Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is no evidence that combination chemotherapy is superior to single agents in the treatment of advanced, hormone-resistant carcinoma of the prostate. We are reporting the preliminary results of a randomized trial comparing cyclophosphamide (CTX) with a combination of 5-fluorouracil, doxorubicin and mitomycin C (FAM'). Thirty-one patients were randomized and 30 of them were evaluable for response. Sixteen patients were treated with CTX and 14 with FAM'. On the CTX arm, eight (50%) of the patients had stable disease (SD) and eight (50%) had progressive disease (PD). On the FAM' arm, one (7%) patient had partial response (PR), five (36%) patients had SD and eight (57%) failed to respond. The difference in response rates between the two regimens was not significant (P greater than .72). The median time to progression (MTP) of all patients treated with CTX was six weeks and the MTP of patients treated with FAM' was 16 weeks (P less than .007). This difference in MTP could be explained in part by the unequal time to reevaluation between the two regimens. The MTP of the responders on CTX however, was 13 weeks, while for FAM' it was 33 weeks (P = .014). This difference suggests that FAM' has superior activity to CTX. Pain alleviation was seen in 25% of patients treated with CTX and in 64% of those treated with FAM' (P less than .01). Toxicity was tolerable on both regimens. We conclude that CTX and FAM' have similar response rates. Patients treated with FAM' enjoyed longer MTP and greater pain alleviation than those treated with CTX.
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PMID:Cyclophosphamide versus 5-fluorouracil, doxorubicin, and mitomycin C (FAM') in the treatment of hormone-resistant metastatic carcinoma of the prostate: a preliminary report of a randomized trial. 383 43

Multiple myeloma causes extensive bone remodeling. Classical biochemical markers such as urinary calcium have poor sensitivity for detecting multiple myeloma bone remodeling. New biochemicals have been developed including a carboxyterminal telopeptide of collagen I (CTX). We used an immunoenzymatic assay to determine urinary CTX in 60 patients with multiple myeloma. This marker was evaluated with regard to total pyridinolines, urinary calcium, radiological features, pain and response to treatment with bisphosphonates. In patients with bone involvement, CTX concentrations were significantly higher (+230%) than those of deoxypyridinoline (DPD) (+175%) and pyridinolines (PYD) (+130%). In all patients we have found a close correlation between CTX and DPD but not between CTX and PYD. Compared to radiological features, CTX was more sensitive (97%) and specific (96%) than DPD. After treatment by bisphosphonates, the fall in CTX concentrations was paralleled to urinary calcium and more marked than pyridinolines. Although our results need to be confirmed, CTX appears to be a potential marker to explore bone involvement in multiple myeloma.
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PMID:Comparison of urinary markers for bone resorption in multiple myeloma. 1095 74

The present study was designed to examine the possible involvement of supraspinal CTX- and PTX-sensitive G-proteins in an opioid-induced antinociception in the formalin test. Morphine (1 microg) and beta-endorphin (1 microg) given i.c.v. displayed near-maximal inhibitory effects against the formalin response in the first (0-5 min) and the second (20-40 min) phases. CTX (0.1-0.5 microg) pretreated i.c.v. produced antinociceptive effects in both phases of the formalin responses. Its effect was more pronounced in the first phase. However, PTX (0.05-0.5 microg) injected i.c.v produced the antinociceptive effect only in the first, but not the second, phase. Both CTX (0.5 microg) and PTX (0.5 microg), at the dose which had no intrinsic effect, significantly reversed the beta-endorphin-induced antinociceptive effect observed during the second, but not the first, phase. However, the antinociceptive effect by morphine failed to be affected by the same dose of treatment with CTX or PTX. Our results indicate that, at the supraspinal level, CTX- and PTX-sensitive G-proteins appear to be involved in the modulation of antinociception induced by supraspinally administered beta-endorphin, but not morphine, in the formalin pain model.
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PMID:Pretreatment with cholera or pertussis toxin differentially modulates morphine- and beta-endorphin-induced antinociception in the mouse formalin test. 1203 Aug 2

omega-Conotoxin MVIIA (CTX MVIIA) is a potent and selective blocker of the N-type voltage-sensitive calcium channel in neurons. Its analgesic and neuroprotective effects may prove useful in treatment of severe pains and ischemia. In this paper, we report that a fusion form of CTX MVIIA with thioredoxin (Trx) has analgesic function. The DNA fragments were chemically synthesized and ligated to form the DNA sequence encoding CTX MVIIA. The synthetic gene was then cloned into the expression vector pET-32a(+) and the fusion protein Trx-CTX MVIIA containing 6x His-tag was purified by one-step metal chelated affinity chromatography (MCAC). The purity of final product was over 95% determined by HPLC and the yield of the fusion protein was approximately 40 mg/L. The analgesic function was detected by using mouse hot-plate assay. After intracranially administering fusion protein with the dose of 0.6 mg/kg, marked analgesia was observed. The analgesic effects (elevated pain thresholds) were dose-dependent and the biological half-life of the fusion toxin was approximately 1.6 h.
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PMID:A fusion protein of conotoxin MVIIA and thioredoxin expressed in Escherichia coli has significant analgesic activity. 1459 43

CORRELATIONS OF BIOLOGICAL MARKERS: Ten biological markers collected from blood or urine were analysed in the ECHODIAH cohort (patients with hip OA with a 3 Years follow up). In multivariate analysis, after adjustment for age, gender, and body mass index, some markers were found to be significantly correlated with clinical and radiological parameters. C-telopeptide of type II collagen (CTX-II) was correlated with pain, functional impairment, joint space narrowing, and subchondral sclerosis. C-reactive protein was correlated with pain. N-propeptide of type I collagen (PINP) was correlated with functional impairment, and cartilage oligomeric matrix protein (COMP) was correlated with inflammation. PREDICTIVE VALUE OF BIOLOGICAL MARKERS: High levels of urinary C-telopeptide of type II collagen (uCTX-II), a marker of cartilage degradation, and serum hyaluronic acid (sAH), a marker of synovial inflammation, were associated with higher risk of structure degeneration in osteoarthritis patients. Combined assay of these two markers could help identify patients with a higher risk of radiological progression, but many questions remain to be resolved.
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PMID:[Biological markers of osteoarthritis: data from the ECHODIAH cohort]. 1522 84

A randomized, double-blind, placebo-controlled multicenter trial involving 107 men receiving bicalutamide ('Casodex') 150 mg/day therapy following radical therapy for prostate cancer assessed tamoxifen ('Nolvadex') 20 mg/day and anastrozole ('Arimidex') 1 mg/day for the prophylaxis and treatment of gynecomastia/breast pain. Tamoxifen, but not anastrozole, significantly reduced the incidence of gynecomastia/breast pain when used prophylactically and therapeutically. Serum testosterone levels increased with tamoxifen relative to placebo but prostate-specific antigen levels declined in all treatment groups. Further studies are needed to define the optimum tamoxifen dose and to assess any impact on cancer control. The use of tamoxifen in this setting remains to be investigated.
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PMID:Prevention and management of bicalutamide-induced gynecomastia and breast pain: randomized endocrinologic and clinical studies with tamoxifen and anastrozole. 1568 54

Hypovitaminosis D is common in patients with peripheral arterial disease (PAD). Subsequent secondary hyperparathyroidism and osteomalacia contribute to bone pain and myalgias, and so aggravate clinical symptoms of claudication. We evaluated 95 out of 297 patients with angiographically confirmed PAD stages II (pain in the calves and/or thighs only during exercise) or IV (history of, or presence of local ulcers) and compared them with 44 matched healthy controls regarding their medical history, bone density measurements of the femoral neck and calcaneal bone ultrasound. Bone pain, myalgias and mobility restriction as well as routine laboratory parameters, serum vitamin D [25(OH)D], crosslaps (CTX), parathyroid hormone (PTH), osteocalcin (OC) and alkaline phosphatase (AP) were recorded and analysed. 25(OH)D was significantly lower in PAD IV patients (9.6+/-4.6 ng/ml, P<0.0001) as compared to PAD II stages and controls (19.0+/-7.6 and 19.1+/-9.1 ng/ml), paralleled by lower serum calcium [2.24+/-0.02 mmol/l, P=0.0002 versus PAD II (2.36+/-0.02) and P<0.0001 versus controls (2.39+/-0.02)] and higher iPTH serum levels (66.3+/-3.6 pg/ml, P<0.0001) as compared to PAD II patients (45.3+/-3.5) and healthy controls (38.5+/-2.4). Alkaline phosphatase and serum crosslaps values were significantly higher and age-adjusted bone density and bone ultrasound measurements significantly lower in PAD IV patients, who were also twice as likely to have bone pain and myalgias as PAD II patients. Bone ultrasound measurements correlated significantly with both clinical severity and pain as well as serological parameters of bone metabolism. Underlying PAD has a significant impact on bone density and metabolism as well as on bone and muscular pain. Patients with PAD are at high risk for osteoporosis and osteomalacia and should be regularly monitored and treated for their vitamin D deficiencies.
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PMID:Hypovitaminosis D, impaired bone turnover and low bone mass are common in patients with peripheral arterial disease. 1572 36

In this study, we assessed the safety, tolerability, and effectiveness of two therapeutic regimens relating to the frequency of zoledronic acid (ZOL) infusion. Sixty adult patients with bone metastases were randomly assigned to two study groups. The first group (group A) received 4 mg ZOL every two weeks, and the second group (group B) received 4 mg ZOL every four weeks. Assessment measures included C-telopeptide (CTX) rate, the Greek Brief Pain Inventory (GBPI), the linear analogue scale assessment (LASA) of quality of life, and biochemical markers. Assessments were made at weeks 12, 24, 36, and 48. Clinical endpoints included effective decrease in bone resorption markers, pain relief and improvement of mobility status. The follow-up period was 48 weeks. No statistically significant differences between groups A and B were found in overall profile of biochemical markers, Eastern Cooperative Oncology Group (ECOG) performance status, and GBPI score at the end of the follow-up period. Assessment of bone metastases revealed a slight difference between the two groups, however this difference was not statistically significant. These findings indicate that administering zoledronic acid at four rather that two weeks has no significant impact on overall outcome.
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PMID:A prospective randomized controlled clinical trial of zoledronic acid for bone metastases. 1645 Jun 62

Objective To investigate the analgesia induced by receptin (REC), a chemically modified cobratoxin (CTX, a long-chain postsynaptic alpha -neurotoxin from Thailand cobra venom), and the effects of atropine and naloxone on antinociceptive activity of REC in rodent pain models. Methods REC was administered intraperitoneally (5 mg/kg, 7.07 mg/kg, or 10 mg/kg, i.p.) or intra-cerebral venticularly (62.5 mu g/kg, i.c.v.). The antinociceptive action was determined using the hot-plate test, the acetic acid writhing test and tail flick assay in mice and rats. The involvement of cholinergic and the opioid peptidergic systems in REC-induced analgesia were examined by pretreatment of animals with atropine (Atr; 0.5 mg/kg, i.m. or 10 mg/kg, i.p.) or naloxone (Nal; 3 mg/kg, i.p.). The effect of REC on motor activity was tested using the Animex test in mice. Results REC (5 mg/kg, 7.07 mg/kg or 10 mg/kg, i.p.) exhibited a dose-dependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. The significant analgesia of REC was seen 2 h to 3 h after its administration. In the rat-tail flick assay, the administration of REC at 62.5 mu g/kg (1/160 of systemic dose; i.c.v.) produced marked analgesic effects. Atropine at 0.5 mg/kg (i.m.), 10 mg/kg (i.p.) or naloxone at 3 mg/kg (i.p.) failed to block the analgesic effects of REC. REC at the highest effective dose of 10 mg/kg did not change the spontaneous mobility of mice. Conclusion These results demonstrate that REC has analgesic effect. This activity appears to be mediated through the peripheral nervous system though central nervous system may contribute to REC' s analgesic effects. The central cholinergic system and opioid peptidergic system appear not to be involved in the antinociceptive action of REC.
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PMID:Analgesic effects of receptin, a chemically modified cobratoxin from Thailand cobra venom. 1769 Jul 26

Although opioids are highly effective analgesics, they are also known to induce cellular adaptations resulting in tolerance. Experimental studies are often performed in the absence of painful tissue injury, which precludes extrapolation to the clinical situation. Here we show that rats with chronic morphine treatment do not develop signs of tolerance at peripheral mu-opioid receptors (micro-receptors) in the presence of painful CFA-induced paw inflammation. In sensory neurons of these animals, internalization of mu-receptors was significantly increased and G protein coupling of mu-receptors as well as inhibition of cAMP accumulation were preserved. Opioid receptor trafficking and signaling were reduced, and tolerance was restored when endogenous opioid peptides in inflamed tissue were removed by antibodies or by depleting opioid-producing granulocytes, monocytes, and lymphocytes with cyclophosphamide (CTX). Our data indicate that the continuous availability of endogenous opioids in inflamed tissue increases recycling and preserves signaling of mu-receptors in sensory neurons, thereby counteracting the development of peripheral opioid tolerance. These findings infer that the use of peripherally acting opioids for the prolonged treatment of inflammatory pain associated with diseases such as chronic arthritis, inflammatory neuropathy, or cancer, is not necessarily accompanied by opioid tolerance.
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PMID:Chronic morphine use does not induce peripheral tolerance in a rat model of inflammatory pain. 1824 98


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