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Biomedical subjects

R Steinberg

Publications and source records attributed to R Steinberg.

At least 91 records · Page 5Linked to original sources

Gain in mass density of bone following strenuous physical activity.

A group of 223 military recruits aged 18-21 years underwent strenuous physical training for a period of 14 weeks. The absolute bone density of the distal tibia in both lower limbs was measured before the training period and at its end. The density was determined by the Compton scattering technique, which has been developed in our laboratory; this method provides the bone mass of all bone constituents per unit volume. The distribution curve of the bone density in both tibiae shifted to higher values at the end of the training period. The mean bone density in the right and left tibia increased significantly by 7.5%. This study indicates that following an intensive physical exercise regime, a significant increase in the mass density of bone can be obtained in young adults within a short period.

Adolescent↗

Cholinomimetic activities of minaprine.

The cholinomimetic activities of the antidepressant drug minaprine have been investigated, in vitro and in vivo, in rodents. Minaprine, and its metabolite SR 95070B [3-(2-morpholinoethylamino)-4-methyl-6-(2-hydroxyphenyl) pyridazine hydrochloride] selectively displaced [3H]-pirenzepine from its cortical and hippocampal binding sites, and only weakly inhibited the binding of [3H]-N-methylscopolamine in either the rat cerebellum, heart and salivary glands, or the guinea-pig ileum. In mice, none of these drugs induced the typical cholinergic side-effects up to lethal doses. Minaprine and SR 95070B antagonized rotations induced by an intrastriatal injection of pirenzepine in mice, after intraperitoneal and/or oral administration. Minaprine also antagonized atropine-induced mydriasis in mice. Both minaprine and SR 95070B potentiated the tremorigenic effect of oxotremorine without inducing tremor when injected alone. Finally, minaprine and SR 95070B, after parenteral and/or oral injection, antagonized the scopolamine-induced deficit in passive avoidance learning, and enhanced short-term retention in the social memory test, in rats. The muscarinic agonists arecoline, oxotremorine and RS 86 [2-ethyl-8-methyl-2,8 diazaspiro-4,5 decan-1,3 dion hydrobromide], as well as the acetylcholine esterase inhibitors physostigmine and tacrine were active in most of these models. These results indicate that minaprine, and its metabolite SR 95070B, have cholinomimetic activities which could be, at least in part, mediated by their selective affinity for M1 muscarinic receptors. Thus minaprine could represent a potential useful drug for the treatment of senile dementias and cognitive impairments occurring in elderly people.

Animals↗

Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy. IV. Brain dysfunction during motor activation measured by EEG mapping.

In parts I-III of this series psychometric evidence was reported of a "psychotic motor syndrome" (PMS) in schizophrenic and endogenous depressed patients, which was not found in non-endogenous depressed or healthy persons. An attempt is reported to establish signs of brain dysfunction in these patient groups during motor activation, using a 16-channel EEG mapping system. "Resting" conditions after a special relaxation procedure were compared with simple and complex motor tasks (and music perception/reproduction; to be reported separately). Two measurements, at least 2 weeks apart, were obtained for each subject, in order to obtain information on the influence of drug treatment and/or psychopathological improvement on brain dysfunction. In all, 23 male and 25 female schizophrenics, 11 male and 18 female non-endogenous depressed patients (not actually mediated, i.e. drug naive or wash-out period of 1 week to 17 years), and 26 male and 37 female endogenous depressed patients (medicated with tri- or tetracyclic antidepressants and/or benzodiazepines; no lithium treatment) were compared with 22 male and 17 female control persons (i.e. total n = 179). Major findings were obtained in the delta and alpha frequency bands yielding signs of "diffuse hyperactivation" in schizophrenic and endogenous depressed patients as compared with the patterns found in healthy persons. However, since in the non-endogenous patients a (less marked) hyperactivation of various EEG parameters was also found, unspecific effects such as anxiety/arousal may have influenced the results in psychotic patients, which was to be explored further. Drug treatment tended to "normalize" the activation pattern both in schizophrenics and endogenous depressed patients. Viewing the findings on schizophrenics using neuroimaging methods [single photon emission computerized tomography-(SPECT), magnetic resonance imaging-(MRI), positron emission tomography-(PET)], these results suggest pathological brain organization connected to an impaired motor performance (evident peripherally as PMS) in schizophrenic and endogenous depressed patients. If it is possible to further "externally validate" (by SPECT/MRI/PET) EEG mapping data this method may exclusively offer the possibility of innocuous long-term follow up of brain dysfunction in psychotic patients ("brain function monitoring"). This could enable the early recognition (and early therapy) of negative symptoms. Finally, the EEG mapping findings provide further neurophysiological basis for the use of motor training programs in the additional therapy of psychiatric patients.

Adult↗

Sodium diethyldithiocarbamate protects against the MPTP-induced inhibition of immune responses in mice.

The effects of 1-methyl-4-phenyl - 1,2,3,6-tetrahydropyridine (MPTP) on immune parameters, and the restorative influence of sodium diethyldithiocarbamate (DTC) or deprenyl were evaluated in mice. The concentrations of dopamine (DA), 3-methoxytyramine (3-MT), 3-4-dihydroxyphenyl acetic acid (DOPAC), and homovanillic acid (HVA), were concomitantly measured in the striatum. MPTP depressed T-cell responses. DTC restored these responses as well as the concentration of striatal DA. Deprenyl had no effect on the concentrations of DA and its metabolites, yet it modified the immune responses alike MPTP. The findings suggest a dopamine pathway could be involved in the brain-controlled immunostimulation afforded by DTC.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

[Modification of the penetration rate of human spermatozoa in the zona pellucida free hamster oocyte system by the use of polyclonal and monoclonal antibodies to human sperm].

Incubation of human spermatozoa with polyclonal anti-sperm antibodies from sterile females reduced the penetration rates in the zona-pellucida-free hamsteroocyte assay significantly. Twelve sera having titers from 1:4,096 to 1:64 were used. Fifty-three ejaculates from men with normozoospermia were tested. A few of the ejaculates used were classified as slightly pathological showing asthenospermia. At an average titer 1:860 the reduction of penetration rate was about 49% (range 9-90%). The degree of reduction was dependent on the agglutination titer of the test serum, the presence of immobilizing antibodies, the amount of antiserum added, and on the quality of the ejaculates to a minor extent. The penetration rate of human spermatozoa in zona-pellucida-free hamster-oocytes was reduced by 4 monoclonal anti-sperm-antibodies (A-24, B-20, III,3, and VII-5) out of 6 tested. The other 2 (VI-1 and VI-16) left the penetration rates virtually unchanged. The extent of penetration rate reduction depended on the concentrations of antibodies A-24, B-20, III-3, and VII-5; if undiluted, they produced a significant reduction of penetration rates, the largest average reduction being almost 50% with undiluted antibody A-24. Decreasing concentrations of the monoclonal anti-sperm-antibodies resulted in significantly smaller reductions of sperm penetration rates. The reason for the reduced penetration rates observed may be a blockage of receptors on the sperm surface by the named monoclonal anti-sperm-antibodies. This can inhibit enzyme reactions of the spermatozoa, or interfere with the interaction between oocyte and spermatozoa membranes. It is noted that only the antibody III-3 caused agglutination of human spermatozoa in the micro-sperm-agglutination and immobilization test. Therefore, the agglutination or immobilization of spermatozoa may not be held responsible for the reduced penetration rates after addition of monoclonal antibodies, as opposed to the findings with polyclonal antibodies.

Antibodies↗

Structural and compositional changes in aging bone: osteopenia in lumbar vertebrae of Wistar female rats.

Changes in vertebral bone mineral content and density during aging were quantified in female Wistar rats. This study represents a longitudinal follow up utilizing single photon absorptiometry for the measurement of bone mineral content (BMC), quantitative computed tomography (QCT) for the measurement of bone mineral density (BMD), and image analysis histomorphometry for the measurement of trabecular bone volume (TBV) and bone cortical area (BCA). The above measurements were accompanied by biochemical assays of calcium concentrations in the respective bones. All aging animals experienced significant decreases in BMC, BMD, TBV, BCA and in the calcium content of their bones. The above features have been further emphasized through the use of scanning electron micrographs showing the age-related structural changes in a three-dimensional fashion. New, advanced technologies will enable the quantitation of 3-dimensional images that are currently obtained from the scanning electron micrograph; thus will provide new consideration as related to trabecular bone compactness (density). Energy dispersive x-ray spectroscopy indicated that the nature of crystals in aging bones does not differ markedly from that encountered in young specimens. Data are also provided with regard to the health of the animals, and it became apparent that aging rats undergo changes in their kidneys yet do not show any significant change in renal functional parameters as measured in both the serum and the urine. Hence, new noninvasive methodologies are currently available for longitudinal studies related to the skeleton in laboratory animals enabling reliable monitoring of age-related and hormonally induced changes in bones (spine and hip) of well defined experimental models.

Absorptiometry, Photon↗

Zymogen granules of mouse parotid acinar cells are acidified in situ in an ATP-dependent manner.

The mechanism for acidification of zymogen granules in acinar cells of mouse parotid gland was explored using acridine orange, lysosomotropic agents, and an inhibitor of cellular ATP production. Methylamine and monensin reversibly collapsed the pH gradient of granules without affecting cellular ATP levels. Depletion of cellular ATP with antimycin A did not collapse the pH gradient. However, recovery of acidity in the granules, after collapse of the pH gradient by methylamine, was blocked by depletion of cellular ATP. These results demonstrate that zymogen granules of parotid gland are acidic in situ and that ATP is required for acidification of the granules.

Adenosine Triphosphate↗

Time estimation of depressive patients: the influence of interval content.

Duration judgements for intervals of different lengths and content were studied in depressive in-patients (n = 47) and a control sample of surgical in-patients (n = 16). As suggested by research on non-clinical subjects, tasks during the intervals influenced the depressed patients' duration judgements. Severely depressed endogenous depressives (n = 17) over-estimated time when left completely unoccupied or when attending to tasks requiring concentration. Endogenous depressives (n = 17) remitted with regard to subjective depression but, exhibiting signs of psychomotor retardation, selectively over-estimated time when required to concentrate under time pressure. Neurotic/reactive depressives (n = 13) with an intermediate level of subjective depression and almost normal psychomotor functioning did not over-estimate any of these intervals. Time estimations of patients and controls did not differ for intervals in the range of seconds and minutes requiring attention to time only, and for a longer part of the experimental session. Alteration of time estimation and results of a time experience inventory corresponded for endogenous depressives but not for neurotic/reactive depressives. Results are discussed in terms of the influence of affective state and subjective concentration effort on the over-estimations observed.

Adult↗

Monoamine oxidase-inhibiting properties of SR 95191, a new pyridazine derivative, in the rat: evidence for selective and reversible inhibition of monoamine oxidase type A in vivo but not in vitro.

In rodents, SR 95191 [3-(2-morpholinoethylamino)-4-cyano-6-phenylpyridazine] has been shown to be active in animal models of depression. The profile of activity of SR 95191 suggests that the compound is a selective and short-acting type A monoamine oxidase (MAO) inhibitor (MAOI) in vivo. In the present study, the interaction of SR 95191 with MAO-A and MAO-B activity was further examined in vivo and in vitro. In brain, liver, and duodenum of pretreated rats, SR 95191 selectively inhibited MAO-A (ED50 = 3-5 mg/kg, p.o.), whereas MAO-B was only weakly inhibited for doses as high as 300 mg/kg, p.o. In vivo, SR 95191 (1-100 mg/kg, p.o.) antagonized, in a dose-dependent fashion, the irreversible inhibition of brain and liver MAO-A induced by phenelzine. Finally, dopamine and 5-hydroxytryptamine depleted from their striatal stores by tetrabenazine were able to displace SR 95191 from the active site of MAO-A. However, ex vivo, kinetic studies showed that the inhibitory effect of SR 95191 (1-10 mg/kg) towards MAO-A was noncompetitive and was unchanged after dilution or dialysis. In vitro, the inhibition of brain MAO-A, but not MAO-B, by SR 95191 was time dependent, with a 19-fold decrease in the IC50 values being observed over a 30-min incubation period (140 to 7.5 microM). At this time, the SR 95191-induced inhibition of MAO-A was not removed by repeated washings. When the reaction was started by adding the homogenate without prior preincubation with SR 95191, the inhibition of brain MAO-A was fully competitive (Ki = 68 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mean age, sex ratio and psychopathology in alcohol psychoses.

In a retrospective study the case histories of 154 patients with acute alcohol psychosis were examined. The obvious diagnostic criteria in the doctor's differential diagnosis between alcohol withdrawal delirium and alcohol hallucinosis was clouding of sensorium and disorientation. 103 patients were diagnosed as having alcohol withdrawal delirium, 51 patients alcohol hallucinosis. Mean age and sex ratio were the same in both groups. Further psychopathological symptoms in both groups supporting differential diagnosis are discussed.

Adult↗

Construction of a low pressure reservoir and achievement of continence after "diversion" and in end stage vesical dysfunction.

Creation of a continent low pressure urinary reservoir was attempted in 33 patients: 11 with a supravesical diversion, 6 with a vesicostomy, 9 treated by catheter drainage and 7 with end stage bladder disease. The common problems were poor urine storage associated with bladder fibrosis, defunctionalization and decentralization or spinal cord injury coupled with a poorly functional urethral continence mechanism. The over-all outcome at a mean of 21 months (range 4 months to 11 years) was excellent in terms of upper tract function, reservoir capability and continence.

Adult↗

Stress fractures and tibial bone width. A risk factor.

A prospective study of 295 infantry recruits has shown that the mediolateral width of the tibia measured radiographically at each of three different levels in the bone had a statistically significant correlation with the total incidence of stress fractures as well as with those in the tibia alone or the femur alone. A narrow tibial width was shown to be a risk factor, but cortical thickness was not found to be significant.

Femoral Fractures↗

SR 95191, a selective inhibitor of type A monoamine oxidase with dopaminergic properties. II. Biochemical characterization of monoamine oxidase inhibition.

SR 95191 [3-(2-morpholino-ethyl-amino)-4-cyano-6-phenylpyridazine] is a novel psychotropic drug which possesses the pharmacological properties of a selective, reversible type A monoamine oxidase inhibitor (MAOI). The MAOI activity of SR 95191 was examined in the rat brain, liver and duodenum and compared to that of clorgyline, harmaline, l-deprenyl, moclobemide and cimoxatone. In vitro, SR 95191 selectively inhibited MAO-A and was less potent than cimoxatone, clorgyline and harmaline, but was more potent than moclobemide. Ex vivo, SR 95191 also preferentially inhibited MAO-A in the brain and was 6 and 13 times less potent than cimoxatone and moclobemide, respectively. Like all MAO-A inhibitors, SR 95191 in vivo caused a dose-dependent increase in striatal 3-methoxytyramine, dopamine, serotonin and in hypothalamic norepinephrine contents. A concomitant decrease in deaminated metabolites was observed. SR 95191 inhibited peripheral MAO activity in liver and duodenum. In brain, liver and duodenum, MAO inhibition induced by SR 95191 was short-lasting. Repeated dosing for 14 days did not enhance MAO-A inhibition. Like all reversible MAOIs, SR 95191 antagonized the long-lasting MAO-A inhibition induced by clorgyline. Finally, SR 95191 did not affect monoamine uptake either in vitro or in vivo and did not interact in vitro with a variety of neurotransmitter or drug receptor sites. Based on these results it is postulated that SR 95191 is a selective and reversible type A MAOI of medium potency, which may be of therapeutic benefit in depressed patients.

Animals↗

External rotation of the hip. A predictor of risk for stress fractures.

External rotation of the hip was found to have a statistically significant correlation with the incidence of stress fractures, in a prospective study among Israeli infantry recruits of possible anthropomorphic predictors of risk for stress fractures. Soldiers in whom hip external rotation was greater than 65 degrees were at a higher risk for tibial and total stress fractures than those with external rotations of less than 65 degrees. The mean hip external rotation in this study of 57 degrees +/- 9.3 degrees was higher than in statistics reported in the American literature. The existence of a larger subpopulation with hip external rotation greater than 65 degrees may partially explain why the reported incidence of stress fractures in the Israeli army is higher than that of the American army.

Adolescent↗

Detection of sodium channel distribution in rat sciatic nerve following lysophosphatidylcholine-induced demyelination.

In vivo application of lysophosphatidylcholine (LPC) to rat sciatic nerve induces impaired hind leg movement within 2 days which is recovered by 6 days. Segmental demyelination was seen at 2 days after LPC application, and remyelination had barely started in a few axons by 6 days. Using sodium channel-specific monoclonal antibodies and immunofluorescence microscopy, we observed altered distribution of sodium channels in demyelinated axons. Bright fluorescent labeling was found along the segmentally demyelinated axolemma at 6 days in contrast to the dim staining of the demyelinated nerve found at 2 days. In addition, radioimmunoassays detected an elevated number of antibody binding sites on sciatic nerve trunk from the sixth day. Our data provide the immunocytochemical evidence for the assumption that recruitment of sodium channels into demyelinated axolemma contributes to the recovery of function following axon demyelination by LPC.

Action Potentials↗

In vivo voltammetric monitoring of catecholamine metabolism in the A1 and A2 regions of the rat medulla oblongata.

Catecholaminergic metabolism was estimated in A1 and A2 noradrenergic nuclei of the rat medulla oblongata using differential normal pulse voltammetry combined with electrochemically treated carbon fiber microelectrodes. In both areas an oxidation peak appearing at +50 mV was recorded. Electrochemical data and pharmacological experiments indicated that 3,4-dihydroxyphenylacetic acid (DOPAC) synthesized by noradrenergic neurons was the major contributor to this signal. Indeed, alpha-methyl-p-tyrosine, by inhibiting tyrosine hydroxylase, and pargyline, by inhibiting monoamine oxidase, both totally suppressed the peak appearing at +50 mV in A1 and A2 areas. Conversely, FLA-63, an inhibitor of dopamine-beta-hydroxylase, increased it. Moreover, a local and unilateral injection of catecholaminergic neurotoxin (6-hydroxydopamine) in the vicinity of A1 induced a 60% decrease in the peak height. This effect was prevented by pretreatment with desipramine, an inhibitor of noradrenaline reuptake, which is known to protect noradrenergic neurons against the action of 6-hydroxydopamine. Finally, specific drugs acting on alpha-2-noradrenergic receptors (clonidine and piperoxane) modulated the peak height recorded from both structures. Thus, as previously shown in the locus ceruleus, the variations in the extracellular DOPAC levels reflect the metabolic activity of A1 and A2 noradrenergic neurons.

3,4-Dihydroxyphenylacetic Acid↗