Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results obtained with a new hormone therapy using medroxyprogesterone acetate (MAP) in previously untested single and total doses in the treatment of advanced breast cancer are reported. Fifty-two postmenopausal patients were treated with an average total dose of 40 g of MAP for a period of 30 days. Nineteen of 44 patients (43%) had complete or partial remission, while the disease remained unchanged in nine of 44 patients (20%). Disease progression occurred in 12 of 44 patients (27%). Partial or complete remission occurred in 12 of 18 (67%) and four of six (67%) of the patients with dominant osseous and soft tissue metastases respectively. Three of ten (16%) of those with visceral metastases had remission. The average duration of remission was 7 months. Average survival times were 15.5 months for patients with remission, 8 months for those with no change, and 2.5 months for those with disease progression. From a subjective standpoint, pain was reduced significantly or disappeared in 34 of 36 patients (94%); this was also the case with respect to dyspnea (13 of 16 patients [81%]), anorexia (24 of 29 [83%]), asthenia (28 of 35 [80%]), and walking impairment (15 of 24 [63%]). When relapse occurred, patients previously treated with massive doses of MAP received further treatment with higher doses of MAP; four of 22 (18%) of the patients attained partial remission once again. Positive effects were also seen in subjective performance status, body weight, and EKG. We also describe the new clinical and toxicologic features of this treatment.
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PMID:A possible new approach to the treatment of metastatic breast cancer: massive doses of medroxyprogesterone acetate. 35 Mar 87

1. L-NG-nitro arginine methyl ester (L-NAME) administered i.p. produces anti-nociception in the mouse assessed by the formalin-induced paw licking and acetic acid-induced abdominal constriction models. The non-steroidal anti-inflammatory drug (NSAID), flurbiprofen, was similarly anti-nociceptive in both models. 2. Combination of a sub-threshold dose of L-NAME (10 mg kg-1) with increasing doses of flurbiprofen (25- 75 mg kg-1) or a sub-threshold dose of flurbiprofen (50 mg kg-1) with increasing doses of L-NAME (10- 100 mg kg-1) resulted in potentiated anti-nociception in the formalin model. Combined therapy with sub-threshold doses of L-NAME (10 mg kg-1) and indomethacin (10 mg kg-1) also resulted in significant anti-nociception. In addition, combining sub-threshold doses of L-NAME (12.5 mg kg-1) and flurbiprofen (2 mg kg-1) significantly reduced acetic acid-induced abdominal constriction. 3. L-NAME (10 mg kg-1) administered i.p. caused a significant (approximately 35%) increase in MAP in the urethane-anaesthetized mouse. Flurbiprofen (50 mg kg-1) was inactive. Combination treatment with L-NAME (10 mg kg-1) and flurbiprofen (50 mg kg-1) failed to elevate MAP above that observed with L-NAME alone. Neither L-NAME (10 mg kg-1) nor flurbiprofen (50 mg kg-1) either alone or in combination significantly altered mouse locomotor activity. 4. These results suggest that L-NAME and flurbiprofen/indomethacin act synergistically in their anti-nociceptive action in the mouse. Combination therapy with L-NAME and flurbiprofen and a similar NSAID may provide an alternative to the clinical control of pain in man.
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PMID:Synergistic anti-nociceptive effect of L-NG-nitro arginine methyl ester (L-NAME) and flurbiprofen in the mouse. 139 74

Forty elderly patients, scheduled for orthopaedic surgery of the hip or knee were studied. Twenty patients received a single-dose spinal anaesthesia with 3 ml of plain 0.5% bupivacaine (SDSA group). Twenty patients received continuous spinal anaesthesia using a 32- or 22-gauge catheter. A bolus of 1.0 ml of plain 0.5% bupivacaine was given to ten patients and 0.5 ml to another ten, continued by an infusion at a rate of 2 ml/h. The spread of analgesia and haemodynamic changes (central venous pressure, arterial pressures, need for sympathomimetic medication) were registered. The mean dose of bupivacaine was 2.9 ml (range 1.5-5 ml) in the CSA group (3.0 ml in the SDSA group). Eight patients in the CSA group needed medication for pain during surgery compared to five patients in the SDSA group (n.s.). The median level of pinprick analgesia at 60 min was T11 in the CSA and T6.5 in the SDSA group (P less than 0.01). The mean maximum decreases in CVP and MAP were quite similar in the CSA and SDSA group (2.1 vs 2.8 mmHg (0.3 vs 0.4 kPa) and 17 vs 21 mmHg (2.3 vs 2.8 kPa), respectively) (n.s.). Six patients in the SDSA group and four patients in the CSA group needed sympathomimetic medication. It is concluded that titration of bupivacaine for spinal anaesthesia caused only minor haemodynamic changes which were similar to those after single-dose spinal bupivacaine.
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PMID:Haemodynamic changes during spinal anaesthesia with slow continuous infusion or single dose of plain bupivacaine. 151 36

Forty premenopausal patients with advanced breast cancer entered a prospective and randomized study in which high-dose medroxyprogesterone acetate (HD MAP) and oophorectomy (OPX) were compared. All the patients were first treated for advanced disease. Twenty-two patients received HD MAP (1,000 mg b.i.d. p.o.) and 18 patients received OPX. Complete remission (CR) was achieved in 2 (9%) in the HD MAP group and in 2 (11%) in the OPX group for a duration of 20-24 and 30-54 months respectively. Partial remission (PR) was achieved in 10 (45%) patients in the HD MAP group and in 4 (22%) patients in the OPX group for a median duration of 9 and 7 months respectively. The objective response rates (CR + PR) were 55% for the HD MAP group and 33% for the OPX group (p = 0.17). Ten patients who received OPX as first-line treatment received HD MAP when the disease progressed and were evaluable for response: PR was achieved in 6 patients (2 responders and 4 nonresponders to OPX) for a median duration of 5 months. Two out of 4 patients who received OPX at progression after objective response to HD MAP presented PR. HD MAP induced a significant decrease in pain intensity and, compared to OPX, a more frequent improvement was induced in performance status. No difference was observed between the two groups in terms of overall survival. This study shows that HD MAP is an active treatment in premenopausal patients with advanced breast cancer and that it can induce a response in some patients resistant to OPX.
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PMID:High-dose medroxyprogesterone acetate versus oophorectomy as first-line therapy of advanced breast cancer in premenopausal patients. 182 98

When we initially used high doses of MAP (greater than 500 mg/day/im or greater than 2000 mg/day p.o.) in advanced cases of breast cancer, we noticed that, even before objective remission became apparent, the treatment induced subjective remission and a strong analgesic effect. Overall, our breast cancer patients treated with MAP at high doses (300 patients) showed a 65% incidence of pain relief. The analgesic effect of MAP does not seem to be closely related to its antitumour effect, because the same effect was also observed in patients with hormone-insensitive tumours. Our pharmacokinetic studies have demonstrated that it is important to use high doses in order to obtain high plasma levels. In order to clarify the mode of action of this MAP analgesy, hot-plate, tail-flick, Randall, writhing and carrageenin-oedema tests were carried out on rats. We found no evidence for central or peripheral analgesic activity, but there was evidence for an antiinflammatory activity of MAP.
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PMID:Analgesic activity of medroxyprogesterone acetate (MAP) in cancer patients: an antiinflammatory mediated activity? 293 9

Twenty-six patients with metastatic breast cancer were treated with high dose medroxyprogesterone acetate (MAP) p.o. according to currently available pharmacokinetic data (2000 mg/day b.i.d. for 30 days, 1000 mg/day for the following 60 days). Objective response (WHO criteria) was obtained in seven patients (CR + PR = 27%), with good results on visceral and soft tissue localizations; performance status improvement and/or pain relief was obtained in twenty-three (88%). Oral high dose MPA seems to be an effective and well tolerated palliative treatment in advanced breast cancer.
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PMID:Oral route administration of medroxyprogesterone acetate (MAP) at high doses in the treatment of advanced breast cancer: clinical results. 624 48

Naloxone has been used as a pharmacological tool to investigate the role of endorphins and opiate receptors in the cardiovascular pathophysiology of shock. It would appear that endorphins act on opiate receptors to contribute to the abnormalities found and that naloxone improves survival as well as cardiovascular function in shock. Preliminary studies in humans and the subhuman primate create cautious optimism regarding the clinical application of this information. Naloxone has served us well as a key to unlock the involvement of endorphins and opiate receptors in shock. However, further advances in our understanding may depend on the development and use of opiate receptor agonists and antagonists specific for the different opiate receptors described, each subserving different functions. Naloxone's disadvantage of increasing pain awareness may limit its clinical usefulness but might be overcome by using drugs that reverse the behavioral and neuroendocrine changes produced by beta-endorphin without altering pain relief. Thyrotropin-releasing hormone (TRH) is just such a "physiological" opiate antagonist which has been shown to increase MAP in experimental endotoxic and hemorrhagic shock [32].
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PMID:Naloxone in endotoxic shock: experimental models and clinical perspective. 630 74

We evaluated 2-chloroprocaine, three per cent, in 44 women having epidural anaesthesia for Caesarean section. All subjects received a minimum dose of 25 ml (750 mg) in increments designed to allow early recognition of accidental subarachnoid or intravascular injection. Further increments were given as needed to achieve a T5 sensory level or higher. We recorded pulse and blood pressure at two-minute intervals and used a simple pain scale to assess analgesia. Ninety-three per cent of subjects had acceptable analgesia. Seventeen mothers required more than 25 ml to attain a T5 level; subjects having a BMI (body mass index) equal to or greater than 35, or over 35 years of age, demonstrated more cephalad spread. Hypotension (MAP 80 per cent of control or less) occurred in 24, mothers (54 per cent), often transiently, but an infused fluid volume exceeding 30 ml X kg-1 at delivery significantly reduced post-delivery hypotension. Nausea and vomiting accompanied the hypotension in 12 mothers. No neonatal depression occurred. We conclude the incremental administration of chloroprocaine, as described, permits safe administration of the drug, with excellent analgesia in most parturients.
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PMID:Three per cent 2-chloroprocaine for caesarean section: appraisal of a standardized dose technique. 649 71

The antinociceptive efficacy of different opioid-receptor agonists following their intrathecal (i.t.) administration was examined in awake, unanesthetized rats in a model of visceral pain. Cumulative i.t. doses of the mu-preferring opioid-receptor agonist morphine produced dose-dependent attenuation of the change (increase) in mean arterial pressure (delta MAP) and elevation of the visceromotor threshold to colorectal distension (CRD). Similar dose-dependent antinociceptive effects were produced after i.t. administration of the mu opioid-receptor-selective agonist DAMPGO. Morphine and DAMPGO were equipotent against the delta MAP to phasic CRD (80 mm Hg, 20 sec), but DAMPGO was more than 6 times more potent than morphine in elevating the visceromotor threshold to an incrementing CRD. Intrathecal administration of the delta opioid-receptor-selective agonist DPDPE produced, like morphine and DAMPGO, a dose-dependent attenuation of the delta MAP to CRD; DPDPE was one-tenth as potent as morphine or DAMPGO. DPDPE also dose-dependently elevated the visceromotor threshold to CRD, but its efficacy was only half that of morphine or DAMPGO. The kappa opioid-receptor-selective agonist U 50488H was without antinociceptive efficacy after i.t. administration, but did attenuate responses to CRD after systemic administration. The antinociceptive effects produced by morphine and DAMPGO were antagonized by i.t. pretreatment with naloxone and the effects produced by DPDPE were antagonized by i.t. pretreatment with the delta opioid-receptor-selective antagonist naltrindole. These data indicate that local mu and delta, but not kappa, opioid receptors can modulate visceral nociceptive transmission in the spinal cord.
Pain 1995 Oct
PMID:Spinal mu and delta, but not kappa, opioid-receptor agonists attenuate responses to noxious colorectal distension in the rat. 857 89

Touch-evoked allodynia, an important symptom of clinical neural injury pain, can be modelled acutely and reversibly in the urethane-anesthetized rat using intrathecal (i.t.) strychnine (STR). Allodynia, after i.t. STR (40 micrograms), is manifest as a significant enhancement of cardiovascular and motor responses evoked by normally innocuous brushing of the hair (hair deflection), as compared to responses evoked by either hair deflection after i.t. saline (SAL), or to i.t. STR (40 micrograms) with no tactile stimulus. The present study investigated: (1) the pharmacology of afferent neural inputs involved in STR-dependent allodynia using neonatal capsaicin and the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX); and (2) the effect of i.t. STR on responses evoked by peripheral noxious stimulation. Neonatal capsaicin (25 mg/kg, s.c., post-natal day (PND) 1, and 50 mg/kg, s.c., PND 2, 3, 4, 11, 25, 55 and 85) significantly attenuated the responses evoked by noxious mechanical, thermal or chemical stimuli, but had no effect on STR-dependent allodynia. All hair deflection-evoked, STR-dependent responses were dose-dependently inhibited by i.t. NBQX. The ED50 values and 95% confidence intervals were 10.4 micrograms (5.5-19.6) for the motor withdrawal response, 14.4 micrograms (8.6-24.0) for changes in MAP and 12.2 micrograms (6.8-21.8) for changes in HR. Cortical EEG synchrony was unchanged by i.t. NBQX confirming its spinal locus of action. Intrathecal STR neither reduced nor enhanced the responses elicited by noxious stimuli in capsaicin- or vehicle-pretreated rats. These results indicate that STR-dependent allodynia is initiated by primary afferents not normally involved in nociception (possibly A beta-fibers), and that STR-sensitive modulation in the spinal cord is selective for non-noxious sensory input. The sensitivity of STR-dependent allodynia to non-NMDA receptor antagonists, and the failure of i.t. STR to produce hyperalgesia to mechanical, thermal or chemical noxious stimuli, confirm the independence of nociceptive pathways and STR-sensitive afferent inputs in this model.
Pain 1996 Aug
PMID:Strychnine-sensitive modulation is selective for non-noxious somatosensory input in the spinal cord of the rat. 888 Aug 56


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