Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A multiclinic double-blind controlled study was performed on the effects of MAP in both inpatients and outpatients with AMT as control drug. 1. Subjects consisted of 41 male and 45 female patients suffering from various types of depression. MAP was assigned to 42 cases and AMT to 44 cases. Of these patients, 14 MAP cases and 10 AMT cases were subsequently dropped for a variety of reasons to obtain 28 MAP cases and 34 AMT cases as evaluable. 2. The global improvement ratings were compared and found not significantly different for any week between the two treatments. 3. The global improvement ratings by the characteristic features of patients did not show any significant difference in any items studied between the two treatments. 4. The symptomatic improvement ratings (on the Hamilton R.S. for assessment by the physician) indicated that AMT was more effective on "anxiety (psychic)." 5. The symptomatic improvement ratings (on the Beck self-assessment scale by the patient) indicated that MAP was more effective on "work" and AMT on "pathos", "feeling of satisfaction", "withdrawal" and "loss of libido." 6. During the treament period, 74.3 percent of the MAP group and 76.9 percent of the AMT group of patients showed some side effects of accompanying symptoms, with no significant difference recognized between the two treatments. Itemwise, however, the incidence of tremor was significantly lower (p-=0.06) in the MAP group. Moreover, the MAP group tended to be less liable to such anticholinergic side effects as dry mouth, constipation, trouble of accomodation, urinary disturbance and palpitation. 7. On the basis of the above findings, it is concluded that MAP is as effective against depression as AMT and less liable to the anticholinergic side effects. It is, therefore, a very useful antidepressant.
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PMID:A double-blind controlled study of clinical efficacy of maprotiline and amitriptyline in depression. 35 Jul 36

Several brominated androgen derivatives were tested for their ability to inactivate microsomal aromatase from term human placenta. In the experimental protocol, the microsomal homogenate was incubated either with androstenedione or a brominated derivative of androstenedione (16alpha-bromo-6-ketoandrostenedione, 16alpha-bromoandrostenedione, 7alpha-(3'-bromoacetoxypropyl)androstenedione, 6alpha-bromoandrostenedione, or 6beta-bromoandrostenedione) and reduced nicotinamide adenine dinucleotide phosphate in a nitrogen saturated buffer composed of glycerol, ethylenediaminetetraacetic acid, and dithiothreitol in tris(hydroxymethyl)aminomethane hydrochloride (pH 7.4) under nitrogen at 4 degrees C with shaking. After the incubation period, the microsomes were recovered by centrifugation and washed once before determining aromatase specific activity. The brominated androgen derivatives which inactivated aromatase were 7alpha-(3'-bromoacetoxypropyl)androstenedione and 6alpha-bromoandrostenedione. The structures of 6alpha- and 6beta-bromoandrostenedione were unequivocally established by single crystal x-ray diffraction techniques. The extent of the enzyme inactivation by 6alpha-bromoandrostenedione was linearly proportional to the logarithm of its concentration. The evidence that this inactivation occurs at the aromatase active site is that androstenedione, when coincubated with 6alpha-bromoandrostenedione, protected aromatase from this inactivation. Progesterone provided much less protection than androstenedione. Furthermore, both 6alpha- and 6beta-bromoandrostenedione are competitive inhibitors of androstenedione aromatization, as determined by a Lineweaver-Burk plot, and 6alpha-bromoandrostenedione gives the same type I cytochrome P-450 binding spectrum with placental microsomes as androstenedione. These data suggest that 6alpha-bromandrostenedione is effective as an active-site-directed inhibitor of placental microsomal aromatase.
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PMID:Active-site-directed inactivation of aromatase from human placental microsomes by brominated androgen derivatives. 97 87

Ninety postmenopausal women with advanced breast cancer were randomly assigned to be treated with HD-MPA administered either by oral route (daily dose 900 mg) or by intramuscular injections (1 g IM daily X 5 q w during 4 consecutive weeks followed by maintenance with 1 g twice weekly). Among 78 evaluable cases, most heavily pretreated, remissions, lasting for a median duration of 11 months, were more frequent on oral (8/37 = 22%) than on IM therapy (5/41 = 12%). In both arms, high estrogen receptor levels and various clinical factors were associated with higher response rates i.e., age greater than 60, Karnofsky greater than 70, light prior systemic treatment. Side-effects, consisting mainly of weight gain, hypertension and tremor occurred with equal frequency on oral or IM treatment. Five patients complained of pain at the sites of IM injections. Thus, we recommended that, whenever possible, the oral route should be preferred. During the same study, in 20 patients (11 on oral and 9 on IM therapy), blood was drawn at 0, 30, and 60 days of treatment for the assessment of MPA and hormone levels. In both arms, at 60 days, comparable levels of circulating MPA were obtained, with a very significant drop of cortisol, androstenedione, and estrone. These endocrine results, together with our clinical data, indicate that HD-MPA therapy is active on estrogen-dependent tumors with the same specificity as that of other modalities aiming to suppress the adrenal function. Its antineoplastic action in humans could be ascribed at least in part to its suppressive action on the adrenals, resulting in a severe estrogenic deprivation in postmenopausal women.
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PMID:Oral versus intramuscular high-dose medroxyprogesterone acetate (HD-MPA) in advanced breast cancer. A randomized study of the Belgian Society of Medical Oncology. 294 41

Twenty-three evaluable patients with advanced breast cancer were treated with MPA, 1,400 mg/m2 daily PO for the first 6 months, and 500 mg/m2 daily PO thereafter. The median total dose was 191,400 mg in 88 days, with the maximum dose given to date 522,600 mg in 282 days. Most patients tolerated high-dose MPA well. Side-effects were minimal and reversible. The commonest side-effects were tremor or edema. The CR plus PR rate was five of 23 (22%). All responding patients were over 50 years of age and had a good performance status. Hormone receptor status was known in four patients only, so that no correlation between receptor status and response could be drawn. MPA appears to be a useful hormone for use in the management of breast cancer. Optimal dosage remains to be determined.
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PMID:A phase II study of high-dose medroxyprogesterone acetate in advanced breast cancer. 622 3

In this report, we present the symptoms, biochemical investigations, 24 hour ambulatory blood pressure and heart rate recordings in a patient before and following removal of a predominantly adrenaline-secreting phaeochromocytoma. The symptoms were of episodic shaking, faintness, nausea, palpitations, sweating and panic, chest and neck pain with headache, and are consistent with previous reports. Ambulatory blood pressure recording demonstrated that mean daily blood pressure was normal, with normal diurnal variation, and two episodes of severe hypertension and bradycardia coincident with symptoms (MAP 150 mmHg and HR 49 beats/minute, MAP 178 mmHg and HR 29 beats/minute, respectively), not reported in predominantly adrenaline-secreting phaeochromocytoma.
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PMID:Twenty-four hour ambulatory blood pressure and heart rate in a patient with a predominantly adrenaline secreting phaeochromocytoma. 793 55

We report 3 patients where Medroxyprogesterone Acetate (MPA = Provera) and Megestrol Acetate (Megace) in doses used for therapy of breast cancer, caused clinical hypercortisolism and Cushing's syndrome. Studies of the toxicity of Medroxyprogesterone Acetate list the commonest adverse events at 500 mg/day as weight gain, water retention, increased blood pressure, tremor, moon face, sweating, muscle cramps, vaginal bleeding and increased appetite. Glucocorticoid-like effects are seen in up to 30% of patients treated for longer than 6 weeks with mostly large doses of the order of 1500 mg/day but Cushing's syndrome has been reported in patients taking 400 mg/day. Neither the glucocorticoid-like effects or Cushing's syndrome have been previously observed with Megestrol Acetate. In the elderly female population receiving progestogens for neoplastic disease the progestogen itself could be an appreciable cause of morbidity both by causing glucocorticoid-like effects and Cushing's syndrome but also by lack of awareness of the danger of sudden withdrawal of these compounds when the hypothalmic-pituitary-adrenal (HPA) axis is suppressed. The signs and symptoms could be easily overlooked unless appropriate testing for Cushing's syndrome is carried out. While the progestogen may have to be continued indefinitely a dose decrease may be feasible with reduction of morbidity.
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PMID:Progestogens and Cushing's syndrome. 852 28

Iometopane [(123)I beta-CIT, GPI 200, RTI 55], a tropane derivative labelled with iodine-123, is a dopamine imaging agent that was under development with Guilford Pharmaceuticals (as Dopascan Injection) for the early diagnosis of Parkinson's disease. Neurochemical imaging with iometopane using conventional single photon emission computerised tomography (SPECT) provided images of the brain for the distinguished diagnosis of Parkinson's disease. The ability of iometopane to bind to the dopamine transporter on presynaptic dopaminergic nerve terminal in the striatum (caudate nucleus and putamen) has been used to differentiate the uptake of the agent by the neurons in the striatum in patients with a Parkinsonian disorder (Parkinson's disease and progressive supranuclear palsy) from patients without a Parkinsonian disorder (essential tremor and healthy controls) with high sensitivity and specificity. The diminished uptake of iometopane in the striatum on the SPECT images of patients with a Parkinsonian disorder can be applied to assess both disease trait and disease state (severity) reflected by the severity of the brain dopamine neuron loss. The rate of clinical progression of Parkinson's disease varies greatly and is currently unpredictable. Imaging with iometopane provides the opportunity to evaluate patients longitudinally from early to late disease using an objective biomarker for dopamine nerve cell degeneration. Diagnostic imaging with Dopascan Injection is thought to differentiate Parkinson's disease from other forms of tremor, eliminate tests such as MRI and CT scans, unnecessary and inappropriate medications (psychotropics), and significantly reduce the number of people remaining on Parkinson's disease medications for life, despite not having Parkinson's disease. Guilford Pharmaceuticals acquired the licence for iometopane from the Research Triangle Institute, US, and sub-licensed it to Daiichi Radioisotope Laboratories for marketing, sales and distribution in Japan, Korea and Taiwan. In July 2003, Daiichi Radioisotope Laboratories paid a milestone payment of $0.55 million to Guilford after filing an application for approval in Japan. In January 2002, Guilford signed an exclusive European development, marketing and sales and distribution agreement for iometopane with MAP Medical Technologies of Finland. Under the terms of the agreement, MAP Medical Technologies will assume responsibility for regulatory approvals, manufacturing, marketing and selling the agent in all member states of the EU and other selected markets. In return, Guilford will receive an upfront payment, milestone payments and royalties on future sales in these territories. In July 2002, MAP Medical Technologies become a subsidiary of Schering AG. In March 2002, Guilford Pharmaceuticals sublicensed iometopane to Molecular Neuroimaging LLC (MNI) of Connecticut, USA. Under the terms of the agreement, MNI will pay a royalty for each administration of iometopane, and also provide Guilford Pharmaceuticals with favourable pricing for the services (including administration of iometopane) for any clinical trials of Guilford's product candidates. This agreement will be terminated upon the US FDA's approval of the product candidate for marketing and sale in the US. Guilford has retained commercial rights to Dopascan Injection in the US. MAP Medical Technologies (Schering AG) submitted a Marketing Authorisation Application (MAA) in Finland for European approval of iometopane for the diagnosis of Parkinson's disease in April 2002. Daiichi Radioisotope Laboratories filed an application for approval of iometopane (Dopascan Injection) for the diagnosis of Parkinson's disease in Japan in July 2003. Guilford Pharmaceuticals is conducting a phase II clinical trial in 200 patients with Parkinson's disease where iometopane imaging is used to assess the effectiveness of GPI 1485, an investigational drug candidate, at baseline and at one year and two years after treatment with either GPI 1485 or placebo. The enrolment is expected to be completed in Q3 of 2003. Guint with either GPI 1485 or placebo. The enrolment is expected to be completed in Q3 of 2003. Guilford Pharmaceuticals decided not to proceed with phase III clinical trials and further development of iometopane due to its inability to contract a suitable manufacturer for the clinical and commercial supply of iometopane on acceptable conditions in the US. Guilford Pharmaceuticals obtained the patent coverage for iometopane in the US, Australia and Europe (Austria, Belgium, Switzerland, Liechtenstein, Germany, Denmark, Spain, France, the United Kingdom, Italy, Luxembourg, the Netherlands, Sweden and Greece). Separate filings were made in Finland, Norway, Japan, Canada and Korea. The manufacturing methods of Dopascan are protected by patents in the US and Europe. Dopascan is a registered trademark in the US, Canada, Europe and Asia.
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PMID:Iometopane: (123)I beta-CIT, dopascan injection, GPI 200, RTI 55. 1295 3

Both tacrolimus and mycophenolate mofetil (MMF) are potent immunosuppressive agents used in combination for prevention of acute rejection in renal transplantation. We studied the efficacy and safety of tacrolimus/MMF-based primary immunosuppression as well as their pharmacokinetics (PK) in Chinese renal transplant recipients. Oral tacrolimus was initiated at about 0.2 mg/kg/d, dose which was adjusted to achieve target trough levels of 10 to 20 ng/mL at 3 months and 5 to 10 ng/mL thereafter. The patients also received MMF (0.5 g bid) and prednisolone. PK profiles were studied at 1 week, and 1, 3, and 6 months posttransplant. Blood samples were taken at 0 (predose), 20, 40, 60, 75, and 90 minutes and 2, 4, 6, 8, 10, and 12 hours postdose for each profile. Plasma MPA and whole blood tacrolimus levels were determined by HPLC and EMIT methods respectively. Eight patients were studied with mean follow-up of 16.1 +/- 2.4 months. One patient (12.5%) experienced a borderline acute rejection episode. Both 1-year graft and patient survival rates were 100%. Posttransplant diabetes, diarrhea, and hand tremor occurred in 12.5%, 12.5%, and 37.5%, respectively. No patient had an opportunistic infection. Tacrolimus trough concentrations showed a fair correlation with AUC(0-12h) (R(2) = 0.587). Mean MPA AUC values at 1, 3, and 6 months were 40.5 +/- 9.4, 44.4 +/- 17.3, and 57.2 +/- 20.7 mug*h/mL, respectively (P = .0486, n = 7). In conclusion, primary immunosuppression with tacrolimus, low-dose MMF (0.5 g bid), and prednisolone is effective and safe with adequate systemic MPA exposure in renal transplant recipients.
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PMID:Primary immunosuppression with tacrolimus and low-dose mycophenolate mofetil in renal transplant recipients. 1551 54

The assignment of the absolute configuration of alpha-chiral primary amines by complexation of their MPA derivatives with Ba2+ and NMR analysis of the changes generated is presented. All that is required is (a) the derivatization of the amine of unknown configuration with one enantiomer of the auxiliary reagent (MPA), either (R) or (S)-alpha-methoxyphenylacetic acid, (b) the recording of the 1H NMR spectrum of the resulting amide in MeCN-d3, (c) the addition of Ba(ClO4)2 to the NMR tube, and (d) the recording of a second spectrum after a few minutes of shaking. The above steps take a few minutes and are followed by an analysis of the shifts (measured as Deltadelta(Ba)) produced on the L1 and L2 substituents of the amine by the addition of Ba2+ and their comparison with those expected from the conformational changes produced by the complexation. The conformational changes initiated by complexation have been subjected to NMR and CD studies, which showed that the formation of the complex shifts the equilibrium from an antiperiplanar (AP) to a synperiplanar (SP) form, leading to an increase of the shielding by the phenyl group of MPA of the substituent of the amine located on the same side. In addition, theoretical calculations [density functional theory (DFT)] provide further support for the formation, structure, and stability of the complexes. The general applicability of this method and the trustworthiness of the resulting configurational assignment were guaranteed with a series of amines of known absolute configuration and varied structures, used as test compounds. The method proposed is simple, fast, and inexpensive, and it requires a very small amount of sample, only one derivatization, and the recording of just two 1H NMR spectra at room temperature. A graphical guide to simplify the application of this method is included.
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PMID:Role of barium(II) in the determination of the absolute configuration of chiral amines by 1H NMR spectroscopy. 1643 30

With the combination of the gold nanoparticle (AuNP)-based visual test with hollow fiber supported liquid membrane (HFSLM) extraction, a highly sensitive and selective method was developed for field detection of mercuric ion (Hg(2+)) in environmental waters. Hg(2+) in water samples was extracted through HFSLM and trapped in the aqueous acceptor and then visually detected based on the red-to-blue color change of 3-mercaptopropionic acid-functionalized AuNP (MPA-AuNP) probe. The highest extraction efficiency of Hg(2+) was obtained by using a 600 mL sample (pH 8.0, 2.0% (w/v) NaCl), approximately 35 microL of acceptor (10 mM of 2,6-pyridinedicarboxylic acid, pH 4.0) filled in the lumen of a polypropylene hollow fiber tubing (55 cm in length, 50 microm wall thickness, 280 microm inner diameter), a liquid membrane of 2.0% (w/v) trioctycphosphine oxide in undecane, and a shaking rate of 250 rpm. The chromegenic reaction was conducted by incubating the mixture of MPA-AuNP stock solution (12 microL, 15 nM), Tris-borate buffer solution (18 microL, 0.2 M, pH 9.5), and acceptor (30 microL) at 30 degrees C for 1 h. The detection limit can be adjusted to 0.8 microg/L Hg(2+) (corresponding to an enrichment factor of approximately 1000 in the HFSLM) and 2.0 microg/L Hg(2+) (the U.S. Environmental Protection Agency limit of [Hg(2+)] for drinkable water) by using extraction times of 3 and 1 h, respectively. The proposed method is extremely specific for Hg(2+) with tolerance to at least 1000-fold of other environmentally relevant heavy and transition metal ions and was successfully applied to detect Hg(2+) in a certified reference water sample, as well as real river, lake, and tap water samples.
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PMID:Visual test of subparts per billion-level mercuric ion with a gold nanoparticle probe after preconcentration by hollow fiber supported liquid membrane. 2040


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