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Biomedical subjects

O Keren

Publications and source records attributed to O Keren.

At least 19 recordsLinked to original sources
PubMed1996

Stimulatory effects of opioids on transmitter release and possible cellular mechanisms: overview and original results.

Opiates and opioid peptides carry out their regulatory effects mainly by inhibiting neuronal activity. At the cellular level, opioids block voltage-dependent calcium channels, activate potassium channels and inhibit adenylate cyclase, thus reducing neurotransmitter release. An increasing body of evidence indicates an additional opposite, stimulatory activity of opioids. The present review summarizes the potentiating effects of opioids on transmitter release and the possible cellular events underlying this potentiation: elevation of cytosolic calcium level (by either activating Ca2+ influx or mobilizing intracellular stores), blockage of K+ channels and stimulation of adenylate cyclase. Biochemical, pharmacological and molecular biology studies suggest several molecular mechanisms of the bimodal activity of opioids, including the coupling of opioid receptors to various GTP-binding proteins, the involvement of different subunits of these proteins, and the activation of several intracellular signal transduction pathways. Among the many experimental preparations used to study the bimodal opioid activity, the SK-N-SH neuroblastoma cell line is presented here as a suitable model for studying the complete chain of events leading from binding to receptors down to regulation of transmitter release, and for elucidating the molecular mechanism involved in the stimulatory effects of opioid agonists.

Adenylyl Cyclases↗
PubMed1994

Dual regulation by opioids of 3H-norepinephrine release in the human neuroblastoma cell-line SK-N-SH.

Depolarization-evoked 3H-norepinephrine release from SK-N-SH cells was found to be regulated by opioid ligands. Opioids exerted either inhibition or augmentation of 3H-norepinephrine release. Both effects were mediated by opioid receptors. In addition, a nonopioid inhibitory effect of opiates on release was observed. The SK-N-SH cell-line provides a suitable model for studying the various mechanisms underlying the opioid regulatory pathways within single cells.

Cell Line↗
PubMed1994

Follow-up studies of somatosensory evoked potentials and auditory brainstem evoked potentials in patients with post-coma unawareness (PCU) of traumatic brain injury.

Some patients who suffer severe traumatic brain injury (TBI) fail to recover higher brain functions in spite of giving the appearance of sleep-wake cycles. Such a state is called post-coma unawareness (PCU) and varies in type and degree. Patients may remain in this state for months or even years. This study focused on the follow-up of upper-limb somatosensory evoked potential (USEP) measurements and auditory brainstem responses (ABR), with an emphasis on dynamic changes, in 10 patients with PCU resulting from TBI. The prognostic value of USEP and ABR was evaluated. Results showed that the presence of ABR in PCU patients had no prognostic value, because ABRs were found both in patients who recovered and those who did not, even a year after the trauma. The presence of normal ABR in PCU patients may suggest that the brainstem has been spared in the pathoanatomy of the PCU condition, with the significant damage occurring above this level, in cortical and subcortical (that is, hemispheral) areas. USEP was graded using the new system of Houlden [1] for 'acute' comatose patients. It was found that USEP measurements had some prognostic value in PCU patients. Most of the patients who remained in the PCU state had grade 2 or less initially, whereas most of the patients who later recovered or achieved at least a 'reduced life' state were grade 4 or more. On initial testing (when all patients were still in the PCU state), defined cortical potential (mainly in the slope of the building NI potential) was seen in only some of the patients who later recovered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Upper limb somatosensory evoked potentials as a predictor of rehabilitation progress in dominant hemisphere stroke patients.

BACKGROUND AND PURPOSE: The aim of this study was to determine the predictive yield of upper limb short latency somatosensory evoked potential (USEP) in patients with first stroke in the dominant hemisphere. METHODS: Nineteen patients (average age, 58 years) were evaluated twice: on arrival at the rehabilitation center, approximately 3 weeks after the stroke, and again approximately 10 weeks later. The clinical assessment included a quantitative evaluation of motor ability, independence in activities of daily living, and communication ability. USEP was recorded during the week of the initial clinical evaluation. Special attention was paid to the relations between USEP parameters and the dynamics of the clinical condition. RESULTS: The seven patients in whom no cortical potential could be detected showed the worst outcomes; however, the existence of cortical potentials in the remaining 12 patients did not provide a precise prediction of their "rehabilitative capacity" (ie, the extent of their progress). A correlation was established between the amplitude of the potentials recorded over both hemispheres and changes in communication ability. Additional findings included an association between shortened central conduction time over the damaged hemisphere during the first month after stroke and improvement in motor ability. CONCLUSIONS: USEP can serve as an adjuvant tool for predicting the recovery progress of stroke patients.

Adult↗
PubMed1993

Selective and interactive down-regulation of mu- and delta-opioid receptors in human neuroblastoma SK-N-SH cells.

Human neuroblastoma SK-N-SH cells, which contain both mu- and delta-opioid receptors, were grown under conditions that provided a mu:delta ratio of 1.5:1. Both receptors were down-regulated after 72 hr of exposure to 100 nM etorphine. Selective down-regulation was demonstrated using selective opioid agonists; the mu agonist Tyr-D-Ala2-Gly-(Me)Phe4-Gly-ol down-regulated mu- but not delta-opioid receptors, whereas prolonged exposure to the selective delta agonist D-Pen2,D-Pen5-enkephalin resulted in delta- but not mu-opioid receptor down-regulation. Morphine, which binds mu- as well as delta-opioid receptors, down-regulated both receptor subtypes. NG108-15 cells, which contain delta receptors exclusively, were also tested. NG108-15 cells did not exhibit delta-opioid receptor down-regulation when exposed to morphine. The discrepancy between the effect of chronic morphine treatment on delta receptors in SK-N-SH cells and in NG108-15 cells raised the question of whether the coexistence of mu receptors in the former allowed morphine to down-regulate delta receptors. The role of mu-opioid receptors in morphine-induced delta receptor down-regulation was studied by using the irreversible mu antagonist beta-funaltrexamine. Pretreatment of SK-N-SH cells with beta-funaltrexamine prevented down-regulation of delta receptors in response to chronic exposure to morphine but did not affect down-regulation of delta receptors in response to D-Pen2,D-Pen5-enkephalin. The experimental data indicate that morphine-induced delta-opioid receptor down-regulation is dependent on the presence of functional mu receptors in the same cell.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

An open trial of vacuum penile tumescence: constriction therapy for neurological impotence.

Sexual dysfunction is a frequent result of traumatic and non traumatic neurological disorders, including spinal cord injury, stroke, traumatic brain injury and autonomic neuropathy (for example, as may be seen in patients with diabetes mellitus). Although many methods have been suggested for the treatment of some of these problems in male patients, most are invasive and have a substantial morbidity. This is the report of a pilot trial of vacuum tumescence constriction therapy for 30 patients with chronic neurological impotence. Seventeen of these patients, following sexual counselling and training, decided to purchase such a device. At follow up, a mean of 21 months, over 50% of those who had purchased the device were still actively using it. The frequency of coitus increased from 0.3/wk to 1.5/wk (t = -5.7; p less than 0.0001). No significant morbidity was reported by patients. Vacuum tumescence constriction therapy shows promise as a noninvasive method for the treatment of neurological impotence.

Adult↗
PubMed1992

Noninvasive treatment for erectile dysfunction in the neurogenically disabled population.

Erectile dysfunction is the most prevalent sexual dysfunction in neurogenically disabled men. Studies of rehabilitation patients indicate that the restoration of sexual functioning is considered an important priority. This article reports on a pilot study of vacuum tumescence constriction therapy as a noninvasive method for use by a population with traumatic or nontraumatic neurologic disorders such as spinal cord injury, stroke, multiple sclerosis, and diabetes mellitus. Of the 30 patients who participated in the study, 17 purchased the device and over 50% of them reported using the device on a long-term basis. Frequency of coitus increased from 0.3/wk to 1.5/wk. Included in the study are methods used by patients to integrate the device into their sex life, the role of the patient's partner in the decision to purchase the device, and the rate of partner satisfaction. There were no reports of substantial morbidity. Thus, this method shows promise as a noninvasive treatment for men who are moderately to severely neurogenically disabled.

Equipment and Supplies↗
PubMed1991

Acute stroke patients: long-term effects of rehabilitation and maintenance of gains.

The efficacy of rehabilitation programs to facilitate recovery after acute stroke remains controversial. To further evaluate this issue, the records of 139 "middle-band" stroke survivors were reviewed retrospectively at admission to, discharge from, and one-year follow-up from inpatient rehabilitation. Patients were divided into two groups (out-patient [O/P] or no O/P) based on their involvement in physical and occupational therapy services. A repeated measures ANOVA indicated that both groups made clinically and statistically significant improvements in all functional indices between stroke onset, discharge from inpatient rehabilitation, and follow-up: O/P therapy: mobility F(1,46) = 1651, p less than .0001; self-care F(1,47) = 1062, p less than .0001; total F (1,47) = 1093, p less than .0001; no O/P therapy: mobility F(91,88) = 5643, p less than .0001; self-care F(1,88) = 5722, p less than .0001; total F(1,88) = 6733, p less than .0001. Pairwise comparisons for all functional indices revealed that all statistically significant changes in function in the no O/P therapy group occurred between stroke onset and discharge: self-care (p less than .0001), mobility (p less than .0001), and total (p less than .0001). Pairwise comparisons of all indices in the O/P therapy group revealed that all differences between stroke onset and discharge functional scores were at the p less than .0001 level, and score differences between discharge from inpatient rehabilitation and follow-up were as follows: self-care (p less than .05), mobility (p less than .001), and total (p less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Juvenile Parkinson's disease and its response to L-dopa therapy.

Four youngsters, between the ages of 13-27 years, presented dystonic foot. Two to three years following the appearance of the dystonic foot, cogwheel rigidity and tremor appeared on the dystonic foot side. Treatment with low doses of levodopa/carbidopa consistently reversed the symptoms. "On-off" phenomena appeared in the first years of treatment and persisted for the entire period of 5 to 15 years of illness. No parkinsonian signs were present when the dystonic foot appeared. Based on our observations and on a review of the literature, we conclude that responsiveness to low doses of L-dopa is the major marker of juvenile Parkinson's disease.

Adolescent↗
PubMed1990

Transverse myelitis associated with mycoplasma pneumoniae: case report.

Acute transverse myelitis (ATM) is a disorder of the spinal region of the central nervous system. In the present case, the clinical course showed ATM associated with mycoplasma pneumoniae (MP) and little recovery; the girl was left with a flaccid paraplegia, and thus differed from other cases in the literature which all reported complete or near-complete recovery.

Adolescent↗
PubMed1988

Affinity crosslinking of 125I-labeled human beta-endorphin to cell lines possessing either mu- or delta-type opioid binding sites.

The specific labeling of opioid receptor-related polypeptides was compared in two cell lines which differ in their opioid receptor population: SK-N-SH which contains predominantly mu-type opioid receptors, and NG-108-15, which contains exclusively delta-type opioid receptors. Labeling of opioid receptors was achieved by affinity cross-linking of membranes, using 125I-labeled human beta-endorphin, followed by solubilization in sodium dodecyl sulphate (SDS), SDS-gel electrophoresis and autoradiography. Different labeling patterns were obtained from these two cell lines. In SK-N-SH cells, 3 major proteins were labeled, corresponding to molecular weights of 92, 65 and 25 kDa, while in the NG-108-15 cells, 53-kDa and 25-kDa polypeptides were the major ones labeled. The radioactivity incorporated into the 92- and 65-kDa peptide bands derived from SK-N-SH cells was displaced by the mu-selective ligand Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO) but not by the delta-selective ligand [D-Pen2,D-Pen5]enkephalin (DPDPE). The radioactivity incorporated into the NG-108-15-derived peptide bands was displaced by the delta-selective ligand, but not by the mu-selective ligand. This confirms our previous finding in mammalian brain which demonstrated that mu- and delta-opioid binding sites can be identified as distinct proteins which differ in molecular size.

Binding Sites↗
PubMed1986

Affinity crosslinking of 125I-human beta-endorphin to cell lines possessing either mu or delta type opioid binding sites.

Affinity crosslinking of human 125I-beta-Endorphin to cell lines possessing either mu or delta binding sites was carried out. Autoradiography of SDS-PAGE gels from these crosslinked cell lines revealed that these two sites contain major peptide subunits that differ in molecular size. This confirms our earlier finding in mammalian brain which demonstrated separate and distinct subunits for mu and delta opioid receptors.

Cell Line↗
PubMed1982

Differential effect of humoral endorphin on the binding of opiate agonists and antagonists.

Humoral (H) endorphin, a novel endogenous factor with opiate-like activity was further characterized using various radioreceptor assays. H-Endorphin displaced both labelled opiates (morphine, ethylketazocine) and opioid peptides (leucine-enkephalin) from their specific binding sites in rat brain membranes. The effect of sodium ions on H-endorphin indicates its agonistic nature which is in agreement with previous pharmacological experiments. However, H-endorphin potentiated the binding of the opiate antagonist naloxone to brain membranes. This peculiar effect of H-endorphin on naloxone, together with the non-conventional interactions observed in various pharmacological assays, clearly distinguishes H-endorphin from other opioid ligands. A multisite model of the opiate receptor is presented. This model, which is compatible with the well documented evidence for receptors heterogeneity also explains non-conventional interactions between various opioid ligands.

Animals↗
PubMed1982

The effect of L-dopa on pupillary diameter in mice.

Injection of L-dopa in mice produces dose-dependent mydriasis. Pre-treatment with peripheral dopa-decarboxylase inhibitors (carbidopa and benserazide) or with an alpha-adrenergic blocking agent (phentolamine) abolishes the pupillary dilation caused by L-dopa. Pretreatment with fusaric acid, an inhibitor of dopamine-beta-hydroxylase, also antagonizes the mydriatic effect of L-dopa. Thus, our results suggest that the mydriasis produced in mice following the injection of L-dopa is caused by its peripheral conversion to noradrenaline, which stimulates alpha-adrenergic receptors in the dilator iridis. There was no evidence that stimulation of specific dopaminergic receptors was involved.

Animals↗
PubMed1982

Effect of amantadine on pupillary diameter in mice.

Amantadine, injected into mice, produces dose-dependent mydriasis. The pupillary dilation caused by amantadine is not abolished by pretreatment with reserpine, or by combined pretreatment with reserpine and alpha-methyl-p-tyrosine, although the mydriasis is reduced by approximately 25%. Thus, release of catecholamines from nerve terminals can account for only 25% of amantadine-produced mydriasis. Haloperidol and phentolamine can partially block the effect of amantadine, but, when given after reserpine, neither of the antagonists increases the blockade produced by reserpine alone. We conclude that the catecholaminergic system contributes only partially to the pupillary effect of amantadine, and that other mechanisms appear to be involved.

Amantadine↗