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)

Skin graft donor sites are partial-thickness wounds that are commonly managed with gauze-type dressings. As such, they often cause more pain and difficulty in healing than the graft-recipient site. A retrospective study was conducted to ascertain the effects of using a castor oil-balsam of Peru-trypsin containing ointment on skin graft donor sites in 36 consecutive patients (16 female, 20 male). All donor sites were epithelialized after 11 days (range 6 to 11 days, mean 8 days) and no wound complications were observed. Given these healing results and product ease of use, this particular formulation has become the facilities' current treatment of choice and further study is indicated and warranted.
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PMID:Using a castor oil-balsam of Peru-trypsin ointment to assist in healing skin graft donor sites. 1287 84

Partially purified kinin, a polypeptide in wasp venom, has been found to be a potent smooth-muscle stimulating and hypotensive agent. Such a preparation was 10 to 100 times more effective than histamine in enhancing capillary permeability on intradermal injection, and 10 times more effective than acetylcholine in evoking pain on a cutaneous blister base. Some differences between the actions of salivary kallikrein and trypsin in releasing kallidin or bradykinin have been observed, and some modifications of previous methods of preparing crude kallidin and bradykinin are suggested. Kallidin and bradykinin are effective enhancers of capillary permeability in the guinea-pig and rabbit. Chemical and pharmacological tests failed to differentiate between kallidin and bradykinin which must be, therefore, closely similar compounds. The possible role of kallidin and bradykinin in physiological or pathological conditions is discussed.
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PMID:A comparative study of kinin, kallidin, and bradykinin. 1344 66

Controlled reports on the successful use of proteolytic enzymes to suppress post-traumatic inflammatory response have been based on animal subjects that were given the drug before inflammation was provoked and in the equivalent of 10 to 1,000 times maximum human dosage. All previous favorable reports on human subjects were based on uncontrolled experiments. In the present study, the first controlled human experiment, identical twins were identically treated with dermal abrasion of the face, to remove deep acne scarring. Using double-blind technique, one of them received "inert" parenteral and buccal vitamin medication. The other received maximum recommended therapeutic dosage of three proteolytic enzymes-streptokinase and streptodornase buccal tablets, and intramuscular trypsin. No differences in edema, inflammatory response, pain or speed of healing were noted.
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PMID:Failure of proteolytic enzymes to suppress post-traumatic inflammation. Double-blind control comparison on identical twins, after dermal abrasion. 1378 39

PARs (protease-activated receptors) are a family of four G-protein-coupled receptors for proteases from the circulation, inflammatory cells and epithelial tissues. This report focuses on PAR(2), which plays an important role in inflammation and pain. Pancreatic (trypsin I and II) and extrapancreatic (trypsin IV) trypsins, mast cell tryptase and coagulation factors VIIa and Xa cleave and activate PAR(2). Proteases cleave PAR(2) to expose a tethered ligand that binds to the cleaved receptor. Despite this irreversible activation, PAR(2) signalling is attenuated by beta-arrestin-mediated desensitization and endocytosis, and by lysosomal targeting and degradation, which requires ubiquitination of PAR(2). beta-Arrestins also act as scaffolds for the assembly of multi-protein signalling complexes that determine the location and function of activated mitogen-activated protein kinases. Observations of PAR(2)-deficient mice support a role for PAR(2) in inflammation, and many of the effects of PAR(2) activators promote inflammation. Inflammation is mediated in part by activation of PAR(2) in the peripheral nervous system, which results in neurogenic inflammation and hyperalgesia.
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PMID:Protease-activated receptor 2: activation, signalling and function. 1464 Oct 24

Certain serine proteases signal to cells by cleaving protease-activated receptors (PARs) and thereby regulate hemostasis, inflammation, pain and healing. However, in many tissues the proteases that activate PARs are unknown. Although pancreatic trypsin may be a physiological agonist of PAR(2) and PAR(4) in the small intestine and pancreas, these receptors are expressed by cells not normally exposed pancreatic trypsin. We investigated whether extrapancreatic forms of trypsin are PAR agonists. Epithelial cells lines from prostate, colon, and airway and human colonic mucosa expressed mRNA encoding PAR(2), trypsinogen IV, and enteropeptidase, which activates the zymogen. Immunoreactive trypsinogen IV was detected in vesicles in these cells. Trypsinogen IV was cloned from PC-3 cells and expressed in CHO cells, where it was also localized to cytoplasmic vesicles. We expressed trypsinogen IV with an N-terminal Igkappa signal peptide to direct constitutive secretion and allow enzymatic characterization. Treatment of conditioned medium with enteropeptidase reduced the apparent molecular mass of trypsinogen IV from 36 to 30 kDa and generated enzymatic activity, consistent with formation of trypsin IV. In contrast to pancreatic trypsin, trypsin IV was completely resistant to inhibition by polypeptide inhibitors. Exposure of cell lines expressing PAR(2) and PAR(4) to trypsin IV increased [Ca(2+)](i) and strongly desensitized cells to PAR agonists, whereas there were no responses in cells lacking these receptors. Thus, trypsin IV is a potential agonist of PAR(2) and PAR(4) in epithelial tissues where its resistance to endogenous trypsin inhibitors may permit prolonged signaling.
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PMID:Trypsin IV, a novel agonist of protease-activated receptors 2 and 4. 1472 24

Comparative trials have shown that enteral feeding (EN) is better than total parenteral nutrition (TPN) in acute pancreatitis. However, the following case report of a 64-year-old man with necrotizing pancreatitis suggests that EN may cause complications in patients with ductular damage. In the second week, this patient with acute pancreatitis developed >50% pancreatic necrosis, resulting in gastroduodenal obstruction and pain, leading to the use of TPN. A trial of EN delivered past the obstruction was associated with increased abdominal pain, leukocytosis, and pancreatic fluid accumulation. Measurement of the pancreatic response to feeding showed a 90% reduction in enzyme secretion compared to healthy volunteers, but no change in the uptake of stable isotope labeled amino acids into secreted trypsin. This suggests that enzymes were being synthesized by the remaining pancreatic tissue, but that some of the secretions were leaking into the inflammatory mass. Symptoms resolved after reinstitution of TPN and bowel rest. A further trial of EN was successful when the tube was advanced to the distal jejunum to avoid pancreatic stimulation. After 3 weeks of home EN, he was readmitted for surgical evacuation of an infected fluid collection. Although enteral feeding is generally better than TPN in the nutritional management of acute pancreatitis, there may be a subgroup of patients with ductular damage due to necrotizing disease in whom TPN and pancreatic rest may be safer.
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PMID:Nutrition in the management of necrotizing pancreatitis. 1501 74

Proteinase-activated receptor (PAR) 2 is expressed on a subset of primary afferent neurons and involved in inflammatory nociception. Transient receptor potential vanilloid subfamily 1 (TRPV1) is a sensory neuron-specific cation channel that responds to capsaicin, protons, or heat stimulus. Here, we show that TRPV1 is coexpressed with PAR2 but not with PAR1 or PAR3, and that TRPV1 can functionally interact with PAR2. In human embryonic kidney 293 cells expressing TRPV1 and PAR2, PAR2 agonists increased capsaicin- or proton-evoked TRPV1 currents through a PKC-dependent pathway. After application of PAR2 agonists, temperature threshold for TRPV1 activation was reduced from 42 degrees C to well below the body temperature. PAR2-mediated Fos expression in spinal cord was decreased in TRPV1-deficient mice. The functional interaction was also observed in mouse DRG neurons and proved at a behavioral level. These represent a novel mechanism through which trypsin or tryptase released in response to tissue inflammation might trigger the sensation of pain by PAR2 activation.
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PMID:Proteinase-activated receptor 2-mediated potentiation of transient receptor potential vanilloid subfamily 1 activity reveals a mechanism for proteinase-induced inflammatory pain. 1512 43

Protease supplementation has been shown to attenuate soft tissue injury resulting from intense exercise. The aim of this study was to evaluate the effects of protease supplementation on muscle soreness and contractile performance after downhill running. Ten matched pairs of male participants ran at a -10% grade for 30 min at 80% of their predicted maximal heart rate. The participants consumed two protease tablets (325 mg pancreatic enzymes, 75 mg trypsin, 50 mg papain, 50 mg bromelain, 10 mg amylase, 10 mg lipase, 10 mg lysozyme, 2 mg chymotrypisn) or a placebo four times a day beginning 1 day before exercise and lasting a total of 4 days. The participants were evaluated for perceived muscle soreness of the front and back of the dominant leg, pressure pain threshold by dolorimetry of the anterior medial, anterior lateral, posterior medial and posterior lateral quadrants of the thigh, and knee extension/flexion torque and power. The experimental group demonstrated superior recovery of contractile function and diminished effects of delayed-onset muscle soreness after downhill running when compared with the placebo group. Our results indicate that protease supplementation may attenuate muscle soreness after downhill running. Protease supplementation may also facilitate muscle healing and allow for faster restoration of contractile function after intense exercise.
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PMID:The effects of protease supplementation on skeletal muscle function and DOMS following downhill running. 1516 Nov 10

The aim of this study was to compare the efficacy and safety of an oral enzyme-rutosid combination (ERC) containing rutosid and the enzymes bromelain and trypsin, with that of diclofenac in patients with osteoarthritis (OA) of the knee. A total of 103 patients presenting with painful episodes of OA of the knee were treated for 6 weeks in two study centers in a randomized, double-blind, parallel group trial. Altogether, 52 patients were treated in the ERC group and 51 patients were treated in the diclofenac group. Primary efficacy criteria were Lequesne's Algofunctional Index (LFI) and a 'complaint index', including pain at rest, pain on motion and restricted function. The efficacy criteria were analyzed by applying the Wilcoxon-Mann-Whitney test that provides the Mann-Whitney estimator (MW) as a measure of relevance. Non-inferiority was considered to be proven if the lower bound of the 97.5% one-sided confidence interval (CI-LB) was higher than MW = 0.36 (benchmark of not yet relevant inferiority). Both treatments resulted in clear improvements. Within the 6-week observation period, the mean value of the LFI decreased from 13.0 to 9.4 in the ERC group and from 12.5 to 9.4 in the diclofenac group. Non-inferiority of ERC was demonstrated by both primary criteria, LFI (MW = 0.5305; CI-LB = 0.4171) and complaint index (MW = 0.5434; CI-LB = 0.4296). Considerable improvements were also seen in secondary efficacy criteria, with a slight tendency towards superiority of ERC. The global judgment of efficacy by physician resulted in at least good ratings for 51.4% of the ERC patients, and for 37.2% of the diclofenac patients. In the majority of patients tolerability was judged in both drug groups as very good or good. The current study indicates that ERC can be considered as an effective and safe alternative to NSAIDs such as diclofenac in the treatment of painful episodes of OA of the knee. Placebo-controlled studies are now needed to confirm these results.
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PMID:Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee--a double-blind prospective randomized study. 1527 53

We report a case of an acute allergic reaction to rectal diclofenac following elective caesarean section in a patient taking ibuprofen. The reaction presented as severe angio-oedema affecting the face and tongue. Serial blood samples failed to show the rise in tryptase levels characteristic of an anaphylactic or anaphylactoid reaction. Diclofenac is widely used for postoperative pain relief in women undergoing caesarean section. To our knowledge this is the first time that an adverse reaction to diclofenac given via this route has been reported in an obstetric patient.
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PMID:Angio-oedema following rectal diclofenac after caesarean section. 1532 29


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