Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:56-45-1 (serine)
 65,846 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha 1-proteinase inhibitor (alpha 1-PI), a serine protease inhibitor, was tested for its efficacy for the treatment of recalcitrant atopic dermatitis. Atopic dermatitis affects both children and adults and has no established etiology. We hypothesized that during inflammation there is an excess of serine proteases and a deficiency of their naturally occurring inhibitors at the local site of tissue injury, even though there is a normal serum level of serine protease inhibitors. This pilot study consisted of a nonblinded trial using alpha 1-PI at a concentration of 20 mg/mL in an aqueous solution in an alternate day schedule in conjunction with a 1% cream of alpha 1-PI (Stage I) and a 5% cream of alpha 1-PI for maintenance therapy (Stage II). Before enrollment in this trial all six patients failed to respond to high potency topical steroids. Safety was gauged by careful clinical monitoring of subjective complaints, objective findings of erythema, edema, and serial measurements of blood chemistries and complete blood counts. Wound healing was documented by serial photography. Written informed consent was obtained from each patient. All six patients showed significant clinical improvement within 6 to 21 days of initiation of alternate day therapy. Alpha 1-PI stopped pain, pruritus, and promoted tissue healing without scarring in all six patients. No adverse side effects of therapy were documented by clinical history, physical examination, or by blood studies after 120 days of therapy. Atopic dermatitis may be one example where inflammation is due to an imbalance of serine proteases and their naturally occurring inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of atopic dermatitis with alpha 1-proteinase inhibitor. 145 82

To test the hypothesis that plasma tryptophan and/or its transport ratio is decreased in primary fibromyalgia (PF), we measured plasma tryptophan and its transport ratio in 29 patients with PF and 30 healthy controls without significant pain, in a blinded manner. Twenty-one other amino acids were also similarly analyzed among these study subjects. Transport ratio of tryptophan was found to be significantly (p less than 0.01) decreased in PF compared with the control group (0.09 +/- 0.02 vs 0.10 +/- 0.02). Plasma tryptophan level was lower in PF (45 +/- 10 nmol/ml) than in healthy controls (51 +/- 15 nmol/ml), showing a trend towards significance (p less than 0.09). Additionally, plasma histidine and serine levels were found to be significantly (p less than 0.01) lower in patients with PF than in controls. Our results suggest that a decreased brain serotonin level, as possibly reflected by a decreased transport ratio of plasma tryptophan, may play a pathophysiologic role in PF.
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PMID:Plasma tryptophan and other amino acids in primary fibromyalgia: a controlled study. 155 7

Extracellular levels of amino acids were measured during the development of experimental arthritis in anesthetized monkeys. Levels of glutamate, aspartate, glycine, serine, glutamine, taurine, cysteic acid and asparagine were each measured in consecutive 30 min samples before, during and for several hours after injection of kaolin and carrageenan into the articular capsule of one knee. Samples were obtained via a microdialysis probe placed in the lumbar dorsal horn ipsilateral to the injected knee and assayed using HPLC with fluorescence detection. Glutamate, aspartate, glycine and serine increased transiently following intra-articular injection of inflammatory agents. During this period glutamine levels decreased. A second phase of release then occurred which included more prolonged changes in amino acid levels that were sometimes of greater magnitude than those immediately following the injection. In animals which were later observed to have depletion of SP in the dorsal horn of the inflamed side, taurine levels increased starting after the Glu, Asp and Gly had plateaued at near baseline concentrations. Thus during the first stages of joint inflammation EAAs are released into the dorsal horn, followed by increased levels of IAAs, possibly representing activation of the descending endogenous analgesia system. This phase is followed by a semiacute response consisting in part of increased extracellular levels of SP and Tau. While SP is presumably part of an ascending nociceptive transmission system, Tau could be part of a second system aimed at reducing excessive neural activity including neural transmission resulting in intense maintained pain.
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PMID:Neural changes in acute arthritis in monkeys. IV. Time-course of amino acid release into the lumbar dorsal horn. 163 74

Free plasma tryptophan levels in patients with fibrositis syndrome were measured by Moldofsky and Warsh with the view that the pathogenesis of fibrositis syndrome might involve a functional deficiency of serotonin. The hypothesis was supported by the finding of an inverse relationship between tryptophan concentration and the severity of musculoskeletal pain. Our study examined the total serum amino acid pool in fibrositis syndrome. Twenty patients with primary fibrositis syndrome and matched normal controls were evaluated clinically. After denaturation of macromolecules, serum amino acids were quantitated by automated analysis. Patients with fibrositis syndrome exhibited significantly lower levels of total serum tryptophan (p = 0.002), as well as 6 other amino acids: alanine (p less than 0.0005), histidine (p = 0.001), lysine (p = 0.02), proline (p = 0.039), serine (p = 0.028), and threonine (p = 0.013). These findings support the serotonin deficiency hypothesis for fibrositis syndrome pathogenesis but also imply a more generalized defect in amino acid homeostasis among affected individuals.
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PMID:Serum amino acids in fibrositis/fibromyalgia syndrome. 260 10

Concentrations of gamma-aminobutyric acid (GABA), glycine and serine have been measured in 44 microdissected areas of the brain of the rat. All three amino acids were ubiquitously present and distributed unevenly in the brain. Very high levels of GABA were found in the anterior hypothalamic and medial preoptic nuclei and the substantia nigra; high levels were found in the interpeduncular and red nuclei in the mesencephalon and in several hypothalamic nuclei. Glycine was distributed fairly uniformly with large concentrations in certain lower brainstem nuclei. In these areas, the concentrations of glycine exceeded those of serine, while the serine-glycine ratio was 4.5:1 in the caudate nucleus, 4:1 in the cerebellum and 2.5:1 in the cerebral cortical areas. Acute stress induced with formalin (pain) resulted in a significant depletion of levels of GABA in the hypothalamus and the lower brainstem but not in the cortical areas. In the same animals, concentrations of glycine doubled in the cerebral cortex and remained unchanged elsewhere in the brain. Increased motor and behavioral activity after the acute administration of a large dose of amphetamine were associated with a 2-5-fold increase in the levels of glycine in brain, and markedly elevated the concentrations of GABA in the major biogenic amine-containing cell groups only (substantia nigra, locus coeruleus and dorsal raphe).
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PMID:Concentrations of GABA and glycine in discrete brain nuclei. Stress-induced changes in the levels of inhibitory amino acids. 309 27

One of the striking features of the proteolytic enzymes as a group is the immense variety of biological functions served by enzymes employing one of a few basic mechanisms. For example, in the higher animals, enzymes for activation of zymogens (trypsin), for digestion of dietary proteins (trypsin, chymotrypsin, elastase), for blood clotting (thrombin), for clot lysis (plasmin), and for sensing pain (kallikrein) all appear to use the same mechanism and to have evolved from the same ancestral gene by the process of gene duplication and subsequent divergent evolution. Equally striking is the variety of chemical solutions of the same functional problem, such as the peptide-bond cleavage by sulfhydryl proteases on the one hand and serine proteases on the other.
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PMID:Evolution of structure and function of proteases. 486 30

Analyses of whole and parotid saliva were performed in ten patients with subjective symptoms resembling galvanic pain and in their eight asymptomatic counterparts. Salivary flow rates, protein, IgA, lysozyme, sodium, potassium, chloride, calcium phosphate, copper, and magnesium contents were measured. The concentrations of protein, sodium, chloride, and phosphate in the whole saliva of the patients with symptoms were significantly higher, but concentrations of calcium, magnesium, and IgA were lower than in the asymptomatic controls. In parotid saliva, too, protein, lysozyme, and calcium concentrations were significantly altered in patients with oral symptoms. The analysis of free amino acids serine, proline, glutamic acid + glutamine, and glycine in the whole saliva did not show any significant differences between the two groups studied. The results suggest the importance of salivary contents in the development of oral soreness. Such changes in the salivary constituents could modulate the amount and character of the salivary macromolecules absorbed onto the teeth. This could lead to passivation or activation of the surfaces in metallic restorations and consequently to the onset of the intraoral electric currents.
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PMID:Salivary content of patients with subjective symptoms resembling galvanic pain. 659 63

An early wave component of the scalp-recorded SER increases in amplitude when cold and electrical stimulation are combined. This change is accompanied by subjective reports of perceptual change in the intensity, domain or painfulness of the electrical stimulus in humans. Further results suggest that observation of the augmentation is dependent on normal functioning of both large and small peripheral fiber populations. This augmentation is also observed in Macaca mulatta monkeys. Under the same conditions, the spinal segmental SER is observed to obtain a new wave. This wave is time-locked to the electrical stimulus and has a latency longer than the earliest, but shorter than the latest traditional slow waves. The interaction of the cold and electrical stimuli to produce the cortical augmentation suggests the existence of a facilitatory mechanism. The level at which this operates and the mechanism through which it functions are discussed. The relationship of this augmentation to arousal phenomena is also examined.
Pain 1982 May
PMID:Low temperature stimulation augments early wave component of somatosensory evoked response in humans and Macaca mulatta monkeys. 711 Jul 45

A search for mutations in the gene for type II procollagen (COL2A1) was carried out in a family with late-onset spondyloepiphyseal dysplasia resulting in short sature, restricted mobility and severe pain in joints, deforming arthritis in the hips, and claudication. Analysis of the HindIII and VNTR polymorphisms at the COL2A1 gene in the family raised the possibility that the gene cosegregated with the disease. Screening for mutations in the COL2A1 gene using PCR-denaturing gradient get electrophoresis suggested a sequence variation in exon 19 of one allele of the COL2A1 gene in the proband. Direct sequencing of the PCR products for exon 19 revealed a single base mutation that converted the codon of -GGT- for glycine at alpha 1-247 to -AGT-, a codon for serine. The mutant that converted the present in all affected family members, but absent in nonaffected members and in a group of 50 unrelated healthy individuals. It was also absent in 20 unrelated patients with chondrodysplasia and 30 unrelated patients with early-onset osteoarthritis.
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PMID:A single base mutation in the type II procollagen gene (COL2A1) that converts glycine alpha 1-247 to serine in a family with late-onset spondyloepiphyseal dysplasia. 801 61

Inflammation is a multicomponent system that involves a network of cellular crosstalk and control. Many different cell types, including neutrophils and platelets, participate as both sources and targets of biological mediators that are generated or released in acute and chronic inflammatory states. Owing to the complex nature of inflammation, the magnitude as well as the spatial and temporal characteristics of the responses are likely to vary with the type, concentration, and duration of the inflammatory stimulus. Despite the potential variations in responses to diverse stimuli, a feature common to and responsible for the major characteristics of inflammation (heat, pain, redness, swelling) is proteases. In the early stages of inflammation, the neutrophil is the predominant cell to infiltrate the tissue, and the extent of inflammatory injury has been shown to be directly dependent on the extent of neutrophil infiltration. Since both cathepsin G and elastase are neutral serine proteases present in large amounts in azurophilic granules and are known to affect platelet function, it is thus likely that these neutrophil enzymes are important contributing factors to inflammatory reactions in general and to neutrophil-platelet interactions specifically.
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PMID:Neutrophil-platelet interactions in inflammation. 803 4


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