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 behaviour of muscular metabolism was investigated in 10 patients with peripheral arterial occlusive disease stage II at rest and after maximum ergometric calf exercise. The intracellular concentrations of phosphocreatine, inorganic phosphate and adenosine triphosphate as well as muscle pH were measured by means of 31P magnetic resonance spectroscopy and compared with those from a control group. In addition, arteriovenous differences in concentrations of lactate, pyruvate, ammonia, hypoxanthine and alanine in the femoral blood were determined. The fall in intracellular phosphocreatine concentration during exercise was significantly greater in the calf muscles of patients with arterial occlusion than in controls and correlated linearly with the increase in femoral arteriovenous differences in lactate, ammonia and alanine. A significant fall in intracellular pH occurred during muscular activity only in the patient group, but not in the identically exercised control group. The fall in pH correlated closely with the rise in arteriovenous lactate difference in the femoral blood. The intramuscular ATP concentration remained constant throughout the exercise procedure. The behaviour of both the directly and indirectly measured metabolites permits the deduction of activation of the creatine kinase reaction, glycolysis, myokinase reaction and the purine nucleotide cycle during exercise-induced hypoxia in the presence of arterial occlusive disease. The anaerobic production of energy is sufficient to maintain the ATP concentration even during claudication pain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Assessment of muscular metabolism in peripheral arterial occlusive disease using 31P nuclear magnetic resonance spectroscopy. Comparison with metabolite concentrations in femoral blood. 279 50

Intermittent claudication is associated with adaptation in muscle metabolism. This study has evaluated the metabolism of amino acids at rest and during non-steady state exercise in patients with arterial insufficiency of at least six months duration in comparison with matched control individuals. The exchange of amino acids were measured during two periods of acute exercise; one initial exercise period with a standardized work load and exercise time and a second exercise period which continued until further exercise was impossible due to pain in the patients and exhaustion in the controls. The maximum blood flow was reduced by 40% in the patients but the maximum oxygen uptake per unit power developed was almost the same in patients and controls. The patients had significantly lower concentrations of glutamine, lysine and taurine at rest compared with the controls. The exchange of amino acids across the resting leg did not differ between the two groups. Exercise increased the efflux of amino acids in both patients and controls. The efflux of glutamine (896 +/- 205 vs. 48 +/- 359 nmol/100 ml/min/watt) was higher in the patients compared to the controls at the first exercise period with inverse changes in the opposite direction of asparagine (149 +/- 105 vs. 799 +/- 121 and 27 +/- 70 vs. 633 +/- 334 nmol/100 ml/min/watt at the first and second exercise, respectively. Alanine release did not differ between the groups. The complementary patterns of glutamine and asparagine during hypoxic exercise in the patients may reflect the fact that these amino acids share a common carrier system. The similarity in the efflux of non-metabolized amino acids, such as methionine, phenylalanine, tyrosine and 3-methylhistidine, indicated that muscle hypoxia in claudication patients did not promote net degradation of either globular or myofibrillar proteins, although exercise increased the efflux of 3-methylhistidine three- to fourfold in both patients and control individuals (from 1 +/- 0.4 to 4 +/- 1.8 and from 0 +/- 0.7 to 6 +/- 2.5 nmol/100 ml/min/watt, respectively). The exercise-induced alterations in leg exchange of amino acids were restored within 10-20 min following exercise regardless of hypoxia. The results demonstrate that patients with arterial insufficiency have altered intermediary metabolism of amino acids during exercise. However, muscle hypoxia in such patients does not seem to promote a negative protein balance or induce serious alterations in cell membrane integrity.
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PMID:Leg exchange of amino acids during exercise in patients with arterial insufficiency. 340 84

Highly sensitive radioimmunoassays were developed and used in studies of the distribution and chromatographic properties of two mammalian FMRF-NH2-like peptides recently isolated from bovine brain; an octapeptide with the structure Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (F-8-F-NH2) and on octadecapeptide, Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe-NH2 (A-18-F-NH2). F-8-F-NH2 and A-18-F-NH2 immunoreactivities are unevenly distributed in bovine brain. The highest concentrations (pmol g-1) of F-8-F-NH2 and A-18-F-NH2 are found in dorsal spinal cord (9.8 and 16.4 respectively), periaqueductal grey (8.6 and 6.8) and pons medulla (7.0 and 8.9); lowest quantities are in cortex, cerebellum and striatum. HPLC analysis coupled with radioimmunoassay reveals that the major immunoreactivities are identical to synthetic F-8-F-NH2 and A-18-F-NH2 while there are additional immunoreactive materials, distinct from NPY, whose structures still remain to be determined. The enrichment of these peptides in dorsal cord and periaqueductal grey, areas important in opioid-mediated pain perception, suggest that they may play a role in mediating antinociception.
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PMID:Distribution and characterization of two putative endogenous opioid antagonist peptides in bovine brain. 362 81

New compounds were designed to fully inhibit the in vitro metabolism of enkephalins, ensured by three different metallopeptidases. For this purpose, bidentate ligands as hydroxamate and N-hydroxy-N-formylamino groups were selected as highly potent metal coordinating agents and introduced on Phe-Gly and Phe-Ala related structures. Compounds corresponding to the general formula HC(O)N(OH)CH2CH(CH2Ph)CONHCH2COOH (compound 7) and HN(OH)C(O)CH2CH(CH2Ph)CONHCH(R)COOH (compound 11, R = H; compound 13, R = CH3) behave as full inhibitors of the three enzymes, with IC50's in the nanomolar range for enkephalinase, from 0.3 microM to 1 nM for dipeptidylaminopeptidase, and in the micromolar range for a biologically relevant aminopeptidase. Two diastereoisomers of the most active inhibitor 13 were separated by HPLC and their stereochemistry was assigned by 1H NMR spectroscopy. Both isomers were efficient as enkephalinase blockers, but only the RS isomer, designated kelatorphan, was able to strongly inhibit aminopeptidase and dipeptidylaminopeptidase. Intracerebroventricular injection in mice of these mixed inhibitors, especially kelatorphan, led to naloxone reversible analgesic responses (hot-plate test) that were slightly better than those produced by a mixture of thiorphan and bestatin, two potent inhibitors of enkephalinase and aminopeptidase, respectively. Kelatorphan was also more efficient in potentiating the analgesia induced by a subanalgesic dose of Met-enkephalin. All these results support a physiological role in pain transmission for enkephalinase and a probably synaptic aminopeptidase M.
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PMID:New bidentates as full inhibitors of enkephalin-degrading enzymes: synthesis and analgesic properties. 389 41

The antinociceptive effect of intracerebroventricular injection (icv) of Asn-Ala-Gly-Ala (NAGA), a partial sequence of beta-lipotropin, was studied in rats. The potassium iontophoresis-induced tail flick was used to measure the pain threshold. The antinociceptive effect of NAGA, which was dose-dependent (icv, 0.03-0.24 mumol/rat) and long-lasting (90 min), was reversed by naloxone (icv, 0.26 mg.kg-1) and inhibited by anti-MEK serum (titre: 1:5000, 5 microliters) or anti-LEK serum (titre: 1:5000, 5 microliters). NAGA-induced antinociception was scarcely affected by anti-beta-EP serum (titre: 1:30,000, 5 microliters) or anti-Dyn A1-13 serum (titre: 1:30,000, 5 microliters). It was suggested that the antinociceptive effect of NAGA may be associated with the release of met-enkephalin and leu-enkephalin in rat brain.
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PMID:Antinociceptive effect of intracerebroventricular injection of a tetrapeptide Asn-Ala-Gly-Ala in rats. 770 46

Disc space infection or discitis, an infection of the intervertebral disc with contiguous subchondral vertebral osteomyelitis, most frequently follows prior intervertebral disc surgery or arises by hematogenous dissemination. The majority of cases are located in the lumbosacral spine and are caused by staphylococci. Clinical findings include localized spinal pain and fever. The diagnosis is suggested by radiologic studies (plain x-ray, bone scan, CT scan and MR imaging) and confirmed by culturing blood or material obtained from the involved disc space. Treatment consists of antimicrobial therapy, spinal immobilization and surgical intervention in selected circumstances. Discitis is associated with a good prognosis but residual back pain, limited spinal mobility and neurologic deficit may occur.
Ala Med 1994 Jan
PMID:Disc space infection. 803 May 85

In order to assess the acute metabolic effects of an intra-arterial infusion of nucleotide-nucleoside-mixture (NNM), 31P-mr-spectroscopy at the site of m. gastrocnemius and metabolite determinations from blood of the femoral artery and vein were carried out in 10 patients with PAOD stage II during ergometric calf exercise to the claudication pain limit. The spectroscopic measurements revealed a greater exercise-induced fall of PCr and a higher increase of Pi in calf muscles during supply of NNM compared with control ergometry. Post-exercise recovery of PCr was distinctly delayed during infusion of NNM. The anaerobic production of energy, however, was sufficient to maintain the ATP concentration to the same extent as under control ergometry. On the other hand, intramuscular lactate acidosis developed to a lower degree with NNM infusion than without NNM. A reduced muscular release of lactate, pyruvate, ammonia and alanine followed from the evaluation of the arteriovenous balance of these metabolites in the femoral vessels indicating a favourable global metabolic effect of NNM infusion in the extremity. The apparent contradiction in the spectroscopic and analytic-biochemical findings can be explained by local blood shunts induced by maximum vasodilation. Noninvasive mr-spectroscopy allows to detect directly and continuously the metabolic impact of ischemia in the calf muscles afflicted by arterial occlusion, whereas the metabolite concentrations in femoral blood are altered by afflux from non-ischemic areas. The known clinical benefit of frequently repeated intra-arterial infusions of NNM is thought to be due to an expansion of collateral circulation and to a favourable influence on endothelial functions.
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PMID:[Effects of a nucleotide-nucleoside mixture on ischemic muscle metabolism in patients with stage II peripheral arterial occlusive disease. MR spectroscopic and biochemical analytic results]. 803 45

This paper is not a study, but rather a clinical evaluation of three endodontic techniques based solely on subjective postoperative symptoms reported by patients. From 1968 to 1972 (four years), the author treated 452 teeth with a traditional endodontic technique. During 1973-1981 (eight years), he treated 625 additional teeth by instrumenting the root canals in the same manner as in the traditional method, but without the employment of sodium hypochlorite. In this procedure, the canals were obturated with a paraformaldehyde-steroid-zinc oxide and eugenol paste (PSZOE). A third "hybrid" endodontic technique was used in treating 522 other teeth during 1982-1991 (nine years). During the latter period, the teeth were instrumented in the same manner as in the first two modes of therapy, sodium hypochlorite was not used, and the root canals were filled with gutta percha cones covered with the PSZOE paste. Based on subjective reports of postoperative swelling and pain, there was a 10% incidence of swelling and a 20% incidence of pain in cases treated by the traditional technique and their root canals filled with gutta percha cones coated with Tubliseal by Kerr Dental Manufacturing Company of Detroit. Based on these same criteria, there was only a 1.6% prevalence of swelling and a 1.9% prevalence of pain when the root canals of 625 teeth were completely filled with a PSZOE paste. When the root canals of 522 other endodontically treated teeth were filled with gutta percha cones coated with PSZOE, postoperative swelling was reported in 1.5% of the cases and postoperative pain in 3.2% of the treated teeth.(ABSTRACT TRUNCATED AT 250 WORDS)
J Ala Dent Assoc 1993
PMID:Patient comfort using three methods of endodontic therapy: traditional, paraformaldehyde, and hybrid sealer techniques. 804 May 17

The mu opiate receptor is a principal brain site for activities of morphine, other opiate drugs, and opioid peptides in modulating pain and altering mood. Recent cloning of cDNAs encoding rat and human mu receptors reveals charged amino acid residues within putative transmembrane domains (TMs) II, III, and VI, a substantial N-terminal extracellular domain, and a C-terminal intracellular domain. Deletion of 64 N-terminal amino acids produced little effect on receptor function (Wang, J.B., Imai, Y., Eppler, C.M., Gregor, P., Spivak, C.E., and Uhl, G.R. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 10230-10234). Further deletion of 33 C-terminal amino acids yielded a receptor at which morphine, but not the substituted enkephalin DAMGO ([D-Ala2,MePhe4,Glyol5]enkephalin), inhibited adenylate cyclase. Alanine substitution for each charged TM residue in the N-terminally deleted receptor reduced affinities for morphine, DAMGO, and the opiate antagonist naloxone. Replacement of TM II Asp114 with asparagine or glutamic acid increased mu receptor affinity for naloxone. TM II and TM III glutamic acid substitutions for Asp114 and Asp147 reduced agonist binding affinities but allowed full inhibition of adenylate cyclase at high agonist concentrations. TM VI histidine substitution with alanine yielded a receptor that produced almost twice the cyclase inhibition displayed by the wild type receptor in parallel transient expression assays. These findings underscore the importance of charged residues in TM II, III, and VI for different receptor functions and the modest involvement of extensive portions of N- and C-terminal receptor domains in these processes.
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PMID:-mu opiate receptor. Charged transmembrane domain amino acids are critical for agonist recognition and intrinsic activity. 805 Nov 54

Bradykinin (BK) is a peptide hormone with sequence Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9 and has been implicated in a multitude of pathophysiological processes such as the ability to lower systemic blood pressure and stimulate pain. Bulky, beta-branched D-aliphatic residues at position 7 combined with bulky L-aliphatic residues at position 8 have now been observed to yield strong antagonists. Nuclear magnetic resonance studies have been carried out on many of these molecules with a view to determining their solution conformations. However, two such analogs, namely DArg-[Hyp3, Thi5, DSer6, DCpg7, Cpg8]-BK [I] and DArg-[Hyp3, DSer6, DCpg7, Cpg8]-BK [II] (Cpg = alpha-cyclopentyl-glycine; Hyp = 4-hydroxy-L-proline, Thi = beta-(2-thienyl)-L-alanine), have exhibited an abnormal, non-linear temperature dependence for the amide NH proton of Cpg8. The NH of Arg9 also shows a slightly non-linear temperature dependence at higher temperatures above 25 degrees C. In addition, a very slow exchange rate for the NH protons of DCpg7, Cpg8 and Arg9 indicated aggregation of these two analogs, which was confirmed using the circular dichroism experiments.
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PMID:The aggregation properties of some bradykinin analogs. 821 42


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