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Vasation of the infusate. He was not considered for any mean calculations and was not replaced. Study design and drug administration. After an overnight fasting period of at least 8 h, the subjects received a single dose of 428 mg of enoxacin 2 ml of 214-mg ml enoxacin ampoule was diluted into 250 ml of an isotonic glucose solution ; intravenously over 60 min. The subjects remained in the fasting state for 4 h after drug administration. They then received a light lunch. Dinner was given approximately 10 h after drug infusion. Between lunch and dinner, two light snacks were allowed. The fluid intake rate was at about 125 ml h. Sample collection. The collection times of all body fluids are summarized in Table 1. Blood was taken from an indwelling intravenous cannula in the arm opposite from the infusion site arm, transferred into heparinized containers, and centrifuged. Urine was collected cumulatively for defined time periods Table 1 ; . Mixed saliva was collected without stimulation over a period of exactly 1 min. The pH of mixed saliva was determined following centrifugation. Nasal secretions were sampled with 25 5 mg of preweighed cotton which had been placed in the right or left nostril. The cotton remained there exactly 20 min. Tears were collected with small glass capillaries after stimulation of tear production with freshly cut onions held in front of the subject's eye. After collection, the capillaries were sealed with paraffin. Sweat production was stimulated by pilocarpine iontophoresis with an Ionto-Cup-Lancer CF Analyzer Wescor ; . Pads were soaked in 0.5% wt vol ; pilocarpine solution cathode ; or 0.1% wt vol ; sodium nitrate solution anode ; , attached to the electrodes of the iontophoresis instrument, and placed at the palmar and dorsal sides of the forearm. After a 5-min stimulation and subsequent cleaning of the skin area, a collecting cup was placed exactly on that part of the skin where iontophoresis had been performed. For further stimulation of sweat production, the forearm was wrapped with aluminum foil and a towel. After 25 min, the cup was withdrawn and the sweat was collected. All samples were immediately frozen at approximately 30 C. Drug analysis. The samples were analyzed for unchanged enoxacin and oxoenoxacin by a reversed-phase high-pressure liquid chromatography HPLC ; assay. The method was slightly modified from that of Goebel et al. 15 ; . The reference compounds were supplied by Godecke AG, Berlin, Germany enoxa cin, lot T 85005 ; , and by Warner Lambert Co., Ann Arbor, Mich. oxoenoxacin, lot P ; . All reagents and chemicals used were of analytical grade; acetonitrile and bidistilled water were of HPLC grade. In brief, a 5- m Spherisorb ODS II C18 column Bischoff GmbH, Leonberg, Germany ; was used as stationary phase. For the determination of enoxacin, the mobile phase consisted of 12 to 14% acetonitrile, 86 to 88% 0.1 M citric acid, 40 mM ammonium perchlorate, and 5 mM tetrabutylammonium hydroxide. For the determination of oxoenoxacin, the acetonitrile content was increased to 16%. The flow rate of the mobile phase ranged between 1.0 and 2.0 ml min. Enoxacin and oxoenoxacin were detected by UV absorption at 340 nm. Chromatographic data were recorded and processed with a Hitachi D 2000 Chromato-Integrator Hitachi Ltd., Tokyo, Japan ; . Plasma and saliva samples 100 l ; were deproteinized by the addition of 25 l mixture of acetonitrile and perchloric acid 80: 20, vol vol ; , they were centrifuged, and 10 l of the supernatant was injected onto the column. Urine samples were diluted 1: 20 or 200 with 0.1 N acetate buffer pH 4.5 ; , and a volume of 10 l was injected. Nasal secretions were eluted from the cotton pads into 300 l of isotonic sodium chloride solution. After 60 min, the cotton was squeezed and 50 l of the centrifuged solution was injected. Recovery from the cotton pad was between 84 and 99%. Tears and sweat samples were injected without any dilution. If the sample volume was not large enough for an injection, the sample was diluted to 1: 2 with bidistilled water. For the analysis of plasma, urine, saliva, tears, and sweat, calibration standards for the respective body fluids were prepared. Nasal secretion standards were prepared in isotonic sodium chloride solution, added to preweighed cotton pads, and extracted like a biological sample. The calibration graphs were linear between 0.039 and 10 g ml plasma and saliva ; , 1.95 and 1, 000 g ml urine ; , 0.078 and 5 g ml nasal secretions ; , and 0.039 and 1.25 g ml tears and sweat ; , with coefficients of correlation greater than 0.999. The calibration graphs for oxoenoxacin were linear from 0.031 to 1 g plasma and saliva ; and from 1.56 to 200 g ml urine ; . The between-day precision of the assay was found to be not higher than 4.8% coefficient of variation ; for enoxacin and 7.1% for oxoenoxacin for any of the fluids investigated. Pharmacokinetic evaluation. Pharmacokinetic parameters were calculated from plasma and urine data by standard noncompartmental methods 33 ; . Peak.
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Kakko J, Svanborg KD, Kreek MJ, Heilig M. 1-year retension and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomized, placebo-controlled trial. Lancet 2003: 361: 662-68.
Investments New collaboration agreements signed during 2005 with Avanir and Astex created intangible assets worth million. Further payments were made in respect of existing licensed in products amounting to million. In December, new collaboration agreements with Protherics PLC, Targacept Inc and Atherogenics Inc. were announced and are recorded as post balance sheet events. We will invest million in the global development and commercialisation agreement with Protherics, being a 4.3% investment in equity and an intangible asset. The licensing and commercialisation agreement with Atherogenics Inc. will initially require a million payment by AstraZeneca and the licensing and research collaboration agreement with Targacept Inc. will initially require a million payment by AstraZeneca. Both of these payments will be recorded as intangible assets. We have also entered into an agreement to acquire the total share capital of KuDOS Pharmaceuticals Limited for 0 million, subject to cash and working capital adjustment. Most of the cost of the investment reflects an intangible representing the oncology technology platform of KuDOS. Our recent focus on licensing in opportunities with third parties will result in additional intangible asset investment in the balance sheet. Should any of these products fail in development, the associated intangibles will need to be written off.
The parotid gland of the sheep stimulated through their nerves lose potassium explosively to the blood and to the saliva during the first minutes.8' This is due to loss of cellular potassium. After the initial loss a new steady state is established. Is the initial loss in our experiments a similar phenomenon? In the perfused submandibular gland of the cat, calcium is essential for the secretory response to acetylcholine as well as to noradrenaline.ls However, lack of calcium does not prevent all reactions of this gland to acetylcholine; the secretory potentials persist.21 In our pilocarpine experiments with calcium the initial loss of rubidium was less than in those without calcium which is the opposite to the situation in the salivary glands. These, however, are quiescent except when stimulated, while in the ciliary processes none of the autonomic receptor blockers stops secretion. One should, therefore, be wary of drawing parallels between the 2 types of glands. Now, certainly the kidney tubules must be continuously active and muscarinic agents do have an inhibitory effect on sodium reabsorption in the dog22 and the chicken.23 We believe that this effect is probably more closely related to the one we have observed, and we doubt that the initial loss of rubidium found by us corresponds to the true excitation loss in previously quiescent salivary gland cells. We have seen virtually no effect of pilocarpine on the later phase of the runout. This could be due to lack of a steady-state effect on the cells. But it is also possible that, once the initial effect is over, the rate-limiting factor for the loss of rubidium in our experiments is not the state of the epithelial cell proper but the supply of water and electrolytes through the stroma. In the experiments of Walinder3 with pilocarpine inhibition of the organic anion transport system, late effects must have been present. In the shrinkage experiments of Berggren, a late effect may be present but not convincingly so Fig. 2 of reference 1 ; . Phenylephrine. No effect whatsoever was.
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Ml ; was placed in Falcon with and twice Grand slight culture cells volume cells in Island, were tubes harheparin. technique'2 was layered Sweden ; washed GIBCO, 106 ml Mononuclear on an equal Mononuclear.
Based on the rate of appearance of a "pupillary bubble" as described previously.38 The assumptions of this technique, which is based on geometry, differ from the assumptions of Jones and Maurice's technique. Also, this technique requires the use of pilocarpine to produce miosis and a well-defined pupillary bubble. Given the fact that pilocarpine has a slight stimulatory effect on the rate of aqueous flow, 50 the agreement between the results derived from the photogrammetric technique and thefluoresceinclearance technique are remarkably good. Also, another technique, in which radioactive albumin was injected intracameraliy into humans, serves as an independent confirmation of the accuracy of Maurice's method.34 A recent analysis of a group of more than 300 normal subjects 3-83 years of age was done using the scanning ocular fluorophotometer Table 2 ; .51 Flow was calculated from clearance offluoresceinapplied 6 hr earlier.52 The rate of aqueous flow, determined from 8 to 4 one eye of each subject was 2.75 0.63 jul min mean standard deviation ; . The 2.5 percentile of this distribution was 1.78 J min, and the 97.5 percentile was 4.26 xl min. Aqueous flow in the morning from 8 to noon was higher, 2.86 0.73, and from noon to 4 was lower, 2.63 0.57, an 8% difference P 0.001 ; . Comparisons were made between simultaneous measurements of the two eyes of the same subject. The coefficient of variation of the difference in flow between the two eyes was 15%. When the flow of an and pima.
The effect of repetitive administration of pilocarpine nitrate on the salivary volume and salivary IgA concentration was studied in the NIH white hamster. One and one-half to three-fold increases in salivary volume, coupled with decreases of 1 3 IgA concentration, occurred as the frequency of administration of pilocarpine increased. J Dent Res 61 12 ; : 1451-1453, December 1982.
Coding For Blood Products and Services In The Hospital Inpatient Setting Inpatient hospital billing for blood and blood services requires several types of codes: ICD-9-CM diagnosis codes, ICD-9-CM procedure codes, Medicare revenue codes to describe the category of service performed, and Medicare value codes to assign amounts or values for blood not applicable when the provider does not charge for the blood itself, but only for blood processing ; . ICD-9-CM Diagnosis Codes Are Used in All Settings, Including Hospital Inpatient ICD-9-CM diagnosis codes are used to describe patient diagnoses in all settings. All payers require hospital and physician billing staff to use ICD-9-CM codes to document patients' diagnoses to the highest level of specificity based on the patient's medical record. Use of blood is associated with many possible diagnoses. Putting such diagnoses on a claim form, when appropriate, optimizes the likelihood of receiving the full, appropriate reimbursement for blood and blood products. Furthermore, assignment of a case to the correct DRG often depends on the proper coding of co-morbidities and complications identified by diagnosis codes. There is no single diagnosis code that will always justify the use of blood or blood products on the claim form. Diagnosis codes are used by hospitals on the Uniform Billing form known as the UB-92 ; to reflect procedures done in the hospital inpatient setting. Identifying the Specific Inpatient Transfusion Procedure Using ICD-9-CM Procedure Codes Medicare and private payers require ICD-9-CM procedure codes on the UB-92 claim form to describe surgical and medical procedures performed in the hospital inpatient setting. These procedure codes also are essential for assignment of a case to the correct DRG. Procedure codes that may be used to reflect the transfusion procedure are summarized in Table 2 and pindolol.
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3. Basler RSW, Lynch PJ. Black galactorrhea as a consequence of minocycline and phenothiazine therapy. Arch Dermatol 1985; 121: 417-8. Saul SH et al. The black thyroid: Its relation to minocycline use in man. Arch Pathol Lab Med 1983; 107: 173-7. Kurosumi M, Fujita H. Fine structural aspects on the fate of rat black thyroids induced by minocycline. Virchows Arch Cell Pathol ; 1986; 51: 207-13. Burette A et al. Acute hepatic injury associated with minocycline. Arch Intern Med 1984; 144: 1491-2. Schultz JC et al. Fatal liver disease after intravenous administration of tetracycline in high dosage. N Engl J Med 1963; 269: 999-1004. Allen ES, Brown WE: Hepatic toxicity of tetracycline in pregnancy. J Obstet Gynecol 1966; 95: 12-8. Rendle-Short TJ. Tetracycline in teeth and bone. Lancet 1962; 1: 1188. Kline AH et al. Transplacental effect of tetracyclines on teeth. Med Assoc 1964; 188: 178-80. Kutscher AH et al. Discoloration of deciduous teeth induced by administrations of tetracycline antepartum. J Obstet Gynecol 1966; 96: 291-2 and pitocin.
Effect of pilocarpine-in a separate human study the effect of pilocarpine hcl was evaluated in a healthy human subject to ensure that pilocarpine indeed increases salivary gland flow.
Atonic urinary retention e.g. postoperatively ; can be treated with neostigmine a cholinomimetic Anticholine esterase ; . Enuresis and incontinence of urine can be treated with atropine substitutes e.g. oxybutinin. Atropine as well drugs with atropine-like action ; may induce urine retention in male patients with prostatic hypertrophy. 6 ; Although Ach induces vasoconstriction by direct effect on vascular smooth muscle; yet it induces more powerful vasodilatation through the release of NO from the endothelial cells. Pilocarpine nitrate may be used topically as hair tonic to increase blood supply to the hair follicles of the scalp. Secretion of all exocrine gland except the mammary gland ; is stimulated by cholinergic nerves. Drugs which act on this mechanism may be very important pharmacological tools in some diseases e.g. 1 ; Hyperhidrosis excessive sweat secretion from the hands & soles ; is treated by atropine 2 ; Excessive pulmonary secretions in orgnophosphorus poisoning can be reduced by massive doses of atropine 3 ; Excessive salivation in Parkinsonism are ameliorated by the anticholinergic antiparkinsonian atropine substitutes e.g. benzatropine and posture.
Tion, Lundbeck had agreed to carry out a post-marketing study. In the same month, Lundbeck terminated its development agreement with the Canadian company Neurochem on the development of a drug candidate for treatment of Alzheimer's disease. In December 2001, Lundbeck announced that the Swedish health authorities had approved Cipralex for treatment of both depression and panic disorder. On this basis, Lundbeck is now commencing the mutual European recognition process and therefore expects Cipralex to be launched on the European market in the first half of 2002.
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Introduction Pilocarpine is a miotic drug which acts as a muscarinic acetylcholine receptor agonist and so as a parasympathomimetic. It is used for the treatment of chronic open-angle glaucoma, ocular hypertension; emergency treatment of acute angle-closure glaucoma; to antagonize effects of mydriasis and cycloplegia following surgery or ophthalmoscopic examination. The other drug listed for the same indication is timolol. Product and dosage This product is available as pilocarpine hydrochloride eye drops, 2% or 4%; or pilocarpine nitrate 2% or 4%. For chronic open-angle glaucoma, it is given by installation into the eye, 1 drop 2% or 4% ; up to times daily. For acute angle-closure glaucoma, before surgery, it is given by installation into the eye, 1 drop 2% ; every 10 minutes for 30-60 minutes, then 1 drop every 1-3 hours until intra-ocular pressure subsides. Evidence of value Pilocarpine and timolol have around the same level of effectiveness in lowering intraocular pressure and range of adverse effects.1 However, pilocarpine is more expensive 0 for 100 x 2% 10mls, which is approximately twice as expensive as Timolol from India or the Netherlands.2 and pram.
Currently the options for publicly-donating cord blood are limited. There are certain regions of the country where this option is available. For more information on public banking, visit the Bone Marrow Foundation at bonemarrow . Looking ahead, the Federal Government, through The Institute of Medicine, has proposed a National Cord Blood Stem Cell Banking System. If this initiative is successful, it is estimated that nearly 90% of patients needing a stem cell transplant, will find an acceptably-matched, unrelated unit.
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Figure 9. Phenylurea XIAP-antagonists active Caspase-3 in Bax Bak double knockout MEF cells. Wild-type MEFs were compared with bax bak double knock-out MEFs. Cells were treated for 24 h with apoptosis-inducing agents 1396-11, 10 M; Staurosporine [STS], 500 nM ; , after which cytoplasmic proteins were extracted and Caspase activity was measured, using Ac-DEVD-AFC as the substrate. Data represent relative fluorescence units RFU ; normalized for protein concentration mean SD; n 3 and pilocarpine.
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