Norephedrine (phenylpropanolamine) stimulates oxygen consumption and lactate production in the perfused rat hindlimb

d,l-Norephedrine (phenylpropanolamine) which is both a demethylated analogue and a metabolite of d,l-ephedrine, is a reputed anorectic agent. In the present study the proposed most active isomer of this mixture, l-norephedrine has been assessed as a peripherally acting thermogenic agent in the isolated perfused rat hindlimb. l-Norephedrine produced a dose-dependent increase in oxygen uptake and perfusion pressure and increased lactate production. Whereas propranolol potentiated the increase in oxygen uptake and perfusion pressure produced by l-norephedrine, prazosin significantly and nitroprusside totally inhibited both of these changes. Nitroprusside also completely inhibited the increase in lactate production. We conclude that norephedrine has a hitherto unrecognized peripheral thermogenic activity in the perfused rat hindlimb resulting from its interaction with alpha 1 adrenergic receptors that control vasoconstriction in this tissue.     

Nature of the inhibitory effect of complex saccharide moieties on the tight binding of human spermatozoa to the human zona pellucida.

Fucoidin and heparin sulfate inhibit binding of human sperm to the human zona pellucida under hemizona assay (HZA) conditions. Here we used the HZA to further assess tight sperm binding with/without preincubation of the sperm with other sulfated and nonsulfated glycoconjugates and charged polymers. Fucoidin significantly inhibited binding compared with controls (greater than 75% inhibition), even if sperm were washed after preincubation with the saccharide. Dextran sulfate also produced significant inhibition, although to a lesser extent (54% inhibition). Chondroitin sulfates A and B, heparin, and dextran did not affect binding. Sodium sulfate and polyglutamic acid did not affect HZA results; polyphosphates produced only moderate inhibition. The potent inhibitory effect of the sulfated carbohydrates fucoidin and dextran is probably competitive (receptor-ligand type) in nature. However, the lack of significant effects of simple charged molecules (nonspecific effects) suggests that the degree of sulfation (charge) may not be crucial to its inhibitory action.     

Cholecystokinin and neuropeptide Y receptors on single rabbit vagal afferent ganglion neurons: site of prejunctional modulation of visceral sensory neurons

A [¹²⁵I]cholecystokinin (CCK) analog and [¹²⁵I]peptide YY (PYY) were used to localize and characterize CCK and neuropeptide Y (NPY) receptor binding sites in the rabbit vagal afferent (nodose) ganglion. High concentrations of CCK and NPY binding sites were observed in 10.6% and 9.2% of the nodose ganglion neurons, respectively. Pharmacological experiments using CCK or NPY analogs suggest that both subtypes of CCK (CCK-A and CCK-B) and NPY (Y1 and Y2) receptor binding sites are expressed by discrete populations of neurons in the nodose ganglion. These results suggest sites at which CCK or NPY, released in either the nucleus of the solitary tract or a peripheral tissue, may modulate the release of neurotransmitters from a select population of visceral primary afferent neurons. Possible functions mediated by these receptors include modulation of satiety, opiate analgesia, and the development of morphine tolerance.     

Long-term survival, prognosis, and life-care planning for 29 patients with chronic locked-in syndrome.

We present a life-table analysis of a cohort of 29 locked-in syndrome (LIS) patients followed for a minimum of five years, and we report on the status of the chronic LIS patient. Twenty-nine LIS patients who remained locked-in for more than one year were identified. Inpatient charts were reviewed for demographic, medical, and functional data. Telephone followup was obtained to examine medical complications after discharge, survival, neurologic recovery, care issues, and permanent disposition. A life-table analysis was performed on survival data. Cerebrovascular disease was the most common cause of LIS. Survival ranged from 2.02 to 18.15 years. Twenty of the 26 patients available for five-year followup survived; hence, five-year survival was 81%. An alternative method of communication and emotional stress for the patient's caregiver was the key issue in patient care. Most patients were cared for in their own homes. Although minimal late neurologic recovery occurs in chronic LIS, survival may, nonetheless, be prolonged with adequate supportive care. Modern computerized technology offers LIS patients the ability to interact with their environment. This information may assist physicians in making ethical and long-term care decisions with the patient rather than for the patient with LIS.     

Two pathways of signal transduction are activated in the same cell by different cytokines.

NFS60, a murine leukemia cell line, responds to both interleukin 3 and 6 by proliferating, apparently by different signal transduction pathways. Although stimulation by both cytokines increases the uptake of 3H-arachidonic acid, the response to IL-6 was much faster. Furthermore, the effect of various arachidonic acid metabolites on the response to cytokine was different. PGE2 inhibited IL-6-induced proliferation and potentiated the response to IL-3. Additionally the G proteins which coupled the IL-3 and IL-6 receptor to the proliferative response are probably different, based on the ability of cholera toxin to inhibit the IL-3 but not the IL-6 response. These data are evidence of two pathways of signal transduction.     

Pharmacological evaluation of the cholinergic system in progressive supranuclear palsy

Severe cholinergic loss occurs in the brains of patients with progressive supranuclear palsy. To evaluate the functional implications of this neuronal deficit, dose-response curves were obtained in patients with progressive supranuclear palsy and normal control subjects undergoing intravenous cholinergic blockade (scopolamine) and stimulation (physo-stigmine). Physostigmine had no significant neurobehavioral effects at any does in patients with progressive supranuclear palsy. Scopolamine, at low and medium doses, significantly impaired memory performance of both groups, but worsened the gait of only the patients. High-dose scopolamine, which could not be tolerated by the patients, resulted in gait deterioration among control subjects. Thus, patients with progressive supranuclear palsy have increased sensitivity to cholinergic blockade compared to control subjects. Since loss of cholinergic neurons appears to contribute to the pathogenesis of certain cognitive and motor deficits found in progressive supranuclear palsy, the use of oral anticholinergics should ordinarily be avoided in this disorder. On the other hand, physostigmine at clinically tolerated dose levels seems to be terapeutically ineffective.     

Voltage-gated Currents in Rabbit Retinal Astrocytes

The voltage-gated currents of the astrocytes associated with the retinal capillaries of the rabbit retina were studied using whole-cell patch clamp recording. The resting potential of these cells was −70 ± 4.8 mV (mean ± SEM; n = 54), and the input resistance and cell capacitance were 558 ± 3.6 MΩ and 19.5 ± 1.8 pF respectively. Depolarization to potentials positive to −50 mV evoked rapidly activating inward and outward currents. The inward current was transient, eliminated by substitution of choline for Na⁺ in the bathing solution, and reduced by 50% in the presence of 1 μM tetrodotoxin. The time-to-peak of the Na⁺ current was more than twice that for the Na⁺ current found in retinal neurons. The glial Na⁺ current was half-inactivated at −55 mV. A transient component of the outward K⁺ current was blocked by external 4-aminopyridine while a more sustained component was blocked by external tetraethylammonium. At potentials between −150 and −50 mV the membrane behaved Ohmically. Voltage-gated currents in retinal astrocytes recorded in situ appear qualitatively similar to those described for some glial cells in vitro.