Fate of the monoamine oxidase inhibitor pargyline in cultured hepatocytes

The interaction of the monoamine oxidase inhibitor pargyline with cultured hepatocytes has been studied. [Phenyl-3, benzyl-3H] pargyline (38 nM) rapidly enters the cells and a plateau of incorporation into a trichloroacetic acid insoluble form (monoamine oxidase) is reached after 2 hr. The level of labelling is lower in freshly isolated cells than in those in later culture. The maximum incorporation accounts for only 6% of the added radioactivity and produces a 9% inhibition of monoamine oxidase activity. The remaining [3H] pargyline is metabolized and quickly accumulates in the cell culture medium in a form which cannot label exogenous mitochondria. The metabolism of pargyline varies both qualitatively and quantitatively with culture age. In 0 hr and 20 hr-cultured cells one metabolite preferentially appears whilst in 140 hr cultured hepatocytes at least three metabolites are formed. The metabolism of [3H] pargyline in early culture is consistent with a cytochrome P-450 involvement. The use of [3H] pargyline to label monoamine oxidase in cultured hepatocytes offers several attractive features for studying the turnover of this enzyme. These include speed of interaction, non-reutilization, application to normal cells, controlled inhibition of monoamine oxidase and metabolism of non-specific label.     

Total-body protein turnover in parenterally fed neonates: effects of energy source studied by using [15N]glycine and [1-13C]leucine

The effects of nonprotein energy source (ie, glucose only vs glucose and lipid) on nitrogen retention and total-body protein turnover were studied in 20 parenterally fed newborn infants. All infants received approximately 3 g amino acids and 80-90 kcal.kg body wt.d. Total-body protein synthesis was estimated by using three constant-infusion, end-product methods: enrichment of urinary urea and ammonia in response to a [15N]glycine label and exhaled carbon dioxide enrichment in response to a [1-13C]leucine label. No differences were seen in nitrogen retention between the two energy sources. The estimate of total-body protein turnover obtained from the 13C label was similar to that obtained with the [15N]urea label. No differences in turnover rates were observed between the two diet groups. Use of the glucose-plus-lipid fuel system enhanced energy storage and the reutilization of amino acid for protein synthesis.     

Cervico-arthrotic myelopathies. Treatment and prognosis

The authors present 50 cases of cervical spondylotic myelopathy treated by anterior or posterior approach. To assess the severity of the pre- and postoperative neurological symptoms, they define an original ten-point classification scale taking into account gait and urinary disturbance, ability to manipulate objects and pain. With C2-C7 laminectomy, 60% of the patients are improved, essentially for walk. A few cases only (14%) are upgraded for upper limbs function. The authors conclude that this surgical treatment should be applied only when there is a multi-level narrowed canal and predominant lower limbs deficits. The efficacy of the anterior approach depends on complete removal of osteophytes. In cases with complete osteophytectomy, this surgical treatment can improve both the upper and lower limbs function and 77.8% good results are obtained. In a few cases it may be necessary to use both approach successively. Discriminant analysis applied to 12 factors shows that pre-operative scores of upper and lower limbs and sagittal diameter of spinal canal are the most important factors for neurological prognosis.     

Neuropeptide Y-like immunoreactivity in neurons of the human retina

The distribution of neuropeptide Y-like immunoreactivity (NPY-LI) was investigated in wholemounts and in transverse sections of the human retina. NPY-LI was localized to the soma and axonal processes of large ganglion cells (GCs) and to the soma and dendritic arborization of amacrine cells (ACs). NPY-LI GCs were unevenly distributed across the retina, the highest density of 875 cells/mm2 was found in the fovea centralis and the lowest density of 15 cells/mm2 in the peripheral retina. The total number of NPY-LI GCs in the retina was estimated to be about 85,000. The soma sizes of NPY-LI GCs increased from 116 microns 2 +/- 23 (s.d.) in the retinal centre to 251 microns 2 +/- 57 in the retinal periphery. The soma size of NPY-LI ACs was in the range of 40 and 50 microns 2. In transverse sections NPY-LI was seen to be localized to the optic fibre layer, to the somata of GCs, to the scleral sublamina of the inner plexiform layer (AC dendrites) and to the innermost part of the inner nuclear layer (somata of ACs). The gradients of soma sizes and retinal distribution of NPY-LI GCs were taken as an indication that they correspond to the class of large to very large GCs, previously identified in the human retina by Golgi impregnation.     

Protection of CGS 10078B against ouabain-induced arrhythmia in the cat

CGS 10078B (CGS; 1-[2,3-dihydro-1,4-(2S)-benzodioxin-2-yl]-5-[2,3-dihydro-1,4-(2R)- benzodioxin-2-yl]-3-(1R,5S)-aza-1,5-pentanediol methane sulfonate) is an agent with alpha- and beta-receptor and calcium channel blocking actions. To study its antiarrhythmic activity, cats were anesthetized with alpha-chloralose, ventilated, and given atropine and gallamine. CGS (10 or 20 mg/kg, i.v.) was infused 15 min prior to ouabain. Bolus injections of ouabain (25 micrograms/kg, i.v.) were given every 15 min until death (D). Some cats were pretreated with reserpine (R; 5 mg/kg, i.p.) 24 h prior to the experiment. In other cats 6-hydroxydopamine (6-OHDA; 20 mg/kg, i.v.) was administered 3 days prior to CGS 20 mg/kg and ouabain. Data were compared with those of Lathers [Eur. J. Pharmacol. 64: 95, 1980], i.e., with 12 cats who received only ouabain and with 11 pretreated with timolol (T; 5 mg/kg, i.v.) prior to ouabain. After CGS (10 or 20 mg/kg, i.v.), but just prior to the first dose of ouabain, the blood pressure (BP) was decreased (p less than 0.05) from control (165 +/- 6 vs. 96 +/- 7, and 136 +/- 5 vs. 90 +/- 10 mm Hg, respectively). Comparable heart rate (HR) values were also decreased (p less than 0.05) from 225 +/- 17 to 166 +/- 14 and from 193 +/- 8 to 152 +/- 6 beats/min. 11 min after T, BP and HR had decreased (p less than 0.05) from 133 +/- 6 to 103 +/- 7 mm Hg and from 134 +/- 4 to 104 +/- 6 beats/min, respectively. Ouabain did not influence these decreases in BP and HR. CGS (10 or 20 mg/kg, i.v.) increased (p less than 0.05) the time to ouabain-induced arrhythmia (AR) and D. The magnitude of the protection appeared to be similar to that afforded by T. R given prior to CGS (20 mg/kg, i.v.) also increased the time to ouabain-induced AR and D while 6-OHDA increased the time to AR. The CGS protection against ouabain-induced AR was still present in animals pretreated with R or 6-OHDA. This indicates that the antiarrhythmic affect is not dependent upon adrenergic neuronal blockade.     

Positive effects of ketamine v. metomidate anesthesia on cardiovascular function, oxygen delivery and survival. Studies with a porcine endotoxin model

Pulmonary and cardiovascular function, oxygen delivery and mortality were compared in endotoxemic pigs spontaneously breathing air and with continuous i.v. infusion of ketamine anesthesia (n = 10) or the equianesthetic dose of metomidate (n = 10). Continuous 6-hour i.v. infusion of endotoxin caused profound pulmonary and cardiovascular derangement in both groups. Cardiac output, mean arterial blood pressure, oxygen delivery and base excess were significantly higher and pulmonary vascular resistance significantly lower from 2-3 hours onwards in the ketamine than in the metomidate group. Six-hour survival was 6/10 and 1/10 in the respective groups. Death was presumably due to insufficient oxygen delivery in relation to tissue demand, reflected in the metomidate group's low base excess values. Control, non-stressed pigs showed no notable physiologic changes with either anesthetic regimen. The study demonstrated the importance of the type of anesthesia in stressful endotoxemic animal models. Although extrapolation of animal data requires great caution, the results may favor use of ketamine over etomidate (the clinical analogue of metomidate) in septic shock states requiring surgical intervention.