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.     

Retained pacemaker leads

Increasingly, functionless pacemaker leads are being abandoned in place because they cannot be safely removed. One hundred eighty-nine intact or partially removed pacemaker leads were abandoned in situ in 152 patients between Jan. 1, 1965, and Dec. 31, 1985. The leads, sometimes several leads in a single patient, were deemed uninfected at the time of abandonment in 137 patients and contaminated with Staphylococcus epidermidis in 15 patients. All of the contaminated leads have remained clinically uninfected during follow-up. One clean lead became infected early after implantation and the patient died after an open cardiac operation to remove that lead and an adjacent abandoned lead that was adherent to the subclavian vein. No other patient has had a late complication during follow-up to 256 months (mean 47.6). Properly managed abandonment of an uninfected lead can carry a very low complication rate.     

Cytophotometric investigations on atypical epithelial cells of the human seminal vesicle

Normal seminal vesicles were studied histologically in 80, and by Feulgen’s cytophotometric method in 10 autopsied cases (males, 44–82 years of age). In every case large, hyperchromatic nuclei were found. By cytophotometry euploid polyploid atypia was also shown in every case, which is characteristic of benign hormonal dysplasia.     

C(3)-cyclopropyl cephems and carbacephems

A series of C(3)-cyclopropyl cephems and carbacephems has been prepared by palladium catalyzed addition of diazomethane to the corresponding C(3)-vinyl derivatives. The phenylglycyl cyclopropyl cephem derivatives exhibit better Gram-positive activity than cephalexin or cefaclor, while the aminothiazole oxime cyclopropyl cephem derivatives were not as active as the corresponding C(3)-vinyl cephems.     

Chemical-shift imaging: a hybrid approach

The hybrid technique of projection-reconstruction echo-planar (PREP) imaging for obtaining chemical-shift images is demonstrated experimentally using a fluorine sample. The technique which is a variation on echo-planar imaging (EPI) relies on a multipass procedure. It is nevertheless quite efficient and consequently chemical-shift images may be produced in a few minutes. The method produces images in 64 chemical-shift regions, each region mapped spatially by 64 X 64 pixels. The imaging time was just over 4 min. These 64 chemical-shifted images can be straightforwardly added together to form an undistorted image of the complete object. In addition the chemical-shift spectrum can be extracted and the various chemical-shift images can be unambiguously assigned to the spectral peaks.     

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.     

Imipenem (N-F-thienamycin) versus netilmicin plus clindamycin. A controlled and randomized comparison in intra-abdominal infections

In a randomized study the clinical and bacteriologic effectiveness of imipenem was compared with the classical combination of netilmicin with clindamycin in patients who had surgery for an intraperitoneal infection, localized or generalized, with positive bacteriologic findings of the specimen taken at surgery. Excluded were all patients who received other antibiotics before surgery, or who died within 3 days after antibiotic therapy was started. Imipenem was given at a dose of 500 mg t.i.d., clindamycin 600 mg t.i.d., and netilmicin according to serum levels. The diagnoses ranged from postoperative peritonitis, gallbladder empyema, perforated gastroduodenal ulcer, small bowel perforation with and without obstruction, and perforated appendicitis to perforation of the colon. The bacteriologic work-up included examination of the primary specimen (aerobic and anaerobic), the urine, feces, and serologic testing for Candida albicans once or twice a week and after the course of antibiotic therapy. In addition, pH measurements of abscesses and drainage fluids were performed. Ninety-three patients entered the study. Forty-seven patients were treated with imipenem (test group), and 46 patients were treated with the combination therapy (control group). The two groups did not show significant differences in age, sex, diagnostic groups, risk factors, primary bacteriology, and duration of therapy (mean: 6.7 days). Thirty-eight patients (80.9%) treated with imipenem were cured, six patients (12.8%) were improved, and there were three (6.4%) failures. The respective numbers for the control group were 31 (67.4%), 10 (21.7%), and 5 (10.9%). The mean duration of hospitalization was 19 days for the test group and 24.5 days for the control group. There were four wound infections in the test group and 11 wound infections in the control group. Imipenem is at least as effective in the adjuvant therapy of intra-abdominal infections as the combination of netilmicin with clindamycin.     

Behavior of acid secretion and clinical results following selective proximal vagotomy in uncomplicated duodenal ulcer

Reported in this paper are postoperative results recorded from 120 patients, 3 years after selective proximal vagotomy for uncomplicated duodenal ulcer. There was no intraoperative lethality and no recurrence in 96.7 per cent of all cases, while Visick grades I on II were recorded from 98.2 per cent. Radiologically and gastroscopically detected pathological processes receded soon. Average postoperative reduction in acid secretion was 66.2 per cent in BAO and 46.8 per cent in MAO. Acid values re-increased thereafter, and three years later reduction rates still amounted to 43.7 per cent in BAO and 28.6 per cent in MAO. Indications for proximal gastric vagotomy are discussed in some detail.