and smoking status), medical history (diabetes mellitus, hypertension and coronary artery disease), laboratory values (blood creatinine, fasting glucose, triglycerides, LDL, HDL and total cholesterol) and distribution of PAD (aortoiliac, femoropopliteal and crural diseases and multisegment involvement). Results: Renal artery disease was found in 33% (207 of 629) of all patients with peripheral arterial disease, and 9.6% of patients (n = 60) had significant ({>=}60%) renal artery stenosis. Only age and hypertension (blood pressure systolic >140 mmHg or diastolic >90 mmHg) were independent risk factors for significant renal artery stenosis on multivariate analysis. Mean age of patients with RAS was 66.5 {+-} 8.9 years compared with 61 {+-} 11.2 years for patients without RAS (p < 0.001). Hypertension was found in 41% of the patients in control group and in 63% of the patients in RAS group (p = 0.01). Conclusion: Incidental renal artery stenosis which can be mild or significant is a relatively common finding among patients with peripheral arterial disease. Advance age and hypertension are closely associated with significant renal artery stenosis.

  12. The prevalence and clinical predictors of incidental atherosclerotic renal artery stenosis

    International Nuclear Information System (INIS)

    Ozkan, Ugur; Oguzkurt, Levent; Tercan, Fahri; Nursal, Tarik Z.

    2009-01-01

    Objective: To evaluate the prevalence of incidental renal artery stenosis due to atherosclerosis and associated risk factors in patients with peripheral arterial disease (PAD). Materials and methods: To determine renal artery stenosis, aortofemoropopliteal digital substraction angiographies (DSA) of 629 consecutive patients with PAD were prospectively reviewed. Angiographies were performed as catheter angiography with automated pump injection. Of the patients, 540 were male (86%) and 89 female (14%) (mean age ± S.D.: 61.5 ± 11.1 years). Statistical analysis was performed to determine the association of significant renal artery stenosis (≥60% diameter stenosis) with patient demographics (age, sex, reason for angiography and smoking status), medical history (diabetes mellitus, hypertension and coronary artery disease), laboratory values (blood creatinine, fasting glucose, triglycerides, LDL, HDL and total cholesterol) and distribution of PAD (aortoiliac, femoropopliteal and crural diseases and multisegment involvement). Results: Renal artery disease was found in 33% (207 of 629) of all patients with peripheral arterial disease, and 9.6% of patients (n = 60) had significant (≥60%) renal artery stenosis. Only age and hypertension (blood pressure systolic >140 mmHg or diastolic >90 mmHg) were independent risk factors for significant renal artery stenosis on multivariate analysis. Mean age of patients with RAS was 66.5 ± 8.9 years compared with 61 ± 11.2 years for patients without RAS (p < 0.001). Hypertension was found in 41% of the patients in control group and in 63% of the patients in RAS group (p = 0.01). Conclusion: Incidental renal artery stenosis which can be mild or significant is a relatively common finding among patients with peripheral arterial disease. Advance age and hypertension are closely associated with significant renal artery stenosis.

  13. Synthesis and in vivo evaluation of [11C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors

    International Nuclear Information System (INIS)

    Dumont, Filip; Waterhouse, Rikki N.; Montoya, Julie A.; Mattner, Filomena; Katsifis, Andrew; Kegeles, Lawrence S.; Laruelle, Marc

    2003-01-01

    The synthesis and evaluation of [ 11 C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors, is reported herein. The reaction of desmethylzolpidem with [ 11 C] methyl iodide afforded the title compound [ 11 C]zolpidem in a yield of 19.19 ± 3.23% in 41 ± 2 min in specific activities of 0.995-1.19 Ci/μmol (1.115 ± 0.105 Ci/μmol) (n = 3; decay corrected, EOB). The amount of radioactivity in the brain after tail vein injection in male Wistar rats was low, and the regional distribution was homogeneous and not consistent with the known distribution of the central benzodiazepine receptors. The frontal cortex/cerebellum ratio was not significantly greater than one (1.007 ± 0.266 at 5 min) and did not increase from 5 to 40 min post-injection. A PET brain imaging study in one baboon confirmed the results obtained in rats. Therefore, it can be concluded that [ 11 C]zolpidem is not a suitable tracer for in vivo visualization of central benzodiazepine receptors

  14. PTSD Symptom Severities, Interpersonal Traumas, and Benzodiazepines Are Associated with Substance-Related Problems in Trauma Patients

    Science.gov (United States)

    Guina, Jeffrey; Nahhas, Ramzi W.; Goldberg, Adam J.; Farnsworth, Seth

    2016-01-01

    Background: Trauma is commonly associated with substance-related problems, yet associations between specific substances and specific posttraumatic stress disorder symptoms (PTSSs) are understudied. We hypothesized that substance-related problems are associated with PTSS severities, interpersonal traumas, and benzodiazepine prescriptions. Methods: Using a cross-sectional survey methodology in a consecutive sample of adult outpatients with trauma histories (n = 472), we used logistic regression to examine substance-related problems in general (primary, confirmatory analysis), as well as alcohol, tobacco, and illicit drug problems specifically (secondary, exploratory analyses) in relation to demographics, trauma type, PTSSs, and benzodiazepine prescriptions. Results: After adjusting for multiple testing, several factors were significantly associated with substance-related problems, particularly benzodiazepines (AOR = 2.78; 1.99 for alcohol, 2.42 for tobacco, 8.02 for illicit drugs), DSM-5 PTSD diagnosis (AOR = 1.92; 2.38 for alcohol, 2.00 for tobacco, 2.14 for illicit drugs), most PTSSs (especially negative beliefs, recklessness, and avoidance), and interpersonal traumas (e.g., assaults and child abuse). Conclusion: In this clinical sample, there were consistent and strong associations between several trauma-related variables and substance-related problems, consistent with our hypotheses. We discuss possible explanations and implications of these findings, which we hope will stimulate further research, and improve screening and treatment. PMID:27517964

  15. PTSD Symptom Severities, Interpersonal Traumas, and Benzodiazepines Are Associated with Substance-Related Problems in Trauma Patients

    Directory of Open Access Journals (Sweden)

    Jeffrey Guina

    2016-08-01

    Full Text Available Background: Trauma is commonly associated with substance-related problems, yet associations between specific substances and specific posttraumatic stress disorder symptoms (PTSSs are understudied. We hypothesized that substance-related problems are associated with PTSS severities, interpersonal traumas, and benzodiazepine prescriptions. Methods: Using a cross-sectional survey methodology in a consecutive sample of adult outpatients with trauma histories (n = 472, we used logistic regression to examine substance-related problems in general (primary, confirmatory analysis, as well as alcohol, tobacco, and illicit drug problems specifically (secondary, exploratory analyses in relation to demographics, trauma type, PTSSs, and benzodiazepine prescriptions. Results: After adjusting for multiple testing, several factors were significantly associated with substance-related problems, particularly benzodiazepines (AOR = 2.78; 1.99 for alcohol, 2.42 for tobacco, 8.02 for illicit drugs, DSM-5 PTSD diagnosis (AOR = 1.92; 2.38 for alcohol, 2.00 for tobacco, 2.14 for illicit drugs, most PTSSs (especially negative beliefs, recklessness, and avoidance, and interpersonal traumas (e.g., assaults and child abuse. Conclusion: In this clinical sample, there were consistent and strong associations between several trauma-related variables and substance-related problems, consistent with our hypotheses. We discuss possible explanations and implications of these findings, which we hope will stimulate further research, and improve screening and treatment.

  16. Synthesis and in vivo evaluation of [{sup 11}C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Dumont, Filip; Waterhouse, Rikki N. E-mail: rnw7@columbia.edu; Montoya, Julie A.; Mattner, Filomena; Katsifis, Andrew; Kegeles, Lawrence S.; Laruelle, Marc

    2003-05-01

    The synthesis and evaluation of [{sup 11}C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors, is reported herein. The reaction of desmethylzolpidem with [{sup 11}C] methyl iodide afforded the title compound [{sup 11}C]zolpidem in a yield of 19.19 {+-} 3.23% in 41 {+-} 2 min in specific activities of 0.995-1.19 Ci/{mu}mol (1.115 {+-} 0.105 Ci/{mu}mol) (n = 3; decay corrected, EOB). The amount of radioactivity in the brain after tail vein injection in male Wistar rats was low, and the regional distribution was homogeneous and not consistent with the known distribution of the central benzodiazepine receptors. The frontal cortex/cerebellum ratio was not significantly greater than one (1.007 {+-} 0.266 at 5 min) and did not increase from 5 to 40 min post-injection. A PET brain imaging study in one baboon confirmed the results obtained in rats. Therefore, it can be concluded that [{sup 11}C]zolpidem is not a suitable tracer for in vivo visualization of central benzodiazepine receptors.

  17. Synthesis and in vivo evaluation of [11C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors.

    Science.gov (United States)

    Dumont, Filip; Waterhouse, Rikki N; Montoya, Julie A; Mattner, Filomena; Katsifis, Andrew; Kegeles, Lawrence S; Laruelle, Marc

    2003-05-01

    The synthesis and evaluation of [(11)C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors, is reported herein. The reaction of desmethylzolpidem with [(11)C] methyl iodide afforded the title compound [(11)C]zolpidem in a yield of 19.19 +/- 3.23% in 41 +/- 2 min in specific activities of 0.995-1.19 Ci/micromol (1.115 +/- 0.105 Ci/micromol) (n = 3; decay corrected, EOB). The amount of radioactivity in the brain after tail vein injection in male Wistar rats was low, and the regional distribution was homogeneous and not consistent with the known distribution of the central benzodiazepine receptors. The frontal cortex/cerebellum ratio was not significantly greater than one (1.007 +/- 0.266 at 5 min) and did not increase from 5 to 40 min post-injection. A PET brain imaging study in one baboon confirmed the results obtained in rats. Therefore, it can be concluded that [(11)C]zolpidem is not a suitable tracer for in vivo visualization of central benzodiazepine receptors.

  18. Simultaneous identification of abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Hei-Hwa Lee

    2016-03-01

    Full Text Available A literature search reveals no studies concerning simultaneous identification of commonly abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry (LC–MS/MS. We developed and validated an LC–MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine from suspected drug abusers. The instrument was operated in multiple-reaction monitoring using an electrospray ionization mode. Chromatograms were separated using an ACE5 C18 column on a gradient of acetonitrile. After liquid–liquid extraction, samples were passed through a 0.22-μm polyvinylidene difluoride filter before injection into the LC–MS/MS. The limits of quantitation ranged from 0.5 ng/mL to 31.3 ng/mL. The linearity ranged from 0.5 ng/mL to 200 ng/mL. The precision results were below 15.4% (intraday and 18.7% (interday. The intraday accuracy ranged from 85.9% to 121.0%; interday accuracy ranged from 66.1% to 128.7%. The proposed method was applied to 769 urine samples. The most common three drugs identified were ketamine, amphetamine, and opiates. The drug positive rate for one or more drugs was 79.6%. Our results demonstrate the suitability of the LC–MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine.

  19. Peripheral T-Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  20. Network node for peripheral sharing

    International Nuclear Information System (INIS)

    Bobbitt, J.; Johnson, M.

    1977-01-01

    A module which enables several independent computer systems to share the peripherals (graphics display and line printer) of a PDP-11 computer is described. The module requires no software support in the PDP-11

  1. Alterations of bone microstructure and strength in end-stage renal failure

    NARCIS (Netherlands)

    Trombetti, A.; Stoermann, C.; Chevalley, T.; Rietbergen, van B.; Hermann, F.R.; Martin, P.Y.; Rizzoli, R.

    2013-01-01

    Summary End-stage renal disease (ESRD) patients have a high risk of fractures. We evaluated bone microstructure and finite-element analysis-estimated strength and stiffness in patients with ESRD by high-resolution peripheral computed tomography. We observed an alteration of cortical and trabecular

  2. Distal renal tubular acidosis in recurrent renal stone formers

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    Renal acidification ability was examined in 90 recurrent renal stone formers, using fasting morning urinary pH levels followed by a short ammonium chloride loading test in subjects with pH levels above 6.0. Fifteen patients (16.6%) revealed a distal renal tubular acidification defect: one patient......, this has important therapeutic implications. The pathological sequence in renal stone formers with dRTA is discussed....

  3. Renal sympathetic denervation: MDCT evaluation of the renal arteries.

    LENUS (Irish Health Repository)

    Hutchinson, Barry D

    2013-08-01

    Percutaneous transluminal renal sympathetic denervation is a new treatment of refractory systemic hypertension. The purpose of this study was to assess the clinical utility of MDCT to evaluate the anatomic configuration of the renal arteries in the context of renal sympathetic denervation.

  4. Imaging chronic renal disease and renal transplant in children

    International Nuclear Information System (INIS)

    Carmichael, Jim; Easty, Marina

    2010-01-01

    At Great Ormond Street Hospital we have the highest number of paediatric renal transplant patients in Europe, taking cases from across the United Kingdom and abroad. Our caseload includes many children with rare complicating medical problems and chronic renal failure related morbidity. This review aims to provide an overview of our experience of imaging children with chronic renal failure and transplants. (orig.)

  5. Eligibility for renal denervation

    DEFF Research Database (Denmark)

    Persu, Alexandre; Jin, Yu; Baelen, Marie

    2014-01-01

    -resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according...... undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility...... (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered....

  6. [Renal colic in pregnancy].

    Science.gov (United States)

    Negru, Irina; Pricop, C; Costăchescu, Gh

    2010-01-01

    Renal colic in pregnant women is a serious condition, mainly when is associated with fever. Our retro-prospective study analyzes 111 cases managed conservatively or with endourological procedures for renal colic--insertion of JJ stents and percutaneous nephrostomy. Clinical evolution determined the insertion of JJ stents in 60 cases and the failure of this procedure imposed percutaneous nephrostomy in 5 cases. In 56 cases urinary tract infection was associated and in 2 cases, despite all efforts, the patients deceased due to sever sepsis. The immediate drainage of the upper urinary tract for renal colic in pregnancy is the recommended treatment, especially when the pain is associated with fever. JJ stens were well tolerated, even when they were replaced after 3 months. Pregnant women with a history of UTI or stone disease should be carefully followed-up.

  7. Renal cell karcinoma trial

    International Nuclear Information System (INIS)

    Werf-Messing, B. van der; Heul, R.O. van der; Ledeboer, R.C.

    1981-01-01

    A total of 174 patients underwent simple nephrectomy in case of clinically operable kidney cancer without demonstrable metastases. Of these 85 received preoperative irradiation to the kidney and the regional lymph nodes (3000-4000 rad in 3-4 weeks). Prognosis was not influenced by preoperative irradiation. The preoperatively assessable prognostic criteria were sex and sedimentation rate: ESR >= 30 and being male worsened prognosis. The clinical T-categories of the UICC were not related to prognosis. Of the microscopic examination of the nephrectomy specimen, renal vein invasion and to a lesser extent a low degree of differentiation appeared to worsen prognosis. The prognostic influence of the P-categories was caused by a higher incidence of renal vein involvement in case of higher P-category. The most important prognostic factors - ESR, renal vein involvement, and sex - were not interrelated. Elective chemotherapy, radiation therapy, and hormone therapy could be considered in certain high-risk groups. (orig.)

  8. Scintigraphy of renal transplant

    International Nuclear Information System (INIS)

    Ramackers, J.M.; Marrast, A.C.; Touraine, J.L.; Peyrin, J.O.

    1995-01-01

    Scintigraphy is useful for monitoring perfusion and function of renal transplant, as well as for diagnosing miscellaneous surgical. This non-invasive imaging technique, which uses no deleterious products, is an attractive alternative for patients. This is especially true for those patients in early post-transplant course, with immunity depression and often impairment of renal function. Otherwise, multiple indices with a large range of inter-patient values has not favoured a methodological and interpretative consensus. Furthermore, the poor specificity of renogram patterns does not allow for discrimination of all etiologies with only one scintigraphy. Nevertheless, follow-up with iterative scintigraphy may be helpful due to the high intra-patient reproducibility and to the early appreciate change of parameters, according to clinical and histological renal post-transplant outcome. (authors). 43 refs., 8 figs

  9. A Review of the Updated Pharmacophore for the Alpha 5 GABA(A Benzodiazepine Receptor Model

    Directory of Open Access Journals (Sweden)

    Terry Clayton

    2015-01-01

    Full Text Available An updated model of the GABA(A benzodiazepine receptor pharmacophore of the α5-BzR/GABA(A subtype has been constructed prompted by the synthesis of subtype selective ligands in light of the recent developments in both ligand synthesis, behavioral studies, and molecular modeling studies of the binding site itself. A number of BzR/GABA(A α5 subtype selective compounds were synthesized, notably α5-subtype selective inverse agonist PWZ-029 (1 which is active in enhancing cognition in both rodents and primates. In addition, a chiral positive allosteric modulator (PAM, SH-053-2′F-R-CH3 (2, has been shown to reverse the deleterious effects in the MAM-model of schizophrenia as well as alleviate constriction in airway smooth muscle. Presented here is an updated model of the pharmacophore for α5β2γ2 Bz/GABA(A receptors, including a rendering of PWZ-029 docked within the α5-binding pocket showing specific interactions of the molecule with the receptor. Differences in the included volume as compared to α1β2γ2, α2β2γ2, and α3β2γ2 will be illustrated for clarity. These new models enhance the ability to understand structural characteristics of ligands which act as agonists, antagonists, or inverse agonists at the Bz BS of GABA(A receptors.

  10. Association between benzodiazepines and recurrent falls: a cross-sectional elderly population-based study.

    Science.gov (United States)

    Rossat, A; Fantino, B; Bongue, B; Colvez, A; Nitenberg, C; Annweiler, C; Beauchet, O

    2011-01-01

    While the association between benzodiazepines (BZD) and single fall is long-known, the association between BZD and recurrent falls has been few studied. The aims of this study were 1) to examine whether BZD were associated with recurrent falls while taking into account the effect of potential confounders, and 2) to determine whether there was an interaction in terms of risk of falls between BZD and balance impairment in a community-dwelling population-based adults aged 65 and older. Cross-sectional. Three health centers in North-East of France. 7643 community-dwelling volunteers aged 65 and older. The use of BZD, the Mini Mental State Examination (MMSE) score, the Clock Drawing Test (CDT), the One Leg Balance (OLB) test, the Five Times Sit-To-Stand test (FTSS), and a history of falls were recorded. Subjects were separated into 4 groups based on the number of falls: 0, 1, 2 and ≥ 3 falls. Among the 1456 (19.2%) fallers, 994 (13.0%) were single fallers and 462 (6.1%) were recurrent fallers (i.e., > 2 falls). The number of falls increased significantly with age (Incident Rate Ratio (IRR)=1.04, P falls. After adjustment only the advance in age (IRR=1.02, P falls. The current study shows that the age, the female gender, the use of clobazam or prazepam and a low score at OLB are related to the recurrence of falls.

  11. Limazepines A-F, pyrrolo[1,4]benzodiazepine Antibiotics from an Indonesian Micrococcus sp.

    Science.gov (United States)

    Fotso, Serge; Zabriskie, T Mark; Proteau, Philip J; Flatt, Patricia M; Santosa, Dwi Andreas; Mahmud, Taifo

    2009-04-01

    In our screening of Indonesian microorganisms for novel bioactive natural products we have isolated seven new compounds, designated as limazepines A, B1 and B2 (isolated as an isomeric mixture), C, D, E, and F, from the culture broth of Micrococcus sp. strain ICBB 8177. In addition, the known natural products prothracarcin and 7-O-succinylmacrolactin A, as well as two previously reported synthetic compounds, 2-amino-3-hydroxy-4-methoxybenzoic acid methyl ester and 4-ethylpyrrole-2-carboxaldehyde, were obtained from the extract. Chemical structures were determined by spectroscopic methods and by comparison with the NMR data of structurally related compounds. The limazepines belong to the growing group of the pyrrolo[1,4]benzodiazepine antitumor antibiotics isolated from various soil bacteria. Limazepines B1/B2 mixture, C, and E were active against the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacterium Escherichia coli. Limazepine D was also active against S. aureus, but was not active against E. coli. Interestingly, only the limazepines B1/B2 mixture and D were active against Pseudomonas aeruginosa.

  12. Benzodiazepine receptor imaging with iomazenil SPECT in aphasic patients with cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Koshi, Yasuhiko; Kitamura, Shin; Ohyama, Masashi [Nippon Medical School, Tokyo (Japan)] (and others)

    1999-08-01

    To investigate the relationship between prognosis of aphasia and neuronal damage in the cerebral cortex, we evaluated the distribution of central-type benzodiazepine receptor (BZR) binding in post-stroke aphasics with [{sup 123}I]iomazenil and SPECT. We performed iomazenil SPECT in six aphasic patients (aged from 45 to 75 years; all right-handed) with unilateral left cerebral infarction. Three patients showed signs of Broca's aphasia and the other three Wernicke's aphasia. Cerebral blood flow (CBF) imaging was performed with [{sup 123}I]iodoamphetamine (IMP). The regions of interest (ROIs) on both images were set in the cerebral cortex, cerebellar cortex and language relevant area in both hemispheres. Three patients were classified in the mild prognosis group and the other three in the moderate prognosis group. The left language-relevant area was more closely concerned with the difference in aphasic symptoms than the right one in both BZR and CBF distribution, but the ipsilateral to the contralateral ratio (I/C ratio) in the language-relevant areas in the BZR distribution was significantly lower in the moderate prognosis group than in the mild prognosis group, although no difference was seen for these values between the two groups in the CBF distribution. These results suggest that BZR imaging, which makes possible an increase in neuronal cell viability in the cerebral cortex, is useful not only for clarifying the aphasic symptoms but also for evaluating the prognosis of aphasia in patients with cerebral infarction. (author)

  13. Benzodiazepine receptor imaging with iomazenil SPECT in aphasic patients with cerebral infarction

    International Nuclear Information System (INIS)

    Koshi, Yasuhiko; Kitamura, Shin; Ohyama, Masashi

    1999-01-01

    To investigate the relationship between prognosis of aphasia and neuronal damage in the cerebral cortex, we evaluated the distribution of central-type benzodiazepine receptor (BZR) binding in post-stroke aphasics with [ 123 I]iomazenil and SPECT. We performed iomazenil SPECT in six aphasic patients (aged from 45 to 75 years; all right-handed) with unilateral left cerebral infarction. Three patients showed signs of Broca's aphasia and the other three Wernicke's aphasia. Cerebral blood flow (CBF) imaging was performed with [ 123 I]iodoamphetamine (IMP). The regions of interest (ROIs) on both images were set in the cerebral cortex, cerebellar cortex and language relevant area in both hemispheres. Three patients were classified in the mild prognosis group and the other three in the moderate prognosis group. The left language-relevant area was more closely concerned with the difference in aphasic symptoms than the right one in both BZR and CBF distribution, but the ipsilateral to the contralateral ratio (I/C ratio) in the language-relevant areas in the BZR distribution was significantly lower in the moderate prognosis group than in the mild prognosis group, although no difference was seen for these values between the two groups in the CBF distribution. These results suggest that BZR imaging, which makes possible an increase in neuronal cell viability in the cerebral cortex, is useful not only for clarifying the aphasic symptoms but also for evaluating the prognosis of aphasia in patients with cerebral infarction. (author)

  14. Prescribing Antidepressants and Benzodiazepines in the Netherlands: Is Chronic Physical Illness Involved?

    Directory of Open Access Journals (Sweden)

    Jacques Th. M. van Eijk

    2010-01-01

    Full Text Available In this study we assessed differences in new and repeat prescriptions of psycho-tropics between patients receiving prescriptions for drugs to treat a common chronic disease and people without such prescriptions. The study used the databases of two Dutch health insurance companies (3 million people. We selected all Dutch men and women aged 45 and older who were registered for six consecutive years (1999–2004. Our analyses both found a consistent relation between psycho-tropics on the one hand and physical illness on the other. People with multi-morbidity were prescribed these drugs most often, especially men and those younger than 65. Epidemiological studies showed a prevalence of depression among people with multi-morbidity to be twice as high as among people without such conditions. According to recent guidelines non-drug treatment may be the first therapy option for patients with non severe depression. If prescribed for a long time, benzodiazepine prescriptions are especially known to be addictive. Our data raise the question to what extent patients with a chronic physical disease suffering from co-occurring mental problems are prescribed psycho-tropics in accord with the guidelines that also advise mental support in case of non severe mental problems. Further research can answer this important question.

  15. The lesser evil? Initiating a benzodiazepine prescription in general practice: a qualitative study on GPs' perspectives.

    Science.gov (United States)

    Anthierens, Sibyl; Habraken, Hilde; Petrovic, Mirko; Christiaens, Thierry

    2007-12-01

    Chronic benzodiazepine (BZD) use is widespread and linked with adverse effects. There is consensus concerning the importance of initiating BZD as a crucial moment. Nevertheless specific research in this field is lacking. This paper addresses the views of GPs on why they start prescribing BZDs to first-time users. Qualitative study with five focus groups analysed using a systematic content analysis. Regions of Ghent and Brussels in Belgium. A total of 35 general practitioners. The GPs' perspective on their initiating of BZD prescribing. GPs reported that they are cautious in initiating BZD usage. At the same time, GPs feel overwhelmed by the psychosocial problems of their patients. They show empathy by prescribing. They feel in certain situations there are no other solutions and they experience BZDs as the lesser evil. They admit to resorting to BZDs because of time restraint and lack of alternatives. GPs do not perceive the addictive nature of BZD consumption as a problem with first-time users. GPs do not specifically mention patients' demand as an element for starting. The main concern of GPs is to help the patient. GPs should be aware of the addictive nature of BZD even in low doses and a non-pharmacological approach should be seen as the best first approach. If GPs decide to prescribe a BZD they should make plain to the patient that the medication is only a "temporary" solution with clear agreements with regard to medication withdrawal.

  16. A Unified Model of the GABA(A) Receptor Comprising Agonist and Benzodiazepine Binding Sites

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning; Bergmann, Rikke; Sørensen, Pernille Louise

    2013-01-01

    We present a full-length a1b2c2 GABA receptor model optimized for agonists and benzodiazepine (BZD) allosteric modulators. We propose binding hypotheses for the agonists GABA, muscimol and THIP and for the allosteric modulator diazepam (DZP). The receptor model is primarily based on the glutamate......-gated chloride channel (GluCl) from C. elegans and includes additional structural information from the prokaryotic ligand-gated ion channel ELIC in a few regions. Available mutational data of the binding sites are well explained by the model and the proposed ligand binding poses. We suggest a GABA binding mode...... of the agonists in the orthosteric site. The carbonyl group of DZP is predicted to interact with two threonines a1T206 and c2T142, similar to the acidic moiety of GABA. The chlorine atom of DZP is placed near the important a1H101 and the N-methyl group near a1Y159, a1T206, and a1Y209. We present a binding mode...

  17. Influence of benzodiazepines on body weight and food intake in obese and lean Zucker rats.

    Science.gov (United States)

    Blasi, C

    2000-05-01

    1. The gamma-aminobutyric acid (GABA)-ergic system, which is functionally altered in obese (fa/fa) Zucker rats, plays an important role in controlling energy balance within the central nervous system. 2. GABA receptors seem to be involved in the dysfunction of the hypothalamic energy homeostasis-controlling mechanisms in these animals due to a genetically-induced defect of the leptin-neuropeptide Y system. 3. To shed further light on the possible role played by the GABA system in the pathogenesis of this rat model, two benzodiazepine (BDZ) receptor agonists (diazepam and clonazepam) and one BDZ antagonist (flumazenil) were administered intraperitoneally in obese and lean Zucker rats. 4. Body weight gain was reduced by the BDZ agonists in both phenotypes, and one receptor-agonist (diazepam) lowered insulin concentration in obese rats. In GABA-antagonist-treated obese rats, the daily amount of body weight gain and food intake acquired an oscillatory rhythm similar to that of normal rodents. 5. By demonstrating the role of BDZ receptors, these findings may help clarify the pathophysiology of obesity and insulin resistance in fatty Zucker rats.

  18. Quality of life in a cohort of high-dose benzodiazepine dependent patients.

    Science.gov (United States)

    Lugoboni, Fabio; Mirijello, Antonio; Faccini, Marco; Casari, Rebecca; Cossari, Anthony; Musi, Gessica; Bissoli, Giorgia; Quaglio, Gianluca; Addolorato, Giovanni

    2014-09-01

    Benzodiazepines (BZD) are among the most widely prescribed drugs in developed countries. Since BZD can produce tolerance and dependence even in a short time, their use is recommended for a very limited time. However, these recommendations have been largely disregarded. The chronic use of BZD causes a number of serious side effects, i.e., cognitive impairment, falls, traffic accidents, dependence and tolerance. The aim of the present study was to evaluate quality of life (QoL) in a cohort of 62 consecutive high-dose BZD-dependent patients seeking a BZD detoxification. Patients seeking BZD detoxification were evaluated using the General Health Questionnaire (GHQ-12) and the short form-36 questionnaire (SF-36). Patients showed a significant reduction of QoL as measured by either SF-36 or GHQ-12. In particular, the greater impairment was observed in the items exploring physical and emotional status. Physical functioning was the item more influenced by the length of BZD abuse. Female patients showed a greater reduction of QoL compared to male, at least in some of the explored items. Social functioning scores were greatly reduced. The present study shows for the first time that high-doses BZD dependent patients have a reduced QoL and a reduced social functioning, along with high levels of psychological distress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Cognitive effects of pregabalin in the treatment of long-term benzodiazepine-use and dependence.

    Science.gov (United States)

    Oulis, Panagiotis; Kalogerakou, Stamatina; Anyfandi, Eleni; Konstantakopoulos, George; Papakosta, Vassiliki-Maria; Masdrakis, Vasilios; Tsaltas, Eleftheria

    2014-05-01

    Long-term benzodiazepine (BDZ) use and dependence affect cognitive functioning adversely and partly irreversibly. Emerging evidence suggests that pregabalin (PGB) might be a safe and efficacious treatment of long-term BDZ use. The aim of the present study was to investigate the changes in several core cognitive functions after successful treatment of long-term BDZ use and dependence with PGB. Fourteen patients with long-term BDZ use (mean duration >15 years) underwent neuropsychological assessment with the mini-mental state examination and four tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery before the initiation of PGB treatment and at a two months follow-up after the cessation of BDZs. Patients' CANTAB percentile score distributions were compared with normative CANTAB data. Patients improved on cognitive measures of global cognitive functioning, time orientation, psychomotor speed, and visuospatial memory and learning with strong effect sizes. By contrast, they failed to improve on measures of attentional flexibility. Despite their significant improvement, patients' scores on most tests remained still at the lower percentiles of CANTAB normative scores. Although preliminary, our findings suggest that successful treatment of long-term BDZ use with PGB is associated with a substantial, though only partial, recovery of BDZ-compromised neuropsychological functioning, at least at a 2-month follow-up. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Decreasing Trend in the Use and Long-Term Use of Benzodiazepines Among Young Adults.

    Science.gov (United States)

    Tähkäpää, Sanna-Mari; Saastamoinen, Leena; Airaksinen, Marja; Tuulio-Henriksson, Annamari; Aalto-Setälä, Terhi; Kurko, Terhi

    2018-03-14

    Patterns of benzodiazepine (BZD) use and long-term use among young adults are not well known. Our aim was to study trends in BZD use and long-term use among 18-25-year-old young adults by gender and active substance in a nationwide retrospective longitudinal register-based setting. All Finns aged 18-25 years with reimbursed purchases of BZDs in 2006-2014 recorded to the Finnish Prescription Register were included. Annual prevalence rates of BZD use and long-term use among young adults were reported overall, according to gender, drug group (anxiolytic or hypnotic), and active substance. Long-term use of BZDs was defined as purchasing ≥180 Defined Daily Doses (DDDs) in at least two drug purchases during a calendar year. Overall prevalence of BZD use among young adults decreased from 24.0 to 18.8 users per 1000 inhabitants in 2006-2014. Prevalence of long-term use decreased from 5.5 to 3.3 users per 1000 inhabitants. Overall BZD use was higher among females, whereas long-term use was more common among males. Use of anxiolytics was more common than use of hypnotics. Oxazepam, alprazolam, zopiclone, and zolpidem were the most used BZDs, whereas alprazolam and clonazepam were the substances with most long-term use. The use and long-term use of BZDs have decreased annually since 2008 among Finnish young adults. Further research is needed to investigate the reasons behind the decline.

  1. 125I-iomazenil-benzodiazepine receptor binding during psychological stress in rats

    International Nuclear Information System (INIS)

    Fukumitsu, Nobuyoshi; Tsuchida, Daisuke; Ogi, Shigeyuki; Uchiyama, Mayuki; Mori, Yutaka

    2002-01-01

    We investigated the changes in 125 I-iomazenil ( 125 I-IMZ) benzodiazepine receptor (BZR) binding with psychological stress in a rat model. Six male Wistar rats were placed under psychological stress for 1 hour by using a communication box. No physical stress was not received. 1.85 MBq of 125 I-IMZ was injected into the lateral tail vein and the rat was killed 3 hours later. Twenty-micormeter-thick sections of the brain were collected and % injected dose per body weight (% ID/BW) of eleven regions (frontal, parietal, temporal, occipital cortices, caudate putamen, accumubens nuclei, globus pallidus, amygdala, thalamus, hippocampus and hypothalamus) were calculated by autoradiography. The %ID/BW of rats which were placed under psychological stress was compared with that of 6 control rats. The %ID/BW of rats which were placed under psychological stress diffusely tended to show a reduction in 125 I-IMZ-BZR binding. A significant decrease in BZR binding was observed in the hippocampus of the rats which were placed under psychological stress. 125 I-IMZ-BZR binding tended to decrease throughout the brain. (author)

  2. Mathematical modeling of tetrahydroimidazole benzodiazepine-1-one derivatives as an anti HIV agent

    Science.gov (United States)

    Ojha, Lokendra Kumar

    2017-07-01

    The goal of the present work is the study of drug receptor interaction via QSAR (Quantitative Structure-Activity Relationship) analysis for 89 set of TIBO (Tetrahydroimidazole Benzodiazepine-1-one) derivatives. MLR (Multiple Linear Regression) method is utilized to generate predictive models of quantitative structure-activity relationships between a set of molecular descriptors and biological activity (IC50). The best QSAR model was selected having a correlation coefficient (r) of 0.9299 and Standard Error of Estimation (SEE) of 0.5022, Fisher Ratio (F) of 159.822 and Quality factor (Q) of 1.852. This model is statistically significant and strongly favours the substitution of sulphur atom, IS i.e. indicator parameter for -Z position of the TIBO derivatives. Two other parameter logP (octanol-water partition coefficient) and SAG (Surface Area Grid) also played a vital role in the generation of best QSAR model. All three descriptor shows very good stability towards data variation in leave-one-out (LOO).

  3. {sup 125}I-iomazenil-benzodiazepine receptor binding during psychological stress in rats

    Energy Technology Data Exchange (ETDEWEB)

    Fukumitsu, Nobuyoshi; Tsuchida, Daisuke; Ogi, Shigeyuki; Uchiyama, Mayuki; Mori, Yutaka [Jikei Univ., Tokyo (Japan). School of Medicine

    2002-05-01

    We investigated the changes in {sup 125}I-iomazenil ({sup 125}I-IMZ) benzodiazepine receptor (BZR) binding with psychological stress in a rat model. Six male Wistar rats were placed under psychological stress for 1 hour by using a communication box. No physical stress was not received. 1.85 MBq of {sup 125}I-IMZ was injected into the lateral tail vein and the rat was killed 3 hours later. Twenty-micormeter-thick sections of the brain were collected and % injected dose per body weight (% ID/BW) of eleven regions (frontal, parietal, temporal, occipital cortices, caudate putamen, accumubens nuclei, globus pallidus, amygdala, thalamus, hippocampus and hypothalamus) were calculated by autoradiography. The %ID/BW of rats which were placed under psychological stress was compared with that of 6 control rats. The %ID/BW of rats which were placed under psychological stress diffusely tended to show a reduction in {sup 125}I-IMZ-BZR binding. A significant decrease in BZR binding was observed in the hippocampus of the rats which were placed under psychological stress. {sup 125}I-IMZ-BZR binding tended to decrease throughout the brain. (author)

  4. Regulation of GABA and benzodiazepine receptors following neurotoxin-induced striatal and medial forebrain bundle lesions

    International Nuclear Information System (INIS)

    Pan, H.S.I.

    1985-01-01

    GABA, a major inhibitory transmitter, is used by many projection neurons of the striatum. To investigate the role of GABA in striatal function, the GABA receptor complex was studied after lesions of the striatum or the nigrostriatal neurons. Quantitative receptor autoradiography using thaw-mounted tissue slices was developed for the study of GABA and benzodiazepine (BDZ) receptors. With the technique established, binding to GABA and BDZ receptors after unilateral striatal kainate lesions was examined. Subsequently, changes in GABA and BDZ receptors were studied following the destruction of dopaminergic nigrostriatal cells by unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. In summary, quantitative receptor autoradiography allowed the detection of GABA and BDZ receptor changes in multiple small areas in each lesioned brain. This technique made it feasible to carry out kinetic saturation, and competition studies using less than 1 mg of tissue. The data suggest that dopamine is functionally inhibitory on striatopallidal neurons but is functionally excitatory on striatoentopeduncular and striatonigral cells which in turn inhibit the thalamus. This quantitative autoradiographic technique can be generalized to study other transmitter receptors and can be combined with 2-deoxyglucose uptake studies

  5. Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines

    Directory of Open Access Journals (Sweden)

    Joel K. Annor-Gyamfi

    2018-02-01

    Full Text Available Cancer remains the second major cause of death in the world. Thus, there is a pressing need to identify potential synthetic route for the development of novel anticancer agents which will serve as lead compounds to effectively combat this life-threatening epidemic. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs have sparked a great interest as lead compounds because of their cancerostatic and anti-infective properties. The twisted molecular structure of PBD analogs provides both helical and chiral elements. In an effort to expand novel PBDs that interact with the key exocyclic amino group of the DNA-guanine base, we hypothesized that construction of a fused cyclic active system, would likely serve as an electrophilic site when compared to traditional electrophilic C11-N10 imine group. To examine our theory, we report herein the synthesis and cell viability/cytotoxicity of a series of PBD analogs using NCI-60 cell lines screening. Thus, compounds 1–13 were synthesized and fully characterized. The selected PBDs were found to have marginal inhibition of growth, up to 30%, for certain cell lines.

  6. Benzodiazepine receptor turnover in embryonic chick brain and spinal cord cell cultures

    International Nuclear Information System (INIS)

    Borden, L.A.

    1985-01-01

    The turnover (synthesis and degradation) of the benzodiazepine receptor (BZD-R) in embryonic chick brain and spinal cord cell cultures was monitored using flunitrazepam (GNZM) as a photoaffinity label. To measure BZD-R appearance, intact cell cultures were incubated with 100 nM RNZM and irradiated with ultraviolet light; this process, referred to as photoinactivation, resulted in a 75% decrease in the subsequent reversible binding of 5 nM [ 3 H]FNZM. Following photoinactivation, [ 3 H]FNZM binding sites reappeared at a rate of 6 +/- 1.5%/hour (n = 7) in brain cultures and at 8%/hour (n = 2) in spinal cord cultures. Reappearance reflects de novo receptors synthesis. To examine the degradation of existing receptors, cultures were photolabeled with 5 nM [ 3 H]FNZM, washed, and then the decrease in cell-associated radioactivity, or the efflux of radioactivity into the medium, was monitored. The released radioactivity did not comigrate with authentic FNZM on thin-layer-chromatographs, indicating that release did not represent dissociation of ligand from the photolabeled receptor. The BZD-R appears to be degraded by an energy-dependent, non-lysosomal pathway. These experiments represent the first direct examination of the turnover of a neurotransmitter receptor localized to the central nervous system; this information will be valuable in elucidating the mechanisms by which receptor levels are altered following chronic drug treatment

  7. Anticonflict effect of alpidem as compared with the benzodiazepine alprazolam in rats.

    Science.gov (United States)

    Hascoët, M; Bourin, M

    1997-02-01

    A comparative study between two drugs acting on the GABAA receptor, alprazolam and alpidem was undertaken, using simple tests such as measurement of spontaneous locomotor activity, four plates test and rotarod in mice. Additional conflict test was further performed using a new conflict paradigm where the opportunity existed for rats to choose during punished periods between immediate, punished reinforcement and delayed non-punished reinforcement. The benzodiazepine alprazolam, demonstrated, as expected, strong anxiolytic effects in mice and increased punished response in rats at non sedative doses (0.5, 1 mg/kg). High doses of alprazolam decreased spontaneous locomotor activity and induced myorelaxant effects in mice. Alpidem, an imidazopyridine derivative, induced motor impairment in mice and only very weak anxiolytic effects in the four plates test in mice (4 mg/kg) and in punished procedure in rats (32 mg/kg). As alprazolam is a full agonist for the GABAA receptor complex and alpidem is a partial agonist acting with specificity on omega 1 GABAA receptor subtypes, the results are discussed. Activity on omega 1 receptor subtypes is perhaps not sufficient in order to obtain a true anti-conflict effect and compounds such as alpidem only relieve some of the symptoms of anxiety disorders.

  8. Benzodiazepines Withdrawal: Initial Outcomes and Long-Term Impact on Falls in a French Nursing Home

    Directory of Open Access Journals (Sweden)

    Hervé Javelot

    2018-04-01

    Full Text Available Long-term use of benzodiazepines (BZDs is known to induce tolerance and dependence, and increase the risk of falls-related injuries in older adults. We present a study carried out in a French nursing home that concerns the implementation of a BZD withdrawal program reassessed at one year. BZD deprescription was achieved by gradual cessation of doses. A secondary benefit of this program was assessed by comparing the number of falls among residents before and after withdrawal. The number of falls was recorded over a six-month period prior to the onset of withdrawal (T1 and then over a six-month period after reassessment at one year (T2. At the beginning, 31 (28.7% of the patients were under BZD. Total deprescription was obtained for 11 patients. The number of falls per patient over the T1 period was not different between the two groups (future non-withdrawn and withdrawn patients in BZD: 2.1 ± 1.3 and 2.3 ± 0.6 falls per resident, respectively. Conversely, the number of falls per patient was significantly decreased in the population completely withdrawn in BZD between the T1 and T2 periods (2.3 ± 0.6 vs. 0.5 ± 0.2 falls, p = 0.01. The results show that BZD deprescription, through a gradual reduction of doses, is possible to achieve.

  9. Maternal Characteristics of Women Exposed to Hypnotic Benzodiazepine Receptor Agonist during Pregnancy

    Directory of Open Access Journals (Sweden)

    Bjarke Askaa

    2014-01-01

    Full Text Available Background. There is little knowledge regarding the characteristics of women treated with hypnotic benzodiazepine receptor agonists (HBRAs during pregnancy. In this large Danish cohort study, we characterize women exposed to HBRA during pregnancy. We determined changes in prevalence of HBRA use from 1997 to 2010 and exposure to HBRAs in relation to pregnancy. Methods. We performed a retrospective cohort study including 911,017 pregnant women in the period from 1997 to 2010. Information was retrieved from The Danish Birth Registry and The Registry of Medicinal Product Statistics to identify pregnant women redeeming a prescription of HBRAs. Results. We identified 2,552 women exposed to HBRAs during pregnancy, increasing from 0.18% in 1997 to 0.23% in 2010. Compared to unexposed women, exposed women were characterized by being older, with higher BMI, in their third or fourth parity, of lower income and education level, more frequently smokers, and more likely to be comedicated with antipsychotic, anxiolytic, or antidepressant drugs (P<0.0001. Conclusion. Women using HBRAs during their pregnancy differ from unexposed women in socioeconomic factors and were more likely to receive comedication. The consumption of HBRAs was reduced during pregnancy compared to before conception.

  10. Further characterization of benzodiazepine receptor differences in long-sleep and short-sleep mice

    International Nuclear Information System (INIS)

    Marley, R.J.; Stinchcomb, A.; Wehner, J.M.

    1988-01-01

    Molecular and conformational characteristics of benzodiazepine (BZ) receptors in cortex and cerebellum from long-sleep and mice were investigated using heat inactivation and beta-carboline competition techniques. To investigate differences in the allosteric coupling between GABA and BZ receptors, the protection of BZ receptors from heat inactivation, by GABA, was also evaluated. The two genotypes do not differ in the affinity or number of BZ receptors in the cortex or cerebellum. They do, however, appear to differ in the molecular structure and/or regulation of the conformational state of the receptor in the cortex, as indicated by a greater sensitivity of LS mice to both heat inactivation and beta-carboline competition of 3 H-flunitrazepam (FNZ) binding in this region. Evidence for differences in the nature of coupling between GABA and BZ receptors is provided by the finding in that in both regions, GABA protected BZ receptors from inactivation to a greater degree in LS mice. The relationship between these differences and the multiplicity of expression of BZ receptors is discussed

  11. Blockade of alcohol's amnestic activity in humans by an alpha5 subtype benzodiazepine receptor inverse agonist.

    Science.gov (United States)

    Nutt, David J; Besson, Marie; Wilson, Susan J; Dawson, Gerard R; Lingford-Hughes, Anne R

    2007-12-01

    Alcohol produces many subjective and objective effects in man including pleasure, sedation, anxiolysis, plus impaired eye movements and memory. In human volunteers we have used a newly available GABA-A/benzodiazepine receptor inverse agonist that is selective for the alpha5 subtype (a5IA) to evaluate the role of this subtype in mediating these effects of alcohol on the brain. After pre-treatment with a5IA, we found almost complete blockade of the marked impairment caused by alcohol (mean breath concentration 150mg/100ml) of word list learning and partial but non-significant reversal of subjective sedation without effects on other measures such as intoxication, liking, and slowing of eye movements. This action was not due to alterations in alcohol kinetics and so provides the first proof of concept that selectively decreasing GABA-A receptor function at a specific receptor subtype can offset some actions of alcohol in humans. It also supports growing evidence for a key role of the alpha5 subtype in memory. Inverse agonists at other GABA-A receptor subtypes may prove able to reverse other actions of alcohol, and so offer a new approach to understanding the actions of alcohol in the human brain and in the treatment of alcohol related disorders in humans.

  12. Drug-induced renal injury

    African Journals Online (AJOL)

    The kidney receives a rich blood flow of 25% of resting cardiac output ... Drugs can cause acute renal failure by causing pre-renal, intrinsic or .... tubular epithelial cells causing cell swelling ... the dose as required or prescribe alternative drugs.

  13. Leiomyosarcoma of the renal pelvis

    Directory of Open Access Journals (Sweden)

    Dhamne Sagar

    2009-10-01

    Full Text Available Leiomyosarcomas are rare malignant tumors of the kidney. They may arise from the renal capsule, renal vein, renal pelvic musculature or renal parenchyma. Renal pelvis is an uncommon site of occurrence, with around 10 cases reported in the literature so far. Here we present a 60-year-old male who presented with increased urinary frequency, lower limb weakness, anorexia and weight loss. Imaging showed a right renal mass. A renal cell carcinoma was suspected clinically. A right nephrectomy was performed, which showed a large circumscribed mass in the hilar region. Histology revealed a tumor mass arising from the renal pelvis. The tumor was composed of spindle cells arranged in fascicles. Immunohistochemistry showed tumor cells to be positive for smooth muscle actin (SMA and desmin (Des and negative for cytokeratin (CK, HMB 45, CD117 (C-kit, and CD34. That confirmed the diagnosis of leiomyosarcoma.

  14. Renal denervation and hypertension.

    Science.gov (United States)

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  15. Renal lithiasis and nutrition

    Directory of Open Access Journals (Sweden)

    Prieto Rafel M

    2006-09-01

    Full Text Available Abstract Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified trough diet, since it must be considered that the urine composition is directly related to diet. In fact, the change of inappropriate habitual diet patterns should be the main measure to prevent kidney stones. In this paper, the relation between different dietary factors (liquid intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins and each type of renal stone (calcium oxalate monohydrate papillary, calcium oxalate monohydrate unattached, calcium oxalate dihydrate, calcium oxalate dihydrate/hydroxyapatite, hydroxyapatite, struvite infectious, brushite, uric acid, calcium oxalate/uric acid and cystine is discussed.

  16. Management of chronic renal failure.

    NARCIS (Netherlands)

    de Zeeuw, D.; Apperloo, AJ; de Jong, P.

    1992-01-01

    There is growing evidence that treatment of patients with renal function impairment will undergo a major shift within the next few years. Along with more or less successful attempts to alleviate the signs and symptoms of reduced renal function, new insights into renal pathophysiology as well as new

  17. Risk of renal allograft rejection following angiography

    International Nuclear Information System (INIS)

    Heideman, M.; Claes, G.; Nilson, A.E.

    1976-01-01

    In a retrospective study of 173 immediately functioning primary kidney transplants, correlation between angiography and renal allograft rejection was studied during the first 14 days. It was found that rejection was more frequent in kidneys undergoing angiography than in those not undergoing angiography. It was also found that in kidneys undergoing angiography an overwhelming number of the rejections started the day after angiography. These differences in rejection frequency could not be explained by differences in HLA matching or the origin of the kidneys. These findings suggest a possible connection indicating that the angiography might elicit an acute rejection episode. A possible mechanism for starting this reaction might be activation of the complement system which was found in 50 percent of the patients undergoing angiography in peripheral blood and in 100 percent when studied in vitro

  18. Screening renal stone formers for distal renal tubular acidosis

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    A group of 110 consecutive renal stone formers were screened for distal renal tubular acidosis (RTA) using morning fasting urinary pH (mfUpH) levels followed by a short ammonium chloride loading test in patients with levels above 6.0. In 14 patients (12.7%) a renal acidification defect was noted...... RTA in renal stone formers. Regardless of whether the acidification defect is primary or secondary to stone formation, however, all renal stone formers with distal RTA can expect to benefit from prophylactic alkaline therapy and it is recommended that the screening procedure, which is easy to use...

  19. Genetic markers of a Munc13 protein family member, BAIAP3, are gender specifically associated with anxiety and benzodiazepine abuse in mice and humans.

    Science.gov (United States)

    Wojcik, Sonja M; Tantra, Martesa; Stepniak, Beata; Man, Kwun-Nok M; Müller-Ribbe, Katja; Begemann, Martin; Ju, Anes; Papiol, Sergi; Ronnenberg, Anja; Gurvich, Artem; Shin, Yong; Augustin, Iris; Brose, Nils; Ehrenreich, Hannelore

    2013-07-24

    Anxiety disorders and substance abuse, including benzodiazepine use disorder, frequently occur together. Unfortunately, treatment of anxiety disorders still includes benzodiazepines, and patients with an existing comorbid benzodiazepine use disorder or a genetic susceptibility for benzodiazepine use disorder may be at risk of adverse treatment outcomes. The identification of genetic predictors for anxiety disorders, and especially for benzodiazepine use disorder, could aid the selection of the best treatment option and improve clinical outcomes. The brain-specific angiogenesis inhibitor I-associated protein 3 (Baiap3) is a member of the mammalian uncoordinated 13 (Munc13) protein family of synaptic regulators of neurotransmitter exocytosis, with a striking expression pattern in amygdalae, hypothalamus and periaqueductal gray. Deletion of Baiap3 in mice leads to enhanced seizure propensity and increased anxiety, with the latter being more pronounced in female than in male animals. We hypothesized that genetic variation in human BAIAP3 may also be associated with anxiety. By using a phenotype-based genetic association study, we identified two human BAIAP3 single-nucleotide polymorphism risk genotypes (AA for rs2235632, TT for rs1132358) that show a significant association with anxiety in women and, surprisingly, with benzodiazepine abuse in men. Returning to mice, we found that male, but not female, Baiap3 knockout (KO) mice develop tolerance to diazepam more quickly than control animals. Analysis of cultured Baiap3 KO hypothalamus slices revealed an increase in basal network activity and an altered response to diazepam withdrawal. Thus, Baiap3/BAIAP3 is gender specifically associated with anxiety and benzodiazepine use disorder, and the analysis of Baiap3/BAIAP3-related functions may help elucidate mechanisms underlying the development of both disorders.

  20. Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on: data derived from a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Lone Baandrup

    2016-10-01

    Full Text Available Abstract Background Patients with severe mental illness often suffer from disruptions in circadian rest-activity cycles, which might partly be attributed to ongoing psychopharmacological medication. Benzodiazepines are frequently prescribed for prolonged periods despite recommendations of only short-term usage. Melatonin, a naturally occurring nocturnal hormone, has the potential to stabilize disrupted circadian rhythmicity. Our aim was to investigate how prolonged-release melatonin affects rest-activity patterns in medicated patients with severe mental illness and if benzodiazepine dose reduction is associated with changes in circadian rhythm parameters. Method Data were derived from a randomized, double-blinded clinical trial with 24 weeks follow-up. Participants were randomized to add-on treatment with prolonged-release melatonin (2 mg or matching placebo, and usual benzodiazepine dosage was gradually tapered. Here we report the results of 72 h of actigraphic assessment of activity-rest cycles performed pre and post tapering. Changes in rest-activity rhythm parameters between the melatonin and placebo group were analyzed using the univariate general linear model. Change in activity counts per 6 h, from baseline to follow-up, in the whole sample was analyzed using paired samples t-test. Results A subsample of 48 patients participated in the actigraphic assessment: 20 in the melatonin group and 28 in the placebo group. Rest-activity cycles varied from regular to highly disrupted. Melatonin significantly increased the interdaily stability and at a trend level decreased the intradaily variability compared with placebo. Benzodiazepine dose reduction was not associated with these circadian rhythm parameters. Activity counts were generally higher after benzodiazepine dose reduction compared with pre tapering, but differences did not reach statistical significance. Conclusion Our data suggest melatonin as an aid during benzodiazepine withdrawal for

  1. Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection.

    Science.gov (United States)

    Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

    2015-11-03

    Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules including chemokine receptor type 5 (CXCR5), inducible T cell co-stimulator (ICOS), programmed death-1 (PD-1), ICOSL, PDL-1 and interleukin-21 (IL-21), of peripheral blood were comparatively measured in 42 primary renal allograft recipients within 1-3 years after transplantation. Among them, 24 patients had definite chronic rejection, while other 18 patients had normal renal function. Tfh-cell ratio was significantly increased with PD-1 down-regulation in the patients with chronic renal allograft rejection, while B cells and the alloimmune-regulating molecules studied did not show any appreciable change in parallel. The patients with chronic renal allograft rejection have a characteristic increase in circulating Tfh cells with a decrease in PD-1 expression. These pathological changes may be a therapeutic target for the treatment of chronic renal allograft rejection and can be useful as a clinical index for monitoring conditions of renal transplant.

  2. Angiography for renal hypertension

    International Nuclear Information System (INIS)

    Chuang, V.P.; Ernst, C.B.

    1985-01-01

    As angioplasty and operative techniques have become more precise and successful, so have evaluation techniques. Preoperative arteriography is indispensible for deciding on the appropriate treatment modality and the specifics of the procedure. Arteriography, therefore, remains the cornerstone in managing renovascular hypertension and renal arterial disease

  3. Dopamins renale virkninger

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1990-01-01

    is frequently employed in cases of acute oliguric renal failure but the results available concerning the therapeutic effect are frequently retrospective and uncontrolled. The results suggest that early treatment with 1-3 micrograms/kg/min dopamine combined with furosemide can postpone or possibly render...

  4. Primary renal graft thrombosis

    NARCIS (Netherlands)

    Bakir, N; Sluiter, WJ; Ploeg, RJ; van Son, WJ; Tegzess, Adam

    Background. Renal allograft thrombosis is a serious complication of kidney transplantation that ultimately leads to graft loss. Its association with acute and hyperacute rejection is well documented; however, in a large proportion of patients the precise cause remains obscure. The exact incidence

  5. Copper and ceruloplasmin contents in the blood serum of peripheral and pre-hepatic veins

    Directory of Open Access Journals (Sweden)

    H. M. Canelas

    1976-03-01

    Full Text Available Copper and ceruloplasmin contents were determined in samples of peripheral and pre-hepatic venous blood of 11 patients with Manson's schistosomiasis and one patient with hepatolenticular degeneration, all of çhich submitted either to porto-caval or spleno-renal shunt. Individual difference were not significant in any of the non-Wilsonian patients. The results are discussed in regard to the current knowledge on the pathogenesis of Wilson's disease.

  6. Interstitial mononuclear cell infiltrates in chronic rejection of the kidney and correlation with peripheral blood.

    OpenAIRE

    Jeong, H. J.; Hong, S. W.; Kim, Y. S.; Kim, M. S.; Choi, I. H.; Park, K.; Choi, I. J.

    1996-01-01

    To investigate the characteristics of interstitial inflammatory cells and possible involvement of nudelta T cells, 16 renal allograft biopsies showing chronic rejection were stained by immunohistochemical method and correlated with the data of peripheral blood evaluated by flow cytometry. For immunophenotyping, fresh frozen sections were stained with monoclonal antibodies against CD3, CD4, CD8, CD68, CD56, TCRdelta1 and HLA DR. Paraffin embedded tissue was stained with CD45RO, CD20-Cy and CD6...

  7. Interarm Difference in Blood Pressure: Reproducibility and Association with Peripheral Vascular Disease

    OpenAIRE

    Mehlsen, Jesper; Wiinberg, Niels

    2014-01-01

    The present study aimed at examining the interarm difference in blood pressure and its use as an indicator of peripheral arterial disease (PAD). Data were included from consecutive patients referred from their general practitioner to our vascular laboratory for possible PAD aged 50 years or older without known cardiac disease, renal disease, or diabetes mellitus. 824 patients (453 women) with mean age of 72 years (range: 50–101) were included. 491 patients had a diagnosi...

  8. Local graft irradiation in renal transplant rejection

    International Nuclear Information System (INIS)

    Kawamura, Masashi; Kataoka, Masaaki; Itoh, Hisao

    1990-01-01

    From 1977 to 1988, of 142 renal transplantations, seven recipients (4.9%) received local graft irradiation following rejective reaction refractory to antirejection medical managements. Concurrent with the administration of pulsed high dose methylprednisolone and other antirejection medical managements, the graft was irradiated with a total dose of 6.0 Gy-150 cGy per fraction every other day at the midplane of the graft using two opposing portals of 4MX Linac. The fields were defined by palpation and echography. All patients had improvements in serum creatinine on the 10th day after beginning the irradiation. Four patients with peripheral lymphocytosis during the irradiation combined with pulsed high dose methylprednisolone improved in renal functions. On the other hand, out of 3 patients with lymphcytopenic changes, in two the transplanted graft was removed due to deteriorations, and the other patient is currently suffering from chronic rejection. Local graft irradiation can be useful in maintaining a rejective graft and reversing its functions in some patients whose rejective reaction failed to respond to the antirejection medical managements. (author)

  9. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

    Directory of Open Access Journals (Sweden)

    Oranje Bob

    2011-10-01

    Full Text Available Abstract Background Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged benzodiazepine administration in patients with schizophrenia. Furthermore, we aim to investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life. Methods/Design Randomized, blinded, two-armed, parallel superiority trial. We plan to include 80 consenting outpatients diagnosed with schizophrenia or schizoaffective disorder, 18-55 years of age, treated with antipsychotic drug(s and at least one benzodiazepine derivative for the last three months before inclusion. Exclusion criteria: currently under treatment for alcohol or drug abuse, aggressive or violent behavior, known mental retardation, pervasive developmental disorder, dementia, epilepsy, terminal illness, severe co morbidity, inability to understand Danish, allergy to melatonin, lactose, starch, gelatin, or talc, hepatic impairment, pregnancy or nursing, or lack of informed consent. After being randomized to prolonged-release melatonin (Circadin® 2 mg daily or matching placebo, participants are required to slowly taper off their benzodiazepine dose. The primary outcome measure is benzodiazepine dose at 6 months follow-up. Secondary outcome measures include sleep, psychophysiological, and neurocognitive measures. Data are collected at baseline and at 6 months follow-up regarding medical treatment, cognition, psychophysiology, sleep, laboratory tests, adverse events, psychopathology, social function, and quality of life. Data on medical treatment, cognition, psychophysiology, adverse events, social function, and quality of life are also collected at 2 and 4

  10. Interankle systolic blood pressure difference and renal outcomes in patients with chronic kidney disease.

    Science.gov (United States)

    Chen, Szu-Chia; Tsai, Yi-Chun; Huang, Jiun-Chi; Lee, Su-Chu; Chang, Jer-Ming; Hwang, Shang-Jyh; Chen, Hung-Chun

    2016-05-01

    Interankle blood pressure (BP) difference has been associated with peripheral artery disease and adverse cardiovascular outcomes. However, the relationship between interankle BP difference and renal outcomes in chronic kidney disease (CKD) has never been evaluated. The purpose of this study was to determine whether interankle BP difference is associated with the rate of renal function decline and progression to renal end points in patients with stage 3-5 CKD. We enrolled 144 patients with CKD from one regional hospital. The BP in four limbs was simultaneously measured using an ABI-form device. The decline in renal function was evaluated using an estimated glomerular filtration rate (eGFR) slope. Rapid renal progression was defined as an eGFR slope < -3 mL/min per 1.73 m(2) per year. The renal end points were defined as ≥ 25% decline in eGFR or commencement of dialysis during the follow-up period. During a mean follow-up period of 3.1 years, 90 patients (62.5%) reached renal end points. Multivariate analysis showed that an increased interankle systolic BP difference (per 5 mmHg) was associated with a worse eGFR slope (regression β, -0.292; 95% confidence interval [CI], -0.482 to -0.102; P = 0.003), rapid renal progression (odds ratio, 1.189; 95% CI, 1.015-1.394; P = 0.032), and an increased risk of progression to renal end points (hazard ratio, 1.126; 95% CI, 1.052-1.204, P = 0.001). Interankle systolic BP difference was associated with rapid renal progression and progression to renal end points in patients with stage 3-5 CKD in our study. © 2015 Asian Pacific Society of Nephrology.

  11. Peripheral nerve conduits: technology update

    Science.gov (United States)

    Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

    2014-01-01

    Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

  12. Bridging the gap between education and appropriate use of benzodiazepines in psychiatric clinical practice

    Directory of Open Access Journals (Sweden)

    Dell’Osso B

    2015-07-01

    Public Health, Clinical and Molecular Medicine, Unit of Psychiatry, University of Cagliari, Cagliari, 18Department of Clinical and Experimental Medicine, Psychiatric Division, University of Insubria, Varese, 19Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant’ Andrea Hospital, Sapienza University of Rome, Rome, 20Department of Medical and Surgical Sciences, Bologna University, Bologna, 21Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy *These authors contributed equally as first authors Abstract: More than half a century after their discovery, benzodiazepines (BDZs still represent one of the largest and most widely prescribed groups of psychotropic compounds, not only in clinical psychiatry but also in the entire medical field. Over the last two decades, however, there has been an increased focus on the development of antidepressants and antipsychotics on the part of the pharmaceutical industry, clinicians, and researchers, with a reduced interest in BDZs, in spite of their widespread clinical use. As a consequence, many psychiatric residents, medical students, nurses, and other mental health professionals might receive poor academic teaching and training regarding these agents, and have the false impression that BDZs represent an outdated chapter in clinical psychopharmacology. However, recent advances in the field, including findings concerning epidemiology, addiction risk, and drug interactions, as well as the introduction of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition with related diagnostic changes, strongly encourage an updated appraisal of the use of BDZs in clinical practice. During a recent thematic event convened with the aim of approaching this topic in a critical manner, a group of young Italian psychiatrists attempted to highlight possible flaws in current teaching pathways, identify the main clinical pros and cons

  13. Temperament and character traits associated with the use of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens: evidence from a large Brazilian web survey

    Directory of Open Access Journals (Sweden)

    Ricardo Schneider Jr.

    2015-03-01

    Full Text Available Objectives: To evaluate how personality traits are associated with occasional use, abuse, and dependence of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens in a large availability sample of adults via online questionnaires. Methods: The sample consisted of 8,646 individuals (24.7% men and 75.3% women who completed an anonymous web survey. Involvement with drugs and temperament/character traits were assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST and the Temperament and Character Inventory - Revised (TCI-R, respectively. Interactions among variables were analyzed using MANOVA with Bonferroni adjustment. Results: Novelty seeking was the trait most associated with increased involvement with alcohol, cannabis, and cocaine. There was a significant association between harm avoidance and benzodiazepine use. Persistence was lower in cannabis-, benzodiazepine-, and cocaine-dependent subjects, as well as in hallucinogen abusers. Self-directedness was reduced in dependents of all drug classes. No strong relationships were found between other temperament or character dimensions and the severity of drug use. Conclusions: Novelty seeking was associated with increased involvement with all drugs studied in this sample, although to a lesser extent with benzodiazepines and hallucinogens. The temperament and character profile for benzodiazepine use was different from that of other drugs due to the relationship with higher harm avoidance and self-transcendence and lower self-directedness.

  14. Development and validation of an EI-GC-MS method for the determination of benzodiazepine drugs and their metabolites in blood: applications in clinical and forensic toxicology.

    Science.gov (United States)

    Papoutsis, Ioannis I; Athanaselis, Sotirios A; Nikolaou, Panagiota D; Pistos, Constantinos M; Spiliopoulou, Chara A; Maravelias, Constantinos P

    2010-08-01

    Benzodiazepines are used widely in daily clinical practice, due to their multiple pharmacological actions. The frequent problems associated with the wide use of benzodiazepines, as well as the multiple incidents of poisonings, led to the necessity for the development of a precise, sensitive and rapid method for the simultaneous determination of the 23 most commonly used benzodiazepines (diazepam, nordiazepam, oxazepam, bromazepam, alprazolam, lorazepam, medazepam, flurazepam, fludiazepam, tetrazepam, chlordiazepoxide, clobazam, midazolam, flunitrazepam, 7-amino-flunitrazepam, triazolam, prazepam, nimetazepam, nitrazepam, temazepam, lormetazepam, clonazepam, camazepam) in blood. A gas chromatographic method combined with mass spectrometric detection was developed, optimized and validated for the determination of the above substances. This method includes liquid-liquid extraction with chloroform at pH 9 and two stages of derivatization using tetramethylammonium hydroxide and propyliodide (propylation), as well as a mixture of triethylamine:propionic anhydride (propionylation). The recoveries were higher than 74% for all the benzodiazepines. The calibration curves were linear within the dynamic range of each benzodiazepine with a correlation coefficient higher than 0.9981. The limits of detection and quantification for each analyte were statistically calculated from the relative calibration curves. Accuracy and precision were also calculated and were found to be less than 8.5% and 11.1%, respectively. The developed method was successfully applied for the investigation of both forensic and clinical toxicological cases of accidental and suicidal poisoning. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  15. Deprescribing Benzodiazepines in Older Patients: Impact of Interventions Targeting Physicians, Pharmacists, and Patients.

    Science.gov (United States)

    Ng, Brendan J; Le Couteur, David G; Hilmer, Sarah N

    2018-04-28

    Benzodiazepines (BZDs; including the related Z-drugs) are frequently targets for deprescribing; long-term use in older people is harmful and often not beneficial. BZDs can result in significant harms, including falls, fractures, cognitive impairment, car crashes and a significant financial and legal burden to society. Deprescribing BZDs is problematic due to a complex interaction of drug, patient, physician and systematic barriers, including concern about a potentially distressing but rarely fatal withdrawal syndrome. Multiple studies have trialled interventions to deprescribe BZDs in older people and are discussed in this narrative review. Reported success rates of deprescribing BZD interventions range between 27 and 80%, and this variability can be attributed to heterogeneity of methodological approaches and limited generalisability to cognitively impaired patients. Interventions targeting the patient and/or carer include raising awareness (direct-to-consumer education, minimal interventions, and 'one-off' geriatrician counselling) and resourcing the patient (gradual dose reduction [GDR] with or without cognitive behavioural therapy, teaching relaxation techniques, and sleep hygiene). These are effective if the patient is motivated to cease and is not significantly cognitively impaired. Interventions targeted to physicians include prescribing interventions by audit, algorithm or medication review, and providing supervised GDR in combination with medication substitution. Pharmacists have less frequently been the targets for studies, but have key roles in several multifaceted interventions. Interventions are evaluated according to the Behaviour Change Wheel. Research supports trialling a stepwise approach in the cognitively intact older person, but having a low threshold to use less-consultative methods in patients with dementia. Several resources are available to support deprescribing of BZDs in clinical practice, including online protocols.

  16. Polysomnographic findings in a cohort of chronic insomnia patients with benzodiazepine abuse.

    Science.gov (United States)

    Mazza, Marianna; Losurdo, Anna; Testani, Elisa; Marano, Giuseppe; Di Nicola, Marco; Dittoni, Serena; Gnoni, Valentina; Di Blasi, Chiara; Giannantoni, Nadia Mariagrazia; Lapenta, Leonardo; Brunetti, Valerio; Bria, Pietro; Janiri, Luigi; Mazza, Salvatore; Della Marca, Giacomo

    2014-01-15

    To evaluate sleep modifications induced by chronic benzodiazepine (BDZ) abuse. Cohort study, comparison of sleep measures between BDZs abusers and controls. Drug Addiction Unit (Institute of Psychiatry) and Unit of Sleep Disorders (Institute of Neurology) of the Catholic University in Rome. Six outpatients affected by chronic BDZ abuse were enrolled, (4 men, 2 women, mean age 53.3 ± 14.8, range: 34-70 years); 55 healthy controls were also enrolled (23 men, 32 women, mean age 54.2 ± 13.0, range: 27-76 years). All patients underwent clinical evaluation, psychometric measures, ambulatory polysomnography, scoring of sleep macrostructure and microstructure (power spectral fast-frequency EEG arousal, cyclic alternating pattern [CAP]), and heart rate variability. BDZ abusers had relevant modification of sleep macrostructure and a marked reduction of fast-frequency EEG arousal in NREM (patients: 6.6 ± 3.7 events/h, controls 13.7 ± 4.9 events/h, U-test: 294, p = 0.002) and REM (patients: 8.4 ± 2.4 events/h, controls 13.3 ± 5.1 events/h, U-test: 264, p = 0.016), and of CAP rate (patients: 15.0 ± 8.6%, controls: 51.2% ± 12.1%, U-test: 325, p < 0.001). BDZ abusers have reduction of arousals associated with increased number of nocturnal awakenings and severe impairment of sleep architecture. The effect of chronic BDZ abuse on sleep may be described as a severe impairment of arousal dynamics; the result is the inability to modulate levels of vigilance.

  17. Comparison of UHPLC and HPLC in benzodiazepines analysis of postmortem samples: a case-control study.

    Science.gov (United States)

    Behnoush, Behnam; Sheikhazadi, Ardeshir; Bazmi, Elham; Fattahi, Akbar; Sheikhazadi, Elham; Saberi Anary, Seyed Hossein

    2015-04-01

    The aim of this study was to compare system efficiency and analysis duration regarding the solvent consumption and system maintenance in high-pressure liquid chromatography (HPLC) and ultra high-pressure liquid chromatography (UHPLC). In a case-control study, standard solutions of 7 benzodiazepines (BZs) and 73 biological samples such as urine, tissue, stomach content, and bile that screened positive for BZs were analyzed by HPLC and UHPLC in laboratory of forensic toxicology during 2012 to 2013. HPLC analysis was performed using a Knauer by 100-5 C-18 column (250 mm × 4.6 mm) and Knauer photodiode array detector (PAD). UHPLC analysis was performed using Knauer PAD detector with cooling autosampler and Eurospher II 100-3 C-18 column (100 mm × 3 mm) and also 2 pumps. The mean retention time, standard deviation, flow rate, and repeatability of analytical results were compared by using 2 methods. Routine runtimes in HPLC and UHPLC took 40 and 15 minutes, respectively. Changes in mobile phase composition of the 2 methods were not required. Flow rate and solvent consumption in UHPLC decreased. Diazepam and flurazepam were detected more frequently in biological samples. In UHPLC, small particle size and short length of column cause effective separation of BZs in a very short time. Reduced flow rate, solvent consumption, and injection volume cause more efficiency and less analysis costs. Thus, in the detection of BZs, UHPLC is an accurate, sensitive, and fast method with less cost of analysis.

  18. Tryptic mapping and membrane topology of the benzodiazepine receptor alpha-subunit

    Energy Technology Data Exchange (ETDEWEB)

    Lentes, K.U.; Venter, J.C.

    1986-05-01

    Rat brain membrane benzodiazepine receptors (BZR) were photoaffinity labelled specifically (in presence or absence of 6 ..mu..M clonazepam) with 10 nM /sup 3/H-flunitrazepam (FNZ). Digestion of the FNZ-labelled, membrane-bound BZR with 200 ..mu..g trypsin/mg membrane protein yielded H/sub 2/O-soluble BZR-fragments of molecular mass (M/sub r/) 34, 31, 28, 24, 21, 18, 16, 12, 10 and 7kDa. Because the 34kDa-peptide is the largest fragment containing a FNZ-binding site they conclude that this represents the extracellular domain of the BZR. In the remaining pellet two labelled peptides with M/sub r/ of 44kDa and 28kDa were found that required the use of detergents for their solubilization; they therefore contain the membrane anchoring domain. Digestion of the 0.5% Na-deoxycholate solubilized, intact BZR (M/sub r/ 51kDa) resulted in the same tryptic pattern as the membrane form of the receptor plus two larger fragments of M/sub r/ 45kDa and 40kDa. Arrangement of all tryptic fragments with reference to the FNZ binding site reveals a membrane topology of the BZR alpha-subunit with 67% (34kDa) for the extracellular domain, 21% (11kDa) for the membrane anchoring domain and 12% (6kDa) for a putative cytoplasmic domain. The overlap between some of the labelled fragments suggest that the BZ binding site must be located near the membrane surface of the extracellular domain.

  19. Reduction in the use of benzodiazepines and cyclopyrrolones in general practice

    Directory of Open Access Journals (Sweden)

    Jørgensen VR

    2008-09-01

    Full Text Available In 2003, the Danish Minister for the Interior and Health instructed general practitioners to reduce prescriptions of benzodiazepines (BZD and cyclopyrrolones (CP by 50%. However, no effective methods were specified. In Denmark, it is estimated that there are approximately 100,000 BZD-dependent patients, constituting approximately 2% of the population. Objective: This article describes the implementation of a successful, simple and voluntary intervention to reduce the use of dependence-inducing drugs, while at the same time challenging practitioners' ingrained habits and prejudices in this field.Methods: The rules implemented were essentially in accordance with the official Danish rules, such that a prescription for BZD and CP could only be issued for one month at a time, and only following consultation. Use was monitored using the Danish registration system, Ordiprax, which monitors sales of prescription medicine. Two Danish general practices, comprising a patient base of approximately 2300 were studied. With the exception of the severely physically or mentally ill, all users of BZD and CP were included.Results: After 2½ years, the use of BZD and CP was reduced by 75% and 90%, respectively. The reorganization of prescription patterns was seen to be significantly easier than physicians had expected. During the first three months, only four to five additional visits per week per 1000 patients were required. Subsequently, this number was stabilized at one to two additional visits. The usual collaborative partners, such as psychiatrists, homecare services, hospitals and substance abuse units were essentially not deployed. No serious withdrawal effects arose.Conclusion: The implementation of the aforementioned simple procedures is to be recommended for the prescription of BZD and CP drugs, as the effect is immediate and easily attainable, with a reasonable work input required on the part of general practitioners.

  20. The interaction of substituted benzamides with brain benzodiazepine binding sites in vitro.

    Science.gov (United States)

    Horton, R W; Lowther, S; Chivers, J; Jenner, P; Marsden, C D; Testa, B

    1988-08-01

    1. The interaction of substituted benzamides with brain benzodiazepine (BDZ) binding sites was examined by their ability to displace [3H]-flunitrazepam ([3H]-FNM) from specific binding sites in bovine cortical membranes in vitro. 2. Clebopride, Delagrange 2674, Delagrange 2335 and BRL 20627 displayed concentration-dependent displacement of [3H]-FNM with IC50 values of 73 nM, 132 nM, 7.7 microM and 5.9 microM, respectively. Other substituted benzamides including metoclopramide, sulpiride, tiapride, sultopride and cisapride were inactive at 10(-5) M. 3. Inhibition by clebopride and Delagrange 2674 of [3H]-FNM binding was apparently competitive and readily reversible. 4. In the presence of gamma-aminobutyric acid (GABA), the ability of diazepam and Delagrange 2674 to displace [3H]-Ro 15-1788 binding was increased 3.6 and 1.6 fold respectively, compared to the absence of GABA, while ethyl beta-carboline-3-carboxylate (beta CCE) and clebopride were less potent in the presence of GABA. 5. Diazepam was 30 fold less potent at displacing [3H]-Ro 15-1788 in membranes that had been photoaffinity labelled with FNM than in control membranes, whereas the potency of beta CCE did not differ. Clebopride and Delagrange 2674 showed a less than two fold loss of potency in photoaffinity labelled membranes. 6. The pattern of binding of clebopride and Delagrange 2674 in these in vitro tests is similar to that found previously with partial agonists or antagonists at BDZ binding sites. 7. Clebopride and Delagrange 2674 inhibited [3H]-FNM binding with similar potency in rat cerebellar and hippocampal membranes, suggesting they have no selectivity for BDZ1 and BDZ2 binding sites. 8. Clebopride and Delagrange 2674 are structurally dissimilar to other BDZ ligands and represent another chemical structure to probe brain BDZ binding sites.