Biomedical subjects

R K Chawla

Publications and source records attributed to R K Chawla.

At least 19 recordsLinked to original sources

PubMed2001

How is the liver primed or sensitized for alcoholic liver disease?

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hidekazu Tsukamoto and Yoshiyuki Takei. The presentations were (1) Tribute to Professor Rajendar K. Chawla, by Craig J. McClain; (2) Dysregulated TNF signaling in alcoholic liver disease, by Craig J. McClain, S. Joshi-Barve, D. Hill, J Schmidt, I. Deaciuc, and S. Barve; (3) The role of mitochondria in ethanol-mediated sensitization of the liver, by Anna Colell, Carmen Garcia-Ruiz, Neil Kaplowitz, and Jose C. Fernandez-Checa; (4) A peroxisome proliferator (bezafibrate) can prevent superoxide anion release into hepatic sinusoid after acute ethanol administration, by Hirokazu Yokoyama, Yukishige Okamura, Yuji Nakamura, and Hiromasa Ishii; (5) S-adenosylmethionine affects tumor necrosis factor-alpha gene expression in macrophages, by Rajendar K. Chawla, S. Barve, S. Joshi-Barve, W. Watson, W. Nelson, and C. McClain; (6) Iron, retinoic acid and hepatic macrophage TNFalpha gene expression in ALD, by Hidekazu Tsukamoto, Min Lin, Mitsuru Ohata, and Kenta Motomura; and (7) Role of Kupffer cells and gut-derived endotoxin in alcoholic liver injury, by N. Enomoto, K. Ikejima, T. Kitamura, H. Oide, Y. Takei, M. Hirose, B. U. Bradford, C. A. Rivera, H. Kono, S. Peter, S. Yamashina, A. Konno, M. Ishikawa, H. Shimizu, N. Sato, and R. Thurman.

Animals↗

PubMed1999

S-adenosylmethionine attenuates the lipopolysaccharide-induced expression of the gene for tumour necrosis factor alpha.

Intracellular deficiency of S-adenosylmethionine (AdoMet) and elevated serum concentrations of tumour necrosis factor alpha (TNF) are hallmarks of toxin-induced liver injury. In these models, the administration of either exogenous AdoMet or antibody/soluble receptor for TNF attenuates the injury. We have demonstrated previously that the administration of exogenous AdoMet to AdoMet-deficient rats attenuated lipopolysaccharide (LPS)-induced liver injury and serum TNF concentrations. Here we report that AdoMet lowered the amount of TNF secreted by LPS-stimulated murine macrophage cells (RAW 264.7) in a dose-dependent manner. The inhibition of TNF release was correlated with changes in the steady-state TNF mRNA concentrations. Changes in TNF mRNA were not due to its altered stability and might have been due to an attenuation of the transcription rate of the TNF gene. The inhibition of TNF release in RAW cells was not mediated by GSH because treatment with AdoMet did not increase intracellular GSH. In addition, N-acetylcysteine, whereas it did increase GSH concentration, had no effect on LPS-stimulated TNF release in these cells. Exogenous AdoMet also attenuated LPS-induced serum TNF levels in normal rats sensitized with lead. Thus AdoMet administration might exert its hepatoprotective effects at least in part by its inhibitory effect on expression of the gene for TNF.

Acetylcysteine↗

PubMed1998

S-adenosylmethionine deficiency and TNF-alpha in lipopolysaccharide-induced hepatic injury.

S-adenosylmethionine (Adomet) is a substrate for de novo synthesis of choline. Adomet deficiency occurs in certain types of liver injury, and the injury is attenuated by exogenous Adomet. Tumor necrosis factor-alpha (TNF-alpha) is also a mediator of these models of hepatotoxicity. We investigated the role of Adomet in lipopolysaccharide (LPS)-induced liver injury in rats made deficient in both Adomet and choline. Rats were maintained on either a methionine-restricted and choline-deficient (MCD) diet or a diet containing sufficient amounts of all nutrients [methionine and choline sufficient (MCS)] and then administered either LPS or saline. MCS-LPS rats had normal liver histology and no change in serum transaminases compared with the MCS-saline control group. MCD-saline rats had hepatosteatosis but no necrosis, and a five- to sevenfold increase in transaminases vs. the MCS-saline group. MCD-LPS rats additionally had hepatonecrosis and a 30- to 50-fold increase in transaminases. Exogenous Adomet administration to MCD-LPS rats corrected the hepatic deficiency of Adomet but not of choline, prevented necrosis but not steatosis, and attenuated transaminases. Serum TNF-alpha was sixfold higher in MCD rats even without LPS challenge and 300-fold higher with LPS challenge. Exogenous Adomet attenuated increased serum TNF-alpha in MCD-LPS rats.

Alanine Transaminase↗

PubMed1997

Choline deficiency augments and antibody to tumor necrosis factor-alpha attenuates endotoxin-induced hepatic injury.

Alcoholic liver disease can be associated with hepatic choline deficiency and hepatic steatosis, abnormalities also observed in rats administered choline-deficient (CD) diets. Bacterial lipopolysaccharides (LPS) have been postulated to play a key role in this choline deficiency model of liver injury, and LPS hepatotoxicity is mediated to a major extent by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). This study addressed the following questions: Does LPS administration exacerbate an in vivo liver injury induced by choline deficiency? If so, do CD rats have increased serum TNF-alpha concentrations and does pretreatment anti-TNF-alpha IgG attenuate this injury? Rats administered choline-sufficient (CS) or CD diets for 16 days were intravenously administered either saline or LPS. One group of CD rats also received a single dose of anti-TNF-alpha IgG before LPS administration. Changes in histology and serum transaminase levels were determined. Both liver histology and serum transaminases were unchanged in the CS group treated with LPS, compared with the CS group treated with saline (control group). However, compared with this control group, transaminases were 5- to 7-fold higher in saline-treated CD rats and 30- to 50-fold higher in LPS-treated CD rats. Livers of saline-treated CD rats had massive fatty infiltration, and no necrosis but livers of LPS-treated CD rats showed both extensive fatty infiltration and large areas of necrosis. Serum TNF-alpha concentrations in CD rats (saline or LPS treated) were significantly elevated, compared with levels in corresponding CS rats. Pretreatment with the anti-TNF-alpha IgG prevented hepatonecrosis in LPS-treated CD rats and lowered their serum transaminases by one-third. Thus, LPS administration exacerbated liver injury induced by choline deficiency, and this injury was probably partially mediated by TNF-alpha and attenuated by anti-TNF-alpha IgG.

Animals↗

PubMed1996

Effect of hypoxia on hepatic DNA methylation and tRNA methyltransferase in rat: similarities to effects of methyl-deficient diets.

Young rats were maintained in a 10% oxygen atmosphere for 2, 6, and 10 days and administered normal rat chow and water ad libitum. Thereafter, their hepatic S-adenosyl-L-methionine (AdoMet) and activity and mRNA levels of AdoMet synthetase were assayed. AdoMet levels decreased by 45% after 10 days; hepatic AdoMet synthetase also declined by approximately 40%. In rats with low hepatic AdoMet, the mRNA level of AdoMet synthetase also declined by up to 80%. No significant change in AdoMet or AdoMet synthetase was noted in pair-fed normoxic rats. DNA hypomethylation was determined in terms of incorporation of [3H]methyl of AdoMet incorporated at unmethylated sites in DNA in reactions mediated by methylases HpaII and SssI. As compared to the normal hepatic DNA, [3H]methyl group incorporation in the 10-day hypoxic DNA was almost double in the HpaII-mediated reaction and approximately 10-fold in the SssI-mediated reaction. Hepatic tRNA methyltransferase activity doubled after 10 days of hypoxia. However, hypoxic rats showed no detectable mRNA transcripts for c-myc and c-fos oncogenes on Northern blot analysis. These observations show that because of subnormal activity of AdoMet synthetase, hypoxic liver is depleted of AdoMet, even when the animals are administered a complete diet. However, unlike rats on chronic lipotrope-deficient diets, hypoxic rats on a complete diet show no aberrant expression of oncogenes.

Animals↗

PubMed1995

Regulation of alpha 1-antichymotrypsin synthesis in cells of epithelial origin.

Oncostatin M, interleukin-1 and the glucocorticoid analog, dexamethasone, have been identified as potent stimulators of alpha 1-antichymotrypsin production in various cells of epithelial origin. Although being able to act individually, these factors exerted a dramatic increase in alpha 1-antichymotrypsin synthesis when administrated in combination. Their stimulatory effect was independent of the levels of constitutive synthesis of this inhibitor, which was already high in lung- and breast- and low in skin-derived epithelial cells. Since alpha 1-antichymotrypsin controls chymotrypsin-like proteinases which are released during inflammation, these data support the concept that local synthesis of this inhibitor may be important in reducing tissue damage associated with this process.

Dexamethasone↗

PubMed1995

Stimulatory effect of inflammatory cytokines on alpha 1-antichymotrypsin expression in human lung-derived epithelial cells.

Although it is a well known fact that hepatocytes are the primary source of plasma proteinase inhibitors, including alpha 1-antichymotrypsin, this protein has also been detected in lung epithelial cells, which may suggest its local production. We have demonstrated that lung-derived epithelial cells are capable of synthesizing high levels of alpha 1-antichymotrypsin. In normal bronchial epithelial cells, as well as in the HTB55 human adenocarcinoma cell line, alpha 1-antichymotrypsin synthesis was under the control of inflammatory cytokines, of which oncostatin M was the most potent stimulator. This finding is consistent with a role for this inhibitor in protecting the lung epithelium from damage by chymotrypsin-like enzymes released from phagocytes such as neutrophils following pathogen invasion.

Adenocarcinoma↗

PubMed1994

Abnormal metabolism of S-adenosyl-L-methionine in hypoxic rat liver. Similarities to its abnormal metabolism in alcoholic cirrhosis.

S-Adenosylmethionine (AdoMet) is an important biologic methylating agent for nucleic acids, phospholipids, biologic amines, and proteins. Previous studies indicated that hepatic AdoMet synthetase and hepatic levels of AdoMet are subnormal in patients with alcoholic cirrhosis. This abnormality limits the patients' capacity to convert phosphatidylethanolamine to phosphatidylcholine by way of phosphatidylethanolamine-N-methyltransferase (PEMT). Because alcoholic consumption appears to be associated with hepatic hypoxia, we previously measured AdoMet concentration in liver cells under acute hypoxia and found the level to be decreased substantially. In the present study, we determined whether a similar metabolic abnormality was also observed in rats maintained under physiologic hypoxia for 9 days and administered standard rat chow. The study showed that AdoMet levels in hypoxic rat (ave +/- SD) were significantly lower than those in the control (36.8 +/- 11.6 vs. 60.4 +/- 2.3 nmol/g liver; P < 0.05). Also significantly lower in the hypoxic group were the activities of AdoMet synthetase (0.60. +/- 0.07 vs. 0.97 +/- 0.20 U; P < 0.05) and PEMT (26.2 +/- 4.2 vs. 35.6 +/- 5.8 U; P < 0.02). The mRNA levels of AdoMet synthetase also declined in hypoxia indicating that hypoxia may modulate the gene expression of hepatic AdoMet synthetase. Thus, in vivo hypoxia may have an important effect on 1-carbon metabolism.

Animals↗

PubMed1992

Cancer-related urinary proteinase inhibitor, EDC1: a new method for its isolation and evidence for multiple forms.

During the past several years, numerous laboratories have reported isolation and purification of proteinase inhibitors from human urine. Many of these molecules were incompletely characterized and some of them may have been artifacts in part because of harsh procedures used for their isolation. Consequently, there is disagreement and confusion regarding the biochemical characteristics of these inhibitors. We previously reported the isolation of a proteinase inhibitor, EDC1, from the urine of a leukemic patient. This molecule, M(r) 30 kDa, was antigenically related to plasma inter-alpha-trypsin inhibitor (IATI) and inhibited the growth of a virally transformed B cell line. Immunoreactive EDC1 was also the major component of low molecular weight proteinuria observed in cancer patients. We now report a new method for the isolation of EDC1 from urine of patients with adenocarcinomas of colon and lung and melanoma and compare its partial amino acid sequence with that of HI 30, a proteinase inhibitor previously isolated from pooled normal urine by Hochstrasser et al. [Hoppe-Seyler's Z Physiol Chem 357:153-162, 1976]. Our method involves i) a batchwise cation exchange, ii) gel filtration chromatography, iii) anion exchange chromatography on FPLC, and iv) reverse phase C18 chromatography on HPLC. This method is mild and results in an overall yield of 0.4 to 1.2 mg of EDC1/liter urine. On the basis of the partial N-terminal amino acid sequence of its N terminal (38 residues) and middle regions (29 residues), EDC1 appears to be identical with HI30. Surprisingly, during this isolation procedure, another proteinase inhibitor, M(r) 22 kDa, which cross-reacted with antisera to EDC1 and IATI, was also isolated. The 22 kDa molecule was a major component of the IATI related urinary molecules and was identical with the 30 kDa EDC1 in which first the 15 N terminal residues were clipped. The lower M(r) inhibitor was not an artifact formed during storage or isolation procedure because the Western blot analysis of fresh cancer and normal urine revealed the 30 and 22 kDa molecules. Thus, both the 30 kDa EDC1 (or HI30) and its clipped variant, the 22 kDa molecule, are physiologic components of IATI related urinary proteinase inhibitors and excretion of both forms may be increased in patients with advanced cancer.

Adenocarcinoma↗

PubMed1991

Adenosine deaminase levels in cerebrospinal fluid in tuberculosis and bacterial meningitis.

Adenosine deaminase activity was measured in cerebrospinal fluid of patients with confirmed tuberculous and bacterial meningitis. The values were compared with those of control subjects without meningitis. A statistically significant increase in the level of this enzyme was noted in the two types of meningitis, but no definite demarcation in the levels was observed between the two types. Therefore increases in adenosine deaminase activity may not be of such diagnostic significance as reported elsewhere.

Adenosine Deaminase↗

PubMed1990

Plasma inter-alpha-trypsin inhibitor-related urinary glycoprotein EDC1 inhibits the growth of a Burkitt's lymphoma cell line.

A homogeneous preparation of a urinary glycoprotein has been isolated from urine of patients with malignant melanoma and advanced adenocarcinomas of colon and lung. This molecule, Mr 30 kDa, is homologous to EDC1, a proteinase inhibitor antigenically related to plasma inter-alpha-trypsin inhibitor (IATI) originally isolated from the urine of a leukemic patient, E.D. The newly isolated EDC1 inhibits cellular proliferation of a Burkitt's lymphoma cell line, Raji, growing in serum-free medium supplemented with insulin, transferrin, selenium, and linoleic acid. This concentration-dependent inhibitory effect was monitored in terms of change in cell number and 3H-thymidine incorporation. The growth of cells treated with approximately 3.3 pmol EDC1/ml was 50% that of the control group by both assays. EDC1 was not cytotoxic to the cells because the EDC1-treated cells excluded trypan blue and resumed normal growth after removal of EDC1. In addition, EDC1 treatment of Raji cells prelabeled with 3H-labeled DNA did not release more radioactivity into the conditioned medium than the untreated labeled cells. EDC1 did not affect the growth of Hs2B2, a B-lymphoblast cell line, and Hs294T, a human malignant melanoma cell line. Equimolar and larger quantities of other proteinase inhibitors with inhibitory profiles similar to that of EDC1 (alpha-1 proteinase inhibitor, soybean trypsin inhibitor, lima bean trypsin inhibitor, and turkey ovomucoid) did not affect the growth of Raji cells. Raji cells have an absolute requirement of transferrin as a nutrient and require insulin to modulate the expression of transferrin receptors. The cells also synthesize interleukin-1 as an autocrine growth stimulator. EDC1 did not form a detectable complex with transferrin, insulin, or any autocrine factor synthesized by the cells.

Alpha-Globulins↗

PubMed1990

Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease.

The major biological functions of S-adenosyl-L-methionine (SAMe) include methylation of various molecules (transmethylation) and synthesis of cysteine (trans-sulphuration). A stable double salt of SAMe has been found to be effective in intrahepatic cholestasis. The mechanism of its therapeutic effect is not fully understood but presumably involves methylation of phospholipids. Methylation of plasma membrane lipids may affect membrane fluidity and viscosity, which modulate the activities of a number of membrane-associated enzymes, for example, the activity of enzymes involved in Na+/Ca++ exchange (e.g. sarcolemmal vesicles), Na+/K+ adenosine triphosphatase (ATPase) [e.g. hepatocyte plasma membranes], and Na+/H+ exchange (e.g. plasma membranes of colonic cells). Recently, patients with cirrhosis were shown to have an acquired metabolic block in the hepatic conversion of methionine to SAMe. These patients, when administered conventional elemental diets, develop abnormally low plasma concentrations of cysteine and choline, 2 nonessential nutrients present in low concentrations in most elemental diets. These low concentrations probably reflect systemic deficiencies attributable to reduced endogenous syntheses of cysteine and choline caused by limited availability of hepatic SAMe. Such cirrhotic patients are often in negative nitrogen balance and have abnormal hepatic functions, which are corrected by cysteine and choline supplements. Noncirrhotic patients on parenteral elemental diets also become deficient in cysteine and choline. Consequently, these patients may require SAMe as an essential nutrient to normalise their overall hepatic transmethylation and trans-sulphuration activities.

Animals↗

PubMed1989

Choline may be an essential nutrient in malnourished patients with cirrhosis.

Elemental diets designed for nutritional support in protein-calorie malnutrition are often deficient in choline, a nonessential nutrient. Previously, malnourished patients on these diets were found to be at risk of developing plasma choline deficiency. We have now estimated the prevalence of this deficiency by determining fasting plasma levels of choline among cirrhotic and noncirrhotic malnourished male subjects maintained on regular hospital mixed food or elemental parenteral and enteral formulas. Plasma choline concentrations (microM, average +/- SD) were as follows: (i) mixed foods, 11.3 +/- 4.3 for cirrhotic (n = 22) and 9.3 +/- 2.4 for noncirrhotic (n = 12) patients; (ii) parenteral formula, 5.3 +/- 1.6 for cirrhotic (n = 5) and 8.6 +/- 5.2 for noncirrhotic (n = 16) subjects; and (iii) enteral formula, 6.1 +/- 1.2 for cirrhotic (n = 5) and 11.7 +/- 1.9 for noncirrhotic (n = 4) subjects. The level for healthy normal subjects eating mixed foods was 12.0 +/- 2.2. The prevalence of plasma choline deficiency, i.e., plasma levels greater than or equal to 2 SD below the normal average, was as follows: parenteral formula, all cirrhotic and 10 of 16 noncirrhotic subjects; enteral formula, all cirrhotic and none of the noncirrhotic subjects. The reversibility of choline deficiency was examined in a longitudinal study of three phases involving 10 patients--5 with alcoholic cirrhosis (all on enteral formula); 5 noncirrhotic (1 on enteral and 4 on parenteral formula). During phase 1 (3-day equilibration period; ad libitum regular hospital diet), plasma choline levels were within the normal range for all subjects. During phase 2 (2 wk, choline depletion phase, elemental formulas), choline levels were subnormal in all cirrhotic subjects (5.1 +/- 2.0 microM) on enteral formula and all noncirrhotic patients on parenteral formula (5.9 +/- 1.3 microM). During phase 3 (2 wk, choline repletion phase, elemental formula + 6 g choline/day), the levels normalized in all patients (cirrhotic 11.4 +/- 3.1 microM and noncirrhotic 11.9 +/- 3.2 microM). Analyses of abdominal computed tomographic scans and plasma liver chemistries in the cirrhotic subjects during the three phases suggested a correlation between plasma choline deficiency and hepatic steatosis and abnormal liver enzyme levels in some patients. Therefore, choline may be an essential nutrient in malnourished cirrhotic patients and its deficiency may be associated with adverse hepatic effects.

Adult↗

PubMed1987

Serum alpha-1 proteinase inhibitor in advanced cancer: mass variants and functionally inert forms.

In 1984, we reported that while immunoreactive levels of serum alpha-1 proteinase inhibitor (API) increased significantly in nine patients with advanced solid tumors, the functional activity of the inhibitor, as measured by the serum trypsin inhibitory capacity, did not increase proportionately. This suggested that a portion of the circulating API was functionally inert. We have now assayed immunoreactive titers and trypsin inhibitory capacity of serum API of 49 patients with advanced carcinomas and 27 healthy controls. Immunoreactive levels of API (expressed as percentage of normal pooled serum which was taken as 100%) in cancer subjects were significantly elevated as compared to normals (mean +/- SE: 233 +/- 9.0% versus 102 +/- 2.0%, P less than 0.05). Although the trypsin inhibitory capacity of the cancer group (16.0 +/- 0.9 units/ml) was significantly elevated (P less than 0.05) as compared to normals (9.9 +/- 0.1 units/ml), this increase was less than that in the immunoreactive titer of API, suggesting the existence of functionally inert API in serum. The fraction of API which was functionally active in this group of cancer patients was 71.0 +/- 3.0% which was significantly less than the normal 98.0 +/- 2.0% (P less than 0.05). In 12 patients followed serially, both immunoreactive levels of API and the trypsin inhibitory capacity increased significantly at the time of clinical progression of disease. There was a significant correlation between increasing absolute granulocyte count and increasing trypsin inhibitory capacity (correlation coefficient 0.66; P less than 0.001). Neither disease progression nor increasing granulocyte count, however, was associated with increasing proportion of functionally inactive API. The inactive form of API had the same molecular weight as the native molecule as shown by gel permeation chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blot analysis of cancer sera. Therefore, the inactive form was not due to a complex between API and a tumor-derived protease or to proteolytic fragmentation of the native API. Elastase inhibitory capacity of cancer sera with subactive API was essentially identical with trypsin inhibitory capacity indicating that the active site methionine was not oxidized in the inert API. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blot analysis showed that both normal and cancer serum API existed as two mass variants, at Mr 58,000 and 56,000. Both variants formed complexes with elastase and were functionally active.

Blood Proteins↗

PubMed1987

Preparation of a monoclonal antibody to a melanoma growth-stimulatory activity released into serum-free culture medium by Hs0294 malignant melanoma cells.

Autostimulatory growth factors may contribute to the ability of malignant cells to escape normal growth controls. We have previously shown that Hs0294 human malignant melanoma cells release into culture medium an acid-soluble, heat-stable, trypsin-sensitive, autostimulatory monolayer mitogen which can be purified from acetic acid extracts of conditioned medium by gel filtration, reverse-phase high-performance liquid chromatography, and preparative electrophoresis. The majority of this melanoma growth-stimulatory activity (MGSA) resides in a 16-Kd moiety, though bioactivity is also associated with 24-26 and less than 14-Kd forms of MGSA (Richmond and Thomas: J Cell Physiol 129:375, 1986). In order to further characterize this growth factor, monoclonal antibodies were prepared against a partially purified preparation of the autostimulatory melanoma mitogen. Monoclonal antibody clones were selected based on supernate inhibition of 3H-thymidine incorporation in serum-free Hs0294 melanoma cultures. One of these, termed FB2AH7, slows, but does not completely block, the growth of Hs0294 cells in serum-free medium in a dose-dependent manner. This antibody does not slow the growth of normal rat kidney fibroblasts, which neither produce nor require this mitogen, in either serum-free medium or medium containing 0.8% calf serum. This monoclonal antibody also blocks the mitogenic effects of partially purified preparations of this melanoma growth stimulatory activity (MGSA) on both Hs0294 cells and normal rat kidney fibroblasts. The FB2AH7 antibody has been demonstrated to bind MGSA by Western blot and by immunoprecipitation procedures. Western blot analysis of reverse-phase high-performance liquid chromatography purified growth factor demonstrated that FB2AH7 antibody binds to the 16-Kd and approximately 13-14-Kd forms of MGSA. FB2AH7 antibody can be used in immunoprecipitation experiments to bind the approximately 13-16-Kd forms of MGSA. The specificity of the binding of FB2AH7 antibody for MGSA but not other growth factors has been demonstrated in a modified dot blot assay. These data thus support the hypothesis that MGSA is an autostimulatory melanoma mitogen distinct from other growth factors.

Animals↗

PubMed1987

Beta-endorphin-induced hyperglycemia in rabbits: effects of a glucose or arginine challenge.

The effects of beta-endorphin on glucose, insulin, and glucagon levels were studied in normal fasted adult male rabbits. An intravenous bolus of glucose (0.7 g/kg body wt) produced a hyperglycemic state (peak plasma glucose 306 +/- 22 mg/dl; means +/- SE) that lasted approximately 90 min. beta-Endorphin (31 micrograms/g body wt; iv) administered immediately prior to the glucose challenge resulted in plasma glucose levels that were significantly higher from 10 to 90 min after the glucose challenge (P less than 0.001-0.05). From 10 to 30 min, plasma insulin levels were significantly lower in the beta-endorphin group (P less than 0.001-0.05), peaking at one-half the control group levels. Glucagon levels were unchanged by the glucose bolus in either the control or beta-endorphin-treated group (means +/- SE = 102.8 +/- 4 pg/ml). In another experiment, a 30-min infusion of L-arginine (13 mg-1 X kg body wt-1 X min iv) in normal fasted rabbits produced a rapid (10 min) increase in plasma insulin and glucagon and a return to base-line levels 60 min after withdrawing the arginine stimulus. Plasma glucose levels were not altered by arginine (mean +/- SE = 94.5 +/- 1 mg/dl). Administration of beta-endorphin (31 micrograms/kg body wt iv) at the start of the arginine infusion resulted in a rapid (10 min) and long-lasting (up to 60 min) hyperglycemic effect associated with a significant decrease in insulin levels (10-20 min; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Cotton dust contains proteolytic and elastolytic enzymes not inhibited by alpha-1-proteinase inhibitor.

Others have found proteolytic activity in cotton dust and correlated this with the prevalence of acute byssinosis. The present study characterized the proteases in aqueous extracts of cotton dust after controlling for potential artifact from microbial contamination. We tested cotton dust, generated in a model card room operated by the U.S. Department of Agriculture (USDA), for total proteolytic activity (hydrolysis of azocasein) and elastolytic activity (degradation of insoluble 3H-elastin). Both coarse dust and a respirable fraction (aerodynamic diameter less than or equal to 1.7 microgram) yielded proteolytic activity. Proteolysis was inhibited by EDTA (39%), diisopropylfluorophosphate (DFP) (33%) and alpha-1-proteinase inhibitor (alpha 1 PI) (30%), but not by iodoacetic acid or pepstatin. Elastolytic activity was also present, and was inhibited by DFP (80%) and alpha 1 PI (70%), but not by EDTA. We conclude that cotton dust contains preformed metallo- and serine proteases, and serine elastolytic protease(s) which are incompletely inhibited by alpha 1 PI. These findings may be relevant to the development of chronic lung disease in people exposed to cotton dust.

Byssinosis↗

PubMed1985

Plasma concentrations of transsulfuration pathway products during nasoenteral and intravenous hyperalimentation of malnourished patients.

We have monitored the plasma concentrations of products of the transsulfuration pathway in 11 undernourished noncirrhotic patients, and in 10 cachectic cirrhotic subjects, before and during nasoenteral nutrition with Vivonex (Norwich-Eaton Pharmaceuticals, Norwich, NY) or total parenteral nutrition (TPN) with FreAmine III (American McGaw, Irvine, CA). In the cirrhotic cases eating a mixed diet, levels of taurine, cysteine, plasma glutathione, and free choline were subnormal. During nasoenteral hyperalimentation, methionine was elevated while cysteine, glutathione, and free choline levels remained depressed. During TPN, levels of taurine, cysteine, protein-bound cysteine, glutathione, free choline, and phosphatidyl choline were depressed and methionine was elevated. In the noncirrhotic cases eating a mixed diet, only the free choline concentration was low. During nasoenteral hyperalimentation, the plasma levels of both free choline and total carnitine were depressed. During TPN, plasma levels of cystine, protein-bound cysteine, total carnitine, free choline, and phosphatidyl choline were subnormal. These data suggest that biosynthesis of several products of the transsulfuration pathway may be inadequate in both cirrhotic and noncirrhotic patients during TPN with FreAmine III.

Adolescent↗