Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GH secretion in response to all provocative stimuli is decreased in patients with obesity. However, the precise mechanism causing this impairment in GH release is unknown. His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To gain further insight into disrupted GH secretion in obesity, GHRP-6 and GH-releasing hormone (GHRH) at a dose of 100 micrograms, i.v., were administered either alone or in combination in a group of 19 obese subjects. In a group of obese patients, GHRP-6 induced GH secretion, with a GH peak (mean +/- SEM) of 15.7 +/- 4.4 micrograms/L and an area under the curve (AUC) of 674 +/- 187, which were larger than those after GHRH stimulation (6.8 +/- 1.1 and 412 +/- 71, respectively). Enhancement of the endogenous cholinergic tone was obtained in another group of obese subjects by means of pyridostigmine (120 mg, orally). Pyridostigmine administered 60 min before GHRP-6, increased both the mean GH peak (32.2 +/- 6.9) and the AUC (1413 +/- 537) after GHRP-6 administration. In a separate group of subjects, the combined administration of GHRP-6 and GHRH induced a massive discharge of GH, with individual responses ranging from 14-86 micrograms/L. GHRP-6 plus GHRH induced a mean GH peak of 42.2 +/- 10.9 and an AUC of 1894 +/- 784 (P < 0.05), clearly indicating a potentiating (synergic) action when the two compounds were administered together. These data show that GH responses to GHRP-6 were almost twice those to GHRH in obese patients. The stimulatory effect exerted by pyridostigmine on GHRP-6-induced GH secretion supported the view of increased somatostatinergic tone in obesity. Finally, the massive GH discharge that followed the administration of GHRH plus GHRP-6 was not observed after any stimulus in obesity, clearly indicating that the impaired GH secretion is a functional and potentially reversible state.
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PMID:Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity. 847 88

The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL4), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS). The KL4 peptide was synthesized to resemble the amino acid pattern of surfactant protein B (SP-B). Forty-seven infants with RDS were treated within 4 h of birth with the KL4-peptide/phospholipid mixture, called KL4-Surfactant. The average arterial-to-alveolar oxygen tension ratios (a/A O2) of 39 patients included in efficacy analyses rose from pretreatment values of 0.14 +/- 0.02 (mean +/- SEM) to 0.40 +/- 0.04 (normal value > or = 0.40) by 12 h of age. Mean airway pressures and oxygenation index values fell concomitantly, and expansion of the lungs was observed on radiographs. The median duration of mechanical ventilation was 5.0 d. Of the 39 included infants, 29 required only a single dose. Radiographic data indicate that those patients requiring a second instillation of KL4-Surfactant but not showing a sustained rise in a/A O2 ratios did, in fact, exhibit expansion of alveoli in the lung. There were no RDS-related deaths; the incidence of complications was no higher than found in other comparable published studies. The data demonstrate that the synthetic peptide, KL4, which mimics the hydrophobic and hydrophilic pattern of SP-B, when formulated in an aqueous dispersion with the phospholipids DPPC and POPG, creates a strong and durable surfactant activity as judged by expansion of pulmonary alveoli and improvement of gas exchange in infants with RDS.
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PMID:The efficacy and safety of KL4-surfactant in preterm infants with respiratory distress syndrome. 854 50

Ileal and fecal gut endogenous nitrogen and amino acid excretions in adult domestic cats were determined. Ileal digesta were collected (10 cm of terminal ileum) from the cats fed either a protein-free diet or an enzymatically hydrolyzed casein-based diet (free amino acids and peptides < 10,000 Da) for 1 wk. Chromic oxide was included in each diet as an indigestible marker. The relative contribution of the hindgut to total endogenous gut excretion was investigated in a separate study by feeding cats a protein-free diet with or without added antibiotics for 10 d. Endogenous ileal nitrogen and amino acid nitrogen excretions of (mean +/- SEM 2.4 +/- 0.27 and 1.9 +/- 0.13 mg/g food dry matter intake, respectively, were found for the cats fed the protein-free diet, whereas higher excretions of 3.6 +/- 0.73 (P = 0.12) and 3.6 +/- 0.76 (P = 0.03) mg/g food dry matter intake were obtained in cats fed the enzymatically hydrolyzed casein. Significantly (P < 0.05) higher endogenous ileal amino acid excretions, for the enzymatically hydrolyzed casein-fed cats compared with those fed the protein-free diet, were found for methionine, aspartic acid, serine, glutamic acid, proline, valine and isoleucine, with the differences in excretions of glycine, alanine, leucine and histidine being significant at the 6% level. Most of the endogenous fecal amino acid excretions were unaffected by the inclusion of the antibiotics in the protein-free diet, although bacterial numbers were significantly lower (69%). Antibiotics addition led to significantly higher fecal endogenous excretions of nitrogen, taurine, threonine, serine and histidine but significantly lower excretions of methionine and lysine. Cats, like other simple-stomached mammals, excrete higher amounts of endogenous amino acids at the terminal ileum when the diet contains peptides.
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PMID:Gut endogenous nitrogen and amino acid excretions in adult domestic cats fed a protein-free diet or an enzymatically hydrolyzed casein-based diet. 861 99

Neutrophil accumulation in the lung is implicated in the pathogenesis of pulmonary emphysema and chronic bronchitis associated with cigarette smoking. To determine whether nicotine contributes to this accumulation through the prolongation of neutrophil survival, we examined the survival rates of isolated neutrophils cultured with or without nicotine. We found that nicotine prolonged neutrophil survival in a dose-dependent fashion, with a maximum effect at 10(-6) mol/L. The survival rate at 72 hours was 35.6% +/- 1.2% in medium with 10(-6) mol/L nicotine, compared with 15.5% +/- 0.5% in control medium (mean +/- SEM; p < 0.01), as determined by trypan blue dye exclusion. This prolongation was brought about by suppression of apoptosis, as evidenced by both transmission electron and fluorescence microscopy, and was associated with the preservation of neutrophil functions such as chemotaxis and O2- generation. The prolongation of survival caused by nicotine was abrogated by the addition of Pro-Lys-Arg-NH2, a competitive inhibitor of the specific binding of nicotine to noncholinergic receptors on neutrophils. However, the prolongation of survival caused by nicotine was not suppressed in the presence of K-252b, an inhibitor of protein kinase C. These findings suggest that nicotine prolongs neutrophil survival through noncholinergic nicotine receptors and new protein synthesis, without activation of protein kinase C.
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PMID:Nicotine prolongs neutrophil survival by suppressing apoptosis. 863 47

Inflammatory response and the subsequent fibrous capsule formation are often used as a screening method to determine biocompatibility of an implanted material. In this study, porous implants of tricalcium phosphate-lysine (TCPL) delivery devices were implanted intraperitoneally (i.p.) and subcutaneously (s.c.) using adult male rats as a model. The fibrous capsule surrounding the implant was studied histochemically to determine the resorbability rate of the devices. Fibrous capsular tissues were carefully dissected away from the capsule noting the tissue closest to the implanted material. Evaluation of the sections (5um, H&E) collected from various areas of the implants (n = 15 per group) revealed that: (1) regardless of the site of surgical implantation, all devices were encapsulated with fibrous tissue within three days post implantation and the thickness of the capsular tissue was found to be directly proportional to duration of implantation, (2) the thickness of fibrous tissues collected from i.p. site were significantly higher than those collected from s.c. site of implantation, (3) vascularity, macrophages, multinucleated giant cells and plasma cells at the TCPL implant-interface were evident after the first week, and the persistence of these cell types and progressive angiogenesis in subsequent weeks was apparent. The formation of distinct cell layers was remarkable in the fifth week phase, (4) SEM and radiographic analysis of retrieved devices showed a significant (P < 0.05) increase in the number of macropores (12 to 36 um2) in TCPL devices implanted s.c. than the number of macropores in TCPL devices implanted i.p. The mechanism of biodegradation process in an in vivo environment is not fully elucidated. This observation and previous observations led us to suggest that the site of surgical implantation is an instrumental key in designing TCPL delivery system.
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PMID:Cytological evaluation of capsular tissue surrounding TCPL implant in adult rats. 867 94

Prostaglandin (PG)D2 is a major product of arachidonic acid metabolism in pulmonary mast cells. We therefore attempted to determine whether measurement of the stable urinary metabolite of PGD2, 9 alpha, 11 beta-PGF2, could serve as a marker of mast cell activation in the lungs. A commercially available enzyme immunoassay was validated and found to be specific and sensitive when applied to unpurified urine. There was no diurnal variation in the levels of 9 alpha, 11 beta-PGF2 in healthy volunteers. Morning baseline values of urinary 9 alpha, 11 beta-PGF2 were measured in three groups--healthy volunteers (n = 9), patients with atopic asthma (n = 14), and aspirin-intolerant patients with asthma (n = 12)--and found to be very similar, 54 +/- 9, 62 +/- 6, and 71 +/- 15 ng/mmol creatinine, respectively (means +/- SEM). Urinary excretion of 9 alpha, 11 beta-PGF2 was increased threefold immediately after allergen-induced bronchoconstriction in nine patients with atopic asthma. Bronchial challenge with inhaled lysine aspirin in eight aspirin-intolerant patients with asthma produced bronchoconstriction without extrapulmonary symptoms and was also followed by a significant increase in the urinary excretion of 9 alpha, 11 beta-PGF2. In addition, challenge with a higher dose of aspirin produced an even greater increase in urinary 9 alpha, 11 beta-PGF2, supporting dose-dependent release of PGD2 during aspirin-induced bronchoconstriction. In contrast, the postchallenge levels of urinary 9 alpha, 11 beta-PGF2 were not increased when bronchoconstriction was induced by histamine challenge in the aspirin-intolerant patients with asthma. The study confirms mast cell involvement in allergen-induced bronchoconstriction and provides novel data, which strongly support the hypothesis that pulmonary mast cells are activated during aspirin-induced airway obstruction. It is finally suggested that measurement of urinary 9 alpha, 11 beta-PGF2 with enzyme immunoassay may be used as a new noninvasive strategy to monitor mast cell activation in vivo.
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PMID:Increased urinary excretion of the prostaglandin D2 metabolite 9 alpha, 11 beta-prostaglandin F2 after aspirin challenge supports mast cell activation in aspirin-induced airway obstruction. 875 20

The short-term effects of extracellular fluid volume depletion on the generation of some bioregulators of the renal function have been studied in healthy women. Eight subjects (SD group) were submitted to a low NaCl dietary intake and natriuretic treatment. At the end of the treatment (6 days) a cumulative sodium deficit of 381 +/- 55 mmol (mean +/- SEM) and a body weight variation of -2.1 +/- 0.28 kg were estimated. The renal function was explored by clearance method during hypotonic polyuria induced by oral water load and subsequent antidiuresis induced by low-dose infusion of lysine-8-vasopressin. The basal values of plasma renin activity were determined just before the water load as well as the urinary aldosterone excretion of the foregoing 24 hours was. During the renal functional exploration the urinary concentrations of PGE2, 6-keto-PGF1 alpha (6KPGF) and TxB2 were determined by RIA method. We report also, as comparison terms, the results obtained either in potassium depletion (KD group, n = 12) or in normal sodium and potassium balance (N group, n = 20). 1) In the SD vs N group-besides the increase in renin and aldosterone secretion-the behaviour of urinary prostanoids is consistent with a stimulation of the renal synthesis of PGI2 and TxA2 as well as of PGE2, at least as a trend. 2) In the KD vs N group an increase in renin secretion occurred while the urinary aldosterone was not significantly decreased. The urinary prostanoid data suggest an inhibition of the renal synthesis of PGE2 and PGI2. All three urinary prostanoids were significantly lower in the KD as compared to the SD group. Thus, in salt depletion the renal prostanoid synthesis was enhanced while it was depressed in potassium depletion, despite the increased renin secretion.
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PMID:Responses of the renal prostanoids to a short-term depletion of sodium or potassium in healthy women. 877 11

The effect of mimosine on a perfused area of skin tissue was studied using an isolated perfusion technique. Four mature Angora wethers (body weight 35 (SE 2.3) kg) were cannulated bilaterally with indwelling silicone catheters in the superficial branches of the deep circumflex iliac artery and vein. Mimosine (40 mg/kg metabolic weight (W)0.75) per d) was infused intra-arterially into one iliac artery of each goat for 3 d and saline was infused in the contralateral (control) iliac artery. Iliac venous blood samples were taken from both sides along with arterial samples from the carotid artery. Mimosine infusion elevated plasma mimosine in the carotid artery (52.6 (SEM 19.21) mumol/l) and iliac vein on the saline-treated side to 54.1 (SEM 16.31) mumol/l and in the iliac vein on the mimosine-treated side to 191.3 (SEM 19.14) mumol/l (P < 0.01). Mimosine decreased feed intake (2.3 v. 0.6 kg/d, SEM 0.29; P < 0.001) and water consumption (5.2 v. 1.3 litres/d, SEM 0.67; P < 0.001). Mimosine did not cause defleecing in the area of infusion and was cleared from the bloodstream within 12 h of cessation of infusion. The following effects were also observed during mimosine infusion: decrease in plasma amino acids to half pre-infusion values (methionine 22.7 v. 13.1 mumol/l, SEM 1.41; lysine 95.9 v. 37.4 mumol/l, SEM 4.28; P < 0.001); decreases in plasma triiodothyronine (1495 v. 695 ng/l, SEM 43.1; P < 0.001), thyroxine (61.5 v. 19.5 micrograms/l, SEM 1.8; P < 0.001) and insulin (28.7 v. 17.3 microIU/ml, SEM 1.89; P < 0.01) concentrations; increase in plasma cortisol (14 v. 62 micrograms/l, SEM 0.35; P < 0.001) concentration; decreases in levels of plasma Zn and Mg (0.97 v. 0.49 mg/l, SEM 0.063; P < 0.001 and 21.4 v. 14.6 mg/l, SEM 1.74; P < 0.001 respectively). All reported variables returned to their normal values 24 h after cessation of mimosine infusion except feed intake which was affected for a longer period. Mohair length and diameter were not affected by mimosine infusion. The toxicity of mimosine may be due to the drastic depletion of Zn and Mg in the blood as mimosine possesses very strong chelating properties and is excreted in the urine as a chelate.
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PMID:Effects of mimosine administered to a perfused area of skin in Angora goats. 878 92

Studies were conducted to assess the efficacy and safety of a synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome (RDS) in preterm (approximately 80% of normal gestation) infant rhesus monkeys. Surfactant was prepared consisting of the phospholipids dipalmitoylphosphatidyl choline and palmitoyl-oleoyl phosphatidyl glycerol and a synthetic peptide modeled after surfactant protein B (SP-B), "KL4-Surfactant" contained a peptide having the sequence KLLLLKLLLLKLLLLKLLLLK, where "K" is lysine and "L" is leucine. The peptide was selected because it mimics the repeating stretches of hydrophobic residues with intermittent basic hydrophilic residues seen in SP-B. KL4-Surfactant was shown to have biophysical activity assessed as the ability to lower surface tension at an air-liquid interface in a pulsating bubble surfactometer. Thirty premature rhesus monkeys were treated shortly after birth with one dose of KL4-Surfactant. The arterial to alveolar oxygen partial pressure ratio (a/A) was found to rise from a pretreatment level of 0.11 +/- 0.01 (mean +/- SEM), indicative of severe RDS, to 0.40 +/- 0.02 at 12-13 h post-treatment. The improvement in oxygenation persisted throughout the study period, with a mean a/A at 22-23 h of 0.45 +/- 0.07. Chest radiographs and gross and microscopic examination of the lungs all confirmed the reversal of the atelectasis seen before treatment. Animals treated with a dose of 200 mg/kg showed a faster, more consistent, and greater response than did a group treated with an average dose of 127 mg/kg. There was no evidence of toxicity after treatment with the higher dose as demonstrated by physiologic, hematologic, biochemical, and pathologic data. The importance of the peptide in the synthetic surfactant was apparent from the results obtained with a control group of nine premature monkeys treated with a non-peptide-containing surfactant; the a/A of this group was 0.15 +/- 0.03 at nine hours of age as compared with a value of 0.38 +/- 0.02 for 30 comparable animals receiving KL4-Surfactant.
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PMID:Efficacy of synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome in preterm infant rhesus monkeys. 884 50

The interaction of arginine analogues, which are known to inhibit nitric oxide synthase, with two cationic amino acid transporters of human erythrocytes (systems y+ and y+L) was studied. Arginine and relevant analogues [NG-monomethyl-L-arginine (L-NMMA); NG-monomethyl-D-arginine (D-NMMA) and NG-nitro-L-arginine (L-NOARG)] were found to inhibit labeled lysine influx into intact erythrocytes. As expected, the pattern of inhibition reflected the contribution of the two distinct transport systems. All analogues showed a higher affinity for system y+L than for system y+. The half-saturation (inhibition) constants estimated for systems y+ and y+L (+/- SEM) were (microM): L-arginine, 55.7 +/- 5.4 and 2.4 +/- 0.1; L-NMMA, 151 +/- 13 and 7.5 +/- 0.5; D-NMMA, 2660 +/- 404 and 269 +/- 25; L-NOARG, 9414 +/- 169 and 594 +/- 35. The transport properties of the analogues were investigated using an assay based on the trans-stimulation of lysine efflux. The addition of saturating concentrations of unlabeled analogues to the external medium stimulated efflux of labeled lysine through systems y+L and y+, showing that the analogues can enter the cell through these pathways.
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PMID:Transport of nitric oxide synthase inhibitors through cationic amino acid carriers in human erythrocytes. 884 21


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