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Biomedical subjects

V Mohsenin

Publications and source records attributed to V Mohsenin.

At least 37 records · Page 2Linked to original sources
PubMed1993

Glucose suppresses superoxide generation in normal neutrophils: interference in phospholipase D activation.

In neutrophils, N-formyl-Met-Leu-Phe (FMLP) stimulates a respiratory burst with subsequent generation of superoxide anion (O2-.) by NADPH oxidase. Signal transduction involved in this process includes FMLP receptor stimulation of phosphoinositide hydrolysis with formation of inositol 1,4,5-trisphosphate and diacylglycerol and phosphatidylcholine hydrolysis with formation of phosphatidic acid. Generation of these second messengers would lead to activation of NADPH oxidase and generation of O2-.. Neutrophils from diabetic subjects and normal neutrophils exposed to glucose have diminished ability to activate the respiratory burst in response to various agonists. The mechanism of this suppression remains unknown. We report herein that treatment of neutrophils with 15 and 50 mM glucose significantly suppresses the O2-. formation in response to receptor-mediated stimulation. The decreased O2-. generation is associated with marked inhibition of phospholipase D (PLD) activity, with limited hydrolysis of phosphatidylcholine and formation of phosphatidic acid. Sorbitol (50 mM), a nonmetabolizable sugar with a similar osmotic effect, has no influence on O2-. generation or PLD activation. The 4 beta-phorbol 12-myristate 13-acetate (PMA)-induced O2-. generation as well as PLD activation are unaffected by glucose. Furthermore, the intracellular Ca2+ transient in response to FMLP is not influenced by glucose. Taken together, these data suggest that glucose differentially interferes with activation of PLD but not phospholipase C. And, the fact that PMA-induced activation of PLD is not altered by glucose further suggests that a protein kinase C independent step leading to the activation of PLD may be altered by glucose.

Calcium↗
PubMed1991

Unsaturated phosphatidylcholines inhibit superoxide production in human neutrophils.

Unsaturated long chain phosphatidylcholines such as phosphatidylcholine dioleoyl and phosphatidylcholine dilinoleoyl in micromolar concentrations inhibited the superoxide production in neutrophils stimulated by the activators of protein kinase C, phorbol 12-myristate 13-acetate and 1,2-dioctanoyl-sn- glycerol. In contrast, the superoxide production induced by surface receptor agonist, formyl-methionyl-leucyl-phenylalanine, was unaffected by the phospholipids. These data suggest that surfactant phosphatidylcholines may have a modulatory role on neutrophil oxidative burst in the lung during inflammation where there is a preponderance of unsaturated phosphatidylcholines.

Analysis of Variance↗
PubMed1991

Lipid peroxidation and antielastase activity in the lung under oxidant stress: role of antioxidant defenses.

The role of lipid peroxidation in the inactivation of alpha 1-protease inhibitor (alpha 1-PI) in the alveolar lining fluid of human subjects has been examined under oxidant stress. Exposure to nitrogen dioxide (NO2) at 4 ppm for 3 h resulted in a significant increase in the amount of lipid peroxidation products in the alveolar lining fluid, with conjugated dienes the predominant species. Four-week supplementation with vitamins C and E before NO2 exposure markedly decreased the levels of conjugated dienes (control 804 +/- 103 pmol/micrograms total phospholipids vs. vitamin-supplemented 369 +/- 58, P = 0.003). Malondialdehydes, although detectable in the lavage fluid, contributed little to the total amount of lipid peroxidation products, and the levels were comparable in both groups. NO2 exposure in the absence of vitamin supplementation caused a significant decrease in the elastase inhibitory capacity (EIC) of the alveolar lining fluid in the control group but not in the vitamin-supplemented group [control 3.67 +/- 0.32 micrograms alpha 1-PI/micrograms porcine pancreatic elastase (PPE) vs. vitamin-supplemented 2.75 +/- 0.17, P less than 0.03]. The vitamin-supplemented group had a lower level of conjugated dienes and a higher EIC. Conversely, the control group had higher levels of conjugated dienes and a lower EIC in their lavage fluid. These studies demonstrate that lipid peroxidation occurs as an early event during oxidant exposure in the lungs of normal subjects. The appearance of lipid peroxidation products in the lavage fluid is associated with a decrease in the EIC of the alveolar lining fluid. Vitamins C and E diminish lipid peroxidation and preserve the EIC of the lower respiratory tract fluid during oxidant stress.

Adult↗
PubMed1990

Respiratory burst in alveolar macrophages of diabetic rats.

Bactericidal ability of alveolar macrophages is depressed in rats with diabetes mellitus. To define the mechanism of this abnormality, we measured the parameters of respiratory burst in alveolar macrophages, peripheral blood monocytes, and neutrophils of rats 8 wk after the induction of diabetes by streptozocin. Superoxide anion (O2-.) generation during basal conditions and after stimulation with phorbol myristate acetate (PMA) was measured as superoxide dismutase-inhibitable cytochrome c reduction. NADPH, the principal substrate for NADPH-oxidase-dependent O2-. generation, was measured in the alveolar macrophages and quick-frozen lungs by the enzyme-cycling method. O2-. generation after PMA was significantly lower in the alveolar macrophages of diabetics than in the controls (14.4 +/- 2.0 nmol.10(6) cells-1.20 min-1 vs. 26.2 +/- 1.9, P less than 0.05). Conversely the peripheral blood monocytes of diabetics demonstrated an enhanced O2-. production after PMA stimulation. There was no significant difference in the neutrophil O2-.-generation between the groups. The alveolar macrophage NADPH (control 0.44 +/- 0.15 nmol/10(6) cells vs. diabetic 0.21 +/- 0.04, P less than 0.05) and lung tissue NADPH levels (control 81.4 +/- 16.3 nmol/g dry wt vs. diabetic 35.8 +/- 20.5, P less than 0.05) were significantly lower in the diabetics than in the controls. These data indicate that the O2-.-generating capacity of alveolar macrophages is markedly depressed in diabetes, whereas their precursors, monocytes, are primed to generate O2-. with PMA stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Oxidation of alpha 1-protease inhibitor: role of lipid peroxidation products.

Previously we demonstrated that in vivo exposure of humans to NO2 resulted in significant inactivation of alpha 1-protease inhibitor (alpha 1-PI) in the bronchoalveolar lavage fluid. However, alpha 1-PI retains its elastase inhibitory activity in vitro when exposed to 10 times the concentration of NO2 used in vivo. We suggested exogenous oxidants such as O2 and NO2 exert their effect in vivo in part through lipid peroxidation. We investigated the mechanism of inactivation of alpha 1-PI in the presence or absence of lipids under oxidant atmosphere. alpha 1-PI in solutions containing phosphate buffer (control), 0.1 mM stearic acid (saturated fatty acid, 18:0), or 0.1 mM linoleic acid (polyunsaturated fatty acid, 18:2) was exposed to either N2 or NO2 (50 ppm for 4 h). Elastase inhibitory capacity of alpha 1-PI was significantly diminished in the presence of 0.1 mM linoleic acid and under NO2 atmosphere (75 +/- 8% of control, P less than 0.01), whereas there was no change in elastase inhibitory capacity of alpha 1-PI in the presence or absence (buffer only) of 0.1 mM stearic acid under a similar condition (109 +/- 11 and 94 +/- 6%, respectively). The inactivated alpha 1-PI as the result of peroxidized lipid could be reactivated by dithiothreitol and methionine sulfoxide peptide reductase, suggesting oxidation of methionine residue at the elastase inhibitory site. Furthermore the inhibitory effect of peroxidized lipid on alpha 1-PI could be prevented by glutathione and glutathione peroxidase and to some extent by alpha-tocopherol.

Antioxidants↗
PubMed1989

Nutrition for the respiratory insufficient patient.

Malnutrition is fairly common in patients with chronic obstructive pulmonary disease, the more severe the airway obstruction the more severe the nutritional status. The consequences of nutritional depletion on respiratory and immune systems are ventilatory compromise and susceptibility to infection. Diaphragm muscle mass and thickness is decreased in patients with COPD. This results in decreased maximum voluntary ventilation and diminished inspiratory pressure. Malnutrition is one of the causes of failure to wean in patients with respiratory failure. Malnutrition also has profound effects on cell-mediated immune response and humoral immunity with reduced levels of secretory IgA. In patients with COPD, colonization of respiratory tract bears a direct relationship with parameters of nutritional status. Patients with significant nutritional impairment have more tracheal cell bacteria adhered to and the tracheas were more frequently colonized by Pseudomonas species. The improvement of nutrition in these patients resulted in less bacterial cell binding to tracheal epithelial cells.

Enteral Nutrition↗
PubMed1988

Airway responsiveness and prostaglandin generation in scorbutic guinea pigs.

Airway responsiveness to histamine aerosol and lung prostaglandin generation were investigated in normal, partially vitamin C deficient and scorbutic guinea pigs. The ascorbic acid content of the lung expressed as microgram/100 mg wet weight lung parenchyma decreased from 22.1 +/- 1.8 (mean +/- SE) in the control group to 9.0 +/- 1.4 and 1.8 +/- 0.4 in tissues from partially ascorbic acid deficient and scorbutic animals, respectively. Guinea pigs on low and ascorbic acid deficient diets developed significant airway hyperresponsiveness to histamine aerosol after 3 and 4 weeks. Indomethacin (30 mg/Kg, i.p.) further increased the airway hyperresponsiveness in scorbutic animals but was without effect in control animals. Prostaglandin generation from different parts of the lung was significantly changed by the diets. However, airway hyperresponsiveness was not directly attributable to altered prostanoid generation. Scorbutic conditions did not alter the electrophysiological characteristics of airway smooth muscle namely, resting membrane potential and electrogenic sodium pump activity. In summary, ascorbic acid deficiency causes airway hyperresponsiveness to histamine in guinea pigs. This alteration seems not to be related to an altered prostaglandin generation by the lung or to the electrophysiological properties of airway smooth muscle.

Aerosols↗
PubMed1988

Bilateral diaphragmatic paralysis: clinical spectrum, prognosis, and diagnostic approach.

In a retrospective review of the clinical course of five patients with nontrauma-related bilateral diaphragmatic paralysis, we found that the diagnosis is generally delayed (median delay: two years) in the presence of moderate to severe respiratory insufficiencies. Orthopnea out of proportion to the underlying cardiopulmonary status and thoracoabdominal paradoxus in the supine position are the clues to the diagnosis. Pulmonary function tests showed a typical restrictive ventilatory defect, and arterial blood gas showed chronic respiratory acidosis. Failure to recognize the diaphragmatic impairment led to cardiopulmonary decompensations such as cor pulmonale and acute respiratory failure. However, with the institution of appropriate therapy, adverse effects resolved and all five patients are alive and continue to lead independent lives. We conclude that nontrauma-related bilateral diaphragmatic paralysis is an underrecognized and underdiagnosed condition. The results also indicate that early diagnosis and treatment can minimize morbidity and mortality, and that excellent long-term, good-quality survival can be expected.

Aged↗
PubMed1987

Airway responses to nitrogen dioxide in asthmatic subjects.

Nitrogen dioxide is a common indoor air pollutant. In order to characterize the respiratory responses to this gas, 10 asthmatics (mean age +/- SD = 30 +/- 8 yrs) were exposed to air and 0.5 ppm NO2 gas for 1 h in a 30-m3 environmental chamber on different days in a double-blind randomized fashion. The forced vital capacity, (VC), functional residual capacity, forced expiratory volume in 1 s, partial expiratory flow at 40% VC (Vp 40), and specific airway conductance were measured before and after exposure. Airway reactivity to methacholine inhalation was determined after each exposure. The dose of methacholine in milligrams per milliliter to cause a 40% decrease in Vp 40 was measured. None of the subjects reported any significant symptoms after exposure. Significant potentiation of airway reactivity was noted after NO2 exposure in asthmatic subjects as a group [PD40(AIR) = 9.2 +/- SD 15.0 versus PD40(NO2) = 4.6 +/- SD 8.2 mg/ml, p = 0.042]. No significant changes were noted in other lung functions after NO2 exposure. These findings indicate that asthmatics exposed to 0.5 ppm NO2 develop heightened airway reactivity.

Adult↗
PubMed1987

Acute effect of nitrogen dioxide exposure on the functional activity of alpha-1-protease inhibitor in bronchoalveolar lavage fluid of normal subjects.

Nitrogen dioxide is one form of an oxidizing free radical that is sufficiently stable to exist in relatively high concentrations in ambient air and cigarette smoke. We examined the effect of NO2 exposure on the functional activity against pancreatic elastase of alpha-1-protease inhibitor (alpha 1PI) in bronchoalveolar lavage (BAL) fluid of nonsmoking subjects. Ten nonsmokers (mean age, 25 +/- 2 SE yr) were exposed to NO2 (3 or 4 ppm) for 3 h with intermittent exercise. Seven nonsmokers (mean age, 24 +/- 2 SE yr) underwent a similar protocol but were exposed to NO2-free air and served as control subjects. Bronchoalveolar lavage was performed 3.5 to 4 h after the end of exposure. Exposure to NO2 caused a 45% decrease in functional activity of alpha 1PI in BAL. There was no significant difference in immunoreactive alpha 1PI between the groups whether expressed as micrograms per 100 ml of recovered fluid or per milligram of albumin. This inactivation of alpha 1PI was not associated with any neutrophil migration into the air spaces of the lung. The "elastaselike" activity of BAL using synthetic elastinlike chromophore substrate succinyl-trialanine-nitroanilide showed no significant difference between the NO2-exposed group (221 +/- 39 SE ng/dl BAL) and the control group (196 +/- 61 SE ng/dl BAL). Assay for human leukocyte elastase (HLE) in concentrated BAL using the synthetic substrate Methoxysuc-Ala3-Pro-Val-aminomethylcoumarin did not detect any HLE activity in the BAL. These results showed that nonsmoking subjects exposed to relatively low concentrations of NO2 for a short time have a significant inactivation of alpha 1PI in the lower respiratory tract fluid than did nonsmoking control subjects.

Adult↗
PubMed1987

Effect of vitamin C on NO2-induced airway hyperresponsiveness in normal subjects. A randomized double-blind experiment.

We conducted a double-blind randomized study to determine the effect of vitamin C on NO2-induced airway hyperresponsiveness in normal subjects. Eleven normal subjects were randomly assigned an order for 4 experimental exposures. For each exposure, subjects took either vitamin C (500 mg 4 times a day for 3 days) or placebo followed by exposure either to clean air or to 2.0 ppm NO2. Measurements of lung mechanics and airway responsiveness to methacholine aerosol were obtained. Serum level of ascorbic acid was determined before each exposure. NO2 exposure with placebo resulted in significant enhancement of airway responsiveness to methacholine aerosol (air-placebo 64 +/- 7 to NO2-placebo 53 +/- 8 mg/ml). Pretreatment with ascorbic acid prevented the significant alteration in airway responsiveness to methacholine aerosol (65 +/- 13 mg/ml, p less than 0.04). These results suggest that airway hyperresponsiveness induced by NO2 in normal subjects is completely prevented by pretreatment with ascorbic acid.

Adolescent↗
PubMed1987

Diaphragmatic dysfunction in siblings with hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease).

Hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease) is characterized by chronic degeneration of peripheral nerves and roots, resulting in distal muscle atrophy, beginning in the feet and legs and later involving the hands. The association of this disease with diaphragmatic dysfunction has not been reported. We studied a patient with hereditary motor and sensory neuropathy type 1 (Charcot-Marie-Tooth disease) and type 2 diabetes mellitus who had severe diaphragmatic impairment. Some of the clinical findings are similar to the sleep apnea syndrome, which could lead to incorrect diagnosis and delay in the administration of appropriate therapy. Transdiaphragmatic pressure studies on the subject's brother, who also has Charcot-Marie-Tooth disease and type 2 diabetes mellitus, revealed subclinical impairment of diaphragmatic function. These findings suggest that phrenic nerve involvement may be part of the spectrum of polyneuropathy in Charcot-Marie-Tooth disease in association with diabetes mellitus.

Aged↗
PubMed1984

Tissue pressure and plasma oncotic pressure during exercise.

Six healthy male subjects exercised on a cycle ergometer for 3 min for assessment of forces involved in transvascular fluid shift during intense exercise. The work load was at 105% of peak O2 uptake of the subjects. This caused a 17.2 +/- 1.2% reduction in plasma volume. The plasma volume loss was associated with an increase in plasma sodium, from 142.6 +/- 0.5 to 148.1 +/- 1.0 meq X 1(-1) (P less than 0.005); chloride, from 101.8 +/- 0.6 to 104.6 +/- 0.9 meq X 1(-1) (P less than 0.005); lactate, from 1.4 +/- 0.2 to 14.0 +/- 1.5 meq X 1(-1) (P less than 0.005); and osmolality, from 283 +/- 2 to 299 +/- 3 mosmol X kg-1 H2O (P less than 0.005) within 2 min after cessation of exercise. Plasma protein increased from 7.0 +/- 0.2 to 8.1 +/- 0.3 g X dl-1 (P less than 0.005), and plasma colloid osmotic pressure from 25.1 +/- 0.6 to 30.6 +/- 1.4 mmHg (P less than 0.005) after exercise. Interstitial fluid pressure in the exercising vastus lateralis muscle increased from a base-line value (SE) of -1.0 +/- 0.9 to + 1.5 +/- 1.1 cmH2O, 14 min after the end of exercise (P less than 0.05). Interstitial fluid pressure of the triceps brachii (inactive) did not change significantly after exercise. Our data suggest that increased transvascular colloid osmotic pressure and elevation of interstitial fluid pressure become increasingly important in preventing loss of plasma volume during maximal exercise.

Adult↗
PubMed1983

Intercompartmental fluid shifts due to glucose release during hemorrhage in rabbits.

Intercompartmental fluid shifts were studied in 18 anesthetized New Zealand White rabbits after hemorrhage. During graded hemorrhage the plasma volume spontaneously replaced was proportional both in time and amount to the hyperosmolar response. This, in turn, was mainly due to hyperglycemia. In 5 fed rabbits and 5 rabbits unfed for 40 h, all subjected to 16 ml/kg of hemorrhage, plasma volume replacement was closely correlated with the hyperglycemic response. Plasma glucose concentration gradually increased in fed animals throughout a 2-h posthemorrhagic period, whereas the hyperglycemic response ceased 15 min after hemorrhage in unfed animals, and further fluid shift also stopped. During the first 30 min after hemorrhage most of the fluid that shifted into the bloodstream came from the interstitial space, as judged by a lack of change in plasma sodium and chloride concentrations. However, during the second hour of the posthemorrhagic period of well-fed rabbits, plasma sodium and chloride concentrations decreased, suggesting that dilute fluid had shifted from the cells to the interstitial space and bloodstream. We concluded that the hyperglycemic response during and after hemorrhage played a significant role in plasma volume replacement, but this was less after a period of food deprivation.

Animals↗
PubMed1983

Intercompartmental fluid shifts after dextran infusion in rabbits.

Intercompartmental fluid shifts were studied in New Zealand White rabbits after infusion of hyperoncotic dextran solution with a mean molecular weight of 64,200 and osmolality of 220 mosmol/kg H2O. In comparison with the control period, it was found that 1) plasma volume increased by a net volume of 83 +/- 12 ml; 2) systemic blood pressure increased slightly but significantly and central venous pressure increased markedly (this was accompanied by a reduction of interstitial fluid pressure from a control of -1 to -8 cmH2O after dextran); 3) plasma volume expansion was not accompanied by plasma sodium and chloride dilution when they were expressed in meq/kg of plasma water; and 4) plasma osmolality did not change after dextran infusions. The increase in plasma volume unaccompanied by any change in plasma sodium, chloride, or osmolality may be explained by a transcapillary fluid shift from the interstitial space to the bloodstream caused by an increase in plasma oncotic pressure. Because the more negative interstitial fluid pressure did not seem to attract any appreciable amount of fluid from the cells, we concluded that the interstitial space did not hydrodynamically couple the intravascular space to the cellular compartment.

Animals↗
PubMed1983

Effect of ascorbic acid on response to methacholine challenge in asthmatic subjects.

We studied the effect of ascorbic acid in 14 mild asthmatic subjects. The effect of ascorbic acid (1.0 g orally) was assessed by the changes in concentration of methacholine required to decrease the specific airway conductance by 40% (pD40). Ascorbic acid increased pD40 from control values of 9.38 +/- 1.97 mg/ml (mean +/- SEM) to 12.59 mg/ml +/- 2.52 (p less than 0.05). Administration of 50 mg of indomethacin, orally, reversed the effect of ascorbic acid. Indomethacin alone had no effect on the mean pD40. The results suggest that ascorbic acid exerts its effect via alteration of arachidonic acid metabolism.

Adult↗