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)

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

Misoprostol, the oral analogue of alprostadil, was used to treat 20 patients (aged 40-60 years) with peripheral arterial disease (PAD) according to Fontaine's classification at stages IIa and IIb. All patients received 200 micrograms of misoprostol 3 times a day during a month. The therapy with misoprostol resulted in 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 duration of pain 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 treatment. Activation of the fibrinolytic system was seen in the course of 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:Treatment of peripheral vascular disease with misoprostol (Cytotec): a pilot study. 970 83

Cilostazol is an antiplatelet agent with vasodilating properties that has been used in the treatment of patients with peripheral ischaemia such as intermittent claudication. The drug inhibits platelet aggregation induced by ADP, collagen and arachidonic acid. Unlike aspirin (acetylsalicylic acid), cilostazol inhibits both primary and secondary aggregation. It also acts as a vascular vasodilator by inhibiting calcium-induced contractions while having no direct effect on contractile proteins. In double-blind randomised trials, patients with intermittent claudication receiving cilostazol showed significant improvements versus placebo in terms of time to initial pain and maximal walking or absolute claudication distance; these findings were confirmed by cilostazol patients' positive responses on subscales measuring physical functioning and quality of life. In a 24-week randomised double-blind trial in patients with intermittent claudication, cilostazol 100mg twice daily produced significant improvements in pain-free and maximum walking distances, compared with pentoxifylline (oxpentifylline) 400mg 3 times daily and placebo. Cilostazol has been well tolerated, with the most common adverse events being headache, diarrhoea, abnormal stools and dizziness.
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PMID:Cilostazol. 1006 9

Compelling evidence has accumulated over the last several years from our laboratory, as well as others, indicating that central hyperactive states resulting from neuronal plastic changes within the spinal cord play a critical role in hyperalgesia associated with nerve injury and inflammation. In our laboratory, chronic constriction injury of the common sciatic nerve, a rat model of neuropathic pain, has been shown to result in activation of central nervous system excitatory amino acid receptors and subsequent intracellular cascades including protein kinase C translocation and activation, nitric oxide production, and nitric oxide-activated poly(ADP ribose) synthetase activation. Similar cellular mechanisms also have been implicated in the development of tolerance to the analgesic effects of morphine. A recently observed phenomenon, the development of "dark neurons," is associated with both chronic constriction injury and morphine tolerance. A site of action involved in both hyperalgesia and morphine tolerance is in the superficial laminae of the spinal cord dorsal horn. These observations suggest that hyperalgesia and morphine tolerance may be interrelated at the level of the superficial laminae of the dorsal horn by common neural substrates that interact at the level of excitatory amino acid receptor activation and subsequent intracellular events. The demonstration of interrelationships between neural mechanisms underlying hyperalgesia and morphine tolerance may lead to a better understanding of the neurobiology of these two phenomena in particular and pain in general. This knowledge may also provide a scientific basis for improved pain management with opiate analgesics.
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PMID:Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions. 1039 89

Pathophysiologic mechanisms in syndrome X (anginal chest pain, positive exercise stress test, and angiographically normal coronary arteries) have been extensively studied. Recent reports suggest an ischemic origin of the pain to be less probable. Other contributing mechanisms that have been hypothesized are enhanced sympathetic drive or sensitivity or an abnormal muscle metabolism. Our aim in this study was to characterize exercise performance, skeletal muscle characteristics, and sympathetic control of blood flow in patients with syndrome X. Seven female patients aged 50 to 65 years and 5 matched controls were tested. Exercise test was performed according to clinical routine. Plasma catecholamine and blood lactate levels were measured before, during, and after exercise. Autonomic blood flow control was measured plethysmographically in the resting contralateral forearm during isometric handgrip. Muscle biopsy specimens were obtained at rest from the lateral part of Musculus vastus at midthigh. The biopsy samples were investigated for the relative number of different fiber types, phosphagen content, and energy charge, calculated as (adenosine triphosphate +/- 1/2 adenosine diphosphate)/[adenosine triphosphate +/- adenosine diphosphate +/- adenosine monophosphate]). Exercise capacity was markedly decreased in syndrome X compared with controls (85 +/- 14 vs 156 +/- 11 W, p <0.0005) and all patients discontinued exercise because of chest pain (Borg CR-10, 5 +/- 3). Peak heart rate was lower in syndrome X (150 +/- 18 vs 176 +/- 7 beats/min, p <0.01), whereas systolic blood pressure and double product did not differ. Peak norepinephrine plasma levels were lower than in controls (11 +/- 6 vs 24 +/- 13 nmol/L, p <0.04), whereas peak blood lactate levels did not differ. Blood flow increase in the resting forearm during isometric handgrip was similar to that in controls. The proportion of different fiber types, phosphagen content, and energy charge were normal. Thus, patients with syndrome X have a reduced physical exercise capacity but no skeletal muscle abnormalities. Catecholamine hypersensitivity may contribute to their condition.
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PMID:Impaired exercise performance but normal skeletal muscle characteristics in female syndrome X patients. 1042 36

Adenosine produces analgesia in the spinal cord and can be formed extracellularly through enzymatic conversion of adenine nucleotides. A transverse push-pull microprobe was developed and characterized to sample extracellular adenosine concentrations of the dorsal horn of the rat spinal cord. Samples collected via this sampling technique reveal that AMP is converted to adenosine in the dorsal horn. This conversion is decreased by the ecto-5'-nucleotidase inhibitor, alpha,beta-methylene ADP. Related behavioral studies demonstrate that AMP administered directly to the spinal cord can reverse the secondary mechanical hyperalgesia characteristic of the intradermal capsaicin model of inflammatory pain. The specific adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) inhibits the antihyperalgesia produced by AMP. This research introduces a novel microprobe that can be used as an adjunct sampling technique to microdialysis and push-pull cannulas. Furthermore, we conclude that AMP is converted to adenosine in the dorsal horn of the spinal cord by ecto-5'-nucleotidase and subsequently may be one source of adenosine, acting through adenosine A(1) receptors in the dorsal horn of the spinal cord, which produce antihyperalgesia.
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PMID:A novel transverse push-pull microprobe: in vitro characterization and in vivo demonstration of the enzymatic production of adenosine in the spinal cord dorsal horn. 1114 97

The bark of Salix species contains several prodrugs of salicylate, mainly salicin. The aim of this study was to investigate if during pain treatment with Salicis cortex extract platelet aggregation was affected. A total of 51 patients were enrolled in the study. Thirty-five patients suffering from acute exacerbations of chronic low back pain received randomly and double-blind either Salicis cortex extract with 240 mg salicin/day (n = 19) or placebo (n = 16). Further sixteen patients with stable chronic ischemic heart disease were given 100 mg acetylsalicylate per day. Platelet aggregation was studied using an aggregometer. As aggregating agents, arachidonic acid (500 micrograms/ml), adenosine di-phosphate (2 x 10(-5) M) and collagen (0.18 microgram/ml) were used. The mean maximal arachidonic acid induced platelet aggregation was 61%, 78% and 13% in the Salicis cortex extract, placebo and acetylsalicylate groups. Acetylsalicylate had a significant inhibitory effect on platelet aggregation compared to Salicis cortex extract (p = 0.001) and placebo (p = 0.001). There was also a significant difference between the placebo and the willow bark-treated groups in the maximal platelet aggregation induced by arachidonic acid (p = 0.04) and ADP (p = 0.01). No statistical difference was found between the groups when collagen was applied to the human platelets. Daily consumption of Salicis cortex extract with 240 mg salicin per day affects platelet aggregation to a far lesser extent than acetylsalicylate. Further investigation needs to clarify if this finding is of clinical relevance in patients with impaired thrombocyte function.
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PMID:Effect of salicis cortex extract on human platelet aggregation. 1134 89

The concept of a purinergic signalling system, using purine nucleotides and nucleosides as extracellular messengers, was first proposed over 30 years ago. After a brief historical review and update of purinoceptor subtypes, this article focuses on the diverse physiological roles of adenosine triphosphate, adenosine diphosphate, uridine triphosphate and adenosine. These molecules mediate short-term (acute) signalling functions in neurotransmission, secretion and vasodilation, and long-term (chronic) signalling functions in development, regeneration, proliferation and cell death. Plasticity of purinoceptor expression in pathological conditions is frequently observed, including an increase in the purinergic component of parasympathetic nervous control of the human bladder in interstitial cystitis and outflow obstruction, and in sympathetic cotransmitter control of blood vessels in hypertensive rats. The antithrombotic action of clopidogrel (Plavix), a P2Y12 receptor antagonist, has been shown to be particularly promising in the prevention of recurrent strokes and heart attacks in recent clinical trials (CAPRIE and CURE). The role of P2X3 receptors in nociception and a new hypothesis concerning purinergic mechanosensory transduction in visceral pain will be considered, as will the therapeutic potential of purinergic agonists or antagonists for the treatment of supraventricular tachycardia, cancer, dry eye, bladder hyperactivity, erectile dysfunction, osteoporosis, diabetes, gut motility and vascular disorders.
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PMID:Potential therapeutic targets in the rapidly expanding field of purinergic signalling. 1187 39

We have previously observed that, while acute stress induces analgesia, chronic stress causes a hyperalgesic response in male rats. No effect was observed in females. There is increasing evidence that both ATP and adenosine can modulate pain. Extracellular ATP and ADP are hydrolyzed by an apyrase in synaptosomes from the peripheral and central nervous systems. In the present study, we investigated the effect of chronic and acute stress on ATPase-ADPase and 5'-nucleotidase activities in spinal cord of male and female rats. Adult male and female Wistar rats were submitted to 1 h restraint stress/day for 1 day (acute) or 40 days (chronic) and were sacrificed 24 h later. ATPase-ADPase activities were assayed in the synaptosomal fraction obtained from the spinal cord of control and stressed animals. ADP hydrolysis was decreased 25% in chronically stressed males, while no change was observed on ATPase activity. There was an increase in the 5'-nucleotidase activity in the same group. No effect on ADPase, ATPase or on 5'-nucleotidase activity was observed in females with chronic stress, or after acute stress neither in males or females. Chronic stress reduced ADP hydrolysis and increased 5'-nucleotidase activity in the spinal cord in male rats.
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PMID:Effect of chronic and acute stress on ectonucleotidase activities in spinal cord. 1189 Sep 46

Low-power, near-infra-red laser irradiation has been used to relieve patients from various kinds of pain, though the precise mechanisms of such biological actions of the laser have not yet been resolved. To investigate the cellular mechanisms by near-infra-red laser on the nervous system, we examined the effect of 830-nm laser irradiation on the energy metabolism of the rat brain. The diode laser was applied for 15 min with an irradiance of 4.8 W/cm(2). Tissue adenosine triphosphate (ATP) content of the irradiated area in the cerebral cortex was 19% higher than that of the non-treated area, whereas the adenosine diphosphate (ADP) content showed no significant difference. Laser irradiation at another wavelength (652 nm) had no effect on either ATP or ADP contents. The temperature of the tissue was increased by 4.4-4.7 degrees C during the irradiation of both wavelengths. These results suggest that the increase in tissue ATP content did not result from the thermal effect, but from a specific effect of the laser operated at the 830-nm wavelength.
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PMID:Effects of near-infra-red laser irradiation on adenosine triphosphate and adenosine diphosphate contents of rat brain tissue. 1195 21


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