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Biomedical subjects

H Steinberg

Publications and source records attributed to H Steinberg.

At least 109 records · Page 6Linked to original sources

Computer analysis, using a digitizer, of ataxic mouse gait due to drugs.

A simple objective method using the irregularity of the spacing of rats' footprints to determine drug-induced locomotor ataxia has been adapted for mice and for computer analysis, by means of a digitizer-based program. Results obtained by the usual manual method of measuring and analyzing the records are compared with results of the computerized method. The computer method improves speed, and perhaps accuracy, of measurement and analysis, especially with large numbers of records, although manual scoring gives satisfactory results and remains essential for unusual records. Inter-observer agreement of the computerized method was high, and there was good agreement between measurements and subjective ratings of ataxia. The use of footprints to measure ataxia, with or without computer aid, is recommended as a routine test in laboratory evaluation of psychoactive drugs. Other uses discussed include determining changes in different characteristics of gait such as step width and step length in animal and human subjects affected not only by drugs, but also by movement disorders such as Parkinsonism.

Amobarbital↗

Depression in hemodialysis patients.

Psychiatric evaluation of depression in medically ill patients using DSM-III-R or Research Diagnostic Criteria (RDC) is difficult because these diagnostic systems have not been validated for this population. Diagnosis of depression has been especially problematic in patients with end-stage renal disease (ESRD). This study found a 17.7% prevalence of RDC-defined minor depression and a 6.5% prevalence of major depression in 124 ESRD patients treated with hemodialysis. Vegetative symptoms of depression were less useful for discriminating between those with and without depression than were the psychological symptoms of suicidal ideation, depressed mood, and discouragement.

Depressive Disorder↗

Subclinical lumbar polyradiculopathy in aged domestic, laboratory, and exotic mammalian species--a light and selected electron microscopic study.

Lumbar polyradiculopathy, characterized by ballooning myelin sheaths and axonal distortion, was documented in multiple, aged, domestic, laboratory, and exotic mammalian species. Animals studied that exhibited this nerve rootlet change included the goat, sheep, pig, white-tailed deer, gerbil, vole, ferret, beaver, hedgehog, chinchilla, North Chinese leopard, lion, cheetah, mountain lion, llama, East African eland, Uganda giraffe, polar bear, and drill. Ultrastructurally, lumbar nerve rootlets from the North Chinese leopard revealed prominent and often multiple lamellar separations in the area of myelin bubbling. Clefts in myelin sheaths contained macrophages with engulfed fragments of myelin. Axons were sometimes variously attenuated, and the axoplasm contained densely packed neurofilaments. In all species, the lesion was subclinical and considered an incidental age-related finding.

Aging↗

Effect of sodium chloride and sodium bicarbonate on blood pressure in stroke-prone spontaneously hypertensive rats.

1. To test the hypothesis that NaCl increases blood pressure, while NaHCO3 does not, we measured the effect of an NaHCO3-containing mineral water on blood pressure in stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto (WKY) rats. We compared mineral water with equimolar amounts of NaCl and demineralized drinking water in six groups of 20 rats each over 24 weeks. 2. NaCl consistently increased blood pressure in both SHR-SP and WKY compared with demineralized water, while mineral water did not. 3. We studied the possible role of sodium-regulating hormones. Sodium, potassium-dependent adenosine triphosphatase activity was decreased by NaCl and by age, but not by mineral water. The concentration of atrial natriuretic peptide was greater in SHR-SP, but was not influenced by the two regimens. Components of the renin-angiotensin-aldosterone system and 18-hydroxydeoxycorticosterone tended to decrease with NaCl, but not with mineral water. 4. Plasma pH values in the six groups of rats were not different; however, SHR-SP had consistently lower PCO2 and HCO3- values and higher anion gap values than WKY rats. These values were not influence by the two regimens. 5. NaCl elevates blood pressure in SHR-SP while NaHCO3 does not. The changes in hormones regulating sodium homoeostasis suggest that NaCl induces volume expansion while NaHCO3 does not. The effect may be related to influences on renal sodium reabsorption by chloride and bicarbonate. The possible role of increased proton excretory activity in SHR-SP remains to be determined.

Animals↗

Effect of a prostacyclin derivative (iloprost) on regional blood flow, sympathetic nerve activity, and baroreceptor reflex in the conscious rat.

We have investigated the hemodynamic actions of iloprost, a stable prostacyclin derivative, in conscious, chronically instrumented rats. Given intravenously by 10-min infusions at doses ranging from 0.0375 to 4 micrograms/min, iloprost lowered mean arterial blood pressure in a dose-dependent and reversible fashion. The effects on blood pressure were accompanied by increases in heart rate (HR); splanchnic nerve activity (SpNA, direct recording); and mesenteric, renal, and hindlimb blood flow (Doppler probes). Doses below the depressor threshold already reduced mesenteric and hindlimb vascular resistance without affecting HR. The reduction of hindlimb resistance outlasted the iloprost infusion period. Chronic sinoaortic deafferentation (SAD) almost abolished the tachycardic reflex responses to intravenous sodium nitroprusside. The reflex increases in SpNA to intravenous iloprost were also largely prevented in SAD animals, but the tachycardic effects of iloprost persisted. In addition, neither beta 1-adrenoceptor blockade alone nor complete cardiac autonomic blockade prevented the heart rate responses to iloprost. Our results show that iloprost is a potent vasodilator that preferentially reduces hindlimb vascular resistance. Low doses of the drug increase regional blood flow without affecting blood pressure or heart rate. The tachycardic effects at higher doses cannot be explained by baroreceptor reflex (BRR) activation alone; they instead suggest a direct action on the heart. The dissociation between vasodilator and depressor effects at low doses may contribute to the therapeutic benefit of the drug in the treatment of vascular disease.

Animals↗

Adenosine transport by the lung.

Adenosine, a nucleoside and potent vasodilator, has been found to be taken up by the lung and converted by deamination into inosine and hypoxanthine. In a single circulation through an isolated rat lung, 69.3 +/- 3.3% of infused [14C]adenosine (10 microM) was removed from the circulation. Uptake of [14C]adenosine remained unchanged when deamination of adenosine was inhibited by 8-azaguanine or coformycin. In a single passage of adenosine through the pulmonary artery, very little of the deaminated products appeared in the pulmonary circulation, but when adenosine was recirculated through the pulmonary circulation inosine and hypoxanthine appeared in the venous effluent. These adenosine metabolites were also taken up by the lung. A major portion of the circulating adenosine was transported into the lung, where it was used to synthesize adenine nucleotides. Inhibition of adenosine kinase by iodotubercidin resulted in reduced formation of ATP and ADP. Uptake of adenosine by the lung was saturable on a concentration gradient and was a passive process because it was not affected by the absence of glucose or the presence of ouabain. Km and Vmax for adenosine transport were 0.227 mM and 4.6 mumol.min-1.g lung-1, respectively. Adenosine transport was inhibited by adenosine analogues, and the inhibitions were found to be competitive in nature. These results suggest that a specific and rate-limiting transport system exists in the lung for adenosine.

Adenosine↗

Substance P induces a cardiovascular defense reaction in the rat: pharmacological characterization.

In this study in conscious rats, we tested the hypothesis that substance P, a central pressor peptide and a potential transmitter substance of pain pathways, could be involved in the cardiovascular defense reaction that is typically associated with unpleasant sensory stimuli. The hemodynamic responses to centrally administered substance P were pharmacologically characterized. The increases in blood pressure and heart rate after intracerebroventricular injections of substance P were accompanied by mesenteric and renal vasoconstriction and hind limb vasodilation (pulsed-Doppler flow probes). The pressor and vasoconstrictor responses were attenuated by peripheral alpha 1-adrenoceptor blockade with prazosin but were not influenced by blockade of vascular vasopressin receptors with d(CH2)5Tyr(Me) arginine vasopressin (AVP). Cardiac beta 1-adrenoceptor blockade with metoprolol abolished the tachycardic and reduced the pressor responses. Substance P-induced hind limb vasodilation was not sensitive to intravenous atropine but was largely prevented by peripheral beta 2-adrenoceptor blockade with ICI 118,551. Thus, the substance P-induced pressor effects are mediated by alpha 1-adrenergic sympathetic vasoconstriction and beta 1-adrenergic cardiac stimulation, whereas the hind limb vasodilation is mainly due to beta 2-adrenergic stimulation. Substance P dose-dependently (0.01-10 micrograms i.c.v.) released oxytocin but not vasopressin or adrenocorticotropic hormone (ACTH) from the pituitary gland. High doses reduced basal ACTH levels. Together with the hemodynamic responses, a behavioral arousal reaction was observed, which included increased locomotion, grooming, scratching, and skin biting. Our results demonstrate that a neuropeptide can induce classic cardiovascular defense reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Effect of high calcium diet on magnesium, catecholamines, and blood pressure of stroke-prone spontaneously hypertensive rats.

To test the effect of a high dietary calcium intake on blood pressure, we fed stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto rats (WKY) diets containing (a) 0.25% Ca/0.08% Mg, (b) 4.0% Ca/0.02% Mg, and (c) 4.0% Ca/0.08% mg, beginning at 6 weeks of age. SHR-SP and WKY rats receiving 4% Ca with the lower Mg content had lower blood pressures, hypomagnesemia, and hypomagnesuria, and grew poorly. SHR-SP receiving 4% Ca and the higher Mg diet had blood pressures no different from those of rats receiving the 0.25% Ca diet, in spite of having lower body weights. Rubidium flux studies in erythrocytes were not influenced by Ca or Mg in the diets. Plasma phosphate values were moderately reduced in rats receiving 4% Ca diets. Epinephrine and norepinephrine values were higher in SHR-SP than in WKY rats. Norepinephrine increased with stress in both strains, independent of diet. Epinephrine values were lower in SHR-SP receiving the 4% Ca diets and showed less of an increase with stress compared to SHR-SP receiving the 0.25% Ca diet. After 26 weeks of diets, SHR-SP and WKY rats were given 0.9% NaCl in their drinking water. NaCl increased blood pressure in SHR-SP irrespective of Ca content of the diet. These data suggest that a high Ca diet influences Mg homeostasis and adrenal medullary function in SHR-SP. Further, SHR-SP appear resistant to any blood pressure lowering effect of Ca irrespective of NaCl intake.

Animals↗

Potential use of indium-111-labeled polymorphonuclear leukocytes for the detection of lung microvascular injury.

The early stages of microvascular injury are often difficult to detect due to the lack of a suitable marker to assess such an injury. We utilized the well known phenomenon of polymorphonuclear leukocyte (PMN) migration to the microvascular bed as a result of acute inflammatory reactions originating from the damaged cells. A radiotracer technique was developed, employing indium-111-labeled PMN for the detection of microvascular injury induced by hyperoxia. New Zealand white rabbits exposed to either 100% oxygen or air for various intervals of time were injected with indium-111-tropolone or oxine-labeled PMNs. Influx of radioactive PMN into the lung was detected in 72 hr/oxygen-exposed animals using gamma scintigraphic technique. Analysis of dry/wet ratios and histological examinations of the lung biopsies indicated noncardiogenic edema formation at this stage. Mortality was 50% beyond 96 hr/oxygen exposure. Our study thus provided a means to detect early microvascular injury during 72 hr/oxygen-exposure, which was not detectable by any other noninvasive techniques. The use of indium-111-labeled PMN thus appears to be a potentially important tool for the clinical assessment of lung microvascular injury.

Animals↗

Role of polymorphonuclear leukocytes in hyperoxic lung injury. Prevention of neutrophil influx into the lung endothelium during oxygen exposure by ibuprofen.

The present study examines the role of PMN in hyperoxic lung injury using a nonsteroidal anti-inflammatory drug, ibuprofen. New Zealand white rabbits were exposed to 100% oxygen or air for 1 to 4 days. The animals were divided into two groups: the treatment group received ibuprofen with drinking water, and the control group received water alone. After exposure to oxygen or air, the rabbits were injected with indium-III-oxine labeled PMN. Influx or radioactive PMN into the lung was detected using gamma scintigraphic technique only in 72 h and 96 h oxygen-exposed animals which were not treated with ibuprofen. Ibuprofen-treated animals did not exhibit any PMN influx into the lung. Blood gas analysis of all 72 h oxygen-exposed animals did not show any abnormal values, although analysis of dry/wet weight ratios and histopathological examinations indicated noncardiogenic edema formation. After 96 h of oxygen exposure, both ibuprofen-treated and untreated groups suffered from severe acidosis. Gross cytoplasmic edema and partial destruction of lung endothelium were also observed. Mortality was 50% after 96 h of oxygen exposure. Our study, thus, demonstrates that ibuprofen cannot prevent hyperoxic lung injury although it inhibits the influx of PMN into the injured lung, suggesting that PMN are not directly involved in the injury process.

Animals↗

Hyperactivity induced by dexamphetamine/chlordiazepoxide mixtures in rats and its attenuation by lithium pretreatment: a role for dopamine?

Dexamphetamine (DEX) and chlordiazepoxide (CDZP) given together as mixtures have previously been shown to induce a characteristic "compulsive" form of locomotor hyperactivity in rats placed in unfamiliar environments, which was much greater than activity obtained with any dose of either drug given separately; acute pretreatment with lithium counteracted mixture-induced hyperactivity. The role of dopamine in these effects was investigated by measuring concurrently the levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. DEX (0.02-2 mg kg-1) increased horizontal (entries) and vertical (rears) activity, and increased DA and decreased DOPAC and HVA in the striatum. Chlordiazepoxide (CDZP) (12.5 or 20 mg kg-1) increased horizontal activity but did not affect vertical activity or DA or its metabolites. Lithium by itself in acute (2 meq kg-1, 24 and 4 h before test) or extended (2 meq kg-1 daily for 9 days) dosage had little effect on horizontal or vertical activity or levels of DA or DOPAC. Given together, DEX and CDZP (1.18 mg kg-1 + 12.5 mg kg-1), as expected, increased entries much more than did either drug given separately, but rears and levels of DA and metabolites remained similar to those with DEX given alone. Acute lithium pretreatment counteracted the mixture-induced increase in entries. Neither acute nor extended lithium pretreatment significantly altered DEX-induced changes in activity or levels of DA or DOPAC.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Neutrophil kinetics in O2-exposed rabbits.

Hyperoxic injury results in an influx of polymorphonuclear leukocytes (PMN) into the lung. To better understand the role of the PMN in this injury, kinetic studies were used to assess the survival of PMNs in the circulation. The rate of deposition of PMNs in the lungs of rabbits exposed to hyperoxia was also examined. The half-lives (T1/2) of [3H]thymidine-labeled PMNs in the circulation in rabbits exposed to air or to 95% O2 for less than or equal to 48 h varied between 3.9 and 4.5 h. After 72 h of hyperoxic exposure, T1/2 fell to 2.2 h, the marginal and circulating PMN pool increased and 3H deposition in the lung increased 10-fold. Autoradiographs confirmed that [3H]thymidine was initially nuclear- and cellular-associated but, with time, [3H]thymidine dispersed throughout the lung, suggesting PMN disintegration. These PMN events seem to occur in the later phases of O2 toxicity, and because PMNs are an additional source of oxyradicals, they may further amplify oxidant injury.

Animals↗

Serotonin receptors in rat lung.

Mammalian lungs have been shown to store and to inactivate serotonin by an active process involving uptake and metabolism. Serotonin has direct action on lung including constrictor effects of pulmonary vascular and tracheobronchial smooth muscle suggesting the presence of serotonin receptors in lung. We have identified several serotonin binding receptors in rat lung. Two separate binding sites are present in a purified mitochondrial fraction. Saturation analysis of (3H)-serotonin binding to outer mitochondrial membranes exhibits temperature-dependent association kinetics and demonstrates a single, high affinity, high capacity binding (dissociation constant = 8.3 +/- 1.2 nM, maximum binding capacity = 0.819 +/- 0.046 pmol/mg protein). The dissociation constant of inner mitochondrial membrane demonstrates a low affinity, low capacity site (dissociation constant = 25.2 +/- 2.2 nM, maximum binding capacity = 0.453 +/- 0.037 pmol/mg protein). The purified microsomal fraction of lung exhibits a moderate affinity, high capacity binding site for (3H)-serotonin (dissociation constant = 14.8 +/- 1.6 nM, maximum binding capacity = 0.760 +/- 0.03 pmol/mg protein). In addition to the lung being the major site for its inactivation, the presence of several specific serotonin receptors may be related to some of the known serotonin actions in lung and may suggest other unknown actions of this amine.

Animals↗

Aging and hematopoiesis. VI. Neutrophilia and other leukocyte changes in aged mice.

The concentration of blood leukocytes rose progressively as mice aged. All blood leukocytes increased, although a greater degree of increase was seen in neutrophils and monocytes than in lymphocytes and eosinophils. The total number of nucleated cells per marrow cavity of the humerus was also higher in aged than in young adult mice, the increase primarily reflecting peroxidase-positive cells. Both blood and marrow neutrophils of aged mice responded to perturbations induced by bleeding or by endotoxin injection in a manner qualitatively similar to that seen in young adults. When hematopoietic chimeras were produced by marrow transplantation, blood and marrow neutrophils were characteristic of the age of the recipient, not the cells; i.e., young mice kept a "young" neutrophil pattern and old mice kept an "old" neutrophil pattern when given marrow from either old or young mice. Colonies of granulocytes and/or monocyte-macrophages were grown from young marrow cells placed in plasma clots in Millipore chambers in the peritoneal cavity. The number of colonies was the same in young and in old mice, suggesting that long-range humoral stimulation of cell growth was similar in young and old. Thus, neutrophilia due to increased neutrophil production appears to be a normal part of the aging process in the mouse. The increase in neutrophil production may be due to a changing hematopoietic microenvironment.

Aging↗

Test-retest reliability of spectral parameters of the EEG.

The topic of this paper is the intraindividual stability of the EEG at rest for repeated recordings with respect to two sets of spectral parameters. Variability arises due to changes in experimental conditions (such as vigilance) and also due to the inherent random elements of the EEG. The two sets of parameters considered are broad-band parameters and parameters characterizing rhythmic and 'diffuse' activity separately, derived from autoregressive fitting. In spite of some imprecision in the definition of the EEG at rest, satisfactory test-retest correlations were found. They proved to be quite homogeneous topographically, but not across frequency bands: delta power is less reliable and to some extent also beta activity, whereas the alpha bands perform well. The frequency of the alpha rhythm shows a good reliability and, given the difficulties involved with the concept, also the degree of synchronization. The power of rhythmic and of diffuse activity showed more modest retest correlations, probably to be attributed to methodological problems in determining these quantities. On the whole, the results confirm that the normal EEG can be treated as an intraindividually rather stable trait, that artifacts play a minor role in this respect and that 20 sec of activity are sufficient to reduce adequately the variability inherent in the EEG.

Adolescent↗

Acrylic resin stents for marsupialization.

Marsupialization is a surgical technique that may be preferred to enucleation in treatment of benign cysts. The acrylic resin obturator maintains the surgical opening during healing and assures success of the surgery. Two basic techniques to construct a stable and retentive obturator prosthesis were described.

Acrylic Resins↗

Introduction to symposium on endorphins and behavioural processes; review of literature on endorphins and exercise.

The first symposium on endorphins and behavioural processes in Britain was held by the British Psychological Society in March 1985. Against a background of the explosive history of the discovery of endogenous opioids, problems of terminology, and basic mechanisms and concepts, five papers reflect the main fields in which outstanding progress has been made: analgesia, feeding, reward mechanisms, social behaviour and aggression, and addiction. A review of the literature on endorphins and exercise stresses both the value and limitations of trying to unravel a fashionable subject. Endorphin research is multi-disciplinary and highly complex, with tricky technical and conceptual problems and inevitable lack of consensus. Investigators should be more aware of the crucial role that outcomes of behaviour experiments play in the attribution of function to opioid systems.

Analgesia↗