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)

The effect of the non-steroidal analgesic diflunisal on platelet aggregation and clinical haemorrhage at a dosage 250 mg twice or 3-times daily, sufficient to relieve musculo-skeletal pain and other painful conditions, was studied in 15 patients and 5 normal subjects. Platelet aggregation was carried out with ADP and collagen before and during treatment with diflunisal. The results indicated that diflunisal is an effective analgesic with no significant adverse effect on platelet function or clinical bleeding.
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PMID:Platelet aggregation in patients treated with diflunisal. 736 51

Three patients (two of them siblings) presented with easy fatiguability and prominent postexercise pain. Muscle biopsy showed that large areas of about one third of the type II fibers were completely devoid of mitochondria. The remaining mitochondria were unusually large in size, but otherwise normal ultrastructurally. In two patients, 31P in vivo MRS showed low phosphocreatine (PCr), high ADP, low phosphorylation potential at rest and slow ADP and PCr recovery after aerobic exercise. This appears to be a pathologically unique form of metabolic myopathy. The cause of the focal mitochondrial depletion is not known. It should be distinguished from the mtDNA depletion syndrome in which muscle mitochondria are not reduced, but proliferate.
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PMID:Familial myopathy with conspicuous depletion of mitochondria in muscle fibers: a morphologically distinct disease. 776 93

A double-blind, placebo-controlled randomized study with BAY U3405, a specific thromboxane A2 (TX A2) receptor blocker, was performed in patients suffering from severe stade II limb arteriopathy. BAY U3405 or placebo was administered in 16 patients at 20 mg four times a day (from day 1 to day 3). Hemostatic studies were done before therapy, and on day 2 and day 3 under therapy. On day 3, BAY U3405 was shown to induce a highly statistically significant decrease of the velocity and the intensity of the aggregations mediated by arachidonic acid (56 +/- 37% for the velocity, 58 +/- 26% for the intensity) or by U46619 endoperoxide analogue (36 +/- 35% for the velocity, 37 +/- 27% for the intensity). Similar results were already observed on day 2. By contrast, such a decrease was not noticed with ADP mediated platelet aggregation. Furthermore, plasma levels of betathromboglobulin and platelet factor 4 remained unchanged. Peripheral hemodynamic parameters were also studied. The peripheral blood flow was measured using a Doppler ultrasound; the pain free walking distance and the total walking ability distance were determined under standardized conditions on a treadmill. These last two parameters show a trend to improvement which nevertheless was not statistically significant. All together these results encourage further in vivo studies using BAY U3405 or related compounds on a long-term administration.
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PMID:Ex vivo inhibition of platelet aggregation in patients with severe limb arteriopathy treated with BAY U3405, a specific TX A2 receptor antagonist. 790 69

A 74-year-old man was admitted because of swelling, pain and ecchymosis in the night lower extremity. A blood analysis revealed that Hb was 11.8g/dl, WBC 37,600/microliters, and platelet count 137.1 x 10(4)/microliters. The NAP value was high. Bone marrow examination disclosed marked megakaryocytic hyperplasia. Chromosomal analysis revealed 47, XY, +9. Hemostatic data were within normal ranges, but the 2nd aggregation of platelet by ADP was diminished. The serum beta-TG was 159, PF-4 56ng/ml, B12 1,100, UB12 BC 1,800pg/ml. Gastric fiberoscopy revealed gastric cancer and CT scan disclosed marked splenomegaly. Essential thrombocythemia (ET) coexisting with gastric cancer was diagnosed based on these examinations. He was treated with anti-platelet agents, busulfan and tegafur uracil, however thromboembolic symptoms suggesting central nervous system and peripheral vascular ischemia and gastrointestinal bleeding occurred. Among diagnostic criteria for ET established by the polycythemia vera study group, there is a category "No known cause for reactive thrombocytosis." The case reported here had gastric cancer which may have contributed to the elevated platelet count, however this case could be diagnosed as ET coexisting with gastric cancer because of the above various clinical signs and laboratory results. Although then are few reports of the coexistence of other malignancies in ET, there may be many more similar cases because of the age preponderance in ET. In order to diagnose ET more precisely, more strict diagnostic criteria are needed.
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PMID:[Coexistence of essential thrombocythemia and gastric cancer]. 849 22

General pharmacological effects of recombinant human basic fibroblast growth factor (bFGF) were investigated. 1. Central nervous system: Basic FGF produced almost no effect on the general symptoms and behaviors of mice. Basic FGF did not influence the spontaneous motor activity, hexobarbital-induced anesthesia, electroshock seizure threshold, pentylenetetrazole-induced seizure in mice and normal body temperature and spinal reflex in rats up to a dose of 1 mg/kg (s.c., i.v.). As regards pain sensation, it inhibited the acetic acid-induced writhing at 1 mg/kg (s.c.). No abnormal waves were observed in spontaneous EEG of the rabbit up to 1 mg/kg (i.v.) of bFGF, but at 0.1 mg/kg it had a slight effect on the ratio of EEG levels and at 1 mg/kg induced an increase in rest period, disappearance in the period of fast wave sleep and a decrease in the period of deep sleep. 2. Somatic nervous system: Basic FGF did not influence the corneal reflex, twitch response of the skin and diaphragm-phrenic nerve preparations. 3. Autonomic nervous system and smooth muscle: Basic FGF showed little effects on the spontaneous movement of the isolated ileum, contraction induced by various agonists in isolated ileum, resting tension and noradrenaline(NA)-induced contraction of the aorta, resting tension and histamine-induced contraction of isolated trachea, spontaneous movement and 5-HT-induced contraction of isolated strips of stomach fundus, NA-induced contraction of isolated vas deferens of the rat up to the concentration of 10(-4) g/ml. Basic FGF augmented the tone of the isolated non-pregnant uterus at the concentrations of 10(-5) g/ml and above and inhibited or tended to inhibit the contractile tension of non-pregnant or pregnant uterus at 10(-4) g/ml, but it did not influence the spontaneous movement of the uterus, either the non-pregnant or pregnant, under in situ conditions even at a dose of 1 mg/kg (i.v.). Basic FGF did not influence the pupil size. 4. Respiratory and circulatory systems: Basic FGF had no effect on the isolated heart. The influence was not exerted on the heart rate for the isolated atria but slight inhibition of contractile force was observed at 10(-4) g/ml. In anesthetized dogs a decrease in blood pressure, a slight increase in heart rate and respiratory rate and a decrease in femoral blood flow were observed at 0.01 and 0.1 mg/kg (i.v.) of bFGF Similarly, a slight increase in heart rate and a slight decrease of blood pressure were observed at 1 mg/kg (s.c.) in conscious rats. 5. Digestive system: Administration of bFGF at 1 mg/kg did not result in changes in the transport capacity within the gastrointestinal tract (s.c., i.v.) and the secretion of the gastric juice (s.c.). 6. Urine output and electrolyte metabolism: Basic FGF produced a decrease in urinary Na+ excretion at 1 mg/kg (s.c.), and showed a tendency to increase in urinary volume at 0.01 and 0.1 mg/kg (i.v.). At 1 mg/kg (i.v.) urinary excretion of Na+ and Cl- was decreased significantly. It had no effect on the ability of rats to excrete PSP (phenol red) up to 1 mg/kg (s.c.). 7. Blood system: Basic FGF did not influence the coagulation time of the whole blood, prothrombin time and activated partial thromboplastin time of rats up to 1 mg/kg (s.c., i.v.). It did not influence the aggregation of rabbit platelets induced by collagen and ADP up to 10(-4) g/ml. Basic FGF at concentration of 10(-4) g/ml exhibited no hemolytic action. 8. Local action: Plantar subcutaneous injection of bFGF at above 0.005 mg/site induced edema by itself on and after the next day, and also reinforced carrageenin-induced edema from 1 day after injection. The results show that bFGF did not produce any acute effects on the somatic nervous system, autonomic nervous system, smooth muscle and blood system. In contrast, bFGF produced slight effects on the circulatory system, central nervous system and kidney function when injected systemically. Subcutaneous administration may produce edema at the s
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PMID:General pharmacology of recombinant human basic fibroblast growth factor. 884 46

The impairment of endothelial function in hypercholesterolaemic animals and humans is known to be reversed by intravenous infusions of L-arginine (L-ARG), the precursor of NO. 22 patients with peripheral arterial obstructive disease (PAOD) received L-ARG (60 mmol) as intravenous infusions, each lasting three hours, daily for seven consecutive days. This treatment resulted in elongation of the painfree and maximum walking distances, as well as shortening of the period of time required for pain relief after walking the maximum distance. A rise in the ankle/arm pressure ratio (AAPR) was associated with an increase of arterial blood flow in both calves. The transcutaneous oxygen tension (tcpO2) in the ischaemic foot was also increased. After the 1st and the 7th infusion of L-ARG the spontaneous (PAR) as well as the ADP- and collagen-induced platelet aggregation were suppressed, the euglobulin clot lysis time (ECLT) shortened, plasma levels of platelet activator inhibitor (PAI) decreased, and cGMP levels increased. These data indicate beneficial effects of L-ARG as a therapeutic agent in patients with PAOD. We presume that in these patients high doses of exogenous L-ARG can be partially converted to NO.
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PMID:Treatment with L-arginine is likely to stimulate generation of nitric oxide in patients with peripheral arterial obstructive disease. 886 84

Pertussis toxin (PTX), which causes the ADP-ribosylation and thereby inactivation of Gi-proteins, has been employed in analgesia testing to elucidate receptors that are coupled to inhibitory G-proteins, such as the mu-opioid receptor. Consistent with previous findings, the antinociceptive effects of morphine (1-10 microg) as measured by tail-flick latency using a 55 degrees C water bath, were blocked by a single intrathecal injection of 0.5 microg PTX 6 days prior to intrathecal morphine administration. In addition, mice treated intrathecally with 0.5 microg of PTX had significantly shorter baseline tail-flick latencies compared with vehicle treated mice using a 55 degrees C water bath when tested 6 days after PTX or vehicle administration. Morphine-induced antinociception was blocked in a dose-dependent manner by PTX with complete blockade of morphine following a 0.3-microg dose of PTX. Further, mice administered 0.1 microg or 0.3 microg PTX intrathecally had significantly shorter tail-flick latencies compared with vehicle injected mice using a 40, 45 or 50 degrees C water bath when tested 7 days after intrathecal injection. Shorter tail-flick latencies were observed at 45 degrees C as early as 48 h after intrathecal administration of 0.03, 0.1 or 0.3 microg PTX and these shorter tail-flick latencies were observed up to 90 days after intrathecal PTX administration. The intrathecal administration of PTX caused hyperalgesia and allodynia that appears similar to the symptoms reported by patients suffering from neuropathic pain, and suggests that deficiencies in inhibitory systems, as compared with increases in excitatory systems, may play a role in the pathophysiology of at least some central or neuropathic pain states.
Pain 1997 Apr
PMID:Intrathecal pertussis toxin produces hyperalgesia and allodynia in mice. 915 Feb 97

Misoprostol, the oral analogue of alprostadil was used for the treatment of 20 patients (aged 40-60) with peripheral arterial disease according to Fontaine's classification at stages IIa and IIb (PAD). All patients received 200 micrograms of misoprostol 3 times a day during a month. The therapy with misoprostol resulted in a clinical improvement in all patients. Elongation of pain free (before treatment 129 m +/- 78 m, after treatment 214 m +/- 109 m) and maximum walking distance (before treatment 304 m +/- 169 m, after treatment 471 m +/- 264 m) was observed. At the same time a shortening of the pain duration was noted (before treatment 100 sec +/- 37 sec, after treatment 71 sec +/- 23 sec). The ankle/arm pressure ratio (AAPR) and arterial blood flow increased in both limbs after 4 weeks of the treatment. Activation of the fibrinolytic system was seen in the course of the therapy (shortening of euglobulin clot lysis time-ECLT and increase in t-PA activity). The platelets became less sensitive to ADP and collagen after intake of misoprostol. The results justify administration of misoprostol as a new therapeutic agent for the treatment of patients with PAD.
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PMID:[Misoprostol--oral prostanoid--the first clinical trial for use in patients with peripheral vascular disease]. 948 Apr 58

The G protein Go is highly expressed in neurons and mediates effects of a group of rhodopsin-like receptors that includes the opioid, alpha2-adrenergic, M2 muscarinic, and somatostatin receptors. In vitro, Go is also activated by growth cone-associated protein of Mr 43,000 (GAP43) and the Alzheimer amyloid precursor protein, but it is not known whether this occurs in intact cells. To learn about the roles that Go may play in intact cells and whole body homeostasis, we disrupted the gene encoding the alpha subunits of Go in embryonic stem cells and derived Go-deficient mice. Mice with a disrupted alphao gene (alphao-/- mice) lived but had an average half-life of only about 7 weeks. No Goalpha was detectable in homogenates of alphao-/- mice by ADP-ribosylation with pertussis toxin. At the cellular level, inhibition of cardiac adenylyl cyclase by carbachol (50-55% at saturation) was unaffected, but inhibition of Ca2+ channel currents by opioid receptor agonist in dorsal root ganglion cells was decreased by 30%, and in 25% of the alphao-/- cells examined, the Ca2+ channel was activated at voltages that were 13.3 +/- 1.7 mV lower than in their counterparts. Loss of alphao was not accompanied by appearance of significant amounts of active free betagamma dimers (prepulse test). At the level of the living animal, Go-deficient mice are hyperalgesic (hot-plate test) and display a severe motor control impairment (falling from rotarods and 1-inch wide beams). In spite of this deficiency, alphao-/- mice are hyperactive and exhibit a turning behavior that has them running in circles for hours on end, both in cages and in open-field tests. Except for one, all alphao-/- mice turned only counterclockwise. These findings indicate that Go plays a major role in motor control, in motor behavior, and in pain perception and also predict involvement of Go in Ca2+ channel regulation by an unknown mechanism.
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PMID:Multiple neurological abnormalities in mice deficient in the G protein Go. 950 Dec 52

An acidic antitumor glycoprotein (SAGP) was purified from a crude extract of Streptococcus pyogenes, Su strain. Intraperitoneal injection with SAGP (20 mg protein/kg/day for 4 consecutive days) prolonged the life span of mice inoculated i.p. with Ehrlich ascite carcinoma cells and methylcholanthrene-induced fibrosarcoma cells (Meth A) up to 244% and 169% of that of the control mice, respectively. These in vivo antitumor effects were reduced in immunosuppressed mice. The effector spleen cells from the Meth A-inoculated and SAGP-injected mice showed a considerable cytostatic activity on Meth A cells in vitro, and immunosuppression studies suggested that carrageenan-sensitive and/or asialo-GM1 positive spleen cells are responsible for the in vivo antitumor effect of SAGP. SAGP inhibited the cell growth of cultured cell lines including transformed hamster embryonic lung cells, murine leukemia L 1210, Meth A and human promyelocytic leukemia HL60 cells. The IC50s for the cell growth of these cells were all below 0.1 microg protein/ml. SAGP inhibited the incorporation of nucleic acid precursors into Meth A cells. It seems that sulfhydryl groups of the SAGP molecule are essential for the expression of the antitumor action of SAGP. The cell growth-inhibitory activity of SAGP was diminished in Meth A cells preincubated with pertussis toxin (IAP), whereas it was augmented in the cells preincubated with cholera toxin (CTX), suggesting the involvement of toxin-sensitive GTP (G)-proteins in the SAGP-action. IAP and CTX-catalyzed ADP ribosylation assays confirmed that SAGP augmented the activity of IAP-sensitive G-protein. In addition, this augmentation was detected neither in Meth A cells incubated with heat-inactivated SAGP nor in SAGP-insensitive L929 cells. SAGP induced apoptosis in Meth A and HL60 cells as assessed by DNA fragmentation. A single dose injection of SAGP (100 mg protein/kg, i.v., s.c., or i.p.) into mice produced no toxic signs except occasional pain responses observed for one week after the injection. Thus, SAGP is a low toxic substance that shows in vivo antitumor activity by modulating immune responses of the host, and also exhibits in vitro cell-growth inhibition through IAP-sensitive G-protein.
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PMID:Characterization of a streptococcal antitumor glycoprotein (SAGP). 951 6


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