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Biomedical subjects

N E Naftchi

Publications and source records attributed to N E Naftchi.

At least 19 recordsLinked to original sources

Autonomic dysreflexia: pharmacological management of hypertensive crises in spinal cord injured patients.

Interruption of autonomic pathways by spinal cord injury (SCI) causes dysfunctional autonomic dysreflexia (AD), which was first described in 1917, still remains unrecognized by those in the medical profession not involved in SCI care. Autonomic dysreflexia is a syndrome generally manifest by cardiovascular symptoms and characterized by paroxysmal hypertension. These symptoms appear in patients with spinal cord injury above the sympathetic outflow from the spinal cord (T6). Since patients with high level SCI are usually hypotensive, the high blood pressures that develop during AD represent pressure changes of a magnitude that can cause cerebrovascular accidents and death of the subject. We discuss the therapeutic interventions that abate and curtail the symptoms and prevent the catastrophic sequelae of autonomic dysreflexia.

Autonomic Nervous System Diseases↗

Treatment of mammalian spinal cord injury with antioxidants.

After spinal cord injury, two groups of cats were treated with a combination of methylprednisolone sodium succinate (MP, 35 mg/kg) and epsilon-aminocaproic acid (EACA, 350 mg/kg), and guanabenz acetate (0.65 mg/kg). Guanabenz acetate was administered twice daily for 8 weeks. In the first group, the treatment significantly increased blood flow in the abdominal aorta. All cats treated with guanabenz acetate 3 hr after spinal cord contusion had return of micturition and none suffered complete paraplegia. Four animals had partial and the other four had complete motor recovery. A superoxide (O2-.) generating system, horseradish peroxidase, decreased [14C]gamma amino butyric acid uptake by mouse cortical slices by 33% but when superoxide dismutase was added to the medium, the uptake was reduced by only 9%. The nerve endings were also protected by superoxide dismutase from morphologic damage by O2-. as observed by electron microscopy. The agents used in these studies produce their ameliorating effects by virtue of their anti-inflammatory, antioxidant, and membrane stabilizing properties, and enhancing the regional microcirculation. In addition to having these properties, guanabenz acetate is also an alpha 2 adrenoceptor agonist.

Animals↗

Acute reduction of brain substance P induced by nicotine.

Ten minutes after a single injection of 0.8 mg/kg nicotine SC (free base) the level of substance P-like immunoreactivity (SPLI) was reduced by 61-73% in rat caudate-putamen, nucleus accumbens, and olfactory tubercle, with smaller and not significant reductions in the frontal cortex, substantia nigra, and ventral tegmental area. The nicotinic receptor antagonist mecamylamine (1.0 mg/kg IP) prevented the reductions in SPLI. The rapidity and the degree of the changes in SPLI after nicotine exceed those previously reported for other agents and implicate substance P neurotransmission as a major component of nicotinic action.

Animals↗

Alterations of neuroendocrine functions in spinal cord injury.

A transverse myelopathy causes a marked dysfunction in the negative feedback of some of the hypothalamo-hypophyseal-target organ axes. Spinal cord injured (SCI) humans with lesions above T6 exhibit significantly lower serum LH and testosterone but not FSH. The parathyroid hormone-thyrocalcitonin regulation of bone metabolism is disturbed; the higher the lesion, the greater is the loss of mineral and matrix components of the bone. Further, the response to insulin induced hypoglycemia is blunted in SCI with high lesions, and their basal levels of norepinephrine, epinephrine, and cortisol are significantly lower than those of controls. Distension of the bladder or rectum, however, produces marked release of norepinephrine and concomitant increase in sympathetic activity. The results suggest impaired hypothalamo-hypophyseal-testicular, -adrenocortical, - adrenomedulary, -sympathetic axis dysfunction.

Adult↗

Alterations of immunoreactive substance P and enkephalins in rat spinal cord after electroacupuncture.

A form of electrically-induced analgesia known as electroacupuncture was administered to rats bilaterally at the point "Huan-tiao." Compared with untreated rats, treated rats showed altered pain thresholds characterized as low, intermediate, and high. From immunocytochemical studies, the spinal cords taken from the treated rats exhibited differences in immunoreactivity for substance P (SP), methionine- and leucine-enkephalins (ME and LE respectively). By densitometry, the altered levels of immunoreactive (IR) peptides correlated with the pain thresholds in specific ways. That is, high pain threshold correlated with the visualization of increased IR-SP adn IR-LE within neuronal processes throughout the dorsal horn substantia gelatinosa. In the same specimens, decreased IR-ME could be seen. In contrast, low pain threshold correlated with decreased IR-SP and IR-ME. IR-LE showed a concomitant decrease in the medial substantia gelatinosa region, and slight, insignificant changes laterally. The data suggest that different degrees of analgesia induced by electroacupuncture result from the variable release of SP, ME, and LE in spinal regions associated with nociception. In terms of current models of pain processing, the data do not entirely support an axo-axonic interaction between enkephalin interneurons and SP terminals. Some modifications and an alternative model are considered.

Acupuncture Therapy↗

Functional restoration of the traumatically injured spinal cord in cats by clonidine.

The long-term, chronic, paralysis resulting from spinal cord injury in the cat has been reversed by the use of an alpha 2-adrenergic receptor agonist, clonidine. Administration of this drug resulted in "normalization" of sensory-motor and autonomic dysfunctions. Preliminary studies of the clonidine in humans with traumatically injured spinal cord indicate that autonomic dysreflexia can be controlled and spasticity minimized. The data suggest that biochemical and pharmacologic manipulation of receptors may ameliorate paralysis following traumatic injury to the spinal cord as well as to the brain and brainstem.

Adrenergic beta-Agonists↗

Alterations in norepinephrine, serotonin, c-AMP, and transsynaptic induction of tyrosine hydroxylase after spinal cord transection in the rat.

Tyrosine hydroxylase (TH) activity and the concentrations of norepinephrine (NE), serotonin (5-HT), and cyclic adenosine 3',5'-monophosphate (c-AMP) were measured in the heart, adrenals, and brain stem of paraplegic rats. Following spinal cord transection NE concentration in the heart dropped to 30% within 24 hours and that of 5-HT decreased to 60% of control. Tyrosine hydroxylase activity in the adrenals reached a peak at five days and was still twice that of sham-operated controls thirty days later. Five days following transection the TH activity and c-AMP levels in the brain stem were elevated while NE concentration remained low. At seven days, however, NE and 5-HT levels were higher than in controls while TH activity and c-AMP concentration dropped to control levels. The increase in TH activity in the brain stem may be due to curtailed end-product feedback inhibition and to reduced receptor activation. The sustained induction of the adrenal TH is probably a consequence of a continual stimulation of splanchnic nerves.

Adrenal Glands↗

Presence of leucine-enkephalin in organotypic explants of fetal mouse spinal cord.

Spinal cord explants with attached dorsal root ganglia (DRGs), from 14-day fetal mice were fixed at 1-3 weeks in vitro and incubated for leucine-enkephalin (LE) immunoreactivity by the peroxidase-anti-peroxidase (PAP) immunohistochemical method. Results show long processes with labeled varicosities seen more often in dorsal regions of the cord explants. Stained punctate bodies and varicosities were often seen close to large cells in these cultures, whereas no label was detected in neuronal perikarya. A prominent laminar array of stained punctate bodies was noted in one cord explant, concentric with the perimeter of the explant. No LE label was detected in the neuritic outgrowths from the cord-DRG explants, whereas high levels of opiate receptors develop in these outgrowths, primarily on the DRG neurites, by 1-2 weeks in culture. The results indicate the presence of LE in explants of fetal mouse spinal cord with attached DRGs and offer an in vitro model system in which the onset and development of peptidergic neurons can be studied as they form functional cellular interrelationships with neurons bearing opioid and monoaminergic receptors in these organotypic cultures.

Animals↗

Substance P and leucine-enkephalin changes after chordotomy and morphine treatment.

Spinal cords of rats, cats and monkeys were transected; the animals were perfused at varying times. Other rats were injected with morphine and perfused 10 days later. Immunocytochemistry shows substance P (SP) present in control animals primarily in the substantia gelatinosa (SG) of the dorsal horn of the spinal cord. Slight SP immunoreactivity is found in the ventral horn and near the central canal. Starting a few days after transection, there is a buildup of reaction product in the dorsal horn, in sections cut from below the lesion; staining above remains the same. With time, after chordotomy, SP immunoreactivity appears in fibers in lamina V, only in sections below the lesion. Leu-enkephalin (LE) is also found in the SG, however, it is also present in quantity in the ventral horn and central canal areas. Chordotomy has no effect on its distribution indicating LE is intrinsic in the cord and probably contained within interneurons. Morphine increases SP immunoreactivity in the SG, laminae I, IV and V, and in the ventral horn, suggesting morphine analgesia is due to inhibition of intraneuronal SP release in regions specifically associated with pain--SG and lamina V.

Animals↗

Head-up tilt effect on glomerular filtration rate, renal plasma flow, and mean arterial pressure in spinal man.

Changes in glomerular filtration rate (GRF), renal plasma flow (RPF), and mean arterial pressure (MAP) were measured in subjects tested in supine and head-up tilt positions with various levels of spinal cord lesion and thus with different degrees of supraspinal sympathetic vasomotor control. Responses of paraplegic subjects to head-up tilt were not significantly different from those of normal controls but GFR and RPF were significantly lower in quadriplegics in the supine position. With tilt, MAP and RPF decreased significantly, but the fall in GFR was not significant. In all 3 groups, the GFR during head-up tilt was similar, indicating that in spite of the great loss of supraspinal sympathetic control, quadriplegic subjects apparently equally-constrict their afferent and efferent renal arterioles during orthostatic stress and thus prevent excessive fall of GFR.

Adult↗

A modified peroxidase--antiperoxidase procedure for improved localization of tissue antigens: localization of substance P in rat spinal cord.

A procedure is presented which modifies the Sternberger peroxidase--antiperoxidase (PAP) technique in order to visualize additional amounts of immunodeposits representing the antigen substance (SP) in 5-micrometer paraffin tissue sections of rat spinal cord. For increased sensitivity, the new procedure utilizes a "double bridge" and diaminobenzidine in low pH buffer. The modifications have made possible the visualization of immunoreactive beaded processes and punctate bodies, which were then traced to determine patterns of SP circuitry. Using the modified PAP procedure, the greatest number of immunoreactive processes appeared in the dorsal horn, where some punctate bodies and varicose processes could be seen adjacent to the myelinated afferent fiber bundles that penetrate the substantia gelatinosa as dorsal root collaterals. Additional immunoreactive processes and punctate bodies coursed through the myelinated afferent fiber bundles that penetrate the dorsolateral white matter, and extend into the intermediolateral gray region. Substance P was also identified within immunoreactive processes found in Rexed's laminae V and VI, as well as the central canal region, the dorsal gray commissure, and the ventral gray and white commissures. Since the modifications improved the visualization of SP-containing processes in sparsely populated regions of the spinal cord, especially the ventral horn, they may be useful in demonstrating other antigens that normally occur in small quantities within tissues.

3,3'-Diaminobenzidine↗

Pituitary-testicular axis dysfunction in spinal cord injury.

Concentrations of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in serum and 17-ketosteroids (17-KS) in urine of 10 paraplegic and 10 quadriplegic subjects were measured from onset of injury and followed once a week for 4 months. Compared with age-matched normal controls, paraplegic subjects showed significantly lower serum levels of LH and FSH for 2 weeks and of testosterone for 6 weeks after spinal cord trauma, following which periods of time these hormones attained normal levels. By contrast, in quadriplegic subjects, serum testosterone concentrations remained significantly lower than those of the controls during the entire 4-month testing period. Furthermore, in another group of 10 chronic (1 to 6 years after onset of injury) paraplegic and 10 chronic quadriplegic subjects, serum testosterone and FSH concentrations were comparable to those of the normal controls. Serum LH concentrations were at control levels in chronic paraplegic but significantly depressed in chronic quadriplegic subjects. The concentrations of urinary 17-KS exhibited sharp fluctuations over the 4-month period and were below control levels in paraplegic but within control limits in quadriplegic subjects. The results indicate that the function of the hypothalamic-pituitary-gonadal axis is disturbed for at least 4 months in quadriplegic subjects.

17-Ketosteroids↗