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Biomedical subjects

S Levin

Publications and source records attributed to S Levin.

At least 19 recordsLinked to original sources
PubMed1992

Atrial natriuretic peptide: direct effects on human red blood cell dynamics.

The ability to deform is an important feature of red blood cells (RBCs) for performing their function of oxygen delivery. Little is known about the hormonal regulation of RBC deformability. Here we report that human atrial natriuretic peptide (ANP) acts directly on human RBCs leading to the elevation of local bending fluctuations of the cell membrane. These changes are accompanied by an increase in the filterability of RBCs. These ANP effects were mimicked by cyclic GMP analogues, suggesting modulation of local membrane bending fluctuations and RBC filterability via a cyclic GMP-dependent pathway. The effect of ANP on the mechanical properties of RBCs suggests that ANP may increase the passage red blood cells through capillaries resulting in an improved oxygen delivery to the tissues.

Atrial Natriuretic Factor↗
PubMed1992

Correlation between local cell membrane displacements and filterability of human red blood cells.

Local mechanical fluctuations of the cell membrane of human erythrocytes were shown to involve MgATP- and Mg(2+)-driven fast membrane displacements. We propose that these local bending deformations of the cell membrane are important for cell passage through capillaries. In order to verify this hypothesis, we examined cell membrane fluctuations and filterability of erythrocytes over a wide range of medium osmolalities (180-675 mosmol/kg H2O). The results indicate the existence of a positive correlation between the amplitude of local cell membrane displacements and cell filterability. We suggest that the occurrence of metabolically driven membrane displacements on the side surface of the red blood cell diminishes its bending stiffness and enables it to fold more efficiently upon entrance into blood capillaries. Thus, local cell membrane displacements seem to play an important role in microcirculation.

Culture Media↗
PubMed1992

Promotional activities of the non-genotoxic carcinogen bemitradine (SC-33643).

Bemitradine (SC-33643), a diuretic antihypertensive agent, was studied for its carcinogenicity in a 2-year bioassay in Charles River CD rats via dietary admix at dosages of 50, 150 and 450 mg kg-1 for up to 97 weeks (after which they were followed for eight additional weeks without treatment). Body weights were decreased compared to controls: 5-15% in the female and 10-12% in the male dosage groups by week 105 of the study. Prolactin values were significantly increased in 150 and 450 mg kg-1 females. The compound caused significant increased incidences of liver, thyroid (both sexes) and mammary (females only) neoplasms. The metabolism of bemitradine was studied in both rats and man. Bemitradine and its primary metabolite (SC-36741; desethylbemitradine) were tested and found to be non-genotoxic in Ames, rat primary hepatocyte UDS, CHO/HGPRT, CHO cytogenetics, in vivo mouse micronucleus and mouse lymphoma TK+/- (bemitradine only) assays. Finally, in an altered hepatic foci (Y-glutamyl transpeptidase positive) promotion assay in female Charles River CD rats, bemitradine was found to be a promotor, though not as potent as phenobarbital. We concluded that bemitradine (which has been dropped from development) is a non-genotoxic carcinogen which appears to act by a hormonally modulated promotional activity in inducing tumors in the liver and mammary glands. Tumors seen in the thyroid were probably secondary to the effects of bemitradine on metabolism.

Animals↗
PubMed1992

Induction of colitis in rats by 2-2'-azobis(2-amidinopropane) dihydrochloride.

Reactive oxygen metabolites (ROM) may play a role in the pathophysiology of inflammatory bowel disease (IBD) and ischemia-reperfusion-induced intestinal injury. Although there are many reports of intestinal mucosal injury associated with neutrophil-derived ROM, free radicals themselves have not been reported to induce intestinal mucosal injury. We administered intrarectally 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) to rats, an azo compound that generates free radicals in vitro. Acute mucosal injury was assessed histologically by light microscopy and biochemically by myeloperoxidase (MPO) activity. Intrarectal administration of AAPH (60, 90, 150 mg/kg) caused erythema, edema, and histologically verifiable mucosal inflammation. MPO activity was increased 9- to 18-fold above the control level. The levels of thiobarbituric acid (TBA) reactants and sulfhydryls (SH) were significantly (P less than 0.01) increased and decreased, respectively, by 90 mg/kg AAPH. Sulfasalazine, 5-aminosalicylic acid, the LTB4 receptor antagonist SC-41930, and the antioxidant glutathione prevented the inflammation. This model of mucosal inflammation may be useful in evaluating new therapeutic agents for the treatment of IBD.

Amidines↗
PubMed1992

Mucosal protective activity of prostaglandin analogs in rodent colonic inflammation.

The mucosal protective prostaglandin analogs misoprostol, enisoprost, and SC-46275 (the 17E-18-cyclopentenyl analog of enisoprost) were tested in mouse and rat colitis induced by the intrarectal instillation of dilute acetic acid. Colitis was assessed by histology and colonic levels of myeloperoxidase (a neutrophil marker enzyme). When given as enemas 30 min ahead of colitis induction, 15(R)-15-methyl-PGE2 (arbaprostil) and 15(S)-15-methyl-PGE1 were inactive; however, misoprostol, enisoprost, and SC-46275 protected against colonic inflammation with ED50 values of 24, 12 and 1.3 micrograms/kg, respectively, in rats and 11, 5, and 1 micrograms/kg, respectively, in mice. These compounds may have utility in the medical management of human inflammatory bowel disease.

Acetates↗
PubMed1992

Abnormalities of smooth pursuit and saccadic control in schizophrenia and affective disorders.

Smooth pursuit abnormalities have been reported in patients with schizophrenia and their first-degree relatives, suggesting that abnormal tracking may serve as a biological marker for schizophrenia. Recent studies in schizophrenic patients have found reduced pursuit gain, low initial acceleration and abnormal gain-corrective saccade interactions. Impaired saccadic initiation has been noted in anti-saccade tasks and in predictive saccade generation, as has saccadic hypometria. While abnormalities have been found in affective disorder patients, studies of their first-degree relatives suggest that abnormalities during pursuit are more closely associated with schizophrenia. Identification of specific defects allows informed speculation about their neural substrates and suggests possible relationships between the ocular motor defects and other cognitive and perceptual abnormalities associated with the major psychiatric disorders.

Humans↗
PubMed1992

Oxygenation-deoxygenation cycle of erythrocytes modulates submicron cell membrane fluctuations.

Low frequency submicron fluctuations of the cell membrane were recently shown to be characteristic for different cell types, nevertheless their physiological role is yet unknown. Point dark-field microscopy based recordings of these local displacements of cell membrane in human erythrocytes, subjected to cyclic oxygenation and deoxygenation, reveals a reversible decrease of displacement amplitudes from 290 +/- 49 to 160 +/- 32 nm, respectively. A higher rate of RBC adhesion to a glass substratum is observed upon deoxygenation, probably due to a low level of fluctuation amplitudes. The variation in the amplitude of these displacements were reconstituted in open RBC ghosts by perfusing them with composite solutions of 2,3 diphosphoglycerate, Mg+2, and MgATP, which mimic the intracellular metabolite concentrations in oxygenated and deoxygenated erythrocytes. The mere change in intracellular Mg+2 during oxygenation-deoxygenation cycle is sufficient to explain these findings. The results imply that the magnitude of fluctuations amplitude is directly connected with cell deformability. This study suggests that the physiological cycle of oxygenation-deoxygenation provides a dynamic control of the bending deformability and adhesiveness characteristics of the RBC via a Mg+2-dependent reversible assembly of membrane-skeleton proteins. The existing coupling between oxygenation-deoxygenation of the RBC and its mechanical properties is expected to play a key role in blood microcirculation and may constitute an example of a general situation for other circulating blood cells, where the metabolic control of cytoskeleton dynamics may modulate their dynamic mechanical properties.

2,3-Diphosphoglycerate↗
PubMed1992

Correlates of a residential pesticide contamination in a self-selected sample.

We evaluated the behavioral, health perception, and physical health correlates of a residential pesticide misapplication on 54 individuals and identified factors differentially related to various levels of distress. Study participants were mainly concerned with health issues and exhibited somatic symptoms. Behavioral actions designed to obtain information regarding exposure levels and to reduce exposure were adopted. We found that factors such as a higher contamination level, involvement in a lawsuit, and belonging to a consumer action group, were strongly related to higher levels of psychological distress and, to a lesser extent, to behaviors, somatic symptoms, and health perceptions.

Adolescent↗
PubMed1992

The interferon system in patients with malignant disease.

Since the interferon (IFN) system involves both IFN producing and IFN responding cells, it is possible to study separately these phenomena, relating them to disease entities as well as to response to therapy. Numerous studies in animals and man suggest effectiveness of IFN and IFN inducer therapy in cancer. However, the competency of the various components of the endogenous IFN system in malignancy has received little attention. These studies show that in malignancy there may be (1) a high incidence of elevated blood levels of IFN; (2) a deficient response of peripheral blood mononuclear cells to endogenous and exogenous IFN; and (3) increased uninduced in vitro IFN production by these cells. These findings indicate that cancer patients are equipped with the ability to produce IFN and suggest that it may be the deficient response of their cells to IFN that plays a role in the development and progression of the disease. Furthermore, the finding of increased spontaneous "uninduced" production of IFN by cells from cancer patients suggests the possibility of an intracellular inducer such as found in persistently virus-infected cells.

Humans↗
PubMed1992

Cost-effectiveness analysis of extended conservative therapy versus surgical intervention in the management of herniated lumbar intervertebral disc.

The management of herniated lumbar intervertebral disc for patients not responding to an initial trial of conservative therapy is generally surgical. Little is known about the effect of continued conservative therapy on patients who have not improved or have deteriorated within the first 3 months. This study assessed which form of treatment, surgical or continued conservative therapy, is more cost-effective once an adequate trial of conservative therapy has failed. The study is a retrospective chart review of 55 white male truck drivers who presented with acutely herniated nucleus pulposus between 1985 and 1989. Twenty-five patients underwent surgery, and 30 underwent continued conservative therapy after initial rehabilitation. No significant difference was found in outcome (80% good or fair in both the surgical and conservative groups) or costs ($55,000 +/- $1,000/case during a 5-year period), hence no difference in the cost-effectiveness between the two treatment modalities (each $63,000 +/- $2,000/adjusted outcome). Conservatively treated patients, however, missed significantly more work. It was concluded that, for a patient not responding to the initial trial of conservative therapy, the option to undergo continued conservative treatment should be made available.

Adult↗
PubMed1992

Levels of pyrimethamine in sera and cerebrospinal and ventricular fluids from infants treated for congenital toxoplasmosis. Toxoplasmosis Study Group.

Pyrimethamine levels in sera, cerebrospinal fluid (CSF), and ventricular fluid were measured by using reversed-phase high-pressure liquid chromatography. The specimens were from 37 infants receiving pyrimethamine for treatment of suspect or proven congenital toxoplasmosis. Pyrimethamine half-life in serum was 64 +/- 12 h when determined by study of terminal-phase kinetics of samples obtained from nine babies. This half-life was significantly different (P = 0.008) from the pyrimethamine half-life (33 +/- 12 h) determined by terminal-phase kinetics for two babies of the same age taking phenobarbital. Serum pyrimethamine levels at various intervals after dosages of pyrimethamine were also lower for infants receiving phenobarbital. Levels measured in sera from babies taking the same dose of pyrimethamine throughout their first year of life did not appear to vary significantly over time or at different ages (P greater than 0.05). Mean +/- standard deviation serum levels 4 h after a pyrimethamine dose were 1.297 +/- 0.54 micrograms/ml for babies taking 1 mg of pyrimethamine per kg of body weight daily and 0.7 +/- 0.26 microgram/ml for babies taking 1 mg/kg each Monday, Wednesday, and Friday. Levels in CSF were approximately 10 to 25% of concomitant levels in serum. Serum folate levels for infants who took 0.64 to 1.7 mg leukovorin per kg ranged from 33 to 663 ng/ml. To determine whether the levels of pyrimethamine in serum and CSF of treated infants were in a range that affected the most virulent, rapidly replicating, and standard laboratory strain of Toxoplasma gondii, effects of various concentrations of pyrimethamine and sulfadiazine on replication of T. gondii in vitro were assessed. The levels of the antimicrobial agents effective in vitro were in the range of levels of pyrimethamine achieved in sera and CSF. Although folinic acid could inhibit the therapeutic effect of pyrimethamine and sulfadiazine in vitro, inhibition was noted only at levels (> or = 4,800 ng/ml) that were considerably higher than the folate levels found in the treated infants' sera.

Chromatography, High Pressure Liquid↗
PubMed1992

Plasma and tissue hormones in the dog after administration of the prostaglandin analogue, misoprostol.

Dogs were given a prostaglandin analogue, misoprostol, at a dose that significantly increases gastrointestinal epithelial cell proliferation. Both basal and postprandial concentrations of gastrin were significantly higher in the misoprostol-treated dogs and more than doubled after the meal in both the controls and in the test group. Plasma enteroglucagon, cholecystokinin, insulin and glucose-dependent insulinotrophic peptide all increased postprandially, with no effect of misoprostol. Tissue concentrations of bombesin, gastrin and somatostatin were unaffected by misoprostol, but the fundic glucagon-like immunoreactivity was significantly increased. Thus high doses of misoprostol have only minor effects on gastrointestinal regulatory peptides, suggesting that the trophic effect of prostaglandins on the intestinal tract may be direct.

Animals↗
PubMed1992

Glycemic control and complications in type II diabetes. Design of a feasibility trial. VA CS Group (CSDM)

OBJECTIVE: To determine, after 1 yr of follow-up in type II diabetes patients, whether a statistically and clinically significant difference can be achieved in HbA1c between a standard therapy group and an intensively treated group, while maintaining HbA1c levels in both groups within ranges acceptable in regular community practice. Secondary objectives include assessment of patient adherence to protocol, side effects, and accuracy of data collection. RESEARCH DESIGN AND METHODS: This is a prospective, randomized, controlled VA CS conducted with 151 patients at five VAMCs. Patients are males, age 40-69 yr, treated at entry with a maximum dose of sulfonylurea or with insulin, exhibiting an HbA1c level > 3 SDs above the normal mean (5.05 + 3 x 0.50 = > 6.55%). Standard control is achieved with insulin and intensive control with a step-up regimen including insulin alone or insulin/glipizide combinations. Education and management of cardiovascular risk factors are handled similarly in both groups. Primary macrovascular end points are nonfatal myocardial infarction, congestive heart failure, stroke, amputation, and cardiovascular death. Primary microvascular end points are appearance and progression of retinopathy, documented by centrally read seven-field-stereo fundus photographs. Other measured indicators include resting and ambulatory ECGs, ventricular function (MUGA scan), serum lipid and apolipoprotein levels, plasma fibrinogen, nonsymptomatic peripheral vasculopathy, neuroautonomic status by heart-beat variation on Valsalva maneuver, and microalbuminuria. CONCLUSIONS: This study may be the basis for a long-term trial, involving 1400 patients, to assess the long-term effects of metabolic control on macro- and microvascular end points.

Adult↗
PubMed1992

Coping with infertility: a new nursing perspective.

Infertility is a major life stressor, and reproductive failure is difficult to accept. Many couples become trapped in a cycle of repeated medical treatment, repeating painful patterns without developing insight or growth, feeling powerless to achieve their goal or move on. The causes of inappropriate coping behaviors are not well understood, and there is little direction for the nurse clinician's efforts to assist the couple with decision making. The use of superstition and ritual (magical thinking or magical ideation) by couples with infertility is discussed, and its role as a potential barrier to resolution is evaluated. A clinical tool for assessing the extent of magical ideation is described and its potential clinical utility explored. Women who have experienced a previous pregnancy may be more likely than nulliparas to substitute magical thinking for coping behaviors that might bring them closer to resolution. Problems with current research in this area are discussed, and directions for developing clinical nursing interventions are suggested.

Adaptation, Psychological↗
PubMed1992

Rembrandt toothpaste stain prevention with and without the use of Peridex.

Sixty-five subjects were assigned to use Crest or Rembrandt dentifrice with either a placebo or Peridex rinse for eight weeks. One group, using Peridex, started with Crest and switched to Rembrandt at week four of the study. There were no significant differences among the groups on gingivitis, plaque, or calculus by the conclusion of the study. On the stain intensity index there was a significant statistical difference on buccal surfaces between Crest and Rembrandt with placebo compared to Crest with Peridex. On lingual surfaces, Rembrandt with placebo rinse was significantly lower than all Peridex rinse groups by the end of the study. From baseline to the conclusion of the study, Crest with placebo had no change in stain intensity, while Rembrandt with placebo had a significant drop on both buccal and lingual surfaces. The Peridex groups had increases on buccal stain intensity. On stain area scores, by the conclusion of the study both Crest and Rembrandt with placebo were significantly different from Crest with Peridex on buccal and lingual surfaces. Over time there was no significant change in stain area for the Crest with placebo groups. Rembrandt and placebo was significantly lower on stain area from baseline to week eight on buccal surfaces. The Peridex groups had increases in stain area over the study period.

Adolescent↗